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  • 201. Cousyn, Louis
    et al.
    Law-Ye, Bruno
    Pyatigorskaya, Nadya
    Debs, Rabab
    Froissart, Roseline
    Piraud, Monique
    Federico, Antonio
    Salvatore, Simona
    Cerase, Alfonso
    Macário, Maria C
    Durães, João
    Kim, Seung H
    Adachi, Hiroshi
    Audoin, Bertrand
    Ayrignac, Xavier
    Da, Yuwei
    Henderson, Robert
    La Piana, Roberta
    Laule, Cornelia
    Nakamagoe, Kiyotaka
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Schols, Ludger
    Sirrs, Sandra M
    Viader, Fausto
    Jastrzębski, Karol
    Leclercq, Delphine
    Nadjar, Yann
    Brain MRI features and scoring of leukodystrophy in adult-onset Krabbe disease2019In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 93, no 7, p. E647-E652Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To perform a systematic analysis and scoring of brain MRI white matter hyperintensities (WMH) in adult-onset Krabbe disease.

    METHODS: We retrospectively collected basic clinical data and the first available brain MRI from patients with confirmed Krabbe disease with first clinical manifestations beyond 10 years of age. Data were obtained from our reference center for lysosomal diseases (n = 6) and from contacted authors of published articles describing patients with adult-onset Krabbe disease (n = 15). T2-weighted fluid-attenuated inversion recovery images of each patient were analyzed and scored using a radiologic score of WMH in a single center.

    RESULTS: The corticospinal tract was always affected by WMH (100% of patients), however, with some distinctions along the tract: the precentral gyrus (100%), corona radiata (95%), and posterior internal capsule (81%) were highly abnormal, whereas the mesencephalon (57%), pons (52%), and medulla oblongata (5%) were less affected. WMH were also frequently present in the posterior lateral periventricular white matter (95%), optic radiations (86%), postcentral gyrus (71%), medial lemniscus (62%), and corpus callosum, especially in the isthmus (71%), whereas the genu was always normal. A few patients did not have the classical MRI pattern but extensive hyperintensities (n = 3), or patchy distribution of hyperintensities mimicking an acquired etiology (n = 2), or very subtle hyperintensities of the corticospinal tract (n = 1).

    CONCLUSIONS: We specified the main locations of WMH, which were observed in the earliest stages of the disease and were also present in patients with atypical MRI pattern, highlighting the importance of radiologic features to guide the diagnosis.

  • 202.
    Cubo, Rubén
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control.
    Jltsova, Elena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Andersson, Helena
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control.
    Medvedev, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control.
    Calculating Directional Deep Brain Stimulation Settings by Constrained OptimizationIn: Article in journal (Refereed)
    Abstract [en]

    Objective: Deep Brain Stimulation (DBS) consists of delivering electrical stimuli to a brain target via an implanted lead to treat neurodegenerative conditions. Individualized stimulation is vital to ensure therapeutic results, since DBS may otherwise become ineffective or cause undesirable side effects. Since the DBS pulse generator is battery-driven, power consumption incurred by the stimulation is important. In this study, target coverage and power consumption are compared over a patient population for clinical and model-based patient-specific settings calculated by constrained optimization. Methods: Brain models for five patients undergoing bilateral DBS were built. Mathematical optimization of activated tissue volume was utilized to calculate stimuli amplitudes, with and without specifying the volumes, where stimulation was not allowed to avoid side effects. Power consumption was estimated using measured impedance values and battery life under both clinical and optimized settings. Results: It was observed that clinical settings are generally less aggressive than the ones suggested by unconstrained model-based optimization, especially under asymmetrical stimulation. The DBS settings satisfying the constraints were close to the clinical values. Conclusion: The use of mathematical models to suggest optimal patient-specific DBS settings that observe technological and safety constraints can save time in clinical practice. It appears though that the considered anatomy-related safety constraints depend on the patient and further research is needed in this regard. Power consumption is important to consider since it increases with the square of the stimuli amplitude and critically affects battery life. Significance: This work highlights the need of specifying the brain volumes to be avoided by stimulation while optimizing the DBS amplitude, in contrast to minimizing general stimuli overspill, and applies the technique to a cohort of patients. It also stresses the importance of taking power consumption into account.

  • 203.
    Cubo, Rubén
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control.
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Jiltsova, Elena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Andersson, Helena
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control.
    Medvedev, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control.
    Calculating Deep Brain Stimulation Amplitudes and Power Consumption by Constrained Optimization2019In: Journal of Neural Engineering, ISSN 1741-2560, E-ISSN 1741-2552, Vol. 16, no 1, article id 016020Article in journal (Refereed)
    Abstract [en]

    Objective: Deep brain stimulation (DBS) consists of delivering electrical stimuli to a brain target via an implanted lead to treat neurological and psychiatric conditions. Individualized stimulation is vital to ensure therapeutic results, since DBS may otherwise become ineffective or cause undesirable side effects. Since the DBS pulse generator is battery-driven, power consumption incurred by the stimulation is important. In this study, target coverage and power consumption are compared over a patient population for clinical and model-based patient-specific settings calculated by constrained optimization.

    Approach: Brain models for five patients undergoing bilateral DBS were built. Mathematical optimization of activated tissue volume was utilized to calculate stimuli amplitudes, with and without specifying the volumes, where stimulation was not allowed to avoid side effects. Power consumption was estimated using measured impedance values and battery life under both clinical and optimized settings.

    Results: It was observed that clinical settings were generally less aggressive than the ones suggested by unconstrained model-based optimization, especially under asymmetrical stimulation. The DBS settings satisfying the constraints were close to the clinical values.

    Significance: The use of mathematical models to suggest optimal patient-specific DBS settings that observe technological and safety constraints can save time in clinical practice. It appears though that the considered safety constraints based on brain anatomy depend on the patient and further research into it is needed. This work highlights the need of specifying the brain volumes to be avoided by stimulation while optimizing the DBS amplitude, in contrast to minimizing general stimuli overspill, and applies the technique to a cohort of patients. It also stresses the importance of considering power consumption in DBS optimization, since it increases with the square of the stimuli amplitude and also critically affects battery life through pulse frequency and duty cycle.

  • 204.
    Cubo, Rubén
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control.
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Dept Biomed Technol Med Phys & IT, Uppsala, Sweden.
    Jiltsova, Elena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Andersson, Helena
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control.
    Medvedev, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control.
    Semi-Individualized electrical models in deep brain stimulation: A variability analysis2017In: 2017 IEEE Conference on Control Technology and Applications (CCTA), IEEE, 2017, p. 517-522Conference paper (Refereed)
    Abstract [en]

    Deep Brain Stimulation (DBS) is a well-established treatment in neurodegenerative diseases, e.g. Parkinson's Disease. It consists of delivering electrical stimuli to a target in the brain via a chronically implanted lead. To expedite the tuning of DBS stimuli to best therapeutical effect, mathematical models have been developed during recent years. The electric field produced by the stimuli in the brain for a given lead position is evaluated by numerically solving a Partial Differential Equation with the medium conductivity as a parameter. The latter is patient- and target-specific but difficult to measure in vivo. Estimating brain tissue conductivity through medical imaging is feasible but time consuming due to registration, segmentation and post-processing. On the other hand, brain atlases are readily available and processed. This study analyzes how alternations in the conductivity due to inter-patient variability or lead position uncertainties affect both the stimulation shape and the activation of a given target. Results suggest that stimulation shapes are similar, with a Dice's Coefficient between 93.2 and 98.8%, with a higher similarity at lower depths. On the other hand, activation shows a significant variation of 17 percentage points, with most of it being at deeper positions as well. It is concluded that, as long as the lead is not too deep, atlases can be used for conductivity maps with acceptable accuracy instead of fully individualized though medical imaging models.

  • 205.
    Cubo, Rubén
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control.
    Jiltsova, Elena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Andersson, Helena
    Medvedev, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control.
    Optimization of deep brain stimulation by means of a patient-specific mathematical model2016Conference paper (Refereed)
  • 206.
    Cunningham, Gregory
    et al.
    Univ Hosp Geneva, Dept Surg, Div Orthoped & Trauma Surg, Geneva, Switzerland..
    Zanchi, Davide
    Univ Hosp Geneva, Dept Imaging & Med Informat, Geneva, Switzerland..
    Emmert, Kirsten
    Univ Hosp Geneva, Dept Imaging & Med Informat, Geneva, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, Lausanne, Switzerland..
    Kopel, Rotem
    Univ Hosp Geneva, Dept Imaging & Med Informat, Geneva, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, Lausanne, Switzerland..
    Van De Ville, Dimitri
    Univ Hosp Geneva, Dept Imaging & Med Informat, Geneva, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, Lausanne, Switzerland..
    Laedermann, Alexandre
    Univ Hosp Geneva, Dept Surg, Div Orthoped & Trauma Surg, Geneva, Switzerland.;Univ Geneva, Fac Med, CH-1227 Geneva, Switzerland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, CH-1227 Geneva, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany.;Ctr Diagnost Radiol Carouge, Affidea, Carouge, Switzerland..
    Hoffmeyer, Pierre
    Univ Hosp Geneva, Dept Surg, Div Orthoped & Trauma Surg, Geneva, Switzerland.;Univ Geneva, Fac Med, CH-1227 Geneva, Switzerland..
    Neural Correlates of Clinical Scores in Patients with Anterior Shoulder Apprehension2015In: Medicine & Science in Sports & Exercise, ISSN 0195-9131, E-ISSN 1530-0315, Vol. 47, no 12, p. 2612-2620Article in journal (Refereed)
    Abstract [en]

    Introduction Anterior shoulder apprehension is a commonly reported complaint in anterior shoulder instability, which may lead to patient morbidity and impede shoulder function. It is the result of a cognitively complex mechanism, which includes anxiety, salience, fear, and anticipation. Purpose The aim of this prospective case-control study was to correlate five clinically established scores using functional magnetic resonance imaging to assess brain activation patterns in patients with apprehension related to anterior shoulder instability. Methods This study includes 28 consecutive male right-handed patients ( mean +/- SEM, 26.8 +/- 1.2 yr) with positive shoulder apprehension test and 10 healthy matched control participants without apprehension or a history of instability. Task- related and functional connectivity functional magnetic resonance imaging activation patterns occurring during apprehension video cue stimulation were correlated with five clinical tests and scores: Visual Analog Scale ( VAS), Rowe score for instability, Simple Shoulder Test, Subjective Shoulder Value ( SSV), and Western Ontario Shoulder Instability ( WOSI). Results Rowe, pain VAS, and WOSI scores correlated with prefrontal cortex, dorsolateral prefrontal cortex, dorsomedial prefrontal cortex, somatosensory area, and parieto-occipital and temporal areas (default mode network). Rowe score additionally correlated with frontal pole, anterior midcingulate cortex, and visual areas. Moreover, SSV correlated with task-related brain activity in the bilateral precentral gyrus, bilateral postcentral gyrus, and bilateral superior parietal lobe. Conclusions Overall, Rowe score provides the strongest link between shoulder apprehension and brain level alterations as it correlates with the highest number of independent components involving areas responsible for both motor and cognitive functions, whereas pain VAS and WOSI occupy an intermediately strong link recruiting less brain networks. Finally, Simple Shoulder Test and SSV have the weakest link at the brain level.

  • 207.
    Dalili, Danoob
    et al.
    Oxford Univ Hosp NHS Fdn Trust, Nuffield Orthopaed Ctr, Dept Radiol, Oxford, England; Kings Coll London, Sch Biomed Engn & Imaging Sci, London, England.
    Isaac, Amanda
    Kings Coll London, Sch Biomed Engn & Imaging Sci, London, England.
    Bazzocchi, Alberto
    IRCCS Ist Ortoped Rizzoli, Diagnost & Intervent Radiol, Bologna, Italy.
    Åström, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Bergh, Jonas
    Karolinska Univ Hosp Stockholm, Karolinska Inst, Dept Oncol, Stockholm, Sweden.
    Lalam, Radhesh
    Robert Jones & Agnes Hunt Orthopaed Hosp, Dept Radiol, Oswestry, Shrops, England.
    Weber, Marc-André
    Univ Med Ctr Rostock, Inst Diagnost & Intervent Radiol, Paediat Radiol & Neuroradiol, Rostock, Germany.
    Fritz, Jan
    NYU, Dept Radiol, Grossman Sch Med, 560 1St Ave, New York, NY 10016 USA.
    Mansour, Ramy
    Oxford Univ Hosp NHS Fdn Trust, Nuffield Orthopaed Ctr, Dept Radiol, Oxford, England.
    Interventional Techniques for Bone and Musculoskeletal Soft Tissue Tumors: Current Practices and Future Directions - Part I. Ablation2020In: Seminars in Musculoskeletal Radiology, ISSN 1089-7860, E-ISSN 1098-898X, Vol. 24, no 06, p. 692-709Article, review/survey (Refereed)
    Abstract [en]

    Musculoskeletal (MSK) image-guided oncologic intervention is an established field within radiology. Numerous studies have described its clinical benefits, safety, cost effectiveness, patient satisfaction, and improved quality of life, thereby establishing image-guided oncologic intervention as a preferred pathway in treating patients presenting with specific benign MSK tumors. But there is a paradigm shift on the horizon because these techniques may also support established pillars (surgery, systemic treatment, radiotherapy) in the treatment of malignant MSK tumors. Unlike benign tumors, where they are used as primary therapy lines with curative intent, such interventions can be selected for malignant tumors as adjuvant treatment in painful or unstable bone or soft tissue lesions or as more palliative therapy strategies. Using examples from our clinical practices, we elaborate on the benefits of applying a multidisciplinary approach (traditionally involving MSK radiologists, oncologists, orthopaedic surgeons, microbiologists, pathologists, physiotherapists, and pain management experts), ideally within a sarcoma treatment center to deliver a patient-specific therapy plan and illustrate methods to assess the benefits of this model of care. In this article, we review the current repertoire of ablation techniques, demonstrate why such procedures offer value-based alternatives to conventional treatments of specific tumors, and reflect on future directions. Additionally, we review the advantages and limitations of each technique and offer guidance to improve outcomes.

  • 208.
    Dalili, Danoob
    et al.
    Oxford Univ Hosp NHS Fdn Trust, Nuffield Orthopaed Ctr, Dept Radiol, Oxford, England.; Kings Coll London, Sch Biomed Engn & Imaging Sci, London, England.
    Isaac, Amanda
    Kings Coll London, Sch Biomed Engn & Imaging Sci, London, England.
    Cazzato, Roberto Luigi
    Hop Univ Strasbourg, Imagerie Intervent, Strasbourg, France.
    Åström, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Bergh, Jonas
    Karolinska Univ Hosp, Karolinska Inst, Dept Oncol, Stockholm, Sweden.
    Mansour, Ramy
    Oxford Univ Hosp NHS Fdn Trust, Nuffield Orthopaed Ctr, Dept Radiol, Oxford, England.
    Weber, Marc-Andre
    Univ Med Ctr Rostock, Inst Diagnost & Intervent Radiol Paediat Radiol &, Rostock, Germany.
    Garnon, Julien
    Hop Univ Strasbourg, Imagerie Intervent, Strasbourg, France.
    Gangi, Afshin
    Kings Coll London, Sch Biomed Engn & Imaging Sci, London, England.; Hop Univ Strasbourg, Imagerie Intervent, Strasbourg, France.
    Interventional Techniques for Bone and Musculoskeletal Soft Tissue Tumors: Current Practices and Future Directions - Part II. Stabilization2020In: Seminars in Musculoskeletal Radiology, ISSN 1089-7860, E-ISSN 1098-898X, Vol. 24, no 06, p. 710-725Article in journal (Refereed)
    Abstract [en]

    Percutaneous image-guided oncologic interventions have rapidly evolved over the last two decades as an independent strategy or used within a first-, second-, or even third-line strategy in the treatment of musculoskeletal (MSK) tumors. Abundant mostly nonrandomized publications have described the safety, efficacy, and reproducibility of implementing percutaneous therapies both with curative and palliative intent. In this article, we continue to share our experience in bone and MSK soft tissue interventions focusing on stabilization and combined ablation and stabilization. We propose a pathway and explore future directions of image-guided interventional oncology related to skeletal disease. We reflect on the advantages and limitations of each technique and offer guidance and pearls to improve outcomes. Representing patterns from our practices, we demonstrate the role of collaborative working within a multidisciplinary team, ideally within a dedicated tumor treatment center, to deliver patient-specific therapy plans that are value based and favored by patients when given the choice.

  • 209.
    Dalili, Danoob
    et al.
    Johns Hopkins Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA.;Oxford Univ Hosp NHS Fdn Trust, Nuffield Orthopaed Ctr, Oxford, England..
    Isaac, Amanda
    Kings Coll London, Sch Biomed Engn & Imaging Sci, London, England..
    Rashidi, Ali
    Johns Hopkins Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA..
    Åström, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ, Dept Immunol Genet & Pathol Oncol, Uppsala, Sweden..
    Fritz, Jan
    Johns Hopkins Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA.;NYU, Grossman Sch Med, Div Musculoskeletal Imaging, Dept Radiol, New York, NY USA..
    Image-guided Sports Medicine and Musculoskeletal Tumor Interventions: A Patient-Centered Model2020In: Seminars in Musculoskeletal Radiology, ISSN 1089-7860, E-ISSN 1098-898X, Vol. 24, no 03, p. 290-309Article in journal (Refereed)
    Abstract [en]

    The spectrum of effective musculoskeletal (MSK) interventions is broadening and rapidly evolving. Increasing demands incite a perpetual need to optimize services and interventions by maximizing the diagnostic and therapeutic yield, reducing exposure to ionizing radiation, increasing cost efficiency, as well as identifying and promoting effective procedures to excel in patient satisfaction ratings and outcomes. MSK interventions for the treatment of oncological conditions, and conditions related to sports injury can be performed with different imaging modalities; however, there is usually one optimal image guidance modality for each procedure and individual patient. We describe our patient-centered workflow as a model of care that incorporates state-of-the-art imaging techniques, up-to-date evidence, and value-based practices with the intent of optimizing procedural success and outcomes at a patient-specific level. This model contrasts interventionalist- and imaging modality-centered practices, where procedures are performed based on local preference and selective availability of imaging modality or interventionalists. We discuss rationales, benefits, and limitations of fluoroscopy, ultrasound, computed tomography, and magnetic resonance imaging procedure guidance for a broad range of image-guided MSK interventions to diagnose and treat sports and tumor-related conditions.

  • 210.
    Dam, G.
    et al.
    Aarhus Univ Hosp, Neuroendocrine Tumor Ctr Excellence, Dept Hepatol & Gastroenterol, Aarhus, Denmark.
    Grønbæk, H.
    Aarhus Univ Hosp, Neuroendocrine Tumor Ctr Excellence, Dept Hepatol & Gastroenterol, Aarhus, Denmark.
    Sørbye, H.
    Haukeland Hosp, Dept Oncol, Bergen, Norway.
    Thiis-Evensen, E.
    Natl Hosp Norway, Oslo Univ Hosp, Dept Transplantat Med, Neuroendocrine Tumor Ctr Excellence, Oslo, Norway.
    Paulsson, B.
    Novartis Sverige AB, Täby, Sweden.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Jensen, C.
    Rigshosp, Neuroendocrine Tumor Ctr Excellence, Dept Radiol, Copenhagen, Denmark.
    Ebbesen, D.
    Aarhus Univ Hosp, Neuroendocrine Tumor Ctr Excellence, Dept Radiol, Aarhus, Denmark.
    Knigge, U.
    Rigshosp, Neuroendocrine Tumor Ctr Excellence, Dept Endocrinol, Copenhagen, Denmark.;Rigshosp, Neuroendocrine Tumor Ctr Excellence, Dept Surg Gastroenterol, Copenhagen, Denmark.
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    A Prospective Nordic Study on the Use of Chromogranin A for the Prediction of Progression in Patients with Pancreatic and Small Intestinal Neuroendocrine Tumors2018In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 106, no Supplement: 1, p. 152-152Article in journal (Other academic)
  • 211.
    Dam, Gitte
    et al.
    Aarhus Univ Hosp, Dept Gastroenterol & Hepatol, Neuroendocrine Tumour Ctr Excellence, DK-8200 Aarhus N, Denmark..
    Gronbaek, Henning
    Aarhus Univ Hosp, Dept Gastroenterol & Hepatol, Neuroendocrine Tumour Ctr Excellence, DK-8200 Aarhus N, Denmark..
    Sorbye, Halfdan
    Haukeland Hosp, Dept Oncol, Bergen, Norway.;Univ Bergen, Clin Sci, Bergen, Norway..
    Evensen, Espen Thiis
    Oslo Univ Hosp, Rigshosp, Dept Transplantat Med, Neuroendocrine Tumor Ctr Excellence, Oslo, Norway..
    Paulsson, Bjorn
    Novartis Sverige AB, Kista, Sweden..
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Neuroendocrine Tumor Ctr Excellence, Uppsala, Sweden..
    Jensen, Claus
    Rigshosp, Neuroendocrine Tumour Ctr Excellence, Dept Radiol, Copenhagen, Denmark..
    Ebbesen, Dyveke
    Aarhus Univ Hosp, Neuroendocrine Tumour Ctr Excellence, Dept Radiol, Aarhus, Denmark..
    Knigge, Ulrich
    Rigshosp, Neuroendocrine Tumour Ctr Excellence, Dept Endocrinol, Copenhagen, Denmark.;Rigshosp, Neuroendocrine Tumour Ctr Excellence, Dept Surg Gastroenterol, Copenhagen, Denmark..
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Prospective Study of Chromogranin A as a Predictor of Progression in Patients with Pancreatic, Small-Intestinal, and Unknown Primary Neuroendocrine Tumors2020In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 110, no 3/4, p. 217-224Article in journal (Refereed)
    Abstract [en]

    Background: Retrospective studies are conflicting but most of them report that an increase in plasma chromogranin A (CgA) predicts tumor progression in neuroendocrine tumor (NET) patients. Prospectively, we investigated if a change in plasma CgA is associated with tumor burden changes in NET patients with disseminated disease. Methods: We included 239 patients treated at 5 NET centers from December 2010 to December 2013. CgA was measured within 6 weeks of a CT or MRI in a patient undergoing at least 2 scan examinations performed over a period of 1-24 months. In a post hoc analysis, CgA measured 3-6 months prior to the CT/MRI was analyzed. Changes in tumor size were evaluated by RECIST1.1. A 25% change in CgA was chosen to discriminate between increased, decreased, or unchanged levels. Results: In 671 events (2 CT/MRI scans and 2 corresponding CgA measurements), we found a weak positive correlation between the RECIST 1.1 responses and change in plasma CgA from baseline (Spearman's rank correlation coefficient: 0.15; p < 0.05). Of 304 events in the post hoc analysis, 58 showed progression, 228 showed stable disease, and 18 showed regression, with a median change in CgA of 19% (IQR: 57 to -20%), -12% (23 to -38%), and -73% (-55 to -83%), respectively. The correlation coefficient for all sites was 0.17 (p = 0.003), and it was 0.16 (p = 0.07), 0.18 (p = 0.04), and 0.20 (p = 0.21) for small-intestinal (n = 137), pancreatic (n = 123), and unknown primary NET (n = 40), respectively. In the 58 patients showing tumor progression, the sensitivity and specificity of an increased CgA concentration were 36 and 82%, respectively, with positive and negative predictive values of 32 and 85%. Conclusions: In this prospective study of gastroenteropancreatic NET patients, we observed only a weak association between a change in plasma CgA and changes in tumor burden. CgA as a single biomarker was thus inadequate to predict tumor progression.

  • 212.
    Dam, Gitte
    et al.
    Department of Hepatology & Gastroenterology, ENETS Center of Excellence, Aarhus University Hospital, & Department of Clinical Medicine, Aarhus University, Aarhus, Denmark..
    Grønbæk, Henning
    Department of Hepatology & Gastroenterology, ENETS Center of Excellence, Aarhus University Hospital, & Department of Clinical Medicine, Aarhus University, Aarhus, Denmark..
    Sundlöv, Anna
    Division of Oncology, Department of Clinical Sciences Lund, Lund University, Sweden..
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Petersen, Rene Horsleben
    Department of Cardiothoracic Surgery, ENETS Center of Excellence, Copenhagen University Hospital, Rigshospitalet, Denmark;f Department of Clinical Medicine, University of Copenhagen, Denmark..
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology. Department of Clinical Physiology and Nuclear Medicine, ENETS Center of Excellence & Cluster for Molecular Imaging, Copenhagen University Hospital–Rigshospitalet..
    Evensen, Espen-Thiis
    Department for Organ Transplantation, Oslo University Hospital, ENETS Center of Excellence, Rikshospitalet, Oslo, Norway..
    Sorbye, Halfdan
    Department of Oncology, Haukeland University Hospital, and Department of Clinical Science, University of Bergen, Bergen, Norway..
    Tabaksblat, Elizaveta
    Department of Oncology, ENETS Center of Excellence, Aarhus University Hospital, Aarhus, Denmark..
    Arveschoug, Anne Kirstine
    Department of Nuclear Medicine & PET Center, Aarhus University Hospital, ENETS Center of Excellence, Aarhus, Denmark..
    Mortensen, Jann
    Department. of Clinical Physiology and Nuclear Medicine, ENETS Center of Excellence & Cluster for Molecular Imaging, Copenhagen University Hospital–Rigshospitalet.; Department of Biomedical Sciences, University of Copenhagen, Denmark..
    Kjaer, Andreas
    Department. of Clinical Physiology and Nuclear Medicine, ENETS Center of Excellence & Cluster for Molecular Imaging, Copenhagen University Hospital–Rigshospitalet.; Department of Biomedical Sciences, University of Copenhagen, Denmark..
    Knigge, Ulrich
    Departments of Gastrointestinal Surgery and Clinical Endocrinology, ENETS Center of Excellence, Copenhagen University Hospital, Rigshospitalet, Denmark..
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Langer, Seppo W.
    Department of Oncology, ENETS Center of Excellence, Copenhagen University Hospital, Rigshospitalet, and Dept. of Clinical Medicine, University of Copenhagen, Denmark..
    Nordic 2023 guidelines for the diagnosis and treatment of lung neuroendocrine neoplasms.2023In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 62, no 5, p. 431-437Article in journal (Refereed)
    Abstract [en]

    Lung neuroendocrine neoplasms (NEN) are a heterogeneous population of neoplasms with different pathology, clinical behavior, and prognosis compared to the more common lung cancers. The diagnostic work-up and treatment of patients with lung- NEN has undergone major recent advances and new methods are currently being introduced into the clinic. These Nordic guidelines summarize and update the Nordic Neuroendocrine Tumor Group's current view on how to diagnose and treat lung NEN-patients and are meant to be useful in the daily practice for clinicians handling these patients. This review reflects our view of the current state of the art of diagnosis and treatment of patients with lung-NEN. Small cell lung carcinoma (SCLC) is not included in these guidelines.

  • 213.
    Danfors, Torsten
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Velickaite, Vilma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Canto Moreira, Nuno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    The role of methionine positron emission tomography in the evaluation of central nervous system tumors in children2016In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 36, no Suppl. 1, p. 394-395, article id 538Article in journal (Other academic)
  • 214. Daouacher, Georgios
    et al.
    von Below, Catrin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Gestblom, Charlotta
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Grzegorek, Rafael
    Wassberg, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Waldén, Mauritz
    Laparoscopic extended pelvic lymph node (LN) dissection as validation of the performance of [(11) C]-acetate positron emission tomography/computer tomography in the detection of LN metastasis in intermediate- and high-risk prostate cancer2016In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 118, no 1, p. 77-83Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To evaluate the accuracy of the radiopharmaceutical [(11) C]-acetate combined with positron emission tomography/computer tomography (acetate-PET/CT) in lymph node (LN) staging in newly diagnosed prostate cancer cases. A second aim was to evaluate the potential discriminative properties of acetate-PET/CT in clinical routine.

    PATIENTS AND METHODS: In a prospective comparative study, from July 2010 to June 2013, 53 men with newly histologically diagnosed intermediate- or high-risk prostate cancer underwent acetate-PET/CT investigation at one regional centre before laparoscopic extended pelvic LN dissection (ePLND) at one referral centre. The sensitivity, specificity and accuracy of acetate-PET/CT were calculated. Comparisons were made between true-positive and false-negative PET/CT cases to identify differences in the clinical parameters: PSA level, Gleason status, lymph metastasis burden and size, calculated risk of LN involvement, and curative treatment decisions.

    RESULTS: In all, 26 patients had surgically/histologically confirmed LN metastasis (LN+). Acetate-PET/CT was true positive in 10 patients, false positive in one, false negative in 16, and true negative in 26. The individual sensitivity was 38%, specificity 96%, and accuracy 68%. The acetate-PET/CT positive cases had significantly more involved LNs (mean 7.9 vs 2.4, P < 0.001) with larger cancer diameters (14.1 vs 4.9 mm, P = 0.001) and fewer eventually had treatment with curative intent (40% vs 94%, P <0.005), although we lack long-term outcome data.

    CONCLUSION: Acetate-PET/CT has too low a sensitivity for routine LN staging but the specificity is high. The acetate-PET/CT positive cases have a very high burden of LN spread.

  • 215. D'Arcangelo, M.
    et al.
    Ekman, S.
    Dougall, W.
    Branstetter, D.
    Bergqvist, M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Liv, Per Erik
    Chan, D.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Hirsch, F.
    Protein expression for receptor activator of NFkB (RANK) and its ligand (RANKL) in non-small cell lung cancer (NSCLC)2014In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 50, p. 114-114, article id 353Article in journal (Other academic)
  • 216.
    Davies, Mark
    et al.
    Royal Orthopaed Hosp, Dept Imaging, Bristol Rd South, Birmingham B31 2AP, W Midlands, England..
    Lalam, Radhesh
    Robert Jones & Agnes Hunt Orthopaed Hosp, Dept Imaging, Oswestry, Shrops, England..
    Woertler, Klaus
    Tech Univ Munich, Dept Imaging, Munich, Germany..
    Bloem, Johan L.
    Leiden Univ, Dept Imaging, Med Ctr, Leiden, Netherlands..
    Åström, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Dept Immunol Genet & Pathol Oncol, Uppsala, Sweden..
    Ten Commandments for the Diagnosis of Bone Tumors2020In: Seminars in Musculoskeletal Radiology, ISSN 1089-7860, E-ISSN 1098-898X, Vol. 24, no 03, p. 203-213Article in journal (Refereed)
    Abstract [en]

    The diagnosis of tumors and tumorlike lesions of bone is a routine part of both general and specialist radiologic practices. The spectrum of disorders ranges from the small incidental lesion to the potentially life-limiting malignancies whether primary or secondary. In this review, authored by experts from several European orthopaedic oncology centers, we present a collection of pieces of advice in the form of 10 commandments. Adherence in daily practice to this guidance should help minimize adverse patient experiences and outcomes.

  • 217. de Boer, Anneloes
    et al.
    Villa, Giulia
    Bane, Octavia
    Bock, Michael
    Cox, Eleanor F
    Dekkers, Ilona A
    Eckerbom, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fernández-Seara, Maria A
    Francis, Susan T
    Haddock, Bryan
    Hall, Michael E
    Hall Barrientos, Pauline
    Hermann, Ingo
    Hockings, Paul D
    Lamb, Hildo J
    Laustsen, Christoffer
    Lim, Ruth P
    Morris, David M
    Ringgaard, Steffen
    Serai, Suraj D
    Sharma, Kanishka
    Sourbron, Steven
    Takehara, Yasuo
    Wentland, Andrew L
    Wolf, Marcos
    Zöllner, Frank G
    Nery, Fabio
    Caroli, Anna
    Consensus-Based Technical Recommendations for Clinical Translation of Renal Phase Contrast MRI2022In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 55, no 2, p. 323-335Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Phase-contrast (PC) MRI is a feasible and valid noninvasive technique to measure renal artery blood flow, showing potential to support diagnosis and monitoring of renal diseases. However, the variability in measured renal blood flow values across studies is large, most likely due to differences in PC-MRI acquisition and processing. Standardized acquisition and processing protocols are therefore needed to minimize this variability and maximize the potential of renal PC-MRI as a clinically useful tool.

    PURPOSE: To build technical recommendations for the acquisition, processing, and analysis of renal 2D PC-MRI data in human subjects to promote standardization of renal blood flow measurements and facilitate the comparability of results across scanners and in multicenter clinical studies.

    STUDY TYPE: Systematic consensus process using a modified Delphi method.

    POPULATION: Not applicable.

    SEQUENCE FIELD/STRENGTH: Renal fast gradient echo-based 2D PC-MRI.

    ASSESSMENT: An international panel of 27 experts from Europe, the USA, Australia, and Japan with 6 (interquartile range 4-10) years of experience in 2D PC-MRI formulated consensus statements on renal 2D PC-MRI in two rounds of surveys. Starting from a recently published systematic review article, literature-based and data-driven statements regarding patient preparation, hardware, acquisition protocol, analysis steps, and data reporting were formulated.

    STATISTICAL TESTS: Consensus was defined as ≥75% unanimity in response, and a clear preference was defined as 60-74% agreement among the experts.

    RESULTS: Among 60 statements, 57 (95%) achieved consensus after the second-round survey, while the remaining three showed a clear preference. Consensus statements resulted in specific recommendations for subject preparation, 2D renal PC-MRI data acquisition, processing, and reporting.

    DATA CONCLUSION: These recommendations might promote a widespread adoption of renal PC-MRI, and may help foster the set-up of multicenter studies aimed at defining reference values and building larger and more definitive evidence, and will facilitate clinical translation of PC-MRI.

    LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.

  • 218. de Herder, Wouter W
    et al.
    Capdevila, Jaume
    Unmet Needs in the Field of Neuroendocrine Neoplasms of the Gastrointestinal Tract, Pancreas, and Respiratory System: Reports by the ENETS Group.2019In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 108, no 1, p. 5-6Article in journal (Refereed)
    Abstract [en]

    On the 10th and 11th of November 2016, 54 international experts in the field of neuroendocrine neoplasms (NEN) of the gastrointestinal tract, pancreas, and respiratory system met in Munich, Germany, to discuss and determine unmet needs in this field. The participating experts were Advisory Board members and invited guests of the European Neuroendocrine Tumor Society (ENETS). The Board members were medical specialists with different clinical or preclinical backgrounds, basic scientists, specialized nurses, and patient representatives.

    According to the Oxford dictionary, “unmet” refers to something (here, a need) which has not been achieved or fulfilled. The NEN expert subgroups succeeded in producing 6 reports on what they identified as the most relevant unmet needs in NEN. They identified several limitations of the current tumor classification, grading, and staging systems for almost all NEN subtypes.

    Apart from the historical separation regarding origin into foregut, midgut, and hindgut, other subentities have now been recognized, each requiring a more tailored approach. There is still a general lack of predictive and prognostic markers, in samples of both tumor tissue and surrogate tissues such as the blood. Tumor visualization making use of radiology and nuclear medicine has seen impressive advances in recent years. However, with regard to determining tumor (metastases) responses, there is still debate as to how best to achieve this with different imaging modalities.

    In spite of more treatment options (locoregional and systemic) being available for metastatic NENs, help is needed to select appropriate treatment strategies (sequencing) and there is also a need for more effective treatments. For some tumor entities, watchful waiting might be considered (e.g., in the case of small pancreatic NENs) but, again, the lack of reliable markers makes it difficult to decide which tumors should undergo resection and which should be monitored only. There are currently no registered or approved adjuvant treatment options for the period after curative resection of some of the isolated or locally advanced NENs (e.g., of the pancreas, appendix, and rectum). It is also unclear which patients might benefit from adjuvant treatment. The follow-up of patients with NENs remains a poorly studied area and is based on loose empirical international guidelines or institutional opinion.

    All of these unmet needs in the field of NENs exponentially increase the complexity of conducting well-designed clinical and translational studies to resolve these issues, with multidisciplinary and international efforts such as the current one led by ENETS being the only way to move forward. We invite all Readers of Neuroendocrinology interested in the field of NENs to study the series of 6 articles reporting on unmet needs in the field of NENs

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  • 219.
    de la Vega, Maria Pagnon
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Michno, Wojciech
    Univ Gothenburg, Dept Psychiat & Neurochem, S-43180 Gothenburg, Sweden.;UCL, Dept Neurosci, London WC1E 6BT, England..
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Guener, Goekhan
    Tech Univ Munich, German Ctr Neurodegenerat Dis DZNE & Neuroprote, Sch Med, Klinikum Rechts Isar, D-81377 Munich, Germany..
    Zielinski, Mara
    Forschungszentrum Julich, Inst Biol Informat Proc, Julich Ctr Struct Biol, Struct Biochem IBI 7, D-52425 Julich, Germany.;Forschungszentrum Julich, JuStruct, Julich Ctr Struct Biol, D-52425 Julich, Germany..
    Degerman Gunnarsson, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Brundin, RoseMarie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Soderberg, Linda
    BioArctic AB, S-11251 Stockholm, Sweden..
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Nilsson, Lars N. G.
    Univ Oslo, Dept Pharmacol, N-0316 Oslo, Norway.;Oslo Univ Hosp, N-0316 Oslo, Norway..
    Erlandsson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Willbold, Dieter
    Forschungszentrum Julich, Inst Biol Informat Proc, Julich Ctr Struct Biol, Struct Biochem IBI 7, D-52425 Julich, Germany.;Forschungszentrum Julich, JuStruct, Julich Ctr Struct Biol, D-52425 Julich, Germany.;Heinrich Heine Univ Dusseldorf, Inst Phys Biol, D-40225 Dusseldorf, Germany.;State Univ, Res Ctr Mol Mech Aging & Age Related Dis, Moscow Inst Phys & Technol, Dolgoprudnyi 141701, Russia..
    Mueller, Stephan A.
    Tech Univ Munich, German Ctr Neurodegenerat Dis DZNE & Neuroprote, Sch Med, Klinikum Rechts Isar, D-81377 Munich, Germany..
    Schroeder, Gunnar F.
    Forschungszentrum Julich, Inst Biol Informat Proc, Julich Ctr Struct Biol, Struct Biochem IBI 7, D-52425 Julich, Germany.;Forschungszentrum Julich, JuStruct, Julich Ctr Struct Biol, D-52425 Julich, Germany.;Heinrich Heine Univ Dusseldorf, Phys Dept, D-40225 Dusseldorf, Germany..
    Hanrieder, Jorg
    Univ Gothenburg, Dept Psychiat & Neurochem, S-43180 Gothenburg, Sweden.;UCL, Dept Neurodegenerat Dis, Queen Sq Inst Neurol, London WC1N 3BG, England..
    Lichtenthaler, Stefan F.
    Tech Univ Munich, German Ctr Neurodegenerat Dis DZNE & Neuroprote, Sch Med, Klinikum Rechts Isar, D-81377 Munich, Germany.;Munich Cluster Syst Neurol SyNergy, D-81377 Munich, Germany..
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sehlin, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    The Uppsala APP deletion causes early onset autosomal dominant Alzheimer's disease by altering APP processing and increasing amyloid beta fibril formation2021In: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 13, no 606, article id eabc6184Article in journal (Refereed)
    Abstract [en]

    Point mutations in the amyloid precursor protein gene (APP) cause familial Alzheimer's disease (AD) by increasing generation or altering conformation of amyloid beta (A beta). Here, we describe the Uppsala APP mutation (Delta 690-695), the first reported deletion causing autosomal dominant AD. Affected individuals have an age at symptom onset in their early forties and suffer from a rapidly progressing disease course. Symptoms and biomarkers are typical of AD, with the exception of normal cerebrospinal fluid (CSF) A beta 42 and only slightly pathological amyloid-positron emission tomography signals. Mass spectrometry and Western blot analyses of patient CSF and media from experimental cell cultures indicate that the Uppsala APP mutation alters APP processing by increasing beta-secretase cleavage and affecting alpha-secretase cleavage. Furthermore, in vitro aggregation studies and analyses of patient brain tissue samples indicate that the longer form of mutated A beta, A beta Upp1-42(Delta 19-24), accelerates the formation of fibrils with unique polymorphs and their deposition into amyloid plaques in the affected brain.

  • 220.
    Dean, Anastasia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Umeå Univ, Dept Surg & Perioperat Sci, Surg, Umeå, Sweden.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Marek, Kuzniar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Grima, Matthew
    Univ Malta, Fac Med & Surg, L Imsida, Malta.
    Zuccon, Gianmarco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Lindström, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Uppsala Academic hospital, Section of vascular surgery, 75185 Uppsala, Sweden.
    In Situ Laser Fenestrations of Aortic Endografts for Emergent Aortic Disease2023In: Annals of Vascular Surgery, ISSN 0890-5096, E-ISSN 1615-5947, Vol. 93, p. 329-337Article in journal (Refereed)
    Abstract [en]

    Background: In situ laser fenestration (ISLF) is a novel endovascular technique which allows customization of a standard stent graft to a patient's anatomy. While most reported cases involve revascularization of the left subclavian artery (LSA), some centers have now reported their initial experience treating branches of the visceral aorta for aortic aneurysms. The aim of this study is to examine the adoption of ISLF in emergent aortic pathology at a specialized aortic center.

    Methods: Between December 2020 and February 2022, all patients who underwent ISLF as part of endovascular intervention for complex aortic pathology at a university hospital were iden-tified. Cases were collected from a prospective aortic database with additional information ob-tained from a retrospective review of electronic hospital records.

    Results: Fifteen patients (11 men and 4 women) underwent emergency ISLF, with a median age of 76 years. Eleven presented with symptomatic or ruptured aortic aneurysms, three with acute complicated aortic dissections and 1 aortic traumatic transection. Most aortic an-eurysms were thoraco-abdominal (n = 7), with 1 arch, 1 thoracic, 1 supra-renal, and one-juxta-renal aortic aneurysm. ISLF was performed to revascularize the LSA in 8 cases, and branches of the reno-visceral aorta in 7 cases. All LSA ISLF cases had left brachial ar -te ry exposure. Femoral access was percutaneous in 14 of 15 cases. Technical success was 96.3% (26/27)). Median ischemic times were: superior mesenteric artery 7 min, renal ar-teries 22 min, and celiac trunk 43.5 min. There were 2 early aortic/fenestration related rein-terventions. There was no stroke and 1 death caused by heparin-induced thrombocytopenia within 30 days. The majority of patients did not require intensive care admission (n = 8). The median intensive care unit stay was 0 days and hospital length of stay 18 days. There was no fenestration endoleak or reintervention post discharge with a median follow-up of 168 days.

    Conclusions: ISLF is a promising new technique that can show excellent technical results in experienced aortic centers, even during the learning curve. While custom-made devices with reinforced fenestrations are preferred in nonemergent situations, ISLF is a feasible option for complex aortic pathology in the acute setting when open surgery is not feasible.

  • 221.
    Delle Fave, G.
    et al.
    Osped St Andrea, Dept Digest & Liver Dis, Rome, Italy.;Univ Roma La Sapienza, Dept Digest & Liver Dis, Via Grottarossa 1035, IT-00189 Rome, Italy..
    O'Toole, D.
    St Vincents Univ, NET Ctr, Dublin, Ireland.;St James Hosp, Dept Clin Med, Dublin 8, Ireland.;Univ Dublin Trinity Coll, Dublin 2, Ireland..
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Taal, B.
    Netherlands Canc Ctr, Lijnden, Netherlands..
    Ferolla, P.
    Univ Perugia, Umbria Reg Canc Network, NET Ctr, I-06100 Perugia, Italy..
    Ramage, J. K.
    Hampshire Hosp NHS Trust, Dept Gastroenterol, Winchester, Hants, England..
    Ferone, D.
    Univ Genoa, Dept Endocrine & Metab Sci, Genoa, Italy..
    Ito, T.
    Kyushu Univ Hosp, Pancreat Dis Branch, Fukuoka 812, Japan..
    Weber, W.
    Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave, New York, NY 10021 USA..
    Zheng-Pei, Z.
    Beijing Union Med Coll Hosp, Dept Endocrinol, Beijing, Peoples R China..
    De Herder, W. W.
    Erasmus MC, Div Endocrinol, Dept Internal Med, Rotterdam, Netherlands..
    Pascher, A.
    Charite, Dept Visceral & Transplant Surg, Campus Virchow Klinikum, D-13353 Berlin, Germany..
    Ruszniewski, P.
    Beaujon Hosp, Dept Gastroenterol, Clichy, France..
    ENETS Consensus Guidelines Update for Gastroduodenal Neuroendocrine Neoplasms2016In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 103, no 2, p. 119-124Article in journal (Refereed)
  • 222.
    Dewey, Marc
    et al.
    Charite Univ Med Berlin, Dept Radiol, Berlin, Germany; Berlin Inst Hlth, Berlin, Germany; DZHK German Ctr Cardiovasc Res Partner Site, Berlin, Germany; .
    Siebes, Maria
    Univ Amsterdam, Med Ctr, Dept Biomed Engn & Phys Translat Physiol, Amsterdam, Netherlands.
    Kachelrieß, Marc
    German Canc Res Ctr, Div Xray Imaging & CT, Heidelberg, Germany.
    Kofoed, Klaus F
    Univ Copenhagen, Rigshosp, Dept Cardiol & radiol, Ctr Heart, Copenhagen, Denmark.
    Maurovich-Horvat, Pál
    Semmelwe Univ, Heart & Vasc Ctr, MTA SE Cardiovasc Imaging Res Grp, Budapest, Hungary.
    Nikolaou, Konstantin
    Univ Klinikum Tubingen, Radiol Klin, Diagnost & Intervent Radiol, Tubingen, Germany.
    Bai, Wenjia
    Imperial Coll London, Dept Comp, Biomed Image Anal Grp, London, England.
    Kofler, Andreas
    Charite Univ Med Berlin, Dept Radiol, Berlin, Germany.
    Manka, Robert
    Univ Zurich, Univ Zurich Hosp, Inst Diagnost & Intervent Radiol, Zurich, Switzerland; Univ Zurich, Univ Zurich Hosp, Dept Cardiol, Zurich, Switzerland ;Univ Zurich, Inst Biomed Engn, Zurich, Switzerland; Swiss Fed Inst Technol, Zurich, Switzerland.
    Kozerke, Sebastian
    Univ Zurich, Inst Biomed Engn, Zurich, Switzerland; Swiss Fed Inst Technol, Zurich, Switzerland.
    Chiribiri, Amedeo
    Kings Coll London, Sch Biomed Engn & Imaging Sci, Dept Cardiovasc Imaging, London, England.
    Schaeffter, Tobias
    Kings Coll London, Sch Biomed Engn & Imaging Sci, Dept Cardiovasc Imaging, London, England; Phys Tech Bundesanstalt, Med Phys & Metrol Informat Technol, Berlin, Germany.
    Michallek, Florian
    Charite Univ Med Berlin, Dept Radiol, Berlin, Germany.
    Bengel, Frank
    Hannover Med Sch, Klin Nukl Med, Hannover, Germany.
    Nekolla, Stephan
    Tech Univ Munich, Klinikum Rechts Isar, Nukl Med Klin & Poliklin, DZHK German Ctr Cardiovasc Res,Partner Site Munic, Munich, Germany.
    Knaapen, Paul
    Vrije Univ Amsterdam Med Ctr, Dept Cardiol, Amsterdam, Netherlands.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Med Phys, Uppsala, Sweden.
    Senior, Roxy
    Royal Brompton Hosp London, Dept Cardiol, London, England.
    Tang, Meng-Xing
    Imperial Coll London, Dept Bioengn, London, England.
    Piek, Jan J
    Univ Amsterdam, Heart Ctr, Med Ctr, Amsterdam, Netherlands.
    van de Hoef, Tim
    Univ Amsterdam, Heart Ctr, Med Ctr, Amsterdam, Netherlands.
    Martens, Johannes
    Wurzburg Univ Clin, Comprehens Heart Failure Ctr, Dept Cellular & Mol Imaging, Wurzburg, Germany.
    Schreiber, Laura
    Wurzburg Univ Clin, Comprehens Heart Failure Ctr, Dept Cellular & Mol Imaging, Wurzburg, Germany.
    Clinical quantitative cardiac imaging for the assessment of myocardial ischaemia2020In: Nature Reviews Cardiology, ISSN 1759-5002, E-ISSN 1759-5010, Vol. 17, no 7, p. 427-450Article in journal (Refereed)
    Abstract [en]

    Cardiac imaging has a pivotal role in the prevention, diagnosis and treatment of ischaemic heart disease. SPECT is most commonly used for clinical myocardial perfusion imaging, whereas PET is the clinical reference standard for the quantification of myocardial perfusion. MRI does not involve exposure to ionizing radiation, similar to echocardiography, which can be performed at the bedside. CT perfusion imaging is not frequently used but CT offers coronary angiography data, and invasive catheter-based methods can measure coronary flow and pressure. Technical improvements to the quantification of pathophysiological parameters of myocardial ischaemia can be achieved. Clinical consensus recommendations on the appropriateness of each technique were derived following a European quantitative cardiac imaging meeting and using a real-time Delphi process. SPECT using new detectors allows the quantification of myocardial blood flow and is now also suited to patients with a high BMI. PET is well suited to patients with multivessel disease to confirm or exclude balanced ischaemia. MRI allows the evaluation of patients with complex disease who would benefit from imaging of function and fibrosis in addition to perfusion. Echocardiography remains the preferred technique for assessing ischaemia in bedside situations, whereas CT has the greatest value for combined quantification of stenosis and characterization of atherosclerosis in relation to myocardial ischaemia. In patients with a high probability of needing invasive treatment, invasive coronary flow and pressure measurement is well suited to guide treatment decisions. In this Consensus Statement, we summarize the strengths and weaknesses as well as the future technological potential of each imaging modality.

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  • 223.
    Dhara, Ashis Kumar
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Arids, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Interactive segmentation of glioblastoma for post-surgical treatment follow-up2018In: Proc. 24th International Conference on Pattern Recognition, IEEE, 2018, p. 1199-1204Conference paper (Refereed)
  • 224.
    Dhara, Ashis Kumar
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction.
    Ayyalasomayajula, Kalyan Ram
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction.
    Arvids, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Segmentation of Post-operative Glioblastoma in MRI by U-Net with Patient-specific Interactive Refinement2019In: Brainlesion: Glioma, Multiple Sclerosis, Stroke and Traumatic Brain Injuries / [ed] Crimi A., Bakas S., Kuijf H., Keyvan F., Reyes M & van Walsum T., Cham: Springer, 2019, p. 115-122Conference paper (Refereed)
    Abstract [en]

    Accurate volumetric change estimation of glioblastoma is very important for post-surgical treatment follow-up. In this paper, an interactive segmentation method was developed and evaluated with the aim to guide volumetric estimation of glioblastoma. U-Net based fully convolutional network is used for initial segmentation of glioblastoma from post contrast MR images. The max flow algorithm is applied on the probability map of U-Net to update the initial segmentation and the result is displayed to the user for interactive refinement. Network update is performed based on the corrected contour by considering patient specific learning to deal with large context variations among different images. The proposed method is evaluated on a clinical MR image database of 15 glioblastoma patients with longitudinal scan data. The experimental results depict an improvement of segmentation performance due to patient specific fine-tuning. The proposed method is computationally fast and efficient as compared to state-of-the-art interactive segmentation tools. This tool could be useful for post-surgical treatment follow-up with minimal user intervention.

  • 225. Di Carli, Marcelo F
    et al.
    Gormsen, Lars C
    Chareonthaitawee, Panithaya
    Johnson, Geoffrey B
    Beanlands, Rob
    DeKemp, Rob
    Schindler, Thomas
    Gropler, Robert
    Kulkarni, Harshad
    McNeely, Parren
    Soman, Prem
    Oz, Orhan
    Zaha, Vlad
    Sorensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Harms, Heinrich
    Orlandi, Cesare
    Vandenbroucke, Emily
    Udelson, James
    Rationale and design of the RAPID-WATER-FLOW trial: Radiolabeled perfusion to identify coronary artery disease using water to evaluate responses of myocardial FLOW.2024In: Journal of Nuclear Cardiology, ISSN 1071-3581, E-ISSN 1532-6551, Vol. 31, p. 101779-, article id 101779Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The objective of this study was to determine the diagnostic performance of 15O-water positron emission tomography (PET) myocardial perfusion imaging to detect coronary artery disease (CAD) using the truth-standard of invasive coronary angiography (ICA) with fractional flow reserve (FFR) or instantaneous wave-Free Ratio (iFR) or coronary computed tomography angiogram (CCTA).

    BACKGROUND: 15O-water has a very high first-pass extraction that allows accurate quantification of myocardial blood flow and detection of flow-limiting CAD. However, the need for an on-site cyclotron and lack of automated production at the point of care and relatively complex image analysis protocol has limited its clinical use to date.

    METHODS: The RAPID WATER FLOW study is an open-label, multicenter, prospective investigation of the accuracy of 15O-water PET to detect obstructive angiographic and physiologically significant stenosis in patients with suspected CAD. The study will include the use of an automated system for producing, dosing, and injecting 15O-water and enrolling approximately 215 individuals with suspected CAD at approximately 10 study sites in North America and Europe. The primary endpoint of the study is the diagnostic sensitivity and specificity of the 15O-water PET study using the truth-standard of ICA with FFR or iFR to determine flow-limiting stenosis, or CCTA to rule out CAD and incorporating a quantitative analytic platform developed for the 15O-water PET acquisitions. Sensitivity and specificity are to be considered positive if the lower bound of the 95% confidence interval is superior to the threshold of 60% for both, consistent with prior registration studies. Subgroup analyses include assessments of diagnostic sensitivity, specificity, and accuracy in female, obese, and diabetic individuals, as well as in those with multivessel disease. All enrolled individuals will be followed for adverse and serious adverse events for up to 32 hours after the index PET scan. The study will have >90% power (one-sided test, α = 0.025) to test the hypothesis that sensitivity and specificity of 15O-water PET are both >60%.

    CONCLUSIONS: The RAPID WATER FLOW study is a prospective, multicenter study to determine the diagnostic sensitivity and specificity of 15O-water PET as compared to ICA with FFR/iFR or CCTA. This study will introduce several novel aspects to imaging registration studies, including a more relevant truth standard incorporating invasive physiologic indexes, coronary CTA to qualify normal individuals for eligibility, and a more quantitative approach to image analysis than has been done in prior pivotal studies.

    CLINICAL TRIAL REGISTRATION INFORMATION: Clinical-Trials.gov (#NCT05134012).

  • 226.
    Diamanti, Klev
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Visvanathar, Robin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Pereira, Maria J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Cavalli, Marco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pan, Gang
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kumar, Chanchal
    Skrtic, Stanko
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical AB, Mölndal, Sweden.
    Komorowski, Jan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics. Institute of Computer Science, PAN, Warsaw, Poland.
    Wadelius, Claes
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical AB, Mölndal, Sweden.
    Integration of whole-body [18F]FDG PET/MRI with non-targeted metabolomics can provide new insights on tissue-specific insulin resistance in type 2 diabetes2020In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1, article id 8343Article in journal (Refereed)
    Abstract [en]

    Alteration of various metabolites has been linked to type 2 diabetes (T2D) and insulin resistance. However, identifying significant associations between metabolites and tissue-specific phenotypes requires a multi-omics approach. In a cohort of 42 subjects with different levels of glucose tolerance (normal, prediabetes and T2D) matched for age and body mass index, we calculated associations between parameters of whole-body positron emission tomography (PET)/magnetic resonance imaging (MRI) during hyperinsulinemic euglycemic clamp and non-targeted metabolomics profiling for subcutaneous adipose tissue (SAT) and plasma. Plasma metabolomics profiling revealed that hepatic fat content was positively associated with tyrosine, and negatively associated with lysoPC(P-16:0). Visceral adipose tissue (VAT) and SAT insulin sensitivity (Ki), were positively associated with several lysophospholipids, while the opposite applied to branched-chain amino acids. The adipose tissue metabolomics revealed a positive association between non-esterified fatty acids and, VAT and liver Ki. Bile acids and carnitines in adipose tissue were inversely associated with VAT Ki. Furthermore, we detected several metabolites that were significantly higher in T2D than normal/prediabetes. In this study we present novel associations between several metabolites from SAT and plasma with the fat fraction, volume and insulin sensitivity of various tissues throughout the body, demonstrating the benefit of an integrative multi-omics approach.

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  • 227.
    Diamanti, Klev
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.
    Visvanathar, Robin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Pereira, Maria J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Cavalli, Marco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pan, Gang
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Kumar, Chanchal
    Translational Science & Experimental Medicine, Early Cardiovascular, Renal and Metabolism, R&D BioPharmaceuticals, AstraZeneca; Karolinska Institute/AstraZeneca Integrated CardioMetabolic Centre (KI/AZ ICMC), Department of Medicine.
    Stanko, Stanko
    Pharmaceutical Technology & Development, AstraZeneca AB; Department of Medicine, Sahlgrenska University Hospital, Gothenburg.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lind, Lars
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wadelius, Claes
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Komorowski, Jan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.
    Integration of whole-body PET/MRI with non-targeted metabolomics provides new insights into insulin sensitivity of various tissuesManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Alteration of various metabolites has been linked to type 2 diabetes (T2D) and insulin resistance. However, identifying significant associations between metabolites and tissue-specific alterations is challenging and requires a multi-omics approach. In this study, we aimed at discovering associations of metabolites from subcutaneous adipose tissue (SAT) and plasma with the volume, the fat fraction (FF) and the insulin sensitivity (Ki) of specific tissues using [18F]FDG PET/MRI.

    Materials and Methods: In a cohort of 42 subjects with different levels of glucose tolerance (normal, prediabetes and T2D) matched for age and body-mass-index (BMI) we calculated associations between parameters of whole-body FDG PET/MRI during clamp and non-targeted metabolomics profiling for SAT and blood plasma. We also used a rule-based classifier to identify a large collection of prevalent patterns of co-dependent metabolites that characterize non-diabetes (ND) and T2D.

    Results: The plasma metabolomics profiling revealed that hepatic fat content was positively associated with tyrosine, and negatively associated with lysoPC(P-16:0). Ki in visceral adipose tissue (VAT) and SAT, was positively associated with several species of lysophospholipids while the opposite applied to branched-chain amino acids (BCAA) and their intermediates. The adipose tissue metabolomics revealed a positive association between non-esterified fatty acids and, VAT and liver Ki. On the contrary, bile acids and carnitines in adipose tissue were inversely associated with VAT Ki. Finally, we presented a transparent machine-learning model that predicted ND or T2D in “unseen” data with an accuracy of 78%.

    Conclusions: Novel associations of several metabolites from SAT and plasma with the FF, volume and insulin senstivity of various tissues throughout the body were discovered using PET/MRI and a new integrative multi-omics approach. A promising computational model that predicted ND and T2D with high certainty, suggested novel non-linear interdependencies of metabolites.

  • 228. Dogra, Prerna
    et al.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Molecular Imaging, Uppsala University Hospital.
    Juhlin, C. Christofer
    Calissendorff, Jan
    Falhammar, Henrik
    Bancos, Irina
    Rare benign adrenal lesions2023In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 188, no 4, p. 407-420Article in journal (Refereed)
    Abstract [en]

    While most benign lesions of the adrenal glands represent either an adrenocortical adenoma or a myelolipoma, the advent and frequent use of high-resolution radiological investigations have led to relatively increased incidental discovery of rare adrenal lesions, specifically benign adrenal cysts, adrenal ganglioneuromas, adrenal schwannomas, adrenal hemorrhage, and adrenal calcifications. Radiological characteristics of the different rare benign adrenal lesions could vary from distinct to indeterminate. Though typically nonfunctional, these rare lesions require evaluation for adrenal hormone excess, as they may phenotypically appear similar to pheochromocytoma or adrenocortical carcinoma and could sometimes be associated with or conceal an underlying functional adrenal tumor. In this review, we discuss the various rare benign adrenal lesions, emphasizing a practical perspective.

  • 229. Dromain, Clarisse
    et al.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Najran, Pavan
    Vidal Trueba, Hector
    Dioguardi Burgio, Marco
    Crona, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Opalinska, Marta
    Carvalho, Luciana
    Franca, Regis
    Borg, Philip
    Vietti Violi, Naik
    Schaefer, Niklaus
    Lopez, Carlos
    Pezzutti, Daniela
    de Mestier, Louis
    Lamarca, Angela
    Costa, Frederico
    Pavel, Marianne
    Ronot, Maxime
    Tumour Growth Rate to predict the outcome of patients with Neuroendocrine Tumours: Performance and sources of variability2021In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 111, no 9, p. 831-839Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Tumor growth rate (TGR), percentage of change in tumor volume/month, has been previously identified as an early radiological biomarker for treatment monitoring in neuroendocrine tumors (NETs) patients. We assessed the performance and reproducibility of TGR 3 months (TGR3m) as a predictor factor of progression-free survival (PFS), including the impact of imaging method and reader variability.

    METHODS: Baseline and 3-months (±1month) CT/MRI images from patients with advanced, grade 1-2 NETs were retrospectively reviewed by 2 readers. Influence of number of targets, tumor burden and location of lesion on the performance of TGR3m to predict PFS was assessed by uni/multivariable Cox regression analysis. Agreement between readers was assessed by the Lin's concordance coefficient (LCC) and Kappa (KC).

    RESULTS: A total of 790 lesions were measured in 222 patients. Median PFS was 22.9 months. On univariable analysis, number of lesions (</≥4), tumor burden and presence of liver metastases were significantly correlated to PFS. On multivariate analysis, ≥4 lesions (HR:1.89 (95%CI:1.01-3.57)), TGR3m ≥0.8%/m (HR:4.01 (95%CI:2.31-6.97)) and watch-and-wait correlated with shorter PFS. No correlation was found between TGR3m and number of lesions (rho:-0.2; p-value:0.1930). No difference in mean TGR3m across organs was shown (p-value:0.6). Concordance between readers was acceptable (LCC:0.52 (95%CI:0.38-0.65); KC:0.57 agreement:81.55%). TGR3m remained a significant prognostic factor when data from second reader was employed (HR:4.35 (95%CI:2.44-7.79); p-value<0.001) and regardless his expertise (HR:1.21 (95%CI:0.70-2.09); p-value:0.493).

    DISCUSSION/CONCLUSION: TGR3m is a robust and early radiological biomarker able to predict PFS. It may be used to identify patients with advanced NETs who require closer radiological follow-up.

  • 230.
    Dromain, Clarisse
    et al.
    Lausanne Univ Hosp, Dept Radiol, CH-1011 Lausanne, Switzerland.;Univ Lausanne, CH-1011 Lausanne, Switzerland.
    Vullierme, Marie-Pierre
    Univ Paris, Hop Univ Paris Nord Val Seine, Hop Beaujon, Dept Radiol, Paris, France.
    Hicks, Rodney J.
    Univ Melbourne, Peter MacCallum Canc Ctr, Neuroendocrine Serv, Melbourne, Vic, Australia.;Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia.
    Prasad, Vikas
    Univ Ulm, Dept Nucl Med, Ulm, Germany.
    O'Toole, Dermot
    St Jamess & St Vincents Univ Hosp, Dublin, Ireland.;Trinity Coll Dublin, Dublin, Ireland.
    de Herder, Wouter W.
    Erasmus MC, Dept Internal Med, Sect Endocrinol, Rotterdam, Netherlands..
    Pavel, Marianne
    Univ Klinikum Erlangen, Dept Med 1, Erlangen, Germany.
    Faggiano, Antongiulio
    Sapienza Univ Rome, St Andrea Hosp, Dept Clin & Mol Med Sapienza, Rome, Italy.
    Kos-Kudla, Beata
    Med Univ Silesia, Dept Endocrinol & Neuroendocrine Tumors, Katowice, Poland.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Krejs, Guenter J.
    Med Univ Graz, Dept Internal Med, Div Gastroenterol & Hepatol, Graz, Austria.
    Grande, Enrique
    MD Anderson Canc Ctr Madrid, Dept Med Oncol, Madrid, Spain.
    Niederle, Bruno
    Med Univ Vienna, Dept Gen Surg, Vienna, Austria.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    ENETS standardized (synoptic) reporting for radiological imaging in neuroendocrine tumours2022In: Journal of neuroendocrinology, ISSN 0953-8194, E-ISSN 1365-2826, Vol. 34, no 3 SI, article id 13044Article in journal (Refereed)
    Abstract [en]

    This expert consensus document represents an initiative by the European Neuroendocrine Tumor Society (ENETS) to provide guidance for synoptic reporting of radiological examinations critical to the diagnosis, grading, staging and treatment of neuroendocrine neoplasms (NENs). Template drafts for initial tumor staging and follow-up by computed tomography (CT) and magnetic resonance imaging (MRI) were established, based on existing institutional and organisational reporting templates relevant for NEN imaging, and applying the RadLex lexicon of radiological information (Radiological Society of North America), for consistency regarding the radiological terms. During the ENETS Scientific Advisory Board meeting 2018, the template drafts were subject to iterative interdisciplinary discussions among experts in imaging, surgery, gastroenterology, oncology and pathology. Members of the imaging group stated a strong preference for a combination of limited and standardised options by way of drop-down menus. Separate templates were produced for the initial work-up and for follow-up, respectively. To provide a detailed description of the radiological findings of the primary tumor and its local extension and spread, different templates were developed for bronchial, pancreatic and gastrointestinal NENs for CT and MRI, respectively. Each template was structured in 10 sections: clinical details, comparative imaging modality, acquisition technique, primary tumor findings, regional lymph node metastases, distant metastases, TNM classification, reference lesions according to RECIST 1.1, additional findings and conclusion. Two templates were developed for follow-up, for CT and MRI, respectively, and were specifically focused on assessment of therapy response. These included a qualitative response assessment, such as decrease of vascularisation and presence of necrosis, and a quantitative assessment according to RECIST 1.1 and the modified RECIST (mRECIST) for assessing tumor response following transarterial chemoembolisation.

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  • 231.
    Dubbelboer, Ilse R
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Lilienberg, Elsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Karalli, Amar
    Karolinska Univ Hosp Huddinge, Dept Radiol, Stockholm.; Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm.
    Axelsson, Rimma
    Karolinska Univ Hosp Huddinge, Dept Radiol, Stockholm.; Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm.
    Brismar, Torkel B
    Karolinska Univ Hosp Huddinge, Dept Radiol, Stockholm.; Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm.
    Ebeling Barbier, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Norén, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Duraj, Frans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Mikael, Hedeland
    Natl Vet Inst SVA, Dept Chem Environm & Feed Hyg, Uppsala.
    Bondesson, Ulf
    Natl Vet Inst SVA, Dept Chem Environm & Feed Hyg, Uppsala.
    Sjögren, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Stål, Per
    Karolinska Inst, Dept Internal Med Huddinge, Unit Gastroenterol, Stockholm.; Karolinska Univ Hosp Huddinge, Dept Digest Dis, Stockholm.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lennernäs, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Reply to "Comment on 'In Vivo Drug Delivery Performance of Lipiodol-Based Emulsion or Drug-Eluting Beads in Patients with Hepatocellular Carcinoma'"2018In: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392, Vol. 15, no 1, p. 336-340Article in journal (Refereed)
  • 232.
    Dubol, Manon
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Neuropsychopharmacology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Immenschuh, Jana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Neuropsychopharmacology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Jonasson, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Takahashi, Kayo
    RIKEN Ctr Biosyst Dynam Res, Kobe, Japan..
    Niwa, Takashi
    RIKEN Ctr Biosyst Dynam Res, Kobe, Japan.;Tokyo Med & Dent Univ, Inst Biomat & Bioengn, Tokyo, Japan..
    Hosoya, Takamitsu
    RIKEN Ctr Biosyst Dynam Res, Kobe, Japan.;Tokyo Med & Dent Univ, Inst Biomat & Bioengn, Tokyo, Japan..
    Roslin, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    Watanabe, Yasuyoshi
    RIKEN Ctr Biosyst Dynam Res, Kobe, Japan..
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Biegon, Anat
    SUNY Stony Brook, Dept Radiol & Neurol, Sch Med, Stony Brook, NY USA..
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Reproductive Health.
    Comasco, Erika
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Neuropsychopharmacology.
    Acute nicotine exposure blocks aromatase in the limbic brain of healthy women: A [11C]cetrozole PET study2023In: Comprehensive Psychiatry, ISSN 0010-440X, E-ISSN 1532-8384, Vol. 123, article id 152381Article in journal (Refereed)
    Abstract [en]

    Background: Of interest to women's mental health, a wealth of studies suggests sex differences in nicotine addiction and treatment response, but their psychoneuroendocrine underpinnings remain largely unknown. A pathway involving sex steroids could indeed be involved in the behavioural effects of nicotine, as it was found to inhibit aromatase in vitro and in vivo in rodents and non-human primates, respectively. Aromatase regulates the synthesis of oestrogens and, of relevance to addiction, is highly expressed in the limbic brain.

    Methods: The present study sought to investigate in vivo aromatase availability in relation to exposure to nicotine in healthy women. Structural magnetic resonance imaging and two [11C]cetrozole positron emission tomography (PET) scans were performed to assess the availability of aromatase before and after administration of nicotine. Gonadal hormones and cotinine levels were measured. Given the region-specific expression of aromatase, a ROI -based approach was employed to assess changes in [11C]cetrozole non-displaceable binding potential.

    Results: The highest availability of aromatase was found in the right and left thalamus. Upon nicotine exposure, [11C]cetrozole binding in the thalamus was acutely decreased bilaterally (Cohen's d =-0.99). In line, cotinine levels were negatively associated with aromatase availability in the thalamus, although as non-significant trend.

    Conclusions: These findings indicate acute blocking of aromatase availability by nicotine in the thalamic area. This suggests a new putative mechanism mediating the effects of nicotine on human behaviour, particularly relevant to sex differences in nicotine addiction.

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  • 233.
    Dubol, Manon
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Neuropsychopharmacology.
    Stiernman, Louise
    Umeå Univ, Dept Clin Sci, S-90185 Umeå, Sweden..
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lanzenberger, Rupert
    Med Univ Vienna, Dept Psychiat & Psychotherapy, A-1090 Vienna, Austria..
    Neill Epperson, C.
    Univ Colorado, Dept Psychiat, Dept Family Med, Sch Med, Anschutz Med Campus, Aurora, CO 80045 USA..
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Reproductive Health.
    Bixo, Marie
    Umeå Univ, Dept Clin Sci, S-90185 Umeå, Sweden..
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Reproductive Health. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Differential grey matter structure in women with premenstrual dysphoric disorder: evidence from brain morphometry and data-driven classification2022In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 12, no 1, article id 250Article in journal (Refereed)
    Abstract [en]

    Premenstrual dysphoric disorder (PMDD) is a female-specific condition classified in the Diagnostic and Statical Manual-5th edition under depressive disorders. Alterations in grey matter volume, cortical thickness and folding metrics have been associated with a number of mood disorders, though little is known regarding brain morphological alterations in PMDD. Here, women with PMDD and healthy controls underwent magnetic resonance imaging (MRI) during the luteal phase of the menstrual cycle. Differences in grey matter structure between the groups were investigated by use of voxel- and surface-based morphometry. Machine learning and multivariate pattern analysis were performed to test whether MRI data could distinguish women with PMDD from healthy controls. Compared to controls, women with PMDD had smaller grey matter volume in ventral posterior cortices and the cerebellum (Cohen's d = 0.45-0.76). Region-of-interest analyses further indicated smaller volume in the right amygdala and putamen of women with PMDD (Cohen's d = 0.34-0.55). Likewise, thinner cortex was observed in women with PMDD compared to controls, particularly in the left hemisphere (Cohen's d = 0.20-0.74). Classification analyses showed that women with PMDD can be distinguished from controls based on grey matter morphology, with an accuracy up to 74%. In line with the hypothesis of an impaired top-down inhibitory circuit involving limbic structures in PMDD, the present findings point to PMDD-specific grey matter anatomy in regions of corticolimbic networks. Furthermore, the results include widespread cortical and cerebellar regions, suggesting the involvement of distinct networks in PMDD pathophysiology.

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  • 234.
    Dubol, Manon
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comasco: Neuropsychopharmacology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lanzenberger, Rupert
    Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
    Epperson, C. Neill
    Department of Psychiatry, Department of Family Medicine, University of Colorado School of Medicine-Anschutz Medical Campus, Aurora, USA.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Reproductive Health.
    Comasco, Erika
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comasco: Neuropsychopharmacology.
    Grey matter correlates of affective and somatic symptoms of premenstrual dysphoric disorder2022In: Scientific Reports, E-ISSN 2045-2322, Vol. 12, no 1, article id 5996Article in journal (Refereed)
    Abstract [en]

    Ovarian hormones fluctuations across the menstrual cycle are experienced by about 58% of women in their fertile age. Maladaptive brain sensitivity to these changes likely leads to the severe psychological, cognitive, and physical symptoms repeatedly experienced by women with Premenstrual Dysphoric Disorder (PMDD) during the late luteal phase of the menstrual cycle. However, the neuroanatomical correlates of these symptoms are unknown. The relationship between grey matter structure and PMDD symptom severity was delineated using structural magnetic resonance imaging during the late luteal phase of fifty-one women diagnosed with PMDD, combined with Voxel- and Surface-Based Morphometry, as well as subcortical volumetric analyses. A negative correlation was found between depression-related symptoms and grey matter volume of the bilateral amygdala. Moreover, the severity of affective and somatic PMDD symptoms correlated with cortical thickness, gyrification, sulcal depth, and complexity metrics, particularly in the prefrontal, cingulate, and parahippocampal gyri. The present findings provide the first evidence of grey matter morphological characteristics associated with PMDD symptomatology in brain regions expressing ovarian hormone receptors and of relevance to cognitive-affective functions, thus potentially having important implications for understanding how structural brain characteristics relate to PMDD symptomatology.

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  • 235.
    Ebeling Barbier, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Garske-Román, Ulrike
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sandström, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Selective internal radiation therapy in patients with progressive neuroendocrine liver metastases2016In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, no 8, p. 1425-1431Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To evaluate the safety and efficacy of selective internal radiation therapy (SIRT) in patients with unresectable liver metastases from neuroendocrine tumours (NETLMs).

    METHODS: This retrospective study included 40 patients with progressive NETLMs (22 women, 18 men, mean age 61.6 years) who underwent SIRT with (90)Y-labelled resin microspheres. Tumour response was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) on CT or MR images. Medical records were reviewed.

    RESULTS: In the 40 patients, 54 evaluable SIRT procedures were performed, 33 to the right liver lobe (mean activity 1.31 GBq), 13 to the left lobe (mean activity 0.85 GBq), and 8 to both lobes (mean activity 1.61 GBq). Late follow-up imaging (mean 20 months) was performed after 44 of the treatments. Objective tumour response and disease control rates were 54 % (29 of 54 treatments) and 94 % (51 treatments), respectively, at the early follow-up examination (mean 3 months) and 34 % (15 treatments) and 57 % (25 treatments), respectively at the late follow-up examination. Mean overall survival from the first SIRT was 34,8 months and survival rates at 1, 2, 3 and 5 years were 76 %, 59 %, 52 % and 35 % respectively. Adverse effects were generally mild and easily manageable, except in one patient who died from radiation-induced liver failure. Of the 45 patients, 18 (45 %) had received peptide receptor radionuclide therapy (PRRT) prior to SIRT.

    CONCLUSION: SIRT with (90)Y-labelled resin microspheres is a safe and effective treatment for patients with progressive NETLM, and also for those who have received prior PRRT.

  • 236.
    Ebeling Barbier, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Heindryckx, Femke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Lennernäs, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Limitations and Possibilities of Transarterial Chemotherapeutic Treatment of Hepatocellular Carcinoma2021In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, no 23, article id 13051Article, review/survey (Refereed)
    Abstract [en]

    Because diagnostic tools for discriminating between hepatocellular carcinoma (HCC) and advanced cirrhosis are poor, HCC is often detected in a stage where transarterial chemoembolization (TACE) is the best treatment option, even though it provides a poor survival gain. Despite having been used worldwide for several decades, TACE still has many limitations. First, there is a vast heterogeneity in the cellular composition and metabolism of HCCs as well as in the patient population, which renders it difficult to identify patients who would benefit from TACE. Often the delivered drug does not penetrate sufficiently selectively and deeply into the tumour and the drug delivery system is not releasing the drug at an optimal clinical rate. In addition, therapeutic effectiveness is limited by the crosstalk between the tumour cells and components of the cirrhotic tumour microenvironment. To improve this widely used treatment of one of our most common and deadly cancers, we need to better understand the complex interactions between drug delivery, local pharmacology, tumour targeting mechanisms, liver pathophysiology, patient and tumour heterogeneity, and resistance mechanisms. This review provides a novel and important overview of clinical data and discusses the role of the tumour microenvironment and lymphatic system in the cirrhotic liver, its potential response to TACE, and current and possible novel DDSs for locoregional treatment.

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  • 237.
    Ebeling Barbier, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lundin, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Melki, Vilyam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Percutaneous Closure in Transfemoral Aortic Valve Implantation: A Single-Centre Experience2015In: Cardiovascular and Interventional Radiology, ISSN 0174-1551, E-ISSN 1432-086X, Vol. 38, no 6, p. 1438-1443Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To report the experience of a percutaneous closure device used for transfemoral transcatheter aortic valve implantation (TAVI) in an unselected patient and operator population.

    MATERIALS AND METHODS: Eighty-two consecutive patients (32 women, 50 men) who underwent transfemoral TAVI between September 2009 and February 2014 at our hospital were retrospectively reviewed for percutaneous closure device (PCD) failure, vascular complications, and bleeding. The diameter and calcification of the common femoral artery (CFA) and the thickness of the subcutaneous fat layer in the groin were assessed on computed tomography images.

    RESULTS: The incidences of PCD failure and minor and major vascular complications were 19.5 % (n = 16/82), 19.5 % (n = 16/82), and 7 % (n = 6/82) respectively. 8.5 % (n = 7/82) had a minor perioperative bleeding, 6 % (n = 5/82) had a major bleeding, and none had any life-threatening bleeding. When PCD failed, haemostasis was obtained with fascia suturing, covered stent placement, or with surgical cutdown. Thirty-day mortality and 1-year all-cause mortality were 8.5 % (n = 7/82) and 19.5 % (n = 16/82), respectively. In a multiple regression analysis, the CFA diameter and the presence of severe calcification were independently related to PCD failure (correlation coefficient = -0.24, p = 0.027 and correlation coefficient = 0.23, p = 0.036, respectively).

    CONCLUSION: PCD failure was related to a small CFA diameter and to a severely calcified CFA. Failure could largely be managed with minimally invasive techniques such as covered stents or fascia suturing.

  • 238.
    Ebeling Barbier, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Eriksson, Lars-Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sangfelt, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Sheikhi, Reza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Vessby, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Placement of a transjugular intrahepatic portosystemic shunt in addition to recanalization of acute and chronic portomesenteric vein occlusions: a retrospective evaluation2020In: Acta Radiologica, Supplement, ISSN 0365-5954, Acta Radiologica Open, Vol. 9, no 10, article id 2058460120964074Article in journal (Refereed)
    Abstract [en]

    Background: Portomesenteric vein thrombosis may be life-threatening due to bowel ischemia caused by venous stasis, or variceal bleeding caused by portal hypertension. Purpose: To evaluate the effectiveness and safety of recanalization combined with transjugular intrahepatic portosystemic shunt in acute and chronic portomesenteric vein thrombosis in patients with and without liver cirrhosis. Material and Methods: 21 consecutive patients (5 women, 16 men; mean 48 years) with portomesenteric vein thrombosis (8 acute, 13 chronic) treated at the Interventional Radiology department between March 2014 and September 2018 were retrospectively reviewed. The main portal vein was completely obliterated and the portomesenteric vein thrombosis extended into the superior mesenteric vein in all patients. The portomesenteric vein thromboses were recanalized transhepatically, a transjugular intrahepatic portosystemic shunt was inserted, thrombectomy was performed in acute portomesenteric vein thrombosis, and angioplasty with or without additional stenting was performed in chronic portomesenteric vein thrombosis. Results: Recanalization was successful in 8/8 patients (100%) with acute portomesenteric vein thrombosis, and in 11/13 patients (85%) with chronic portomesenteric vein thrombosis. In 12 patients, blood flow was restored in one session. Several sessions were more frequently needed in patients with acute portomesenteric vein thrombosis compared to those with chronic portomesenteric vein thrombosis (p = 0.003). Re-occlusion occurred and was recanalized in 10/19 patients and was more frequent in patients with chronic (n = 8/11) than on those with acute (n = 2/8) portomesenteric vein thrombosis (p = 0.04). Adverse events occurred in five patients. There was no 30-day mortality. Conclusion: Recanalization and insertion of a transjugular intrahepatic portosystemic shunt is safe and effective in patients with acute and chronic portomesenteric vein thrombosis with or without cirrhosis. Recanalization was more likely to stay patent in acute compared with chronic portomesenteric vein thrombosis.

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  • 239.
    Ebeling Barbier, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Themudo, Raquel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bjerner, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Long-term prognosis of unrecognized myocardial infarction detected with cardiovascular magnetic resonance in an elderly population2016In: Journal of Cardiovascular Magnetic Resonance, ISSN 1097-6647, E-ISSN 1532-429X, Vol. 18, no 1, p. 43-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Individuals with unrecognized myocardial infarctions (UMIs) detected with cardiovascular magnetic resonance (CMR) constitute a recently defined group whose prognosis has not been fully evaluated. However, increasing evidence indicate that these individuals may be at considerable cardiovascular risk. The aim of the present study was to investigate the prognostic impact of CMR detected UMIs for major adverse cardiac events (MACE) in community living elderly individuals.

    METHODS: Late gadolinium enhancement CMR was performed in 248 randomly chosen 70-year-olds. Individuals with myocardial infarction (MI) scars, with or without a hospital diagnosis of MI were classified as recognized MI (RMI) or UMI, respectively. Medical records and death certificates were scrutinized. MACE was defined as cardiac death, non-fatal MI, a new diagnosis of angina pectoris, or symptom-driven coronary artery revascularization.

    RESULTS: During follow-up (mean 11 years) MACE occurred in 10 % (n = 18/182) of the individuals without MI scars, in 20 % (n = 11/55) of the individuals with UMI, and in 45 % (n = 5/11) of the individuals with RMI, with a significant difference between the UMI group and the group without MI scars (p = 0.045), and between the RMI group and the group without MI scars (p = 0.0004). Cardiac death and/or non-fatal MI occurred in 15, 5, and 3 of the individuals in the NoMI, UMI, and RMI group respectively. Hazards ratios for MACE adjusted for risk factors and sex were 2.55 (95 % CI 1.20-5.42; p = 0.015) for UMI and 3.28 (95 % CI1.16-9.22; p = 0.025) for RMI.

    CONCLUSIONS: The presence of a CMR detected UMI entailed a more than double risk for MACE in community living 70-year-old individuals.

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  • 240.
    Ebeling-Barbier, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Garske-Roman, Ulrike
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Antonodimitrakis, Pantelis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Sandström, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Radioembolization with 90Y-Labelled Resin Microspheres in Patients with Liver Metastases from Neuroendocrine Tumors2015In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 102, no 1-2, p. 136-137Article in journal (Other academic)
  • 241.
    Ebrahimi, Sheida
    et al.
    Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA..
    Lundström, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA.;Univ Uppsala Hosp, Ctr Med Imaging, S-75185 Uppsala, Sweden..
    Batasin, Summer J.
    Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA..
    Hedlund, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Stålberg, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Reproductive Health.
    Ehman, Eric C.
    Dept Radiol, Mayo Clin, Rochester, MN 55905 USA..
    Sheth, Vipul R.
    Stanford Univ, Dept Radiol, Palo Alto, CA 94305 USA..
    Iranpour, Negaur
    Stanford Univ, Dept Radiol, Palo Alto, CA 94305 USA..
    Loubrie, Stephane
    Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA..
    Schlein, Alexandra
    Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA..
    Rakow-Penner, Rebecca
    Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA.;Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA..
    Application of PET/MRI in Gynecologic Malignancies2024In: Cancers, ISSN 2072-6694, Vol. 16, no 8, article id 1478Article, review/survey (Refereed)
    Abstract [en]

    Simple Summary This article reviews the value of Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) in evaluating female pelvic cancers. It also provides a comparative analysis of PET/MRI with other imaging modalities in the context of female pelvic malignancies and outlines their respective strengths and limitations. The aim of this narrative review is to introduce to clinicians up and coming technology and how it may be valuable to their assessment of female pelvic cancers.Abstract The diagnosis, treatment, and management of gynecologic malignancies benefit from both positron emission tomography/computed tomography (PET/CT) and MRI. PET/CT provides important information on the local extent of disease as well as diffuse metastatic involvement. MRI offers soft tissue delineation and loco-regional disease involvement. The combination of these two technologies is key in diagnosis, treatment planning, and evaluating treatment response in gynecological malignancies. This review aims to assess the performance of PET/MRI in gynecologic cancer patients and outlines the technical challenges and clinical advantages of PET/MR systems when specifically applied to gynecologic malignancies.

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  • 242.
    Eckerbom, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Assessment of Renal Physiology Using Functional MRI2022Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Kidney injury is a major cause of morbidity and mortality throughout the world, leading to substantial individual suffering and to a heavy financial burden for the society. A large number of common conditions such as diabetes, hypertension, autoimmune diseases and infections are highly associated with kidney injury. Disturbances in renal perfusion and oxygenation are believed to be involved in the pathogenesis of kidney injury and are therefore of interest to investigate closely. Studies to further the understanding of kidney injury have previously most often involved invasive procedures or ionizing radiation which have limited studies in humans due to ethical reasons. Hence there is a need to explore and implement noninvasive, nonionizing techniques to carry out human studies of renal physiology in health and disease. This thesis aimed to do so using a number of novel, noninvasive magnetic resonance imaging (MRI) techniques. 

    In the first study of this thesis, we scanned the kidneys of healthy volunteers with noninvasive MRI and found significant differences between the renal cortex, inner and outer medulla regarding blood flow, oxygenation, water diffusion and tissue characteristics. In the second study we scanned the kidneys with MRI and collected urine from healthy volunteers every fourth hour for 24 hours and found circadian variations for total renal blood flow as well as for a number of urinary parameters. Renal oxygenation was stable with only small diurnal variations. In the third study we implemented the MRI techniques used in study 1 and 2 and one additional MRI technique in COVID-19 patients admitted to the intensive care unit for severe respiratory failure, with and without acute kidney injury (AKI). We found significantly reduced total renal blood flow as well as  cortical and medullary perfusion in patients with AKI compared to patients without AKI. No significant difference was found between the two groups regarding renal oxygenation, water diffusion or tissue characteristics. In the fourth study we used the same MRI techniques as in study 3 to follow up patients previously treated for severe COVID-19 without and with different degrees of AKI. We found significantly reduced apparent diffusion coefficient (ADC) and total renal blood flow in patients that had high grade AKI compared to patients that did not have AKI during hospitalization for COVID-19. No significant difference regarding oxygenation was found between the groups.

    In conclusion, this thesis shows that it is possible to use multiparametric noninvasive MRI for renal studies in clinical practice. 

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  • 243.
    Eckerbom, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Hansell, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Cox, Eleanor
    Buchanan, Charlotte
    Weis, Jan
    Department of Medical Physics, Uppsala University Hospital.
    Palm, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Francis, Susan
    Liss, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Circadian variation in renal blood flow and kidney function in healthy volunteers monitored with noninvasive magnetic resonance imaging2020In: American Journal of Physiology - Renal Physiology, ISSN 1931-857X, E-ISSN 1522-1466, Vol. 319, no 6, p. F966-F978Article in journal (Refereed)
    Abstract [en]

    Circadian regulation of kidney function is involved in maintaining whole body homeostasis, and dysfunctional circadian rhythm can potentially be involved in disease development. Magnetic resonance imaging (MRI) provides reliable and reproducible repetitive estimates of kidney function noninvasively without the risk of adverse events associated with contrast agents and ionizing radiation. The purpose of this study was to estimate circadian variations in kidney function in healthy human subjects with MRI and to relate the findings to urinary excretions of electrolytes and markers of kidney function. Phase-contrast imaging, arterial spin labeling, and blood oxygen level-dependent transverse relaxation rate (R2*) mapping were used to assess total renal blood flow and regional perfusion as well as intrarenal oxygenation in eight female and eight male healthy volunteers every fourth hour during a 24-h period. Parallel with MRI scans, standard urinary and plasma parameters were quantified. Significant circadian variations of total renal blood flow were found over 24 h, with increasing flow from noon to midnight and decreasing flow during the night. In contrast, no circadian variation in intrarenal oxygenation was detected. Urinary excretions of electrolytes, osmotically active particles, creatinine, and urea all displayed circadian variations, peaking during the afternoon and evening hours. In conclusion, total renal blood flow and kidney function, as estimated from excretion of electrolytes and waste products, display profound circadian variations, whereas intrarenal oxygenation displays significantly less circadian variation.

  • 244.
    Eckerbom, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Hansell, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Cox, Eleanor
    Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom.
    Buchanan, Charlotte
    Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom.
    Weis, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Palm, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Francis, Susan
    Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom.
    Liss, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Multiparametric assessment of renal physiology in healthy volunteers using noninvasive magnetic resonance imaging2019In: American Journal of Physiology - Renal Physiology, ISSN 1931-857X, E-ISSN 1522-1466, Vol. 316, no 4, p. F693-F702Article in journal (Refereed)
    Abstract [en]

    Non-invasive methods of magnetic resonance imaging (MRI) can quantify parameters of kidney function. The main purpose of this study was to determine baseline values of such parameters in healthy volunteers. In 28 healthy volunteers (15 females, 13 males), Arterial Spin Labeling (ASL) to estimate regional renal perfusion, Blood Oxygen Level Dependent (BOLD) transverse relaxation rate (R2*) to estimate oxygenation, and Apparent Diffusion Coefficient (ADC), true diffusion (D) and longitudinal relaxation time (T1) to estimate tissue properties were determined bilaterally in the cortex, outer and inner medulla. Additionally, phase contrast (PC) MRI was applied in the renal arteries to quantify total renal blood flow. The results demonstrated profound gradients of perfusion, ADC and D with highest values in the kidney cortex and a decrease towards the inner medulla. R2* and T1 were lowest in kidney cortex and increased towards the inner medulla. Total renal blood flow correlated with body surface area, body mass index and renal volume. Similar patterns in all investigated parameters were observed in females and males. In conclusion, non-invasive MRI provides useful tools to evaluate intra renal differences in blood flow, perfusion, diffusion, oxygenation and structural properties of the kidney tissue. As such, this experimental approach has the potential to advance our current understanding regarding normal physiology and the pathological processes associated with acute and chronic kidney disease.

  • 245.
    Eckerbom, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Luther, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Cox, Eleanor
    Sir Peter Mansfield Imaging Centre, School of Physics & Astronomy, University of Nottingham, Nottingham, UK .
    Weis, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Hultström, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Lipcsey, Miklos
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Palm, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Francis, Susan
    Sir Peter Mansfield Imaging Centre, School of Physics & Astronomy, University of Nottingham, Nottingham, UK .
    Liss, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Reduced Renal Apparent Diffusion Coefficient at Follow Up after COVID-19 Associated Acute Kidney InjuryManuscript (preprint) (Other academic)
    Abstract [en]

    Severe Corona virus disease 2019 (COVID-19) with acute kidney injury (AKI) increases the risk of developing chronic kidney disease (CKD). In the present study we aimed to investigate the effects of severe COVID-19 on renal blood flow, perfusion, oxygenation and tissue characteristics in recovered patients using noninvasive multiparametric magnetic resonance imaging (MRI). Twenty-two patients, previously treated in the intensive care unit for COVID-19 were stratified depending on their degree of AKI during hospitalization. Patients without AKI were matched with those with AKI grade 1 and AKI grade 3 regarding age, sex, height, weight, body surface area (BSA) and body mass index (BMI). All patients had a normal measurement of creatinine within two years before hospitalization. An MRI scan was conducted 21±6 weeks after the first day of intensive care. Cortical and medullary apparent diffusion coefficients (ADC) were significantly lower in the ´AKI grade 3´group compared to the ´no AKI´ group, 1.83±0.11 vs 2.16±0.13 x 10-3 mm2/s (p=0.001) for cortex and 1.84±0.04 vs 2.09±0.13 x 10-3 mm2/s (p=0.007) for medulla. Also, total renal blood flow (tRBF) and global perfusion were significantly lower in the ´AKI grade 3´ group compared to the ´no AKI´ group. No differences regarding renal oxygenation, T1 or T2 were found. 

    We conclude that patients treated for severe COVID-19 with high grade AKI, show decreased cortical and medullary ADC and reduced total renal blood flow and global perfusion compared to similar patients without AKI at follow up approximately five months after intensive care. These findings might indicate incipient development of renal fibrosis. 

  • 246.
    Edfeldt, Katarina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Nursing Research.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Granberg, Dan
    Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden.
    Lagergren, Pernilla
    Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden.
    Thiis‐Evensen, Espen
    Department of Transplantation Medicine Oslo University Hospital Oslo Norway.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Andersson, Camilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Improved health‐related quality of life during peptide receptor radionuclide therapy in patients with neuroendocrine tumours2023In: Journal of neuroendocrinology, ISSN 0953-8194, E-ISSN 1365-2826, Vol. 35, no 10Article in journal (Refereed)
    Abstract [en]

    Neuroendocrine tumours (NETs) can arise in different locations in the body, and may give rise to hormonal symptoms, which amongst other factors may affect patients' health-related quality of life (HRQoL). Up to four cycles of peptide receptor radionuclide therapy (PRRT) have been shown effective for symptom alleviation and prolonging progression-free survival. The aim of this study was to assess the patient's perspective regarding changes in their HRQoL during PRRT. HRQoL was assessed using the questionnaires for cancer in general, EORTC QLQ-C30, and the gastrointestinal NET-specifically EORTC QLQ-GINET21. Patients with NET (n = 204) rated their HRQoL before PRRT cycles one and four. The medical records of patients were reviewed and their HRQoL was compared to a matched reference population (n = 4910). HRQoL was found to improve during PRRT in aspects of global quality of life; role, social, and emotional functioning, and multiple symptom relief. Potential risk groups for worse HRQoL during PRRT were patients with overweight (BMI >25) who completed four cycles of PRRT and older patients (>65 years old). In conclusion, we found that PRRT improves HRQoL in patients with NETs. The results of this study may be used to improve person-centred care.

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  • 247.
    Edholm, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Karlsson, F Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Haenni, Arvo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Changes in liver volume and body composition during 4 weeks of low calorie diet before laparoscopic gastric bypass2015In: Surgery for Obesity and Related Diseases, ISSN 1550-7289, E-ISSN 1878-7533, Vol. 11, no 3, p. 602-606Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Weight loss before laparoscopic Roux-en-Y gastric bypass (LRYGB) is desirable, because it can reduce liver volume and thereby facilitate the procedure. The optimal duration of a low-calorie diet (LCD) has not been established. The objective of this study was to assess changes in liver volume and body composition during 4 weeks of LCD.

    METHODS:

    Ten women (aged 43±8.9 years, 114±12.1 kg, and body mass index 42±2.6 kg/m2) were examined on days 0, 3, 7, 14, and 28 after commencing the LCD. At each evaluation, body composition was assessed through bioelectric impedance analysis, and liver volume and intrahepatic fat content were assessed by magnetic resonance imaging. Serum and urine samples were obtained. Questionnaires regarding quality of life and LCD-related symptoms were administered.

    RESULTS:

    In total, mean weight decreased by 7.4±1.2 kg (range 5.7-9.1 kg), and 71% of the weight loss consisted of fat mass according to bioelectric impedance analysis. From day 0 to day 3, the weight loss (2.0 kg) consisted mainly of water. Liver volume decreased by 18%±6.2%, from 2.1 to 1.7 liters (P<.01), during the first 2 weeks with no further change thereafter. A continuous 51%±16% decrease was seen in intrahepatic fat content. Systolic blood pressure, insulin, and lipids improved, while liver enzymes, glucose levels, and quality of life were unaffected.

    CONCLUSION:

    A significant decrease in liver volume (18%) occurred during the first 2 weeks of LCD treatment, and intrahepatic fat gradually decreased throughout the study period. A preoperative 2-week LCD treatment seems sufficient in similar patients.

  • 248.
    Ehrstedt, Christoffer
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology.
    Canto Moreira, Nuno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Casar Borota, Olivera
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Strömberg, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology.
    Ahlsten, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology.
    Glioneuronal tumors in childhood - Before and after surgery. A long-term follow-up study2017In: Epilepsy & Behavior, ISSN 1525-5050, E-ISSN 1525-5069, Vol. 72, p. 82-88Article in journal (Refereed)
    Abstract [en]

    Aim: To give a detailed description of the long-term outcome of a cohort of children with glioneuronal tumors regarding pre-and postsurgical factors, including "dual" and "double" pathology, seizure freedom, and psychosocial outcome.

    Methods: During a fifteen-year period (1995-2009), all patients (age 0-17.99 years) with a glioneuronal brain tumor diagnosed and treated at Uppsala University Children's Hospital were identified from the National Brain Tumor Registry and the National Epilepsy Surgery Registry. Hospital medical records were reviewed and neuroradiological and neuropathological findings were re-evaluated. A cross-sectional long-term follow-up prospective evaluation, including an interview, neurologic examination, and electroencephalogram, was accomplished in patients accepting participants in the study.

    Results: A total of 25 out of 28 (89%) eligible patientswere included. The M: F ratiowas 1.5: 1. Mean follow-up time after surgery was 12.1 years (range 5.0-19.3). Twenty patients were adults (N18 years) at follow-up. Seizure freedomwas achieved in 64%. Gross total resection (GTR) was the only preoperative factor significantly correlating to seizure freedom (p= 0.027). Thirty-eight percent were at some time postoperatively admitted for a psychiatric evaluation. There was a trend towards both higher educational level and employment status in adults who became seizure free.

    Conclusion: Long-termoutcome is good regarding seizure freedom if GTR can be achieved, but late seizure recurrence can occur. "Dual" and "double" pathology is uncommon and does not influence seizure outcome. Obtaining seizure freedomseems to be important for psychosocial outcome, but there is a risk for psychiatric comorbidities and long-term follow-up by a multi-professional team is advisable.

  • 249. Ekblom-Bak, Elin
    et al.
    Börjesson, Mats
    Ekblom, Örjan
    Angerås, Oskar
    Bergman, Frida
    Berntsson, Caroline
    Carlhäll, Carl-Johan
    Engström, Gunnar
    Engvall, Jan
    Fagman, Erika
    Flinck, Agneta
    Johansson, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Jujic, Amra
    Kero, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Medical Image Centre, Uppsala University Hospital, Uppsala, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Mannila, Maria
    Ostenfeld, Ellen
    Persson, Anders
    Persson, Jonas
    Persson, Margaretha
    Redfors, Björn
    Sandberg, Camilla
    Wennberg, Patrik
    Öhlin, Jerry
    Östgren, Carl Johan
    Jernberg, Tomas
    Accelerometer derived physical activity and subclinical coronary and carotid atherosclerosis: cross-sectional analyses in 22 703 middle-aged men and women in the SCAPIS study2023In: BMJ Open, E-ISSN 2044-6055, Vol. 13, no 11, article id e073380Article in journal (Refereed)
    Abstract [en]

    Objectives The aim included investigation of the associations between sedentary (SED), low-intensity physical activity (LIPA), moderate-to-vigorous intensity PA (MVPA) and the prevalence of subclinical atherosclerosis in both coronaries and carotids and the estimated difference in prevalence by theoretical reallocation of time in different PA behaviours.

    Design Cross-sectional.

    Setting Multisite study at university hospitals.

    Participants A total of 22 670 participants without cardiovascular disease (51% women, 57.4 years, SD 4.3) from the population-based Swedish CArdioPulmonary bioImage study were included. SED, LIPA and MVPA were assessed by hip-worn accelerometer.

    Primary and secondary outcomes Any and significant subclinical coronary atherosclerosis (CA), Coronary Artery Calcium Score (CACS) and carotid atherosclerosis (CarA) were derived from imaging data from coronary CT angiography and carotid ultrasound.

    Results High daily SED (>70% ≈10.5 hours/day) associated with a higher OR 1.44 (95% CI 1.09 to 1.91), for significant CA, and with lower OR 0.77 (95% CI 0.63 to 0.95), for significant CarA. High LIPA (>55% ≈8 hours/day) associated with lower OR for significant CA 0.70 (95% CI 0.51 to 0.96), and CACS, 0.71 (95% CI 0.51 to 0.97), but with higher OR for CarA 1.41 (95% CI 1.12 to 1.76). MVPA above reference level, >2% ≈20 min/day, associated with lower OR for significant CA (OR range 0.61–0.67), CACS (OR range 0.71–0.75) and CarA (OR range 0.72–0.79). Theoretical replacement of 30 min of SED into an equal amount of MVPA associated with lower OR for significant CA, especially in participants with high SED 0.84 (95% CI 0.76 to 0.96) or low MVPA 0.51 (0.36 to 0.73).

    Conclusions MVPA was associated with a lower risk for significant atherosclerosis in both coronaries and carotids, while the association varied in strength and direction for SED and LIPA, respectively. If causal, clinical implications include avoiding high levels of daily SED and low levels of MVPA to reduce the risk of developing significant subclinical atherosclerosis.

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  • 250.
    Ekman, Simon
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Harmenberg, Johan
    Frödin, Jan-Erik
    Bergström, Stefan
    Wassberg, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eksborg, Staffan
    Larsson, Olle
    Axelson, Magnus
    Jerling, Markus
    Abrahmsen, Lars
    Hedlund, Åsa
    Alvfors, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ståhl, Birgitta
    Bergqvist, Michael
    A novel oral insulin-like growth factor-1 receptor pathway modulator and its implications for patients with non-small cell lung carcinoma: A phase I clinical trial.2016In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 2, p. 140-148Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A phase Ia/b dose-escalation study was performed to characterize the safety, efficacy and pharmacokinetic properties of the oral small molecule insulin-like growth factor-1-receptor pathway modulator AXL1717 in patients with advanced solid tumors.

    MATERIAL AND METHODS: This was a prospective, single-armed, open label, dose-finding phase Ia/b study with the aim of single day dosing (phase Ia) to define the starting dose for multi-day dosing (phase Ib), and phase Ib to define and confirm recommended phase II dose (RP2D) and if possible maximum tolerated dose (MTD) for repeated dosing.

    RESULTS AND CONCLUSION: Phase Ia enrolled 16 patients and dose escalations up to 2900 mg BID were successfully performed without any dose limiting toxicity (DLT). A total of 39 patients were treated in phase Ib. AXL1717 was well tolerated with neutropenia as the only dose-related, reversible, DLT. RP2D dose was found to be 390 mg BID for four weeks. Some patients, mainly with NSCLC, demonstrated signs of clinical benefit, including four partial tumor responses (one according to RECIST and three according to PET). The 15 patients with NSCLC with treatment duration longer than two weeks with single agent AXL1717 in third or fourth line of therapy showed a median progression-free survival of 31 weeks and overall survival of 60 weeks. Down-regulation of IGF-1R on granulocytes and increases of free serum levels of IGF-1 were seen in patients treated with AXL1717. AXL1717 had an acceptable safety profile and demonstrated promising efficacy in this heavily pretreated patient cohort, especially in patients with NSCLC. RP2D was concluded to be 390 mg BID for four weeks. Trial number is NCT01062620.

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