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  • 1.
    Almby, Kristina E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Lundqvist, Martin H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Abrahamsson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Kvernby, Sofia
    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.
    Pereira, Maria J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Gingnell, Malin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Cervenka: Psychiatry.
    Karlsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Fanni, Giovanni
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Wiklund, Urban
    Umeå Univ, Dept Radiat Sci, Umeå, Sweden..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, Geneva, Switzerland..
    Lubberink, Mark
    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.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Effects of Gastric Bypass Surgery on the Brain: Simultaneous Assessment of Glucose Uptake, Blood Flow, Neural Activity, and Cognitive Function During Normo- and Hypoglycemia2021In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 70, no 6, p. 1265-1277Article in journal (Refereed)
    Abstract [en]

    While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and prevents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated counterregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are unclear. In this study, 11 subjects without diabetes with severe obesity were investigated pre- and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by F-18-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post- versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normoglycemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post- and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hypoglycemia, attenuated responses of counterregulatory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post- versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be further elucidated.

  • 2.
    Badoud, Simon
    et al.
    Univ Hosp Geneva, Neurol Unit, Dept Clin Neurosci, Geneva, Switzerland.;Univ Fribourg CH, Neurophysiol Unit, Dept Med, Fribourg, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland..
    Nicastro, Nicolas
    Univ Hosp Geneva, Neurol Unit, Dept Clin Neurosci, Geneva, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland..
    Garibotto, Valentina
    Univ Geneva, Fac Med, Geneva, Switzerland.;Geneva Univ Hosp, Nucl Med & Mol Imaging Unit, Dept Med Imaging, Geneva, Switzerland..
    Burkhard, Pierre R.
    Univ Hosp Geneva, Neurol Unit, Dept Clin Neurosci, Geneva, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, Geneva, Switzerland.;Ctr Diagnost Radiolog Carouge, Geneva, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany..
    Distinct spatiotemporal patterns for disease duration and stage in Parkinson's disease2016In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, no 3, p. 509-516Article in journal (Refereed)
    Abstract [en]

    Purpose To assess correlations between the degree of dopaminergic depletion measured using single-photon emission computed tomography (SPECT) and different clinical parameters of disease progression in Parkinson's disease (PD). Methods This retrospective study included 970 consecutive patients undergoing I-123-ioflupane SPECT scans in our institution between 2003 and 2013, from which we selected a study population of 411 patients according to their clinical diagnosis: 301 patients with PD (69.4 +/- 11.0 years, of age, 163 men) and 110 patients with nondegenerative conditions included as controls (72.7 +/- 8.0 years of age, 55 men). Comprehensive and operator-independent data analysis included spatial normalization into standard space, estimation of the mean uptake values in the striatum (caudate nucleus + putamen) and voxel-wise correlation between SPECT signal intensity and disease stage as well as disease duration in order to investigate the spatiotemporal pattern of the dopaminergic nigrostriatal degeneration. To compensate for potential interactions between disease stage and disease duration, one parameter was used as nonexplanatory coregressor for the other. Results Increasing disease stage was associated with an exponential decrease in I-123-ioflupane uptake (R (2) = 0.1501) particularly in the head of the ipsilateral caudate nucleus (p < 0.0001), whereas increasing disease duration was associated with a linear decrease in I-123-ioflupane uptake (p < 0.0001; R (2) = 0.1532) particularly in the contralateral anterior putamen (p < 0.0001). Conclusion We observed two distinct spatiotemporal patterns of posterior to anterior dopaminergic depletion associated with disease stage and disease duration in patients with PD. The developed operator-independent reference database of 411 I-123-ioflupane SPECT scans can be used for clinical and research applications.

  • 3. Badoud, Simon
    et al.
    Van De Ville, Dimitri
    Nicastro, Nicolas
    Garibotto, Valentina
    Burkhard, Pierre R
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Discriminating among degenerative parkinsonisms using advanced (123)I-ioflupane SPECT analyses2016In: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 12, p. 234-240Article in journal (Refereed)
    Abstract [en]

    (123)I-ioflupane single photon emission computed tomography (SPECT) is a sensitive and well established imaging tool in Parkinson's disease (PD) and atypical parkinsonian syndromes (APS), yet a discrimination between PD and APS has been considered inconsistent at least based on visual inspection or simple region of interest analyses. We here reappraise this issue by applying advanced image analysis techniques to separate PD from the various APS. This study included 392 consecutive patients with degenerative parkinsonism undergoing (123)I-ioflupane SPECT at our institution over the last decade: 306 PD, 24 multiple system atrophy (MSA), 32 progressive supranuclear palsy (PSP) and 30 corticobasal degeneration (CBD) patients. Data analysis included voxel-wise univariate statistical parametric mapping and multivariate pattern recognition using linear discriminant classifiers. MSA and PSP showed less ioflupane uptake in the head of caudate nucleus relative to PD and CBD, yet there was no difference between MSA and PSP. CBD had higher uptake in both putamen relative to PD, MSA and PSP. Classification was significant for PD versus APS (AUC 0.69, p < 0.05) and between APS subtypes (MSA vs CBD AUC 0.80, p < 0.05; MSA vs PSP AUC 0.69 p < 0.05; CBD vs PSP AUC 0.69 p < 0.05). Both striatal and extra-striatal regions contain classification information, yet the combination of both regions does not significantly improve classification accuracy. PD, MSA, PSP and CBD have distinct patterns of dopaminergic depletion on (123)I-ioflupane SPECT. The high specificity of 84-90% for PD versus APS indicates that the classifier is particularly useful for confirming APS cases.

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  • 4.
    Barnaure, I.
    et al.
    Univ Hosp Geneva, Div Neuroradiol, Geneva, Switzerland.
    Montandon, M-L.
    Univ Hosp Geneva, Dept Mental Hlth & Psychiat, Geneva, Switzerland.
    Rodriguez, C.
    Univ Hosp Geneva, Dept Mental Hlth & Psychiat, Geneva, Switzerland.
    Herrmann, F.
    Univ Hosp Geneva, Dept Internal Med, Geneva, Switzerland; Univ Hosp Geneva, Dept Rehabil, Geneva, Switzerland; Univ Hosp Geneva, Dept Geriatr, Geneva, Switzerland.
    Lövblad, K. O.
    Univ Hosp Geneva, Div Neuroradiol, Geneva, Switzerland.
    Giannakopoulos, P.
    Univ Hosp Geneva, Dept Mental Hlth & Psychiat, Geneva, Switzerland.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany; Univ Geneva, Fac Med, Geneva, Switzerland.
    Clinicoradiologic Correlations of Cerebral Microbleeds in Advanced Age2017In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 38, p. 39-45Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: The presence of cerebral microbleeds has been associated with dementia and cognitive decline, although studies report conflicting results. Our aim was to determine the potential role of the presence and location of cerebral microbleeds in early stages of cognitive decline.

    MATERIALS AND METHODS: Baseline 3T MR imaging examinations including SWI sequences of 328 cognitively intact community-dwelling controls and 72 subjects with mild cognitive impairment were analyzed with respect to the presence and distribution of cerebral microbleeds. A neuropsychological follow-up of controls was performed at 18 months post inclusion and identified cases with subtle cognitive deficits were referred to as controls with a deteriorating condition. Group differences in radiologic parameters were studied by using nonparametric tests, 1-way analysis of variance, and Spearman correlation coefficients.

    RESULTS: Cerebral microbleed prevalence was similar in subjects with mild cognitive impairment and controls with stable and cognitively deteriorating conditions (25%-31.9%). In all diagnostic groups, lobar cerebral microbleeds were more common. They occurred in 20.1% of all cases compared with 6.5% of cases with deep cerebral microbleeds. None of the investigated variables (age, sex, microbleed number, location and depth, baseline Mini-Mental State Examination score, and the Fazekas score) were significantly associated with cognitive deterioration with the exception of education of >12 years showing a slight but significant protective effect (OR, 0.44; 95% CI, 0.22-0.92; P = .028). The Mini-Mental State Examination and the Buschke total score were correlated with neither the total number nor lobar-versus-deep location of cerebral microbleeds.

    CONCLUSIONS: Cerebral microbleed presence, location, and severity are not related to the early stages of cognitive decline in advanced age.

  • 5. Beckmann, Katrin M.
    et al.
    Wang-Leandro, Adriano
    Dennler, Matthias
    Carrera, Ines
    Richter, Henning
    Bektas, Rima N.
    Steiner, Aline
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Faculty of Medicine of the University of Geneva, Geneva, Switzerland.
    Resting state networks of the canine brain under sevoflurane anaesthesia2020In: PLOS ONE, E-ISSN 1932-6203, Vol. 15, no 4, article id e0231955Article in journal (Refereed)
    Abstract [en]

    Resting-state functional Magnetic Resonance Imaging (rs-fMRI) has become an established technique in humans and reliably determines several resting state networks (RSNs) simultaneously. Limited data exist about RSN in dogs. The aim of this study was to investigate the RSNs in 10 healthy beagle dogs using a 3 tesla MRI scanner and subsequently perform group-level independent component analysis (ICA) to identify functionally connected brain networks. Rs-fMRI sequences were performed under steady state sevoflurane inhalation anaesthesia. Anaesthetic depth was titrated to the minimum level needed for immobilisation and mechanical ventilation of the patient. This required a sevoflurane MAC between 0.8 to 1.2. Group-level ICA dimensionality of 20 components revealed distributed sensory, motor and higher-order networks in the dogs' brain. We identified in total 7 RSNs (default mode, primary and higher order visual, auditory, two putative motor-somatosensory and one putative somatosensory), which are common to other mammals including humans. Identified RSN are remarkably similar to those identified in awake dogs. This study proves the feasibility of rs-fMRI in anesthetized dogs and describes several RSNs, which may set the basis for investigating pathophysiological characteristics of various canine brain diseases.

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  • 6.
    Beckmann, Katrin M.
    et al.
    Univ Zurich, Vetsuisse Fac Zurich, Dept Small Anim, Sect Neurol, Zurich, Switzerland..
    Wang-Leandro, Adriano
    Univ Zurich, Vetsuisse Fac Zurich, Dept Diagnost & Clin Serv, Clin Diagnost Imaging, Zurich, Switzerland..
    Richter, Henning
    Univ Zurich, Vetsuisse Fac Zurich, Dept Diagnost & Clin Serv, Clin Diagnost Imaging, Zurich, Switzerland.;Univ Hosp Bonn, Clin Neuroradiol, Bonn, Germany..
    Bektas, Rima N.
    Univ Zurich, Vetsuisse Fac, Dept Diagnost & Clin Serv, Sect Anaesthesiol, Zurich, Switzerland..
    Steffen, Frank
    Univ Zurich, Vetsuisse Fac Zurich, Dept Small Anim, Sect Neurol, Zurich, Switzerland..
    Dennler, Matthias
    Univ Zurich, Vetsuisse Fac Zurich, Dept Diagnost & Clin Serv, Clin Diagnost Imaging, Zurich, Switzerland..
    Carrera, Ines
    Willows Vet Ctr & Referral Serv, Highlands Rd, Shirley, England..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, Geneva, Switzerland..
    Increased resting state connectivity in the anterior default mode network of idiopathic epileptic dogs2021In: Scientific Reports, E-ISSN 2045-2322, Vol. 11, no 1, article id 23854Article in journal (Refereed)
    Abstract [en]

    Epilepsy is one of the most common chronic, neurological diseases in humans and dogs and considered to be a network disease. In human epilepsy altered functional connectivity in different large-scale networks have been identified with functional resting state magnetic resonance imaging. Since large-scale resting state networks have been consistently identified in anesthetised dogs' application of this technique became promising in canine epilepsy research. The aim of the present study was to investigate differences in large-scale resting state networks in epileptic dogs compared to healthy controls. Our hypothesis was, that large-scale networks differ between epileptic dogs and healthy control dogs. A group of 17 dogs (Border Collies and Greater Swiss Mountain Dogs) with idiopathic epilepsy was compared to 20 healthy control dogs under a standardized sevoflurane anaesthesia protocol. Group level independent component analysis with dimensionality of 20 components, dual regression and two-sample t test were performed and revealed significantly increased functional connectivity in the anterior default mode network of idiopathic epileptic dogs compared to healthy control dogs (p = 0.00060). This group level differences between epileptic dogs and healthy control dogs identified using a rather simple data driven approach could serve as a starting point for more advanced resting state network analysis in epileptic dogs.

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  • 7.
    Beckmann, Katrin M.
    et al.
    Univ Zurich, Vetsuisse Fac Zurich, Dept Small Anim, Sect Neurol, Zurich, Switzerland.;Univ Bern, Grad Sch Cellular & Biomed Sci, Bern, Switzerland..
    Wang-Leandro, Adriano
    Univ Zurich, Vetsuisse Fac Zurich, Dept Diagnost & Clin Serv, Clin Diagnost Imaging, Zurich, Switzerland.;Univ Vet Med Hannover, Dept Small Anim Med & Surg, Hannover, Germany..
    Steffen, Frank
    Univ Zurich, Vetsuisse Fac Zurich, Dept Small Anim, Sect Neurol, Zurich, Switzerland..
    Richter, Henning
    Univ Zurich, Vetsuisse Fac Zurich, Dept Diagnost & Clin Serv, Clin Diagnost Imaging, Zurich, Switzerland..
    Dennler, Matthias
    Univ Zurich, Vetsuisse Fac Zurich, Dept Diagnost & Clin Serv, Clin Diagnost Imaging, Zurich, Switzerland..
    Bektas, Rima
    Univ Zurich, Vetsuisse Fac, Dept Clin Diagnost & Serv, Sect Anaesthesiol, Zurich, Switzerland..
    Carrera, Ines
    Vet Oracle Teleradiol, Norfolk, England..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, Geneva, Switzerland..
    Diffusion tensor-based analysis of white matter in dogs with idiopathic epilepsy2023In: Frontiers in Veterinary Science, E-ISSN 2297-1769, Vol. 10, article id 1325521Article in journal (Refereed)
    Abstract [en]

    Introduction: The understanding of epileptic seizure pathogenesis has evolved over time, and it is now generally accepted that not only are cortical and subcortical areas involved but also the connection of these regions in the white matter (WM). Recent human neuroimaging studies confirmed the involvement of the WM in several epilepsy syndromes. Neuroimaging studies investigating WM integrity with diffusion tensor imaging (DTI) in canine idiopathic epilepsy are lacking. This study aimed to test the hypothesis that WM diffusion changes can be found in dogs affected by idiopathic epilepsy.

    Method: Twenty-six dogs with idiopathic epilepsy (15 Border Collies and 11 Greater Swiss Mountain dogs) and 24 healthy controls (11 Beagle dogs, 5 Border Collies, and 8 Greater Swiss Mountain dogs) were prospectively enrolled. Most dogs with idiopathic epilepsy (17/26) were enrolled within 3 months after seizure onset. Diffusion tensor imaging of the brain with 32 diffusion directions (low b value = 0 s/mm2; maximal b value = 800 s/mm2) was performed in a 3 Tesla scanner. Tract-based spatial statistics (TBSS), a voxel-based approach, was used to investigate changes in fractional anisotropy (FA) and mean diffusivity (MD) in the idiopathic epilepsy group compared to the healthy control group. Additionally, FA and MD were investigated in the region of corpus callosum and cingulate white matter in both groups.

    Results: We observed subtle changes in WM DTI between the idiopathic epilepsy group and the healthy control group limited to cingulate WM, with a significantly lower FA in the idiopathic epilepsy group compared to the healthy control group in the region of interest (ROI) approach (p = 0.027). No significant changes were found between the idiopathic epilepsy group and the healthy control group in the TBSS analysis and in the corpus callosum in the ROI approach.

    Conclusion: This study supports the cingulate area as a target structure in canine epilepsy. The subtle changes only might be explained by the short duration of epilepsy, small sample sizes, and the higher variability in canine brain anatomy. Furthermore, all included dogs showed generalized tonic-clonic seizures, possibly affected by generalized epilepsy syndrome, which are also associated with less pronounced DTI changes in humans than focal epilepsy syndromes.

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  • 8.
    Boccalini, Cecilia
    et al.
    Univ Geneva, Geneva Univ, Neuroctr, Lab Neuroimaging & Innovat Mol Tracers NIMTlab, Geneva, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland.;Univ Vita Salute San Raffaele, Milan, Italy.;IRCCS, San Raffaele Sci Inst, Div Neurosci, In Vivo Human Mol & Struct Neuroimaging Unit, Milan, Italy..
    Peretti, Debora Elisa
    Univ Geneva, Geneva Univ, Neuroctr, Lab Neuroimaging & Innovat Mol Tracers NIMTlab, Geneva, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland..
    Ribaldi, Federica
    Univ Geneva, Lab Neuroimaging Aging LANVIE, Geneva, Switzerland.;Geneva Univ Hosp, Memory Clin, Geneva, Switzerland..
    Scheffler, Max
    Geneva Univ Hosp, Diagnost Dept, Div Radiol, Geneva, Switzerland..
    Stampacchia, Sara
    Univ Geneva, Geneva Univ, Neuroctr, Lab Neuroimaging & Innovat Mol Tracers NIMTlab, Geneva, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland..
    Tomczyk, Szymon
    Univ Geneva, Lab Neuroimaging Aging LANVIE, Geneva, Switzerland..
    Rodriguez, Cristelle
    Univ Hosp Geneva, Div Inst Measures, Med Direct, Geneva, Switzerland.;Univ Geneva, Fac Med, Dept Psychiat, Geneva, Switzerland..
    Montandon, Marie-Louise
    Univ Geneva, Fac Med, Dept Psychiat, Geneva, Switzerland.;Geneva Univ Hosp, Dept Rehabil & Geriatr, Geneva, Switzerland.;Univ Geneva, Geneva, Switzerland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. CIMC Ctr Imagerie Med Cornavin, Geneva, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland.;Capital Med Univ, Beijing Tiantan Hosp, Dept Radiol, Beijing, Peoples R China..
    Giannakopoulos, Panteleimon
    Univ Hosp Geneva, Div Inst Measures, Med Direct, Geneva, Switzerland.;Univ Geneva, Fac Med, Dept Psychiat, Geneva, Switzerland..
    Frisoni, Giovanni B.
    Univ Geneva, Lab Neuroimaging Aging LANVIE, Geneva, Switzerland.;Geneva Univ Hosp, Memory Clin, Geneva, Switzerland..
    Perani, Daniela
    Univ Vita Salute San Raffaele, Milan, Italy.;IRCCS, San Raffaele Sci Inst, Div Neurosci, In Vivo Human Mol & Struct Neuroimaging Unit, Milan, Italy.;Osped San Raffaele, Nucl Med Unit, Milan, Italy..
    Garibotto, Valentina
    Univ Geneva, Geneva Univ, Neuroctr, Lab Neuroimaging & Innovat Mol Tracers NIMTlab, Geneva, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland.;Geneva Univ Hosp, Div Nucl Med & Mol Imaging, Geneva, Switzerland.;CIBM Ctr Biomed Imaging, Geneva, Switzerland..
    Early-Phase 18F-Florbetapir and 18F-Flutemetamol Images as Proxies of Brain Metabolism in a Memory Clinic Setting2023In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 64, no 2, p. 266-273Article in journal (Refereed)
    Abstract [en]

    Alzheimer disease (AD) neuropathologic changes are 6-amyloid (A6) deposition, pathologic tau, and neurodegeneration. Dual-phase amy-loid PET might be able to evaluate A6 deposition and neurodegenera-tion with a single tracer injection. Early-phase amyloid PET scans provide a proxy for cerebral perfusion, which has shown good correla-tions with neural dysfunction measured through metabolic consump-tion, whereas the late frames depict amyloid distribution. Our study aimed to assess the comparability between early-phase amyloid PET scans and 18F-FDG PET brain topography at the individual level and their ability to discriminate patients. Methods: One hundred sixty-six subjects evaluated at the Geneva Memory Center, ranging from no cognitive impairment to mild cognitive impairment and dementia, underwent early-phase amyloid PET-using either 18F-florbetapir (eFBP) (n = 94) or 18F-flutemetamol (eFMM) (n = 72)-and 18F-FDG PET. A6 status was assessed. SUV ratios (SUVRs) were extracted to evaluate the correlation of eFBP/eFMM and their respective 18F-FDG PET scans. The single-subject procedure was applied to investigate hypometabolism and hypoperfusion maps and their spatial overlap by the Dice coefficient. Receiver-operating-characteristic analyses were performed to compare the discriminative power of eFBP/eFMM and 18F-FDG PET SUVR in AD-related meta-regions of interest between A6-negative healthy controls and cases in the AD continuum. Results: Positive correlations were found between eFBP/eFMM and 18F-FDG PET SUVR independently of A6 status and A6 radiotracer (R> 0.72, P< 0.001). eFBP/eFMM single-subject analysis revealed clusters of significant hypoperfusion with good correspondence to hypometabo-lism topographies, independently of the underlying neurodegenerative patterns. Both eFBP/eFMM and 18F-FDG PET SUVR significantly dis-criminated AD patients from controls in the AD-related meta-regions of interest (eFBP area under the curve [AUC], 0.888; eFMM AUC, 0.801), with 18F-FDG PET performing slightly better, although not sig-nificantly (all P values higher than 0.05), than others (18F-FDG AUC, 0.915 and 0.832 for subjects evaluated with eFBP and eFMM, respec-tively). Conclusion: The distribution of perfusion was comparable to that of metabolism at the single-subject level by parametric analysis, particularly in the presence of a high neurodegeneration burden. Our findings indicate that eFBP and eFMM imaging can replace 18F-FDG PET imaging, as they reveal typical neurodegenerative patterns or allow exclusion of the presence of neurodegeneration. The findings show cost-saving capacities of amyloid PET and support routine use of the modality for individual classification in clinical practice.

  • 9.
    Collij, Lyduine E.
    et al.
    Vrije Univ Amsterdam, Amsterdam UMC, Dept Radiol & Nucl Med, Amsterdam, Netherlands..
    Salvado, Gemma
    Pasqual Maragall Fdn, Barcelona Eta Brain Res Ctr BBRC, Barcelona, Spain.;IMIM Hosp del Mar Med Res Inst, Barcelona, Spain..
    Wottschel, Viktor
    Vrije Univ Amsterdam, Amsterdam UMC, Dept Radiol & Nucl Med, Amsterdam, Netherlands..
    Mastenbroek, Sophie E.
    Vrije Univ Amsterdam, Amsterdam UMC, Dept Radiol & Nucl Med, Amsterdam, Netherlands..
    Schoenmakers, Pierre
    Vrije Univ Amsterdam, Amsterdam UMC, Dept Radiol & Nucl Med, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Amsterdam UMC, Dept Neurol, Amsterdam, Netherlands..
    Heeman, Fiona
    Vrije Univ Amsterdam, Amsterdam UMC, Dept Radiol & Nucl Med, Amsterdam, Netherlands..
    Aksman, Leon
    Univ Southern Calif, Stevens Neuroimaging & Informat Inst, Keck Sch Med, Los Angeles, CA 90007 USA..
    Wink, Alle Meije
    Vrije Univ Amsterdam, Amsterdam UMC, Dept Radiol & Nucl Med, Amsterdam, Netherlands..
    Berckel, Bart N. M.
    Vrije Univ Amsterdam, Amsterdam UMC, Dept Radiol & Nucl Med, Amsterdam, Netherlands..
    van de Flier, Wiesje M.
    Vrije Univ Amsterdam, Amsterdam UMC, Alzheimer Ctr, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Amsterdam UMC, Dept Neurol, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Amsterdam UMC, Dept Epidemiol & Data Sci, Amsterdam, Netherlands..
    Scheltens, Philip
    Vrije Univ Amsterdam, Amsterdam UMC, Alzheimer Ctr, Amsterdam, Netherlands..
    Visser, Pieter Jelle
    Vrije Univ Amsterdam, Amsterdam UMC, Alzheimer Ctr, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Amsterdam UMC, Dept Neurol, Amsterdam, Netherlands..
    Barkhof, Frederik
    Vrije Univ Amsterdam, Amsterdam UMC, Dept Radiol & Nucl Med, Amsterdam, Netherlands.;UCL, Ctr Med Image Comp, London, England.;UCL, Queen Sq Inst Neurol, London, England..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, Geneva, Switzerland.;CIMC Ctr Imagerie Med Cornavin, Geneva, Switzerland.;Capital Med Univ, Beijing Tiantan Hosp, Dept Radiol, Beijing, Peoples R China..
    Domingo Gispert, Juan
    Pasqual Maragall Fdn, Barcelona Eta Brain Res Ctr BBRC, Barcelona, Spain.;IMIM Hosp del Mar Med Res Inst, Barcelona, Spain.;Ctr Invest Biomed Red Bioingn Biomat & Nanomed CI, Madrid, Spain..
    Alves, Isadora Lopes
    Vrije Univ Amsterdam, Amsterdam UMC, Dept Radiol & Nucl Med, Amsterdam, Netherlands..
    Spatial-Temporal Patterns of beta-Amyloid Accumulation A Subtype and Stage Inference Model Analysis2022In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 98, no 17, p. E1692-E1703Article in journal (Refereed)
    Abstract [en]

    Background and Objectives beta-amyloid (A beta) staging models assume a single spatial-temporal progression of amyloid accumulation. We assessed evidence for A beta accumulation subtypes by applying the data-driven Subtype and Stage Inference (SuStaIn) model to amyloid-PET data. Methods Amyloid-PET data of 3,010 participants were pooled from 6 cohorts (ALFA+, EMIF-AD, ABIDE, OASIS, and ADNI). Standardized uptake value ratios were calculated for 17 regions. We applied the SuStaIn algorithm to identify consistent subtypes in the pooled dataset based on the cross-validation information criterion and the most probable subtype/stage classification per scan. The effects of demographics and risk factors on subtype assignment were assessed using multinomial logistic regression. Results Participants were mostly cognitively unimpaired (n = 1890 [62.8%]), had a mean age of 68.72 (SD 9.1) years, 42.1% were APOE epsilon 4 carriers, and 51.8% were female. A 1-subtype model recovered the traditional amyloid accumulation trajectory, but SuStaIn identified 3 optimal subtypes, referred to as frontal, parietal, and occipital based on the first regions to show abnormality. Of the 788 (26.2%) with strong subtype assignment (>50% probability), the majority was assigned to frontal (n = 415 [52.5%]), followed by parietal (n = 199 [25.3%]) and occipital subtypes (n = 175 [22.2%]). Significant differences across subtypes included distinct proportions of APOE epsilon 4 carriers (frontal 61.8%, parietal 57.1%, occipital 49.4%), participants with dementia (frontal 19.7%, parietal 19.1%, occipital 31.0%), and lower age for the parietal subtype (frontal/occipital 72.1 years, parietal 69.3 years). Higher amyloid (Centiloid) and CSF p-tau burden was observed for the frontal subtype; parietal and occipital subtypes did not differ. At follow-up, most participants (81.1%) maintained baseline subtype assignment and 25.6% progressed to a later stage. Discussion Whereas a 1-trajectory model recovers the established pattern of amyloid accumulation, SuStaIn determined that 3 subtypes were optimal, showing distinct associations with Alzheimer disease risk factors. Further analyses to determine clinical utility are warranted.

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  • 10.
    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.

  • 11. Emmert, Kirsten
    et al.
    Breimhorst, Markus
    Bauermann, Thomas
    Birklein, Frank
    Rebhorn, Cora
    Van De Ville, Dimitri
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Centre de Diagnostic Radiologique de Carouge CDRC, Geneva, Switzerland; Faculty of Medicine of the University of Geneva, Geneva, Switzerland; Department of Neuroradiology, University Hospital Freiburg, Freiburg im Breisgau, Germany.
    Active pain coping is associated with the response in real-time fMRI neurofeedback during pain2017In: Brain Imaging and Behavior, ISSN 1931-7557, E-ISSN 1931-7565, Vol. 11, no 3, p. 712-721Article in journal (Refereed)
    Abstract [en]

    Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback is used as a tool to gain voluntary control of activity in various brain regions. Little emphasis has been put on the influence of cognitive and personality traits on neurofeedback efficacy and baseline activity. Here, we assessed the effect of individual pain coping on rt-fMRI neurofeedback during heat-induced pain. Twenty-eight healthy subjects completed the Coping Strategies Questionnaire (CSQ) prior to scanning. The first part of the fMRI experiment identified target regions using painful heat stimulation. Then, subjects were asked to down-regulate the pain target brain region during four neurofeedback runs with painful heat stimulation. Functional MRI analysis included correlation analysis between fMRI activation and pain ratings as well as CSQ ratings. At the behavioral level, the active pain coping (first principal component of CSQ) was correlated with pain ratings during neurofeedback. Concerning neuroimaging, pain sensitive regions were negatively correlated with pain coping. During neurofeedback, the pain coping was positively correlated with activation in the anterior cingulate cortex, prefrontal cortex, hippocampus and visual cortex. Thermode temperature was negatively correlated with anterior insula and dorsolateral prefrontal cortex activation. In conclusion, self-reported pain coping mechanisms and pain sensitivity are a source of variance during rt-fMRI neurofeedback possibly explaining variations in regulation success. In particular, active coping seems to be associated with successful pain regulation.

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  • 12.
    Emmert, Kirsten
    et al.
    Univ Hosp Geneva, Dept Radiol & Med informat, Switzerland.
    Kopel, Rotem
    Univ Hosp Geneva, Dept Radiol & Med informat, Switzerland.
    Koush, Yury
    Univ Hosp Geneva, Dept Radiol & Med informat, Switzerland.
    Maire, Raphael
    Univ Hosp Lausanne, Neurotol & Audiol Unit, Dept ENT Head & Neck Surg, Switzerland.
    Senn, Pascal
    Univ Hosp Geneva, Dept Clin Neurosci, Switzerland.
    Van De Ville, Dimitri
    Univ Hosp Geneva, Dept Radiol & Med informat, Switzerland.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Continuous vs. intermittent neurofeedback to regulate auditory cortex activity of tinnitus patients using real-time fMRI: A pilot study2017In: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 14, p. 97-104Article in journal (Refereed)
    Abstract [en]

    The emerging technique of real-time fMRI neurofeedback trains individuals to regulate their own brain activity via feedback from an fMRI measure of neural activity. Optimum feedback presentation has yet to be determined, particularly when working with clinical populations. To this end, we compared continuous against intermittent feedback in subjects with tinnitus.

    Fourteen participants with tinnitus completed the whole experiment consisting of nine runs (3 runs × 3 days). Prior to the neurofeedback, the target region was localized within the auditory cortex using auditory stimulation (1 kHz tone pulsating at 6 Hz) in an ON-OFF block design. During neurofeedback runs, participants received either continuous (n = 7, age 46.84 ± 12.01, Tinnitus Functional Index (TFI) 49.43 ± 15.70) or intermittent feedback (only after the regulation block) (n = 7, age 47.42 ± 12.39, TFI 49.82 ± 20.28). Participants were asked to decrease auditory cortex activity that was presented to them by a moving bar. In the first and the last session, participants also underwent arterial spin labeling (ASL) and resting-state fMRI imaging. We assessed tinnitus severity using the TFI questionnaire before all sessions, directly after all sessions and six weeks after all sessions. We then compared neuroimaging results from neurofeedback using a general linear model (GLM) and region-of-interest analysis as well as behavior measures employing a repeated-measures ANOVA. In addition, we looked at the seed-based connectivity of the auditory cortex using resting-state data and the cerebral blood flow using ASL data.

    GLM group analysis revealed that a considerable part of the target region within the auditory cortex was significantly deactivated during neurofeedback. When comparing continuous and intermittent feedback groups, the continuous group showed a stronger deactivation of parts of the target region, specifically the secondary auditory cortex. This result was confirmed in the region-of-interest analysis that showed a significant down-regulation effect for the continuous but not the intermittent group. Additionally, continuous feedback led to a slightly stronger effect over time while intermittent feedback showed best results in the first session. Behaviorally, there was no significant effect on the total TFI score, though on a descriptive level TFI scores tended to decrease after all sessions and in the six weeks follow up in the continuous group. Seed-based connectivity with a fixed-effects analysis revealed that functional connectivity increased over sessions in the posterior cingulate cortex, premotor area and part of the insula when looking at all patients while cerebral blood flow did not change significantly over time.

    Overall, these results show that continuous feedback is suitable for long-term neurofeedback experiments while intermittent feedback presentation promises good results for single session experiments when using the auditory cortex as a target region. In particular, the down-regulation effect is more pronounced in the secondary auditory cortex, which might be more susceptible to voluntary modulation in comparison to a primary sensory region.

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  • 13.
    Emmert, Kirsten
    et al.
    Univ Geneva, Dept Radiol & Med Informat, Geneva, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, Med Image Proc Lab, Lausanne, Switzerland..
    Kopel, Rotem
    Univ Geneva, Dept Radiol & Med Informat, Geneva, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, Med Image Proc Lab, Lausanne, Switzerland..
    Sulzer, James
    Univ Texas Austin, Dept Mech Engn, Austin, TX 78712 USA..
    Bruehl, Annette B.
    Univ Zurich, Hosp Psychiat, Dept Psychiat Psychotherapy & Psychosomat, Zurich, Switzerland.;Univ Cambridge, Behav & Clin Neurosci Inst, Dept Psychiat, Cambridge, England..
    Berman, Brian D.
    Univ Colorado, Dept Neurol, Aurora, CO USA..
    Linden, David E. J.
    Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF10 3AX, S Glam, Wales..
    Horovitz, Silvina G.
    NINDS, NIH, Bethesda, MD 20892 USA..
    Breimhorst, Markus
    Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Neurol, D-55122 Mainz, Germany..
    Caria, Andrea
    Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Tubingen, Germany..
    Frank, Sabine
    Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Tubingen, Germany..
    Johnston, Stephen
    Long, Zhiying
    Swansea Univ, Dept Psychol, Swansea, W Glam, Wales.;Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China.;Beijing Normal Univ, IDG McGovern Inst Brain Res, Beijing 100875, Peoples R China..
    Paret, Christian
    Heidelberg Univ Mannheim, Med Fac Mannheim, Cent Inst Mental Hlth Mannheim, Dept Psychosomat Med & Psychotherapy, Mannheim, Germany.;Heidelberg Univ Mannheim, Med Fac Mannheim, Cent Inst Mental Hlth Mannheim, Dept Neuroimaging, Mannheim, Germany..
    Robineau, Fabien
    Univ Geneva, Dept Neurosci, Lab Neurol & Imaging Cognit, CH-1211 Geneva 4, Switzerland..
    Veit, Ralf
    Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Tubingen, Germany.;Univ Tubingen, Helmholtz Ctr Munich, Inst Diabet Res & Metab Dis, Tubingen, Germany..
    Bartsch, Andreas
    Heidelberg Univ, Dept Neuroradiol, Heidelberg, Germany.;Univ Wurzburg, Dept Neuroradiol, D-97070 Wurzburg, Germany.;Univ Oxford, FMRIB Ctr, Oxford, England.;Bamberg Hosp, Dept Radiol, Bamberg, Germany..
    Beckmann, Christian F.
    Radboud Univ Nijmegen, Ctr Cognit Neuroimaging, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neuroimaging, NL-6525 ED Nijmegen, Netherlands.;Univ Oxford, Oxford Ctr Funct MRI Brain, Nuffield Dept Clin Neurosci, Oxford OX1 2JD, England..
    Van De Ville, Dimitri
    Univ Geneva, Dept Radiol & Med Informat, Geneva, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, Med Image Proc Lab, Lausanne, Switzerland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Ctr Diagnost Radiolog Carouge CDRC, Geneva, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany.;Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland..
    Meta-analysis of real-time fMRI neurofeedback studies using individual participant data: How is brain regulation mediated?2016In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 124, no Part A, p. 806-812Article in journal (Refereed)
    Abstract [en]

    An increasing number of studies using real-time fMRI neurofeedback have demonstrated that successful regulation of neural activity is possible in various brain regions. Since these studies focused on the regulated region(s), little is known about the target-independent mechanisms associated with neurofeedback-guided control of brain activation, i.e. the regulating network. While the specificity of the activation during self-regulation is an important factor, no study has effectively determined the network involved in self-regulation in general. In an effort to detect regions that are responsible for the act of brain regulation, we performed a post-hoc analysis of data involving different target regions based on studies from different research groups. We included twelve suitable studies that examined nine different target regions amounting to a total of 175 subjects and 899 neurofeedback runs. Data analysis included a standard first-(single subject, extracting main paradigm) and second-level (single subject, all runs) general linear model (GLM) analysis of all participants taking into account the individual timing. Subsequently, at the third level, a random effects model GLM included all subjects of all studies, resulting in an overall mixed effects model. Since four of the twelve studies had a reduced field of view (FoV), we repeated the same analysis in a subsample of eight studies that had a well-overlapping FoV to obtain a more global picture of self-regulation. The GLM analysis revealed that the anterior insula as well as the basal ganglia, notably the striatum, were consistently active during the regulation of brain activation across the studies. The anterior insula has been implicated in interoceptive awareness of the body and cognitive control. Basal ganglia are involved in procedural learning, visuomotor integration and other higher cognitive processes including motivation. The larger FoV analysis yielded additional activations in the anterior cingulate cortex, the dorsolateral and ventrolateral prefrontal cortex, the temporo-parietal area and the visual association areas including the temporo-occipital junction. In conclusion, we demonstrate that several key regions, such as the anterior insula and the basal ganglia, are consistently activated during self-regulation in real-time fMRI neurofeedback independent of the targeted region-ofinterest. Our results imply that if the real-time fMRI neurofeedback studies target regions of this regulation network, such as the anterior insula, care should be given whether activation changes are related to successful regulation, or related to the regulation process per se. Furthermore, future research is needed to determine how activation within this regulation network is related to neurofeedback success.

  • 14.
    Emmert, Kirsten
    et al.
    Univ Geneva, Fac Med, Geneva, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, Med Image Proc Lab, Geneva, Switzerland..
    Zoller, Daniela
    Ecole Polytech Fed Lausanne, Inst Bioengn, Med Image Proc Lab, Geneva, Switzerland.;Univ Geneva, Dept Psychiat, Off Medicopedag, Geneva, Switzerland..
    Preti, Maria Giulia
    Univ Geneva, Fac Med, Geneva, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, Med Image Proc Lab, Geneva, Switzerland..
    Van De Ville, Dimitri
    Univ Geneva, Fac Med, Geneva, Switzerland.;Ecole Polytech Fed Lausanne, Inst Bioengn, Med Image Proc Lab, Geneva, Switzerland..
    Giannakopoulos, Panteleimon
    Univ Geneva, Dept Psychiat, Geneva, Switzerland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, Geneva, Switzerland.;Affidea Ctr Diagnost Radiol Carouge CDRC, Carouge, Switzerland..
    Influence of Vascular Variant of the Posterior Cerebral Artery (PCA) on Cerebral Blood Flow, Vascular Response to CO2 and Static Functional Connectivity2016In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 8, article id e0161121Article in journal (Refereed)
    Abstract [en]

    Introduction The fetal origin of the posterior cerebral artery (fPCA) is a frequent vascular variant in 11-29% of the population. For the fPCA, blood flow in the PCA originates from the anterior instead of the posterior circulation. We tested whether this blood supply variant impacts the cerebral blood flow assessed by arterial spin labeling (ASL), cerebrovascular reserve as well as resting-state static functional connectivity (sFC) in the sense of a systematic confound. Methods The study included 385 healthy, elderly subjects (mean age: 74.18 years [range: 68.9-90.4]; 243 female). Participants were classified into normal vascular supply (n = 296, 76.88%), right fetal origin (n = 23, 5.97%), left fetal origin (n = 16, 4.16%), bilateral fetal origin (n = 4, 1.04%), and intermediate (n = 46, 11.95%, excluded from further analysis) groups. ASL-derived relative cerebral blood flow (relCBF) maps and cerebrovascular reserve (CVR) maps derived from a CO2 challenge with blocks of 7% CO2 were compared. Additionally, sFC between 90 regions of interest (ROIs) was compared between the groups. Results CVR was significantly reduced in subjects with ipsilateral fPCA, most prominently in the temporal lobe. ASL yielded a non-significant trend towards reduced relCBF in bilateral posterior watershed areas. In contrast, conventional atlas-based sFC did not differ between groups. Conclusions In conclusion, fPCA presence may bias the assessment of cerebrovascular reserve by reducing the response to CO2. In contrast, its effect on ASL-assessed baseline perfusion was marginal. Moreover, fPCA presence did not systematically impact resting-state sFC. Taken together, this data implies that perfusion variables should take into account the vascularization patterns.

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  • 15.
    Fanni, Giovanni
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Kagios, Christakis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Roman, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. CIMC—Centre d’Imagerie Médicale de Cornavin, Geneva, Switzerland.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Effects of gastric bypass surgery on brain connectivity responses to hypoglycemia2023In: Endocrine, ISSN 1355-008X, E-ISSN 1559-0100, Vol. 79, no 2, p. 304-312Article in journal (Refereed)
    Abstract [en]

    Introduction

    Roux-en-Y gastric bypass (RYGB) leads to beneficial effects on glucose homeostasis, and attenuated hormonal counterregulatory responses to hypoglycemia are likely to contribute. RYGB also induces alterations in neural activity of cortical and subcortical brain regions. We aimed to characterize RYGB-induced changes in resting-state connectivity of specific brain regions of interest for energy homeostasis and behavioral control during hypoglycemia.

    Method

    Ten patients with BMI > 35 kg/m2 were investigated with brain PET/MR imaging during a hyperinsulinemic normo- and hypoglycemic clamp, before and 4 months after RYGB. Hormonal levels were assessed throughout the clamp. Resting-state (RS) fMRI scans were acquired in the glucose-lowering phase of the clamp, and they were analyzed with a seed-to-voxel approach.

    Results

    RS connectivity during initiation of hypoglycemia was significantly altered after RYGB between nucleus accumbens, thalamus, caudate, hypothalamus and their crosstalk with cortical and subcortical regions. Connectivity between the nucleus accumbens and the frontal pole was increased after RYGB, and this was associated with a reduction of ACTH (r = −0.639, p = 0.047) and cortisol (r = −0.635, p = 0.048) responses. Instead, connectivity between the caudate and the frontal pole after RYGB was reduced and this was associated with less attenuation of glucagon response during the hypoglycemic clamp (r = −0.728, p = 0.017), smaller reduction in fasting glucose (r = −0.798, p = 0.007) and less excess weight loss (r = 0.753, p = 0.012). No other significant associations were found between post-RYGB changes in ROI-to-voxel regional connectivity hormonal responses and metabolic or anthropometric outcomes.

    Conclusion

    RYGB alters brain connectivity during hypoglycemia of several neural pathways involved in reward, inhibitory control, and energy homeostasis. These changes are associated with altered hormonal responses to hypoglycemia and may be involved in the glucometabolic outcome of RYGB.

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  • 16.
    Fällmar, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Med Ctr Freiburg, Dept Neuroradiol, Freiburg, Germany.; Univ Geneva, Fac Med, Geneva, Switzerland.; Affidea CDRC Ctr Diagnost Radiol Carouge, Carouge, Switzerland..
    Lilja, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Hermes Med Solut, Stockholm, Sweden.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Tolboom, Nelleke
    Vrije Univ Amsterdam, Dept Radiol & Nucl Med, Med Ctr, Neurosci Campus, Amsterdam, Netherlands.
    Egger, Karl
    Univ Med Ctr Freiburg, Dept Neuroradiol, Freiburg, Germany.
    Kellner, Elias
    Univ Freiburg, Dept Radiol, Med Ctr, Fac Med,Med Phys, Freiburg, Germany.
    Croon, Philip M
    Vrije Univ Amsterdam, Dept Radiol & Nucl Med, Med Ctr, Neurosci Campus, Amsterdam, Netherlands.
    Verfaillie, Sander C J
    Vrije Univ Amsterdam, Alzheimer Ctr Amsterdam, Dept Neurol, Med Ctr, Amsterdam, Netherlands.
    van Berckel, Bart N M
    Vrije Univ Amsterdam, Dept Radiol & Nucl Med, Med Ctr, Neurosci Campus, Amsterdam, Netherlands.
    Ossenkoppele, Rik
    Vrije Univ Amsterdam, Alzheimer Ctr Amsterdam, Dept Neurol, Med Ctr, Amsterdam, Netherlands.
    Barkhof, Frederik
    Vrije Univ Amsterdam, Dept Radiol & Nucl Med, Med Ctr, Neurosci Campus, Amsterdam, Netherlands.; UCL, Inst Neurol & Healthcare Engn, London, England..
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Arterial spin labeling-based Z-maps have high specificity and positive predictive value for neurodegenerative dementia compared to FDG-PET.2017In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 27, no 10, p. 4237-4246Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Cerebral perfusion analysis based on arterial spin labeling (ASL) MRI has been proposed as an alternative to FDG-PET in patients with neurodegenerative disease. Z-maps show normal distribution values relating an image to a database of controls. They are routinely used for FDG-PET to demonstrate disease-specific patterns of hypometabolism at the individual level. This study aimed to compare the performance of Z-maps based on ASL to FDG-PET.

    METHODS: Data were combined from two separate sites, each cohort consisting of patients with Alzheimer's disease (n = 18 + 7), frontotemporal dementia (n = 12 + 8) and controls (n = 9 + 29). Subjects underwent pseudocontinuous ASL and FDG-PET. Z-maps were created for each subject and modality. Four experienced physicians visually assessed the 166 Z-maps in random order, blinded to modality and diagnosis.

    RESULTS: Discrimination of patients versus controls using ASL-based Z-maps yielded high specificity (84%) and positive predictive value (80%), but significantly lower sensitivity compared to FDG-PET-based Z-maps (53% vs. 96%, p < 0.001). Among true-positive cases, correct diagnoses were made in 76% (ASL) and 84% (FDG-PET) (p = 0.168).

    CONCLUSION: ASL-based Z-maps can be used for visual assessment of neurodegenerative dementia with high specificity and positive predictive value, but with inferior sensitivity compared to FDG-PET.

    KEY POINTS: • ASL-based Z-maps yielded high specificity and positive predictive value in neurodegenerative dementia. • ASL-based Z-maps had significantly lower sensitivity compared to FDG-PET-based Z-maps. • FDG-PET might be reserved for ASL-negative cases where clinical suspicion persists. • Findings were similar at two study sites.

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  • 17. Garibotto, Valentina
    et al.
    Corpataux, Thibault
    Dupuis-Lozeron, Elise
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Faculty of Medicine, Geneva University;Centre d'Imagerie Rive Droite, Geneva.
    Fontolliet, Timothée
    Picard, Fabienne
    Higher nicotinic receptor availability in the cingulo-insular network is associated with lower cardiac parasympathetic tone2019In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 527, no 18, p. 3014-3022Article in journal (Refereed)
    Abstract [en]

    The dorsal anterior cingulate cortex (dACC) and the anterior insula (AI) constitute the salience network and form as well the major cortical components of the central autonomic nervous system. These two cortical regions have the highest density in α4β2 nicotinic acetylcholine receptors (nAChRs) within the whole cortex.The aim of the study was to test the association between nAChRs density/availability in the salience network and the heart rate variability in humans. We selected subjects from a previous positron emission tomography (PET) imaging study in epilepsy with 18F-FA-85380, a specific marker for α4β2 nAChRs, including 10 healthy controls, 10 patients with nonlesional focal epilepsy and 8 patients with idiopathic generalized epilepsy. Participants underwent a 10 min-resting electrocardiogram as they were lying still in a semi-supine position while watching an emotionally neutral video. We tested the association between parasympathetic tone and the regional brain nAChR availability, as measured by 18F-F-A-85380 binding potential (BP), using linear regression. We observed an association between higher nAChRs availability in the bilateral dACC and the right dorsal AI/frontal operculum and a lower parasympathetic tone, without significant effect of the clinical group on this relation. Our study is the first one to show a neurochemical correlate to the parasympathetic role of the anterior cingulate cortex and the AI. The nicotinic system, which plays a major role in the peripheral autonomic nervous system intervening both in the parasympathetic and sympathetic chains, seems also to play a role in the central autonomic nervous system.

  • 18.
    Garibotto, Valentina
    et al.
    Univ Hosp Geneva, Nucl Med & Mol Imaging Div, Dept Med Imaging, Geneva, Switzerland; Univ Geneva, Fac Med, Geneva, Switzerland.
    Wissmeyer, Michael
    Univ Hosp Geneva, Nucl Med & Mol Imaging Div, Dept Med Imaging, Geneva, Switzerland.
    Giavri, Zoi
    Advantis Med Imaging, Eindhoven, Netherlands.
    Goldstein, Rachel
    Univ Hosp Geneva, EEG & Epilepsy Unit, Dept Neurol, Geneva, Switzerland.
    Seimbille, Yann
    Univ Hosp Geneva, Nucl Med & Mol Imaging Div, Dept Med Imaging, Geneva, Switzerland.
    Seeck, Margitta
    Univ Geneva, Fac Med, Geneva, Switzerland; Univ Hosp Geneva, EEG & Epilepsy Unit, Dept Neurol, Geneva, Switzerland.
    Ratib, Osman
    Univ Hosp Geneva, Nucl Med & Mol Imaging Div, Dept Med Imaging, Geneva, Switzerland.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, Geneva, Switzerland; CIRD, Geneva, Switzerland.
    Picard, Fabienne
    Univ Geneva, Fac Med, Geneva, Switzerland; Univ Hosp Geneva, EEG & Epilepsy Unit, Dept Neurol, Geneva, Switzerland.
    Nicotinic receptor abnormalities as a biomarker in idiopathic generalized epilepsy2019In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 46, no 2, p. 385-395Article in journal (Refereed)
    Abstract [en]

    Purpose: Mutations of cholinergic neuronal nicotinic receptors have been identified in the autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), associated with changes on PET images using [18F]-F-85380-A (F-A-85380), an α4β2 nicotinic receptor ligand. The aim of the present study was to evaluate potential changes in nicotinic receptor availability in other types of epilepsy.

    Methods: We included 34 male participants, 12 patients with idiopathic generalized epilepsy (IGE), 10 with non-lesional diurnal focal epilepsy, and 12 age-matched healthy controls. All patients underwent PET/CT using F-A-85380 and [18F]-fluorodeoxyglucose (FDG), 3D T1 MRI and diffusion tensor imaging (DTI). F-A-85380 and FDG images were compared with the control group using a voxel-wise (SPM12) and a volumes of interest (VOI) analysis.

    Results: In the group of patients with IGE, the voxel-wise and VOI analyses showed a significant increase of F-A-85380 ratio index of binding potential (BPRI, corresponding to the receptor availability) in the anterior cingulate cortex (ACC), without structural changes on MRI. At an individual level, F-A-85380 BPRI increase in the ACC could distinguish IGE patients from controls and from patients with focal epilepsy with good accuracy.

    Conclusions: We observed focal changes of density/availability of nicotinic receptors in IGE, namely an increase in the ACC. These data suggest that the modulation of α4β2 nicotinic receptors plays a role not only in ADNFLE, but also in other genetic epileptic syndromes such as IGE and could serve as a biomarker of epilepsy syndromes with a genetic background.

  • 19.
    Georgiopoulos, Charalampos
    et al.
    Department of Radiology and Department ofMedical and Health Sciences, Linköping University; Center for Medical ImageScience and Visualization (CMIV), Linköping University.
    Warntjes, Marcel
    Center for Medical ImageScience and Visualization (CMIV), Linköping University; SyntheticMR AB .
    Dizdar, Nil
    Department of Neurology and Department of Clinical and Experimental Medicine, Linköping University.
    Zachrisson, Helene
    Center for Medical ImageScience and Visualization (CMIV), Linköping University; Department of Clinical Physiology and Departmentof Medical and Health Sciences, Linköping University, Linköping.
    Engström, Maria
    Center for Medical ImageScience and Visualization (CMIV), Linköping University, Linköping; Department of Medical andHealth Sciences, Linköping University, Linköping.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea CDRC Centre de Diagnostic Radiologiquede Carouge SA, Geneva, Switzerland .
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Olfactory Impairment in Parkinson's Disease Studied with Diffusion Tensor and Magnetization Transfer Imaging.2017In: Journal of Parkinson's Disease, ISSN 1877-7171, E-ISSN 1877-718X, Vol. 7, no 2, p. 301-311Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Olfactory impairment is an early manifestation of Parkinson's disease (PD). Diffusion Tensor Imaging (DTI) and Magnetization Transfer (MT) are two imaging techniques that allow noninvasive detection of microstructural changes in the cerebral white matter.

    OBJECTIVE: To assess white matter alterations associated with olfactory impairment in PD, using a binary imaging approach with DTI and MT.

    METHODS: 22 PD patients and 13 healthy controls were examined with DTI, MT and an odor discrimination test. DTI data were first analyzed with tract-based spatial statistics (TBSS) in order to detect differences in fractional anisotropy, mean, radial and axial diffusivity between PD patients and controls. Voxelwise randomized permutation was employed for the MT analysis, after spatial and intensity normalization. Additionally, ROI analysis was performed on both the DTI and MT data, focused on the white matter adjacent to olfactory brain regions.

    RESULTS: Whole brain voxelwise analysis revealed decreased axial diffusivity in the left uncinate fasciculus and the white matter adjacent to the left olfactory sulcus of PD patients. ROI analysis demonstrated decreased axial diffusivity in the right orbitofrontal cortex, as well as decreased mean diffusivity and axial diffusivity in the white matter of the left entorhinal cortex of PD patients. There were no significant differences regarding fractional anisotropy, radial diffusivity or MT between patients and controls.

    CONCLUSIONS: ROI analysis of DTI could detect microstructural changes in the white matter adjacent to olfactory areas in PD patients, whereas MT imaging could not.

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  • 20. Georgiopoulos, Charalampos
    et al.
    Witt, Suzanne T
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Dizdar, Nil
    Zachrisson, Helene
    Engström, Maria
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    A study of neural activity and functional connectivity within the olfactory brain network in Parkinson's disease2019In: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 23, article id 101946Article in journal (Refereed)
    Abstract [en]

    Olfactory dysfunction is an early manifestation of Parkinson's disease (PD). The present study aimed to illustrate potential differences between PD patients and healthy controls in terms of neural activity and functional connectivity within the olfactory brain network. Twenty PD patients and twenty healthy controls were examined with olfactory fMRI and resting-state fMRI. Data analysis of olfactory fMRI included data-driven tensorial independent component (ICA) and task-driven general linear model (GLM) analyses. Data analysis of resting-state fMRI included probabilistic ICA based on temporal concatenation and functional connectivity analysis within the olfactory network. ICA of olfactory fMRI identified an olfactory network consisting of the posterior piriform cortex, insula, right orbitofrontal cortex and thalamus. Recruitment of this network was less significant for PD patients. GLM analysis revealed significantly lower activity in the insula bilaterally and the right orbitofrontal cortex in PD compared to healthy controls but no significant differences in the olfactory cortex itself. Analysis of resting-state fMRI did not reveal any differences in the functional connectivity within the olfactory, default mode, salience or central executive networks between the two groups. In conclusion, olfactory dysfunction in PD is associated with less significant recruitment of the olfactory brain network. ICA could demonstrate differences in both the olfactory cortex and its main projections, compared to GLM that revealed differences only on the latter. Resting-state fMRI did not reveal any significant differences in functional connectivity within the olfactory, default mode, salience and central executive networks in this cohort.

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  • 21. Georgiopoulos, Charalampos
    et al.
    Witt, Suzanne T
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea CDRC Centre de Diagnostic Radiologique de Carouge SA, Geneva, Switzerland.
    Dizdar, Nil
    Zachrisson, Helene
    Engström, Maria
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Olfactory fMRI: implications of stimulation length and repetition time2018In: Chemical Senses, ISSN 0379-864X, E-ISSN 1464-3553, Vol. 43, no 6, p. 389-398Article in journal (Refereed)
    Abstract [en]

    Studying olfaction with functional Magnetic Resonance imaging (fMRI) poses various methodological challenges. This study aimed to investigate the effects of stimulation length and repetition time (TR) on the activation pattern of four olfactory brain regions: the anterior and the posterior piriform cortex, the orbitofrontal cortex and the insula. 22 healthy participants with normal olfaction were examined with fMRI, with two stimulation lengths (6 seconds and 15 seconds) and two TRs (0.901 seconds and 1.34 seconds). Data were analyzed using General Linear Model (GLM), Tensorial Independent Component Analysis (TICA) and by plotting the event related time course of brain activation in the four olfactory regions of interest. The statistical analysis of the time courses revealed that short TR was associated with more pronounced signal increase and short stimulation was associated with shorter time to peak signal. Additionally, both long stimulation and short TR were associated with oscillatory time courses, whereas both short stimulation and short TR resulted in more typical time courses. GLM analysis showed that the combination of short stimulation and short TR could result in visually larger activation within these olfactory areas. TICA validated that the tested paradigm was spatially and temporally associated with a functionally connected network that included all four olfactory regions. In conclusion, the combination of short stimulation and short TR is associated with higher signal increase and shorter time to peak, making it more amenable to standard GLM-type analyses than long stimulation and long TR, and it should, thus, be preferable for olfactory fMRI.

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  • 22. Giannakopoulos, Panteleimon
    et al.
    Montandon, Marie-Louise
    Herrmann, François R
    Hedderich, Dennis
    Gaser, Christian
    Kellner, Elias
    Rodriguez, Cristelle
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Alzheimer resemblance atrophy index, BrainAGE, and normal pressure hydrocephalus score in the prediction of subtle cognitive decline: added value compared to existing MR imaging markers.2022In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 32, no 11, p. 7833-7842Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Established visual brain MRI markers for dementia include hippocampal atrophy (mesio-temporal atrophy MTA), white matter lesions (Fazekas score), and number of cerebral microbleeds (CMBs). We assessed whether novel quantitative, artificial intelligence (AI)-based volumetric scores provide additional value in predicting subsequent cognitive decline in elderly controls.

    METHODS: A prospective study including 80 individuals (46 females, mean age 73.4 ± 3.5 years). 3T MR imaging was performed at baseline. Extensive neuropsychological assessment was performed at baseline and at 4.5-year follow-up. AI-based volumetric scores were derived from 3DT1: Alzheimer Disease Resemblance Atrophy Index (AD-RAI), Brain Age Gap Estimate (BrainAGE), and normal pressure hydrocephalus (NPH) index. Analyses included regression models between cognitive scores and imaging markers.

    RESULTS: AD-RAI score at baseline was associated with Corsi (visuospatial memory) decline (10.6% of cognitive variability in multiple regression models). After inclusion of MTA, CMB, and Fazekas scores simultaneously, the AD-RAI score remained as the sole valid predictor of the cognitive outcome explaining 16.7% of its variability. Its percentage reached 21.4% when amyloid positivity was considered an additional explanatory factor. BrainAGE score was associated with Trail Making B (executive functions) decrease (8.5% of cognitive variability). Among the conventional MRI markers, only the Fazekas score at baseline was positively related to the cognitive outcome (8.7% of cognitive variability). The addition of the BrainAGE score as an independent variable significantly increased the percentage of cognitive variability explained by the regression model (from 8.7 to 14%). The addition of amyloid positivity led to a further increase in this percentage reaching 21.8%.

    CONCLUSIONS: The AI-based AD-RAI index and BrainAGE scores have limited but significant added value in predicting the subsequent cognitive decline in elderly controls when compared to the established visual MRI markers of brain aging, notably MTA, Fazekas score, and number of CMBs.

    KEY POINTS: • AD-RAI score at baseline was associated with Corsi score (visuospatial memory) decline. • BrainAGE score was associated with Trail Making B (executive functions) decrease. • AD-RAI index and BrainAGE scores have limited but significant added value in predicting the subsequent cognitive decline in elderly controls when compared to the established visual MRI markers of brain aging, notably MTA, Fazekas score, and number of CMBs.

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  • 23.
    Giannakopoulos, Panteleimon
    et al.
    Univ Geneva, Dept Psychiat, Geneva, Switzerland.;Geneva Univ Hosp, Med Direct, Geneva, Switzerland..
    Montandon, Marie-Louise
    Univ Geneva, Dept Psychiat, Geneva, Switzerland.;Geneva Univ Hosp, Dept Rehabil & Geriatr, Geneva, Switzerland.;Univ Geneva, Geneva, Switzerland..
    Rodriguez, Cristelle
    Univ Geneva, Dept Psychiat, Geneva, Switzerland.;Geneva Univ Hosp, Med Direct, Geneva, Switzerland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Dept Neuroradiol, Fac Med, Geneva, Switzerland.;CIRO Ctr Imagerie Rive Droite, Geneva, Switzerland.;Uppsala Univ, Dept Surg Sci, Radiol, Uppsala, Sweden..
    Garibotto, Valentina
    Univ Geneva, Geneva, Switzerland.;Geneva Univ Hosp, Dept Nucl Med & Mol Imaging, Diagnost Dept, Geneva, Switzerland..
    Herrmann, Francois R.
    Geneva Univ Hosp, Dept Rehabil & Geriatr, Geneva, Switzerland.;Univ Geneva, Geneva, Switzerland..
    Prediction of Subtle Cognitive Decline in Normal Aging: Added Value of Quantitative MRI and PET Imaging2021In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 13, article id 664224Article in journal (Refereed)
    Abstract [en]

    Quantitative imaging processing tools have been proposed to improve clinic-radiological correlations but their added value at the initial stages of cognitive decline is still a matter of debate. We performed a longitudinal study in 90 community-dwelling elders with three neuropsychological assessments during a 4.5 year follow-up period, and visual assessment of medial temporal atrophy (MTA), white matter hyperintensities, cortical microbleeds (CMB) as well as amyloid positivity, and presence of abnormal FDG-PET patterns. Quantitative imaging data concerned ROI analysis of MRI volume, amyloid burden, and FDG-PET metabolism in several AD-signature areas. Multiple regression models, likelihood-ratio tests, and areas under the receiver operating characteristic curve (AUC) were used to compare quantitative imaging markers to visual inspection. The presence of more or equal to four CMB at inclusion and slight atrophy of the right MTL at follow-up were the only parameters to be independently related to the worst cognitive score explaining 6% of its variance. This percentage increased to 24.5% when the ROI-defined volume loss in the posterior cingulate cortex, baseline hippocampus volume, and MTL metabolism were also considered. When binary classification of cognition was made, the area under the ROC curve increased from 0.69 for the qualitative to 0.79 for the mixed imaging model. Our data reveal that the inclusion of quantitative imaging data significantly increases the prediction of cognitive changes in elderly controls compared to the single consideration of visual inspection.

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  • 24.
    Giannakopoulos, Panteleimon
    et al.
    Univ Geneva, Dept Psychiat, Geneva, Switzerland.;Geneva Univ Hosp, Med Direct, Geneva, Switzerland..
    Rodriguez, Cristelle
    Univ Geneva, Dept Psychiat, Geneva, Switzerland.;Geneva Univ Hosp, Med Direct, Geneva, Switzerland..
    Montandon, Marie-Louise
    Univ Geneva, Dept Psychiat, Geneva, Switzerland.;Geneva Univ Hosp, Med Direct, Geneva, Switzerland.;Geneva Univ Hosp, Dept Rehabil & Geriatr, Geneva, Switzerland.;Univ Geneva, Geneva, Switzerland..
    Garibotto, Valentina
    Geneva Univ Hosp, Diagnost Dept, Div Nucl Med & Mol Imaging, Geneva, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, Geneva, Switzerland.;CIRD, Geneva, Switzerland.
    Herrmann, Francois R.
    Geneva Univ Hosp, Dept Rehabil & Geriatr, Geneva, Switzerland.;Univ Geneva, Geneva, Switzerland..
    Less agreeable, better preserved?: A PET amyloid and MRI study in a community-based cohort2020In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 89, p. 24-31Article in journal (Refereed)
    Abstract [en]

    The relationship between personality profiles and brain integrity in old age is still a matter of debate. We examined the association between Big Five factor and facet scores and MRI brain volume changes on a 54-month follow-up in 65 elderly controls with 3 neurocognitive assessments (baseline, 18 months, and 54 months), structural brain MRI (baseline and 54 months), brain amyloid PET during follow-up, and APOE genotyping. Personality was assessed with the Neuroticism Extraversion Openness Personality Inventory-Revised. Regression models were used to identify predictors of volume loss including time, age, sex, personality, amyloid load, presence of APOE epsilon 4 allele, and cognitive evolution. Lower agreeableness factor scores (and 4 of its facets) were associated with lower volume loss in the hippocampus, entorhinal cortex, amygdala, mesial temporal lobe, and precuneus bilaterally. Higher openness factor scores (and 2 of its facets) were also associated with lower volume loss in the left hippocampus. Our findings persisted when adjusting for confounders in multivariable models. These data suggest that the combination of low agreeableness and high openness is an independent predictor of better preservation of brain volume in areas vulnerable to neurodegeneration. (C) 2020 Elsevier Inc. All rights reserved.

  • 25.
    Giannakopoulos, Panteleimon
    et al.
    Univ Geneva, Dept Psychiat, Geneva, Switzerland; Geneva Univ Hosp, Med Direct, Geneva, Switzerland.
    Rodriguez, Cristelle
    Univ Geneva, Dept Psychiat, Geneva, Switzerland; Geneva Univ Hosp, Med Direct, Geneva, Switzerland.
    Montandon, Marie-Louise
    Univ Geneva, Dept Psychiat, Geneva, Switzerland; Geneva Univ Hosp, Med Direct, Geneva, Switzerland; Geneva Univ Hosp, Dept Readaptat & Geriatr, Geneva, Switzerland; Univ Geneva, Geneva, Switzerland.
    Garibotto, Valentina
    Geneva Univ Hosp, Div Nucl Med & Mol Imaging, Diagnost Dept, Geneva, Switzerland; Univ Geneva, Fac Med, Geneva, Switzerland.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, Geneva, Switzerland; CIRD Ctr Rive Droite, Geneva, Switzerland.
    Herrmann, Francois R.
    Geneva Univ Hosp, Dept Readaptat & Geriatr, Geneva, Switzerland; Univ Geneva, Geneva, Switzerland.
    Personality Factors' Impact on the Structural Integrity of Mentalizing Network in Old Age: A Combined PET-MRI Study2020In: Frontiers in Psychiatry, E-ISSN 1664-0640, Vol. 11, article id 552037Article in journal (Refereed)
    Abstract [en]

    The mentalizing network (MN) treats social interactions based on our understanding of other people's intentions and includes the medial prefrontal cortex (mPFC), temporoparietal junction (TPJ), posterior cingulate cortex (PCC), precuneus (PC), and amygdala. Not all elders are equally affected by the aging-related decrease of mentalizing abilities. Personality has recently emerged as a strong determinant of functional connectivity in MN areas. However, its impact on volumetric changes across the MN in brain aging is still unknown. To address this issue, we explored the determinants of volume decrease in MN components including amyloid burden, personality, and APOE genotyping in a previously established cohort of 130 healthy elders with a mean follow-up of 54 months. Personality was assessed with the Neuroticism Extraversion Openness Personality Inventory-Revised. Regression models corrected for multiple comparisons were used to identify predictors of volume loss including time, age, sex, personality, amyloid load, presence of APOE epsilon 4 allele, and cognitive evolution. In cases with higher Agreeableness scores, there were lower volume losses in PCC, PC, and amygdala bilaterally. This was also the case for the right mPFC in elders displaying lower Agreeableness and Conscientiousness. In multiple regression models, the effect of Agreeableness was still observed in left PC and right amygdala and that of Conscientiousness was still observed in right mPFC volume loss (26.3% of variability, significant age and sex). Several Agreeableness (Modesty) and Conscientiousness (order, dutifulness, achievement striving, and self-discipline) facets were positively related to increased volume loss in cortical components of the MN. In conclusion, these data challenge the beneficial role of higher levels of Agreeableness and Conscientiousness in old age, showing that they are associated with an increased rate of volume loss within the MN.

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  • 26.
    Giannakopoulos, Panteleimon
    et al.
    Univ Geneva, Dept Psychiat, Geneva, Switzerland.;Geneva Univ Hosp, Med Direct, Geneva, Switzerland..
    Rodriguez, Cristelle
    Univ Geneva, Dept Psychiat, Geneva, Switzerland.;Geneva Univ Hosp, Med Direct, Geneva, Switzerland..
    Montandon, Marie-Louise
    Univ Geneva, Dept Psychiat, Geneva, Switzerland.;Geneva Univ Hosp, Dept Rehabil & Geriatr, Geneva, Switzerland.;Univ Geneva, Geneva, Switzerland..
    Garibotto, Valentina
    Univ Geneva, Geneva, Switzerland.;Geneva Univ Hosp, Dept Nucl Med & Mol Imaging, Diagnost Dept, Geneva, Switzerland..
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. CIMC Ctr Imagerie Med Cornavin, Geneva, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland.;Capital Med Univ, Beijing Tiantan Hosp, Dept Radiol, Beijing, Peoples R China..
    Herrmann, Francois R.
    Geneva Univ Hosp, Dept Rehabil & Geriatr, Geneva, Switzerland.;Univ Geneva, Geneva, Switzerland..
    Personality Impact on Alzheimer's Disease - Signature and Vascular Imaging Markers: A PET-MRI Study2022In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 85, no 4, p. 1807-1817Article in journal (Refereed)
    Abstract [en]

    Background: Several studies postulated that personality is an independent determinant of cognitive trajectories in old age. Objective: This study explores the impact of personality on widely used Alzheimer's disease (AD) and vascular imaging markers. Methods: We examined the association between personality and three classical AD imaging markers (centiloid-based-amyloid load, MRI volumetry in hippocampus, and media temporal lobe atrophy), and two vascular MRI parameters (Fazekas score and number of cortical microbleeds) assessed at baseline and upon a 54-month-follow-up. Personality was assessed with the Neuroticism Extraversion Openness Personality Inventory-Revised. Regression models were used to identify predictors of imaging markers including sex, personality factors, presence of APOE epsilon 4 allele and cognitive evolution over time. Results: Cortical GM volumes were negatively associated with higher levels of Conscientiousness both at baseline and follow-up. In contrast, higher scores of Openness were related to better preservation of left hippocampal volumes in these two time points and negatively associated with medial temporal atrophy at baseline. Amyloid load was not affected by personality factors. Cases with higher Extraversion scores displayed higher numbers of cortical microbleeds at baseline. Conclusion: Personality impact on brain morphometry is detected only in some among the routinely used imaging markers. The most robust associations concern the positive role of high levels of Conscientiousness and Openness on AD-signature MRI markers. Higher extraversion levels are associated with increased vulnerability to cortical microbleeds pointing to the fact that the socially favorable traits may have a detrimental effect on brain integrity in old age.

  • 27. Gninenko, Nicolas
    et al.
    Trznadel, Stéphanie
    Daskalou, Dimitrios
    Gramatica, Luca
    Vanoy, Julie
    Voruz, François
    Robyn, Claudia Lardi
    Spadazzi, Anne
    Yulzari, Aude
    Sitaram, Ranganatha
    Van De Ville, Dimitri
    Senn, Pascal
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Functional MRI Neurofeedback Outperforms Cognitive Behavioral Therapy for Reducing Tinnitus Distress: A Prospective Randomized Clinical Trial.2024In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 310, no 2, p. e231143-, article id e231143Article in journal (Refereed)
    Abstract [en]

    Background Cognitive behavioral therapy (CBT) is the current standard treatment for chronic severe tinnitus; however, preliminary evidence suggests that real-time functional MRI (fMRI) neurofeedback therapy may be more effective. Purpose To compare the efficacy of real-time fMRI neurofeedback against CBT for reducing chronic tinnitus distress. Materials and Methods In this prospective controlled trial, participants with chronic severe tinnitus were randomized from December 2017 to December 2021 to receive either CBT (CBT group) for 10 weekly group sessions or real-time fMRI neurofeedback (fMRI group) individually during 15 weekly sessions. Change in the Tinnitus Handicap Inventory (THI) score (range, 0-100) from baseline to 6 or 12 months was assessed. Secondary outcomes included four quality-of-life questionnaires (Beck Depression Inventory, Pittsburgh Sleep Quality Index, State-Trait Anxiety Inventory, and World Health Organization Disability Assessment Schedule). Questionnaire scores between treatment groups and between time points were assessed using repeated measures analysis of variance and the nonparametric Wilcoxon signed rank test. Results The fMRI group included 21 participants (mean age, 49 years ± 11.4 [SD]; 16 male participants) and the CBT group included 22 participants (mean age, 53.6 years ± 8.8; 16 male participants). The fMRI group showed a greater reduction in THI scores compared with the CBT group at both 6 months (mean score change, -28.21 points ± 18.66 vs -12.09 points ± 18.86; P = .005) and 12 months (mean score change, -30 points ± 25.44 vs -4 points ± 17.2; P = .01). Compared with baseline, the fMRI group showed improved sleep (mean score, 8.62 points ± 4.59 vs 7.25 points ± 3.61; P = .006) and trait anxiety (mean score, 44 points ± 11.5 vs 39.84 points ± 10.5; P = .02) at 1 month and improved depression (mean score, 13.71 points ± 9.27 vs 6.53 points ± 5.17; P = .01) and general functioning (mean score, 24.91 points ± 17.05 vs 13.06 points ± 10.1; P = .01) at 6 months. No difference in these metrics over time was observed for the CBT group (P value range, .14 to >.99). Conclusion Real-time fMRI neurofeedback therapy led to a greater reduction in tinnitus distress than the current standard treatment of CBT. ClinicalTrials.gov registration no.: NCT05737888; Swiss Ethics registration no.: BASEC2017-00813 © RSNA, 2024 Supplemental material is available for this article.

  • 28.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea CDRC Ctr Diagnost Radiolog Carouge Clos d, CH-1227 Carouge, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany.;Univ Geneva, Fac Med, Geneva, Switzerland.
    Advance MR imaging in sports-related concussion and mild traumatic brain injury: ready for clinical use? (Commentary on Tremblay et al. 2017)2017In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 46, no 4, p. 1954-1955Article in journal (Other academic)
  • 29. Haller, Sven
    Can AI Predict the Need for Surgery in Traumatic Brain Injury?2024In: Radiology: Artificial Intelligence, E-ISSN 2638-6100, Vol. 6, no 2, p. e230587-, article id e230587Article in journal (Refereed)
  • 30.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Ctr Imagerie Med Cornavin, Pl Cornavin 18, CH-1201 Geneva, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland.;Capital Med Univ, Dept Radiol, Beijing Tiantan Hosp, Beijing, Peoples R China..
    Deep Learning to Predict Outcome in Severe Traumatic Brain Injury2022In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 304, no 2, p. 395-396Article in journal (Other academic)
  • 31.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Ctr Diagnost Radiol Carouge CDRC, Geneva, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany.
    Is Hippocampal Volumetry Really All That Matters?2017In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 38, no 9, p. E60-E61Article in journal (Other academic)
  • 32.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Ctr Diagnost Radiol Carouge CDRC, Geneva, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany.;Univ Geneva, Fac Med, Geneva, Switzerland.
    The Concept of "Number Needed to Image"2017In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 38, no 10, p. E79-E80Article in journal (Other academic)
  • 33.
    Haller, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Ctr Diagnost Radiol Carouge CDRC, Carouge, Switzerland; Univ Geneva, Dept Radiol, Geneva, Switzerland .
    Use of MR Imaging-defined Connectome to Predict the Recovery of Patients after Cardiac Arrest.2018In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 287, no 1, p. 256-257Article in journal (Refereed)
  • 34.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Ctr Diagnost Radiol Carouge CDRC, Geneva, Switzerland.; Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany.; Univ Geneva, Fac Med, Geneva, Switzerland..
    Barkhof, Frederik
    Vrije Univ Amsterdam, Med Ctr, Dept Radiol & Nucl Med & PET Res, Amsterdam, Netherlands.; UCL, Inst Neurol, London, England.; UCL, Inst Healthcare Engn, London, England..
    Interaction of Vascular Damage and Alzheimer Dementia: Focal Damage and Disconnection2017In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 282, no 2, p. 311-313Article in journal (Refereed)
    Abstract [en]

    Dementia is a major health and socioeconomic problem with ever-increasing prevalence due to the increasing age of the population (1). Alzheimer disease (AD) and vascular dementia are both common disorders in the elderly, and although they are commonly co-occurring, they are generally considered to be separate nosologic entities. Neuroimaging biomarkers have evolved considerably over the past decade and demonstrate new insights into disease mechanisms in dementia. Of particular interest is the evolving view of interaction between pathophysiological mechanisms in AD and vascular dementia, as demonstrated with neuroimaging.

  • 35.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Centre d’Imagerie Rive Droite (CIRD)1201 Geneva, Switzerland; Faculty of Medicine, Geneva University, Geneva, Switzerland.
    Barkhof, Frederik
    Neuroimaging in Dementia: A Clinical Approach2018In: Clinical Neuroradiology: The ESNR Textbook / [ed] Frederik Barkhof, Rolf Jager, Majda Thurnher, Alex Rovira Cañellas, Springer, 2018Chapter in book (Refereed)
    Abstract [en]

    Dementia is not a diagnosis or a specific disease entity but a syndrome that describes a wide range of symptoms leading to a decline in mental ability severe enough to interfere with daily life.

    Neurodegenerative disorders including dementing disorders and movement disorders may present with overlapping clinical symptoms. Likewise, the underlying molecular and cellular pathology may be overlapping. Consequently, dementia syndromes and movement disorders may be considered as a spectrum of diseases, and symptoms may vary over time. Moreover, there is no direct link between clinical symptoms and imaging findings: the same degree of brain atrophy or metabolic abnormality may be associated to a variable degree of cognitive impairment, or from the other perspective, the same degree of cognitive impairment may be associated with variable level of brain atrophy or metabolic abnormality. Finally, it is not uncommon to have coexisting pathology, for example, Alzheimer type neurodegeneration and a vascular contribution.

    In the first part, we review basic clinical presentations of dementia syndromes. In the second part, we review the radiological techniques and typical clinical neuroradiology findings of the various types of dementia, including Alzheimer dementia (hippocampal atrophy, hypometabolism/hypoperfusion in posterior cingulate and bilateral parietal areas), vascular dementia (small and large vessel disease), fronto-temporal lobar degeneration (fronto-temporal/peri-insular atrophy and hypometabolism/hypoperfusion), and dementia with Lewy Bodies (reduced dopamine uptake in striatum, abnormality of the nigrosome1). Additionally, we review unusual clinical presentations of dementia, including young-onset dementia and rapidly progressive dementia. Finally, we briefly discuss the overlapping clinical presentation and underlying pathology between dementia and movement disorders.

  • 36.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea CDRC Ctr Diagnost Radiol Carouge, Geneva, Switzerland; Univ Geneva, Med Fac, Geneva, Switzerland.
    Barkhof, Frederik
    Vrije Univ Amsterdam, Med Ctr, Dept Radiol & Nucl Med, Amsterdam, Netherlands; UCL, Inst Neurol, Dept Neuroradiol, London, England.
    Peri-hippocampal developmental venous anomalies and memory loss: more than a normal variant?2018In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 60, no 6, p. 579-582Article in journal (Refereed)
  • 37.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Barkhof, Frederik
    Thomas, David
    Lovblad, Karl-Olof
    Golay, Xavier
    Zaharchuk, Greg
    Further Implications of Off-Label Use of Acetazolamide in the Management of Moyamoya Disease in Japan: Response.2017In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 284, no 1, p. 301-303Article in journal (Refereed)
  • 38.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Ctr Diagnost Radiologique Carouge CDRC, Geneva, Switzerland.;Univ Geneva, Fac Med, Rue Gabrielle Perret Gentil 4, CH-1211 Geneva 14, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany..
    Barkhof, Frederik
    UCL, Neuroradiol Acad Unit, Dept Brain Repair & Rehabil, Inst Neurol, London, England.;UCL, Dept Healthcare Engn, London, England.;Vrije Univ Amsterdam, Med Ctr, Dept Radiol & Nucl Med, Amsterdam, Netherlands..
    Thomas, David
    UCL Institute of Neurology, University College Hospital, London, England.
    Lovblad, Karl-Olof
    Univ Hosp Geneva, Dept Neuroradiol, Geneva, Switzerland..
    Golay, Xavier
    Univ Coll Hosp, UCL Inst Neurol, London, England..
    Zaharchuk, Greg
    Stanford Univ, Dept Radiol, Stanford, CA 94305 USA..
    Response to: Further Implications of Off-Label Use of Acetazolamide in the Management of Moyamoya Disease in Japan Response2017In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 284, no 1, p. 302-303Article in journal (Other academic)
  • 39.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea CDRC Ctr Diagnost Radiol Carouge, Clos Fonderie 1, CH-1277 Carouge, Switzerland.
    Burke, Michael
    GE Healthcare GmbH, Munich, Germany.
    Mueller, Thomas L
    Pearl Technol AG, Schlieren, Switzerland.
    MR skin signal loss effect/artifact2018In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 60, no 6, p. 661-662Article in journal (Refereed)
  • 40.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. CIMC Ctr Imagerie Med Cornavin, Geneva, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland.;Capital Med Univ, Dept Radiol, Beijing Tiantan Hosp, Beijing, Peoples R China..
    Davidsson, Anette
    Linköping Univ, Dept Clin Physiol, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden..
    Tisell, Anders
    Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Dept Med Radiat Phys, Linköping, Sweden.;Linköping Univ, Ctr Med Image Sci & Visualizat CMIV, Linköping, Sweden..
    Ochoa-Figueroa, Miguel
    Linköping Univ, Dept Clin Physiol, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Ctr Med Image Sci & Visualizat CMIV, Linköping, Sweden.;Linköping Univ, Dept Radiol, Linköping, Sweden..
    Georgiopoulos, Charalampos
    Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Ctr Med Image Sci & Visualizat CMIV, Linköping, Sweden.;Linköping Univ, Dept Radiol, Linköping, Sweden..
    MRI of nigrosome-1: A potential triage tool for patients with suspected parkinsonism2022In: Journal of Neuroimaging, ISSN 1051-2284, E-ISSN 1552-6569, Vol. 32, no 2, p. 273-278Article in journal (Refereed)
    Abstract [en]

    Background and Purpose Susceptibility-weighted imaging (SWI) of nigrosome-1 is an emerging and clinically applicable imaging marker for parkinsonism, which can be derived from routinely performed brain MRI. The purpose of the study was to assess whether SWI can be used as a triage tool for more efficient selection of subsequent Dopamine Transporter Scan (DaTSCAN) single-photon emission computed tomography (SPECT). Methods We examined 72 consecutive patients with suspected parkinsonism with both DaTSCAN SPECT and SWI (48 in Philips Ingenia, 24 in GE Signa). Additionally, we examined 24 healthy controls with SWI (14 in Philips Ingenia, 10 in GE Signa). Diagnostic performance of SWI and DaTSCAN SPECT was assessed on the basis of clinical diagnosis, in terms of sensitivity, specificity, and diagnostic accuracy. Results A total of 54 parkinsonism patients (69 years +/- 9, 32 men), 18 nonparkinsonism patients (69.4 years +/- 9, 10 men), and 24 healthy controls (62 years +/- 8, 10 men) were recruited. SWI had a specificity of 92% and a sensitivity of 74%, whereas DaTSCAN SPECT had 83% and 94%, respectively. By preselecting patients with abnormal or inconclusive SWI, the diagnostic performance of DaTSCAN SPECT improved (specificity 100%, sensitivity 95%). Scans from Philips were associated with significantly lower image quality compared to GE (p < .001). The experienced rater outperformed the less experienced one in diagnostic accuracy (82% vs. 68%). Conclusions SWI can be used as triage tool because normal SWI can in most cases rule out parkinsonism. However, the performance of SWI depends on acquisition parameters and rater's experience.

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  • 41.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Geneva, Fac Med, Geneva, Switzerland.;Ctr Diagnost Radiol Carouge, Carouge, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany..
    Etienne, L.
    Univ Hosp Geneva, Dept Radiol, Geneva, Switzerland..
    Koevari, E.
    Univ Hosp Geneva, Dept Psychiat, Geneva, Switzerland..
    Varoquaux, A. D.
    Univ Hosp La Timone, Dept Radiol, Marseille, France..
    Urbach, H.
    Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany..
    Becker, M.
    Univ Hosp Geneva, Dept Radiol, Geneva, Switzerland..
    Imaging of Neurovascular Compression Syndromes: Trigeminal Neuralgia, Hemifacial Spasm, Vestibular Paroxysmia, and Glossopharyngeal Neuralgia2016In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 37, no 8, p. 1384-1392Article, review/survey (Refereed)
    Abstract [en]

    Neurovascular compression syndromes are usually caused by arteries that directly contact the cisternal portion of a cranial nerve. Not all cases of neurovascular contact are clinically symptomatic. The transition zone between the central and peripheral myelin is the most vulnerable region for symptomatic neurovascular compression syndromes. Trigeminal neuralgia (cranial nerve V) has an incidence of 4-20/100,000, a transition zone of 4 mm, with symptomatic neurovascular compression typically proximal. Hemifacial spasm (cranial nerve VII) has an incidence of 1/100,000, a transition zone of 2.5 mm, with symptomatic neurovascular compression typically proximal. Vestibular paroxysmia (cranial nerve VIII) has an unknown incidence, a transition zone of 11 mm, with symptomatic neurovascular compression typically at the internal auditory canal. Glossopharyngeal neuralgia (cranial nerve IX) has an incidence of 0.5/100,000, a transition zone of 1.5 mm, with symptomatic neurovascular compression typically proximal. The transition zone overlaps the root entry zone close to the brain stem in cranial nerves V, VII, and IX, yet it is more distal and does not overlap the root entry zone in cranial nerve VIII. Although symptomatic neurovascular compression syndromes may also occur if the neurovascular contact is outside the transition zone, symptomatic neurovascular compression syndromes are more common if the neurovascular contact occurs at the transition zone or central myelin section, in particular when associated with nerve displacement and atrophy.

  • 42.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea CDRC Ctr Diagnost Radiol Carouge SA, Clos Fonderie 1, CH-1227 Geneva, Switzerland.
    Fällmar, David
    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.
    Susceptibility weighted imaging in dementia with Lewy bodies: will it resolve the blind spot of MRI?2016In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 58, no 2, p. 217-218Article in journal (Refereed)
  • 43.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. CIRD Ctr Imagerie Rive Droite, Geneva, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland.;Uppsala Univ, Dept Surg Sci, Div Radiol, Uppsala, Sweden.;CIMC Ctr Imagerie Med Cornavin, Geneva, Switzerland..
    Haacke, E. Mark
    Wayne State Univ, Dept Neurol, Detroit, MI USA.;Wayne State Univ, Dept Radiol, Detroit, MI USA..
    Thurnher, Majda M.
    Med Univ Vienna, Dept Biomed Imaging & Image Guided Therapy, Vienna, Austria..
    Barkhof, Frederik
    UCL, Queen Sq Inst Neurol, London, England.;UCL, Ctr Med Image Comp CMIC, Inst Healthcare Engn, London, England.;Univ Amsterdam, Dept Radiol & Nucl Med, Med Ctr, Amsterdam, Netherlands..
    Susceptibility-weighted Imaging: Technical Essentials and Clinical Neurologic Applications2021In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 299, no 1, p. 3-26Article in journal (Refereed)
    Abstract [en]

    Susceptibility-weighted imaging (SWI) evolved from simple two-dimensional T2*-weighted sequences to three-dimensional sequences with improved spatial resolution and enhanced susceptibility contrast. SWI is an MRI sequence sensitive to compounds that distort the local magnetic field (eg, calcium and iron), in which the phase information can differentiate. But the term SWI is colloquially used to denote high-spatial-resolution susceptibility-enhanced sequences across different MRI vendors and sequences even when phase information is not used. The imaging appearance of SWI and related sequences strongly depends on the acquisition technique. Initially, SWI and related sequences were mostly used to improve the depiction of findings already known from standard two-dimensional T2*-weighted neuroimaging: more microbleeds in patients who are aging or with dementia or mild brain trauma; increased conspicuity of superficial siderosis in Alzheimer disease and amyloid angiopathy; and iron deposition in neurodegenerative diseases or abnormal vascular structures, such as capillary telangiectasia. But SWI also helps to identify findings not visible on standard T2*-weighted images: the nigrosome 1 in Parkinson disease and dementia with Lewy bodies, the central vein and peripheral rim signs in multiple sclerosis, the peripheral rim sign in abscesses, arterial signal loss related to thrombus, asymmetrically prominent cortical veins in stroke, and intratumoral susceptibility signals in brain neoplasms. (C) RSNA, 2021

  • 44.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Jäger, Hans Rolf
    Vernooij, Meike W
    Barkhof, Frederik
    Neuroimaging in Dementia: More than Typical Alzheimer Disease2023In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 308, no 3, article id e230173Article in journal (Refereed)
    Abstract [en]

    Alzheimer disease (AD) is the most common cause of dementia. The prevailing theory of the underlying pathology assumes amyloid accumulation followed by tau protein aggregation and neurodegeneration. However, the current antiamyloid and antitau treatments show only variable clinical efficacy. Three relevant points are important for the radiologic assessment of dementia. First, besides various dementing disorders (including AD, frontotemporal dementia, and dementia with Lewy bodies), clinical variants and imaging subtypes of AD include both typical and atypical AD. Second, atypical AD has overlapping radiologic and clinical findings with other disorders. Third, the diagnostic process should consider mixed pathologies in neurodegeneration, especially concurrent cerebrovascular disease, which is frequent in older age. Neuronal loss is often present at, or even before, the onset of cognitive decline. Thus, for effective emerging treatments, early diagnosis before the onset of clinical symptoms is essential to slow down or stop subsequent neuronal loss, requiring molecular imaging or plasma biomarkers. Neuroimaging, particularly MRI, provides multiple imaging parameters for neurodegenerative and cerebrovascular disease. With emerging treatments for AD, it is increasingly important to recognize AD variants and other disorders that mimic AD. Describing the individual composition of neurodegenerative and cerebrovascular disease markers while considering overlapping and mixed diseases is necessary to better understand AD and develop efficient individualized therapies.

  • 45.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Ctr Diagnost Radiol Carouge, Geneva, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland.;Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany..
    Montandon, M. -L
    Univ Hosp Geneva, Dept Mental Hlth & Psychiat, Geneva, Switzerland.
    Rodriguez, C.
    Univ Hosp Geneva, Div Inst Measures, Med Direct, Geneva, Switzerland..
    Ackermann, M.
    Univ Hosp Geneva, Dept Mental Hlth & Psychiat, Geneva, Switzerland..
    Herrmann, F. R.
    Univ Geneva, Fac Med, Geneva, Switzerland.;Univ Hosp Geneva, Div Geriatr, Dept Internal Med Rehabil & Geriatr, Geneva, Switzerland..
    Giannakopoulos, P.
    Univ Geneva, Fac Med, Geneva, Switzerland.;Univ Hosp Geneva, Div Inst Measures, Med Direct, Geneva, Switzerland..
    APOE*E4 Is Associated with Gray Matter Loss in the Posterior Cingulate Cortex in Healthy Elderly Controls Subsequently Developing Subtle Cognitive Decline2017In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 38, no 7, p. 1335-1342Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: The presence of apolipoprotein E4 (APOE*E4) is the strongest currently known genetic risk factor for Alzheimer disease and is associated with brain gray matter loss, notably in areas involved in Alzheimer disease pathology. Our objective was to assess the effect of APOE*E4 on brain structures in healthy elderly controls who subsequently developed subtle cognitive decline.

    MATERIALS AND METHODS: This prospective study included 382 community-dwelling elderly controls. At baseline, participants underwent MR imaging at 3T, extensive neuropsychological testing, and genotyping. After neuropsychological follow-up at 18 months, participants were classified into cognitively stable controls and cognitively deteriorating controls. Data analysis included whole-brain voxel-based morphometry and ROI analysis of GM.

    RESULTS: APOE*E4-related GM loss at baseline was found only in the cognitively deteriorating controls in the posterior cingulate cortex. There was no APOE*E4-related effect in the hippocampus, mesial temporal lobe, or brain areas not involved in Alzheimer disease pathology. Controls in the cognitively deteriorating group had slightly lower GM concentration in the hippocampus at baseline. Higher GM densities in the hippocampus, middle temporal lobe, and amygdala were associated with a decreased risk for cognitively deteriorating group status at follow-up.

    CONCLUSIONS: APOE*E4-related GM loss in the posterior cingulate cortex (an area involved in Alzheimer disease pathology) was found only in those elderly controls who subsequently developed subtle cognitive decline but not in cognitively stable controls. This finding might explain the partially conflicting results of previous studies that typically did not include detailed neuropsychological assessment and follow-up. Most important, APOE*E4 status had no impact on GM density in areas affected early by neurofibrillary tangle formation such as the hippocampus and mesial temporal lobe.

  • 46.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Affidea Ctr Diagnost Radiol Carouge CDRC, Carouge, Switzerland.; Med Sch Univ, Geneva, Switzerland.; Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany. .
    Montandon, Marie-Louise
    Med Sch Univ, Geneva, Switzerland.
    Lazeyras, François
    Univ Geneva, Dept Mental Hlth & Psychiat, Geneva, Switzerland.
    Scheffler, Max
    Univ Geneva, Dept Mental Hlth & Psychiat, Geneva, Switzerland.
    Meckel, Stephan
    Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany.
    Herrmann, Francois R
    Med Sch Univ, Geneva, Switzerland.; Univ Hosp Geneva, Dept Internal Med Rehabil & Geriatr, Div Geriatr, Geneva, Switzerland.
    Giannakopoulos, Panteleimon
    Med Sch Univ, Geneva, Switzerland.; Univ Hosp Geneva, Geneva, Switzerland.
    Kövari, Enikö
    Med Sch Univ, Geneva, Switzerland.
    Radiologic-Histopathologic Correlation of Cerebral Microbleeds Using Pre-Mortem and Post-Mortem MRI2016In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 12, article id e0167743Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Cerebral microbleeds (CMB), also known as cerebral microhemorrhages, are small areas of susceptibility on brain magnetic resonance imaging (MRI), that are increasingly detected due to the higher availability of high-field MRI systems and dedicated pulse sequences. The prevalence of CMBs increases in cases with cognitive decline. The current investigation assessed the poorly investigated radiologic-histopathologic correlation of CMBs on MRI.

    METHODS: The local ethical committee approved the current investigation. We retrospectively assessed a consecutive series of 1303 autopsy cases hospitalized in Geneva University Hospitals between 2000-2014. Of 112 cases with pre-mortem T2* sequences, we included 25 cases (mean age 77.3 ± 9.6, 9 females) with at least one CMB. We compared pre-mortem CMBs with targeted histopathology and post-mortem MRI.

    RESULTS: 25 cases had 31 CMB lesions detected by pre-mortem MRI. 25 additional CMB were detected on histopathology. 4 CMBs on pre-mortem MRI were false positives, resulting in a total of 52 CMBs. 27 CMBs on pre-mortem MRI were confirmed on histopathology, corresponding to a sensitivity or true positive rate of 51.9% (95% CI 37.6-66.0%). The false negative rate of pre-mortem MRI was 48.1% (95% CI 34.0-62.4%). Post-mortem MRI showed only 3 cases with additional CMBs. Overall, pre-mortem MRI significantly underestimated CMBs (p = 0.0001).

    CONCLUSIONS: Routine clinical brain MRI underestimates the prevalence of CMBs by approximately 50%, and 12% of radiologic pre-mortem MRI CMBs were false positives. Post-mortem MRI confirmed that this discordance is not explained by microbleeds occurring after the pre-mortem MRI.

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  • 47.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. CIRD Ctr Imagerie Rive Droite, Geneva, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland..
    Montandon, Marie-Louise
    Geneva Univ Hosp, Dept Rehabil & Geriatr, Geneva, Switzerland.;Univ Geneva, Geneva, Switzerland.;Univ Geneva, Dept Psychiat, Geneva, Switzerland..
    Lilja, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Lund Univ, Dept Clin Sci, Clin Memory Res Unit, Malmö, Sweden.;Hermes Med Solut, Stockholm, Sweden..
    Rodriguez, Cristelle
    Univ Geneva, Dept Psychiat, Geneva, Switzerland.;Geneva Univ Hosp, Div Inst Measures, Med Direct, Geneva, Switzerland..
    Garibotto, Valentina
    Univ Geneva, Fac Med, Geneva, Switzerland.;Geneva Univ Hosp, Div Nucl Med & Mol Imaging, Diagnost Dept, Geneva, Switzerland..
    Herrmann, Francois R.
    Geneva Univ Hosp, Dept Rehabil & Geriatr, Geneva, Switzerland.;Univ Geneva, Geneva, Switzerland..
    Giannakopoulos, Panteleimon
    Univ Geneva, Dept Psychiat, Geneva, Switzerland.;Geneva Univ Hosp, Div Inst Measures, Med Direct, Geneva, Switzerland..
    PET amyloid in normal aging: direct comparison of visual and automatic processing methods2020In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, article id 16665Article in journal (Refereed)
    Abstract [en]

    Assessment of amyloid deposits is a critical step for the identification of Alzheimer disease (AD) signature in asymptomatic elders. Whether the different amyloid processing methods impacts on the quality of clinico-radiological correlations is still unclear. We directly compared in 155 elderly controls with extensive neuropsychological testing at baseline and 4.5 years follow-up three approaches: (i) operator-dependent standard visual reading, (ii) operator-independent automatic SUVR with four different reference regions, and (iii) novel operator and region of reference-independent automatic A beta-index. The coefficient of variance was used to examine inter-individual variability for each processing method. Using visually-established amyloid positivity as the gold standard, the area under the receiver operating characteristic curve (ROC) was computed. Linear regression models were used to assess the association between changes in continuous cognitive score and amyloid uptake values. In SUVR analyses, the coefficient of variance varied from 1.718 to 1.762 according to the area of reference and was of - 3.045 for the A beta-index method. Compared to the visual rating, A beta-index method showed the largest area under the ROC curve [0.9568 (95% CI 0.9252, 0.98833)]. The best cut-off score was of - 0.3359 with sensitivity and specificity values of 0.97 and 0.83, respectively. Only the A beta-index was related to more severe decrement of cognitive performances [regression coefficient: 9.103 (95% CI 1.148, 17.058)]. The A beta-index is considered as preferred option in asymptomatic elders, since it is operator-independent, avoids the selection of reference area, is closer to established visual scoring and correlates with the evolution of cognitive performances.

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  • 48.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. CIRD Centre d’Imagerie Rive Droite, Geneva, Switzerland; Faculty of Medicine, University of Geneva, Geneva, Switzerland.
    Montandon, Marie-Louise
    Rodriguez, Cristelle
    Garibotto, Valentina
    Herrmann, François R.
    Giannakopoulos, Panteleimon
    Hippocampal Volume Loss, Brain Amyloid Accumulation, and APOE Status in Cognitively Intact Elderly Subjects2019In: Neurodegenerative Diseases, ISSN 1660-2854, E-ISSN 1660-2862, Vol. 19, no 3-4, p. 139-147Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Hippocampal volume loss (HVL), PET-documented brain amyloid accumulation, and APOE-ε4 status are predictive biomarkers of the transition from mild cognitive impairment to Alzheimer disease (AD). In asymptomatic cases, the role of these biomarkers remains ambiguous. In contrast to the idea that HVL occurs in late phases of neurodegeneration, recent contributions indicate that it might occur before abnormal amyloid PET occurrence in elderly subjects and that its severity could be only marginally related to APOE variants. Using a longitudinal design, we examined the determinants of HVL in our sample, i.e., brain amyloid burden and the presence of APOE-ε4, and made a longitudinal assessment of cognitive functions.

    METHODS: We performed a 4.5-year longitudinal study on 81 elderly community dwellers (all right-handed;, 48 (59.3%) women; mean age 73.7 ± 3.7 years) including MRI at baseline and follow-up, PET amyloid during follow-up, neuropsychological assessment at 18 and 54 months, and APOE genotyping. All cases were assessed using a continuous cognitive score (CCS) that took into account the global evolution of neuropsychological performance. Linear regression models were used to identify predictors of HVL.

    RESULTS: There was a negative association between the CCS and HVL bilaterally. In multivariate models adjusting for demographic variables, the presence of APOE-ε4 was related to increased HVL bilaterally. A trend of significance was observed with respect to the impact of amyloid positivity on HVL in the left hemisphere. No significant interaction was found between amyloid positivity and the APOE-ε4 allele.

    CONCLUSION: The progressive decrement of neuropsychological performance is associated with HVL long before the emergence of clinically overt symptoms. In this cohort of healthy individuals, the presence of the APOE-ε4 allele was shown to be an independent predictor of worst hippocampal integrity in asymptomatic cases independently of amyloid positivity.

  • 49.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. CIRD, Geneva, Switzerland; Univ Geneva, Fac Med, Geneva, Switzerland.
    Montandon, Marie-Louise
    Univ Geneva, Univ Hosp Geneva, Dept Rehabil & Geriatr, Geneva, Switzerland;Univ Geneva, Dept Psychiat, Geneva, Switzerland.
    Rodriguez, Cristelle
    Univ Geneva, Dept Psychiat, Geneva, Switzerland;Geneva Univ Hosp, Div Inst Measures, Med Direct, Geneva, Switzerland.
    Garibotto, Valentina
    Geneva Univ Hosp, Dept Diagnost, Div Nucl Med & Mol Imaging, Geneva, Switzerland.
    Lilja, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Hermes Med Solut, Stockholm, Sweden.
    Herrmann, Francois R.
    Univ Geneva, Univ Hosp Geneva, Dept Rehabil & Geriatr, Geneva, Switzerland.
    Giannakopoulos, Panteleimon
    Univ Geneva, Dept Psychiat, Geneva, Switzerland;Geneva Univ Hosp, Div Inst Measures, Med Direct, Geneva, Switzerland.
    Amyloid Load, Hippocampal Volume Loss, and Diffusion Tensor Imaging Changes in Early Phases of Brain Aging2019In: Frontiers in Neuroscience, ISSN 1662-4548, E-ISSN 1662-453X, Vol. 13, article id 1228Article in journal (Refereed)
    Abstract [en]

    Background and Purpose Amyloid imaging, gray matter (GM) morphometry and diffusion tensor imaging (DTI) have all been used as predictive biomarkers in dementia. Our objective was to define the imaging profile of healthy elderly controls as a function of their cognitive trajectories and explore whether amyloid burden and white matter (WM) microstructure changes are associated with subtle decrement of neuropsychological performances in old age. Materials and Methods We performed a 4.5-year longitudinal study in 133 elderly individuals who underwent cognitive testing at inclusion and follow-up, amyloid PET, MRI including DTI sequences at inclusion, and APOE epsilon 4 genotyping. All cases were assessed using a continuous cognitive score (CCS) taking into account the global evolution of neuropsychological performances. Data processing included region of interest analysis of amyloid PET analysis, GM densities and tract-based spatial statistics (TBSS)-DTI. Regression models were built to explore the association between the CCS and imaging parameters controlling for significant demographic and clinical covariates. Results Amyloid uptake was not related to the cognitive outcome. In contrast, GM densities in bilateral hippocampus were associated with worst CCS at follow-up. In addition, radial and axial diffusivities in left hippocampus were negatively associated with CCS. Amyloid load was associated with decreased VBM and increased radial and axial diffusivity in the same area. These associations persisted when adjusting for gender and APOE4 genotype. Importantly, they were absent in amygdala and neocortical areas studied. Conclusion The progressive decrement of neuropsychological performances in normal aging is associated with volume loss and WM microstructure changes in hippocampus long before the emergence of clinically overt symptoms. Higher amyloid load in hippocampus is compatible with cognitive preservation in cases with better preservation of GM densities and WM microstructure in this area.

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  • 50.
    Haller, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. CIMC Ctr Imagerie Med Cornavin, Geneva, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland.;Capital Med Univ, Beijing Tiantan Hosp, Dept Radiol, Beijing, Peoples R China..
    Montandon, Marie-Louise
    Univ Geneva, Geneva Univ Hosp, Dept Rehabil & Geriatr, Geneva, Switzerland..
    Rodriguez, Cristelle
    Geneva Univ Hosp, Div Inst Measures, Med Direct, Geneva, Switzerland..
    Herrmann, Francois R.
    Univ Geneva, Geneva Univ Hosp, Dept Rehabil & Geriatr, Geneva, Switzerland..
    Giannakopoulos, Panteleimon
    Geneva Univ Hosp, Div Inst Measures, Med Direct, Geneva, Switzerland.;Univ Geneva, Fac Med, Dept Psychiat, Geneva, Switzerland..
    Automatic MRI volumetry in asymptomatic cases at risk for normal pressure hydrocephalus2023In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 15, article id 1242158Article in journal (Refereed)
    Abstract [en]

    The occurrence of significant Alzheimer's disease (AD) pathology was described in approximately 30% of normal pressure hydrocephalus (NPH) cases, leading to the distinction between neurodegenerative and idiopathic forms of this disorder. Whether or not there is a specific MRI signature of NPH remains a matter of debate. The present study focuses on asymptomatic cases at risk for NPH as defined with automatic machine learning tools and combines automatic MRI assessment of cortical and white matter volumetry, risk of AD (AD-RAI), and brain age gap estimation (BrainAge). Our hypothesis was that brain aging and AD process-independent volumetric changes occur in asymptomatic NPH-positive cases. We explored the volumetric changes in normal aging-sensitive (entorhinal cortex and parahippocampal gyrus/PHG) and AD-signature areas (hippocampus), four control cortical areas (frontal, parietal, occipital, and temporal), and cerebral and cerebellar white matter in 30 asymptomatic cases at risk for NPH (NPH probability >30) compared to 30 NPH-negative cases (NPH probability <5) with preserved cognition. In univariate regression models, NPH positivity was associated with decreased volumes in the hippocampus, parahippocampal gyrus (PHG), and entorhinal cortex bilaterally. The strongest negative association was found in the left hippocampus that persisted when adjusting for AD-RAI and Brain Age values. A combined model including the three parameters explained 36.5% of the variance, left hippocampal volumes, and BrainAge values, which remained independent predictors of the NPH status. Bilateral PHG and entorhinal cortex volumes were negatively associated with NPH-positive status in univariate models but this relationship did not persist when adjusting for BrainAge, the latter remaining the only predictor of the NPH status. We also found a negative association between bilateral cerebral and cerebellar white matter volumes and NPH status that persisted after controlling for AD-RAI or Brain Age values, explaining between 50 and 65% of its variance. These observations support the idea that in cases at risk for NPH, as defined by support vector machine assessment of NPH-related MRI markers, brain aging-related and brain aging and AD-independent volumetric changes coexist. The latter concerns volume loss in restricted hippocampal and white matter areas that could be considered as the MRI signature of idiopathic forms of NPH.

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