Precise anatomic localization of insulinomas is crucial for surgical treatment. Current routine noninvasive imaging techniques, including CT, MRI, and ⁶⁸Ga-DOTA-somatostatin analog (DOTA-SSA) PET/CT, have limited sensitivity. Endoscopic ultrasound is highly sensitive but invasive. In this prospective multicenter study, we compared the diagnostic accuracy of ⁶⁸Ga-NODAGA-exendin-4 (exendin) PET/CT with all routine imaging procedures for the localization of insulinomas. Methods: Sixty-nine adults with biochemically proven adult endogenous hyperinsulinemic hypoglycemia underwent exendin PET/CT and current routine imaging. Images were evaluated in a clinical reading and in an expert reading. Image quality was determined by quantitative analysis. Results: Based on clinical readings, the accuracy of exendin PET/CT (94.4%; 95% CI, 84.6%-98.8%) was greater than that of DOTA-SSA PET/CT (64.8%; 95% CI, 50.6%-77.3%), contrast-enhanced CT/contrast-enhanced diffusion-weighted imaging-MRI (83.3%; 95% CI, 70.7%-92.1%), and endoscopic ultrasound (82.8%; 95% CI, 64.1%-94.1%). In 13% of patients, a correct diagnosis was only reached after exendin PET/CT. Interobserver agreement between readings was higher for exendin PET/CT than for DOTA-SSA PET/CT and contrast-enhanced CT/contrast-enhanced diffusion-weighted imaging-MRI (Cohen κ, 1.0 vs. 0.5 and 0.55). Exendin PET/CT provided a higher insulinoma-to-background ratio (15.3 ± 6.7 vs. 5.2 ± 3.0) and contrast-to-noise ratio (22.6 ± 11.1 vs. 5.1 ± 3.7) than did DOTA-SSA PET/CT. Conclusion: This study demonstrates the superiority of exendin PET/CT in a unique prospective comparison to all current routine imaging modalities for preoperative localization of benign insulinomas, providing the level of evidence needed for clinical implementation.

Purpose & Methods Neuroendocrine neoplasms are a heterogenous group of tumours, for which nuclear medicine plays an important role in the diagnostic work-up as well as in the targeted therapeutic options. This guideline is aimed to assist nuclear medicine physicians in recommending, performing, reporting and interpreting the results of somatostatin receptor (SSTR) PET/CT imaging using Ga-68-DOTA-conjugated peptides, as well as F-18-DOPA imaging for various neuroendocrine neoplasms. Results & Conclusion The previous procedural guideline by EANM regarding the use PET/CT tumour imaging with Ga-68-conjugated peptides has been revised and updated with the relevant and recent literature in the field with contribution of distinguished experts.

The determination of tumor human epidermal growth factor receptor type 2 (HER2) status is of increasing importance with the recent approval of more efficacious HER2-targeted treatments. There is a lack of suitable methods for clinical in vivo HER2 expression assessment. Affibody molecules are small affinity proteins ideal for imaging detection of receptors, which are engineered using a small (molecular weight 6.5 kDa) nonimmunoglobulin scaffold. Labeling of Affibody molecules with positron emitters enabled the development of sensitive and specific agents for molecular imaging. The development of probes for SPECT would permit the use of Affibody-based imaging in regions where PET is not available. In this first-in-human study, we evaluated the safety, biodistribution, and dosimetry of the Tc-99m-ZHER2:41071 Affibody molecule developed for SPECT/CT imaging of HER2 expression.Methods: Thirty-one patients with primary breast cancer were enrolled and divided into three cohorts (injected with 500, 1000, or 1500 mu g ZHER2:41071) comprising at least five patients with high (positive) HER2 tumor expression (IHC score 3+ or 2+ and ISH positive) and five patients with low (IHC score 2+ or 1+ and ISH negative) or absent HER2 tumor expression. Patients were injected with 451 +/- 71 MBq Tc-99m-ZHER2:4107. Planar scintigraphy was performed after 2, 4, 6 and 24 h, and SPECT/CT imaging followed planar imaging 2, 4 and 6 h after injection.Results: Injections of Tc-99m-ZHER2:41071 were well tolerated and not associated with adverse events. Normal organs with the highest accumulation were the kidney and liver. The effective dose was 0.019 +/- 0.004 mSv/MBq. Injection of 1000 mu g provided the best standard discrimination between HER2-positive and HER2-low or HER2-negative tumors 2 h after injection (SUVmax 16.9 +/- 7.6 vs. 3.6 +/- 1.4, p < 0.005). The Tc-99m-ZHER2:41071 uptake in HER2-positive lymph node metastases (SUVmax 6.9 +/- 2.4, n = 5) was significantly (p < 0.05) higher than that in HER2-low/negative lymph nodes (SUVmax 3.5 +/- 1.2, n = 4). Tc-99m-ZHER2:41071 visualized hepatic metastases in a patient with liver involvement.Conclusions: Injections of Tc-99m-ZHER2:41071 appear safe and exhibit favorable dosimetry. The protein dose of 1000 mu g provides the best discrimination between HER2-positive and HER2-low/negative expression of HER2 according to the definition used for current HER2-targeting drugs.

Radionuclide molecular imaging of human epidermal growth factor receptor type 2 (HER2) expression may enable a noninvasive discrimination between HER2-positive and HER2-negative breast cancers for stratification of patients for HER2-targeted treatments. DARPin (designed ankyrin repeat proteins) G3 is a small (molecular weight, 14 kDa) scaffold protein with picomolar affinity to HER2. The aim of this first-in-humans study was to evaluate the safety, biodistribution, and dosimetry of ^99mTc-(HE)₃-G3.

Methods: Three cohorts of patients with primary breast cancer (each including at least 4 patients with HER2-negative and 5 patients with HER2-positive tumors) were injected with 1,000, 2,000, or 3,000 μg of ^99mTc-(HE)₃-G3 (287 ± 170 MBq). Whole-body planar imaging followed by SPECT was performed at 2, 4, 6, and 24 h after injection. Vital signs and possible side effects were monitored during imaging and up to 7 d after injection.

Results: All injections were well tolerated. No side effects were observed. The results of blood and urine analyses did not differ before and after studies. ^99mTc-(HE)₃-G3 cleared rapidly from the blood. The highest uptake was detected in the kidneys and liver followed by the lungs, breasts, and small intestinal content. The hepatic uptake after injection of 2,000 or 3,000 μg was significantly (P < 0.05) lower than the uptake after injection of 1,000 μg. Effective doses did not differ significantly between cohorts (average, 0.011 ± 0.004 mSv/MBq). Tumor–to–contralateral site ratios for HER-positive tumors were significantly (P < 0.05) higher than for HER2-negative at 2 and 4 h after injection.

Conclusion: Imaging of HER2 expression using ^99mTc-(HE)₃-G3 is safe and well tolerated and provides a low absorbed dose burden on patients. This imaging enables discernment of HER2-positive and HER2-negative breast cancer. Phase I study data justify further clinical development of ^99mTc-(HE)₃-G3.

Previous Phase I clinical evaluations of the radiolabelled scaffold proteins [Tc-99m]Tc-ADAPT6 and DARPin [Tc-99m]Tc-(HE)(3)-G3 in breast cancer patients have demonstrated their safety and indicated their capability to discriminate between HER2-positive and HER2-negative tumours. The objective of this study was to compare the imaging of HER2-positive tumours in the same patients using [Tc-99m]Tc-ADAPT6 and [Tc-99m]Tc-(HE)(3)-G3. Eleven treatment-naive female patients (26-65 years) with HER2-positive primary and metastatic breast cancer were included in the study. Each patient was intravenously injected with [Tc-99m]Tc-ADAPT6, followed by an [Tc-99m]Tc-(HE)(3)-G3 injection 3-4 days later and chest SPECT/CT was performed. All primary tumours were clearly visualized using both tracers. The uptake of [Tc-99m]Tc-ADAPT6 in primary tumours (SUVmax = 4.7 & PLUSMN; 2.1) was significantly higher (p < 0.005) than the uptake of [Tc-99m]Tc-(HE)(3)-G3 (SUVmax = 3.5 & PLUSMN; 1.7). There was no significant difference in primary tumour-to-contralateral site values for [Tc-99m]Tc-ADAPT6 (15.2 & PLUSMN; 7.4) and [Tc-99m]Tc-(HE)(3)-G3 (19.6 & PLUSMN; 12.4). All known lymph node metastases were visualized using both tracers. The uptake of [Tc-99m]Tc-ADAPT6 in all extrahepatic soft tissue lesions was significantly (p < 0.0004) higher than the uptake of [Tc-99m]Tc-(HE)(3)-G3. In conclusion, [Tc-99m]Tc-ADAPT6 and [Tc-99m]Tc-(HE)(3)-G3 are suitable for the visualization of HER2-positive breast cancer. At the selected time points, [Tc-99m]Tc-ADAPT6 has a significantly higher uptake in soft tissue lesions, which might be an advantage for the visualization of small metastases.

Radionuclide molecular imaging of human epidermal growth factor (HER2) expression may be helpful to stratify breast and gastroesophageal cancer patients for HER2-targeting therapies. ADAPTs (albumin-binding domain derived affinity proteins) are a new type of small (46-59 amino acids) proteins useful as probes for molecular imaging. The aim of this first-in-human study was to evaluate biodistribution, dosimetry, and safety of the HER2-specific ^99mTc-ADAPT6.

METHODS: Twenty-nine patients with primary breast cancerwere included. In 22 patients with HER2-positive (n = 11) or HER2-negative (n = 11) histopathology an intravenous injection with 385±125 MBq ^99mTc-ADAPT6 was performed, randomized to an injected protein mass of either 500 µg (n = 11) or 1000 µg (n = 11). Planar scintigraphy followed by SPECT imaging was performed after 2, 4, 6 and 24 h. An additional cohort (n = 7) was injected with 165±29 MBq (injected protein mass 250 µg) and imaging was performed after 2 h only.

RESULTS: Injections of ^99mTc-ADAPT6 at all injected mass levels were well tolerated and not associated with adverse effects. ^99mTc-ADAPT6 cleared rapidly from blood and most other tissues. The normal organs with the highest accumulation were kidney, liver and lung. Effective doses were 0.009±0.002 and 0.010±0.003 mSv/MBq for injected protein masses of 500 and 1000 µg, respectively. Injection of 500 µg resulted in excellent discrimination between HER2-positive and HER2-negative tumors already 2 h after injection (tumor-to-contralateral breast ratio was 37±19 vs 5±2, p<0.01). The tumor-to-contralateral breast ratios for HER2-positive tumors were significantly (p<0.05) higher for injected mass of 500 µg than for both 250 and 1000 µg.

CONCLUSION: Injections of ^99mTc-ADAPT6 are safe and associated with low absorbed and effective doses. Protein dose of 500 µg is preferable for discrimination between tumors with high and low expression of HER2. Further studies are justified to evaluate if ^99mTc-ADAPT6 can be used as an imaging probe for stratification of patients for HER2-targeting therapy in the areas where PET imaging is not readily available.

Bakgrund: Inom röntgensjuksköterskans profession ligger stor vikt på att undersökningarna är så effektiva som möjligt för att hinna med avdelningarnas patientflöden. I dessa sammanhang hamnar patienten lätt i skymundan. Person- och patientcentrerad vård har blivit mer aktuella under de senaste åren, där personcentrerad vård är en del av professionens målbild, vilket lett till ett behov av ökad medvetenhet om begreppen och deras skillnader.

Syfte: Studiens syfte var att ta reda på om röntgensjuksköterskor är medvetna om de jobbar med person- eller patientcentrerad vård samt om de vet skillnaden mellan dessa två begrepp och om detta följs upp antingen via utbildningar, föreläsningar eller på arbetsplatsträffar.

Metod: En kvalitativ intervjustudie utfördes semistrukturerat med öppna frågor. Intervjuerna utfördes med 15 röntgensjuksköterskor vid två sjukhus. Intervjuerna analyserades med en induktiv manifest innehållsanalys och delades upp utefter domäner, subteman och teman.

Resultat: Majoriteten av informanterna på sjukhusen hade någon kunskap angående begreppet patientcentrerad vård från sin utbildning eller arbetsplats. Några få informanter hade hört talas om begreppet personcentrerad vård men för flertalet var detta ett nytt begrepp. Begreppen förväxlades ofta och informanterna kände inte till någon tydlig skillnad. Informanterna kände flera gånger en avsaknad av informering om begreppen från sina avdelningar.

Slutsats: Röntgensjuksköterskornas avsaknad av kännedom om begreppet personcentrerad vård visar att det är lång väg kvar innan professionens mål om personcentrerad vård är uppnått på röntgenavdelningar. Genom vidare informering kan medvetenheten om begreppen öka. Tidsbrist var det största hindret för röntgensjuksköterskorna att kunna arbeta utifrån patientens behov.

Background: Lumbar punctures are a common examination in the work-up of patients with idiopathic normal pressure hydrocephalus (iNPH) and cerebrospinal fluid (CSF) biomarkers should therefore be available for use in selection of shunt candidates. The aim of this study was to investigate if CSF biomarkers are associated with outcome after shunt surgery alone or in combination with comorbidity and imaging markers, and investigate associations between CSF biomarkers and symptoms

Methods: Preoperative CSF biomarkers were analyzed in 455 patients operated with shunt surgery for iNPH at a single center during 2011–2018. Symptoms before and 12 months after shunt surgery were graded with the Swedish iNPH scale. Neurofilament light chain protein (NfL), total tau (T-tau), phosphorylated tau (P-tau) and amyloid beta1-42 (Aβ1-42) CSF levels were measured. Evans’ index and disproportionately enlarged subarachnoid space hydrocephalus were measured on preoperative CT-scans. Preoperative evaluation and follow-up 12 months after shunt surgery were available in 376 patients.

Result: Higher levels of NfL and T-tau were associated with less improvement after shunt surgery (β = − 3.10, p = 0.016 and β = − 2.45, p = 0.012, respectively). Patients whose symptoms deteriorated after shunt surgery had higher preoperative levels of NfL (1250 ng/L [IQR:1020–2220] vs. 1020 [770–1649], p < 0.001) and T-tau (221 ng/L [IQR: 159–346] vs. 190 [135–261], p = 0.0039) than patients with postoperative improvement on the iNPH scale. Among the patients who improved ≥ 5 levels on the iNPH scale (55%), NfL was abnormal in 22%, T-tau in 14%, P-tau in 6% and Aβ1-42 in 45%, compared with normal reference limits. The inclusion of CSF biomarkers, imaging markers and comorbidity in multivariate predictive Orthogonal Projections to Latent Structures (OPLS) models to did not improve predictability in outcome after shunt surgery.

Conclusions: Higher levels of T-tau and NfL were associated with a less favorable response to shunt surgery, suggesting a more active neurodegeneration in this group of patients. However, CSF levels of these biomarkers can be elevated also in patients who respond to shunt surgery. Thus, none of these CSF biomarkers, alone or used in combination, are suitable for excluding patients from surgery.

Purpose: Voxel-level hypothesis testing on images suffers from test multiplicity. Numerous correction methods exist, mainly applied and evaluated on neuroimaging and synthetic datasets. However, newly developed approaches like Imiomics, using different data and less common analysis types, also require multiplicity correction for more reliable inference. To handle the multiple comparisons in Imiomics, we aim to evaluate correction methods on whole-body MRI and correlation analyses, and to develop techniques specifically suited for the given analyses. Approach: We evaluate the most common familywise error rate (FWER) limiting procedures on whole-body correlation analyses via standard (synthetic no-activation) nominal error rate estimation as well as smaller prior-knowledge based stringency analysis. Their performance is compared to our anatomy-based method extensions. Results: Results show that nonparametric methods behave better for the given analyses. The proposed prior-knowledge based evaluation shows that the devised extensions including anatomical priors can achieve the same power while keeping the FWER closer to the desired rate. Conclusions: Permutation-based approaches perform adequately and can be used within Imiomics. They can be improved by including information on image structure. We expect such method extensions to become even more relevant with new applications and larger datasets.

Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10^-8), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait. Half of the alleles associated with higher proinsulin showed higher rather than lower effects on glucose levels, corresponding to different mechanisms. Proinsulin loci included genes that affect prohormone convertases, beta-cell dysfunction, vesicle trafficking, beta-cell transcriptional regulation, and lysosomes/autophagy processes. We colocalized 11 proinsulin signals with islet expression quantitative trait locus (eQTL) data, suggesting candidate genes, including ARSG, WIPI1, SLC7A14, and SIX3. The NKX6-3/ANK1 proinsulin signal colocalized with a T2D signal and an adipose ANK1 eQTL signal but not the islet NKX6-3 eQTL. Signals were enriched for islet enhancers, and we showed a plausible islet regulatory mechanism for the lead signal in the MADD locus. These results show how detailed genetic studies of an intermediate phenotype can elucidate mechanisms that may predispose one to disease.

Background and purpose - Early implant migration is known to be a predictive factor of clinical loosening in total hip arthroplasty (THA). Radiostereometric analysis (RSA) is the gold standard used to measure early migration in patients. However, RSA requires costly, specialized imaging equipment and the image process is complex. We determined the precision of an alternative, commercially available, CT method in 3 ongoing clinical THA studies, comprising 3 different cups.

Materials and methods - 24 CT double examinations of 24 hip cups were selected consecutively from 3 ongoing prospective studies: 2 primary THA (1 cemented and 1 uncemented) and 1 THA (cemented) revision study. Precision of the CT-based implant motion analysis (CTMA) system was calculated separately for each study, using both the surface anatomy of the pelvis and metal beads placed in the pelvis.

Results - For the CTMA analysis using the surface anatomy of the pelvis, the precision ranged between 0.07 and 0.31 mm in translation and 0.20° and 0.39° for rotation, respectively. For the CTMA analysis using beads the precision ranged between 0.08 and 0.20 mm in translation and between 0.20° and 0.43° for rotations. The radiation dose ranged between 0.2 and 2.3 mSv.

Interpretation - CTMA achieved a clinically relevant and consistent precision between the 3 different hip cups studied. The use of different hip cup types, different CT scanners, or registration method (beads or surface anatomy) had no discernible effect on precision. Therefore, CTMA without the use of bone markers could potentially be an alternative to RSA to measure early migration.

We consider thinning methods to extract one dimensional skeletons from discrete objects defined on the body-centered cubic (bcc) lattice. In Strand (2004), a condition has been given that guarantees the preservation of the object's topology in such a thinning process. In this paper, we present stronger conditions that even allow the topological invariant point removal in a parallelized process. These conditions for p-simplicity can be efficiently evaluated which leads to a very fast thinning process. We show that p-simplicity is a new concept that cannot be obtained by adapting the checking plane conditions of Tsao and Fu to the bcc lattice. Furthermore, we introduce distance information and an optional pruning mechanism into the thinning process to improve the quality of the resulting skeletons. The presented results show that our method generates high quality skeletons that reproduce the symmetries of the models even under the condition of added noise and contain only very few spurious branches. The presented running times demonstrate the linear run-time behavior of our algorithm and the speedup that is achieved by the parallelization. (C) 2022 Elsevier Ltd. All rights reserved.

AIMS/HYPOTHESIS: Maternal obesity predisposes offspring to adulthood morbidities, including type 2 diabetes. Type 2 diabetes and insulin resistance have been associated with shortened telomere length. First, we aimed to investigate whether or not maternal obesity influences insulin sensitivity and its relationship with leucocyte telomere length (LTL) in elderly women. Second, we tested whether or not resistance exercise training improves insulin sensitivity in elderly frail women.

METHODS: Forty-six elderly women, of whom 20 were frail offspring of lean/normal weight mothers (OLM, BMI ≤26.3 kg/m(2)) and 17 were frail offspring of overweight/obese mothers (OOM, BMI ≥28.1 kg/m(2)), were studied before and after a 4 month resistance training (RT) intervention. Muscle insulin sensitivity of glucose uptake was measured using (18)F-fluoro-2-deoxyglucose and positron emission tomography with computed tomography during a hyperinsulinaemic-euglycaemic clamp. Muscle mass and lipid content were measured using magnetic resonance and LTL was measured using real-time PCR.

RESULTS: The OOM group had lower thigh muscle insulin sensitivity compared with the OLM group (p = 0.048) but similar whole body insulin sensitivity. RT improved whole body and skeletal muscle insulin sensitivity in the OOM group only (p = 0.004 and p = 0.013, respectively), and increased muscle mass in both groups (p < 0.01). In addition, in the OOM group, LTL correlated with different thigh muscle groups insulin sensitivity (ρ ≥ 0.53; p ≤ 0.05). Individuals with shorter LTL showed a higher increase in skeletal muscle insulin sensitivity after training (ρ ≥ -0.61; p ≤ 0.05).

CONCLUSIONS/INTERPRETATION: Maternal obesity and having telomere shortening were associated with insulin resistance in adult offspring. A resistance exercise training programme may reverse this disadvantage among offspring of obese mothers.

TRIAL REGISTRATION: ClinicalTrials.gov NCT01931540.

YKL-40 (CHI3L1) is a glycoprotein predominantly produced by reactive astrocytes in chronic active MS lesions, which are common in secondary progressive MS. In this study, YKL-40 was investigated in different stages of MS and in relation to MRI findings. YKL-40 levels in CSF samples from two independent patient cohorts of MS patients were determined with ELISA. CSF YKL-40 was increased in patients with active relapsing-remitting MS and correlated with the number of gadolinium enhancing lesions. Patients with secondary progressive MS had similar high levels of YKL-40, whereas not active relapsing-remitting MS patients had YKL-40 levels comparable to healthy controls.

Context

Women with congenital adrenal hyperplasia (CAH) may present with androgen excess that is difficult to control with conventional suppressive doses of glucocorticoids. Clinical management is challenging, and the woman is at great risk of developing steroid-induced complications.

Patients and Methods

A 32-year-old woman with salt-wasting CAH due to 21-hydroxylase deficiency underwent right-sided adrenalectomy because of a large myelolipoma. Over the years, androgens became increasingly difficult to suppress on prednisolone 5 + 0 + 2.5 mg daily, and at age 39 years the left adrenal with an enlarging myelolipoma was removed. A month later serum testosterone levels had increased from 4.1 preoperatively to 18.3 nmol/L (reference 0.2-1.8 nmol/L), and adrenocorticotropin levels from 32 to 283 pmol/L (reference < 14 pmol/L). No adrenal parenchyma was visualized on computed tomography (CT). In the further search for the source of the markedly elevated testosterone, positron emission tomography (PET) was performed with 2 different tracers, ¹⁸fluorodeoxyglucose (¹⁸FDG) reflecting glucose metabolism and ¹¹C-metomidate, an inhibitor of 11-β-hydroxylase targeting adrenocortical tissue.

Results

¹⁸FDG-PET/CT with cosyntropin stimulation showed ovarian/paraovarian hypermetabolism, suggestive of adrenal rest tumors. Further characterization with ¹¹C-metomidate PET/CT showed uptakes localized to the ovaries/adnexa, behind the spleen, and between the right crus diaphragmaticus and inferior vena cava.

Conclusion

Adrenal rest tumors can give rise to high androgen levels in spite of suppressive supraphysiological glucocorticoid doses. This case illustrates, for the first time, the value of ¹¹C-metomidate PET as a sensitive method in documenting adrenal rest tumors, currently considered rare in women with CAH.

Adrenal cysts are rare lesions representing approximately 1-2% of adrenal incidentalomas. The majority of these rare lesions are benign. Rarely, phaeochromocytomas and adrenal malignant masses can present as cystic lesions and can occasionally be difficult to distinguish from benign cysts. Histologically, adrenal cysts are subdivided into pseudocysts, endothelial cysts, epithelial cysts and parasitic cysts. The radiological appearance of an adrenal cyst is generally similar to that of cysts in the kidney. They are thus well demarcated, usually rounded, with a thin wall and homogenous internal structure, low attenuating (<20 Hounsfield Units) on CT, low signalling on T1-weighted MRI sequences and high signalling on T2-weighted MRI sequences, and anechoic or hypoechoic on ultrasonography. Benign adrenal cysts have a slight female predominance and are usually diagnosed between the ages of 40 and 60. Most adrenal cysts are asymptomatic and are detected incidentally, although very large adrenal cysts can lead to mass effect symptoms, with surgery required to alleviate the symptoms. Thus, conservative management is usually recommended for asymptomatic cysts. However, when uncertainty exists regarding the benign nature of the cyst, additional work-up or follow-up is needed. The management of an adrenal cyst should preferably be discussed at an adrenal multidisciplinary team meeting.

Adrenal myelolipomas are benign, lipomatous tumours with elements of myeloid cells, most of which present as adrenal incidentalomas and comprise 3·3-6·5% of all adrenal masses. Adrenal myelolipomas are usually unilateral (in 95% of cases), variable in size, most often found during midlife, and affect both sexes almost equally. On imaging, adrenal myelolipomas show pathognomonic imaging features consistent with the presence of macroscopic fat. Large adrenal myelolipomas can cause symptoms of mass effect, and can occasionally be complicated by haemorrhage. In the event of a concomitant adrenal cortical adenoma or hyperplasia, adrenal hormone excess might be detected in patients with adrenal myelolipoma. Patients with congenital adrenal hyperplasia exhibit a higher prevalence of adrenal myelolipomas than other patient groups, and are at risk of developing large and bilateral lesions. This Review discusses the pathogenesis, clinical presentation, and management of adrenal myelolipomas.

Introduction: The purpose of the study was to evaluate the ability of brain-targeted MRI to assess the anatomy of the fetal upper lip and palate.

Methods: Two independent readers made a blind retrospective review of 60 MRI of fetuses of 20 to 38 gestational weeks (GW). Fifty-five fetuses had normal post-natal follow-up.  Five fetuses had oro-facial anomalies at post-natal follow-up, including five cleft lips (two bilateral, three unilateral), four cleft primary palates (two bilateral, two unilateral) and two cleft secondary palates.

The upper lip, primary palate, secondary palate and nasal septum were scored into four levels, from evidently normal to evidently abnormal. In case of a suspected pathology, the readers attempted a diagnosis.

Results: Interobserver agreement (weighted kappa) was 0.79 for the upper lip, 0.70 for the primary palate, 0.86 for the secondary palate, and 0.90 for the nasal septum. The scoring levels of the readers did not change significantly across gestational age.

The readers identified 100% of all pathological cases. The normality was correctly scored in 96-100% of the normal lips and primary palates and in 93-97% of the normal secondary palates depending on the reader. A deviated septum was only scored in two fetuses with unilateral cleft palates.

Conclusion:  MRI in experienced hands seems reliable for assessment of the fetal lip and palate, even in brain-targeted examinations. Attention should therefore be paid to the lip and palate in all fetal MRI examinations, since unsuspected clefts may be revealed.

Hybrid imaging consists of a combination of two or more imaging modalities, which equally contribute to image information. To date, hybrid cardiovascular imaging can be performed by either merging images acquired on different scanners, or with truly hybrid PET/CT and PET/MR scanners. The European Association of Nuclear Medicine (EANM), and the European Association of Cardiovascular Imaging (EACVI) of the European Society of Cardiology (ESC) aim to review clinical situations that may benefit from the use of hybrid cardiac imaging and provide advice on acquisition protocols providing the most relevant information to reach diagnosis in various clinical situations.

Unmet medical needs are not infrequent in oncology, and these needs are usually of higher magnitude in rare cancers. The field of neuroendocrine neoplasms (NENs) has evolved rapidly during the last decade, and, currently, a new WHO classification is being implemented and several treatment options are available in the metastatic setting after the results of prospective phase III clinical trials. However, several questions are still unanswered, and decisions in our daily clinical practice should be made with limited evidence. In the 2016 meeting of the advisory board of the European Neuroendocrine Tumor Society (ENETS), the main unmet medical needs in the metastatic NENs setting were deeply discussed, and several proposals to try to solve them are presented in this article, including biomarkers, imaging, and therapy.

In order to further advance the field of diabetes research there is a great need for establishing validated non-invasive quantitative techniques to study the pancreas and other tissues of importance for blood glucose regulation. The general aim of this thesis was to explore magnetic resonance techniques and positron emission tomography as such tools.

In paper I pancreatic perfusion under basal conditions and in response to glucose in nondiabetic and type 1 diabetic individuals was studied with [¹⁵O]H₂O PET/CT. Individuals with type 1 diabetes were found to have reduced basal pancreatic perfusion and a severely impaired pancreatic and splanchnic perfusion response to intravenous glucose stimulation.

In paper II four groups of subjects at different stages of type 2 diabetes development and a control group of individuals without diabetes were examined with PET/CT and MRI. The [¹¹C]5-HTP uptake in pancreas was hypothesized to correlate with remaining functional capacity of the β-cells. The progressive loss of β-cell function indicated by metabolic testing was not mirrored by a decrease in [¹¹C]5-HTP tracer accumulation in the pancreas. This provides evidence of retained islet mass despite decreased β-cell function, indicating that β-cell dysfunction or dedifferentiation, and not necessarily endocrine cell loss, constitutes a major cause of β-cell failure in type 2 diabetes.

In paper III the feasibility of using ex-vivo MR spectroscopy for assessment of viability of human pancreas grafts prior to transplantation was studied. It was found that ³¹P-MRS may provide quantitative parameters for evaluating graft viability ex vivo, and is a promising tool for objective non-invasive assessment of the quality of human pancreas grafts.

In paper IV the Imiomics method for automatic image analysis was validated in whole-body [¹⁸F]-FDG PET/MR images in subjects with varying degree of insulin resistance. Imiomics was found to provide association screening and timesaving analysis of whole-body data and detected differences in glucose uptake and tissue composition between subjects on voxel-level. However, it did not show complete correlation with traditional volume of interest based tissue analysis in a small cohort.

AIM: We wanted to explore if whole-body magnetic resonance imaging (MRI) including diffusion-weighted (DW) and liver-specific contrast agent-enhanced imaging could be valuable in lesion detection of neuroendocrine tumors (NET). [11C]-5-Hydroxytryptophan positron emission tomography/computed tomography (5-HTP PET/CT) was used for comparison.

MATERIALS AND METHODS: Twenty-one patients with NET were investigated with whole-body MRI, including DW imaging (DWI) and contrast-enhanced imaging of the liver, and whole-body 5-HTP PET/CT. Seven additional patients underwent upper abdomen MRI including DWI, liver-specific contrast agent-enhanced imaging, and 5-HTP PET/CT.

RESULTS: There was a patient-based concordance of 61% and a lesion-based concordance of 53% between the modalities. MRI showed good concordance with PET in detecting bone metastases but was less sensitive in detecting metastases in mediastinal lymph nodes. MRI detected more liver metastases than 5-HTP PET/CT.

CONCLUSION: Whole-body MRI with DWI did not detect all NET lesions found with whole-body 5-HTP PET/CT. Our findings indicate that MRI of the liver including liver-specific contrast agent-enhanced imaging and DWI could be a useful complement to whole-body 5-HTP PET/CT.

AIMS/HYPOTHESIS: The aim of this study was to investigate pancreatic perfusion and its response to a glucose load in patients with type 1 diabetes mellitus compared with non-diabetic ('healthy') individuals.

METHODS: Eight individuals with longstanding type 1 diabetes and ten sex-, age- and BMI-matched healthy controls underwent dynamic positron emission tomography scanning with (15)O-labelled water before and after intravenous administration of glucose. Perfusion in the pancreas was measured. Portal and arterial hepatic perfusion were recorded as references.

RESULTS: Under fasting conditions, total pancreatic perfusion was on average 23% lower in the individuals with diabetes compared with healthy individuals. Glucose increased total pancreatic and portal hepatic blood perfusion in healthy individuals by 48% and 38%, respectively. In individuals with diabetes there was no significant increase in either total pancreatic or portal hepatic perfusion.

CONCLUSIONS/INTERPRETATION: Individuals with type 1 diabetes have reduced basal pancreatic perfusion and a severely impaired pancreatic and splanchnic perfusion response to intravenous glucose stimulation.

[(11)C]5-hydroxy-tryptophan ([(11)C]5-HTP) PET of the pancreas has been shown to be a surrogate imaging biomarker of pancreatic islet mass. The change in islet mass in different stages of type 2 diabetes (T2D) as measured by non-invasive imaging is currently unknown. Here, we describe a cross-sectional study where subjects at different stages of T2D development with expected stratification of pancreatic islet mass were examined in relation to non-diabetic individuals. The primary outcome was the [(11)C]5-HTP uptake and retention in pancreas, as a surrogate marker for the endogenous islet mass.We found that metabolic testing indicated a progressive loss of beta cell function, but that this was not mirrored by a decrease in [(11)C]5-HTP tracer accumulation in the pancreas. This provides evidence of retained islet mass despite decreased beta cell function. The results herein indicates that beta cell dedifferentiation, and not necessarily endocrine cell loss, constitute a major cause of beta cell failure in T2D.

Objective: To investigate the feasibility of using (31)P-MRS for objective non-invasive quality assessment of human pancreas grafts prior to transplantation or islet isolation.

Materials and methods: Pancreata from 5 human donors, 3 males and 2 females, aged 49-78years, with body mass index (BMI) 22-31kg/m(2), were included. Pancreata were perfused with histidine-tryptophan-ketoglutarate solution during procurement and stored in hypothermic condition (4°C) for 21-44h. During the period of hypothermic storage repeated spectra were obtained for each graft by (31)P-MRS (1.5Tesla) to measure the cold ischemia time (CIT) dependent changes of the phosphorous metabolites adenosine triphosphate (ATP), phosphomonoesters (PME), phosphodiesters (PDE) and inorganic phosphate (Pi), in the grafts. Graft temperature was measured immediately before and after MR-examination. Reference spectrum for non-viable tissue was obtained after graft exposure to room temperature.

Results: PME/Pi, PDE/Pi and ATP/Pi spectral intensities ratios decreased with increasing CIT, reflecting the decreased viability of the grafts. PME/Pi ratio was the most discriminatory variable at prolonged CIT. (31)P-MRS could be performed without significantly increasing graft temperature.

Conclusions: (31)P-MRS may provide quantitative parameters for evaluating graft viability ex vivo, and is a promising tool for objective non-invasive assessment of the quality of human pancreas grafts prior to transplantation or islet isolation.

SAMMANFATTNING

Nyckelord: barnröntgen, patientinformation, röntgensjuksköterska, barnkonventionen

Bakgrund: För röntgensjuksköterskor är det utmanande att informera barnpatienter utifrån barnkonventionens riktlinjer, som är svensk lag sedan 2020. 

Syfte: Syftet med denna enkätstudie var att ta reda på vilken patientinformation som röntgensjuksköterskan ansåg var viktig att ge till barnpatienter i samband med konventionell skelettröntgenundersökning samt vilka förutsättningar som var viktiga för att kunna tilldela den informationen. Ett ytterligare syfte var att ta reda på om röntgensjuksköterskan hade kännedom om barnkonventionen och dess betydelse i samband med barnröntgenundersökning samt om det fanns någon skillnad mellan röntgensjuksköterskor verksamma på sjukhus A och sjukhus B gällande deras uppfattning om information till barnpatienter. 

Metod: En empirisk kvantitativ enkätstudie genomfördes. Urvalet bestod av röntgensjuksköterskor med erfarenhet att utföra konventionella skelettundersökningar på barn. Totalt 35 enkäter analyserades. 

Resultat: Som viktigaste information valdes allmän strålsäkerhet och varför barnet ska ligga/sitta stilla. De viktigaste förutsättningarna för att ge information ansågs vara förberedda föräldrar, förberett röntgenlabb samt att vända sig till barnet vid samtal. Majoriteten svarade att röntgenmottagningarna inte erbjöd en barnanpassad miljö och instämde delvis till att kommunikationen skulle underlättas på ett barnanpassat labb. Röntgensjuksköterskorna instämmer till stor del att de har kännedom om barnkonventionens riktlinjer och att dessa har stor betydelse vid barnröntgenundersökningar. Ingen signifikant skillnad visades mellan sjukhusen.

Slutsats: Respondenterna från sjukhusen enades om att viktigast att informera om var strålsäkerhet och vikten av att vara still. Röntgenmottagningarna ansågs inte ha en barnanpassad miljö. Röntgensjuksköterskornas kännedom om barnkonventionen behöver ständigt aktualiseras och diskuteras i vårdsammanhang. 

Bakgrund: 18F-FDG-PET/DT är en undersökning som påvisar cellers glukosmetabolism och en viktig metod inom diagnostik. Undersökningen kräver förberedelser som patienten utför på egen hand polikliniskt. Vid missad förberedelse kan undersökningen bli fördröjd eller inställd och ombokad. Det är därför viktigt med tydlig och förståelig information.  

Syfte: Syftet med studien var att undersöka hur patienter upplevde informationen inför en 18F-FDG-PET/DT-undersökning och vad som kunde förbättras. Ett ytterligare syfte var att undersöka om det fanns ett samband mellan patientens ålder/kön och upplevelse av information innan undersökning. 

Metod: Studien var en empirisk kvantitativ enkätstudie med inslag av kvalitativa data. Enkäten innehöll 9 frågor om patientens upplevelse av information inför undersökningen. Patienter som hade genomgått en 18F-FDG-PET/DT-helkroppsundersökning på en nuklearmedicinsk avdelning inkluderades.

Resultat: Studien samlade in 86 besvarade enkäter med totalt 101 tillfrågade. Resultatet visade att 83 patienter var nöjda med informationen men att det finns förbättringspotential. Majoriteten av deltagarna i studien föredrog skriftlig information. Kvalitativa data analyserades och delades in i tre kategorier: nuvarande upplevelser, förbättringspotential och individanpassad information, vilket gav konkreta förslag på vad patienten upplever kan förbättras. Den kvantitativa analysen visade att det inte fanns något samband mellan kön och upplevelse av information, respektive ålder och upplevelse av information.  

Slutsats: Studien visade att majoriteten av patienterna som skulle genomgå en 18F-FDG-PET/DT-undersökning var nöjda med informationen i kallelsen och kände sig förberedda inför undersökningen. Det fanns dock förbättringspotential för att ytterligare underlätta patientförberedelserna och resultatet av den här studien kan användas för att optimera informationen innan undersökningen. 

Macroencapsulation devices provide the dual possibility to immunoprotect transplanted cells while also being retrievable; the latter bearing importance for safety in future trials with stem-cell derived cells. However, macroencapsulation entails a problem with oxygen supply to the encapsulated cells. The βAir device solves this with an incorporated refillable oxygen tank. This phase 1 study evaluated the safety and efficacy of implanting the βAir device containing allogeneic human pancreatic islets to patients with type 1 diabetes. Four patients were transplanted with 1-2 βAir devices, each containing 155000-180000 IEQ (i.e. 1800-4600 IEQ per kg body weight), and monitored for 3-6 months, followed by the recovery of devices. Implantation of the βAir device was safe and successfully prevented immunization and rejection of the transplanted tissue. However, although beta cells survived in the device, only minute levels of circulating C-peptide were observed with no impact on metabolic control. Fibrotic tissue with immune cells was formed in capsule surroundings. Recovered devices displayed a blunted glucose-stimulated insulin response, and amyloid formation in the endocrine tissue. We conclude that the βAir device is safe and can support survival of allogeneic islets for several months, although the function of the transplanted cells was limited.

Differential diagnosis based on morphology and immunohistochemistry between a clinically nonfunctioning pituitary neuroendocrine tumor (NET)/pituitary adenoma and a primary or secondary NET of nonpituitary origin in the sellar region may be difficult. Serotonin, a frequently expressed marker in the NETs, has not been systematically evaluated in pituitary NETs. Although mutations in ATRX or DAXX have been reported in a significant proportion of pancreatic NETs, the mutational status of ATRX and DAXX and their possible pathogenetic role in pituitary NETs are unknown. Facing a difficult diagnostic case of an invasive serotonin and adrenocorticotroph hormone immunoreactive NET in the sellar region, we explored the immunohistochemical expression of serotonin, ATRX, and DAXX in a large series of pituitary endocrine tumors of different types from 246 patients and in 2 corticotroph carcinomas. None of the pituitary tumors expressed serotonin, suggesting that serotonin immunoreactive sellar tumors represent primary or secondary NETs of nonpituitary origin. Normal expression of ATRX and DAXX in pituitary tumors suggests that ATRX and DAXX do not play a role in the pathogenesis of pituitary endocrine tumors that remain localized to the sellar and perisellar region. A lack of ATRX or DAXX in a sellar NET suggests a nonpituitary NET, probably of pancreatic origin. One of the 2 examined corticotroph carcinomas, however, demonstrated negative ATRX immunolabeling due to an ATRX gene mutation. Further studies on a larger cohort of pituitary carcinomas are needed to clarify whether ATRX mutations may contribute to the metastatic potential in a subset of pituitary NETs.

Background: First-line treatment of isolated resectable colorectal peritoneal metastases remains unclear. This study (the Swedish peritoneal study) compares cytoreductive surgery and intraperitoneal chemotherapy (surgery arm) with systemic chemotherapy (chemotherapy arm). Methods: Patients deemed resectable preoperatively were randomised to surgery and intraperitoneal 5-fluorouracil 550 mg/m(2) /d for 6 d with repeated courses every month or to systemic oxaliplatin and 5-fluorouracil regimen every second week. Both treatments continued for 6 months. Primary end-point was overall survival (OS) and secondary end-points were progression-free survival (PFS), and morbidity. Results: The study terminated prematurely when 48 eligible patients (24/arm) were included due to recruitment difficulties. Two-year OS was 54% in the surgery arm and 38% in the chemotherapy arm (p = 0.04). After 5 years, 8 versus 1 patient were alive, respectively (p = 0.02). Median OS was 25 months versus 18 months, respectively, hazard ratio 0.51 (95% confidence interval: 0.27-0.96, p = 0.04). PFS in the surgery arm was 12 months versus 11 months in the chemotherapy arm (p = 0.16) with 17% versus 0% 5-year PFS. Grade III-IV morbidity was seen in 42% and 50% of the patients, respectively. No mortalities. Conclusions: Cytoreductive surgery with intraperitoneal chemotherapy may be superior to systemic oxaliplatin-based treatment of colorectal cancer with resectable isolated peritoneal metastases.(ClinicalTrials. gov nr: NCT01524094).

Background

Fetal ultrasound has limitations, especially if the patient is obese or in cases with oligohydramnios. Magnetic resonance imaging (MRI) can then be used as a complement, but only few studies have focused on examinations in the second trimester.

Purpose

To validate MRI as a complement to diagnose fetal anomalies in the second trimester.

Material and Methods

This retrospective study retrieved data from January 2008 to July 2012 from the Fetal Medicine Unit and Department of Radiology at Uppsala University Hospital. Ultrasound and MRI findings were reviewed in 121 fetuses in relation to the final diagnosis, including postpartum follow-up and autopsy results.

Results

Of the 121 fetuses, 51 (42%) had a CNS anomaly and 70 (58%) a non-CNS anomaly diagnosed or suspected. MRI provided additional information in 21% of all cases without changing the management and revealed information that changed the management of the pregnancy in 13%. When a CNS anomaly was detected or suspected, the MRI provided additional information in 22% and changed the management in 10%. The corresponding figures for non-CNS cases were 21% and 16%, respectively. The proportion of cases with additional information that changed the management was especially high in patients with a BMI >30 kg/m² (25%) and in patients with oligohydramnios (38%). In five cases in category III, false-positive ultrasound findings were identified.

Conclusions

MRI in the second trimester complements ultrasound and improves diagnosis of fetal CNS- and non-CNS anomalies especially when oligohydramnios or maternal obesity is present.

Mental disorders represent an increasing source of disability and high costs for societies globally. Molecular imaging techniques such as positron emission tomography (PET) represent powerful tools with the potential to advance knowledge regarding disease mechanisms, allowing the development of new treatment approaches. Thus far, most PET research on pathophysiology in psychiatric disorders has focused on the monoaminergic neurotransmission systems, and although a series of discoveries have been made, the results have not led to any material changes in clinical practice. We outline areas of methodological development that can address some of the important obstacles to fruitful progress. First, we point towards new radioligands and targets that can lead to the identification of processes upstream, or parallel to disturbances in monoaminergic systems. Second, we describe the development of new methods of PET data quantification and PET systems that may facilitate research in psychiatric populations. Third, we review the application of multimodal imaging that can link molecular imaging data to other aspects of brain function, thus deepening our understanding of disease processes. Fourth, we highlight the need to develop imaging study protocols to include longitudinal and interventional paradigms, as well as frameworks to assess dimensional symptoms such that the field can move beyond cross-sectional studies within current diagnostic boundaries. Particular effort should be paid to include also the most severely ill patients. Finally, we discuss the importance of harmonizing data collection and promoting data sharing to reach the desired sample sizes needed to fully capture the phenotype of psychiatric conditions.

Introduction

Person-centred care (PCC) emphasises the need for the health care professional to prioritise individual patient needs, thereby fostering a collaborative and emphatic environment that empowers patients to actively participate in their own care. This article will explore the purpose of PCC in Nuclear Medicine (NM), while discussing strategies that may be used to implement PCC during diagnostic NM examinations performed on adult patients.

Methods

The scoping review was conducted in accordance with the Joanna Briggs Institute methodology. The search was performed on PubMed, Embase and Cinhal in June 2023 and included studies in English, Spanish, Portuguese and Italian. The research equation combined keywords and Medical Subject Heading terms (MeSH) related to person-centred care (PCC), for all types of nuclear medicine diagnostic examinations performed. Three independent review authors screened all abstracts and titles, and all eligible full-text publications were included in this scoping review.

Results

Fifty-three articles, published between 1993 and 2022, met the inclusion criteria for this scoping review. Seven articles were published in 2015 while 56.6 % of all included studies were performed in Europe. Most studies (n = 39/53) focused on the patients only, with the identified patient benefits being: improve patient experience (67.9 %), increase patient comfort (13.2 %), increase patient knowledge (5.7 %), reduction of patient anxiety (9.4 %) and reduction of waiting/scan time (3.8 %).

Conclusion

The scoping review identified a lack of research investigating the use of person-centred care strategies in NM. Future research will focus on using an international survey to explore this topic in nuclear medicine departments overseas.

Implications for practice

By applying PCC principles, the NM professional can improve the patient care pathway and increase patient satisfaction, leading to enhanced clinical outcomes.

Aims To define endotypes of carotid subclinical atherosclerosis. Methods and results We integrated demographic, clinical, and molecular data (n = 124) with ultrasonographic carotid measurements from study participants in the IMPROVE cohort (n = 3340). We applied a neural network algorithm and hierarchical clustering to identify carotid atherosclerosis endotypes. A measure of carotid subclinical atherosclerosis, the c-IMTmean-max, was used to extract atherosclerosis-related features and SHapley Additive exPlanations (SHAP) to reveal endotypes. The association of endotypes with carotid ultrasonographic measurements at baseline, after 30 months, and with the 3-year atherosclerotic cardiovascular disease (ASCVD) risk was estimated by linear (& beta;, SE) and Cox [hazard ratio (HR), 95% confidence interval (CI)] regression models. Crude estimates were adjusted by common cardiovascular risk factors, and baseline ultrasonographic measures. Improvement in ASCVD risk prediction was evaluated by C-statistic and by net reclassification improvement with reference to SCORE2, c-IMTmean-max, and presence of carotid plaques. An ensemble stacking model was used to predict endotypes in an independent validation cohort, the PIVUS (n = 1061). We identified four endotypes able to differentiate carotid atherosclerosis risk profiles from mild (endotype 1) to severe (endotype 4). SHAP identified endotype-shared variables (age, biological sex, and systolic blood pressure) and endotype-specific biomarkers. In the IMPROVE, as compared to endotype 1, endotype 4 associated with the thickest c-IMT at baseline (& beta;, SE) 0.36 (0.014), the highest number of plaques 1.65 (0.075), the fastest c-IMT progression 0.06 (0.013), and the highest ASCVD risk (HR, 95% CI) (1.95, 1.18-3.23). Baseline and progression measures of carotid subclinical atherosclerosis and ASCVD risk were associated with the predicted endotypes in the PIVUS. Endotypes consistently improved measures of ASCVD risk discrimination and reclassification in both study populations. Conclusions We report four replicable subclinical carotid atherosclerosis-endotypes associated with progression of atherosclerosis and ASCVD risk in two independent populations. Our approach based on endotypes can be applied for precision medicine in ASCVD prevention.

Similar to [F-18]-FDG, [Tc-99m]Tc-1-thio-D-glucose ([Tc-99m]Tc-TG) also binds to GLUT receptors. The aim of this Phase I study was to evaluate the safety, biodistribution and dosimetry of [Tc-99m]Tc-TG. Twelve lymphoma patients were injected with 729 +/- 102 MBq [Tc-99m]Tc-TG. Whole-body planar imaging was performed in 10 patients at 2, 4, 6 and 24 h after injection. In all 12 patients, SPECT/CT (at 2 h) and SPECT (at 4 and 6 h) imaging was performed. Vital signs and possible side effects were monitored during imaging and up to 7 days after injection. [Tc-99m]Tc-TG injections were well-tolerated and no side effects or alterations in blood and urine analyses data were observed. The highest absorbed dose was in the kidneys and urinary bladder wall, followed by the adrenals, prostate, bone marrow, lungs, myocardium, ovaries, uterus, liver and gall bladder wall. [Tc-99m]Tc-TG SPECT/CT revealed foci of high activity uptake in the lymph nodes of all nine patients with known nodal lesions. Extranodal lesions were detected in all nine cases. In one patient, a lesion in the humerus head, which was not detected by CT, was visualized using [Tc-99m]Tc-TG. Potentially, [Tc-99m]Tc-TG can be considered as an additional diagnostic method for imaging GLUT receptors in lymphoma patients.

The gastrin-releasing peptide receptor (GRPR) is overexpressed in prostate cancer (PCa) and in hormone-driven breast cancer (BCa). The aim of this phase I clinical trial was to evaluate safety, biodistribution, and dosimetry after the administration of the recently developed GRPR-targeting antagonistic bombesin analogue [Tc-99m]Tc-maSSS-PEG(2)-RM26 in PCa and BCa patients. Planar and whole-body SPECT/CT imaging was performed in six PCa patients and seven BCa patients 2, 4, 6, and 24 h post the intravenous administration of 40 mu g of [Tc-99m]Tc-maSSS-PEG(2)-RM26 (600-700 MBq). No adverse events or pathological changes were observed. The rapid blood clearance of [Tc-99m]Tc-maSSS-PEG(2)-RM26 was observed with predominantly hepatobiliary excretion. The effective doses were 0.0053 +/- 0.0007 for male patients and 0.008 +/- 0.003 mSv/MBq for female patients. The accumulation of [Tc-99m]Tc-maSSS-PEG(2)-RM26 in tumors was observed in four out of six PCa and in seven out of seven BCa patients. In four BCa patients, a high uptake of the agent into the axillary lymph nodes was detected. Immunohistochemistry revealed positive GRPR expression in 60% of primary PCa, 71.4% of BCa tumors, and 50% of examined BCa lymph nodes. In conclusion, a single administration of [Tc-99m]Tc-maSSS-PEG(2)-RM26 was safe and well tolerated. [Tc-99m]Tc-maSSS-PEG(2)-RM26 SPECT may be useful for tumor detection in PCa and BCa patients, pending further studies.

The development of tau-specific positron emission tomography (PET) tracers allows imaging in vivo the regional load of tau pathology in Alzheimer's disease (AD) and other tauopathies. Eighteen patients with baseline investigations enroled in a 17-month follow-up study, including 16 with AD (10 had mild cognitive impairment and a positive amyloid PET scan, that is, prodromal AD, and six had AD dementia) and two with corticobasal syndrome. All patients underwent PET scans with [(18)F]THK5317 (tau deposition) and [(18)F]FDG (glucose metabolism) at baseline and follow-up, neuropsychological assessment at baseline and follow-up and a scan with [(11)C]PIB (amyloid-β deposition) at baseline only. At a group level, patients with AD (prodromal or dementia) showed unchanged [(18)F]THK5317 retention over time, in contrast to significant decreases in [(18)F]FDG uptake in temporoparietal areas. The pattern of changes in [(18)F]THK5317 retention was heterogeneous across all patients, with qualitative differences both between the two AD groups (prodromal and dementia) and among individual patients. High [(18)F]THK5317 retention was significantly associated over time with low episodic memory encoding scores, while low [(18)F]FDG uptake was significantly associated over time with both low global cognition and episodic memory encoding scores. Both patients with corticobasal syndrome had a negative [(11)C]PIB scan, high [(18)F]THK5317 retention with a different regional distribution from that in AD, and a homogeneous pattern of increased [(18)F]THK5317 retention in the basal ganglia over time. These findings highlight the heterogeneous propagation of tau pathology among patients with symptomatic AD, in contrast to the homogeneous changes seen in glucose metabolism, which better tracked clinical progression.Molecular Psychiatry advance online publication, 16 May 2017; doi:10.1038/mp.2017.108.

PURPOSE: The aim of this study was to explore the cerebral distribution of the tau-specific PET tracer [(18)F]THK5317 (also known as (S)-[(18)F]THK5117) retention in different stages of Alzheimer's disease; and study any associations with markers of hypometabolism and amyloid-beta deposition.

METHODS: Thirty-three individuals were enrolled, including nine patients with Alzheimer's disease dementia, thirteen with mild cognitive impairment (MCI), two with non-Alzheimer's disease dementia, and nine healthy controls (five young and four elderly). In a multi-tracer PET design [(18)F]THK5317, [(11)C] Pittsburgh compound B ([(11)C]PIB), and [(18)F]FDG were used to assess tau pathology, amyloid-beta deposition and cerebral glucose metabolism, respectively. The MCI patients were further divided into MCI [(11)C]PIB-positive (n = 11) and MCI [(11)C]PIB-negative (n = 2) groups.

RESULTS: Test-retest variability for [(18)F]THK5317-PET was very low (1.17-3.81 %), as shown by retesting five patients. The patients with prodromal (MCI [(11)C]PIB-positive) and dementia-stage Alzheimer's disease had significantly higher [(18)F]THK5317 retention than healthy controls (p = 0.002 and p = 0.001, respectively) in areas exceeding limbic regions, and their discrimination from this control group (using the area under the curve) was >98 %. Focal negative correlations between [(18)F]THK5317 retention and [(18)F]FDG uptake were observed mainly in the frontal cortex, and focal positive correlations were found between [(18)F]THK5317 and [(11)C]PIB retentions isocortically. One patient with corticobasal degeneration syndrome and one with progressive supranuclear palsy showed no [(11)C]PIB but high [(18)F]THK5317 retentions with a different regional distribution from that in Alzheimer's disease patients.

CONCLUSIONS: The tau-specific PET tracer [(18)F]THK5317 images in vivo the expected regional distribution of tau pathology. This distribution contrasts with the different patterns of hypometabolism and amyloid-beta deposition.

Cross-sectional studies have indicated potential for positron emission tomography (PET) in imaging tau pathology in Alzheimer's disease (AD); however, its prognostic utility remains unproven. In a longitudinal, multi-modal, prognostic study of cognitive decline, 20 patients with a clinical biomarker-based diagnosis in the AD spectrum (mild cognitive impairment or dementia and a positive amyloid-beta PET scan) were recruited from the Cognitive Clinic at Karolinska University Hospital. The participants underwent baseline neuropsychological assessment, PET imaging with [F-18]THK5317, [C-11]PIB and [F-18]FDG, magnetic resonance imaging, and in a subgroup cerebrospinal fluid (CSF) sampling, with clinical follow-up after a median 48 months (interquartile range = 32:56). In total, 11 patients declined cognitively over time, while 9 remained cognitively stable. The accuracy of baseline [F-18]THK5317 binding in temporal areas was excellent at predicting future cognitive decline (area under the receiver operating curve 0.84-1.00) and the biomarker levels were strongly associated with the rate of cognitive decline (beta estimate -33.67 to -31.02,p < 0.05). The predictive accuracy of the other baseline biomarkers was poor (area under the receiver operating curve 0.58-0.77) and their levels were not associated with the rate of cognitive decline (beta estimate -4.64 to 15.78,p > 0.05). Baseline [F-18]THK5317 binding and CSF tau levels were more strongly associated with the MMSE score at follow-up than at baseline (p < 0.05). These findings support a temporal dissociation between tau deposition and cognitive impairment, and suggest that [F-18]THK5317 predicts future cognitive decline better than other biomarkers. The use of imaging markers for tau pathology could prove useful for clinical prognostic assessment and screening before inclusion in relevant clinical trials.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia and early and accurate diagnosis is important. Olfactory dysfunction is an early sign of AD. The contribution by test of olfactory function has been surveyed in AD vs a line of conditions but remains to be settled in the workup of unselected patients referred with suspected dementia.

METHODS: We performed a two-step investigation: first, a comparative study of healthy controls and probable AD patients to test the applicability of the chosen scents (cuisine study); second, a study of consecutive patients referred to our geriatric outpatient clinic for suspected dementia with the investigating personnel blinded to the results of the Olfactory Test (blinded study).

RESULTS: The sum of scents detected discriminated patients with probable AD from controls in the cuisine study (n = 40; p < 0.001; area under ROC curve 0.94). In the blinded study (n = 50) the diagnosis was probable AD in 48%, minimal cognitive impairment in 24%, vascular dementia in 8%, alcohol induced impairment in 12%, depression in 4%, and Parkinson's disease and Lewy body dementia in 2%. Area under the ROC-curve was 0.67. The odds ratio for probable AD with 2+ smell errors was 12 (95%-CI: 1.3-101; p = 0.026 (reference 0-1 smell errors)) age adjusted. None in the AD group had zero smell errors (Negative Predictive Value 100%).

CONCLUSION: Olfactory testing may support to dismiss the diagnosis of probable AD in the workup of a mixed group of patients referred with cognitive impairment. Still, it had a low sensitivity for probable AD.

BACKGROUND: Patient motion constitutes a limitation to ¹⁵O-water cardiac PET imaging. We examined the ability of image readers to detect and correct patient motion using simulated motion data and clinical patient scans.

METHODS: Simulated data consisting of 16 motions applied to 10 motion-free scans were motion corrected using two approaches, pre-analysis and post-analysis for motion identification. Both approaches employed a manual frame-by-frame correction method. In addition, a clinical cohort was analyzed for assessment of prevalence and effect of motion and motion correction.

RESULTS: Motion correction was performed on 94% (pre-analysis) and 64% (post-analysis) of the scans. Large motion artifacts were corrected in 91% (pre-analysis) and 74% (post-analysis) of scans. Artifacts in MBF were reduced in 56% (pre-analysis) and 58% (post-analysis) of the scans. The prevalence of motion in the clinical patient cohort (n = 762) was 10%. Motion correction altered exam interpretation in only 10 (1.3%) clinical patient exams.

CONCLUSION: Frame-by-frame motion correction after visual inspection is useful in reducing motion artifacts in cardiac ¹⁵O-water PET. Reviewing the initial results (parametric images and polar maps) as part of the motion correction process, reduced erroneous corrections in motion-free scans. In a large clinical cohort, the impact of motion correction was limited to few patients.

BACKGROUND: Localizing and removing the infected sequestrum in long-standing trauma-related chronic osteomyelitis remains a clinical challenge. PET/CT with 18F-fluorodeoxyglucose (FDG-PET) has a high sensitivity for chronic osteomyelitis and 18F-sodium-fluoride PET/CT (NaF-PET) has a high specificity for identifying non-viable bone. Combining both, high signal on FDG-PET in the bone without signal on NaF-PET could potentially guide surgery to become more precise with curative intent. Eight patients with long-standing (average 22 years) posttraumatic (n = 7) or postoperative (n = 1) chronic osteomyelitis in the lower extremity and with multiple futile attempts for curative surgery were recruited in this prospective pilot study. FDG-PET and NaF-PET were performed within a week in between using standard scanning protocols. The most likely location of the culprit sequestrum was identified and was surgically removed. Based on perioperative tissue cultures, antibiotics were given for 6-8 months. Dual-tracer (FDG- and NaF-PET/CT) was performed again after 12 months to rule out persisting signs of infection.

RESULTS: A likely culprit sequestrum could preoperatively be identified by dual-tracer PET in all eight cases and in four cases an additional sequestrum was identified at a location with no clinical sign of infection. The infected necrotic tissue was removed during surgery. Follow-up dual-tracer PET revealed no signs of persistent infection. All patients recovered with no clinical signs of recurrence for a follow-up of mean 4.5 (SD 1.3) years.

CONCLUSIONS: Dual-tracer PET/CT with FDG and NaF allows successful precise surgery with curative intent in patients with long-standing complicated posttraumatic chronic osteomyelitis with severely deranged anatomy.

Objective The aim of the present study was to compare the reliability and agreement between a computer tomography-based method (CT) and digitalised 2D radiographs (XR) when measuring change in dorsal angulation over time in distal radius fractures. Materials and methods Radiographs from 33 distal radius fractures treated with external fixation were retrospectively analysed. All fractures had been examined using both XR and CT at six times over 6 months postoperatively. The changes in dorsal angulation between the first reference images and the following examinations in every patient were calculated from 133 follow-up measurements by two assessors and repeated at two different time points. The measurements were analysed using Bland-Altman plots, comparing intra- and inter-observer agreement within and between XR and CT. Results The mean differences in intra- and inter-observer measurements for XR, CT, and between XR and CT were close to zero, implying equal validity. The average intra- and inter-observer limits of agreement for XR, CT, and between XR and CT were +/- 4.4 degrees, +/- 1.9 degrees and +/- 6.8 degrees respectively. Conclusions For scientific purpose, the reliability of XR seems unacceptably low when measuring changes in dorsal angulation in distal radius fractures, whereas the reliability for the semi-automatic CT-based method was higher and is therefore preferable when a more precise method is requested.

The anatomical position of the facial nerve is a critical factor in determining surgical candidacy in patients with congenital aural atresia (CAA). All patients with CAA must preoperatively be evaluated using a grading score based on information gained from a high resolution CT scan. In patients not suitable for surgical reconstruction, implantation of novel hearing implants is increasingly used for hearing rehabilitation. We, here, describe a bifurcation of the intratemporal part of the facial nerve in a 5-year old boy with CAA undergoing implantation with a bone conductive hearing device.