Positron Emission Tomography MRI Research Articles

Circadian copeptin and oxytocin profiles in anorexia nervosa: Exploring the interplay with neurohypophysis opioid tone.

Neurohypophysis (NH) function in eating disorders (ED) remains poorly elucidated. Studies on vasopressin and oxytocin display inconclusive findings regarding their levels and associations with psychological complications in ED. The profile of opioid tone, a crucial NH activity regulator, is also unknown. To characterise the circadian profile of NH hormones and NH opioid tone using positron emission tomography/MRI (PET/MRI) imaging in patients with ED compared to healthy controls. Twelve-point plasma circadian profiles of copeptin and oxytocin, alongside nutritional and psychological scores, were assessed in age-matched female participants: 13 patients with anorexia nervosa restrictive-type (ANR), 12 patients recovered from AN (ANrec), 14 patients with bulimia nervosa and 12 controls. Neurohypophysis PET/MRI [11C] diprenorphin binding potential (BPND) was evaluated in AN, ANrec and controls. Results revealed lower copeptin circadian levels in both ANR and ANrec compared to controls, with no oxytocin differences. Bulimia nervosa exhibited elevated copeptin and low oxytocin levels. [11C] diprenorphin pituitary binding was fully localised in NH. Anorexia nervosa restrictive-type displayed lower NH [11C] diprenorphin BPND (indicating higher opioid tone) and volume than controls. In ANR, copeptin inversely correlated with osmolarity. Neurohypophysis [11C] diprenorphin BPND did not correlated with copeptin or oxytocin. Copeptin demonstrated significant group differences, highlighting its potential diagnostic and prognostic value. Oxytocin levels exhibited conflicting results, questioning the reliability of peripheral blood assessment. Increased NH opioid tone in anorexia nervosa may influence the vasopressin or oxytocin release, suggesting potential therapeutic applications.

In vivo translocator protein in females with autism spectrum disorder: a pilot study

Sex-based differences in the prevalence of autism spectrum disorder (ASD) are well-documented, with a male-to-female ratio of approximately 4:1. The clinical presentation of the core symptoms of ASD can also vary between sexes. Previously, positron emission tomography (PET) studies have identified alterations in the in vivo levels of translocator protein (TSPO)—a mitochondrial protein—in primarily or only male adults with ASD, with our group reporting lower TSPO relative to whole brain mean in males with ASD. However, whether in vivo TSPO levels are altered in females with ASD, specifically, is unknown. This is the first pilot study to measure in vivo TSPO in the brain in adult females with ASD using [11C]PBR28 PET-magnetic resonance imaging (MRI). Twelve adult females with ASD and 10 age- and TSPO genotype-matched controls (CON) completed one or two [11C]PBR28 PET–MRI scans. Females with ASD exhibited elevated [11C]PBR28 standardized uptake value ratio (SUVR) in the midcingulate cortex and splenium of the corpus callosum compared to CON. No brain area showed lower [11C]PBR28 SUVR in females with ASD compared to CON. Test-retest over several months showed stable [11C]PBR28 SUVR across time in both groups. Elevated regional [11C]PBR28 SUVR in females with ASD stand in stark contrast to our previous findings of lower regional [11C]PBR28 SUVR in males with ASD. Preliminary evidence of regionally elevated mitochondrial protein TSPO relative to whole brain mean in ASD females may reflect neuroimmuno-metabolic alterations specific to females with ASD.

Positron emission tomography (PET) imaging of neuroinflammation in healthy and Alzheimer disease participants using TSPO tracers

AbstractBackgroundAlzheimer’s disease (AD) is the most common type of dementia. In addition to the widely recognized accumulation of amyloid and tau protein being the core pathology of AD, neuroinflammation is another cause of brain dysfunction and structural change. Expression of translocator protein (TSPO) on the outer mitochondrial membrane of activated microglia is strongly associated with neuroinflammation. With the development of TSPO positron emission tomography (PET) tracer, we were able to evaluate neuroinflammation non‐invasively in a clinical cohort of AD spectrum.MethodCognitively impaired patients (including AD and mild cognitive impairment (MCI)) and cognitively normal controls (CN) were recruited from single dementia clinic. [18F]FEPPA, the second‐generation PET ligand specifically binds TSPO was synthesized fully automated. Structural brain MRI and functional PET imaging were performed simultaneously with a PET/MR scanner (SIGNA, GE Company, USA). Kinetic analyses were performed using PMOD 4.2 modeling software. Total distribution volume (VT) in each ROI, including frontal, temporal, inferiolateral parietal, occipital, hippocampus and cerebellum, were derived from a two‐tissue compartment model (2‐TCM). In addition, APOE and rs6971 polymorphism genotyping were conducted in all subjects. Mann‐Whitney U Tet, Kruskal‐Wallis Test and linear correlation were performed.ResultA total of 39 participants (23 males and 16 females) participated, including 13 cognitively normal, 9 with MCI and 17 with Alzheimer’s disease. The rs6971 genotype had no significant effect on [18F]FEPPA binding to TSPO. The amount of TSPO expression was independent of age, gender, and APOE ε4 carrier status. The VT of each ROI did not differ significantly between cognitive groups. VT of frontal, temporal, inferiolateral parietal and occipital lobe were all negatively correlated with MMSE, Boston Naming Test and Trial Making A performance. However, such association was not observed between VT of hippocampus and cognitive tests.ConclusionAlthough there was no difference between TSPO expression in each ROI among cognitive groups, we still observed that higher TSPO expression in the cortex was associated with worse performance in certain cognitive tests. This implied that the increase in neuroinflammation was related to the decline of cognitive performance regardless of cognitive diagnosis.

Parametric Response Mapping of Co-Registered Ivim MRI and PET to Identify Radioresistant Sub-Volumes in Locally Advanced Cervical Carcinoma Undergoing CCRT

To investigate parametric response mapping (PRM) of co-registered positron emission tomography (PET) and intravoxel incoherent motion (IVIM) MRI in locally advanced cervical carcinoma patients to identify sub-volumes that may predict treatment response to adjuvant concurrent chemoradiation therapy (CCRT). Pre- and on-treatment (∼after four weeks of CCRT) diffusion weighted images (DWIs) MRI and pre-treatment PET were performed on 20 cervical cancer patients (median [range] age: 63 [41 to 85]; FIGO staging: 3 IIB, 1 IIIB, 10 IIIC1, 4 IIIC2, 2 IVA; histology: 11 squamous cell carcinoma, 4 endocervical adenocarcinoma; LN status: 4 negative, 16 positive). IVIM MRI maps were generated by Bayesian fitting of a two-compartment IVIM model to the DWIs to produce three-dimensional diffusion coefficient (D) and perfusion fraction (f). Three-dimensional IVIM D and f maps were co-registered to PET standardized uptake value (SUV) maps. Population means of PET SUV, IVIM D and f from pre-treatment scans were calculated to generate thresholds to identify low versus high metabolic (μSUV) regions, low versus high diffused (μD) regions as well as low versus high perfused (μf) regions, respectively. PRM maps were generated using voxel-wise joint histogram analysis to classify voxels within the tumor as highly metabolic and with low cellular density (SUV↑D↑), highly metabolic and with high cellular density (SUV↑D↓), metabolically inactive and with high cellular density (SUV↓D↓), or metabolically inactive and with low cellular density (SUV↓D↑) tissue based on the population mean thresholds. Similar PRM maps were generated using the joint histogram analysis with SUV and f. Summary statistics for these and other imaging parameters were calculated pre- and on-treatment. Univariate analysis was performed to determine relationships between relative change in gross tumor volume (ΔGTV) and pre-treatment imaging measurements. In tumors, on- versus pre-treatment tumor volume (p<.001) significantly decreased, while IVIM f (p = .002) and D (p = .03) significantly increased. Pre-treatment tumor volume (r = .45, p = .04) and PRM SUV↑D↓ (r = .65, p = .002) regions were positively related with ΔGTV, while pre-treatment IVIM D (r = -.64, p = .002), PRM SUV↓f↑ (r = -.52, p = .02) and PRM SUV↓D↑ (r = -.74, p<.001) regions were negatively related with ΔGTV. The latter PRM result suggests that larger regions of low cellular density (as represented by elevated D) + low metabolism result in a reduced change in tumor volume on-treatment, potentially representing a radioresistant sub-volume. PRM, generated from PET and IVIM MRI, was applied to patients with locally advanced cervical carcinoma and radioresistant sub-volumes were identified which may predict treatment response. The complementary information provided from PET and IVIM, combined using PRM, may assist in decision-making to individualize therapies, such as with image guided brachytherapy, to improve patient outcomes.

P15.10.A USE OF DUAL TRACERS PET AS A PREDICTIVE BIOMARKER OF THE SITE OF RECURRENCE IN HIGH GRADE GLIOMA

Abstract BACKGROUND High grade glioma has poor survival rate and tumour recurrence occurs despite current treatments. Positron emission tomography (PET) with [11C](R)PK11195 can evaluate translocator protein (TSPO) and [11C]methionine can assess amino acid transport. PET imaging might have the potential to detect tumour regions at baseline that will later develop as the site of recurrence. We compare TSPO measured using [11C](R)PK11195 and amino acid transport using [11C]methionine at baseline and investigate to what extend the two tracers can predict the site of tumour recurrence. MATERIAL AND METHODS Twelve patients with newly diagnosed high grade glioma underwent multimodal imaging studies. Preoperative MRI, [11C](R)PK11195 PET, [11C]methionine PET and postoperative (follow-up) MRI were co-registered. [11C](R)PK11195 binding potential (BPND) maps were generated using the simplified reference tissue model with grey matter cerebellar time-activity curve as tissue input function. [11C]methionine uptake was calculated as tumour to background ratio (TBR). Contrast enhancing volumes of interest (VOI) were defined on T1W post contrast. The VOI of [11C]methionine high uptake was standardized as TBR&amp;gt;1.7. For [11C](R)PK11195 VOI, the mean BPND + SD of grey matter voxels was calculated from individual maps of healthy control (HC; n = 50). Afterward, 95% confidence interval threshold (HC mean + 1.96 × SD) was used to describe high voxel activity in tumour (BPND&amp;gt;0.35). Tumour recurrence VOI was defined as contrast enhancement on the follow-up images. RESULTS The mean percentage overlap between high [11C](R)PK11195 BPND and [11C]methionine uptake was 48±17%. The mean percentage of each VOI showing exclusively high [11C](R)PK11195 BPND or exclusively high [11C]methionine was 25±21 or 27±22 respectively. The mean percentage overlap between high [11C](R)PK11195 and contrast enhancement is 36±14. The mean percentage of exclusively hight [11C](R)PK11195 or exclusively contrast enhancement were 38±18 or 26±25 respectively. The mean percentage overlap between high [11C]methionine and contrast enhancement were 47±12. The mean percentage of exclusively [11C]methionine or contrast enhancement were 36±20 or 17±17 respectively. The percentage volume overlap between contrast enhancing regions at recurrence and baseline [11C](R)PK11195 or [11C]methionine was 20±13 or 25±13 respectively. CONCLUSION The two PET tracers have high overlap although some regions are specific for high TSPO binding without high methionine uptake which could reflect an inflammatory component within the tumour microenvironment. The common regions between methionine and contrast enhancement is larger than TSPO binding which could represent that TSPO binding is less effected by disrupted blood-brain barrier. The mean percentage overlap with VOI representing tumour recurrence were similar.

NIMG-26. UPTAKE OF [18F]GE-180 IN TSPO PET IS ASSOCIATED WITH SURVIVAL IN PATIENTS WITH RECURRENT GLIOMA

Abstract OBJECTIVE The 18 kDa translocator protein (TSPO) is expressed in both activated microglia and glioma cells. Elevated expression of TSPO has been reported to be associated with higher WHO grade. Here we analyze whether TSPO positron emission tomography (PET) signal using the tracer [18F]GE-180 is correlated with clinical outcome in a cohort of patients with recurrent glioma. METHODS Patients with suspected glioma recurrence received a [18F]GE-180 TSPO PET. All recurrent tumors were confirmed either by stereotactic biopsy or resection. Maximum standard uptake value SUVmax as well as tumor volume in MRI and, if available, in [18F]FET PET were evaluated together with patient characteristics (age, sex, Karnofsky-Performance score) and neuropathological features (WHO grade, IDH-mutation status). Uni- and multivariate Cox regression and Kaplan-Meier survival analyses were performed to identify prognostic factors for post-recurrence survival (PRS) and time to treatment failure (TTF). RESULTS 88 consecutive patients were evaluated. TSPO tracer uptake correlated with tumor grade at recurrence (p&amp;lt; 0.05), with no significant differences between IDH-wildtype and IDH-mutant tumors. Within the subgroup of IDH-mutant glioma (n= 46), patients with low SUVmax (median split, ≤ 1.60) had a significantly longer PRS (median 41.6 vs. 25.3 months, p= 0.031) and TTF (32.2 vs 8.7 months, p= 0.001). Also among IDH-wildtype tumors (n= 42), patients with low SUVmax (≤ 1.89) had a significantly longer PRS (median not reached vs 8.2 months, p= 0.002). SUVmax remained an independent prognostic factor for PRS in a multivariate analysis including WHO grade, IDH status and age. Tumor volume defined by [18F]FET PET or contrast-enhanced MRI correlated weakly with TSPO tracer uptake. Treatment regimen did not differ between the subgroups. CONCLUSION Our data suggest that uptake of [18F]GE-180 in TSPO PET can add prognostic information in patients with recurrent glioma even in molecular defined subgroups and might serve as an imaging biomarker.

TSPO PET signal using [18F]GE180 is associated with survival in recurrent gliomas

PurposeGlioma patients, especially recurrent glioma, suffer from a poor prognosis. While advances to classify glioma on a molecular level improved prognostication at initial diagnosis, markers to prognosticate survival in the recurrent situation are still needed. As 18 kDa translocator protein (TSPO) was previously reported to be associated with aggressive histopathological glioma features, we correlated the TSPO positron emission tomography (PET) signal using [18F]GE180 in a large cohort of recurrent glioma patients with their clinical outcome.MethodsIn patients with [18F]GE180 PET at glioma recurrence, [18F]GE180 PET parameters (e.g., SUVmax) as well as other imaging features (e.g., MRI volume, [18F]FET PET parameters when available) were evaluated together with patient characteristics (age, sex, Karnofsky-Performance score) and neuropathological features (e.g. WHO 2021 grade, IDH-mutation status). Uni- and multivariate Cox regression and Kaplan–Meier survival analyses were performed to identify prognostic factors for post-recurrence survival (PRS) and time to treatment failure (TTF).ResultsEighty-eight consecutive patients were evaluated. TSPO tracer uptake correlated with tumor grade at recurrence (p < 0.05), with no significant differences in IDH-wild-type versus IDH-mutant tumors. Within the subgroup of IDH-mutant glioma (n = 46), patients with low SUVmax (median split, ≤ 1.60) had a significantly longer PRS (median 41.6 vs. 25.3 months, p = 0.031) and TTF (32.2 vs 8.7 months, p = 0.001). Also among IDH-wild-type glioblastoma (n = 42), patients with low SUVmax (≤ 1.89) had a significantly longer PRS (median not reached vs 8.2 months, p = 0.002). SUVmax remained an independent prognostic factor for PRS in the multivariate analysis including CNS WHO 2021 grade, IDH status, and age. Tumor volume defined by [18F]FET PET or contrast-enhanced MRI correlated weakly with TSPO tracer uptake. Treatment regimen did not differ among the median split subgroups.ConclusionOur data suggest that TSPO PET using [18F]GE180 can help to prognosticate recurrent glioma patients even among homogeneous molecular subgroups and may therefore serve as valuable non-invasive biomarker for individualized patient management.Graphical abstract

Characterization of tumor thrombus in renal cell carcinoma with prostate specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT).

Venous tumor thrombus (TT) occurs as part of the natural history of renal cell carcinoma (RCC) local progression in a small minority of cases. MRI is currently the most accurate imaging modality for determining TT extent. PSMA PET/CT may improve RCC staging and IVC TT characterization. The objective of this study was to investigate the role of PSMA PET/CT in defining superior extent of TT in RCC and TT IVC tributary vessel spread, with comparative accuracy vs. MRI, to assess suitability for resection and inform preoperative surgical planning. Patients who underwent PSMA PET/CT for assessment of renal malignancy with TT from 2015 to 2020 at 3 tertiary hospitals in Brisbane, Australia, were retrospectively identified. TT extent was classified using Mayo Clinic levels and compared according to imaging modality. Fourteen patients were included, all of which were clear cell RCC. Ten patients also underwent MRI, 6 of which were concordant in extent according to MRI and PSMA PET. Discordant extent occurred in 4 patients, of which 2 patients had non-PSMA avid thrombus (Mayo level 0 and level 3 on MRI). Further discordance was seen in a patient with adrenal vein and lumbar vein TT only seen on MRI and PSMA PET/CT, respectively. Finally, discordant extent was seen in another patient with Mayo level 4 TT without lumbar vein involvement on MRI vs. level 3 on PSMA PET/CT with lumbar vein involvement. PSMA PET/CT can provide additional information about TT extent in RCC which may not be seen on MRI. Additional information from PSMA PET/CT in this setting may assist surgical planning, in addition to detection of metastatic disease.

High prostate-specific membrane antigen (PSMA) positron emission tomography (PET) maximum standardized uptake value in men with PI-RADS score 4 or 5 confers a high probability of significant prostate cancer.

High prostate-specific membrane antigen (PSMA) positron emission tomography (PET) maximum standardized uptake value in men with PI-RADS score 4 or 5 confers a high probability of significant prostate cancer.

Unified Deep Learning-Based Mouse Brain MR Segmentation: Template-Based Individual Brain Positron Emission Tomography Volumes-of-Interest Generation Without Spatial Normalization in Mouse Alzheimer Model.

Although skull-stripping and brain region segmentation are essential for precise quantitative analysis of positron emission tomography (PET) of mouse brains, deep learning (DL)-based unified solutions, particularly for spatial normalization (SN), have posed a challenging problem in DL-based image processing. In this study, we propose an approach based on DL to resolve these issues. We generated both skull-stripping masks and individual brain-specific volumes-of-interest (VOIs—cortex, hippocampus, striatum, thalamus, and cerebellum) based on inverse spatial normalization (iSN) and deep convolutional neural network (deep CNN) models. We applied the proposed methods to mutated amyloid precursor protein and presenilin-1 mouse model of Alzheimer’s disease. Eighteen mice underwent T2-weighted MRI and 18F FDG PET scans two times, before and after the administration of human immunoglobulin or antibody-based treatments. For training the CNN, manually traced brain masks and iSN-based target VOIs were used as the label. We compared our CNN-based VOIs with conventional (template-based) VOIs in terms of the correlation of standardized uptake value ratio (SUVR) by both methods and two-sample t-tests of SUVR % changes in target VOIs before and after treatment. Our deep CNN-based method successfully generated brain parenchyma mask and target VOIs, which shows no significant difference from conventional VOI methods in SUVR correlation analysis, thus establishing methods of template-based VOI without SN.

In‐depth investigation in tau positron emission tomography tracers off‐target binding with voxel‐to‐voxel correlation analysis of tau and amyloid PET signal to histological iron and tau deposit in non‐Alzheimer tauopathies

AbstractBackgroundTau pathology strongly correlates with neuronal loss and clinical decline across tauopathies, emphasizing the need to detect and monitor tau pathology in living patients. Positron Emission Tomography(PET) using radiotracers like Flortaucipir ([18F]AV‐1451) enables good visualization of AD tau pathology. However, recent reports of its off‐targeting binding behavior raise concerns about the sensitivity and specificity of this tracer to visualize tau deposits in non‐AD tauopathies, especially with its similar pattern to iron accumulation. PET‐to‐autopsy validation has been challenging because of issues with tissue deformation and large‐scale pathological analysis. Here, we present i) an interdisciplinary approach combining immunohistochemistry, computer vision, and convolution neural network(CNN) to 3D‐reconstructed, billion‐pixel digital pathology tau and iron images of human brain hemispheres, co‐register them to PET and ii) preliminary PET‐to‐pathology voxel‐to‐voxel correlation analyses.MethodWe employed a pipeline developed in‐house combining whole‐brain processing, free‐floating immunohistochemistry and computer‐based algorithms for 2D and 3D registration. SlideNet, our CNN for segmenting tau inclusions in digital images (Fig. 1E,F), aims at generating quantitative, 3D‐tau‐maps. Iron maps are generated via Fiji's Weka segmentation (Fig. 1A‐B). Pipeline was applied to whole hemisphere sections in case#1(Cortico‐Basal‐Degeneration), case#3(TDP‐43), case#8(Frontaltemperal‐lobar‐disease w/ MAPT mutation), case#5(Alzheimer’s Disease) and case#7(Progressive‐Supranuclear‐Palsy) labeled by immunohistochemistry(CP‐13 antibody, Ser202, Fig. 2D)and Prussian Blue (Fig. 2A). Demographics of cases are shown in Table 1. We registered the resulting heatmaps (Fig. 1B,F) to MRI and PET coordinates (Fig. 3 &amp; 1C,D,G,H), enabling voxel‐to‐voxel comparisons.ResultCNN output three categories: tau in neurons, tau in glia/processes, and background (Fig. 2E). Weka segmentation output Iron in tissue and background (Fig. 2B). Obtaining the result with proper thresholding (Fig. 2C,F) We first registered the histology‐based iron maps, Tau and Amyloid PET scans onto the 3D MRI space (Fig. 1C‐D), following with registration of 3D Tau maps to PET scans and Iron maps to analyze the effect of iron to PET tracer binding quantitatively (Fig. 1G‐H). Preliminary correlation analysis generated between MRI resolution Iron map and PET scans via MATLAB. (Table 2)ConclusionIron histological segmentations shows a mild positive association between iron deposit and Tau signal binding, showing that iron likely play a role in the Tau PET tracer off‐target binding. Ongoing regional analysis with Tau maps will provide more granular correlations, especially in areas known for off‐target binding, and we are finalizing it. (Table 2,3)

Glioma Imaging by O-(2-18F-Fluoroethyl)-L-Tyrosine PET and Diffusion-Weighted MRI and Correlation With Molecular Phenotypes, Validated by PET/MR-Guided Biopsies.

Gliomas exhibit high intra-tumoral histological and molecular heterogeneity. Introducing stereotactic biopsy, we achieved a superior molecular analysis of glioma using O-(2-18F-fluoroethyl)-L-tyrosine (FET)-positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DWI). Patients underwent simultaneous DWI and FET-PET scans. Correlations between biopsy-derived tumor tissue values, such as the tumor-to-background ratio (TBR) and apparent diffusion coefficient (ADC)/exponential ADC (eADC) and histopathological diagnoses and those between relevant genes and TBR and ADC values were determined. Tumor regions with human telomerase reverse transcriptase (hTERT) mutation had higher TBR and lower ADC values. Tumor protein P53 mutation correlated with lower TBR and higher ADC values. α-thalassemia/mental-retardation-syndrome-X-linked gene (ATRX) correlated with higher ADC values. 1p/19q codeletion and epidermal growth factor receptor (EGFR) mutations correlated with lower ADC values. Isocitrate dehydrogenase 1 (IDH1) mutations correlated with higher TBRmean values. No correlation existed between TBRmax/TBRmean/ADC/eADC values and phosphatase and tensin homolog mutations (PTEN) or O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation. Furthermore, TBR/ADC combination had a higher diagnostic accuracy than each single imaging method for high-grade and IDH1-, hTERT-, and EGFR-mutated gliomas. This is the first study establishing the accurate diagnostic criteria for glioma based on FET-PET and DWI.

Imaging Coronary Allograft Vasculopathy with Cardiac PET and Cardiac MRI.

Coronary allograft vasculopathy (CAV) is a leading cause of morbidity and mortality in heart transplant patients. It presents a diagnostic challenge as early CAV is often clinically silent, and it affects both epicardial coronary arteries and microvasculature. This review outlines the role of cardiac positron emission tomography (PET) and cardiac magnetic resonance imaging (CMR) in the diagnosis and prognosis of CAV. Relative myocardial perfusion imaging (MPI) and quantitative myocardial blood flow using cardiac PET are useful in the diagnosis and prognosis of CAV. Late gadolinium enhancement (LGE) and quantitative measures including myocardial perfusion reserve and mean diastolic rate using CMR are useful in the diagnosis and prognosis of CAV. Cardiac PET is now established as a non-invasive imaging modality for screening and monitoring for CAV, and CMR has demonstrated promise in this application. Further investigation of these modalities is needed with larger, multicenter studies that follow patients serially to demonstrate the clinical implications of using these modalities to detect early CAV and alter therapies to improve patient outcomes.

Primitive neuroectodermal tumor of the pericardium: a case report and literature review

BackgroundThe primitive neuroectodermal tumors (PNETs) are a family of highly malignant tumors with a multidirectional differential potential. The tumors are characterized by aggressive small round tumor cells that originate from the spinal cord of the central and sympathetic nervous systems. Cases involving the pericardium are extremely rare. Herein, we present a case of peripheral primitive neuroectodermal tumor (pPNET) that originated in the pericardium.Case presentationA 23-year-old woman presented with cough and progressive dyspnea for 1 month, followed by eyelid and facial edema for 10 days, without any apparent cause. Significantly elevated tumor markers were detected in her blood. A cardiac ultrasound revealed a 74 mm × 61 mm spherical mass that was attached to the left pericardium, as well as massive pericardial effusion. Positron emission tomography-CT (PET-CT) showed focal hypermetabolism in the left pericardium. Via histopathology and immunohistochemistry, the spherical mass was identified as PNETS. The patient was successfully treated with a combination of surgical resection via thoracotomy and postoperative chemotherapy, and she was disease-free for 7 years at follow-up. Unfortunately, at 7 years after the treatment, the patient’s pPNET recurred. Positron emission tomography-MRI (PET-MRI) and 64-slice coronary CTA revealed that the aorta and multiple coronary arteries were involved. Subsequently, the patient refused a heart transplant and voluntarily left the hospital.ConclusionsThis paper reports on a rare and recurrent case of PNET in the parietal pericardium. With respect to the different biologic characteristics and prognoses of pPNETs (compared to other known pericardium tumors), it is essential to consider this entity as a differential diagnosis in pericardium tumors.

Imaging of inflammatory disease of the pancreas.

Increasingly acute and chronic pancreatitis (AP and CP) are considered a continuum of a single entity. Nonetheless, if, after flare-up, the pancreas shows no residual inflammation, it is classified as AP. CP is characterised by a long cycle of worsening and waning glandular inflammation without the pancreas ever returning to its baseline structure or function. According to the International Consensus Guidelines on Early Chronic Pancreatitis, pancreatic inflammation must last at least 6 months before it can be labelled CP. The distinction is important because, unlike AP, CP can destroy endocrine and exocrine pancreatic function, emphasising the importance of early diagnosis. As typical AP can be diagnosed by clinical symptoms plus laboratory tests, imaging is usually reserved for those with recurrent, complicated or CP. Imaging typically starts with ultrasound and more frequently with contrast-enhanced computed tomography (CECT). MRI and/or MR cholangiopancreatography can be used as a problem-solving tool to confirm indirect signs of pancreatic mass, differentiate between solid and cystic lesions, and to exclude pancreatic duct anomalies, as may occur with recurrent AP, or to visualise early signs of CP. MR cholangiopancreatography has replaced diagnostic endoscopic retrograde cholangiopancreatography (ERCP). However, ERCP, and/or endoscopic ultrasound (EUS) remain necessary for transpapillary biliary or pancreatic duct stenting and transgastric cystic fluid drainage or pancreatic tissue sampling, respectively. Finally, positron emission tomography-MRI or positron emission tomography-CT are usually reserved for complicated cases and/or to search for extra pancreatic systemic manifestations. In this article, we discuss a broad spectrum of inflammatory pancreatic disorders and the utility of various modalities in diagnosing acute and chronic pancreatitis.

68Ga-PSMA-11 PET, 18F-PSMA-1007 PET, and MRI for Gross Tumor Volume Delineation in Primary Prostate Cancer: Intermodality and Intertracer Variability

PurposeTo assess the intermodality and intertracer variability of gallium-68 (68Ga)- or fluorine-18 (18F)-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET) and biparametric magnetic resonance imaging (bpMRI)-based gross tumor volume (GTV) delineation for focal boosting in primary prostate cancer. MethodsNineteen prospectively enrolled patients with prostate cancer underwent a PSMA PET/MRI scan, divided into a 1:1 ratio between 68Ga-PSMA-11 and 18F-PSMA-1007, before radical prostatectomy (IWT140193). Four delineation teams performed manual contouring of the GTV based on bpMRI and PSMA PET imaging, separately. Index lesion coverage (overlap%) and interobserver variability were assessed. Furthermore, the distribution of the voxelwise normalized standardized uptake values (SUV%) was determined for the majority-voted (>50%) GTV (GTVmajority) and whole prostate gland to investigate intertracer variability. The median patientwise SUV% contrast ratio (SUV%-CR, calculated as median GTVmajority SUV% / median prostate gland without GTVmajority SUV%) was calculated according to the tracer used. ResultsA significant difference in overlap% favoring PSMA PET compared with bpMRI was found in the 18F subgroup (median, 63.0% vs 53.1%; P = .004) but was not present in the 68Ga subgroup (32.5% vs 50.6%; P = .100). Regarding interobserver variability, measured Sørensen-Dice coefficients (0.58 vs 0.72) and calculated mean distances to agreement (2.44 mm vs 1.22 mm) were statistically significantly lower and higher, respectively, for the 18F cohort compared with the 68Ga cohort. For the bpMRI-based delineations, the median Sørensen-Dice coefficient and mean distance to agreement were 0.63 and 1.76 mm, respectively. Median patientwise SUV%-CRs of 1.8 (interquartile range [IQR], 1.6-2.7) for 18F-PSMA and 3.3 (IQR, 2.7-5.9) for 68Ga-PSMA PET images were found. ConclusionsBoth MRI and PSMA PET provided consistent intraprostatic GTV lesion detection. However, the PSMA tracer seems to have a major influence on the contour characteristics, owing to an apparent difference in SUV% distribution in the prostate gland.

68Ga-PSMA-11-PET, 18F-PSMA-1007-PET and MRI for Gross Tumor Volume Delineation in Primary Prostate Cancer: Intermodality and Inter-tracer Variability

Abstract Purpose To assess the intermodality and intertracer variability of gallium-68 (68Ga)- or fluorine-18 (18F)-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET) and biparametric magnetic resonance imaging (bpMRI)-based gross tumor volume (GTV) delineation for focal boosting in primary prostate cancer. Methods Nineteen prospectively enrolled patients with prostate cancer underwent a PSMA PET/MRI scan, divided into a 1:1 ratio between 68Ga-PSMA-11 and 18F-PSMA-1007, before radical prostatectomy (IWT140193). Four delineation teams performed manual contouring of the GTV based on bpMRI and PSMA PET imaging, separately. Index lesion coverage (overlap%) and interobserver variability were assessed. Furthermore, the distribution of the voxelwise normalized standardized uptake values (SUV%) was determined for the majority-voted (>50%) GTV (GTVmajority) and whole prostate gland to investigate intertracer variability. The median patientwise SUV% contrast ratio (SUV%-CR, calculated as median GTVmajority SUV% / median prostate gland without GTVmajority SUV%) was calculated according to the tracer used. Results A significant difference in overlap% favoring PSMA PET compared with bpMRI was found in the 18F subgroup (median, 63.0% vs 53.1%; P = .004) but was not present in the 68Ga subgroup (32.5% vs 50.6%; P = .100). Regarding interobserver variability, measured Sorensen-Dice coefficients (0.58 vs 0.72) and calculated mean distances to agreement (2.44 mm vs 1.22 mm) were statistically significantly lower and higher, respectively, for the 18F cohort compared with the 68Ga cohort. For the bpMRI-based delineations, the median Sorensen-Dice coefficient and mean distance to agreement were 0.63 and 1.76 mm, respectively. Median patientwise SUV%-CRs of 1.8 (interquartile range [IQR], 1.6-2.7) for 18F-PSMA and 3.3 (IQR, 2.7-5.9) for 68Ga-PSMA PET images were found. Conclusions Both MRI and PSMA PET provided consistent intraprostatic GTV lesion detection. However, the PSMA tracer seems to have a major influence on the contour characteristics, owing to an apparent difference in SUV% distribution in the prostate gland.

Investigation of reactive astrogliosis effect on post-stroke cognitive impairment

BackgroundThe aim of this study is to investigate the associations between post-stroke cognitive impairment (PSCI) severity and reactive astrogliosis (RA) extent on normalized 18F-THK-5351 positron-emission tomography (PET) imaging in amyloid-negative patients with first-ever stroke.MethodsWe prospectively enrolled 63 amyloid-negative patients with first-ever stroke. Neurocognitive evaluation, MRI, 18F-THK-5351, and 18F-florbetapir PET were performed around 3 months after stroke. The 18F-THK-5351 uptake intensity was normalized using a signal distribution template to obtain the Z-SUM scores as the RA extent in the whole brain and cerebral hemisphere ipsilateral to stroke lesion. We evaluated stroke volume, leukoaraiosis, and brain atrophy on MRI. We used a comprehensive neurocognitive battery to obtain composite cognitive scores, and defined PSCI as a general cognitive function score < − 1. We analyzed the influence of Z-SUM scores on PSCI severity after adjusting for demographic, vascular, and neurodegenerative variables.ResultsTwenty-five of 63 stroke patients had PSCI. Patients with PSCI had older age, lower education, and more severe cortical atrophy and total Z-SUM scores. Total Z-SUM scores were significantly associated with general cognitive and executive functions at multiple regression models. Path analyses showed that stroke can exert cognitive influence directly by stroke itself as well as indirectly through RA, including total and ipsilateral Z-SUM scores, in patients with either right or left hemisphere stroke.ConclusionThe patterns and intensity of 18F-THK-5351 uptake in amyloid-negative patients with first-ever stroke were associated with PSCI manifestations, which suggests that RA presents a modulating effect in PSCI development.

Head and neck sarcomas in adulthood: current trends and evolving management concepts.

Sarcomas are rare, malignant bone and soft-tissue tumours of mesenchymal origin, and their overall incidence accounts for 1% and 0.2%, respectively, of all malignancies. The aim of this article is to provide a reference on the evolving management concepts and trends of treatment of adult sarcomas of the head and neck in a major head and neck sarcoma centre. Early diagnosis remains a challenge due to non-specific symptomatology. Imaging such as ultrasound (US), magnetic resonance (MRI), computed tomography (CT), and positron emission tomography (PET) CT assist with diagnosis and staging, and biopsy is essential for diagnosis, tumour differentiation, and grading. Staging is dependent on histological grade, size of tumour, and metastasis. Sarcomas spread via the haematogenous route. Adequate clearance of locoregional disease and prevention of distant micrometastases are key to improved disease-free survival outcomes so multimodal treatment at a sarcoma reference centre is imperative. In the head and neck, the treatment for most bone sarcomas is neoadjuvant chemotherapy followed by compartmental resection. The interim tumour response to neoadjuvant chemotherapy is evaluated by PET CT and MRI. Heavy-particle therapy (proton beam) in combination with surgery is increasingly being used to treat otherwise unresectable disease, particularly in children. For soft tissue sarcomas of the head and neck, treatment is complex and depends on grade. Surgery is the principle mode of treatment in low-grade tumours that are amenable to resection. High-grade tumours can be treated with neoadjuvant chemotherapy followed by surgery and radiotherapy. In such cases, the response to the chemotherapy might be used as a guide of potential biological aggressiveness, and has an impact on the planning of the operation and the type and extent of radiotherapy. As a general rule, radiotherapy is reserved for high-grade, advanced soft-tissue sarcomas of the head and neck. Those of bone are radioresistant, and radiotherapy is only administered for palliative purposes when no surgical option exists, an exception being Ewing sarcoma. The role of proton beam therapy is promising, but to our knowledge no long-term data currently exist. The survival advantage of innate immune-modulation remains uncertain for disease in the head and neck.

O11.3. SYNAPTIC MARKER PROTEIN SV2A IS REDUCED IN SCHIZOPHRENIA IN VIVO AND UNAFFECTED BY ANTIPSYCHOTICS IN RATS

BackgroundThe synaptic dysfunction hypothesis of schizophrenia is supported by multiple lines of evidence. However, in vivo evidence is lacking. Moreover, it is not known if antipsychotics alter synaptic protein levels. We addressed this in a combined clinical study using [11C]UCB-J, a positron emission tomography (PET) radioligand specific for synaptic vesicle glycoprotein 2A (SV2A), and rodent study of clinically relevant antipsychotic drug exposure.MethodsWe scanned 18 subjects with schizophrenia (SCZ) and 18 healthy volunteers (HV) with [11C]UCB-J PET and T1-weighted MRI, estimating grey matter volumes of distribution (VT) and corrected grey matter volumes (GMV) for the frontal cortex (FC), anterior cingulate cortex (ACC) and hippocampus. In addition, we estimated the [11C]UCB-J distribution volume ratio (DVR) in these regions, using the centrum semiovale (CS) as a pseudoreference region. We collected clinical data including PANSS score, chlorpromazine-equivalent antipsychotic dose (CPZ) and duration of illness (DOI). In parallel, we investigated the effects of olanzapine and haloperidol administration on SV2A levels in the Sprague-Dawley rat frontal cortex using western blotting, [3H]UCB-J autoradiography and immunostaining with confocal microscopy. We used two-way analysis of variance (ANOVA) to test effects of group, ROI and group-by-ROI interaction on VT and DVR. We used planned post hoc t-tests to test group effects at each ROI, with false discovery-rate adjustment for multiple comparisons. We used two-way ANOVA with Bonferroni’s post-hoc test to analyse autoradiography and SV2A immunostaining data, and the Kruskal-Wallis test, with alpha=0.05, to analyse western blot data.ResultsClinical study: We found significant group-by-region interaction (F2, 68=7.472, p=0.001), group (F1, 34=6.170, p=0.02) and ROI (F2, 68=426.0, p<0.0001) effects on VT, with significant reductions in mean [SEM] VT of large effect size in the SCZ group in the FC (SCZ=16.93 [0.80]; HV=19.50 [0.64]; t=2.51, df=34.0, p=0.03, Cohen’s d=0.8) and ACC (SCZ=19.55 [0.75]; HV=22.49 [0.72]; t=2.83, df=34.0, p=0.02, Cohen’s d=0.9), but not in the hippocampus (SCZ=14.09 [0.59]; HV=15.44 [0.50]; t=1.75, df=34.0, p=0.09, Cohen’s d=0.6). Furthermore, we found significant group-by-region interaction (F2, 68=7.97, p=0.0008), group (F1, 34=8.1, p=0.007) and ROI (F2, 68=510.9, p<0.0001) effects on DVR, with significant reductions of large effect size in the FC (SCZ=2.93 [0.17]; HV=3.48 [0.09]; t=2.89, df=34.0, p=0.01, Cohen’s d=1.0), ACC (SCZ=3.39 [0.17]; HV=3.99 [0.09]; t=3.05, df=34.0, p=0.01, Cohen’s d=1.0) and, additionally, hippocampus (SCZ=2.40 [0.12]; HV=2.74 [0.07]; t=2.32, df=34.0, p=0.03, Cohen’s d=0.8). There were no significant relationships (p>0.05) between VT and GMV, PANSS score, DOI and CPZ.Preclinical study: Chronic olanzapine or haloperidol exposure did not significantly affect total SV2A immunostaining intensity (p=0.97 and p=0.71 respectively) in the rat frontal cortex as compared to vehicle-exposed controls. Moreover, chronic haloperidol exposure did not significantly affect [3H]UCB-J specific binding (p=0.27) or SV2A protein levels (relative to GAPDH, p=0.71).DiscussionThese findings provide evidence for the first time that presynaptic marker protein levels are reduced in schizophrenia in vivo and that antipsychotic drug exposure is unlikely to account for this, consistent with the synaptic dysfunction hypothesis.