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We compared the feasibility of quantitative analysis methods using bone SPECT/CT with those using planar bone scans to assess active sacroiliitis.We retrospectively reviewed whole-body bone scans and pelvic bone SPECT/CTs of 8 patients who had clinically confirmed sacroiliitis and enrolled 24 patients without sacroiliitis as references. The volume of interest of each sacroiliac joint, including both the ilium and sacrum, was drawn. Active arthritis zone (AAZ) was defined as the zone of voxels with higher SUV than sacral mean SUV within the VOI of SI joint. Then, the following SPECT/CT quantitative parameters, SUVmax (maximum SUV), SUV50% (mean SUV in highest 50% of SUV), and SUV-AAZ, and the ratio of those values to sacral mean SUV (SUVmax/S, SUV50%/S, SUV-AAZ/S) were calculated. For the planar bone scan, the mean count ratio of SI joint/sacrum (SI/S) was conventionally measured.Most of the SPECT/CT parameters of the sacroiliitis group were significantly higher than the normal group, whereas SI/S of the planar bone scan was not significantly different between the two groups. In receiver operating characteristic curve analysis, SUV-AAZ/S showed the highest AUC of 0.992, followed by SUV50%/S and SUVmax/S. All ratio parameters of the SPECT/CT showed higher AUC values than the SUV parameters of SI joint or SI/S of the planar scan.The quantitative analyses of bone SPECT/CT showed better performance in assessing active sacroiliitis than the planar bone scan. SPECT/CT parameters using the ratio of the SI joint to sacrum showed more favorable results than SUV parameters such as SUVmax, SUV50%, and SUV-AAZ.

Background: Cerebral amyloid angiopathy (CAA) often presents as cognitive impairment, but the mechanism of cognitive decline is unclear. Recent studies showed that number of microbleeds were associated with cognitive decline. Objective: We aimed to investigate how microbleeds contribute to cognitive impairment in association with white matter tract abnormalities or cortical thickness in CAA. Methods: This retrospective comparative study involved patients with probable CAA according to the Boston criteria (Aβ+ CAA) and patients with Alzheimer’s disease (Aβ+ AD), all of whom showed severe amyloid deposition on amyloid PET. Using mediation analysis, we investigated how FA or cortical thickness mediates the correlation between the number of lobar microbleeds and cognition. Results: We analyzed 30 patients with Aβ+ CAA (age 72.2±7.6, female 53.3%) and 30 patients with Aβ+ AD (age 71.5±7.6, female 53.3%). The two groups showed similar degrees of cortical amyloid deposition in AD-related regions. The Aβ+ CAA group had significantly lower FA values in the clusters of the posterior area than did the Aβ+ AD group (family-wise error-corrected p

We aimed to evaluate the diagnostic ability for the prediction of histologic grades and prognostic values on recurrence and death of pretreatment 2-[18F]FDG PET/CT in patients with resectable thymic epithelial tumours (TETs). One hundred and fourteen patients with TETs who underwent pretreatment 2-[18F]FDG PET/CT between 2012 and 2018 were retrospectively evaluated. TETs were classified into three histologic subtypes: low-risk thymoma (LRT, WHO classification A/AB/B1), high-risk thymoma (HRT, B2/B3), and thymic carcinoma (TC). Area under the receiver operating characteristics curve (AUC) was used to assess the diagnostic performance of PET/CT variables (maximum standardised uptake value [SUVmax], metabolic tumour volume [MTV], total lesion glycolysis [TLG], maximum diameter). Cox proportional hazards models were built using PET/CT and clinical variables. The tumours included 52 LRT, 33 HRT, and 29 TC. SUVmax showed good diagnostic ability for differentiating HRT/TC from LRT (AUC 0.84, 95% confidence interval [CI] 0.76 − 0.92) and excellent ability for differentiating TC from LRT/HRT (AUC 0.94, 95% CI 0.90 − 0.98), with significantly higher values than MTV, TLG, and maximum diameter. With an optimal cut-off value of 6.4, the sensitivity, specificity, and accuracy for differentiating TC from LRT/HRT were 69%, 96%, and 89%, respectively. In the multivariable Cox proportional hazards analyses for freedom-from-recurrence, SUVmax was an independent prognostic factor (p

We evaluated the performance of deep learning classifiers for bone scans of prostate cancer patients. A total of 9113 consecutive bone scans (5342 prostate cancer patients) were initially evaluated. Bone scans were labeled as positive/negative for bone metastasis using clinical reports and image review for ground truth diagnosis. Two different 2D convolutional neural network (CNN) architectures were proposed: (1) whole body–based (WB) and (2) tandem architectures integrating whole body and local patches, here named as “global–local unified emphasis” (GLUE). Both models were trained using abundant (72%:8%:20% for training:validation:test sets) and limited training data (10%:40%:50%). The allocation of test sets was rotated across all images: therefore, fivefold and twofold cross-validation test results were available for abundant and limited settings, respectively. A total of 2991 positive and 6142 negative bone scans were used as input. For the abundant training setting, the receiver operating characteristics curves of both the GLUE and WB models indicated excellent diagnostic ability in terms of the area under the curve (GLUE: 0.936–0.955, WB: 0.933–0.957, P > 0.05 in four of the fivefold tests). The overall accuracies of the GLUE and WB models were 0.900 and 0.889, respectively. With the limited training setting, the GLUE models showed significantly higher AUCs than the WB models (0.894–0.908 vs. 0.870–0.877, P

Introduction Apraxia is a core clinical feature of corticobasal syndrome (CBS). Among the subtypes of apraxia, ideomotor and imitation apraxia are frequently found in CBS. However, little is known about the brain networks that are characteristic of each apraxia subtype or their clinical implication. In this study, we used 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to explore the specific patterns of glucose hypometabolism that are characteristic of apraxia subtypes by focusing on ideomotor and imitation apraxia. Methods We compared the areas of glucose hypometabolism in the brains of 52 patients with CBS and 13 healthy controls, both as a whole and according to apraxia subtypes. In addition, we investigated the relationship between the apraxia subtypes and the clinical phenotype of CBS. Results In patients with CBS, common hypometabolism was observed in the frontal gyrus, precentral gyrus and caudate regardless of apraxia subtypes. In particular, ideomotor apraxia was associated with hypometabolism in the angular gyrus, while imitation apraxia was associated with hypometabolism in the posterior part including the postcentral gyrus, precuneus, and posterior cingulate gyrus. Patients who showed both ideomotor and imitation apraxia were more likely to show the typical features of CBS and progressive supranuclear palsy compared with patients showing only one type of apraxia. Conclusion Group comparison analysis using FDG-PET revealed distinct pathways of ideomotor and imitation apraxia in CBS. These findings add to our understanding of the brain networks underlying apraxia in association with the clinical features of CBS.

The aim of this study was to develop a deep learning (DL)-based segmentation algorithm for automatic measurement of metabolic parameters of 18F-FDG PET/CT in thymic epithelial tumors (TETs), comparable performance to manual volumes of interest.A total of 186 consecutive patients with resectable TETs and preoperative 18F-FDG PET/CT were retrospectively enrolled (145 thymomas, 41 thymic carcinomas). A quasi-3D U-net architecture was trained to resemble ground-truth volumes of interest. Segmentation performance was assessed using the Dice similarity coefficient. Agreements between manual and DL-based automated extraction of SUVmax, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and 63 radiomics features were evaluated via concordance correlation coefficients (CCCs) and linear regression slopes. Diagnostic and prognostic values were compared in terms of area under the receiver operating characteristics curve (AUC) for thymic carcinoma and hazards ratios (HRs) for freedom from recurrence.The mean Dice similarity coefficient was 0.83 ± 0.34. Automatically measured SUVmax (slope, 0.97; CCC, 0.92), MTV (slope, 0.94; CCC, 0.96), and TLG (slope, 0.96; CCC, 0.96) were in good agreement with manual measurements. The mean CCC and slopes were 0.88 ± 0.06 and 0.89 ± 0.05, respectively, for the radiomics parameters. Automatically measured SUVmax, MTV, and TLG showed good diagnostic accuracy for thymic carcinoma (AUCs: SUVmax, 0.95; MTV, 0.85; TLG, 0.87) and significant prognostic value (HRs: SUVmax, 1.31 [95% confidence interval, 1.16-1.48]; MTV, 2.11 [1.09-4.06]; TLG, 1.90 [1.12-3.23]). No significant differences in the AUCs or HRs were found between automatic and manual measurements for any of the metabolic parameters.Our DL-based model provides comparable segmentation performance and metabolic parameter values to manual measurements in TETs.

Imaging biomarkers support the diagnosis of Alzheimer’s disease (AD). We aimed to determine whether combining automated brain volumetry on MRI and quantitative measurement of tau deposition on [18F] THK-5351 PET can aid discrimination of AD spectrum. From a prospective database in an IRB-approved multicenter study (NCT02656498), 113 subjects (32 healthy control, 55 mild cognitive impairment, and 26 Alzheimer disease) with baseline structural MRI and [18F] THK-5351 PET were included. Cortical volumes were quantified from FDA-approved software for automated volumetric MRI analysis (NeuroQuant). Standardized uptake value ratio (SUVR) was calculated from tau PET images for 6 composite FreeSurfer-derived regions-of-interests approximating in vivo Braak stage (Braak ROIs). On volumetric MRI analysis, stepwise logistic regression analyses identified the cingulate isthmus and inferior parietal lobule as significant regions in discriminating AD from HC and MCI. The combined model incorporating automated volumes of selected brain regions on MRI (cingulate isthmus, inferior parietal lobule, hippocampus) and SUVRs of Braak ROIs on [18F] THK-5351 PET showed higher performance than SUVRs of Braak ROIs on [18F] THK-5351 PET in discriminating AD from HC (0.98 vs 0.88, P = 0.033) but not in discriminating AD from MCI (0.85 vs 0.79, P = 0.178). The combined model showed comparable performance to automated volumes of selected brain regions on MRI in discriminating AD from HC (0.98 vs 0.94, P = 0.094) and MCI (0.85 vs 0.78; P = 0.065).

BACKGROUND: To date, the clinical significance of visually equivocal amyloid positron emission tomography (PET) has not been well established. OBJECTIVE: We studied the clinical significance of equivocal amyloid PET images from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). METHODS: Subjects with F-18 florbetapir PET scans at baseline who were followed up for 4 years were selected. Clinical characteristics, imaging biomarkers, cognitive function, and rate of conversion to AD were compared in subjects with visually equivocal findings. RESULTS: Of 249 subjects who completed the follow-up, 153 (61.4%), 20 (8.0%), and 129 (30.5%) were F-18 florbetapir-negative, -equivocal, and -positive, respectively. The mean standardized uptake value ratios (SUVR) of F-18 florbetapir PET were 0.75 ± 0.04, 0.85 ± 0.10, and 1.00 ± 0.09 for each group (p

Purpose: To evaluate the association between genomic data and imaging features of dual time point 18F-FET PET/CT in patients with primary brain tumor for radiogenomic mapping. Methods: From June 2021 to July 2022, we prospectively enrolled the patients under suspicious of de novo primary brain tumor in Asan Medical Center. Prior to the surgery, contrast-enhanced MRI and 18F-FET PET/CT scans were routinely performed. Twenty minutes after the post-injecting (p.i.) approximately 5 mCi of 18F-FET, patients underwent early PET/CT acquisition (20-40 min p.i.). Delay PET/CT (80-100 min p.i) was subsequently obtained after 40-minute break. SUVmax, maximum tumor-to-brain ratios and PET-positive volumes using different isocontours of SUVmax (I30, I60, I90%) in tumor were calculated in each sum images. Histopathologic results were made based on 2016 WHO classification and, isocitrate dehydrogenase (IDH) mutation, O6-methylguanine-DNA methyltransferase (MGMT) methylation, telomerase reverse transcriptase (TERT) mutation and co-deletion of 1p19q status were investigated as well. Spearman’s correlation coefficient (r), logistic regression and AUC-ROC analysis were employed using aforementioned radiomics information. Results: A total of 42 patients (median age 55.5 yrs, range 21-84; M:F=31:11) were recruited and, 29 patients had glioblastoma with grade IV. Except TERT mutation (n=25), IDH mutation (n=11), MGMT methylation (n=19) and co-deletion of 1p19q (n=8) had statistically significant correlation each other (IDH vs. MGMT, r=0.55; IDH vs. 1p19q, r=0.53; MGMT vs. 1p19q, r=0.42). Early scan of I60% was closely related with IDH mutation (positive, 3.92 ± 3.04 vs. negative, 7.96 ± 5.36; p=0.005) meanwhile delay scan of I30% had significant association with co-deletion of 1p19q (present, 34.16 ± 18.67 vs. absent, 71.99 ± 38.79; p=0.01). The accuracy of logistic regression and the corresponding AUC-ROC values for IDH/MGMT/TERT/co-deletion of 1p19q status were 0.86/0.73/0.78/0.85, and 0.88/0.76/0.78/0.91, respectively. Conclusion: Although this is a preliminary and interim analysis during our prospective study being slated to enroll the patients until December 2023, we suggest that the information acquired from both genetics and 18F-FET could be integrated into better characterization of primary brain tumor. Citation Format: Dong Yun Lee, Sang Woo Song, Seungjoo Lee, Minyoung Oh, Jungsu S. Oh, Jaeseung Kim. Radiogenomic analysis in the patients with primary brain tumor using dual time point 18F-FET PET/CT. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5620.

18F-labeled fluoropropyl-carbomethoxylodopropyl-nor-s-tropane ([18F]FP-CIT) positron emission tomography (PET) is a useful tool for evaluating disease progression in Parkinson’s disease (PD) patients. We evaluated the test–retest reproducibility of [18F]FP-CIT PET measures in essential tremor (ET) and PD patients. Fifteen ET (68.9 ± 6.6 years) and 10 PD patients (70.5 ± 6.3 years; Hoehn and Yahr stage, 2.3 ± 0.8) underwent two [18F]FP-CIT PET/CT scans with an interval of 48 ± 7 day. For both the test and retest studies, standardized uptake value ratios were estimated for 90-min and 3-h acquisitions for the caudate, anterior putamen, and posterior putamen using T1-MRI-based normalization (automatic) and fixed-VOI (manual) methods, with the occipital lobe as a reference. Reproducibility was evaluated by the bias, variability, percent test–retest, within-subject coefficient of variation, repeatability coefficient, and intraclass correlation coefficient (ICC). Reproducibility was excellent, with low variability (ET: 6.99–8.02%, PD: 3.51–6.94%) and high reliability (ICC; ET: 0.88–0.96, PD: 0.98–0.99). The ET group showed higher variability and lower ICCs than the PD group. The variability in the 90-min images (ET: 7.85–8.59%, PD: 1.52–2.75%) was comparable to that in the 3-h images (ET: 6.99–8.02%, PD: 3.51–6.94%). There were no differences in variability among the subregions in the ET group. In the PD group, the variability was high in the posterior putamen (automatic method: 6.94%, manual method: 11.80%). The test–retest variability and ICCs were similar for the manual and automatic methods. [18F]FP-CIT PET is reproducible for the quantitative measurement of DAT binding in both ET and PD individuals, independent of the acquisition time or analysis method. Also, the automatic method is more suitable for evaluating early loss of DAT binding in patients with PD

A comprehensive understanding of the link between 18F-FDG PET/CT and the tumor immune microenvironment (TIM) is lacking. We, therefore, investigated the TIM in regard to the gene signature of 18F-FDG PET/CT in head and neck squamous cell carcinoma (HNSC). The mRNA sequence data of 480 HNSC patients on The Cancer Genome Atlas portal were used to explore genes showing high associations with maximum standardised uptake value (SUVmax) on 18F-FDG PET/CT based on Pearson correlation test. Hierarchical clustering of the selected gene signature was performed and divided patients into high and low SUV clusters. Principal component analysis was performed to derive the summarised expression profile of the gene signature and defined the first principal component scores as the SUV signature scores (SUVSSs). The SUV clusters and SUVSS based on the gene signature were characterised by overall survival, clinical variables, and the immune microenvironment in terms of overall immune score, immune cell type enrichment score, expression of immunomodulator genes as well as somatic copy number alterations (SCNA) possibly contributing to immune cell recognition. The high SUV cluster classified by the gene signature (191 genes) was an independent predictor of overall survival (adjusted hazard ratio 1.40, p = 0.022). The SUVSS values differed across the molecular subtypes of HNSC (p

Purpose PET is a useful tool for detecting the presence and extent of brain tau accumulation. However, most first-generation tau PET tracers are limited for high off-target binding and detection of tau in non-Alzheimer disease (AD). This study evaluated potential clinical applications of F-PI-2620 as a novel PET tracer with a high binding affinity for tau deposition in AD and non-AD tauopathies. Methods Twenty-six participants diagnosed with either mild cognitive impairment, probable AD, frontotemporal dementia, or parkinsonism, as well as healthy controls underwent a 60- to 90-minute brain PET scan after 7 mci (259 MBq) injection of F-PI-2620. Some participants had previous PET scans using F-THK-5351 or F-FP-CIT for dopamine transporter imaging. Results All participants showed no increase in off-target binding in basal ganglia on F-PI-2620 PET images, as noted for first-generation tau tracers. Aβ+ mild cognitive impairment or AD patients showed diverse cortical F-PI-2620 uptake in frontotemporoparietal cortex that correlated with Mini-Mental Status Examination (ρ = -0.692, P = 0.013). Aβ+ Parkinson disease with dementia and (Aβ unknown) primary progressive aphasia patients also showed increased F-PI-2620 uptakes in the frontotemporoparietal cortex. Patients with parkinsonism showed increased uptakes in the pallidum compared with Aβ- healthy controls (left: 1.41 ± 0.14 vs 1.04 ± 0.13, P = 0.014; right: 1.18 ± 0.16 vs 0.95 ± 0.07, P = 0.014). Conclusions F-PI-2620 PET might be a sensitive tool to detect cortical tau deposits in patients with Aβ+ AD and Aβ+ non-AD tauopathies. Furthermore, this study showed that "off-target" binding in the basal ganglia does not affect F-PI-2620.

Fatigue is one of the most common non-motor symptoms in Parkinson’s disease (PD). Despite its clinical importance, there are few studies on the cause or mechanism of fatigue. Our aim was to find brain areas related to fatigue and to explore the association between striatal dopaminergic dysfunction and fatigue. We consecutively screened forty-seven patients with de novo PD from 2012 to 2017 and enrolled 32 patients. The gray matter volumes, white matter tracts, and striatal dopaminergic activity between PD without fatigue and with fatigue were compared. The correlation between fatigue and striatal dopaminergic activity was also analyzed. Our data did not show any significant difference in gray matter volume between PD without fatigue and with fatigue (familywise error [FWE] corrected p > 0.05) but revealed significantly higher mean fractional anisotropy (FA) values for all analyzed white matter tracts in PD with fatigue (false discovery rate [FDR] corrected p 0.06); lower mean diffusivity (MD) values for all analyzed white matter tracts in PD with fatigue (FDR corrected p 0.05). The mean radial diffusivity (RD) values, except for the left CH (FDR corrected p = 0.0576), were also significantly lower (FDR corrected p 0.50). The alteration of the white matter tract may reflect the degree of fatigue in PD. This is not true of the gray matter and striatal dopaminergic activity. These results show the possibility that white matter changes can be used as a biomarker for fatigue.

Although most deep learning (DL) studies have reported excellent classification accuracy, these studies usually target typical Alzheimer’s disease (AD) and normal cognition (NC) for which conventional visual assessment performs well. A clinically relevant issue is the selection of high-risk subjects who need active surveillance among equivocal cases. We validated the clinical feasibility of DL compared with visual rating or quantitative measurement for assessing the diagnosis and prognosis of subjects with equivocal amyloid scans. 18F-florbetaben scans of 430 cases (85 NC, 233 mild cognitive impairment, and 112 AD) were assessed through visual rating-based, quantification-based, and DL-based methods. DL was trained using 280 two-dimensional PET images (80%) and tested by randomly assigning the remaining (70 cases, 20%) cases and a clinical validation set of 54 equivocal cases. In the equivocal cases, we assessed the agreement among the visual rating, quantification, and DL and compared the clinical outcome according to each modality-based amyloid status. The visual reading was positive in 175 cases, equivocal in 54 cases, and negative in 201 cases. The composite SUVR cutoff value was 1.32 (AUC 0.99). The subject-level performance of DL using the test set was 100%. Among the 54 equivocal cases, 37 cases were classified as positive (Eq(deep+)) by DL, 40 cases were classified by a second-round visual assessment, and 40 cases were classified by quantification. The DL- and quantification-based classifications showed good agreement (83%, κ = 0.59). The composite SUVRs differed between Eq(deep+) (1.47 [0.13]) and Eq(deep−) (1.29 [0.10]; P < 0.001). DL, but not the visual rating, showed a significant difference in the Mini-Mental Status Examination score change during the follow-up between Eq(deep+) (− 4.21 [0.57]) and Eq(deep−) (− 1.74 [0.76]; P = 0.023) (mean duration, 1.76 years). In visually equivocal scans, DL was more related to quantification than to visual assessment, and the negative cases selected by DL showed no decline in cognitive outcome. DL is useful for clinical diagnosis and prognosis assessment in subjects with visually equivocal amyloid scans.

Cognitive impairment is a common non-motor feature of Parkinson's disease (PD). However, the underlying pathophysiology of cognitive decline is unclear. We investigated the association of striatal dopamine transporter (DAT) loss with cognitive function and cerebral cortical metabolism in PD.Twenty-eight patients (63.1 ± 7.1 yrs, M:F = 15:13) with advanced stage of PD were enrolled, including 15 (53.6%) diagnosed with mild cognitive impairment (MCI). All patients underwent FP-CIT PET/CT, neuropsychological tests, and FDG PET/CT within a 2-week interval. We calculated the specific to non-specific binding ratio on FP-CIT PET images in 12 striatal subregional VOIs, using one occipital VOI template as a reference. Age-adjusted normalized specific to non-specific binding ratios (%BRs) of striatal subregions were compared in two groups: PD with MCI versus PD (without cognitive impairment).There were no statistical differences in age, age at onset, disease duration, motor symptoms, or level of education between the two groups. The PD with MCI had lower %BRs in all striatal subregions (P0.05) except the posterior putamen, compared with the PD. Striatal DAT availability correlated with frontal/executive function (r = 0.567, P = 0.003) and visuospatial function (r = 0.614, P = 0.001) but not with memory function. Dopamine transporter binding of striatal subregions also correlated with posterior cortical metabolism.This study suggest that DAT loss in the striatum, except in the posterior putamen, is associated with cognitive dysfunction, specifically frontal/executive function and visuospatial function in PD subjects.

The pathogenesis of isolated rapid eye movement sleep behavior disorders (iRBD) is poorly understood. The severity of RBD may reflect its pathogenesis.We compared motor function and non-motor symptoms (NMSs) between iRBD patients and healthy volunteers. We correlated motor function, NMSs, and striatal dopaminergic activity with RBD severity using video-polysomnography.Twenty-one iRBD patients and 17 controls participated. The Unified Parkinson's Disease Rating Scale part III scores were higher in patients compared to controls (iRBD is a multisystem neurodegenerative disorder, and gait abnormalities may be a disease characteristic, possibly related to the akinetic-rigid phenotype of Parkinson's disease. The correlation between pain/visuospatial dysfunction and RBD severity may be related to its pathogenesis.

We examined whether

A substantial amount of amyloid-beta (Aβ) accumulates in the occipital cortices, however, it draws less attention. We investigated the clinical implications of Aβ accumulation in the occipital lobes in the Alzheimer’s disease (AD) continuum. [18F]-Florbetaben amyloid PET scans were performed in a total of 121 AD or amnestic mild cognitive impairment (aMCI) patients. Of the 121 patients, 74 Aβ positive patients were divided into occipital Aβ positive (OCC+) and occipital Aβ negative (OCC−) groups based on Aβ accumulation in the bilateral occipital lobes. The OCC+ group (41/74, 55.4%) was younger and had a younger age at onset than the OCC− group. The OCC+ group also had an increased standard uptake value ratio in the occipital lobes and greater cortical thinning in relevant areas. The OCC+ group had a higher global deterioration scale, lower performance for the copy, immediate recall, delayed recall, and recognition in Rey–Osterrieth Complex Figure tests than the OCC- group, although both groups had similar disease durations. AD or aMCI patients in the OCC+ group exhibited features noted in early onset AD with relevant neuropsychological and image findings. Occipital Aβ positivity in amyloid PET scans need to be considered as an underestimated marker of early onset AD continuum.

PURPOSE OF THE REPORT Oxidative stress is a leading factor in the pathogenesis of idiopathic Parkinson disease (IPD). Two intrinsic antioxidative molecules, bilirubin and uric acid, are known to protect dopaminergic neurons from oxidative stress in IPD. The objective of this study was to determine the relationship between basal serum levels of 2 molecules and dopaminergic deficit assessed by dopamine transporter imaging with F-fluorinated-N-3-fluoropropyl-2-β-carboxymethoxy-3-β-(4-iodophenyl)nortropane ([F]FP-CIT) PET/CT in patients with early-stage drug-naive IPD. METHODS Cases of IPD patients who possess the levels of uric acid and bilirubin within a month from [F]FP-CIT PET/CT from January 2011 to December 2016 were retrospectively reviewed. As a control, the same criteria applied to patients with essential tremor (ET). PET images were analyzed using volume-of-interest templates for 12 striatal subregions and 1 occipital area, and the specific-to-nonspecific binding ratio (SNBR) was calculated. RESULTS One hundred five patients with drug-naive, early-stage IPD and 62 patients with ET were finally included. Levels of bilirubin were significantly higher in the IPD group than in controls (P = 0.026), and bilirubin level was the factor showing the most correlations with SNBR in IPD (P < 0.001), whereas uric acid showed no such difference or relationship. Furthermore, levels of bilirubin showed a positive correlation with SNBR in more affected posterior putamen in the IPD group (Pearson correlation coefficient, ρ = 0.456; P < 0.001), but a negative one in the ET group (ρ = -0.440, P < 0.001). CONCLUSIONS Bilirubin, not uric acid, was the most significant antioxidant marker for dopaminergic deficit in early-stage drug-naive IPD assessed by [F]FP-CIT PET/CT.

Motor dysfunctions in Parkinson disease (PD) patients are not completely normalized by deep brain stimulation (DBS), and there is an obvious difference in the degree of symptom improvement after DBS for each patient.To test our hypothesis that each patient has their own restoration capacity for motor improvement after DBS, and to investigate whether regional cerebral glucose metabolism in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scans is associated with the capacity for off-medication motor improvement (MIoff) after DBS.The MIoff (%) was calculated using the Unified Parkinson's Disease Rating Scale part III in 27 PD patients undergoing DBS in the globus pallidus interna. The standardized uptake value ratios (SUVRs) on FDG-PET were quantitatively measured, and the areas where the SUVR correlated with the MIoff (%) were identified. Also, the areas where the SUVR was significantly different between the 2 MIoff groups (≥60% vs 60%) were determined.Ten patients achieved MIoff 60% at 12 mo after DBS. In general, the MIoff (%) was positively correlated with preoperative SUVR in the temporo-parieto-occipital lobes, while it was inversely correlated with the metabolism in the primary motor cortex. The patients in the MIoff 60% group showed a significant decrease in SUVR in the parieto-occipital lobes, while parieto-occipital metabolism in those with MIoff ≥ 60% was relatively preserved (Mann-Whitney U test, P = .03).Our findings suggest that the parieto-occipital lobes may be implicated more generally in the prognosis of motor improvement after DBS in advanced PD than other regions.

Purpose 4-(3S)-3-[5-(2-[18F]-fluoroethoxy)pyridin-3-yl]-3-[({(3R)-1-[3-(piperidin-4-yl)propanoyl]-piperidin-3-yl}carbonyl)amino]propanoic acid ([18F]GP1) is a radiotracer developed for targeted imaging of activated platelet glycoprotein IIb/IIIa receptors with positron emission tomography/computed tomography (PET/CT) in acute thromboembolism. We evaluated here radiation dosimetry of [18F]GP1 in humans. Procedures We studied 30 subjects (10 with deep vein thrombosis, 10 with pulmonary embolism, and 10 with arterial thromboembolism) who had signs or symptoms of acute thromboembolism, and were confirmed to have thromboembolic foci by imaging studies. Dynamic whole-body PET/CT images were acquired for up to 140 min after injection of 250 MBq of [18F]GP1. Radiation absorbed dose and effective dose were calculated using the OLINDA/EXM software. Results [18F]GP1 PET images showed high initial uptake of the tracer in the heart, spleen, kidney, and liver. [18F]GP1 activity was cleared by hepatobiliary and urinary excretion. The organ receiving the highest radiation absorbed dose (mGy/MBq) was the urinary bladder (0.0884 ± 0.0458), followed by upper large intestine (0.0498 ± 0.0189), small intestine (0.0454 ± 0.0166), and kidneys (0.0350 ± 0.0231). The effective dose (mSv/MBq) was 0.0212 ± 0.0027 (ICRP 103). ED was not significantly different between the three disease groups (p = 0.94). A 45-minute voiding reduced the urinary bladder wall radiation dose to 0.0495 ± 0.0140 mGy/MBq, and effective dose (ICRP 103) to 0.0186 ± 0.0030. Conclusions [18F]GP1 has favorable radiation dosimetry profile for clinical PET/CT imaging. The ED is comparable to commonly used 18F PET tracers.

Tau and amyloid β (Aβ), 2 key pathogenic proteins in Alzheimer’s disease (AD), reportedly spread throughout the brain as the disease progresses. Models of how these pathogenic proteins spread from affected to unaffected areas had been proposed based on the observation that these proteins could transmit to other regions either through neural fibers (transneuronal spread model) or through extracellular space (local spread model). In this study, we modeled the spread of tau and Aβ using a graph theoretical approach based on resting-state functional magnetic resonance imaging. We tested whether these models predict the distribution of tau and Aβ in the brains of AD spectrum patients. To assess the models’ performance, we calculated spatial correlation between the model-predicted map and the actual map from tau and amyloid positron emission tomography. The transneuronal spread model predicted the distribution of tau and Aβ deposition with significantly higher accuracy than the local spread model. Compared with tau, the local spread model also predicted a comparable portion of Aβ deposition. These findings provide evidence of transneuronal spread of AD pathogenic proteins in a large-scale brain network and furthermore suggest different contributions of spread models for tau and Aβ in AD.

We aimed to evaluate the diagnostic ability for the prediction of histologic grades and prognostic values on recurrence and death of pretreatment 2-[One hundred and fourteen patients with TETs who underwent pretreatment 2-[The tumours included 52 LRT, 33 HRT, and 29 TC. SUVmax showed good diagnostic ability for differentiating HRT/TC from LRT (AUC 0.84, 95% confidence interval [CI] 0.76 - 0.92) and excellent ability for differentiating TC from LRT/HRT (AUC 0.94, 95% CI 0.90 - 0.98), with significantly higher values than MTV, TLG, and maximum diameter. With an optimal cut-off value of 6.4, the sensitivity, specificity, and accuracy for differentiating TC from LRT/HRT were 69%, 96%, and 89%, respectively. In the multivariable Cox proportional hazards analyses for freedom-from-recurrence, SUVmax was an independent prognostic factor (p 0.001), whereas MTV and TLG were not. SUVmax was a significant predictor for overall survival in conjunction with clinical stage and resection margin.SUVmax showed excellent diagnostic performance for prediction of TC and significant prognostic value in terms of recurrence and survival.• Maximum standardised uptake value (SUVmax) shows excellent performance in the differentiation of thymic carcinoma from low- and high-risk thymoma. • SUVmax is an independent prognostic factor for freedom-from-recurrence in the multivariable Cox proportional hazard model and a significant predictor for overall survival. • 2-[

Highlights • 18F-FDG PET/CT visualizes altered glucose metabolism which is underpinned by the alteration of specific genes and signaling pathways. • Our analysis of TCGA-HNSC data showed a positive correlation of FDG uptake with the total and non-silent mutation rates, genetic heterogeneity, and copy number alterations. • Significant higher FDG uptake was noted in patients with alterations in cell cycle (CDKN2A gene), or TP53 oncogenic signaling pathways (TP53 gene)., Background We investigated the relationship between genetic alterations and 18F-FDG PET/CT findings in head and neck squamous cell carcinoma (HNSC). Methods Using mRNA-sequences of HNSC samples (480 patients) from the Cancer Genome Atlas (TCGA) portal, gene coexpression networks were constructed via a weighted correlation network analysis (WGCNA) algorithm, and their association with the tumor-to-blood signal ratio on 18F-FDG PET/CT data (21 patients) was explored. An elastic-net regression model was developed to estimate the PET tumor-to-blood ratio from the gene networks and to derive an FDG signature score (FDGSS). The FDGSS was evaluated with regard to clinical variables and general mutational profiles, as well as alterations to oncogenic signaling pathways. Findings The FDGSS values differed across clinical stages (p = 0.027), HPV-status (p< 0.001), and molecular subtypes of HNSC (p< 0.001). Multivariate Cox regression demonstrated that FDGSS was an independent predictor for overall (p = 0.019) and progression-free survival (p = 0.024). FDGSS positively correlated with total mutation rate (p = 0.016), aneuploidy (p

A comprehensive understanding of the link betweenThe mRNA sequence data of 480 HNSC patients on The Cancer Genome Atlas portal were used to explore genes showing high associations with maximum standardised uptake value (SUVmax) onThe high SUV cluster classified by the gene signature (191 genes) was an independent predictor of overall survival (adjusted hazard ratio 1.40, p = 0.022). The SUVSS values differed across the molecular subtypes of HNSC (p 0.001), and HPV status (p = 0.024). Tumors in the low SUV cluster exhibited significantly higher overall immune score and lower SCNA scores (p 0.05 for all) compared with tumors in the high SUV cluster. The low SUV cluster showed an immune cell composition consisting of high levels of T cells, B cells, mast cells, neutrophils, monocytes, and eosinophils, but lower basophils and similar macrophage levels to the high SUV cluster. Differential gene expression analysis demonstrated SUV cluster-distinct expression of several immunomodulators including PD-1, CD40LG, IL2RA, TLR4, BTLA, and TIGIT.HNSC exhibited the distinct TIM according to the gene signature reflecting SUVmax on

Background To compare the diagnostic sensitivity of [18F]fluoroestradiol ([18F]FES) and [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) for breast cancer recurrence in patients with estrogen receptor (ER)-positive primary breast cancer. Methods Our database of consecutive patients enrolled in a previous prospective cohort study to assess [18F]FES PET/CT was reviewed to identify eligible patients who had ER-positive primary breast cancer with suspected first recurrence at presentation and who underwent [18F]FDG PET/CT. The sensitivity of qualitative [18F]FES and [18F]FDG PET/CT interpretations was assessed, comparing them with histological diagnoses. Results Of the 46 enrolled patients, 45 were confirmed as having recurrent breast cancer, while one was diagnosed with chronic granulomatous inflammation. Forty (89%) patients were ER-positive, four (9%) were ER-negative, and one (2%) patient did not undergo an ER assay. The sensitivity of [18F]FES PET/CT was 71.1% (32/45, 95% CI, 55.7–83.6), while that of [18F]FDG PET/CT was 80.0% (36/45, 95% CI, 65.4–90.4) with a threshold of positive interpretation, and 93.3% (42/45, 95% CI, 81.7–98.6) when a threshold of equivocal was used. There was no significant difference in sensitivity between [18F]FES and [18F]FDG PET/CT (P = 0.48) with a threshold of positive [18F]FDG uptake, but the sensitivity of [18F]FDG was significantly higher than [18F]FES (P = 0.013) with a threshold of equivocal [18F]FDG uptake. One patient with a benign lesion showed negative [18F]FES but positive [18F]FDG uptake. Conclusions The restaging of patients who had ER-positive primary breast cancer and present with recurrent disease may include [18F]FES PET/CT as an initial test when standard imaging studies are equivocal or suspicious.

This study aimed to establish an optimal protocol for 99mTc-sestamibi parathyroid imaging for lesion localization in patients with hyperparathyroidism (HPT). We retrospectively enrolled 35 consecutive patients who underwent dual-phase (at 10 minutes and 120 minutes) 99mTc-sestamibi parathyroid scintigraphy with single-photon emission computed tomography (SPECT)/computed tomography (CT). Twenty seven patients had primary HPT, and 8 had secondary or tertiary HPT. Three nuclear medicine physicians independently analyzed the parathyroid images for lesion localization at 9 predefined parathyroid locations using the following 4 different image sets blinded to the clinical information: 1. dual-phase SPECT, 2. early SPECT/CT, 3. delayed SPECT/CT, 4. dual-phase SPECT/CT. All SPECT or SPECT/CT image sets were analyzed with dual-phase planar images. The image results were compared with the histopathological results after surgery. Dual-phase SPECT/CT showed the highest positive rate of 85.7% in the patient-based analysis and 13.7% in the location-based analysis. Of 35 patients, surgical pathological results were available in 21 (16 adenomas in 16 primary HPTs and 16 hyperplasias in 5 secondary or tertiary HPTs). Dual-phase SPECT/CT showed the sensitivity values of 100% and 84.4% in the patient-based and location-based analysis, respectively, which were the highest sensitivity values among all image sets. In the primary HPT subgroup, dual-phase SPECT/CT showed the highest sensitivity value of 93.8% in the location-based analyses, whereas dual-phase SPECT, early SPECT/CT, and delayed SPECT/CT showed the sensitivity values of 62.5%, 81.3%, and 81.3%, respectively. In the secondary or tertiary HPT subgroup, dual-phase SPECT/CT also showed the highest sensitivity value of 75.0%, whereas early SPECT/CT, delayed SPECT/CT, and dual-phase SPECT showed the sensitivity values of 43.8%, 56.3%, and 68.8%, respectively. Compared with dual-phase SPECT or single-phase SPECT/CT, the dual-phase SPECT/CT imaging protocol for 99mTc-sestamibi scintigraphy showed the highest positive rate and sensitivity, and was optimal for parathyroid lesion localization.