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Due to reversal blood flow in the diastolic phase, outpouchings at the aortic isthmus may carry the risk of thrombus formation and subsequent thromboembolism. The objective was to evaluate the association between aortic ductus diverticula (ADDs) and ischemic brain alterations in cerebral magnetic resonance imaging.A retrospective analysis of 218 patients who received both a dedicated computed tomography angiography of the thoracic aorta and a brain magnetic resonance imaging was performed. Two radiologists independently reviewed all examinations for the presence of ADD as well as ischemic alterations of the brain. The association between this anatomical variant and ischemic brain alterations was evaluated by univariate and bivariate logistic regression analyses.ADDs were identified/present in 35 of 218 patients (16%). Ischemic brain alterations were found in 57% of patients (20/35) with an ADD and in 42% of the control group (77/183, P = 0.1). The presence of an ADD did not prove to be an independent risk factor for ischemic brain alterations after multivariate adjustment (odds ratio = 1.7, 95% confidence interval = 0.72-3.96, P = 0.225).In the present study, ADDs were not significantly associated with ischemic brain alterations. Therefore, ADDs seem to be an innocent bystander with respect to the pathogenesis of ischemic brain alterations.

The spreading hypothesis of neurodegeneration assumes an expansion of neural pathologies along existing neural pathways. Multimodal neuroimaging studies have demonstrated distinct topographic patterns of cerebral pathologies in neurodegeneration. For Parkinson’s disease the hypothesis so far rests largely on histopathological evidence of α-synuclein spreading in a characteristic pattern and progressive nigrostriatal dopamine depletion. Functional consequences of nigrostriatal dysfunction on cortical activity remain to be elucidated. Our goal was to investigate multimodal imaging correlates of degenerative processes in Parkinson’s disease by assessing dopamine depletion and its potential effect on striatocortical connectivity networks and cortical metabolism in relation to parkinsonian symptoms. We combined 18F-DOPA-PET, 18F-fluorodeoxyglucose (FDG)-PET and resting state functional MRI to multimodally characterize network alterations in Parkinson’s disease. Forty-two patients with mild-to-moderate stage Parkinson’s disease and 14 age-matched healthy control subjects underwent a multimodal imaging protocol and comprehensive clinical examination. A voxel-wise group comparison of 18F-DOPA uptake identified the exact location and extent of putaminal dopamine depletion in patients. Resulting clusters were defined as seeds for a seed-to-voxel functional connectivity analysis. 18F-FDG metabolism was compared between groups at a whole-brain level and uptake values were extracted from regions with reduced putaminal connectivity. To unravel associations between dopaminergic activity, striatocortical connectivity, glucose metabolism and symptom severity, correlations between normalized uptake values, seed-to-cluster β-values and clinical parameters were tested while controlling for age and dopaminergic medication. Aside from cortical hypometabolism, 18F-FDG-PET data for the first time revealed a hypometabolic midbrain cluster in patients with Parkinson’s disease that comprised caudal parts of the bilateral substantia nigra pars compacta. Putaminal dopamine synthesis capacity was significantly reduced in the bilateral posterior putamen and correlated with ipsilateral nigral 18F-FDG uptake. Resting state functional MRI data indicated significantly reduced functional connectivity between the dopamine depleted putaminal seed and cortical areas primarily belonging to the sensorimotor network in patients with Parkinson’s disease. In the inferior parietal cortex, hypoconnectivity in patients was significantly correlated with lower metabolism (left P = 0.021, right P = 0.018). Of note, unilateral network alterations quantified with different modalities corresponded with contralateral motor impairments. In conclusion, our results support the hypothesis that degeneration of nigrostriatal fibres functionally impairs distinct striatocortical connections, disturbing the efficient interplay between motor processing areas and impairing motor control in patients with Parkinson’s disease. The present study is the first to reveal trimodal evidence for network-dependent degeneration in Parkinson’s disease by outlining the impact of functional nigrostriatal pathway impairment on striatocortical functional connectivity networks and cortical metabolism.

To examine the clinical benefit of Lu-177-PSMA-617 radioligand therapy for patients with metastatic castration-resistant prostate cancer (mCRPC).Between November 2014 and December 2018, a total of 56 consecutive patients (median age 69.5 years; range 55-84 years) with mCRPC were included in this retrospective analysis. Patients received between 1 and 4 therapy cycles with a mean activity of 6.8 GBq per cycle. Biochemical response was evaluated using Prostate Cancer Working Group Criteria 3 (PCWG 3). Survival was assessed using Kaplan-Meier estimates and Cox proportional hazards regression analysis. This retrospective study was approved by the local ethics committee.A total of 139 treatment cycles with Lu-177-PSMA-617 were performed. A decline of 50% or more of prostate-specific antigen (PSA) level occurred in 54% and a PSA decline of any amount in 65% of patients. The estimated median overall survival (OS) was 16 months, in the chemotherapy subgroup 14 months. A longer OS was associated with a PSA-decline ≥50%, more than 2 cycles of therapy, cumulative activity15 GBq and an initial alkaline phosphatase ≤ 220 [U/l]. These identified predictors remained significant on uni- and multivariate Cox regression analysis. Moreover, 40% of the patients who were non-responders after the first therapy cycle turned into responders after the second one.PSA-decline ≥50%, a cumulative activity15 GBq and an initial alkaline phosphatase ≤ 220 [U/l] were identified as key predictors of prolonged OS in patients with mCRPC. In contrast rapid clinical deterioration mostly due to skeletal carcinomatosis resulted in early treatment failure.ZIEL: Es sollte der klinische Nutzen der Lu-177-PSMA-617-Radioligandentherapie bei Patienten mit metastasiertem kastrationsresistentem Prostatakrebs (mCRPC) untersucht werden.In diese retrospektive Analyse zwischen November 2014 und Dezember 2018 wurden insgesamt 56 konsekutive Patienten (medianes Alter 69,5 Jahre; Bereich 55–84 Jahre) mit mCRPC eingeschlossen. Die Patienten erhielten zwischen 1 und 4 Therapiezyklen mit einer mittleren Aktivität von 6,8 GBq pro Zyklus. Das biochemische Ansprechen wurde anhand der Kriterien der „Prostate Cancer Working Group“ (PCWG 3) bewertet. Das Überleben wurde mittels Kaplan-Meier-Schätzer und einer proportionalen Cox-Hazard-Regressionsanalyse bewertet. Diese retrospektive Studie wurde von der zuständigen Ethikkommission genehmigt.Insgesamt wurden 139 Behandlungszyklen mit Lu-177-PSMA-617 durchgeführt. Eine Abnahme des Prostata-spezifischen Antigens (PSA) um 50 % oder mehr trat bei 54 % und eine PSA-Abnahme in beliebiger Höhe bei 65 % der Patienten auf. Das geschätzte mediane Gesamtüberleben (OS) betrug 16 Monate, in der Chemotherapie-Untergruppe 14 Monate. Ein längeres OS war verbunden mit einem PSA-Abfall ≥50%, mehr als 2 Therapiezyklen, einer kumulativen Aktivität15 GBq und einem initialen Wert für alkalischen Phosphatase ≤220 [U/l]. Diese identifizierten Prädiktoren blieben in der uni- und multivariaten Cox-Regressionsanalyse signifikant. Außerdem wurden 40 % der Patienten, die nach dem ersten Therapiezyklus nicht auf die Therapie ansprachen (Non-Responder), nach dem zweiten Zyklus zu Respondern.Ein PSA-Abfall von ≥50%, eine kumulative Aktivität von15 GBq und ein initialer Wert für alkalische Phosphatase von ≤220 [U/l] wurden als Schlüsselprädiktoren für ein längeres OS bei Patienten mit mCRPC identifiziert. Im Gegensatz dazu führte eine rasche klinische Verschlechterung, meist aufgrund einer Skelettkarzinose, zu einem frühen Therapieversagen.

The prevailing network perspective of Parkinson’s disease (PD) emerges not least from the ascending neuropathology traceable in histological studies. However, whether longitudinal in vivo correlates of network degeneration in PD can be observed remains unresolved. Here, we applied a trimodal imaging protocol combining 18F-fluorodeoxyglucose (FDG)- and 18F-fluoro-L-Dopa- (FDOPA)-PET with resting-state functional MRI to assess longitudinal changes in midbrain metabolism, striatal dopamine depletion and striatocortical dysconnectivity in 17 well-characterized PD patients. Whole-brain (un)paired-t-tests with focus on midbrain or striatum were performed between visits and in relation to 14 healthy controls (HC) in PET modalities. Resulting clusters of FDOPA-PET comparisons provided volumes for seed-based functional connectivity (FC) analyses between visits and in relation to HC. FDG metabolism in the left midbrain decreased compared to baseline along with caudatal FDOPA-uptake. This caudate cluster exhibited a longitudinal FC decrease to sensorimotor and frontal areas. Compared to healthy subjects, dopamine-depleted putamina indicated stronger decline in striatocortical FC at follow-up with respect to baseline. Increasing nigrostriatal deficits and striatocortical decoupling were associated with deterioration in motor scores between visits in repeated-measures correlations. In summary, our results demonstrate the feasibility of in-vivo tracking of progressive network degeneration using a multimodal imaging approach. Specifically, our data suggest advancing striatal and widespread striatocortical dysfunction via an anterior-posterior gradient originating from a hypometabolic midbrain cluster within a well-characterized and only mild to moderately affected PD cohort during a relatively short period.

In preclinical trials, the recently developed tracer 2-methoxy-18F-DCFPyL (18F-JK-prostate-specific membrane antigen [PSMA]-7) has shown favorable properties regarding clinical performance and radiochemical accessibility. The aim of this study was to evaluate the clinical utility of 18F-JK-PSMA-7 for PET/CT imaging of patients with prostate cancer. Methods: In an Institutional Review Board–approved pilot study, the initial clinical utility of PET/CT imaging with 18F-JK-PSMA-7 was directly compared with 68Ga-PSMA-11 PET/CT in a group of 10 patients with prostate cancer. The 2 PSMA tracers were administered to each patient less than 3 wk apart. Next, we analyzed the data of 75 consecutive patients who had undergone clinical 18F-JK-PSMA-7 PET/CT imaging for tumor localization of biochemical recurrence (BCR). Results: The pilot study in 10 patients who were examined with both PSMA tracers demonstrated that 18F-JK-PSMA-7 was at least equivalent to 68Ga-PSMA-11. All unequivocally 68Ga-PSMA-11–positive lesions could be also detected using 18F-JK-PSMA-7, and in 4 patients additional suspected PSMA-positive lesions were identified (1 patient changed from PSMA-negative to PSMA-positive). In patients with BCR (after prostatectomy or radiotherapy), the capacity of 18F-JK-PSMA-7 PET/CT to detect at least one PSMA-positive lesion was 84.8%. The prostate-specific antigen (PSA)–stratified detection rate of 18F-JK-PSMA-7 after prostatectomy varied among 54.5% (6/11 patients; PSA < 0.5 μg/L), 87.5% (14/16 patients; PSA 0.5–2 μg/L), and 90.9% (20/22 patients; PSA > 2 μg/L). Conclusion: The tracer 18F-JK-PSMA-7 was found to be safe and clinically useful. We demonstrated that 18F-JK-PSMA-7 was not inferior when directly compared with 68Ga-PSMA-11 in a pilot study but indeed identified additional PSMA-avid suspected lesions in oligometastasized patients with BCR. In a subsequent analysis of a clinical cohort of BCR patients, 18F-JK-PSMA-7 was useful in tumor localization. 18F-JK-PSMA-7 is recommended for future prospective trials.

Impulsive-compulsive behaviours like pathological gambling or hypersexuality are a frequent side effect of dopamine replacement therapy in patients with Parkinson's disease. Multiple imaging studies suggest a significant reduction of presynaptic dopamine transporters in the nucleus accumbens to be a predisposing factor, reflecting either a reduction of mesolimbic projections or, alternatively, a lower presynaptic dopamine transporter expression per se. Here, we aimed to test the hypothesis of fewer mesolimbic projections as a risk factor by using dopamine synthesis capacity as a proxy of dopaminergic terminal density. Furthermore, previous studies have demonstrated a reduction of fronto-striatal connectivity to be associated with increased risk of impulsive-compulsive behaviour in Parkinson's disease. Therefore, another aim of this study was to investigate the relationship between severity of impulsive-compulsive behaviour, dopamine synthesis capacity and fronto-striatal connectivity. Eighty participants underwent resting state functional MRI and anatomical T1-weighted images [mean age: 68 ± 9.9 years, 67% male (patients)]. In 59 participants, 18F-DOPA-PET was obtained and voxel-wise Patlak slopes indicating dopamine synthesis capacity were calculated. All participants completed the QUIP-RS questionnaire, a well validated test to quantify severity of impulsive-compulsive behaviour in Parkinson's disease. A voxel-wise correlation analysis between dopamine synthesis capacity and QUIP-RS score was calculated for striatal regions. To investigate the relationship between symptom severity and functional connectivity, voxel-wise correlations were performed. A negative correlation was found between dopamine synthesis capacity and QUIP-RS score in the nucleus accumbens (r = -0.57, P = 0.001), a region functionally connected to the rostral anterior cingulate cortex. The connectivity strength was modulated by QUIP-RS, i.e. patients with more severe impulsive-compulsive behaviours had a weaker functional connectivity between rostral anterior cingulate cortex and the nucleus accumbens. In addition, cortical thickness and severity of impulsive-compulsive behaviour were positively correlated in the subgenual rostral anterior cingulate cortex. We found three factors to be associated with severity of impulsive-compulsive behaviour: (i) decreased dopamine synthesis capacity in the nucleus accumbens; (ii) decreased functional connectivity of the rostral anterior cingulate cortex with the nucleus accumbens; and (iii) increased cortical thickness of the subgenual rostral anterior cingulate cortex. Rather than a downregulation of dopamine transporters, a reduction of mesolimbic dopaminergic projections in conjunction with a dysfunctional rostral anterior cingulate cortex-a region known to play a key role in impulse control-could be the most crucial neurobiological risk factor for the development of impulsive-compulsive behaviours in patients with Parkinson's disease under dopamine replacement therapy.

Purpose Radioiodine has been used for the treatment of benign thyroid diseases for over 70 years. However, internationally, there is no common standard for pretherapeutic dosimetry to optimally define the individual therapy activity. Here, we analyze how absorbed tissue doses are influenced by different approaches to pretherapeutic activity calculation of varying complexity. Methods Pretherapeutic determination of treatment activity was retrospectively recalculated in 666 patients who had undergone radioiodine therapy for benign thyroid diseases (Graves’ disease, non-toxic goiter, and uni- and multinodular goiter). Approaches considering none, some, or all of a set of individual factors, including target volume, maximum radioiodine uptake, and effective half-life, were applied. Assuming individually stable radioiodine kinetics, which had been monitored twice a day under therapy, hypothetically achieved tissue doses based on hypothetically administered activities resulting from the different methods of activity calculation were compared to intended target doses. Results The Marinelli formula yields the smallest deviations of hypothetically achieved doses from intended target doses. Approaches taking individual target volume into consideration perform better than fixed therapy activities, which lead to high variances in achieved doses and high deviations of hypothetically achieved doses from intended target doses. Conclusion Elaborate pretherapeutic dose planning, taking individual radioiodine uptake, half-life, and target volume into consideration, should be used whenever possible. The use of disease-specific fixed activities cannot be recommended. Deviations of achieved tissue doses from target doses can already be significantly lowered by application of volume-adapted treatment activities if more elaborate means are not available.

To date, 3 18F-labeled PET tracers have been approved for assessing cerebral amyloid plaque pathology in the diagnostic workup of suspected Alzheimer disease (AD). Although scanning protocols are relatively similar across tracers, U.S. Food and Drug Administration- and the European Medicines Agency-approved visual rating protocols differ among the 3 tracers. This proof-of-concept study assessed the comparability of the 3 approved visual rating protocols to classify a scan as amyloid-positive or -negative, when applied by groups of experts and nonexperts to all 3 amyloid tracers. Methods: In an international multicenter approach, both expert (n = 4) and nonexpert raters (n = 3) rated scans acquired with 18F-florbetaben, 18F-florbetapir and 18F-flutemetamol. Scans obtained with each tracer were presented for reading according to all 3 approved visual rating protocols. In a randomized order, every single scan was rated by each reader according to all 3 protocols. Raters were blinded for the amyloid tracer used and asked to rate each scan as positive or negative, giving a confidence judgment after each response. Percentage of visual reader agreement, interrater reliability, and agreement of each visual read with binary quantitative measures (fixed SUV ratio threshold for positive or negative scans) were computed. These metrics were analyzed separately for expert and nonexpert groups. Results: No significant differences in using the different approved visual rating protocols were observed across the different metrics of agreement in the group of experts. Nominal differences suggested that the 18F-florbetaben visual rating protocol achieved the highest interrater reliability and accuracy especially under low confidence conditions. For the group of nonexpert raters, significant differences between the different visual rating protocols were observed with overall moderate-to-fair accuracy and with the highest reliability for the 18F-florbetapir visual rating protocol. Conclusion: We observed high interrater agreement despite applying different visual rating protocols for all 18F-labeled amyloid tracers. This implies that the results of the visual interpretation of amyloid imaging can be well standardized and do not depend on the rating protocol in experts. Consequently, the creation of a universal visual assessment protocol for all amyloid imaging tracers appears feasible, which could benefit especially the less-experienced readers. ispartof: JOURNAL OF NUCLEAR MEDICINE vol:62 issue:7 pages:999-1005 ispartof: location:United States status: published

The novel tau-PET tracer [18F]PI-2620 detects the 3/4-repeat-(R)-tauopathy Alzheimer’s disease (AD) and the 4R-tauopathies corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP). We determined whether [18F]PI-2620 binding characteristics deriving from non-invasive reference tissue modelling differentiate 3/4R- and 4R-tauopathies. Ten patients with a 3/4R tauopathy (AD continuum) and 29 patients with a 4R tauopathy (CBS, PSP) were evaluated. [18F]PI-2620 PET scans were acquired 0-60 min p.i. and the distribution volume ratio (DVR) was calculated. [18F]PI-2620-positive clusters (DVR ≥ 2.5 SD vs. 11 healthy controls) were evaluated by non-invasive kinetic modelling. R1 (delivery), k2 & k2a (efflux), DVR, 30-60 min standardized-uptake-value-ratios (SUVR30-60) and the linear slope of post-perfusion phase SUVR (9-60 min p.i.) were compared between 3/4R- and 4R-tauopathies. Cortical clusters of 4R-tau cases indicated higher delivery (R1SRTM: 0.92 ± 0.21 vs. 0.83 ± 0.10, p = 0.0007), higher efflux (k2SRTM: 0.17/min ±0.21/min vs. 0.06/min ± 0.07/min, p 30-60 (1.3 ± 0.2 vs. 1.8 ± 0.3, p 9-60: 0.006/min ± 0.007/min vs. 0.016/min ± 0.008/min, p 18F]PI-2620 binding characteristics in cortical regions differentiate 3/4R- and 4R-tauopathies. Higher tracer clearance indicates less stable binding in 4R tauopathies when compared to 3/4R-tauopathies.

Purpose Dynamic 60-min positron emission tomography (PET) imaging with the novel tau radiotracer [18F]PI-2620 facilitated accurate discrimination between patients with progressive supranuclear palsy (PSP) and healthy controls (HCs). This study investigated if truncated acquisition and static time windows can be used for [18F]PI-2620 tau-PET imaging of PSP. Methods Thirty-seven patients with PSP Richardson syndrome (PSP-RS) were evaluated together with ten HCs. [18F]PI-2620 PET was performed by a dynamic 60-min scan. Distribution volume ratios (DVRs) were calculated using full and truncated scan durations (0–60, 0–50, 0–40, 0–30, and 0–20 min p.i.). Standardized uptake value ratios (SUVrs) were obtained 20–40, 30–50, and 40–60 min p.i.. All DVR and SUVr data were compared with regard to their potential to discriminate patients with PSP-RS from HCs in predefined subcortical and cortical target regions (effect size, area under the curve (AUC), multi-region classifier). Results 0–50 and 0–40 DVR showed equivalent effect sizes as 0–60 DVR (averaged Cohen’s d: 1.22 and 1.16 vs. 1.26), whereas the performance dropped for 0–30 or 0–20 DVR. The 20–40 SUVr indicated the best performance of all static acquisition windows (averaged Cohen’s d: 0.99). The globus pallidus internus discriminated patients with PSP-RS and HCs at a similarly high level for 0–60 DVR (AUC: 0.96), 0–40 DVR (AUC: 0.96), and 20–40 SUVr (AUC: 0.94). The multi-region classifier sensitivity of these time windows was consistently 86%. Conclusion Truncated and static imaging windows can be used for [18F]PI-2620 PET imaging of PSP. 0–40 min dynamic scanning offers the best balance between accuracy and economic scanning.

Tau protein aggregations are a hallmark of amyloid-associated Alzheimer disease and some forms of non–amyloid-associated frontotemporal lobar degeneration. In recent years, several tracers for in vivo tau imaging have been under evaluation. This study investigated the ability of 18F-flortaucipir PET not only to assess tau positivity but also to differentiate between amyloid-positive and -negative forms of neurodegeneration on the basis of different 18F-flortaucipir PET signatures. Methods: The 18F-flortaucipir PET data of 35 patients with amyloid-positive neurodegeneration, 19 patients with amyloid-negative neurodegeneration, and 17 healthy controls were included in a data-driven scaled subprofile model (SSM)/principal-component analysis (PCA) identifying spatial covariance patterns. SSM/PCA pattern expression strengths were tested for their ability to predict amyloid status in a receiver-operating-characteristic analysis and validated with a leave-one-out approach. Results: Pattern expression strengths predicted amyloid status with a sensitivity of 0.94 and a specificity of 0.83. A support vector machine classification based on pattern expression strengths in 2 different SSM/PCA components yielded a prediction accuracy of 98%. Anatomically, prediction performance was driven by parietooccipital gray matter in amyloid-positive patients versus predominant white matter binding in amyloid-negative patients. Conclusion: SSM/PCA-derived binding patterns of 18F-flortaucipir differentiate between amyloid-positive and -negative neurodegenerative diseases with high accuracy. 18F-flortaucipir PET alone may convey additional information equivalent to that from amyloid PET. Together with a perfusion-weighted early-phase acquisition (18F-FDG PET–equivalent), a single scan potentially contains comprehensive information on amyloid (A), tau (T), and neurodegeneration (N) status as required by recent biomarker classification algorithms (A/T/N).

Graphical abstract, Highlights • Freezers exhibited a dopaminergic deficit in the left caudate. • The dopamine depleted caudate shows altered striatocortical functional connectivity. • Ventral tegmental area displays increased coupling with regions of the DMN. • Molecular connectivity revealed a specific impairment in mesocorticolimbic pathways., Freezing of gait is a common phenomenon of advanced Parkinson’s disease. Besides locomotor function per se, a role of cognitive deficits has been suggested. Limited evidence of associated dopaminergic deficits points to caudatal denervation. Further, altered functional connectivity within resting-state networks with importance for cognitive functions has been described in freezers. A potential pathophysiological link between both imaging findings has not yet been addressed. The current study sought to investigate the association between dopaminergic pathway dysintegrity and functional dysconnectivity in relation to FOG severity and cognitive performance in a well-characterized PD cohort undergoing high-resolution 6-[18F]fluoro-L-Dopa PET and functional MRI. The freezing of gait questionnaire was applied to categorize patients (n = 59) into freezers and non-freezers. A voxel-wise group comparison of 6-[18F]fluoro-L-Dopa PET scans with focus on striatum was performed between both well-matched and neuropsychologically characterized patient groups. Seed-to-voxel resting-state functional connectivity maps of the resulting dopamine depleted structures and dopaminergic midbrain regions were created and compared between both groups. For a direct between-group comparison of dopaminergic pathway integrity, a molecular connectivity approach was conducted on 6-[18F]fluoro-L-Dopa scans. With respect to striatal regions, freezers showed significant dopaminergic deficits in the left caudate nucleus, which exhibited altered functional connectivity with regions of the visual network. Regarding midbrain structures, the bilateral ventral tegmental area showed altered functional coupling to regions of the default mode network. An explorative examination of the integrity of dopaminergic pathways by molecular connectivity analysis revealed freezing-associated impairments in mesolimbic and mesocortical pathways. This study represents the first characterization of a link between dopaminergic pathway dysintegrity and altered functional connectivity in Parkinson’s disease with freezing of gait and hints at a specific involvement of striatocortical and mesocorticolimbic pathways in freezers.

To date, 3

54 Background: Progressive supranuclear palsy (PSP) is a 4-repeat (4R) tauopathy and region-specific tau deposits establish the neuropathological diagnosis of “definite PSP” post mortem. Future interventional trials against tau in PSP would strongly benefit from biomarkers to validate the specific presence of the target and to monitor the target’s magnitude during therapy. First generation tau positron-emission-tomography (PET) ligands such as 18F-THK5351 or 18F-AV1451 were somewhat able to distinguish PSP patients from healthy controls (HC) or from patients with other neurodegenerative diseases, but relevant fractions of the PET signal in PSP may have been related to concomitant monoamine-oxidase (MAO) increases. The novel second generation tau-PET ligand 18F-PI2620 proved absent off-target binding to MAO and high affinity to 3/4R tau in Alzheimer’s disease (AD). The aim of this multicenter-evaluation was to investigate 18F-PI2620 in patients with suspected 4R tau pathology in clinically diagnosed PSP. Methods: Seventeen patients (70±7 y, n=8 female) with probable or possible PSP Richardson syndrome according to MDS-PSP criteria underwent 18F-PI2620 PET at four different centers together with ten HC and seven disease controls (Multi-system atrophy, Parkinson’s disease, and AD). PET scans were acquired 0-60 min p.i. followed by coregistration to a 18F-PI2620 template in the MNI space. Standardized uptake value ratios (SUVr) of predefined brain regions in the basal ganglia were generated using cerebellar scaling of a 30-60 min p.i. frame after inspection of the full dynamic range. SUVr data were compared between PSP, HC, and disease controls by an ANOVA including Bonferroni post hoc correction. Statistical parametric mapping (SPM, V12) was performed between PSP and HC (t-test). SUVr and SPM data were corrected for different centers. Additionally, disease severity measured by the PSP rating scale (PSPRS) was correlated with PET findings. An in vitro pilot autoradiography using 18F-PI2620 incubation of brain slices was performed for the globus pallidus of a single PSP patient and compared to the cortical binding in a specimen from an AD patient. Results: Our study indicates significantly elevated mean 18F-PI2620 SUVr in PSP patients (PSPRS: 40±17; range 13-71) in the globus pallidus (1.34±0.16; p = 0.001; d = 1.68) and the substantia nigra (1.33±0.14; p = 0.003; d = 1.49) when compared to HC (1.12±0.09 / 1.15±0.08). Disease controls showed a similar signal in the globus pallidus (1.11±0.06; p = n.s.) and a slight elevation in the substantia nigra (1.23±0.09; p = n.s.) when compared to HC. A voxel-wise analysis SPM revealed elevated 18F-PI2620 uptake in the globus pallidus, the substantia nigra as well as in the frontal and parietal cortex (all p 0.2). Subjects with low disease severity (PSPRS ≤ 30; n=4) already had a significantly elevated 18F-PI2620 uptake in the globus pallidus when compared to HC (1.38±0.13 vs. 1.12±0.09; p = 0.001; d = 2.32). Preliminary in vitro autoradiography showed distinguishable 18F-PI2620 binding in the globus pallidus of a PSP patient which was however far lower when compared to cortical binding in AD. Conclusions: The results of this preliminary multi-center evaluation indicate a value of 18F-PI2620 to diagnose and differentiate suspected PSP patients in vivo. The magnitude of tracer binding between patients seems to be variably expressed but not correlated with disease severity. These results indicate that 18F-PI2620 may show potential as a biomarker to assess tau pathology in PSP patients and that it may be helpful to establish earlier and more reliable diagnosis of PSP.

Tau protein aggregations are a hallmark of amyloid-associated Alzheimer disease and some forms of non-amyloid-associated frontotemporal lobar degeneration. In recent years, several tracers for in vivo tau imaging have been under evaluation. This study investigated the ability of

Purpose To evaluate the correlation between left atrial diverticula (LAD) and left-sided septal pouches (LSSP) with ischemic brain alterations in MRI. Methods A retrospective analysis of 174 patients who received both, a dedicated cardiac CT angiography (CCTA) and a brain MRI examination was performed. Two radiologists independently reviewed all examinations for the presence of LAD and LSSP as well as ischemic alterations of the brain. Subsequently, the correlation between these cardiac and cerebral findings as well as to other potentially related risk factors was assessed. Results 71 LAD (total prevalence 41%) and 65 LSSP (total prevalence 37%) were identified in 174 patients. Combined prevalence was 10%. Ischemic brain alterations were found in patients with a LAD in 42.3% (30/71) and with a LSSP in 64.6% (42/65). Patients without any anatomical variant in the left atrium showed ischemic brain alterations in 39.4% (26/66). The presence of a LSSP was associated with an increased risk for ischemic brain alterations in multivariate logistic regression analysis after adjusting for other risk factors (OR = 3.57, 95% CI = 0.51–2.09, p Conclusion In our study cohort LAD and LSSP are highly prevalent anatomical structures within the left atrium. Patients with LSSP showed an approximated 3.5-fold higher probability for ischemic brain alterations. Therefore, LSSP should be considered as a potential risk factor for cardioembolic strokes and its presence should be stated in cardiac CT reports.

18F-prostate-specific membrane antigen (PSMA)-1007 is excreted mainly through the liver. We benchmarked the performance of 18F-PSMA-1007 against 3 renally excreted PSMA tracers. Methods: Among 668 patients, we selected 27 in whom PET/CT results obtained with 68Ga-PSMA-11, 18F-DCFPyL (2-(3-(1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid), or 18F-JK-PSMA-7 (JK, Juelich-Koeln) were interpreted as equivocal or negative or as oligometastatic disease (PET-1). Within 3 wk, a second PET scan with 18F-PSMA-1007 was performed (PET-2). The confidence in the interpretation of PSMA-positive locoregional findings was scored on a 5-point scale, first in routine diagnostics (reader 1) and then by an independent second evaluation (reader 2). Discordant PSMA-positive skeletal findings were examined by contrast-enhanced MRI. Results: For both readers, 18F-PSMA-1007 facilitated the interpretability of 27 locoregional lesions. In PET-2, the clinical readout led to a significantly lower number of equivocal locoregional lesions (P = 0.024), and reader 2 reported a significantly higher rate of suspected lesions that were falsely interpreted as probably benign in PET-1 (P = 0.023). Exclusively in PET-2, we observed a total of 15 PSMA-positive spots in the bone marrow of 6 patients (22%). None of the 15 discordant spots had a morphologic correlate on the corresponding CT scan or on the subsequent MRI scan. Thus, 18F-PSMA-1007 exhibits a significantly higher rate of unspecific medullary spots (P = 0.0006). Conclusion: 18F-PSMA-1007 may increase confidence in interpreting small locoregional lesions adjacent to the urinary tract but may decrease the interpretability of skeletal lesions.

This cross-sectional study investigates the potential of novel tau radiotracer 18F-PI-2620 as a biomarker in patients with clinically diagnosed progressive supranuclear palsy., Key Points Question Can tau–positron emission tomography imaging with the novel tau radiotracer 18F-PI-2620 differentiate patients with progressive supranuclear palsy (PSP) from healthy controls and controls with disease? Findings In this cross-sectional study of 60 patients with PSP, 10 healthy controls, and 20 controls with disease, there was significantly higher 18F-PI-2620 binding in target regions of patients with PSP compared with controls regardless of disease severity. Individual patients with PSP with Richardson syndrome were separated with high sensitivity and specificity. Meaning 18F-PI-2620 tau–positron emission tomography differentiates patients with PSP from controls at the single-patient level, potentially facilitating a more reliable diagnosis., Importance Progressive supranuclear palsy (PSP) is a 4-repeat tauopathy. Region-specific tau aggregates establish the neuropathologic diagnosis of definite PSP post mortem. Future interventional trials against tau in PSP would strongly benefit from biomarkers that support diagnosis. Objective To investigate the potential of the novel tau radiotracer 18F-PI-2620 as a biomarker in patients with clinically diagnosed PSP. Design, Setting, and Participants In this cross-sectional study, participants underwent dynamic 18F-PI-2620 positron emission tomography (PET) from 0 to 60 minutes after injection at 5 different centers (3 in Germany, 1 in the US, and 1 in Australia). Patients with PSP (including those with Richardson syndrome [RS]) according to Movement Disorder Society PSP criteria were examined together with healthy controls and controls with disease. Four additionally referred individuals with PSP-RS and 2 with PSP–non-RS were excluded from final data analysis owing to incomplete dynamic PET scans. Data were collected from December 2016 to October 2019 and were analyzed from December 2018 to December 2019. Main Outcomes and Measures Postmortem autoradiography was performed in independent PSP-RS and healthy control samples. By in vivo PET imaging, 18F-PI-2620 distribution volume ratios were obtained in globus pallidus internus and externus, putamen, subthalamic nucleus, substantia nigra, dorsal midbrain, dentate nucleus, dorsolateral, and medial prefrontal cortex. PET data were compared between patients with PSP and control groups and were corrected for center, age, and sex. Results Of 60 patients with PSP, 40 (66.7%) had RS (22 men [55.0%]; mean [SD] age, 71 [6] years; mean [SD] PSP rating scale score, 38 [15]; score range, 13-71) and 20 (33.3%) had PSP–non-RS (11 men [55.0%]; mean [SD] age, 71 [9] years; mean [SD] PSP rating scale score, 24 [11]; score range, 11-41). Ten healthy controls (2 men; mean [SD] age, 67 [7] years) and 20 controls with disease (of 10 [50.0%] with Parkinson disease and multiple system atrophy, 7 were men; mean [SD] age, 61 [8] years; of 10 [50.0%] with Alzheimer disease, 5 were men; mean [SD] age, 69 [10] years). Postmortem autoradiography showed blockable 18F-PI-2620 binding in patients with PSP and no binding in healthy controls. The in vivo findings from the first large-scale observational study in PSP with 18F-PI-2620 indicated significant elevation of tracer binding in PSP target regions with strongest differences in PSP vs control groups in the globus pallidus internus (mean [SD] distribution volume ratios: PSP-RS, 1.21 [0.10]; PSP–non-RS, 1.12 [0.11]; healthy controls, 1.00 [0.08]; Parkinson disease/multiple system atrophy, 1.03 [0.05]; Alzheimer disease, 1.08 [0.06]). Sensitivity and specificity for detection of PSP-RS vs any control group were 85% and 77%, respectively, when using classification by at least 1 positive target region. Conclusions and Relevance This multicenter evaluation indicates a value of 18F-PI-2620 to differentiate suspected patients with PSP, potentially facilitating more reliable diagnosis of PSP.

Purpose Second-generation tau radiotracers for use with positron emission tomography (PET) have been developed for visualization of tau deposits in vivo. For several β-amyloid and first-generation tau-PET radiotracers, it has been shown that early-phase images can be used as a surrogate of neuronal injury. Therefore, we investigated the performance of early acquisitions of the novel tau-PET radiotracer [18F]PI-2620 as a potential substitute for [18F]fluorodeoxyglucose ([18F]FDG). Methods Twenty-six subjects were referred with suspected tauopathies or overlapping parkinsonian syndromes (Alzheimer’s disease, progressive supranuclear palsy, corticobasal syndrome, multi-system atrophy, Parkinson’s disease, multi-system atrophy, Parkinson's disease, frontotemporal dementia) and received a dynamic [18F]PI-2620 tau-PET (0–60 min p.i.) and static [18F]FDG-PET (30–50 min p.i.). Regional standardized uptake value ratios of early-phase images (single frame SUVr) and the blood flow estimate (R1) of [18F]PI-2620-PET were correlated with corresponding quantification of [18F]FDG-PET (global mean/cerebellar normalization). Reduced tracer uptake in cortical target regions was also interpreted visually using 3-dimensional stereotactic surface projections by three more and three less experienced readers. Spearman rank correlation coefficients were calculated between early-phase [18F]PI-2620 tau-PET and [18F]FDG-PET images for all cortical regions and frequencies of disagreement between images were compared for both more and less experienced readers. Results Highest agreement with [18F]FDG-PET quantification was reached for [18F]PI-2620-PET acquisition from 0.5 to 2.5 min p.i. for global mean (lowest R = 0.69) and cerebellar scaling (lowest R = 0.63). Correlation coefficients (summed 0.5–2.5 min SUVr & R1) displayed strong agreement in all cortical target regions for global mean (RSUVr 0.76, RR1 = 0.77) and cerebellar normalization (RSUVr 0.68, RR1 = 0.68). Visual interpretation revealed high regional correlations between early-phase tau-PET and [18F]FDG-PET. There were no relevant differences between more and less experienced readers. Conclusion Early-phase imaging of [18F]PI-2620 can serve as a surrogate biomarker for neuronal injury. Dynamic imaging or a dual time-point protocol for tau-PET imaging could supersede additional [18F]FDG-PET imaging by indexing both the distribution of tau and the extent of neuronal injury.

Our aim was to evaluate the benefit of early (1 h post-injection (p.i.)) and late (3 h p.i.) [68Ga]PSMA-HBED-CC positron emission tomography (PET)/x-ray computed tomography (CT) imaging for detection of biochemical recurrence (BCR) of prostate cancer (PCa). Seventy patients with BCR of the PCa and prostate-specific antigen (PSA) levels of less than 2.0 μg/l were subjected to [68Ga]PSMA-HBED-CC PET (mean injected activity 180 MBq). While early imaging contained whole body scans, late imaging was confined to the pelvis and the lower abdomen. Uptake in suspicious lesions was analyzed by peak and maximum standardized uptake values (SUVpeak/max). Tumor-to-background ratios were calculated for all lesions in which the liver served as reference organ. The Wilcoxon matched-pair signed-rank test was used to compare the uptake in suspicious lesions between early and late imaging. Follow-up data were used to validate the existence of the additionally detected lesions. Forty-four of the 70 patients thus examined were interpreted as PSMA-positive in early and/or late scans while 26 remained without suspicion of PSMA tracer uptake. A total of 70 suspicious lesions were analyzed. Ten tumor-suspicious lesions from seven different patients were better or exclusively visible in the late measurements while three tumor-suspicious lesions from three different patients were better or exclusively visible in the early images. A validation by follow-up data was possible for 11 of these 13 additionally detected lesions. In direct comparison between early and late imaging, the mean SUVmax in PSMA-positive lesions was 74 % higher (p

Current disease models suggest that many neurodegenerative disorders are associated with pathological protein aggregations that start to develop in the brain long before the onset of clinical symptoms. Therefore, biomarkers allowing early and reliable characterization of neurodegenerative disease are required. Here we illustrate the potential value of neuroimaging procedures by means of selected examples. Multimodal imaging data of exemplary patients who underwent FDG, Amyloid and AV-1451-PET, FP-CIT-SPECT and MRI imaging in the routine clinical workup in our department is presented and the currently available literature on the topic of imaging in neurodegenerative diseases was reviewed. The complementary value of the applied imaging methods is demonstrated in pairs of representative cases. Depending on the clinical question, individual methods or a meaningful multimodal combination is required to achieve optimal diagnostic benefit. Imaging biomarkers have high potential for early diagnosis, differential diagnosis and follow-up of patients with neurodegenerative diseases already and will gain an even higher importance in the future, when specific pathology-targeted therapies will be evaluated in clinical trials.

Background: Cognitive impairment is a very frequent and severe nonmotor symptom of Parkinson’s disease (PD). Early intervention in this at-risk group for cognitive decline may be crucial for long-term preservation of cognitive functions. Computerized working memory training (WMT) has been proven beneficial in non-PD patient populations, but such evidence is still needed for patients with PD. Objective: This study aimed to evaluate the effect of WMT on visuo-spatial working memory (WM) in cognitively unimpaired patients with PD. Methods: A single-blind randomized controlled trial encompassing 76 patients with PD but no cognitive impairment according to level II diagnostic criteria was conducted. Thirty-seven patients engaged in home-based adaptive WMT 5 times per week for a period of 5 weeks, whereas the remaining patients were in the waiting list arm of the study (control group [CG]). Working memory performance was evaluated using a computerized task before and after intervention and at 14-week follow-up, allowing to quantify the precision of WM on a continuous scale, ie, to test not only if an item was remembered but also how well the location of this item was retained. Results: Coincidently, the WMT group showed slightly worse WM performance compared with the CG at baseline, which was ameliorated after WMT. This training-induced effect remained stable until follow-up. Conclusion: Patients showing relatively low WM performance, despite not formally diagnosable as Parkinson’s disease with mild cognitive impairment (PD-MCI), seem to benefit from home-based WMT. Thus, WMT could potentially be implemented in future trials as a time- and cost-efficient route to counteract subtle cognitive changes in early disease stages. Trial registration: German Clinical Trial Register (drks.de, DRKS00009379)

Recent approaches have suggested that deep brain stimulation (DBS) for obsessive-compulsive disorder relies on distributed networks rather than local brain modulation. However, there is insufficient data on how DBS affects brain metabolism both locally and globally. We enrolled three patients with treatment-refractory obsessive-compulsive disorder with ongoing DBS of the bilateral ventral capsule/ventral striatum. Patients underwent resting-state 18F-fluorodeoxyglucose and positron emission tomography in both stimulation ON and OFF conditions. All subjects showed relative hypometabolism in prefronto-basal ganglia-thalamic networks compared to a healthy control cohort when stimulation was switched OFF. Switching the stimulation ON resulted in differential changes in brain metabolism. Locally, volumes of activated tissue at stimulation sites (n = 6) showed a significant increase in metabolism during DBS ON compared to DBS OFF (Mean difference 4.5 % &plusmn, SD 2.8, p = 0.012). Globally, differential changes were observed across patients encompassing prefrontal increase in metabolism in ON vs. OFF condition. Bearing in mind limitations of the small sample size, we conclude that DBS of the ventral capsule/ventral striatum for obsessive-compulsive disorder increases brain metabolism locally. Across distributed global networks, DBS appears to exert differential effects, possibly depending on localization of stimulation sites and response to the intervention.

Aim We investigated the whole-body distribution and the radiation dosimetry of [18F]-JK-PSMA-7, a novel 18F-labeled PSMA-ligand for PET/CT imaging of prostate cancer. Methods Ten patients with prostate cancer and biochemical recurrence or radiologic evidence of metastatic diseases were examined with 329–384 MBq (mean 359 ± 17 MBq) [18F]-JK-PSMA-7. Eight sequential positron emission tomography (PET) scans were acquired from 20 min to 3 h after injection with IRB approval. The kidneys, liver, lungs, spleen, and salivary glands were segmented into volumes of interest using the QDOSE dosimetry software suite (ABX-CRO, Germany). Absorbed and effective dose were calculated using the ICRP-endorsed IDAC 1.0 package. The absorbed dose of the salivary glands was determined using the spherical model of OLINDA 1.1. PSMA-positive lesions were evaluated separately. Quantitative assessment of the uptake in suspicious lesions was performed by analysis of maximum (max) and peak SUV values. The gluteus maximus muscle (SUVmean) served as a reference region for the calculation of tumor-to-background ratios (TBR’s). Results Physiologic radiotracer accumulation was observed in the salivary and lacrimal glands, liver, spleen, and intestines, in a pattern resembling the distribution known from other PSMA-tracers with excretion via urinary and biliary pathways. The effective dose from [18F]-JK-PSMA-7 for the whole body was calculated to be 1.09E−02 mGy/MBq. The highest radiation dose was observed in the kidneys (1.76E−01 mGy/MBq), followed by liver (7.61E−02 mGy/MBq), salivary glands (4.68E−02 mGy/MBq), spleen (1.89E−02 mGy/MBq), and lungs (1.10E-2 mGy/MBq). No adverse effects of tracer injection were observed. Six out of ten patients were scored as PSMA-positive. A total of 18 suspicious lesions were analyzed, which included six bone lesions, nine lymph nodes, and three local lesions within the prostate fossa. The values for the SUVmax and SUVpeak in the PSMA-positive lesions increased until 60 min p.i. and remained at this intensity in the PET/CT scans until 140 min. In the period between 170 and 200 min after injection, a further significant increase in SUVmax and SUVpeak within the PSMA-positive lesions was observed. Conclusions The highest TBR of [18F]-JK-PSMA-7 was found 3 h after injection. From the kinetically collected data, it can be concluded that this trend may also continue in the further course. The start of the PET/CT acquisition should be chosen as late as possible. The high uptake in suspicious lesions in terms of absolute SUVmax and relative TBR values indicates potentially high sensitivity of the tracer for detection of prostate cancer manifestations.

In a multimodal PET imaging approach, we determined the differential contribution of neurofibrillary tangles (measured with [18F]AV‐1451) and beta‐amyloid burden (measured with [11C]PiB) on degree of neurodegeneration (i.e., glucose metabolism measured with [18F]FDG‐PET) in patients with Alzheimer's disease. Across brain regions, we observed an interactive effect of beta‐amyloid burden and tau deposition on glucose metabolism which was most pronounced in the parietal lobe. Elevated beta‐amyloid burden was associated with a stronger influence of tau accumulation on glucose metabolism. Our data provide the first in vivo insights into the differential contribution of Aβ and tau to neurodegeneration in Alzheimer's disease.

Differential diagnosis of atypical Parkinson syndromes (APS) is difficult as clinical presentations may vary and as there is a strong overlap between disease entities. Aggregations of misfolded and hyperphosphorylated tau proteins are the common denominator of many of these diseases. Several tau targeting positron emission tomography (PET) tracers have been evaluated as possible biomarkers in APS in the recent years. For Parkinson’s disease, dementia with Lewy bodies, progressive supranuclear palsy, and corticobasal degeneration, promising results have been reported with regard to the ability to detect the presence of disease and to discriminate patients from controls. However, the discussion about the specificity of the first-generation radiotracers and their value in the clinical context is ongoing. A combined interpretation of signal strength and distribution pattern in PET scans with first- and second-generation tracers may be helpful in clinical diagnosis and follow-up of patients with APS.

See Whitwell (doi:10.1093/brain/awy001) for a scientific commentary on this article.A stereotypical anatomical propagation of tau pathology has been described in Alzheimer's disease. According to recent concepts (network degeneration hypothesis), this propagation is thought to be indicative of misfolded tau proteins possibly spreading along functional networks. If true, tau pathology accumulation should correlate in functionally connected brain regions. Therefore, we examined whether independent components could be identified in the distribution pattern of in vivo tau pathology and whether these components correspond with specific functional connectivity networks. Twenty-two 18F-AV-1451 PET scans of patients with amnestic Alzheimer's disease (mean age = 66.00 ± 7.22 years, 14 males/eight females) were spatially normalized, intensity standardized to the cerebellum, and z-transformed using the mean and deviation image of a healthy control sample to assess Alzheimer's disease-related tau pathology. First, to detect distinct tau pathology networks, the deviation maps were subjected to an independent component analysis. Second, to investigate if regions of high tau burden are associated with functional connectivity networks, we extracted the region with the maximum z-value in each of the generated tau pathology networks and used them as seeds in a subsequent resting-state functional MRI analysis, conducted in a group of healthy adults (n = 26) who were part of the 1000 Functional Connectomes Project. Third, to examine if tau pathology co-localizes with functional connectivity networks, we quantified the spatial overlap between the seed-based networks and the corresponding tau pathology network by calculating the Dice similarity coefficient. Additionally, we assessed if the tau-dependent seed-based networks correspond with known functional resting-state networks. Finally, we examined the relevance of the identified components in regard to the neuropathological Braak stages. We identified 10 independently coherent tau pathology networks with the majority showing a symmetrical bi-hemispheric expansion and coinciding with highly functionally connected brain regions such as the precuneus and cingulate cortex. A fair-to-moderate overlap was observed between the tau pathology networks and corresponding seed-based networks (Dice range: 0.13-0.57), which in turn resembled known resting-state networks, particularly the default mode network (Dice range: 0.42-0.56). Moreover, greater tau burden in the tau pathology networks was associated with more advanced Braak stages. Using the data-driven approach of an independent component analysis, we observed a set of independently coherent tau pathology networks in Alzheimer's disease, which were associated with disease progression and coincided with functional networks previously reported to be impaired in Alzheimer's disease. Together, our results provide novel information regarding the impact of tau pathology networks on the mechanistic pathway of Alzheimer's disease.

Prostate-specific membrane antigen (PSMA) PET/CT has a high diagnostic accuracy for lesion detection in metastatic prostate cancer, including bone metastases. Novel therapeutic approaches require valid biomarkers for standardized disease staging and for evaluation of progression and therapy response. Here, we introduce EBONI (Evaluation of Bone Involvement), a software tool to automatically quantify the bone metastasis load in PSMA PET/CT. Lesion quantity, mean and maximum lesional SUV, z score, and percentage of affected bone volume are determined. EBONI is open source and freely available. Methods: To validate EBONI, the results of automated quantification of 38 PSMA PET/CT scans with different levels of bone involvement were compared with visual expert reading. The influence of SUV threshold and Hounsfield unit thresholds was analyzed. Results: A high correlation between bone lesion quantity as determined visually and automatically was found (SUVmax, r2 = 0.97; SUVmean, r2 = 0.88; lesion count, r2 = 0.97). The Hounsfield unit threshold had no significant influence, whereas an SUV threshold of 2.5 proved optimal for automated lesion quantification. The systematic error of false-positive tissue misclassification was low, occurred mainly around the salivary and lacrimal glands, and could easily be corrected. There were no false-negative ratings. Conclusion: EBONI analysis is robust, quick (

A 76-year-old man with biochemical relapse of prostate cancer underwent Ga-prostate-specific membrane antigen PET/CT. Besides a local lymph node metastasis, a nodular structure inside the left orbit caudal to the optic nerve showed increased uptake. A metastasis in this location is unlikely. The subsequently performed MRI showed the structure being T1 hypointense, T2 indifferent, and strongly gadolinium contrast agent enhancing. Histopathologic examination after surgical removal identified the tumor as hemangiopericytoma, which rarely occurs in the orbit. Regarding the intense uptake observed, prostate-specific membrane antigen-targeting PET tracers could bear potential for staging purposes of this tumor entity.

Cerebral glucose metabolism measured with [18F]-FDG PET is a well established marker of neuronal dysfunction in neurodegeneration. The tau-protein tracer [18F]-AV-1451 PET is currently under evaluation and shows promising results. Here, we assess the feasibility of early perfusion imaging with AV-1451 as a substite for FDG PET in assessing neuronal injury.Twenty patients with suspected neurodegeneration underwent FDG and early phase AV-1451 PET imaging. Ten one-minute timeframes were acquired after application of 200 MBq AV-1451. FDG images were acquired on a different date according to clinical protocol. Early AV-1451 timeframes were coregistered to individual FDG-scans and spatially normalized. Voxel-wise intermodal correlations were calculated on within-subject level for every possible time window. The window with highest pooled correlation was considered optimal. Z-transformed deviation maps (ZMs) were created from both FDG and early AV-1451 images, comparing against FDG images of healthy controls.Regional patterns and extent of perfusion deficits were highly comparable to metabolic deficits. Best results were observed in a time window from 60 to 360 s (r = 0.86). Correlation strength ranged from r = 0.96 (subcortical gray matter) to 0.83 (frontal lobe) in regional analysis. ZMs of early AV-1451 and FDG images were highly similar.Perfusion imaging with AV-1451 is a valid biomarker for assessment of neuronal dysfunction in neurodegenerative diseases. Radiation exposure and complexity of the diagnostic workup could be reduced significantly by routine acquisition of early AV-1451 images, sparing additional FDG PET.

Cerebral glucose metabolism measured with [18F]-FDG PET is a well established marker of neuronal dysfunction in neurodegeneration. The tau-protein tracer [18F]-AV-1451 PET is currently under evaluation and shows promising results. Here, we assess the feasibility of early perfusion imaging with AV-1451 as a substite for FDG PET in assessing neuronal injury. Twenty patients with suspected neurodegeneration underwent FDG and early phase AV-1451 PET imaging. Ten one-minute timeframes were acquired after application of 200 MBq AV-1451. FDG images were acquired on a different date according to clinical protocol. Early AV-1451 timeframes were coregistered to individual FDG-scans and spatially normalized. Voxel-wise intermodal correlations were calculated on within-subject level for every possible time window. The window with highest pooled correlation was considered optimal. Z-transformed deviation maps (ZMs) were created from both FDG and early AV-1451 images, comparing against FDG images of healthy controls. Regional patterns and extent of perfusion deficits were highly comparable to metabolic deficits. Best results were observed in a time window from 60 to 360 s (r = 0.86). Correlation strength ranged from r = 0.96 (subcortical gray matter) to 0.83 (frontal lobe) in regional analysis. ZMs of early AV-1451 and FDG images were highly similar. Perfusion imaging with AV-1451 is a valid biomarker for assessment of neuronal dysfunction in neurodegenerative diseases. Radiation exposure and complexity of the diagnostic workup could be reduced significantly by routine acquisition of early AV-1451 images, sparing additional FDG PET.

Cognitive reserve (CR) is defined as the ability to maintain functionality despite accumulating pathology. Education has been used as a proxy for CR. For example, by using positron emission tomography imaging, higher educated Alzheimer's disease (AD) patients presented increased amyloid β pathology than lower educated patients despite equal symptomatology. Whether similar associations exist for in vivo tau pathology remains elusive. We utilized [18F]AV-1451 positron emission tomography imaging to examine whether high-educated AD patients (n = 12) present more severe tau pathology compared with low-educated patients (n = 12) despite equal clinical severity in regions of interest corresponding to the pathologic disease stages defined by Braak & Braak. We report tau pathology in advanced Braak stages associated with parietal and frontal regions in high-educated AD patients, whereas in low-educated AD patients tau accumulation is still confined to lower Braak stages associated with temporal and cingulate regions. Highly educated AD patients seem to be able to tolerate more tau tangle pathology than lower educated patients with comparable cognitive impairment supporting the cognitive reserve hypothesis.

Introduction [68Ga]PSMA-HBED-CC and [18F]DCFPyL show a high potential for the detection of recurrent prostate cancer. While 18F-based tracers have several advantages in availability and image resolution, their sensitivity in the skeleton might be impaired by released [18F]fluoride due to its high bone affinity. In turn, chemically unbound trivalent 68Ga might also accumulate in osseous tissue, in cases of occupied binding sites of plasma proteins and thereby influence bone signal. Methods A comparison of average bone SUV was performed in 17 bone-negative and 4 bone-positive patients. All patients underwent PET/CT 125 minutes after application of [18F]DCFPyL and 73 minutes after application of [68Ga]PSMA-HBED-CC at another date. Results Native SUVs in unaffected bone tissue and SUVs relative to liver uptake were lower in [18F]DCFPyL (0.49) than in [68Ga]PSMA-HBED-CC scans (0.52). SUVs relative to gluteal muscles did not differ between the two tracers. Average lesional SUVs did not differ between tracers. Conclusion No difference of average bone signal intensity was observed for [18F]DCFPyL-PET/CT in comparison to [68Ga]PSMA-HBED-CC scans indicating that diagnostic assessment of the skeleton is not affected by non-specific accumulation of free [18F]fluoride or 68Ga.

The recommended target dose in radioiodine therapy of solitary hyperfunctioning thyroid nodules is 300-400 Gy and therefore higher than in other radiotherapies. This is due to the fact that an unknown, yet significant portion of the activity is stored in extranodular areas but is neglected in the calculatory dosimetry. We investigate the feasibility of determining the ratio of nodular and extranodular activity concentrations (uptakes) from post-therapeutically acquired planar scintigrams with Monte Carlo simulations in GATE. The geometry of a gamma camera with a high energy collimator was emulated in GATE (Version 5). A geometrical thyroid-neck phantom (GP) and the ICRP reference voxel phantoms “Adult Female” (AF, 16 ml thyroid) and “Adult Male” (AM, 19 ml thyroid) were used as source regions. Nodules of 1 ml and 3 ml volume were placed in the phantoms. For each phantom and each nodule 200 scintigraphic acquisitions were simulated. Uptake ratios of nodule and rest of thyroid ranging from 1 to 20 could be created by summation. Quantitative image analysis was performed by investigating the number of simulated counts in regions of interest (ROIs). ROIs were created by perpendicular projection of the phantom onto the camera plane to avoid a user dependant bias. The ratio of count densities in ROIs over the nodule and over the contralateral lobe, which should be least affected by nodular activity, was taken to be the best available measure for the uptake ratios. However, the predefined uptake ratios are underestimated by these count density ratios: For an uptake ratio of 20 the count ratios range from 4.5 (AF, 1 ml nodule) to 15.3 (AM, 3 ml nodule). Furthermore, the contralateral ROI is more strongly affected by nodular activity than expected: For an uptake ratio of 20 between nodule and rest of thyroid up to 29% of total counts in the ROI over the contralateral lobe are caused by decays in the nodule (AF 3 ml). In the case of the 1 ml nodules this effect is smaller: 9-11% (AF) respectively 7-8% (AM). For each phantom, the dependency of count density ratios upon uptake ratios can be modeled well by both linear and quadratic regression (quadratic: r 2 > 0.99), yielding sets of parameters which in reverse allow the computation of uptake ratios (and thus dose) from count density ratios. A single regression model obtained by fitting the data of all simulations simultaneously did not provide satisfactory results except for GP, while underestimating the true uptake ratios in AF and overestimating them in AM. The scintigraphic count density ratios depend upon the uptake ratios between nodule and rest of thyroid, upon their volumes, and their respective position in a non-trivial way. Further investigations are required to derive a comprehensive rule to calculate the uptake or dose ratios based on post-therapeutic scintigraphy.

Summary Aim: After therapeutical application of radionuclides the patient has to be regarded as a radioactive source. The radiation exposure differs from diagnostic nuclear medicine due to the amount of radioactivity and due to β-radiation. Measurements of photon dose rates were carried out and estimates of β-radiation outside the patient using Monte-Carlo methods. Calculations of maximum β-ranges in tissue were also performed. Detailed knowledge of the radiation exposure close to the patient is of major importance with respect to radiation protection of the staff. Method: Photon dose rates for 32 patients were determined after treatment with [131I]NaI and [131I]meta-iodobenzylguanidin, [32P]Na2HPO4, [90Y]Zevalin and [153Sm]EDTMP. Readings were taken immediately after application at eight distances. Results: For therapies with 131I photon dose rates amount to 2 mSv·h-1·GBq-1 close to the patient. Taking the typical activities of 3.7 GBq for thyroid carcinoma and up to 11 GBq for mIBG therapies into account this leads to a considerable radiation exposure of approximately 7.5 mSv/h and 20 mSv/h, respectively. At a distance of 2 m the dose rates fall to 1/100 compared to the vicinity. For 153Sm the maximum of 100 μSv·h-1·GBq-1 is significantly lower compared to therapies using radioiodine. After application of 32P or 90Y all photon dose rates are lower (>10 μSv·h-1·GBq-1) but in both cases high energy β-particles associated with high maximum ranges exceeding 1 cm in tissue have to be considered. Conclusion: The remarkable difference of the dose rates in the vicinity of the radioactive patient compared to readings at 2 m distance underlines the major importance of the distance for radiation protection. After application of nuclides emitting high energy β-particles their contribution outside the patient should be considered. For typical procedures in the patient's vicinty the radiation exposure of the personnel remains below the annual limit of 20 mSv.