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Background: The voxel size in ECG-gated myocardial SPECT (GSPECT) is a compromise between geometric resolution and count statistics with varying values and is rather inconsistent in different centers. We investigated the influence of typical acquisition matrix sizes for GSPECT on the reproducibility and accuracy of left ventricular function parameters using a dynamic heart phantom. Methods: Ten paired acquisitions, each pair with slightly different phantom positions, were obtained using identical imaging parameters except acquisition matrix: 128 × 128 matrix (3.3 mm voxel) and 64 × 64 matrix (6.6 mm voxel). In the next step, 128 × 128 data sets were compressed to an additional set of 64 × 64 matrix images. Results: Nominal value of left ventricular ejection fraction (LVEF) of the phantom was 67%. Both acquisition matrices led to significant overestimation of the LVEF. Overestimation was more pronounced in 64 × 64 than in 128 × 128 studies (79.8 ± 2.5% vs. 73.6 ± 1.4%, p

Background: In myocardial gated single-photon emission computed tomography (GSPECT), to differentiate true changes of left ventricular ejection fraction (LVEF) from inherent methodical variability is clinically relevant; however, data about repeatability of GSPECT LVEF in the same patients are rather inconsistent in literature. The aim of this study was therefore to determine repeatability coefficient (RC) of GSPECT LVEF at rest and to investigate the effect of the introduction of processing constraints in left ventricular edge detection. Methods: Thirty-five patients referred for one-day myocardial GSPECT stress-rest scan were included. After the routine stress-rest study, patients were completely repositioned on the imaging table for a second rest acquisition using the same acquisition parameters. LVEF was computed using Corridor 4DM software without and with manual alignment of valve plane. Repeatability was assessed using the Bland-Altman method. Results: RC of LVEF from unaligned datasets was 7.6% with upper and lower limits of agreement of 7.4% to −7.8%. After valve plane and ventricular long-axis length alignment, RC improved to 3.6% with upper and lower limits of agreement of 3.4% to −3.8%. Conclusions: RC using unaligned determination of GSPECT LVEF was comparable to that from previous publications. However, RC using valve plane alignment could be improved to below 4% on 95% confidence level.

PSMA PET/CT is the recommended imaging test in cases with prostate-specific antigen (PSA) recurrence after primary therapy of prostate cancer (PCa). However, imaging protocols remain a topic of active research. The aim of the presented study was to examine the impact of additional late scans of the pelvis in [A total of 297 patients (median PSA 0.35 ng/ml, interquartile range (IQR) 0.2-0.8) who underwent early whole-body [One hundred and thirty-four (45.1%) [Additional late scans of the pelvis in [

Purpose The specific binding ratio (SBR) of 123I-FP-CIT (FP-CIT) in the putamen decreases with age by about 5% per decade and most likely is about 10% higher in females. However, the clinical utility of age and sex correction of the SBR is still a matter of debate. This study tested the impact of age and sex correction on the diagnostic performance of the putamen SBR in three independent patient samples. Methods Research sample: 207 healthy controls (HC) and 438 Parkinson’s disease (PD) patients. Clinical sample A: 183 patients with neurodegenerative parkinsonian syndrome (PS) and 183 patients with non-neurodegenerative PS from one site. Clinical sample B: 84 patients with neurodegenerative PS and 38 patients with non-neurodegenerative PS from another site. Correction for age and sex of the putamen SBR was based on linear regression in the HC or non-neurodegenerative PS, separately in each sample. The area under the ROC curve (AUC) was used as performance measure. Results The putamen SBR was higher in females compared to males (PPMI: 14%, p p p = 0.361). Age-related decline of the putamen SBR ranged between 3.3 and 10.4% (p ≤ 0.019). In subjects ≥ 50 years, age and sex explained p = 0.025) and in clinical sample A (0.9448 versus 0.9519, p = 0.057). There was a small, non-significant AUC increase in clinical sample B (0.9828 versus 0.9743, p = 0.232). Conclusion These findings do not support age and sex correction of the putaminal FP-CIT SBR in the diagnostic workup of parkinsonian syndromes. This most likely is explained by the fact that the proportion of between-subjects variance caused by age and sex is considerably below the symptom threshold of about 50% reduction in neurodegenerative PS.

Background: Positron emission tomography (PET) of the brain with 2-[F-18]-fluoro-2-deoxy-D-glucose (FDG) is widely used for the etiological diagnosis of clinically uncertain cognitive impairment (CUCI). Acute full-blown delirium can cause reversible alterations of FDG uptake that mimic neurodegenerative disease. Objective: This study tested whether delirium in remission affects the performance of FDG PET for differentiation between neurodegenerative and non-neurodegenerative etiology of CUCI. Methods: The study included 88 patients (82.0±5.7 y) with newly detected CUCI during hospitalization in a geriatric unit. Twenty-seven (31%) of the patients were diagnosed with delirium during their current hospital stay, which, however, at time of enrollment was in remission so that delirium was not considered the primary cause of the CUCI. Cases were categorized as neurodegenerative or non-neurodegenerative etiology based on visual inspection of FDG PET. The diagnosis at clinical follow-up after ≥12 months served as ground truth to evaluate the diagnostic performance of FDG PET. Results: FDG PET was categorized as neurodegenerative in 51 (58%) of the patients. Follow-up after 16±3 months was obtained in 68 (77%) of the patients. The clinical follow-up diagnosis confirmed the FDG PET-based categorization in 60 patients (88%, 4 false negative and 4 false positive cases with respect to detection of neurodegeneration). The fraction of correct PET-based categorization did not differ between patients with delirium in remission and patients without delirium (86% versus 89%, p = 0.666). Conclusion: Brain FDG PET is useful for the etiological diagnosis of CUCI in hospitalized geriatric patients, as well as in patients with delirium in remission.

Background The specific binding ratio (SBR) of 123I-FP-CIT in the putamen is widely used to support the interpretation of dopamine transporter (DAT) SPECT. Automatic methods for computation of the putamen SBR often include stereotactical normalization of the individual DAT-SPECT image to an anatomical standard space. This study compared using a single 123I-FP-CIT template image as target for stereotactical normalization versus multiple templates representative of normal and different levels of Parkinson-typical reduction of striatal 123I-FP-CIT uptake. Methods 123I-FP-CIT SPECT images of 1738 patients (66.2 ± 11.6y) were stereotactically normalized (affine) to the anatomical space of the Montreal Neurological Institute (MNI) with SPM12 either using a single custom-made FP-CIT template representative of normal striatal uptake or using eight different templates representative of normal and different levels of Parkinson-typical reduction of striatal FP-CIT uptake with and without attenuation and scatter correction. In the latter case, SPM finds the linear combination of these templates that best matches the patient’s image. The putamen SBR was obtained using hottest voxels analysis in large unilateral regions of interest predefined in MNI space. The histogram of the putamen SBR in the whole sample was fitted by the sum of two Gaussian functions. The power to differentiate between reduced and normal SBR was estimated by the effect size of the distance between the two Gaussian functions computed as the differences between their mean values scaled to their pooled standard deviation. Results The effect size of the distance between the two Gaussian functions was 3.84 with the single template versus 3.96 with multiple templates for stereotactical normalization. Conclusions Multiple templates representative of normal and different levels of Parkinson-typical reduction for stereotactical normalization of DAT-SPECT provide improved separation between normal and reduced putamen SBR, suggesting slightly improved power for the detection of nigrostriatal degeneration.

This case series evaluated the feasibility of prostate-specific membrane antigen (PSMA) radioguided surgery (RGS) with

[Purpose ] The aim of this study was to evaluate brain FDG PET for short- to medium-term prediction of cognitive decline, need for assisted living, and survival in acutely hospitalized geriatric patients with newly detected clinically uncertain cognitive impairment (CUCI)., [Materials and Methods ] The study included 96 patients (62 females, 81.4 ± 5.4 years) hospitalized due to (sub)acute admission indications with newly detected CUCI (German Clinical Trials Register DRKS00005041). FDG PET was categorized as “neurodegenerative” (DEG+) or “nonneurodegenerative” (DEG−) based on visual inspection by 2 independent readers. In addition, each individual PET was tested voxel-wise against healthy controls (P < 0.001 uncorrected). The resulting total hypometabolic volume (THV) served as reader-independent measure of the spatial extent of neuronal dysfunction/degeneration. FDG PET findings at baseline were tested for association with the change in living situation and change in vital status 12 to 24 months after PET. The association with the annual change of the CDR-SB (Clinical Dementia Rating Sum of Boxes) after PET was tested in a subsample of 72 patients., [Results ] The mean time between PET and follow-up did not differ between DEG+ and DEG− patients (1.37 ± 0.27 vs 1.41 ± 0.27 years, P = 0.539). Annual change of CDR-SB was higher in DEG+ compared with DEG− patients (2.78 ± 2.44 vs 0.99 ± 1.81, P = 0.001), and it was positively correlated with THV (age-corrected Spearman ρ = 0.392, P = 0.001). DEG+ patients moved from at home to assisted living significantly earlier than DEG− patients (P = 0.050). Survival was not associated with DEG status or with THV., [Conclusions ] In acutely hospitalized geriatric patients with newly detected CUCI, the brain FDG PET can contribute to the prediction of further cognitive/functional decline and the need for assisted living within 1 to 2 years.

This study used explainable artificial intelligence for data-driven identification of extrastriatal brain regions that can contribute to the interpretation of dopamine transporter SPECT with 123I-FP-CIT in parkinsonian syndromes. A total of 1306 123I-FP-CIT-SPECT were included retrospectively. Binary classification as ‘reduced’ or ‘normal’ striatal 123I-FP-CIT uptake by an experienced reader served as standard-of-truth. A custom-made 3-dimensional convolutional neural network (CNN) was trained for classification of the SPECT images with 1006 randomly selected images in three different settings: “full image”, “striatum only” (3-dimensional region covering the striata cropped from the full image), “without striatum” (full image with striatal region removed). The remaining 300 SPECT images were used to test the CNN classification performance. Layer-wise relevance propagation (LRP) was used for voxelwise quantification of the relevance for the CNN-based classification in this test set. Overall accuracy of CNN-based classification was 97.0%, 95.7%, and 69.3% in the “full image”, “striatum only”, and “without striatum” setting. Prominent contributions in the LRP-based relevance maps beyond the striatal signal were detected in insula, amygdala, ventromedial prefrontal cortex, thalamus, anterior temporal cortex, superior frontal lobe, and pons, suggesting that 123I-FP-CIT uptake in these brain regions provides clinically useful information for the differentiation of neurodegenerative and non-neurodegenerative parkinsonian syndromes.

Aim Few small-scaled studies performed systematic analysis of the benefits of extending prostate specific membrane antigen positron-emission tomography/ computed tomography (68Ga-PSMA I&T PET/CT) to the lower extremities in prostate cancer (PCa) patients. We hypothesized that 68Ga-PSMA I&T PET/CT positive lesions are rare in lower extremities of prostate cancer (PCa) patients, the clinical implication is negligible and may therefore be omitted. Methods We retrospectively analyzed 1,068 PCa patients who received 68Ga-PSMA I&T PET/CT in a single institution (2016–2018). Of those, 285 (26.7%) were newly diagnosed, 529 (49.5%) had biochemical recurrence (BCR) and 254 (23.8%) were castration-resistant prostate cancer (CRPC) patients. Results Of 1,068 68Ga-PSMA I&T PET/CTs, positive lesions in the lower extremities were identified in 6.9% patients (n=74). Positive lesions in the lower extremities were most common in CRPC patients (19.7%; n=50), followed by newly diagnosed (3.2%; n=9) and BCR (2.8%; n=15) PCa patients. Only 3 patients presented with exclusive lesions in the lower extremities, respectively 0.8% (n=2) in CRPC and 0.4% (n=1) in newly diagnosed PCa. Both CRPC (94.1%, n=47) and BCR (80.0%, n=12) patients with PSMA-positive lesions predominantly received systemic therapy. Conclusion Identification of lower extremities lesions with PSMA PET/CT is uncommon and exclusive lesions are rare. PSMA PET/CT findings of the lower extremities did not change therapy management. Thus, scanning of the lower extremities can be omitted in standard protocols.

PURPOSE Ictal brain perfusion SPECT with the tracer 99mTc-HMPAO or 99mTc-ECD is widely used for identification of the epileptic seizure onset zone (SOZ) in presurgical evaluation if standard pointers are uncertain or inconsistent. For both tracers, there are theoretical arguments to favor it over the other for this task. The aim of this study was to compare the performance of ictal brain perfusion SPECT between 99mTc-HMPAO and 99mTc-ECD in a rather large patient sample. PATIENTS AND METHODS The study retrospectively included 196 patients from clinical routine in whom ictal perfusion SPECT had been performed with stabilized 99mTc-HMPAO (n = 110) or 99mTc-ECD (n = 86). Lateralization and localization of the SOZ were obtained by the consensus of 2 independent readers based on visual inspection of the SPECT images. RESULTS The 99mTc-HMPAO group and the 99mTc-ECD group were well matched with respect to age, sex, age at first seizure, duration of disease, seizure frequency, history of previous brain surgery, and findings of presurgical MRI. The proportion of lateralizing ictal SPECT did not differ significantly between 99mTc-HMPAO and 99mTc-ECD (65.5% vs 72.1%, P = 0.36). Sensitivity of ictal perfusion SPECT (independent of the tracer) for correct localization of the SOZ in 62 patients with temporal lobe epilepsy and at least worthwhile improvement (Engel scale ≤ III) 12 months after temporal epilepsy surgery was 63%. CONCLUSIONS This study does not provide evidence to favor 99mTc-HMPAO or 99mTc-ECD for identification of the SOZ by ictal perfusion SPECT.

PURPOSE The present study investigated possible associations between cortical dysfunction/degeneration as measured by F-FDG PET and nigrostriatal degeneration according to the specific I-FP-CIT binding ratio (SBR) in striatal subregions defined by striato-cortical anatomical connectivity in Parkinson disease (PD) patients. MATERIALS AND METHODS The study included 41 patients (61.4 ± 12.8 years) with PD-typical reduction of striatal FP-CIT SBR and no sign of atypical parkinsonian syndrome on FDG PET. FP-CIT SBR was determined separately in the cognitive (composite of executive and limbic) and sensorimotor part of the striatum according to the Oxford-GSK-Imanova Striatal Connectivity Atlas. Scaled FDG uptake was tested voxelwise for correlation with FP-CIT SBR (familywise error corrected P < 0.05). RESULTS A large cluster (17.6 mL) of significant correlation of scaled FDG uptake with FP-CIT SBR in the cognitive part of the striatum, corrected for SBR in the sensorimotor part, was detected in the bilateral medial frontal cortex and the anterior cingulate cortex (partial correlation coefficient R = 0.767); small clusters were detected in ipsilateral caudate and ipsilateral thalamus. There was a small contralateral occipital cluster (3.0 mL) of significant correlation between FDG uptake and sensorimotor SBR corrected for cognitive SBR (R = 0.709). CONCLUSIONS The correlation between nigrostriatal degeneration in the cognitive striatum and reduced cerebral glucose metabolism in the medial parts of the frontal cortex including the anterior cingulate suggests that nigrostriatal degeneration is specifically involved in the pathogenesis of cognitive deficits associated with medial frontal dysfunction such as impaired inhibitory control.

Deep Learning hat in den letzten Jahren in vielen Bereichen spektakuläre Erfolge erzielt, nicht zuletzt in der medizinischen Bildverarbeitung. Nach einer kurzen Einführung in die grundlegenden Ideen von Deep Learning sollen in diesem Übersichtsartikel einige ausgewählte Anwendungen in der SPECT und PET des Gehirns vorgestellt werden.

This study investigated the potential of deep convolutional neural networks (CNN) for automatic classification of FP-CIT SPECT in multi-site or multi-camera settings with variable image characteristics. The study included FP-CIT SPECT of 645 subjects from the Parkinson’s Progression Marker Initiative (PPMI), 207 healthy controls, and 438 Parkinson’s disease patients. SPECT images were smoothed with an isotropic 18-mm Gaussian kernel resulting in 3 different PPMI settings: (i) original (unsmoothed), (ii) smoothed, and (iii) mixed setting comprising all original and all smoothed images. A deep CNN with 2,872,642 parameters was trained, validated, and tested separately for each setting using 10 random splits with 60/20/20% allocation to training/validation/test sample. The putaminal specific binding ratio (SBR) was computed using a standard anatomical ROI predefined in MNI space (AAL atlas) or using the hottest voxels (HV) analysis. Both SBR measures were trained (ROC analysis, Youden criterion) using the same random splits as for the CNN. CNN and SBR trained in the mixed PPMI setting were also tested in an independent sample from clinical routine patient care (149 with non-neurodegenerative and 149 with neurodegenerative parkinsonian syndrome). Both SBR measures performed worse in the mixed PPMI setting compared to the pure PPMI settings (e.g., AAL-SBR accuracy = 0.900 ± 0.029 in the mixed setting versus 0.957 ± 0.017 and 0.952 ± 0.015 in original and smoothed setting, both p

The hypoxia-inducible transcription factor HIF-1 is appreciated as a promising target for cancer therapy. However, conditional deletion of HIF-1 and HIF-1 target genes in cells of the tumor microenvironment can result in accelerated tumor growth, calling for a detailed characterization of the cellular context to fully comprehend HIF-1's role in tumorigenesis. We dissected cell type-specific functions of HIF-1 for intestinal tumorigenesis by lineage-restricted deletion of the Hif1a locus. Intestinal epithelial cell-specific Hif1a loss reduced activation of Wnt/beta-catenin, tumor-specific metabolism and inflammation, significantly inhibiting tumor growth. Deletion of Hif1a in myeloid cells reduced the expression of fibroblast-activating factors in tumor-associated macrophages resulting in decreased abundance of tumor-associated fibroblasts (TAF) and robustly reduced tumor formation. Interestingly, hypoxia was detectable only sparsely and without spatial association with HIF-1 alpha, arguing for an importance of hypoxia-independent, i.e., non-canonical, HIF-1 stabilization for intestinal tumorigenesis that has not been previously appreciated. This adds a further layer of complexity to the regulation of HIF-1 and suggests that hypoxia and HIF-1 alpha stabilization can be uncoupled in cancer. Collectively, our data show that HIF-1 is a pivotal pro-tumorigenic factor for intestinal tumor formation, controlling key oncogenic programs in both the epithelial tumor compartment and the tumor microenvironment.

BACKGROUND: Today, the standardized uptake value (SUV) is essentially the only means for quantitative evaluation of static [18F-]fluorodeoxyglucose (FDG) positron emission tomography (PET) investigations. However, the SUV approach has several well-known shortcomings which adversely affect the reliability of the SUV as a surrogate of the metabolic rate of glucose consumption. The standard uptake ratio (SUR), i.e., the uptake time-corrected ratio of tumor SUV to image-derived arterial blood SUV, has been shown in the first clinical studies to overcome most of these shortcomings, to decrease test-retest variability, and to increase the prognostic value in comparison to SUV. However, it is unclear, to what extent the SUR approach is vulnerable to observer variability of the additionally required blood SUV (BSUV) determination. The goal of the present work was the investigation of the interobserver variability of image-derived BSUV. METHODS: FDG PET/CT scans from 83 patients (72 male, 11 female) with non-small cell lung cancer (N = 46) or head and neck cancer (N = 37) were included. BSUV was determined by 8 individuals, each applying a dedicated delineation tool for the BSUV determination in the aorta. Two of the observers applied two further tools. Altogether, five different delineation tools were used. With each used tool, delineation was performed for the whole patient group, resulting in 12 distinct observations per patient. Intersubject variability of BSUV determination was assessed using the fractional deviations for the individual patients from the patient group average and was quantified as standard deviation (SD is), 95% confidence interval, and range. Interobserver variability of BSUV determination was assessed using the fractional deviations of the individual observers from the observer-average for the considered patient and quantified as standard deviations (SD p, SD d) or root mean square (RMS), 95% confidence interval, and range in each patient, each observer, and the pooled data respectively. RESULTS: Interobserver variability in the pooled data amounts to RMS = 2.8% and is much smaller than the intersubject variability of BSUV (SD is= 16%). Averaged over the whole patient group, deviations of individual observers from the observer average are very small and fall in the range [ - 0.96, 1.05]%. However, interobserver variability partly differs distinctly for different patients, covering a range of [0.7, 7.4]% in the investigated patient group. CONCLUSION: The present investigation demonstrates that the image-based manual determination of BSUV in the aorta is sufficiently reproducible across different observers and delineation tools which is a prerequisite for accurate SUR determination. This finding is in line with the already demonstrated superior prognostic value of SUR in comparison to SUV in the first clinical studies. ispartof: EJNMMI RESEARCH vol:9 issue:1 ispartof: location:Germany status: published

Previous studies on the utility of specific perfusion patterns in ictal brain perfusion SPECT for predicting the outcome of temporal lobe epilepsy surgery used qualitative visual pattern classification, semi-quantitative region-of-interest analysis or conventional univariate voxel-based testing, which are limited by intra- and inter-rater variability and/or low sensitivity to capture functional interactions among brain regions. The present study performed covariance pattern analysis of ictal perfusion SPECT using the Scaled Subprofile Model for unbiased identification of predictive covariance patterns. Methods: The study retrospectively included 18 responders to temporal lobe epilepsy surgery (Engel I-A at 12 months follow-up) and 18 non-responders (≥ Engel I-B). Ictal SPECT images were analyzed with the Scaled Subprofile Model blinded to group membership for unbiased identification of the 16 covariance patterns explaining the highest proportion of variance in the whole data set. Individual expression scores of the covariance patterns were evaluated for predicting seizure freedom after temporal lobe surgery by ROC analysis. Kaplan-Meier analysis including all available follow-up data (up to 60 months after surgery) was also performed. Results: Amongst the 16 covariance patterns only one showed a different expression between responders and non-responders (P = 0.03). This ‘favorable ictal perfusion pattern’ resembled the typical ictal perfusion pattern in temporomesial epilepsy. The expression score of the pattern provided an area of 0.744 (95%-confidence interval 0.577-0.911, P = 0.004) under the ROC curve. Kaplan-Meier analysis revealed a statistical trend towards longer seizure freedom in patients with positive expression score (P = 0.06). The median estimated seizure free time was 48 months in patients with positive expression score versus 6 months in patients with negative expression score. Conclusion: The expression of the ‘favorable ictal perfusion pattern’ identified by covariance analysis of ictal brain perfusion SPECT provides independent (from demographical and clinical variables) information for the prediction of seizure freedom after temporal lobe epilepsy surgery. The expression of this pattern is easily computed for new ictal SPECT images and, therefore, might be used to support the decision for or against temporal lobe surgery in clinical patient care.

Purpose Deep convolutional neural networks (CNN) provide high accuracy for automatic classification of dopamine transporter (DAT) SPECT images. However, CNN are inherently black-box in nature lacking any kind of explanation for their decisions. This limits their acceptance for clinical use. This study tested layer-wise relevance propagation (LRP) to explain CNN-based classification of DAT-SPECT in patients with clinically uncertain parkinsonian syndromes. Methods The study retrospectively included 1296 clinical DAT-SPECT with visual binary interpretation as “normal” or “reduced” by two experienced readers as standard-of-truth. A custom-made CNN was trained with 1008 randomly selected DAT-SPECT. The remaining 288 DAT-SPECT were used to assess classification performance of the CNN and to test LRP for explanation of the CNN-based classification. Results Overall accuracy, sensitivity, and specificity of the CNN were 95.8%, 92.8%, and 98.7%, respectively. LRP provided relevance maps that were easy to interpret in each individual DAT-SPECT. In particular, the putamen in the hemisphere most affected by nigrostriatal degeneration was the most relevant brain region for CNN-based classification in all reduced DAT-SPECT. Some misclassified DAT-SPECT showed an “inconsistent” relevance map more typical for the true class label. Conclusion LRP is useful to provide explanation of CNN-based decisions in individual DAT-SPECT and, therefore, can be recommended to support CNN-based classification of DAT-SPECT in clinical routine. Total computation time of 3 s is compatible with busy clinical workflow. The utility of “inconsistent” relevance maps to identify misclassified cases requires further investigation.

Background: The chemical microspheres 99mTc-HMPAO and 99mTc-ECD are widely used as tracers in ictal brain perfusion SPECT for identification of the seizure onset zone (SOZ) in presurgical evaluation of patients with drug-resistant epilepsy and uncertainty of SOZ localization after standard diagnostic workup. For both tracers there are theoretical arguments to favor it over the other for this task. The aim of this study was to compare the performance of ictal brain perfusion SPECT between 99mTc-HMPAO and 99mTc-ECD in a rather large patient sample.Methods: The study retrospectively included 196 patients from clinical routine in whom ictal perfusion SPECT had been performed with stabilized 99mTc-HMPAO (n = 110) or 99mTc-ECD (n = 86). Lateralization and localization of the SOZ was obtained by the consensus of two independent readers who visually inspected the SPECT images retrospectively. Results: The 99mTc-HMPAO group and the 99mTc-ECD group were well matched with respect to age, sex, age at first seizure, duration of disease, seizure frequency, history of previous brain surgery, and findings of presurgical MRI. The tracer groups differed significantly with respect to the latency of tracer injection (median latency 4 s longer in the 99mTc-HMPAO group), duration of the seizure after tracer injection (25 s shorter in the 99mTc-HMPAO group), tracer dose (70 MBq higher in the 99mTc-HMPAO group), and delay of the SPECT acquisition after tracer injection (63 min longer in the 99mTc-HMPAO group). The fraction of lateralising ictal SPECT did not differ significantly between the 99mTc-HMPAO and the 99mTc-ECD group (65.5% versus 72.1%, p = 0.355). Sensitivity of ictal perfusion SPECT (independent of the tracer) for correct localization of the SOZ in 62 patients with temporal lobe epilepsy and at least worthwhile improvement (Engel scale ≤ III) 12 months after temporal epilepsy surgery was 63%.Conclusions: This study does not provide evidence to favor 99mTc-HMPAO or 99mTc-ECD for identification of the SOZ by ictal perfusion SPECT in patients with drug resistant epilepsy.

Alzheimer’s Disease Neuroimaging Initiative., [Background] Research in rodents identified specific neuron populations encoding information for spatial navigation with particularly high density in the medial part of the entorhinal cortex (ERC), which may be homologous with Brodmann area 34 (BA34) in the human brain., [Objective] The aim of this study was to test whether impaired spatial navigation frequently occurring in mild cognitive impairment (MCI) is specifically associated with neurodegeneration in BA34., [Methods] The study included baseline data of MCI patients enrolled in the Alzheimer’s Disease Neuroimaging Initiative with high-resolution structural MRI, brain FDG PET, and complete visuospatial ability scores of the Everyday Cognition test (VS-ECog) within 30 days of PET. A standard mask of BA34 predefined in MNI space was mapped to individual native space to determine grey matter volume and metabolic activity in BA34 on MRI and on (partial volume corrected) FDG PET, respectively. The association of the VS-ECog sum score with grey matter volume and metabolic activity in BA34, APOE4 carrier status, age, education, and global cognition (ADAS-cog-13 score) was tested by linear regression. BA28, which constitutes the lateral part of the ERC, was used as control region., [Results] The eligibility criteria led to inclusion of 379 MCI subjects. The VS-ECog sum score was negatively correlated with grey matter volume in BA34 (β= –0.229, p = 0.022) and age (β= –0.124, p = 0.036), and was positively correlated with ADAS-cog-13 (β= 0.175, p = 0.003). None of the other predictor variables contributed significantly., [Conclusion] Impairment of spatial navigation in MCI is weakly associated with BA34 atrophy.

PURPOSE Cognitive decline in diseases of the Lewy body spectrum (LBS) is linked to dysfunction/degeneration of the basal forebrain (BF). Assessment of glucose metabolism in the BF by FDG PET is hampered by the small size of the BF and limited spatial resolution of conventional PET. This pilot study tested the feasibility of assessing BF glucose metabolism by high-resolution digital PET (dPET). PATIENTS AND METHODS The retrospective study included 12 LBS patients (61-86 years, 5 demented). Whole-brain stereotactic normalization to anatomical standard space was followed by local stereotactic normalization of a 7 × 7 × 7-cm box around the BF to a custom-made 1 × 1 × 1-mm FDG dPET template. FDG uptake was scaled voxelwise to mean FDG uptake in the pons. Scaled FDG uptake in the BF was compared between demented and nondemented LBS patients and tested for correlation with cortical FDG uptake. RESULTS Scaled FDG uptake in the BF was significantly lower in demented compared with nondemented patients (1.14 ± 0.09 vs 1.25 ± 0.06, P = 0.031). Brain-wide voxel-based testing for correlations with scaled FDG uptake in the BF revealed a large cluster comprising medial and ventrolateral frontal cortex, anterior cingulate cortex, insular cortex, and striatum as well as smaller clusters in motor cortex and occipital cortex (P < 0.001, uncorrected). CONCLUSIONS These results suggest that dementia-associated BF degeneration in LBS can be sensitively measured as reduced BF FDG uptake on dPET. More accurate delineation of the BF based on individual high-resolution MRI might be useful to make optimal use of improved spatial resolution of dPET and to correct for possible disease- and age-dependent partial volume effects.

Pavlovian biases influence instrumental learning by coupling reward seeking with action invigoration and punishment avoidance with action suppression. Using a probabilistic go/no-go task designed to orthogonalize action (go/no-go) and valence (reward/punishment), recent studies have shown that the interaction between the two is dependent on the striatum and its key neuromodulator dopamine. Using this task, we sought to identify how structural and neuromodulatory age-related differences in the striatum may influence Pavlovian biases and instrumental learning in 25 young and 31 older adults. Computational modeling revealed a significant age-related reduction in reward and punishment sensitivity and marked (albeit not significant) reduction in learning rate and lapse rate (irreducible noise). Voxel-based morphometry analysis using 7 Tesla MRI images showed that individual differences in learning rate in older adults were related to the volume of the caudate nucleus. In contrast, dopamine synthesis capacity in the dorsal striatum, assessed using [18F]-DOPA positron emission tomography in 22 of these older adults, was not associated with learning performance and did not moderate the relationship between caudate volume and learning rate. This multiparametric approach suggests that age-related differences in striatal volume may influence learning proficiency in old age.

The caption in Figure 1 mistakenly omits that the figure was adapted from Richter et al., 2014 (Front Syst Neurosci 2014; 8:140). The authors apologize for this error. The full citation is reported below.Richter A, Guitart-Masip M, Barman A, Libeau C, Behnisch G, Czerney S, Schanze D, Assmann A, Klein M, Düzel E, Zenker M, Seidenbecher CI, Schott BH. Valenced action/inhibition learning in humans is modulated by a genetic variant linked to dopamine D2 receptor expression. Front Syst Neurosci. 2014; 8:140.

Structural deterioration and volume loss of the hippocampal formation is observed in many diseases associated with memory decline. Paradoxically, glucose metabolism of the hippocampal formation can be increased at the same time. This might be a consequence of compensatory (beneficial) or maladaptive (detrimental) mechanisms. Aim of this study was to differentiate between compensation and maladaptation by analyzing the association between glucose metabolism in the hippocampal formation measured by positron emission tomography with the glucose analogue 18F-fluorodeoxyglucose and cognitive performance as characterized by the extended Consortium to Establish a Registry for Alzheimer's Disease test battery in a sample of 87 patients (81.8 ± 5.4 years) with mild cognitive impairment or mild dementia and varying etiological diagnoses. Glucose metabolism in the hippocampal formation was negatively correlated with the performance in several cognitive subdomains, most pronounced for verbal semantic fluency, independent of overall neuronal dysfunction, presence of clinical Alzheimer's disease, and overall cognitive performance. This finding provides evidence that increased glucose metabolism in the hippocampal formation of cognitively impaired patients indicates detrimental maladaptation rather than a beneficial compensatory reaction. Excess glucose metabolism in the hippocampal formation might be a useful therapeutic target in these patients.

Purpose Dopamine transporter SPECT with I-FP-CIT is registered for detection (or exclusion) of nigrostriatal degeneration to support the etiologic classification of parkinsonian syndromes. In case of uncertainty in the interpretation of SPECT findings or unexpected clinical course, follow-up SPECT might be useful. However, the utility of follow-up FP-CIT SPECT has not yet been clarified. Methods One hundred forty-one patients (65.1 ± 10.4 years) from 3 sites with follow-up FP-CIT SPECT 22.4 ± 13.7 months after baseline SPECT were included. Retrospective visual interpretation of FP-CIT SPECT scans was performed by 2 experienced readers according to the following 7-point score: "normal," some minor degree of uncertainty due to "mild asymmetry" or mild to moderate "uniform reduction," "Parkinson disease (PD) reduction type 1/2/3," and "atypical reduction." Results Normal FP-CIT SPECT or PD characteristic reduction was confirmed by follow-up SPECT in all cases (n = 58). Among patients with some minor degree of uncertainty at baseline (n = 65), the majority (72%) did now show abnormalities in follow-up SPECT, but 20% showed clear progression suggesting nigrostriatal degeneration. The latter was very rare at age younger than 60 years. The final categorization as normal or neurodegenerative was not affected by the time delay between baseline and follow-up SPECT. Conclusions Follow-up FP-CIT SPECT cannot be generally recommended in case of completely normal baseline SPECT or PD characteristic reduction. It also cannot be recommended in patients younger than 60 years, even in case of some minor degree of uncertainty in the baseline SPECT. There is no evidence to delay follow-up FP-CIT SPECT longer than 12 months.

Quantitative assessment of radio- and chemotherapy response with 18F-FDG whole-body PET has attracted increasing interest in recent years. In most published work, SUV has been used for this purpose. In the context of therapy response assessment, the reliability of lesion SUVs, notably their test–retest stability, thus becomes crucial. However, a recent study demonstrated substantial test–retest variability (TRV) in SUVs. The purpose of the present study was to investigate whether the tumor-to-blood SUV ratio (SUR) can improve TRV in tracer uptake. Methods: 73 patients with advanced non–small cell lung cancer from the prospective multicenter trials ACRIN 6678 (n = 34) and MK-0646-008 (n = 39) were included in this study. All patients underwent two 18F-FDG PET/CT investigations on two different days (time difference, 3.6 ± 2.1 d; range, 1–7 d) before therapy. For each patient, up to 7 tumor lesions were evaluated. For each lesion, SUVmax and SUVpeak were determined. Blood SUV was determined as the mean value of a 3-dimensional aortic region of interest that was delineated on the attenuation CT image and transferred to the PET image. SURs were computed as the ratio of tumor SUV to blood SUV and were uptake time–corrected to 75 min after injection. TRV was quantified as 1.96 multiplied by the root-mean-square deviation of the fractional paired differences in SUV and SUR. The combined effect of blood normalization and uptake time correction was inspected by considering RTRV (TRVSUR/TRVSUV), a ratio reflecting the reduction in the TRV in SUR relative to SUV. RTRV was correlated with the group-averaged-value difference (δ) in CFmean (δCFmean) of the quantity δCF = |CF – 1|, where CF is the numeric factor that converts individual ratios of paired SUVs into corresponding SURs. This correlation analysis was performed by successively increasing a threshold value δCFmin and computing δCFmean and RTRV for the remaining subgroup of patients/lesions with δCF ≥ δCFmin. Results: The group-averaged TRVSUV and TRVSUR were 32.1 and 29.0, respectively, which correspond to a reduction of variability in SUR by an RTRV factor of 0.9 in comparison to SUV. This rather marginal improvement can be understood to be a consequence of the atypically low intrasubject variability in blood SUV and uptake time and the accordingly small δCF values in the investigated prospective study groups. In fact, subgroup analysis with increasing δCFmin thresholds revealed a pronounced negative correlation (Spearman ρ = −0.99, P < 0.001) between RTRV and δCFmean, where RTRV ≈ 0.4 in the δCFmin = 20% subgroup, corresponding to a more than 2-fold reduction of TRVSUR compared with TRVSUV. Conclusion: Variability in blood SUV and uptake time has been identified as a causal factor in the TRV in lesion SUV. Therefore, TRV in lesion uptake measurements can be reduced by replacing SUV with SUR as the uptake measure. The improvement becomes substantial for the level of variability in blood SUV and uptake time typically observed in the clinical context.

Summary Aim: After detection of obstructive uropathy (OU), the indication for or against surgery is primarily based on the differential renal function (DRF). This is to compare functional magnetic resonance urography (fMRU) with dynamic renal scintigraphy (DRS) to assess OU and DRF in infants and children. Patients, methods: Retrospective analysis in 30 patients (female: 16; male: 14; median age: 5.5 years [0.2-16.5]), divided into subgroup A (age: 0-2 years; n = 16) and B (> 2-17 years; n = 14). fMRU was assessed by measuring renal transit time (RTT) and volumetric DRF with CHOP fMRU tool (CT) and ImageJ MRU plug-in (IJ). OU detection by fMRU was compared with DRS (standard of reference) using areas under the curves (AUC) in ROC analyses. Concordant DRF was assumed if absolute deviation between fMRU and DRS was < 5 %. Results: DRS confirmed fixed OU in 4/31 kidneys (12.9 %) in subgroup A. AUC of CT was 0.94 compared with 0.93 by IJ. Subgroup B showed fixed OU in 1/21 kidneys (4.8 %) with AUCs of 0.98 each. RTT measured neither by CT nor by IJ in confirmed fixed OU was < 1200 s – resulting in negative predictive values of 1.0 each. In subgroup A, DRF was concordant in 81.3 % of the kidneys for CT and DRS compared with 75.0 % for IJ and DRS. In subgroup B, CT and DRS were concordant in 91.7 %, and IJ and DRS in 45.8 % of the kidneys. Conclusion: fMRU accurately excluded fixed OU in infants and children, independent from the software used for quantification. However, assessment of DRF with fMRU deviated from DRS especially in infants who may profit most from early intervention. Thus, fMRU cannot fully replace DRS as primary functional examination. If, for clinical reasons, fMRU is performed in first place and it cannot exclude fixed OU, it should be followed by DRS for validation and DRF quantification.

Background Parkinsonian syndromes are classified by etiology mainly on clinical grounds, that is, on the basis of the clinical manifestations and with the aid of conventional ancillary studies. In most cases, the clinical diagnosis is clear. In up to 30% of cases, however, the etiological classification remains uncertain after completion of the basic clinical diagnostic evaluation, and additional investigation with nuclear imaging may be indicated. In particular, cerebral single-photon emission computed tomography (SPECT) with dopamine transporter (DAT) ligands may be helpful. DAT-SPECT can be used to demonstrate or rule out nigrostriatal degeneration and thereby differentiate neurodegenerative parkinsonian syndromes from symptomatic parkinsonian syndromes and other differential diagnoses. Positron emission tomography (PET) with the glucose analogue [18F]fluorodeoxyglucose (FDG) can be used to identify disease-specific patterns of neuronal dysfunction/degeneration in order to differentiate the various neurodegenerative parkinsonian syndromes from one another. Methods In this review, we summarize the current state of the evidence on DAT-SPECT and FDG-PET for the indications mentioned above on the basis of a selective review of the literature. Results DAT-SPECT has been adequately validated as an in vivo marker for nigrostriatal degeneration. Studies using the clinical diagnosis of a movement disorders specialist over the course of the disease as a reference have shown that DAT- SPECT is 78-100% sensitive (median, 93%) and 70-100% specific (median, 89%) for the differentiation of neurodegenerative parkinsonian syndromes from symptomatic parkinsonism and other differential diagnoses in clinically unclear cases. DAT- SPECT scanning led to a change of diagnosis in 27-56% of patients (median, 43%) and to a change of treatment in 33-72% (median, 43%). FDG-PET enables the differentiation of atypical neurodegenerative parkinsonian syndromes from the idiopathic parkinsonian syndrome (i.e., Parkinson's disease proper) with high sensitivity and specificity (both approximately 90%), when the clinical diagnosis by a movement disorders specialist over the course of the disease is used as a reference. Conclusion DAT-SPECT has been well documented to be highly diagnostically accurate and to have a relevant influence on the diagnosis and treatment of patients with clinically uncertain parkinsonian or tremor syndrome. It has not yet been shown to improve patient-relevant endpoints such as mortality, morbidity, and health-related quality of life; proof of this will probably have to await the introduction of neuroprotective treatments. The current evidence for the high differential diagnostic accuracy of FDG-PET in neurodegenerative parkinsonian syndromes needs to be reinforced by prospective studies with neuropathological verification of the diagnosis.