Short post-injection seizure duration is associated with reduced power of ictal brain perfusion SPECT to lateralize the seizure onset zone.

BACKGROUND: The aim of this study was to assess the impact of the post-injection electrical seizure duration on the identification of the seizure onset zone (SOZ) in ictal brain perfusion SPECT in presurgical evaluation of drug-resistant epilepsy. METHODS: 176 ictal SPECT performed with 99mTc-HMPAO (n = 140) or -ECD (n = 36) were included retrospectively. Visual interpretation of the SPECT images (together with individual MRI and statistical hyperperfusion maps) with respect to lateralization (right, left, none) and localization (temporal, frontal, parietal, occipital) of the SOZ was performed by 3 independent readers. Between-readers agreement was characterized by Fleiss' κ. An ictal SPECT was considered "lateralizing" if all readers agreed on right or left hemisphere. It was considered "localizing" if it was lateralizing and all readers agreed on the same lobe within the same hemisphere. The impact of injection latency and post-injection seizure duration on the proportion of lateralizing/localizing SPECT was tested by ANOVA with dichotomized (by the median) injection latency and post-injection seizure duration as between-subjects factors. RESULTS: Median [interquartile range] (full range) of injection latency and post-injection seizure duration were 30 [24, 40] (3-120) s and 50 [27, 70] (-20-660) s, respectively. Fleiss' κ for lateralization of the SOZ was largest for the combination of early (< 30 s) injection and long (> 50 s) post-injection seizure duration (κ = 0.894, all other combinations κ = 0.659-0.734). Regarding Fleiss' κ for localization of the SOZ in the 141 (80.1%) lateralizing SPECT, it was largest for early injection and short post-injection seizure duration (κ = 0.575, all other combinations κ = 0.329-0.368). The proportion of lateralizing SPECT was lower with short compared to long post-injection seizure duration (estimated marginal means 74.3% versus 86.3%, p = 0.047). The effect was mainly driven by cases with very short post-injection seizure duration ≤ 10 s (53.8% lateralizing). Injection latency in the considered range had no significant impact on the proportion of lateralizing SPECT (p = 0.390). The proportion of localizing SPECT among the lateralizing cases did not depend on injection latency or post-injection seizure duration (p ≥ 0.603). CONCLUSIONS: Short post-injection seizure duration is associated with a lower proportion of lateralizing cases in ictal brain perfusion SPECT.

Discrimination of benign, atypical, and malignant peripheral nerve sheath tumors in neurofibromatosis type 1 using diffusion-weighted MRI.

Background: Neurofibromatosis type 1 (NF1) is associated with the development of benign (BPNST) and malignant (MPNST) peripheral nerve sheath tumors. Recently described atypical neurofibromas (ANF) are considered pre-malignant precursor lesions to MPNSTs. Previous studies indicate that diffusion-weighted magnetic resonance imaging (DW-MRI) can reliably discriminate MPNSTs from BPNSTs. We therefore investigated the diagnostic accuracy of DW-MRI for the discrimination of benign, atypical, and malignant peripheral nerve sheath tumors. Methods: In this prospective explorative single-center phase II diagnostic study, 44 NF1 patients (23 male; 30.1 ±â€…11.8 years) underwent DW-MRI (b-values 0-800 s/mm²) at 3T. Two radiologists independently assessed mean and minimum apparent diffusion coefficients (ADCmean/min) in areas of largest tumor diameters and ADCdark in areas of lowest signal intensity by manual contouring of the tumor margins of 60 BPNSTs, 13 ANFs, and 21 MPNSTs. Follow-up of ≥ 24 months (BPNSTs) or histopathological evaluation (ANFs + MPNSTs) served as diagnostic reference standard. Diagnostic ADC-based cut-off values for discrimination of the three tumor groups were chosen to yield the highest possible specificity while maintaining a clinically acceptable sensitivity. Results: ADC values of pre-malignant ANFs clustered between BPNSTs and MPNSTs. Best BPNST vs. ANF + MPNST discrimination was obtained using ADCdark at a cut-off value of 1.6 × 10-3 mm2/s (85.3% sensitivity, 93.3% specificity), corresponding to an AUC of 94.3% (95% confidence interval: 85.2-98.0). Regarding BPNST + ANF vs. MPNST, best discrimination was obtained using an ADCdark cut-off value of 1.4 × 10-3 mm2/s (83.3% sensitivity, 94.5% specificity). Conclusions: DW-MRI using ADCdark allows specific and noninvasive discrimination of benign, atypical, and malignant nerve sheath tumors in NF1.

Removing outliers from the normative database improves regional atrophy detection in single-subject voxel-based morphometry.

PURPOSE: Single-subject voxel-based morphometry (VBM) compares an individual T1-weighted MRI to a sample of normal MRI in a normative database (NDB) to detect regional atrophy. Outliers in the NDB might result in reduced sensitivity of VBM. The primary aim of the current study was to propose a method for outlier removal ("NDB cleaning") and to test its impact on the performance of VBM for detection of Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). METHODS: T1-weighted MRI of 81 patients with biomarker-confirmed AD (n = 51) or FTLD (n = 30) and 37 healthy subjects with simultaneous FDG-PET/MRI were included as test dataset. Two different NDBs were used: a scanner-specific NDB (37 healthy controls from the test dataset) and a non-scanner-specific NDB comprising 164 normal T1-weighted MRI from 164 different MRI scanners. Three different quality metrics based on leave-one-out testing of the scans in the NDB were implemented. A scan was removed if it was an outlier with respect to one or more quality metrics. VBM maps generated with and without NDB cleaning were assessed visually for the presence of AD or FTLD. RESULTS: Specificity of visual interpretation of the VBM maps for detection of AD or FTLD was 100% in all settings. Sensitivity was increased by NDB cleaning with both NDBs. The effect was statistically significant for the multiple-scanner NDB (from 0.47 [95%-CI 0.36-0.58] to 0.61 [0.49-0.71]). CONCLUSION: NDB cleaning has the potential to improve the sensitivity of VBM for the detection of AD or FTLD without increasing the risk of false positive findings.

Increased off-target binding of [18F]florbetaben in the skull of women with reduced skull density.

AIM: To investigate the relationship between off-target binding of the amyloid tracer [18F]florbetaben (FBB) in the skull and skull density. METHODS: Forty-three consecutive patients were included retrospectively (age 70.2±7.5y, 42% females, 65% amyloid-positive). For each patient, CT skull density (in Hounsfield units) and (late) FBB uptake in the skull were obtained using an individual skull mask generated by warping the skull tissue probability map provided by the statistical parametric mapping software package (version SPM12) to the native patient space. Skull FBB uptake (mean of the 10% hottest voxels) was scaled to the individual median FBB uptake in the pons. The association between skull FBB uptake and skull density was tested by correlation analyses. Univariate analysis of variance (ANOVA) of skull FBB uptake with dichotomized skull density (low: ≤ median, high), sex (female, male) and amyloid-status (positive, negative) as between-subjects factors was used to assess the impact of sex and amyloid status. RESULTS: There was a significant inverse correlation between skull FBB uptake and skull density (Pearson correlation coefficient -0.518, p < 0.001; Spearman rho -0.321, p = 0.036). The ANOVA confirmed the bone density effect on the FBB uptake in the skull (p = 0.019). In addition, sex (p = 0.012) and density*sex interaction (p = 0.016) had a significant impact. Skull FBB uptake was significantly higher in females with low skull density than for all other combinations of sex and skull density. Amyloid status did not reach statistical significance (p = 0.092). CONCLUSION: Off-target binding of FBB in the skull is inversely associated with skull density. The relationship is mainly driven by females. Amyloid status does not have a major impact on skull FBB binding.

Dopamine Transporter SPECT with 12-Minute Scan Duration Using Multiple-Pinhole Collimators.

This study evaluated the potential to reduce the scan duration in dopamine transporter (DAT) SPECT when using a second-generation multiple-pinhole (MPH) collimator designed for brain SPECT with improved count sensitivity and improved spatial resolution compared with parallel-hole and fanbeam collimators. Methods: The retrospective study included 640 consecutive clinical DAT SPECT studies that had been acquired in list mode with a triple-head SPECT system with MPH collimators and a 30-min net scan duration after injection of 181 ± 10 MBq of [123I]FP-CIT. Raw data corresponding to scan durations of 20, 15, 12, 8, 6, and 4 min were obtained by restricting the events to a proportionally reduced time interval of the list-mode data for each projection angle. SPECT images were reconstructed iteratively with the same parameter settings irrespective of scan duration. The resulting 5,120 SPECT images were assessed for a neurodegeneration-typical reduction in striatal signal by visual assessment, conventional specific binding ratio analysis, and a deep convolutional neural network trained on 30-min scans. Results: Regarding visual interpretation, image quality was considered diagnostic for all 640 patients down to a 12-min scan duration. The proportion of discrepant visual interpretations between 30 and 12 min (1.2%) was not larger than the proportion of discrepant visual interpretations between 2 reading sessions of the same reader at a 30-min scan duration (1.5%). Agreement with the putamen specific binding ratio from the 30-min images was better than expected for 5% test-retest variability down to a 10-min scan duration. A relevant change in convolutional neural network-based automatic classification was observed at a 6-min scan duration or less. Conclusion: The triple-head SPECT system with MPH collimators allows reliable DAT SPECT after administration of about 180 MBq of [123I]FP-CIT with a 12-min scan duration.

Asymmetry of thalamic hypometabolism on FDG-PET/CT in neurofibromatosis type 1: Association with peripheral tumor burden.

BACKGROUND AND PURPOSE: Thalamic hypometabolism is a consistent finding in brain PET with F-18 fluorodeoxyglucose (FDG) in patients with neurofibromatosis type 1 (NF1). However, the pathophysiology of this metabolic alteration is unknown. We hypothesized that it might be secondary to disturbance of peripheral input to the thalamus by NF1-characteristic peripheral nerve sheath tumors (PNSTs). To test this hypothesis, we investigated the relationship between thalamic FDG uptake and the number, volume, and localization of PNSTs. METHODS: This retrospective study included 22 adult NF1 patients (41% women, 36.2 ± 13.0 years) referred to whole-body FDG-PET/contrast-enhanced CT for suspected malignant transformation of PNSTs and 22 sex- and age-matched controls. Brain FDG uptake was scaled voxelwise to the individual median uptake in cerebellar gray matter. Bilateral mean and left-right asymmetry of thalamic FDG uptake were determined using a left-right symmetric anatomical thalamus mask. PNSTs were manually segmented in contrast-enhanced CT. RESULTS: Thalamic FDG uptake was reduced in NF1 patients by 2.0 standard deviations (p < .0005) compared to controls. Left-right asymmetry was increased by 1.3 standard deviations (p = .013). Thalamic hypometabolism was higher in NF1 patients with ≥3 PNSTs than in patients with ≤2 PNSTs (2.6 vs. 1.6 standard deviations, p = .032). The impact of the occurrence of paraspinal/paravertebral PNSTs and of the mean PNST volume on thalamic FDG uptake did not reach statistical significance (p = .098 and p = .189). Left-right asymmetry of thalamic FDG uptake was not associated with left-right asymmetry of PNST burden (p = .658). CONCLUSIONS: This study provides first evidence of left-right asymmetry of thalamic hypometabolism in NF1 and that it might be mediated by NF1-associated peripheral tumors.

Prostate-specific membrane antigen radioguided surgery with negative histopathology: an in-depth analysis.

PURPOSE: To identify reasons for negative histopathology of specimens from prostate-specific membrane antigen (PSMA) radioguided surgery (PSMA-RGS) in recurrent prostate cancer (PCa) after prostatectomy. METHODS: Of 302 patients who underwent PSMA-RGS, 17 (5.6%) demonstrated a negative histopathology. Preoperative data, PSMA PET, PSMA SPECT, and follow-up information were analyzed retrospectively to differentiate true/false positive (TP/FP) from true/false negative (TN/FN) lesions. RESULTS: The median prostate-specific antigen at PET was 0.4 ng/ml (interquartile range [IQR] 0.3-1.2). Twenty-five index lesions (median short axis 7 mm, IQR 5-8; median long-axis 12 mm, IQR 8-17) had a median SUVmax of 4 (IQR 2.6-6; median PSMA expression score 1, IQR 1-1). Six lesions were TP, twelve were FP, one was TN, and six remained unclear. All TP lesions were in the prostatic fossa or adjacent to the internal iliac arteries. Three suspected local recurrences were FP. All FP lymph nodes were located at the distal external iliac arteries or outside the pelvis. A low PSMA-expressing TN node was identified next to a common iliac artery. Unclear lesions were located next to the external iliac arteries or outside the pelvis. CONCLUSION: In most cases with a negative histopathology from PSMA-RGS, lesions were FP on PSMA PET. Unspecific uptake should be considered in low PSMA-expressing lymph nodes at the distal external iliac arteries or outside the pelvis, especially if no PSMA-positive lymph nodes closer to the prostatic fossa are evident. Rarely, true positive metastases were missed by surgery or histopathology.

Automated identification of uncertain cases in deep learning-based classification of dopamine transporter SPECT to improve clinical utility and acceptance.

PURPOSE: Deep convolutional neural networks (CNN) are promising for automatic classification of dopamine transporter (DAT)-SPECT images. Reporting the certainty of CNN-based decisions is highly desired to flag cases that might be misclassified and, therefore, require particularly careful inspection by the user. The aim of the current study was to design and validate a CNN-based system for the identification of uncertain cases. METHODS: A network ensemble (NE) combining five CNNs was trained for binary classification of [123I]FP-CIT DAT-SPECT images as "normal" or "neurodegeneration-typical reduction" with high accuracy (NE for classification, NEfC). An uncertainty detection module (UDM) was obtained by combining two additional NE, one trained for detection of "reduced" DAT-SPECT with high sensitivity, the other with high specificity. A case was considered "uncertain" if the "high sensitivity" NE and the "high specificity" NE disagreed. An internal "development" dataset of 1740 clinical DAT-SPECT images was used for training (n = 1250) and testing (n = 490). Two independent datasets with different image characteristics were used for testing only (n = 640, 645). Three established approaches for uncertainty detection were used for comparison (sigmoid, dropout, model averaging). RESULTS: In the test data from the development dataset, the NEfC achieved 98.0% accuracy. 4.3% of all test cases were flagged as "uncertain" by the UDM: 2.5% of the correctly classified cases and 90% of the misclassified cases. NEfC accuracy among "certain" cases was 99.8%. The three comparison methods were less effective in labelling misclassified cases as "uncertain" (40-80%). These findings were confirmed in both additional test datasets. CONCLUSION: The UDM allows reliable identification of uncertain [123I]FP-CIT SPECT with high risk of misclassification. We recommend that automatic classification of [123I]FP-CIT SPECT images is combined with an UDM to improve clinical utility and acceptance. The proposed UDM method ("high sensitivity versus high specificity") might be useful also for DAT imaging with other ligands and for other binary classification tasks.

Combination of tumor asphericity and an extracellular matrix-related prognostic gene signature in non-small cell lung cancer patients.

One important aim of precision oncology is a personalized treatment of patients. This can be achieved by various biomarkers, especially imaging parameters and gene expression signatures are commonly used. So far, combination approaches are sparse. The aim of the study was to independently validate the prognostic value of the novel positron emission tomography (PET) parameter tumor asphericity (ASP) in non small cell lung cancer (NSCLC) patients and to investigate associations between published gene expression profiles and ASP. This was a retrospective evaluation of PET imaging and gene expression data from three public databases and two institutional datasets. The whole cohort comprised 253 NSCLC patients, all treated with curative intent surgery. Clinical parameters, standard PET parameters and ASP were evaluated in all patients. Additional gene expression data were available for 120 patients. Univariate Cox regression and Kaplan-Meier analysis was performed for the primary endpoint progression-free survival (PFS) and additional endpoints. Furthermore, multivariate cox regression testing was performed including clinically significant parameters, ASP, and the extracellular matrix-related prognostic gene signature (EPPI). In the whole cohort, a significant association with PFS was observed for ASP (p < 0.001) and EPPI (p = 0.012). Upon multivariate testing, EPPI remained significantly associated with PFS (p = 0.018) in the subgroup of patients with additional gene expression data, while ASP was significantly associated with PFS in the whole cohort (p = 0.012). In stage II patients, ASP was significantly associated with PFS (p = 0.009), and a previously published cutoff value for ASP (19.5%) was successfully validated (p = 0.008). In patients with additional gene expression data, EPPI showed a significant association with PFS, too (p = 0.033). The exploratory combination of ASP and EPPI showed that the combinatory approach has potential to further improve patient stratification compared to the use of only one parameter. We report the first successful validation of EPPI and ASP in stage II NSCLC patients. The combination of both parameters seems to be a very promising approach for improvement of risk stratification in a group of patients with urgent need for a more personalized treatment approach.

Automatic covariance pattern analysis outperforms visual reading of 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in variant progressive supranuclear palsy.

BACKGROUND: To date, studies on positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG) in progressive supranuclear palsy (PSP) usually included PSP cohorts overrepresenting patients with Richardson's syndrome (PSP-RS). OBJECTIVES: To evaluate FDG-PET in a patient sample representing the broad phenotypic PSP spectrum typically encountered in routine clinical practice. METHODS: This retrospective, multicenter study included 41 PSP patients, 21 (51%) with RS and 20 (49%) with non-RS variants of PSP (vPSP), and 46 age-matched healthy controls. Two state-of-the art methods for the interpretation of FDG-PET were compared: visual analysis supported by voxel-based statistical testing (five readers) and automatic covariance pattern analysis using a predefined PSP-related pattern. RESULTS: Sensitivity and specificity of the majority visual read for the detection of PSP in the whole cohort were 74% and 72%, respectively. The percentage of false-negative cases was 10% in the PSP-RS subsample and 43% in the vPSP subsample. Automatic covariance pattern analysis provided sensitivity and specificity of 93% and 83% in the whole cohort. The percentage of false-negative cases was 0% in the PSP-RS subsample and 15% in the vPSP subsample. CONCLUSIONS: Visual interpretation of FDG-PET supported by voxel-based testing provides good accuracy for the detection of PSP-RS, but only fair sensitivity for vPSP. Automatic covariance pattern analysis outperforms visual interpretation in the detection of PSP-RS, provides clinically useful sensitivity for vPSP, and reduces the rate of false-positive findings. Thus, pattern expression analysis is clinically useful to complement visual reading and voxel-based testing of FDG-PET in suspected PSP. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Brain MRI in Progressive Supranuclear Palsy with Richardson's Syndrome and Variant Phenotypes.

BACKGROUND: Brain magnetic resonance imaging (MRI) is used to support the diagnosis of progressive supranuclear palsy (PSP). However, the value of visual descriptive, manual planimetric, automatic volumetric MRI markers and fully automatic categorization is unclear, particularly regarding PSP predominance types other than Richardson's syndrome (RS). OBJECTIVES: To compare different visual reading strategies and automatic classification of T1-weighted MRI for detection of PSP in a typical clinical cohort including PSP-RS and (non-RS) variant PSP (vPSP) patients. METHODS: Forty-one patients (21 RS, 20 vPSP) and 46 healthy controls were included. Three readers using three strategies performed MRI analysis: exclusively visual reading using descriptive signs (hummingbird, morning-glory, Mickey-Mouse), visual reading supported by manual planimetry measures, and visual reading supported by automatic volumetry. Fully automatic classification was performed using a pre-trained support vector machine (SVM) on the results of atlas-based volumetry. RESULTS: All tested methods achieved higher specificity than sensitivity. Limited sensitivity was driven to large extent by false negative vPSP cases. Support by automatic volumetry resulted in the highest accuracy (75.1% ± 3.5%) among the visual strategies, but performed not better than the midbrain area (75.9%), the best single planimetric measure. Automatic classification by SVM clearly outperformed all other methods (accuracy, 87.4%), representing the only method to provide clinically useful sensitivity also in vPSP (70.0%). CONCLUSIONS: Fully automatic classification of volumetric MRI measures using machine learning methods outperforms visual MRI analysis without and with planimetry or volumetry support, particularly regarding diagnosis of vPSP, suggesting the use in settings with a broad phenotypic PSP spectrum. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Individualized Summary Assessment of Detailed Neuropsychological Testing for the Etiological Diagnosis of Newly Detected Cognitive Impairment in Hospitalized Geriatric Patients.

BACKGROUND: Neuropsychological testing (NPT) of geriatric inpatients can be affected by the acute illness and/or the hospitalization. OBJECTIVE: To test individualized interpretation of detailed NPT for the differentiation between primary 'neurodegenerative' etiologies (predominantly Alzheimer's disease) and 'other' etiologies (including cerebrovascular disease) of newly detected cognitive impairment in geriatric inpatients without and with delirium in remission. METHODS: 96 geriatric inpatients (81.9±5.6 years, 64.6% females) with clinically uncertain cognitive impairment were included. 31.3% had delirium in remission that was not considered the primary cause of the cognitive impairment. Categorization of the most likely etiology as 'neurodegenerative' or 'other' was established retrospectively by a study neuropsychologist based on individualized summary assessment of detailed NPT compiled in a standardized vignette. The etiological diagnosis based on FDG-PET served as gold standard (54.2% 'neurodegenerative', 45.8% 'other'). RESULTS: Individualized summary assessment by the study neuropsychologist was correct in 80 patients (83.3%, 8 false positive, 8 false negative). The impact of delirium in remission was not significant (p = 0.237). Individualized summary assessment by an independent neuropsychologist resulted in more false positive cases (n = 22) at the same rate of false negative cases (n = 8). Automatic categorization with a decision tree model based on the most discriminative NPT scores was correct in 68 patients (70.8%, 14 false positive, 14 false negative). CONCLUSION: Individualized summary assessment of detailed NPT in the context of relevant clinical information might be useful for the etiological diagnosis of newly detected cognitive impairment in hospitalized geriatric patients, also in patients with delirium in remission, but requires task-specific expertise.

PSMA hybrid imaging in prostate cancer - current applications and perspectives. / PSMA-Hybridbildgebung in der Diagnostik des Prostatakarzinoms ­ aktuelle Anwendungen und Perspektiven.

BACKGROUND: Prostate cancer (PCa) is the most common malignancy in men and the second most common tumor-associated cause of death in the male population in Germany. Prostate-specific membrane antigen (PSMA)-targeted hybrid imaging using positron emission tomography (PET) in combination with CT or MRI represents a comparably new method that gained increasing importance in the diagnostic process of PCa in recent years. METHOD: Current applications of PSMA hybrid imaging were summarized according to the German and European guidelines on PCa. New developments were elaborated based on a literature review of PubMed conducted in 10/22. RESULTS: PSMA-PET/CT demonstrated higher detection rates for metastases in high-risk PCa and recurrent PCa after primary therapy than established imaging methods (CT, MRI, and bone scan). Despite promising results from prospective trials in both scenarios and substantial influence on clinical decision making, data regarding the influence of PSMA-PET on PCa-specific and overall survival are still lacking. Hence, PSMA PET/CT is recommended with a "weak" strength rating in most situations. However, its importance in new treatment options like metastasis-directed therapy or PSMA-radioligand therapy expands the scope of PSMA-PET in the clinical routine. CONCLUSION: PSMA-targeting hybrid imaging represents the most sensitive diagnostic test in several stages of PCa and allows the development of new treatment strategies. Prospective studies are needed to evaluate the influence of PSMA-PET on patient survival. KEY POINTS: · PSMA-PET/CT is superior to conventional imaging in the primary staging of high-risk prostate cancer.. · PSMA hybrid imaging can detect metastases in patients with biochemical recurrence at low PSA values.. · Clinical decision making is frequently influenced by results of PSMA-PET/CT.. CITATION FORMAT: · Koehler D, Berliner C, Shenas F et al. PSMA hybrid imaging in prostate cancer - current applications and perspectives. Fortschr Röntgenstr 2023; 195: 1001 - 1008.

No impact of attenuation and scatter correction on the interpretation of dopamine transporter SPECT in patients with clinically uncertain parkinsonian syndrome.

PURPOSE: The benefit from attenuation and scatter correction (ASC) of dopamine transporter (DAT)-SPECT for the detection of nigrostriatal degeneration in clinical routine is still a matter of debate. The current study evaluated the impact of ASC on visual interpretation and semi-quantitative analysis of DAT-SPECT in a large patient sample. METHODS: One thousand seven hundred forty consecutive DAT-SPECT with 123I-FP-CIT from clinical routine were included retrospectively. SPECT images were reconstructed iteratively without and with ASC. Attenuation correction was based on uniform attenuation maps, scatter correction on simulation. All SPECT images were categorized with respect to the presence versus the absence of Parkinson-typical reduction of striatal 123I-FP-CIT uptake by three independent readers. Image reading was performed twice to assess intra-reader variability. The specific 123I-FP-CIT binding ratio (SBR) was used for automatic categorization, separately with and without ASC. RESULTS: The mean proportion of cases with discrepant categorization by the same reader between the two reading sessions was practically the same without and with ASC, about 2.2%. The proportion of DAT-SPECT with discrepant categorization without versus with ASC by the same reader was 1.66% ± 0.50% (1.09-1.95%), not exceeding the benchmark of 2.2% from intra-reader variability. This also applied to automatic categorization of the DAT-SPECT images based on the putamen SBR (1.78% discrepant cases between without versus with ASC). CONCLUSION: Given the large sample size, the current findings provide strong evidence against a relevant impact of ASC with uniform attenuation and simulation-based scatter correction on the clinical utility of DAT-SPECT to detect nigrostriatal degeneration in patients with clinically uncertain parkinsonian syndrome.

Stereotactical normalization with multiple templates representative of normal and Parkinson-typical reduction of striatal uptake improves the discriminative power of automatic semi-quantitative analysis in dopamine transporter SPECT.

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: 1702 clinical 123I-FP-CIT SPECT images were stereotactically normalized (affine) to the anatomical space of the Montreal Neurological Institute (MNI) with SPM12 either using a single custom-made 123I-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 the multiple 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 Gaussians. The power to differentiate between reduced and normal SBR was estimated by the effect size of the distance between the two Gaussians computed as the differences between their mean values scaled to their pooled standard deviation. RESULTS: The effect size of the distance between the two Gaussians was 3.83 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 might provide improved separation between normal and reduced putamen SBR that could result in slightly improved power for the detection of nigrostriatal degeneration.

Feasibility of 99mTc-MIP-1404 for SPECT/CT Imaging and Subsequent PSMA-Radioguided Surgery in Early Biochemically Recurrent Prostate Cancer: A Case Series of 9 Patients.

This case series evaluated the feasibility of prostate-specific membrane antigen (PSMA)-radioguided surgery (RGS) with 99mTc-MIP-1404 in recurrent prostate cancer. Methods: Nine patients with PSMA-positive lesions on PET/CT received 99mTc-MIP-1404 (median, 747 MBq; interquartile range [IQR], 710-764 MBq) 17.2 h (IQR, 16.9-17.5 h) before SPECT/CT and 22.3 h (IQR, 20.8-24.0 h) before RGS. Results: Seventeen PSMA-positive lesions were detected on PET/CT (median short-axis diameter, 4 mm; IQR, 3-6 mm; median SUVmax, 8.9; IQR, 5.2-12.6). Nine of 17 (52.9%) were visible on SPECT/CT (median SUVmax, 13.8; IQR, 8.0-17.9). Except for 2 foci, all PET/CT-positive findings demonstrated intraoperative count rates above the background level (median count, 31; IQR, 17-89) and were lymph node metastases. Moreover, PSMA-RGS identified 2 additional metastases compared with PET/CT. Prostate-specific antigen values decreased after RGS in 6 of 9 patients (67%). Conclusion: PSMA-RGS with 99mTc-MIP-1404 identified lymph node metastases in all patients, including 2 additional lesions compared with PET/CT.

Evaluation of [68 Ga]Ga-PSMA-I&T PET/CT with additional late scans of the pelvis in prostate-specific antigen recurrence using the PROMISE criteria.

BACKGROUND: 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 [68 Ga]Ga-PSMA-I&T PET/CT of patients with rising PSA after prostatectomy. METHODS: A total of 297 patients (median PSA 0.35 ng/ml, interquartile range (IQR) 0.2-0.8) who underwent early whole-body [68 Ga]Ga-PSMA-I&T PET/CT (median dose 141 MBq, IQR 120-163; median 86 min, IQR 56-107) and additional late scans of the pelvis (median 180 min, IQR 170-191) were investigated retrospectively. Early and late images were staged separately according to the PROMISE criteria and compared with a final consensus of both. Standardized uptake values were analyzed for early and late scans. RESULTS: One hundred and thirty-four (45.1%) [68 Ga]Ga-PSMA-I&T PET/CT showed evidence of recurrent PCa (114/38.4% early, 131/44.1% late). Of 195 lesions, 144 (73.8%) were identified correctly on early scans. 191 (97.9%) lesions were detected on late imaging. The lesion SUVmax (median 3.4, IQR 0.4-6.5 vs. median 3.9, IQR 2.6-8.2) as well as the SUVmax to background ratio (median 9.4, IQR 1.7-19.1 vs. median 15.5, IQR 9.6-34.1) increased significantly between the imaging time points (p < 0.01, respectively). Compared to the final consensus, the miTNM-staging of early scans changed in 58 (19.5%) cases. Of these, 31 patients (10.4%) with negative early scans (T0 N0 M0) were upstaged. Twenty-seven (9.1%) patients with PCa characteristic lesions on early imaging (> T0 N0 M0) were up- and/or downstaged. In 4 (1.3%) cases, PCa-related lesions were only detectable on early PET/CT leading to upstagings of late imaging. CONCLUSIONS: Additional late scans of the pelvis in [68 Ga]Ga-PSMA-I&T PET/CT detected more lesions and an increasing contrast compared to early imaging. This influenced the final miTNM-staging substantially.

Multiple-pinhole collimators improve intra- and between-rater agreement and the certainty of the visual interpretation in dopamine transporter SPECT.

BACKGROUND: Multiple-pinhole (MPH) collimators improve the resolution-sensitivity trade-off compared to parallel-hole collimators. This study evaluated the impact of MPH collimators on intra- and between-rater agreement, and on the certainty of visual interpretation in dopamine transporter (DAT)-SPECT. METHODS: The study included 71 patients (62.1 ± 12.7 y). Two SPECT acquisitions were performed in randomized order after a single injection of 182 ± 9 MBq 123I-FP-CIT, one with MPH and one with low-energy-high-resolution-high-sensitivity (LEHRHS) collimators. MPH projections were reconstructed with an iterative 3d Monte Carlo algorithm. LEHRHS projections were reconstructed with filtered backprojection (FBP) or with ordered-subsets expectation-maximization and resolution recovery (OSEM). Images were visually evaluated twice by three independent raters with respect to presence/absence of Parkinson-typical reduction of striatal 123I-FP-CIT uptake using a Likert 6-score (- 3 = clearly normal, …, 3 = clearly reduced). In case of intra-rater discrepancy, an intra-rater consensus was obtained. Intra- and between-rater agreement with respect to the Likert score (6-score and dichotomized score) was characterized by Cohen's kappa. RESULTS: Intra-rater kappa of visual scoring of MPH/LEHRHS-OSEM/LEHRHS-FBP images was 0.84 ± 0.12/0.73 ± 0.06/0.73 ± 0.08 (6-score, mean of three raters) and 1.00 ± 0.00/0.96 ± 0.04/0.97 ± 0.03 (dichotomized score). Between-rater kappa of visual scoring (intra-rater consensus) of MPH/LEHRHS-OSEM/LEHRHS-FBP images was 0.70 ± 0.06/0.63 ± 0.08/0.48 ± 0.05 (6-score, mean of three pairs of raters) and 1.00 ± 0.00/0.92 ± 0.04/0.90 ± 0.06 (dichotomized score). There was a decrease of (negative) Likert scores in normal DAT-SPECT by 0.87 ± 0.18 points from the LEHRHS-OSEM to the MPH setting. The (positive) Likert scores of reduced DAT-SPECT did not change on average. CONCLUSIONS: MPH collimators improve intra- and between-rater agreement as well as the certainty of the visual interpretation of DAT-SPECT.

Brain FDG PET for Short- to Medium-Term Prediction of Further Cognitive Decline and Need for Assisted Living in Acutely Hospitalized Geriatric Patients With Newly Detected Clinically Uncertain Cognitive Impairment.

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.

Predicting the Outcome of Epilepsy Surgery by Covariance Pattern Analysis of Ictal Perfusion SPECT.

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, semiquantitative region-of-interest analysis, or conventional univariate voxel-based testing, which are limited by intra- and interrater variability 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 mo follow-up) and 18 nonresponders (≥Engel I-B). Ictal SPECT images were analyzed with the scaled subprofile model masked to group membership for unbiased identification of the 16 covariance patterns explaining the highest proportion of variance in the whole dataset. Individual expression scores of the covariance patterns were evaluated for predicting seizure freedom after temporal lobe surgery by receiver-operating-characteristic analysis. Kaplan-Meier analysis including all available follow-up data (up to 60 mo after surgery) was also performed. Results: Among the 16 covariance patterns only 1 showed a different expression between responders and nonresponders (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% CI, 0.577-0.911, P = 0.004) under the receiver-operating-characteristic curve. Kaplan-Meier analysis revealed a statistical trend toward longer seizure freedom in patients with positive expression score (P = 0.06). The median estimated seizure-free time was 48 mo in patients with positive expression score versus 6 mo 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 demographic 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.