Quantitative myocardial perfusion SPECT/CT for the assessment of myocardial tracer uptake in patients with three-vessel coronary artery disease: Initial experiences and results

BACKGROUND To evaluate quantitative myocardial perfusion SPECT/CT datasets for routine clinical reporting and the assessment of myocardial tracer uptake in patients with severe TVCAD. METHODS MPS scans were reconstructed as quantitative SPECT datasets using CTs from internal (SPECT/CT, Q_INT) and external (PET/CT, Q_EXT) sources for attenuation correction. TPD was calculated and compared to the TPD from non-quantitative SPECT datasets of the same patients. SUVmax, SUVpeak, and SUVmean were compared between Q_INT and Q_EXT SPECT datasets. Global SUVmax and SUVpeak were compared between patients with and without TVCAD. RESULTS Quantitative reconstruction was feasible. TPD showed an excellent correlation between quantitative and non-quantitative SPECT datasets. SUVmax, SUVpeak, and SUVmean showed an excellent correlation between Q_INT and Q_EXT SPECT datasets, though mean SUVmean differed significantly between the two groups. Global SUVmax and SUVpeak were significantly reduced in patients with TVCAD. CONCLUSIONS Absolute quantification of myocardial tracer uptake is feasible. The method seems to be robust and principally suitable for routine clinical reporting. Quantitative SPECT might become a valuable tool for the assessment of severe coronary artery disease in a setting of balanced ischemia, where potentially life-threatening conditions might otherwise go undetected

The Halos and Environments of Nearby Galaxies (HERON) Survey

We have used dedicated 0.7m telescopes in California and Israel to image the halos of ~200 galaxies in the Local Volume to 29 mag/sq arcsec, the sample mainly drawn from the 2MASS Large Galaxy Atlas (LGA). We supplement the LGA sample with dwarf galaxies and more distant giant ellipticals. Low surface brightness halos exceeding 50 kpc in diameter are found only in galaxies more luminous than L* and classic interaction signatures are relatively infrequent. Halo diameter is correlated with total galaxy luminosity. Extended low surface brightness halos are present even in galaxies as faint as M_V=-18. Edge-on galaxies with boxy bulges tend to lack extended spheroidal halos, while those with large classical bulges exhibit extended round halos, supporting the notions that boxy or barlike bulges originate from disks. Most face-on spiral galaxies present features that appear to be irregular extensions of spiral arms, although rare cases show smooth boundaries with no sign of star formation. Although we serendipitously discovered a dwarf galaxy undergoing tidal disruption in the halo of NGC 4449, we found no comparable examples in our general survey. A search for similar examples in the Local Volume identified hcc087, a tidally disrupting dwarf galaxy in the Hercules Cluster, but we do not confirm an anomalously large half-light radius reported for the dwarf VCC 1661

The haloes and environments of nearby galaxies (HERON) -- III. A 45 kpc spiral structure in the GLSB galaxy UGC 4599

We use a 0.7-m telescope in the framework of the Halos and Environments of Nearby Galaxies (HERON) survey to probe low surface brightness structures in nearby galaxies. One of our targets, UGC 4599, is usually classified as an early-type galaxy surrounded by a blue ring making it a potential Hoag's Object analog. Prior photometric studies of UGC 4599 were focused on its bright core and the blue ring. However, the HERON survey allows us to study its faint extended regions. With an eight hour integration, we detect an extremely faint outer disk with an extrapolated central surface brightness of $\mu_\mathrm{0,d}(r)=25.5$ mag arcsec$^{-2}$ down to 31 mag arcsec$^{-2}$ and a scale length of 15 kpc. We identify two distinct spiral arms of pitch angle ~6{\deg} surrounding the ring. The spiral arms are detected out to ~45 kpc in radius and the faint disk continues to ~70 kpc. These features are also seen in the GALEX FUV and NUV bands, in a deep u-band image from the 4.3m Lowell Discovery Telescope (which reveals inner spiral structure emerging from the core), and in HI. We compare this galaxy to ordinary spiral and elliptical galaxies, giant low surface brightness (GLSB) galaxies, and Hoag's Object itself using several standard galaxy scaling relations. We conclude that the pseudobulge and disk properties of UGC 4599 significantly differ from those of Hoag's Object and of normal galaxies, pointing toward a GLSB galaxy nature and filamentary accretion of gas to generate its outer disk.Comment: 17 pages, 14 figures, accepted for publication in MNRA

Feasibility of radiomic feature harmonization for pooling of [18F]FET or [18F]GE-180 PET images of gliomas

Introduction: Large datasets are required to ensure reliable non-invasive glioma assessment with radiomics-based machine learning methods. This can often only be achieved by pooling images from different centers. Moreover, trained models should perform with high accuracy when applied to data from different centers. In this study, the impact of reconstruction settings and segmentation methods on radiomic features derived from amino acid and TSPO PET images of glioma patients was examined. Additionally, the ability to model and thus reduce feature differences was investigated.Methods: [(18)FJFET and [(18)FJGE-180 PET data were acquired from 19 glioma patients. For each acquisition, 10 reconstruction settings and 9 segmentation methods were included to emulate multicentric data. Statistical robustness measures were calculated before and after ComBat harmonization. Differences between features due to setting variations were assessed using Friedman test, coefficient of variation (CV) and inter-rater reliability measures, including intraclass and Spearman's rank correlation coefficients and Fleiss' Kappa.Results: According to Friedman analyses, most features (>60%) showed significant differences. Yet, CV and interrater reliability measures indicated higher robustness. ComBat resulted in almost complete harmonization (>87%) according to Friedman test and little to no improvement according to CV and inter-rater reliability measures. [(18)FJGE-180 features were more sensitive to reconstruction settings than [(18)FJFET features.Conclusions: According to Friedman test, feature distributions could be successfully aligned using ComBat. However, depending on settings, changes in patient ranks were observed for some features and could not be eliminated by harmo-nization. Thus, for clinical utilization it is recommended to exclude affected features

Patient-specific image-based bone marrow dosimetry in Lu-177-[DOTA(0),Tyr(3)]-Octreotate and Lu-177-DKFZ-PSMA-617 therapy: investigation of a new hybrid image approach

Background: The bone marrow (BM) is a main organ at risk in Lu-177-PSMA-617 therapy of prostate cancer and Lu-177-Octreotate therapy of neuroendocrine tumours. BM dosimetry is challenging and time-consuming, as different sequential quantitative measurements must be combined. The BM absorbed dose from the remainder of the body (ROB) can be determined from sequential whole-body planar (WB-P) imaging, while quantitative Lu-177-SPECT allows for more robust tumour and organ absorbed doses. The aim was to investigate a time-efficient and patient-friendly hybrid protocol (HP) for the ROB absorbed dose to the BM. It combines three abdominal quantitative SPECT (QSPECT) scans with a single WB-P acquisition and was compared with a reference protocol (RP) using sequential WB-P in combination with sequential QSPECT images. We investigated five patients receiving 7. 4 GBq Lu-177-Octreotate and five patients treated with 3.7 GBq Lu-177-PSMA-617. Each patient had WB-P and abdominal SPECT acquisitions 24 (+ CT), 48, and 72 h post-injection. Blood samples were drawn 30 min, 80 min, 24 h, 48 h, and 72 h post-injection. BM absorbed doses from the ROB were estimated from sequential WB-P images (RP), via a mono-exponential fit and mass-scaled organ-level S values. For the HP, a mono-exponential fit on the QSPECT data was scaled with the activity of one WB-P image acquired either 24, 48, or 72 h post-injection (HP24, HP48, HP72). Total BM absorbed doses were determined as a sum of ROB, blood, major organ, and tumour contributions. Results: Compared with the RP and for Lu-177-Octreotate therapy, median differences of the total BM absorbed doses were 13% (9-17%), 8% (4-15%), and 1% (0-5%) for the HP24, HP48, and HP72, respectively. For Lu-177-PSMA-617 therapy, total BM absorbed doses deviated 10% (2-20%), 3% (0-6%), and 2% (0-6%). Conclusion: For both Lu-177-Octreotate and Lu-177-PSMA-617 therapy, BM dosimetry via sequential QSPECT imaging and a single WB-P acquisition is feasible, if this WB-P image is acquired at a late time point (48 or 72 h post-injection). The reliability of the HP can be well accepted considering the uncertainties of quantitative Lu-177 imaging and BM dosimetry using standardised organ-level S values

3D Monte Carlo bone marrow dosimetry for Lu-177-PSMA therapy with guidance of non-invasive 3D localization of active bone marrow via Tc-99m-anti-granulocyte antibody SPECT/CT

Background: The bone marrow (BM) is a main risk organ during Lu-177-PSMA ligand therapy of metastasized castration-resistant prostate cancer (mCRPC) patients. So far, BM dosimetry relies on S values, which are pre-computed for reference anatomies, simplified activity distributions, and a physiological BM distribution. However, mCRPC patients may show a considerable bone lesion load, which leads to a heterogeneous and patient-specific activity accumulation close to BM-bearing sites. Furthermore, the patient-specific BM distribution might be significantly altered in the presence of bone lesions. The aim was to perform BM absorbed dose calculations through Monte Carlo (MC) simulations and to investigate the potential value of image-based BM localization. This study is based on 11 Lu-177-PSMA-617 therapy cycles of 10 patients (10 first cycles), who obtained a pre-therapeutic Ga-68-PSMA-11 PET/CT; quantitative Lu-177 SPECT acquisitions of the abdomen 24 (+CT), 48, and 72 h p.i.; and a Lu-177 whole-body planar acquisition at 24 h post-therapy. Patient-specific 3D volumes of interest were segmented from the Ga-68-PSMA-11 PET/CT, filled with activity information from the Lu-177 data, and imported into the FLUKA MC code together with the patient CT. MC simulations of the BM absorbed dose were performed assuming a physiological BM distribution according to the ICRP 110 reference male (MC1) or a displacement of active BM from the direct location of bone lesions (MC2). Results were compared with those from S values (SMIRD). BM absorbed doses were correlated with the decrease of lymphocytes, total white blood cells, hemoglobin level, and platelets. For two patients, an additional pre-therapeutic Tc-99m-anti-granulocyte antibody SPECT/CT was performed for BM localization. Results: Median BM absorbed doses were 130, 37, and 11 mGy/GBq for MC1, MC2, and SMIRD, respectively. Significant strong correlation with the decrease of platelet counts was found, with highest correlation for MC2 (MC1: r = − 0.63, p = 0.04; MC2: r = − 0.71, p = 0.01; SMIRD: r = − 0.62, p = 0.04). For both investigated patients, BM localization via Tc-99m-anti-granulocyte antibody SPECT/CT indicated a displacement of active BM from the direct location of lesions similar to model MC2 and led to a reduction in the BM absorbed dose of 40 and 41% compared to MC1. Conclusion: Higher BM absorbed doses were observed for MC-based models; however, for MC2, all absorbed doses were still below 2 Gy. MC1 resulted in critical values for some patients, but is suspected to yield strongly exaggerated absorbed doses by neglecting bone marrow displacement. Image-based BM localization might be beneficial, and future studies are recommended to support an improvement for the prediction of hematoxicities

Voxel-wise analysis of dynamic F-18-FET PET: a novel approach for non-invasive glioma characterisation

Background: Glioma grading with dynamic F-18-FET PET (0-40 min p.i.) is typically performed by analysing the mean time-activity curve of the entire tumour or a suspicious area within a heterogeneous tumour. This work aimed to ensure a reader-independent glioma characterisation and identification of aggressive sub-volumes by performing a voxel-based analysis with diagnostically relevant kinetic and static 18F-FET PET parameters. One hundred sixty-two patients with a newly diagnosed glioma classified according to histologic and molecular genetic properties were evaluated. The biological tumour volume (BTV) was segmented in static 20-40 min p.i. F-18-FET PET images using the established threshold of 1.6 x background activity. For each enclosed voxel, the time-to-peak (TTP), the late slope (Slope(15-40)), and the tumour-to-background ratios (TBR5-15, TBR20-40) obtained from 5 to 15 min p.i. and 20 to 40 min p.i. images were determined. The percentage portion of these values within the BTV was evaluated with percentage volume fractions (PVFs) and cumulated percentage volume histograms (PVHs). The ability to differentiate histologic and molecular genetic classes was assessed and compared to volume-of-interest (VOI)-based parameters. Results: Aggressive WHO grades III and IV and IDH-wildtype gliomas were dominated by a high proportion of voxels with an early peak, negative slope, and high TBR, whereby the PVHs with TTP 2 yielded the most significant differences between glioma grades. We found significant differences of the parameters between WHO grades and IDH mutation status, where the effect size was predominantly higher for voxel-based PVHs compared to the corresponding VOI-based parameters. A low overlap of BTV sub-volumes defined by TTP ) (2)- and TBR20-40 (> 2)-defined hotspots was observed. Conclusions: The presented approach applying voxel-wise analysis of dynamic F-18-FET PET enables an enhanced characterisation of gliomas and might potentially provide a fast identification of aggressive sub-volumes within the BTV. Parametric 3D F-18-FET PET information as investigated in this study has the potential to guide individual therapy instrumentation and may be included in future biopsy studies

Effects of polygenic risk for major mental disorders and cross-disorder on cortical complexity

Background MRI-derived cortical folding measures are an indicator of largely genetically driven early developmental processes. However, the effects of genetic risk for major mental disorders on early brain development are not well understood. Methods We extracted cortical complexity values from structural MRI data of 580 healthy participants using the CAT12 toolbox. Polygenic risk scores (PRS) for schizophrenia, bipolar disorder, major depression, and cross-disorder (incorporating cumulative genetic risk for depression, schizophrenia, bipolar disorder, autism spectrum disorder, and attention-deficit hyperactivity disorder) were computed and used in separate general linear models with cortical complexity as the regressand. In brain regions that showed a significant association between polygenic risk for mental disorders and cortical complexity, volume of interest (VOI)/region of interest (ROI) analyses were conducted to investigate additional changes in their volume and cortical thickness. Results The PRS for depression was associated with cortical complexity in the right orbitofrontal cortex (right hemisphere: p = 0.006). A subsequent VOI/ROI analysis showed no association between polygenic risk for depression and either grey matter volume or cortical thickness. We found no associations between cortical complexity and polygenic risk for either schizophrenia, bipolar disorder or psychiatric cross-disorder when correcting for multiple testing. Conclusions Changes in cortical complexity associated with polygenic risk for depression might facilitate well-established volume changes in orbitofrontal cortices in depression. Despite the absence of psychopathology, changed cortical complexity that parallels polygenic risk for depression might also change reward systems, which are also structurally affected in patients with depressive syndrome

Interaction of developmental factors and ordinary stressful life events on brain structure in adults

An interplay of early environmental and genetic risk factors with recent stressful life events (SLEs) in adulthood increases the risk for adverse mental health outcomes. The interaction of early risk and current SLEs on brain structure has hardly been investigated. Whole brain voxel-based morphometry analysis was performed in N = 786 (64.6% female, mean age = 33.39) healthy subjects to identify correlations of brain clusters with commonplace recent SLEs. Genetic and early environmental risk factors, operationalized as those for severe psychopathology (i.e., polygenic scores for neuroticism, childhood maltreatment, urban upbringing and paternal age) were assessed as modulators of the impact of SLEs on the brain. SLEs were negatively correlated with grey matter volume in the left medial orbitofrontal cortex (mOFC, FWE p = 0.003). This association was present for both, positive and negative, life events. Cognitive-emotional variables, i.e., neuroticism, perceived stress, trait anxiety, intelligence, and current depressive symptoms did not account for the SLE-mOFC association. Further, genetic and environmental risk factors were not correlated with grey matter volume in the left mOFC cluster and did not affect the association between SLEs and left mOFC grey matter volume. The orbitofrontal cortex has been implicated in stress-related psychopathology, particularly major depression in previous studies. We find that SLEs are associated with this area. Important early life risk factors do not interact with current SLEs on brain morphology in healthy subjects