Variability of Manual Segmentation of the Prostate in Axial T2-weighted MRI: A Multi-Reader Study

Purpose To evaluate the interreader variability in prostate and seminal vesicle (SV) segmentation on T2w MRI. Methods Six readers segmented the peripheral zone (PZ), transitional zone (TZ) and SV slice-wise on axial T2w prostate MRI examinations of n = 80 patients. Twenty different similarity scores, including dice score (DS), Hausdorff distance (HD) and volumetric similarity coefficient (VS), were computed with the VISCERAL EvaluateSegmentation software for all structures combined and separately for the whole gland (WG = PZ + TZ), TZ and SV. Differences between base, midgland and apex were evaluated with DS slice-wise. Descriptive statistics for similarity scores were computed. Wilcoxon testing to evaluate differences of DS, HD and VS was performed. Results Overall segmentation variability was good with a mean DS of 0.859 (±SD = 0.0542), HD of 36.6 (±34.9 voxels) and VS of 0.926 (±0.065). The WG showed a DS, HD and VS of 0.738 (±0.144), 36.2 (±35.6 vx) and 0.853 (±0.143), respectively. The TZ showed generally lower variability with a DS of 0.738 (±0.144), HD of 24.8 (±16 vx) and VS of 0.908 (±0.126). The lowest variability was found for the SV with DS of 0.884 (±0.0407), HD of 17 (±10.9 vx) and VS of 0.936 (±0.0509). We found a markedly lower DS of the segmentations in the apex (0.85 ± 0.12) compared to the base (0.87 ± 0.10, p < 0.01) and the midgland (0.89 ± 0.10, p < 0.001). Conclusions We report baseline values for interreader variability of prostate and SV segmentation on T2w MRI. Variability was highest in the apex, lower in the base, and lowest in the midgland

Quantitative imaging parameters to predict the local staging of prostate cancer in intermediate- to high-risk patients

Objectives: PSMA PET/MRI showed the potential to increase the sensitivity for extraprostatic disease (EPD) assessment over mpMRI; however, the interreader variability for EPD is still high. Therefore, we aimed to assess whether quantitative PSMA and mpMRI imaging parameters could yield a more robust EPD prediction. Methods: We retrospectively evaluated PCa patients who underwent staging mpMRI and [68Ga]PSMA-PET, followed by radical prostatectomy at our institution between 01.02.2016 and 31.07.2019. Fifty-eight cases with PET/MRI and 15 cases with PET/CT were identified. EPD was determined on histopathology and correlated with quantitative PSMA and mpMRI parameters assessed by two readers: ADC (mm2/1000 s), longest capsular contact (LCC, mm), tumor volume (cm3), PSMA-SUVmax and volume-based parameters using a fixed threshold at SUV > 4 to delineate PSMAtotal (g/ml) and PSMAvol (cm3). The t test was used to compare means, Pearson's test for categorical correlation, and ROC curve to determine the best cutoff. Interclass correlation (ICC) was performed for interreader agreement (95% CI). Results: Seventy-three patients were included (64.5 ± 6.0 years; PSA 14.4 ± 17.1 ng/ml), and 31 had EPD (42.5%). From mpMRI, only LCC reached significance (p = 0.005), while both volume-based PET parameters PSMAtotal and PSMAvol were significantly associated with EPD (p = 0.008 and p = 0.004, respectively). On ROC analysis, LCC, PSMAtotal, and PSMAvol reached an AUC of 0.712 (p = 0.002), 0.709 (p = 0.002), and 0.718 (p = 0.002), respectively. ICC was moderate-good for LCC 0.727 (0.565-0.828) and excellent for PSMAtotal and PSMAvol with 0.944 (0.990-0.996) and 0.985 (0.976-0.991), respectively. Conclusions: Quantitative PSMA parameters have a similar potential as mpMRI LCC to predict EPD of PCa, with a significantly higher interreader agreement. Keywords: Extracapsular extension; PSMA PET (MRI) Prostate cancer; Prediction; Seminal vesicle infiltration

Whole-body hybrid positron emission tomography imaging yields clinically relevant information in the staging and restaging of sinonasal tumors

BACKGROUND Whole-body hybrid positron emission tomography (PET) imaging is increasingly used for sinonasal tumors. However, only empirical data exist on the additional, clinically relevant information derived from these techniques. METHODS This study included 96 regionalized magnetic resonance imaging (MRI) of the sinonasal tract/neck and separate hybrid FDG-PET/CT or FDG-PET/MRI in 74 patients. Additional radiological information (ARI) obtained from each hybrid examination was analyzed and its clinically relevance was determined. Clinically relevant information (CRI) was categorized with regard to primary tumor site, regional lymph node metastases, distant metastases, second primary tumors, and non-neoplastic findings. RESULTS A total of 45/96 (46.9%) hybrid PET examinations revealed ARI. CRI was found in 32/96 (33.3%) examinations and concerned the primary tumor site (6.1%), regional lymph node metastases (4.1%), distant metastases (14.3%), second primary tumors (7.3%), and non-neoplastic findings (5.1%). CONCLUSIONS Hybrid PET imaging yields additional radiological information translating into clinically relevant information in a substantial proportion of patients with sinonasal tumors

Impact of time-of-flight PET on quantification accuracy and lesion detection in simultaneous F-choline PET/MRI for prostate cancer

BACKGROUND Accurate attenuation correction (AC) is an inherent problem of positron emission tomography magnetic resonance imaging (PET/MRI) systems. Simulation studies showed that time-of-flight (TOF) detectors can reduce PET quantification errors in MRI-based AC. However, its impact on lesion detection in a clinical setting with F-choline has not yet been evaluated. Therefore, we compared TOF and non-TOF F-choline PET for absolute and relative difference in standard uptake values (SUV) and investigated the detection rate of metastases in prostate cancer patients. RESULTS Non-TOF SUV was significantly lower compared to TOF in all osseous structures, except the skull, in primary lesions of the prostate, and in pelvic nodal and osseous metastasis. Concerning lymph node metastases, both experienced readers detected 16/19 (84%) on TOF PET, whereas on non-TOF PET readers 1 and 2 detected 11 (58%), and 14 (73%), respectively. With TOF PET readers 1 and 2 detected 14/15 (93%) and 11/15 (73%) bone metastases, respectively, whereas detection rate with non-TOF PET was 73% (11/15) for reader 1 and 53% (8/15) for reader 2. The interreader agreement was good for osseous metastasis detection on TOF (kappa 0.636, 95% confidence interval [CI] 0.453-0.810) and moderate on non-TOF (kappa = 0.600, CI 0.438-0.780). CONCLUSION TOF reconstruction for F-choline PET/MRI shows higher SUV measurements compared to non-TOF reconstructions in physiological osseous structures as well as pelvic malignancies. Our results suggest that addition of TOF information has a positive impact on lesion detection rate for lymph node and bone metastasis in prostate cancer patients

The central zone has increased Ga-PSMA-11 uptake: "Mickey Mouse ears" can be hot on Ga-PSMA-11 PET

PURPOSE Given the good correlation between PSMA expression and intraglandular tumour aggressiveness based on immunohistochemistry, there is increasing interest in Ga-PSMA-11 PET/MRI for staging prostate cancer (PCA). Therefore, accurate knowledge of prostate anatomy as well as normal distribution of PSMA within the prostate gland is becoming essential. The aim of this study was to investigate the physiological intraprostatic distribution of Ga-PSMA-11. METHODS We retrospectively analysed all patients who underwent a staging Ga-PSMA-11 PET/MRI scan between June 2016 and January 2018 for high-risk PCA, underwent radical prostatectomy in our institution, and gave written consent for further data analysis. In each patient, standardized volumes of interest (VOIs) were placed bilaterally in the central, transition and peripheral zones within the zonal anatomy according to T2 weighted sequences in the axial and coronal planes. VOIs were only placed if they were safely within healthy tissue without spillover from the PCA. SUV and SUV were determined and their differences among the regions were assessed using the Wilcoxon signed-ranks test. RESULTS Of 283 consecutive patients scanned with Ga-PSMA-11 PET/MR, 31 were analysed. A total of 133 VOIs were placed, 46 in the central zone, 41 in the transition zone and 46 in the peripheral zone. Differences in SUV between the central zone (mean 3.9 ± 0.58) and transition zone (mean 3.2 ± 0.59) and between the central zone and peripheral zone (mean 2.7 ± 0.54) were statistically significant (both p < 0.001). CONCLUSION Our results suggest that higher Ga-PSMA-11 accumulation in the central zone than in the transition and peripheral zones is normal, and leads to a pattern resembling "Mickey Mouse ears" on Ga-PSMA-11 PET. This pattern could be helpful in avoiding false-positive interpretations of PET scans

First clinico-pathological evidence of a non PSMA-related uptake mechanism for 68Ga-PSMA-11 in salivary glands

The intense accumulation of PSMA radioligands in salivary glands is still not well understood. It is of concern for therapeutic applications of PSMA radioligands, as therapeutic radiation will damage these glands. A better understanding of the uptake mechanism is, therefore, crucial to allow the finding of solutions to reduce toxicity. The aim of this study was to investigate on whether or not the accumulation of PSMA-targeting radioligands in submandibular glands (SMG) can be explained with PSMA expression levels using the methods of autoradiography (ARG) and immunohistochemistry (IHC). Methods: All patients gave written informed consent for further utility of the biological material. SMG of 9 patients, pancreatic tissue of 4 patients and prostate cancer (PCA) lesions of 9 patients were analyzed. Fresh tissue specimen were analyzed by means of PSMA-IHC (using an anti-PSMA-antibody and an immunoreactivity score system - IRS) and ARG using 177Lu-PSMA-617 (with quantification of the relative signal intensity compared to a PSMA-positive standard). The SUVmax in salivary glands, pancreas and PCA tissues were quantified in 60 clinical 68Ga-PSMA-11 PET scans for recurrent disease, as well as the 9 primary tumors selected for ARG and IHC. Results: PCA tissue samples revealed a wide range of PSMA staining intensity on IHC (IRS 70–300) as well as in ARG (1.33 – 21.98%). This variability on PCA tissue could also be observed in 68Ga-PSMA-11 PET (SUVmax 4.4-16) with a significant correlation between ARG and SUVmax (P < 0.001, R2 = 0.897). On IHC, ARG and 68Ga-PSMA-11 PET, the pancreatic tissue was negative (IRS = 0, ARG = 0.1±0.05%, SUVmax of 3.1±1.1). The SMG tissue displayed only focal expression of PSMA limited to the intercalated ducts on IHC (IRS 10-15) and a minimal signal on ARG (1.3±0.9%). In contrast, all SMG showed a high 68Ga-PSMA-11 accumulation on PET scans (SUVmax 23.5±5.2). Conclusion: Our results indicate that the high accumulation of PSMA radioligands in salivary glands does not correspond to a high PSMA expression levels determined using ARG and IHC. These findings provide evidence, that the significant accumulation of PSMA radioligands in SMG is not primarily a result of PSMA-mediated uptake

Association between resting amygdalar activity and abnormal cardiac function in women and men: a retrospective cohort study

AIMS Cardiovascular outcomes of women with coronary artery disease (CAD) are perceived as relatively worse when compared to men. Amygdalar metabolic activity has recently been shown to independently predict cardiovascular events in patients without known cardiovascular disease. Given that traditional algorithms for risk prediction perform worse in women than in men, we sought to assess sex-specific associations between amygdalar metabolic activity and cardiac dysfunction with suspected or known CAD. METHODS AND RESULTS This retrospective study included 302 patients (mean age 66.8 ± 10.2 years, 29.1% women) selected for evaluation of CAD, malignant, or inflammatory disease. All patients had undergone both, myocardial perfusion imaging by single photon emission computed tomography (MPI-SPECT) and whole-body fluoro-18-deoxyglucose (18F-FDG) positron emission tomography (PET), within 6 months. 18F-FDG resting amygdalar uptake was significantly increased in women with abnormal MPI scans (standardized uptake value 33.4 ± 6.5 vs. 30.4 ± 4.7, P = 0.043), while no such difference was observed in men (P = 0.808). In women, but not in men, a negative association between 18F-FDG resting amygdalar activity and left ventricular ejection fraction (LVEF) was observed (Pearson r = -0.308, P = 0.004). Accordingly, either LVEF [B-coefficient (standard error, SE) = -0.232 (0.109), P = 0.045] or abnormal MPI [B-coefficient (SE) = 8.264 (2.449), P = 0.003] were selected as significant predictors of high amygdalar 18F-FDG uptake in a fully adjusted linear regression model in women, and a first order interaction term consisting of sex and LVEF or sex and abnormal MPI was significant (P = 0.035 and P = 0.001, respectively). CONCLUSION Resting amygdalar metabolic activity is associated with abnormal cardiac function and perfusion in women, suggesting a link between emotional stress and cardiovascular disease in women

Metabolic Activity in Central Neural Structures of Patients With Myocardial Injury

Background Increasing evidence suggests a psychosomatic link between neural systems and the heart. In light of the growing burden of ischemic cardiovascular disease across the globe, a better understanding of heart-brain interactions and their implications for cardiovascular treatment strategies is needed. Thus, we sought to investigate the interaction between myocardial injury and metabolic alterations in central neural areas in patients with suspected or known coronary artery disease. Methods and Results The association between resting metabolic activity in distinct neural structures and cardiac function was analyzed in 302 patients (aged 66.8±10.2 years; 70.9% men) undergoing fluor-18-deoxyglucose positron emission tomography and 99mTc-tetrofosmin single-photon emission computed tomography myocardial perfusion imaging. There was evidence for reduction of callosal, caudate, and brainstem fluor-18-deoxyglucose uptake in patients with impaired left ventricular ejection fraction (<55% versus ≥55%: P=0.047, P=0.022, and P=0.013, respectively) and/or in the presence of myocardial ischemia (versus normal perfusion: P=0.010, P=0.013, and P=0.016, respectively). In a sex-stratified analysis, these differences were observed in men, but not in women. A first-order interaction term consisting of sex and impaired left ventricular ejection fraction or myocardial ischemia was identified as predictor of metabolic activity in these neural regions (left ventricular ejection fraction: P=0.015 for brainstem; myocardial ischemia: P=0.004, P=0.018, and P=0.003 for callosal, caudate, or brainstem metabolism, respectively). Conclusions Myocardial dysfunction and injury are associated with reduced resting metabolic activity of central neural structures, including the corpus callosum, the caudate nucleus, and the brainstem. These associations differ in women and men, suggesting sex differences in the pathophysiological interplay of the nervous and cardiovascular systems