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

Quantitative performance and optimal regularization parameter in block sequential regularized expectation maximization reconstructions in clinical 68Ga-PSMA PET/MR.

BACKGROUND: In contrast to ordered subset expectation maximization (OSEM), block sequential regularized expectation maximization (BSREM) positron emission tomography (PET) reconstruction algorithms can run until full convergence while controlling image quality and noise. Recent studies with BSREM and F-FDG PET reported higher signal-to-noise ratios and higher standardized uptake values (SUV). In this study, we investigate the optimal regularization parameter (β) for clinical Ga-PSMA PET/MR reconstructions in the pelvic region applying time-of-flight (TOF) BSREM in comparison to TOF OSEM. Two-minute emission data from the pelvic region of 25 patients who underwent Ga-PSMA PET/MR were retrospectively reconstructed. Reference OSEM reconstructions had 28 subsets and 2 iterations. BSREM reconstructions were performed with 15 β values between 150 and 1200. Regions of interest (ROIs) were drawn around lesions and in uniform background. Background SUVmean (average) and SUVstd (standard deviation), and lesion SUVmax (average of 5 hottest voxels) were calculated. Differences were analyzed using the Wilcoxon matched pairs signed-rank test. RESULTS: A total of 40 lesions were identified in the pelvic region. Background noise (SUVstd) and lesions SUVmax decreased with increasing β. Image reconstructions with β values lower than 400 have higher (p < 0.01) background noise, compared to the reference OSEM reconstructions, and are therefore less useful. Lesions with low activity on images reconstructed with β values higher than 600 have a lower (p < 0.05) SUVmax compared to the reference. These reconstructions are likely visually appealing due to the lower background noise, but the lower SUVmax could possibly render small low-uptake lesions invisible. CONCLUSIONS: In our study, we showed that PET images reconstructed with TOF BSREM in combination with the Ga-PSMA tracer result in lower background noise and higher SUVmax values in lesions compared to TOF OSEM. Our study indicates that a β value between 400 and 550 might be the optimal compromise between high SUVmax and low background noise

Illuminating hydrological processes at the soil-vegetation-atmosphere interface with water stable isotopes

Funded by DFG research project “From Catchments as Organised Systems to Models based on Functional Units” (FOR 1Peer reviewedPublisher PDFPublisher PD

Focal unspecific bone uptake on [ 18 F]-PSMA-1007 PET: a multicenter retrospective evaluation of the distribution, frequency, and quantitative parameters of a potential pitfall in prostate cancer imaging

Purpose: Improved logistics and availability led to a rapid increase in the use of [18F]-PSMA-1007 for prostate cancer PET imaging. Initial data suggests increased uptake in benign lesions compared to [68 Ga]-PSMA-11, and clinical observations found increased unspecific bone uptake (UBU). We therefore investigate the frequency and characteristics of UBU in [18F]-PSMA-1007 PET. Methods: We retrospectively analyzed [18F]-PSMA-1007 PET scans from four centers for the presence of UBU, defined as a focal mild-to-moderate uptake (SUVmax < 10.0) not obviously related to a benign or malignant cause. If present, up to three leading UBUs were quantified (SUVmax), localized, and correlated to clinical parameters, such as age, PSA, injected dose, Gleason score, tumor size (T1-T4), and type of PET scanner (analog vs. digital). Additionally, clinical and imaging follow-up results and therapeutic impact were evaluated. Results: UBUs were identified in 179 out of 348 patients (51.4%). The most frequent localizations were ribs (57.5%) and pelvis (24.8%). The frequency of UBUs was not associated with PSA, Gleason score, tumor size, age, or the injected [18F]-PSMA-1007 dose. UBUs were significantly more frequent in images obtained with digital PET/CT scans (n = 74, 82%) than analog PET/CT scans (n = 221, 40.3%) (p = .0001) but not in digital PET/MR (n = 53, 51%) (p = .1599). In 80 out of 179 patients (44.7%), the interpretation of UBUs was critical for therapeutic management and therefore considered clinically relevant. For 65 UBUs, follow-ups were available: three biopsies, three radiotherapies with PSA follow-up, and 59 cases with imaging. After follow-up, UBUs were still considered unclear in 28 of 65 patients (43%), benign in 28 (43%), and malignant in nine (14%) patients. Conclusion: UBUs occur in two-thirds of patients imaged with [18F]-PSMA-1007 PET/CT and are significantly more frequent on digital PET scanners than analog scanners. UBUs should be interpreted carefully to avoid over-staging. Keywords: Bone metastasis; PET/CT; PET/MR; Restaging; Staging; [18F]-PSMA

Anatomical Grading for Metabolic Activity of Brown Adipose Tissue

BACKGROUND Recent advances in obesity research suggest that BAT activity, or absence thereof, may be an important factor in the growing epidemic of obesity and its manifold complications. It is thus important to assess larger populations for BAT-activating and deactivating factors. 18FDG-PET/CT is the standard method to detect and quantify metabolic BAT activity, however, the manual measurement is not suitable for large studies due to its time-consuming nature and poor reproducibility across different software and devices. METHODOLOGY/MAIN FINDINGS In a retrospective study, 1060 consecutive scans of 1031 patients receiving a diagnostic 18FDG-PET/CT were examined for the presence of active BAT. Patients were classified according to a 3-tier system (supraclavicular, mediastinal, infradiaphragmatic) depending on the anatomical location of their active BAT depots, with the most caudal location being the decisive factor. The metabolic parameters (maximum activity, total volume and total glycolysis) were measured on a standard PET/CT workstation. Mean age of the population was 60±14.6y. 41.61% of patients were female. Metabolically active BAT was found in 53 patients (5.1%). Female, younger and leaner patients tended to have more active BAT, higher metabolic activity and more caudally active BAT. In total, 15 patients showed only supraclavicular, 27 additional mediastinal, and 11 infradiaphragmal activity. Interestingly, the activation of BAT always followed a cranio-caudal gradient. This anatomical pattern correlated with age and BMI as well as with all metabolic parameters, including maximum and total glycolysis (p<0.001). CONCLUSION Based on our data we propose a simple method to grade or quantify the degree of BAT amount/activity in patients based on the most caudally activated depot. As new modalities for BAT visualization may arise in the future, this system would allow direct comparability with other modalities, in contrary to the PET-metrics, which are restricted to 18FDG-PET/CT

Brown fat does not cause cachexia in cancer patients: A large retrospective longitudinal FDG-PET/CT cohort study

BACKGROUND Brown adipose tissue (BAT) is a specialized form of adipose tissue, able to increase energy expenditure by heat generation in response to various stimuli. Recently, its pathological activation has been implicated in the pathogenesis of cancer cachexia. To establish a causal relationship, we retrospectively investigated the longitudinal changes in BAT and cancer in a large FDG-PET/CT cohort. METHODS We retrospectively analyzed 13 461 FDG-PET/CT examinations of n = 8 409 patients at our institution from the winter months of 2007-2015. We graded the activation strength of BAT based on the anatomical location of the most caudally activated BAT depot into three tiers, and the stage of the cancer into five general grades. We validated the cancer grading by an interreader analysis and correlation with histopathological stage. Ambient temperature data (seven-day average before the examination) was obtained from a meteorological station close to the hospital. Changes of BAT, cancer, body mass index (BMI) and temperature between the different examinations were examined with Spearman's test and a mixed linear model for correlation, and with a causal inference algorithm for causality. RESULTS We found n = 283 patients with at least two examinations and active BAT in at least one of them. There was no significant interaction between the changes in BAT activation, cancer burden or BMI. Temperature changes exhibited a strong negative correlation with BAT activity (ϱ = -0.57, p<0.00001). These results were confirmed with the mixed linear model. Causal inference revealed a link of Temperature ➜ BAT in all subjects and also of BMI ➜ BAT in subjects who had lost weight and increased cancer burden, but no role of cancer and no causal links of BAT ➜ BMI. CONCLUSIONS Our data did not confirm the hypothesis that BAT plays a major role in cancer-mediated weight loss. Temperature changes are the main driver of incidental BAT activity on FDG-PET scans

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

Integrierte Losgrößenoptimierung auf Basis einer Prozesskostenrechnung

In einer guten Kunden-Lieferanten-Beziehung, geprägt von einer Win-Win-Situation, wird die Festlegung der Bestell- und Produktionslosgröße häufig diskutiert. Um die kostenoptimale Lösung für das Gesamtsystem zu finden, ist ein ganzheitlicher Ansatz auf Prozesskostenbasis erforderlich. In diesem Beitrag wird ein integrierter Ansatz zur Bestimmung der optimalen Losgröße dargestellt, der basierend auf einer prozesskostenbasierten Berechnung noch weitere Parameter miteinbezieht

Hot needles can confirm accurate lesion sampling intraoperatively using [ 18 F]PSMA-1007 PET/CT-guided biopsy in patients with suspected prostate cancer

Purpose: Prostate-specific membrane antigen (PSMA)-targeted PET is increasingly used for staging prostate cancer (PCa) with high accuracy to detect significant PCa (sigPCa). [68 Ga]PSMA-11 PET/MRI-guided biopsy showed promising results but also persisting limitation of sampling error, due to impaired image fusion. We aimed to assess the possibility of intraoperative quantification of [18F]PSMA-1007 PET/CT uptake in core biopsies as an instant confirmation for accurate lesion sampling. Methods: In this IRB-approved, prospective, proof-of-concept study, we included five consecutive patients with suspected PCa. All underwent [18F]PSMA-1007 PET/CT scans followed by immediate PET/CT-guided and saturation template biopsy (3.1 ± 0.3 h after PET). The activity in biopsy cores was measured as counts per minute (cpm) in a gamma spectrometer. Pearson's test was used to correlate counts with histopathology (WHO/ISUP), tumor length, and membranous PSMA expression on immunohistochemistry (IHC). Results: In 43 of 113 needles, PCa was present. The mean cpm was overall significantly higher in needles with PCa (263 ± 396 cpm) compared to needles without PCa (73 ± 44 cpm, p < 0.001). In one patient with moderate PSMA uptake (SUVmax 8.7), 13 out of 24 needles had increased counts (100-200 cpm) but only signs of inflammation and PSMA expression in benign glands on IHC. Excluding this case, ROC analysis resulted in an AUC of 0.81, with an optimal cut-off to confirm PCa at 75 cpm (sens/spec of 65.1%/87%). In all 4 patients with PCa, the first or second PSMA PET-guided needle was positive for sigPCa with high counts (156-2079 cpm). Conclusions: [18F]PSMA-1007 uptake in PCa can be used to confirm accurate lesion sampling of the dominant tumor intraoperatively. This technique could improve confidence in imaging-based biopsy guidance and reduce the need for saturation biopsy. Trial registration number: NCT03187990, 15/06/2017. Keywords: Biopsy guidance; PSMA PET; Primary staging; Targeted biopsy; Template biopsy

Morphological differences in BAT activity.

<p>Morphological differences in BAT activity.</p