Reconstructed spatial resolution and contrast recovery with Bayesian penalized likelihood reconstruction (Q.Clear) for FDG-PET compared to time-of-flight (TOF) with point spread function (PSF)

BACKGROUND: Bayesian penalized likelihood reconstruction for PET (e.g., GE Q.Clear) aims at improving convergence of lesion activity while ensuring sufficient signal-to-noise ratio (SNR). This study evaluated reconstructed spatial resolution, maximum/peak contrast recovery (CRmax/CRpeak) and SNR of Q.Clear compared to time-of-flight (TOF) OSEM with and without point spread function (PSF) modeling. METHODS: The NEMA IEC Body phantom was scanned five times (3 min scan duration, 30 min between scans, background, 1.5-3.9 kBq/ml F18) with a GE Discovery MI PET/CT (3-ring detector) with spheres filled with 8-, 4-, or 2-fold the background activity concentration (SBR 8:1, 4:1, 2:1). Reconstruction included Q.Clear (beta, 150/300/450), "PSF+TOF4/16" (iterations, 4; subsets, 16; in-plane filter, 2.0 mm), "OSEM+TOF4/16" (identical parameters), "PSF+TOF2/17" (2 it, 17 ss, 2.0 mm filter), "OSEM+TOF2/17" (identical), "PSF+TOF4/8" (4 it, 8 ss, 6.4 mm), and "OSEM+TOF2/8" (2 it, 8 ss, 6.4 mm). Spatial resolution was derived from 3D sphere activity profiles. RC as (sphere activity concentration [AC]/true AC). SNR as (background mean AC/background AC standard deviation). RESULTS: Spatial resolution of Q.Clear150 was significantly better than all conventional algorithms at SBR 8:1 and 4:1 (Wilcoxon, each p < 0.05). At SBR 4:1 and 2:1, the spatial resolution of Q.Clear300/450 was similar or inferior to PSF+TOF4/16 and OSEM+TOF4/16. Small sphere CRpeak generally underestimated true AC, and it was similar for Q.Clear150/300/450 as with PSF+TOF4/16 or PSF+TOF2/17 (i.e., relative differences < 10%). Q.Clear provided similar or higher CRpeak as OSEM+TOF4/16 and OSEM+TOF2/17 resulting in a consistently better tradeoff between CRpeak and SNR with Q.Clear. Compared to PSF+TOF4/8/OSEM+TOF2/8, Q.Clear150/300/450 showed lower SNR but higher CRpeak. CONCLUSIONS: Q.Clear consistently improved reconstructed spatial resolution at high and medium SBR compared to PSF+TOF and OSEM+TOF, but only with beta = 150. However, this is at the cost of inferior SNR with Q.Clear150 compared to Q.Clear300/450 and PSF+TOF4/16/PSF+TOF2/17 while CRpeak for the small spheres did not improve considerably. This suggests that Q.Clear300/450 may be advantageous for the 3-ring detector configuration because the tradeoff between CR and SNR with Q.Clear300/450 was superior to PSF+TOF4/16, OSEM+TOF4/16, and OSEM+TOF2/17. However, it requires validation by systematic evaluation in patients at different activity and acquisition protocols

Evaluation of T1 relaxation time in prostate cancer and benign prostate tissue using a Modified Look-Locker inversion recovery sequence

Purpose of this study was to evaluate the diagnostic performance of T1 relaxation time (T1) for differentiating prostate cancer (PCa) from benign tissue as well as high- from low-grade PCa. Twenty-three patients with suspicion for PCa were included in this prospective study. 3 T MRI including a Modified Look-Locker inversion recovery sequence was acquired. Subsequent targeted and systematic prostate biopsy served as a reference standard. T1 and apparent diffusion coefficient (ADC) value in PCa and reference regions without malignancy as well as high- and low-grade PCa were compared using the Mann-Whitney U test. The performance of T1, ADC value, and a combination of both to differentiate PCa and reference regions was assessed by receiver operating characteristic (ROC) analysis. T1 and ADC value were lower in PCa compared to reference regions in the peripheral and transition zone (p < 0.001). ROC analysis revealed high AUCs for T1 (0.92; 95%-CI, 0.87-0.98) and ADC value (0.97; 95%-CI, 0.94 to 1.0) when differentiating PCa and reference regions. A combination of T1 and ADC value yielded an even higher AUC. The difference was statistically significant comparing it to the AUC for ADC value alone (p = 0.02). No significant differences were found between high- and low-grade PCa for T1 (p = 0.31) and ADC value (p = 0.8). T1 relaxation time differs significantly between PCa and benign prostate tissue with lower T1 in PCa. It could represent an imaging biomarker for PCa

Prognostic Value of the Largest Lesion Size for Progression-Free Survival in Patients with NET Undergoing Salvage PRRT with [177Lu]Lu-DOTATOC

Simple Summary: Peptide receptor radionuclide therapy (PRRT) using radionuclide-labeled somatostatin analogues is based on the overexpression of somatostatin receptors on neuroendocrine tumors and is shown to have a good safety profile and efficacy in different types of metastatic neuroendocrine tumors. As this therapy is usually not curative, most patients experience disease progression after initial PRRT. In these cases, retreatment with PRRT, also called salvage PRRT, can be a treatment option, but little is known about the efficacy and possible risk factors. In this retrospective study that included 32 patients, we found that the size of the largest lesion is a significant predictor of disease progression after salvage PRRT. This risk factor is easy to obtain and can help identify patients who may benefit from intensified follow-up strategies. Abstract: (1) Background: retreatment with radionuclide-labeled somatostatin analogues following disease progression after initial treatment cycles is often referred to as salvage peptide receptor radionuclide therapy (salvage PRRT). Salvage PRRT is shown to have a favorable safety profile in patients with metastatic neuroendocrine tumors (NETs), but numerous questions about the efficacy and prognostic or predictive factors remain to be answered. The purpose of this study was to evaluate two parameters that have shown prognostic significance in progression-free survival (PFS) in initial PRRT treatment, namely the size of the largest lesion (LLS) and the De Ritis ratio (aspartate aminotransferase (AST)/alanine aminotransferase (ALT)), as prognostic factors in the context of salvage PRRT. In addition, the PFS after initial PRRT was evaluated as a predictor of the PFS following salvage PRRT. (2) Methods: retrospective, monocentric analysis in 32 patients with NETs (gastroenteropancreatic, 23; unknown primary, 7; kidney, 1; lung, 1) and progression after initial PRRT undergoing retreatment with [Lu-177]Lu-DOTATOC. The prognostic values of LLS, the De Ritis ratio, and PFS after initial treatment cycles regarding PFS following salvage PRRT were evaluated with univariable and multivariable Cox regression. PFS was defined as the time from treatment start until tumor progression according to RECIST 1.1 criteria, death from any cause or start of a new treatment due to progression of cancer-related symptoms (namely carcinoid syndrome). (3) Results: progression after salvage PRRT was observed in 29 of 32 patients with median PFS of 10.8 months (95% confidence interval (CI), 8.0-15.9 months). A higher LLS (hazard ratio (HR): 1.03; p = 0.002) and a higher De Ritis ratio (HR: 2.64; p = 0.047) were associated with shorter PFS after salvage PRRT in univariable Cox regression. PFS after initial PRRT was not associated with PFS following salvage PRRT. In multivariable Cox regression, only LLS remained a significant predictor. (4) Conclusions: the size of the largest lesion is easy to obtain and might help identify patients at risk of early disease progression after salvage PRRT. Validation is required

Intermediate-term outcome after PSMA-PET guided high-dose radiotherapy of recurrent high-risk prostate cancer patients

Background By the use of PSMA positron emission tomography (PET) detection of prostate cancer lesions with a high sensitivity and specificity combined with a favorable lesion to background contrast is feasible. Therefore, PSMA-PET is increasingly used for planning of radiotherapy treatment; however, any data on intermediate-term outcome is missing so far. Methods Patients with high-risk or very high risk prostate cancer, referred for salvage radiotherapy (SRT, n = 22) between 2013 and 2015, underwent PSMA-PET prior to therapy. Irradiation was planned on PET data with boost to macroscopic tumors/metastases. Treatment related toxicity was measured using Common Terminology Criteria for Adverse Events (CTCAE, v4.0). Result Findings in PSMA-PET led to treatment modifications in 77% of SRT patients compared to available CT information. One patient did not receive irradiation due to disseminated disease, the other patients received increased boost doses to macroscopic disease and/or inclusion of additional target volumes. Toxicity was low as only 2 patients reported toxicities > grade 1. With a Median follow-up time of 29 in patients that were not lost to follow-up, prolonged PSA responses below baseline were observed in the majority of patients (14 of 20). In hormone-naïve SRT patients (n = 11), radiotherapy led to prolonged PSA decrease in 8/11 patients, however with 3 of these 8 patients receiving repeated PSMA based irradiation of novel lesions during follow-up. Conclusion PSMA-PET guided planning of radiotherapy led to change of treatment in the majority of patients. Treatment related toxicity was well tolerated and promising results regarding intermediate-term PSA decrease were observed. Trial registration No trial registration was performed due to retrospective evaluation

The association of intra-therapeutic heterogeneity of somatostatin receptor expression with morphological treatment response in patients undergoing PRRT with [177Lu]-DOTATATE

AIM: Purpose of this study was to evaluate the association of the spatial heterogeneity (asphericity, ASP) in intra-therapeutic SPECT/ CT imaging of somatostatin receptor (SSR) positive metastatic gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) for morphological treatment response to peptide receptor radionuclide therapy (PRRT). Secondly, we correlated ASP derived form a pre-therapeutic OctreoScan (ASP[In]) and an intra-therapeutic [177Lu]-SPECT/CT (ASP[Lu]). MATERIALS AND METHODS: Data from first therapy cycle [177Lu-DOTA0-Tyr3]octreotate ([177Lu]-DOTATATE)-PRRT was retrospectively analyzed in 33 patients (m = 20; w = 13; median age, 72 [46-88] years). The evaluation of response to PRRT was performed according to RECIST 1.1 in responding lesions [RL (SD, PR, CR), n = 104] and non-responding lesions [NRL (PD), n = 27]. The association of SSR tumor heterogeneity with morphological response was evaluated by Kruskal-Wallis test and receiver operating characteristic curve (ROC). The optimal threshold for separation (RL vs. NRL) was calculated using the Youden-index. Relationship between pre- and intra-therapeutic ASP was determined with Spearman's rank correlation coefficient (ρ) and Bland-Altman plots. RESULTS: A total of 131 lesions (liver: n = 59, lymph nodes: n = 48, bone: n = 19, pancreas: n = 5) were analyzed. Lesions with higher ASP values showed a significantly poorer response to PRRT (PD, median: 11.3, IQR: 8.5-15.5; SD, median: 3.4, IQR: 2.1-4.5; PR, median 1.7, IQR: 0.9-2.8; CR, median: 0.5, IQR: 0.0-1.3); Kruskal-Wallis, p5.45% (sensitivity 96% and specificity 82%). The correlation coefficient of pre- and intra-therapeutic ASP revealed ρ = 0.72 (p <0.01). The mean absolute difference between ASP[In] and ASP[Lu] was -0.04 (95% Limits of Agreement, -6.1-6.0). CONCLUSION: Pre- and intra-therapeutic ASP shows a strong correlation and might be an useful tool for therapy monitoring

Inferring FDG-PET-positivity of lymph node metastases in proven lung cancer from contrast-enhanced CT using radiomics and machine learning

Background: We evaluated the role of radiomics applied to contrast-enhanced computed tomography (CT) in the detection of lymph node (LN) metastases in patients with known lung cancer compared to 18F-fluorodeoxyglucose positron emission tomography (PET)/CT as a reference. Methods: This retrospective analysis included 381 patients with 1,799 lymph nodes (450 malignant, 1,349 negative). The data set was divided into a training and validation set. A radiomics analysis with 4 filters and 6 algorithms resulting in 24 different radiomics signatures and a bootstrap algorithm (Bagging) with 30 bootstrap iterations was performed. A decision curve analysis was applied to generate a net benefit to compare the radiomics signature to two expert radiologists as one-by-one and as a prescreening tool in combination with the respective radiologist and only the radiologists. Results: All 24 modeling methods showed good and reliable discrimination for malignant/benign LNs (area under the curve 0.75-0.87). The decision curve analysis showed a net benefit for the least absolute shrinkage and selection operator (LASSO) classifier for the entire probability range and outperformed the expert radiologists except for the high probability range. Using the radiomics signature as a prescreening tool for the radiologists did not improve net benefit. Conclusions: Radiomics showed good discrimination power irrespective of the modeling technique in detecting LN metastases in patients with known lung cancer. The LASSO classifier was a suitable diagnostic tool and even outperformed the expert radiologists, except for high probabilities. Radiomics failed to improve clinical benefit as a prescreening tool

PET measured hypoxia and MRI parameters in re-irradiated head and neck squamous cell carcinomas: findings of a prospective pilot study [version 2; peer review: 2 approved]

Background: Tumor hypoxia measured by dedicated tracers like [ 18F]fluoromisonidazole (FMISO) is a well-established prognostic factor in head and neck squamous cell carcinomas (HNSCC) treated with definitive chemoradiation (CRT). However, prevalence and characteristics of positron emission tomography (PET) measured hypoxia in patients with relapse after previous irradiation is missing. Here we report imaging findings of a prospective pilot study in HNSCC patients treated with re-irradiation. Methods: In 8 patients with recurrent HNSCC, diagnosed at a median of 18 months after initial radiotherapy/CRT, [ 18F]fluorodeoxyglucose (FDG)-PET/CT (n=8) and FMISO-PET/MRI (n=7) or FMISO-PET/CT (n=1) were performed. Static FMISO-PET was performed after 180 min. MRI sequences in PET/MRI included diffusion-weighted imaging with apparent diffusion coefficient (ADC) values and contrast enhanced T1w imaging (StarVIBE). Lesions (primary tumor recurrence, 4; cervical lymph node, 1; both, 3) were delineated on FDG-PET and FMISO-PET data using a background-adapted threshold-based method. SUV max and SUV mean in FDG- and FMISO-PET were derived, as well as maximum tumor-to-muscle ratio (TMR max) and hypoxic volume with 1.6-fold muscle SUV mean (HV 1.6) in FMISO-PET. Intensity of lesional contrast enhancement was rated relative to contralateral normal tissue. Average ADC values were derived from a 2D region of interest in the tumor. Results: In FMISO-PET, median TMR max was 1.7 (range: 1.1-1.8). Median HV 1.6 was 0.05 ml (range: 0-7.3 ml). Only in 2/8 patients, HV 1.6 was ≥1.0 ml. In FDG-PET, median SUV max was 9.3 (range: 5.0-20.1). On contrast enhanced imaging four lesions showed decreased and four lesions increased contrast enhancement compared to non-pathologic reference tissue. Median average ADC was 1,060 ×10 6 mm 2/s (range: 840-1,400 ×10 6 mm 2/s). Conclusions: This pilot study implies that hypoxia detectable by FMISO-PET may not be as prevalent as expected among loco-regional recurrent, HPV negative HNSCC. ADC values were only mildly reduced, and contrast enhancement was variable. The results require confirmation in larger sample sizes

Quantitative assessment of the asphericity of pretherapeutic FDG uptake as an independent predictor of outcome in NSCLC

Background The aim of the present study was to evaluate the predictive value of a novel quantitative measure for the spatial heterogeneity of FDG uptake, the asphericity (ASP) in patients with non-small cell lung cancer (NSCLC). Methods FDG-PET/CT had been performed in 60 patients (15 women, 45 men; median age, 65.5 years) with newly diagnosed NSCLC prior to therapy. The FDG-PET image of the primary tumor was segmented using the ROVER 3D segmentation tool based on thresholding at the volume-reproducing intensity threshold after subtraction of local background. ASP was defined as the relative deviation of the tumor’s shape from a sphere. Univariate and multivariate Cox regression as well as Kaplan-Meier (KM) analysis and log-rank test with respect to overall (OAS) and progression-free survival (PFS) were performed for clinical variables, SUVmax/mean, metabolically active tumor volume (MTV), total lesion glycolysis (TLG), ASP and “solidity”, another measure of shape irregularity. Results ASP, solidity and “primary surgical treatment” were significant independent predictors of PFS in multivariate Cox regression with binarized parameters (HR, 3.66; p < 0.001, HR, 2.11; p = 0.05 and HR, 2.09; p = 0.05), ASP and “primary surgical treatment” of OAS (HR, 3.19; p = 0.02 and HR, 3.78; p = 0.01, respectively). None of the other semi-quantitative PET parameters showed significant predictive value with respect to OAS or PFS. Kaplan-Meier analysis revealed a probability of 2-year PFS of 52% in patients with low ASP compared to 12% in patients with high ASP (p < 0.001). Furthermore, it showed a higher OAS rate in the case of low versus high ASP (1-year-OAS, 91% vs. 67%: p = 0.02). Conclusions The novel parameter asphericity of pretherapeutic FDG uptake seems to provide better prognostic value for PFS and OAS in NCSLC compared to SUV, metabolic tumor volume, total lesion glycolysis and solidity

Diffusion-weighted magnetic resonance imaging using a preclinical 1 T PET/MRI in healthy and tumor-bearing rats

Background: Hybrid positron emission tomography and magnetic resonance imaging (PET/MRI) scanners are increasingly used for both clinical and preclinical imaging. Especially functional MRI sequences such as diffusionweighted imaging (DWI) are of great interest as they provide information on a molecular level, thus, can be used as surrogate biomarkers. Due to technical restrictions, MR sequences need to be adapted for each system to perform reliable imaging. There is, to our knowledge, no suitable DWI protocol for 1 Tesla PET/MRI scanners. We aimed to establish such DWI protocol with focus on the choice of b values, suitable for longitudinal monitoring of tumor characteristics in a rat liver tumor model. Material and methods: DWI was first performed in 18 healthy rat livers using the scanner-dependent maximum of 4 b values (0, 100, 200, 300 s/mm2). Apparent diffusion coefficients (ADC) were calculated from different b value combinations and compared to the reference measurement with four b values. T2-weighted MRI and optimized DWI with best agreement between accuracy, scanning time, and system performance stability were used to monitor orthotopic hepatocellular carcinomas (HCC) in five rats of which three underwent additional 2-deoxy-2-(18F)fluoro-D-glucose(FDG)-PET imaging. ADCs were calculated for the tumor and the surrounding liver parenchyma and verified by histopathological analysis. Results: Compared to the reference measurements, the combination b = 0, 200, 300 s/mm2 showed the highest correlation coefficient (rs = 0.92) and agreement while reducing the acquisition time. However, measurements with less than four b values yielded significantly higher ADCs (p < 0.001). When monitoring the HCC, an expected drop of the ADC was observed over time. These findings were paralleled by FDG-PET showing both an increase in tumor size and uptake heterogeneity. Interestingly, surrounding liver parenchyma also showed a change in ADC values revealing varying levels of inflammation by immunohistochemistry. Conclusion: We established a respiratory-gated DWI protocol for a preclinical 1 T PET/MRI scanner allowing to monitor growth-related changes in ADC values of orthotopic HCC liver tumors. By monitoring the changes in tumor ADCs over time, different cellular stages were described. However, each study needs to adapt the protocol further according to their question to generate best possible results