BSREM for Brain Metastasis Detection with 18F-FDG-PET/CT in Lung Cancer Patients.

The aim of the study was to analyze the use of block sequential regularized expectation maximization (BSREM) with different ß-values for the detection of brain metastases in digital fluorine-18 labeled 2-deoxy-2-fluoro-D-glucose (18F-FDG) PET/CT in lung cancer patients. We retrospectively analyzed staging/restaging 18F-FDG PET/CT scans of 40 consecutive lung cancer patients with new brain metastases, confirmed by MRI. PET images were reconstructed using BSREM (ß-values of 100, 200, 300, 400, 500, 600, 700) and OSEM. Two independent blinded readers (R1 and R2) evaluated each reconstruction using a 4-point scale for general image quality, noise, and lesion detectability. SUVmax of metastases, brain background, target-to-background ratio (TBR), and contrast recovery (CR) ratio were recorded for each reconstruction. Among all reconstruction techniques, differences in qualitative parameters were analyzed using non-parametric Friedman test, while differences in quantitative parameters were compared using analysis of variances for repeated measures. Cohen's kappa (k) was used to measure inter-reader agreement. The overall detectability of brain metastases was highest for BSREM200 (R1: 2.83 ± 1.17; R2: 2.68 ± 1.32) and BSREM300 (R1: 2.78 ± 1.23; R2: 2.68 ± 1.36), followed by BSREM100, which had lower accuracy owing to noise. The highest median TBR was found for BSREM100 (R1: 2.19 ± 1.05; R2: 2.42 ± 1.08), followed by BSREM200 and BSREM300. Image quality ratings were significantly different among reconstructions (p < 0.001). The median quality score was higher for BSREM100-300, and both noise and metastases' SUVmax decreased with increasing ß-value. Inter-reader agreement was particularly high for the detectability of photopenic metastases and blurring (all k > 0.65). BSREM200 and BSREM300 yielded the best results for the detection of brain metastases, surpassing both BSREM400 and OSEM, typically used in clinical practice.

Improved detection of in-transit metastases of malignant melanoma with BSREM reconstruction in digital [18F]FDG PET/CT.

OBJECTIVES: To compare block sequential regularized expectation maximization (BSREM) and ordered subset expectation maximization (OSEM) for the detection of in-transit metastasis (ITM) of malignant melanoma in digital [18F]FDG PET/CT. METHODS: We retrospectively analyzed a cohort of 100 [18F]FDG PET/CT scans of melanoma patients with ITM, performed between May 2017 and January 2020. PET images were reconstructed with both OSEM and BSREM algorithms. SUVmax, target-to-background ratio (TBR), and metabolic tumor volume (MTV) were recorded for each ITM. Differences in PET parameters were analyzed with the Wilcoxon signed-rank test. Differences in image quality for different reconstructions were tested using the Man-Whitney U test. RESULTS: BSREM reconstruction led to the detection of 287 ITM (39% more than OSEM). PET parameters of ITM were significantly different between BSREM and OSEM reconstructions (p < 0.001). SUVmax and TBR were higher (76.5% and 77.7%, respectively) and MTV lower (49.5%) on BSREM. ITM missed with OSEM had significantly lower SUVmax (mean 2.03 vs. 3.84) and TBR (mean 1.18 vs. 2.22) and higher MTV (mean 2.92 vs. 1.01) on OSEM compared to BSREM (all p < 0.001). CONCLUSIONS: BSREM detects significantly more ITM than OSEM, owing to higher SUVmax, higher TBR, and less blurring. BSREM is particularly helpful in small and less avid lesions, which are more often missed with OSEM. KEY POINTS: • In melanoma patients, [18F]FDG PET/CT helps to detect in-transit metastases (ITM), and their detection is improved by using BSREM instead of OSEM reconstruction. • BSREM is particularly useful in small lesions.

Lung uptake of fluorine-18 fluoroethyl-choline PET-CT in patients with prostate cancer.

BACKGROUND: Metastatic spreading to the lungs is a negative prognostic factor in patients with prostate cancer (PC). Aim of our study was to assess the prevalence of lung PC metastases in patients with fluorine-18 fluoroethyl-choline (F-18-FECh) PET-CT positive lung lesions and the role of Gleason Score (GS) and common biochemical markers in predicting metastatic spreading to the lungs. METHODS: We retrospectively evaluated the scans of 1283 patients ongoing (F-18-FECh) PET-CT for PC between May 2010 and July 2014. Patients with lung lesion with F-18-FECh uptake were included. Data concerning GS at diagnosis, "trigger" prostate-specific antigen (PSAtr), PSA doubling time (PSAdt), PSA velocity (PSAvel) and ongoing androgen deprivation therapy were collected. PET-CT findings were confirmed by histology or follow-up (FU) and classified as follows: inflammation, primary lung cancer or metastases from tumor other than PC, and lung metastases from PC. RESULTS: Twenty-two patients with F-18-FECh positive lung lesion and available histology or FU were identified. PSAdt was significantly (P=0.029) shorter in patients with lung metastases from PC (median PSAdt 1.7 months, interquartile range [IQR] 1.5-4.1 months) than in patients without lung PC relapse (median PSAdt 6.7 months, IQR 3.9-7.8); PSAvel was significantly (P=0.019) higher in patients with lung metastases from PC (median PSAvel 3.2 ng/mL/month, IQR 0.65-6.65 ng/mL/month) than in patients without lung PC relapse (median PSAvel 0.3 ng/mL/month, IQR 0.2-0.5 ng/mL/month). Patients with lung metastases from PC had significantly (P=0.006) higher GS at diagnosis (median GS 8) than the other ones (median GS 7). CONCLUSIONS: Our analysis shows that the prevalence of F-18-FECh positive lung metastases in patients with PC, especially with higher GS at diagnosis, is higher in presence of a steady increase in PSA values, confirmed by higher PSAvel and shorter PSAdt.

The central zone has increased 68Ga-PSMA-11 uptake: "Mickey Mouse ears" can be hot on 68Ga-PSMA-11 PET.

PURPOSE: Given the good correlation between PSMA expression and intraglandular tumour aggressiveness based on immunohistochemistry, there is increasing interest in 68Ga-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 68Ga-PSMA-11. METHODS: We retrospectively analysed all patients who underwent a staging 68Ga-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. SUVmax and SUVmean were determined and their differences among the regions were assessed using the Wilcoxon signed-ranks test. RESULTS: Of 283 consecutive patients scanned with 68Ga-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 SUVmax 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 68Ga-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 68Ga-PSMA-11 PET. This pattern could be helpful in avoiding false-positive interpretations of PET scans.

Clinical Value of PET/CT in Staging Melanoma and Potential New Radiotracers.

BACKGROUND: 18F-FDG PET/CT has been suggested as an effective tool to stage patients affected by melanoma. In the latest years, new radiopharmaceuticals have been proposed and the use of hybrid PET/ceCT has emerged. OBJECTIVE: To review recent evidence on the role of PET/CT in melanoma staging as well as its potential for future developments. METHODS: A comprehensive computer literature search of PubMed/MEDLINE was carried out to find relevant published articles concerning the feasibility of PET/CT in patients with malignant melanoma. RESULTS: Some recent studies about potentials and limitations of 18F-FDG PET/CT in staging melanoma, new PET radiotracers beyond 18F-FDG and application of hybrid PET/ceCT have been reviewed and discussed. CONCLUSION: PET/CT plays an important role in the staging workup of patients affected by melanoma. New radiopharmaceuticals and hybrid PET/ceCT could improve the potential of this diagnostic tool in this field.

The Monocle Sign in FDG-PET: A Sign of Contralateral Facial Nerve Palsy.

We report three cases of unilateral F-FDG uptake in the orbicularis oculi muscle in subjects with contralateral peripheral facial nerve palsy. We argue that this asymmetric uptake pattern in fact reflects lack of metabolism on the side affected by facial nerve palsy, owing to denervation. Since the unilateral periorbital uptake resembles a monocle, we chose to call this finding the monocle sign. The monocle sign should not be confused with inflammation or tumor, but should prompt a neurological assessment for facial nerve palsy and a potential underlying disease.

Fluoro-deoxy-glucose uptake in the mylohyoid muscle: a common misconception.

AIM: The mylohyoid muscle is often believed to exhibit high physiologic fluoro-deoxy-glucose (FDG) uptake. Aim of this study was to use PET/MR for adequately assessing the normal FDG distribution in floor of the mouth (FOM) muscles and neighboring major salivary glands. MATERIALS AND METHODS: Patients scanned with a simultaneous PET/MRI system for initial staging or follow-up of head and neck tumors, with no malignant lesions in salivary glands or in FOM, were included. Volumes-of-interest (VOIs) were positioned separately for bilateral mylohyoid, digastric, genioglossus, and geniohyoid muscles, based on T2-weighted and T1-weighted images, and for bilateral parotid, submandibular, and sublingual glands in the same way. SUVmax was measured for each VOI. RESULTS: Six hundred and ninety-two VOIs were positioned. FDG uptake in mylohyoid (SUVmax = 1.94 ± 0.37) and digastric muscles (SUVmax = 2.01 ± 0.37) were significantly higher compared to that in geniohyoid (SUVmax = 1.67 ± 0.53) and genioglossus muscles (SUVmax = 1.75 ± 0.54) (Friedman's test; P < 0.001). FDG uptake in the sublingual glands (SUVmax = 3.77 ± 1.63) was significantly higher compared to the parotid glands (SUVmax = 2.34 ± 0.60) and submandibular glands (SUVmax = 2.51 ± 0.59) (Wilcoxon signed-ranks test; P < 0.001). FDG uptake in sublingual glands was significantly higher than FDG uptake in the mylohyoid muscles (P < 0.001). FDG uptake in the parotid, submandibular, and sublingual glands was inversely correlated to the age of subjects (Spearman' rho coefficient: -0.397/P = 0.004; -0.329/P = 0.021; -0.535/P < 0.001, respectively). CONCLUSION: The sublingual glands yield the highest physiologic FDG uptake in the FOM. High FDG uptake in the mylohyoid muscle is a common misconception.

Detection Rate of 18F-Labeled PSMA PET/CT in Biochemical Recurrent Prostate Cancer: A Systematic Review and a Meta-Analysis.

Background: The use of radiolabeled prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) for biochemical recurrent prostate cancer (BRPCa) is increasing worldwide. Recently, 18F-labeled PSMA agents have become available. We performed a systematic review and meta-analysis regarding the detection rate (DR) of 18F-labeled PSMA PET/CT in BRPCa to provide evidence-based data in this setting. Methods: A comprehensive literature search of PubMed/MEDLINE, EMBASE, and Cochrane Library databases through 23 April 2019 was performed. Pooled DR was calculated on a per-patient basis, with pooled proportion and 95% confidence interval (95% CI). Furthermore, pooled DR of 18F-PSMA PET/CT using different cut-off values of prostate-specific antigen (PSA) was obtained. Results: Six articles (645 patients) were included in the meta-analysis. The pooled DR of 18F-labeled PSMA PET/CT in BRPCa was 81% (95% CI: 71-88%). The pooled DR was 86% for PSA ≥ 0.5 ng/mL (95% CI: 78-93%) and 49% for PSA < 0.5 ng/mL (95% CI: 23-74%). Statistical heterogeneity was found. Conclusions: 18F-labeled PSMA PET/CT demonstrated a good DR in BRPCa. DR of 18F-labeled PSMA PET/CT is related to PSA values with significant lower DR in patients with PSA < 0.5 ng/mL. Prospective multicentric trials are needed to confirm these findings.

Use of MRI and FDG-PET/CT to predict fixation of advanced hypopharyngeal squamous cell carcinoma to prevertebral space.

BACKGROUND: We evaluated the ability of different (18F)fluoro-deoxy-d-glucose (FDG)-positron emission tomography (PET)-based and magnetic resonance (MR)-based parameters to identify prevertebral space (PVS) infiltration by hypopharyngeal carcinoma. METHODS: Retrospective study on 59 patients with advanced hypopharyngeal squamous cell carcinoma undergoing cross-sectional imaging and triple endoscopy for staging. RESULTS: Obliteration of retropharyngeal fat plane on T1-weighted MR images was found more often (P < .001) in tumors fixated to the PVS. Complete fat plane obliteration best predicted tumor fixation to PVS (accuracy 99%; CI: 97%-100%; P < .001). With similar accuracy, PET-based models predicted PVS fixation (combination of standardized uptake value [SUVmax ] of the primary tumor and presence of focal FDG-uptake in prevertebral muscles [accuracy 98%; CI 94%-100%; P < .001]; metabolic tumor volume [MTV] [accuracy 98%; CI 95%-100%; P < .001]). CONCLUSION: Both the MR-based parameter of complete fat plane obliteration and PET-based models (increased SUVmax in combination with presence of focal FDG-uptake of prevertebral muscles; increased MTV) predict PVS involvement independently with high accuracy.

First Clinicopathologic Evidence of a Non-PSMA-Related Uptake Mechanism for 68Ga-PSMA-11 in Salivary Glands.

The intense accumulation of prostate-specific membrane antigen (PSMA) radioligands in salivary glands is still not well understood. It is of concern for therapeutic applications of PSMA radioligands, because therapeutic radiation will damage these glands. A better understanding of the uptake mechanism is, therefore, crucial to find solutions to reduce toxicity. The aim of this study was to investigate whether the accumulation of PSMA-targeting radioligands in submandibular glands (SMGs) can be explained with PSMA expression levels using autoradiography (ARG) and immunohistochemistry (IHC). Methods: All patients gave written informed consent for further utility of the biologic material. The SMG of 9 patients, pancreatic tissue of 4 patients, and prostate cancer (PCA) lesions of 9 patients were analyzed. Tissue specimens 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 with 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 (1.3%-22% of standard). 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 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.

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 18F-FDG PET reported higher signal-to-noise ratios and higher standardized uptake values (SUV). In this study, we investigate the optimal regularization parameter (ß) for clinical 68Ga-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 68Ga-PSMA PET/MR were retrospectively reconstructed. Reference OSEM reconstructions had 28 subsets and 2 iterations. BSREM reconstructions were performed with 15 ß 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 ß. Image reconstructions with ß 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 ß 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 68Ga-PSMA tracer result in lower background noise and higher SUVmax values in lesions compared to TOF OSEM. Our study indicates that a ß value between 400 and 550 might be the optimal compromise between high SUVmax and low background noise.

Deep Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex in Alcohol Use Disorder Patients: Effects on Dopamine Transporter Availability and Alcohol Intake.

Repetitive Transcranial Magnetic Stimulation (rTMS) of the dorsolateral prefrontal cortex may affect neuro-adaptations associated with alcohol use disorder (AUD), potentially influencing craving and alcohol intake. We investigated alcohol intake and dopamine transporter (DAT) availability by Single Photon Emission Computed Tomography (SPECT) in the striatum of AUD patients before and after deep rTMS. Fourteen patients underwent baseline clinical and SPECT assessment. Eleven out of fourteen patients were randomized into two groups for the REAL (n.5) or SHAM (n.6) treatment. Clinical and SPECT evaluations were then carried out after four weeks of rTMS sessions (T1). At baseline, AUD patients showed higher striatal DAT availability than healthy control subjects (HC). Patients receiving the REAL stimulation revealed a reduction in DAT availability at T1, whereas the SHAM-treated group did not. In addition, patients receiving the REAL stimulation had a decrease in alcohol intake. The results of this longitudinal pilot study may suggest a modulatory effect of deep rTMS on dopaminergic terminals and a potential clinical efficacy in reducing alcohol intake in AUD patients. Further investigations are required to confirm these preliminary data.