The Effect of Including Bone in DIXON-based Attenuation Correction for 18F-fluciclovine PET/MRI of Prostate Cancer

The objective of this study was to evaluate the effect of including bone in DIXON-based attenuation correction for 18F-fluciclovine Positron Emission Tomography (PET) / Magnetic Resonance Imaging (MRI) of primary and recurrent prostate cancer. Methods:18F-fluciclovine PET data from two PET/MRI studies - one for staging of high-risk prostate cancer (28 patients) and one for diagnosis of recurrent prostate cancer (81 patients) - were reconstructed with a 4-compartment (reference) and 5-compartment attenuation map. In the latter, continuous linear attenuation coefficients for bone were included by co-registration with an atlas. The maximum and mean 50% isocontour standardized uptake values (SUVmax and SUViso, respectively) of primary, locally recurrent, and metastatic lesions were compared between the two reconstruction methods using linear mixed-effects models. In addition, mean SUVs were obtained from bone marrow in the third lumbar vertebra (L3) to investigate the effect of including bone attenuation on lesion-to-bone marrow SUV ratios (SUVRmax and SUVRiso; recurrence study only). The 5-compartment attenuation maps were visually compared to the in-phase DIXON MR images for evaluation of bone registration errors near the lesions. P-values < 0.05 were considered significant. Results: Sixty-two (62) lesions from 39 patients were evaluated. Bone registration errors were found near 19 (31%) of these lesions. In the remaining 8 primary prostate tumors, 7 locally recurrent lesions, and 28 lymph node metastases without bone registration errors, using the 5-compartment attenuation map was associated with small but significant increases in SUVmax [2.5%; 95% confidence interval (CI) 2.0%-3.0%; p<0.001] and SUViso (2.5%; 95% CI 1.9%-3.0%; p<0.001), but not SUVRmax (0.2%; 95% CI -0.5%-0.9%; P = 0.604) and SUVRiso (0.2%; 95% CI -0.6%-1.0%; P = 0.581), in comparison to the 4-compartment attenuation map. Conclusion: The investigated method for atlas-based inclusion of bone in 18F-fluciclovine PET/MRI attenuation correction has only a small effect on the SUVs of soft-tissue prostate cancer lesions, and no effect on their lesion-to-bone marrow SUVRs when using signal from L3 as a reference. The attenuation maps should always be checked for registration artefacts for lesions in or close to the bones

Multiparametric Prostate MRI in Biopsy-Naïve Men: A Prospective Evaluation of Performance and Biopsy Strategies

Objectives: This study aims to prospectively estimate the diagnostic performance of multiparametric prostate MRI (mpMRI) and compare the detection rates of prostate cancer using cognitive targeted transrectal ultrasound (TRUS) guided biopsies, targeted MR-guided in-bore biopsies (MRGB), or both methods combined in biopsy-naïve men. Methods: The biopsy-naïve men referred for mpMRI (including T2-weighted, diffusion-weighted and dynamic contrast enhanced MRI) due to prostate cancer suspicion (elevated prostate-specific antigen or abnormal digital rectal examination) were eligible for inclusion. The images were scored according to Prostate Imaging Reporting and Data System (PI-RADS) v2, and men with PI-RADS 1–2 lesions were referred for routine systematic TRUS, while those with PI-RADS 3–5 lesions were randomized to MRGB or cognitive targeted TRUS. Men randomized to MRGB were referred to a secondary TRUS 2 weeks after MRGB. Gleason grade group ≥2 was defined as clinically significant prostate cancer. The performance of mpMRI was estimated using prostate cancer detected by any biopsy method as the reference test. Results: A total of 210 men were included. There was no suspicion of prostate cancer after mpMRI (PI-RADS 1–2) in 48% of the men. Among these, significant and insignificant prostate cancer was diagnosed in five and 11 men, respectively. Thirty-five men who scored as PI-RADS 1–2 did not undergo biopsy and were therefore excluded from the calculation of diagnostic accuracy. The overall sensitivity, specificity, negative predictive value, and positive predictive value of mpMRI for the detection of significant prostate cancer were 0.94, 0.63, 0.92, and 0.67, respectively. In patients with PI-RADS 3–5 lesions, the detection rates for significant prostate cancer were not significantly different between cognitive targeted TRUS (68.4%), MRGB (57.7%), and the combination of the two biopsy methods (64.4%). The median numbers of biopsy cores taken per patient undergoing systematic TRUS, cognitive targeted TRUS, and MRGB were 14 [8-16], 12 [6-17], and 2 [1-4] respectively. Conclusions: mpMRI, in a cohort of biopsy-naïve men, has high negative predictive value, and our results support that it is safe to avoid biopsy after negative mpMRI. Furthermore, MRGB provides a similar diagnosis to the cognitive targeted TRUS but with fewer biopsies

A PET/MRI study towards finding the optimal [18F]Fluciclovine PET protocol for detection and characterisation of primary prostate cancer.

Purpose: [18F]Fluciclovine PET imaging shows promise for the assessment of prostate cancer. The purpose of this PET/MRI study is to optimise the PET imaging protocol for detection and characterisation of primary prostate cancer, by quantitative evaluation of the dynamic uptake of [18F]Fluciclovine in cancerous and benign tissue. Methods: Patients diagnosed with high-risk primary prostate cancer underwent an integrated [18F]Fluciclovine PET/MRI exam before robot-assisted radical prostatectomy with extended pelvic lymph node dissection. Volumes-of-interest (VOIs) of selected organs (prostate, bladder, blood pool) and sub-glandular prostate structures (tumour, benign prostatic hyperplasia (BPH), inflammation, healthy tissue) were delineated on T2-weighted MR images, using whole-mount histology samples as a reference. Three candidate windows for optimal PET imaging were identified based on the dynamic curves of the mean and maximum standardised uptake value (SUVmean and SUVmax, respectively). The statistical significance of differences in SUV between VOIs were analysed using Wilcoxon rank sum tests (p<0.05, adjusted for multiple testing). Results: Twenty-eight (28) patients [median (range) age: 66 (55-72) years] were included. An early (W1: 5-10 minutes post-injection) and two late candidate windows (W2: 18-23; W3: 33-38 minutes post-injection) were selected. Late compared with early imaging was better able to distinguish between malignant and benign tissue [W3, SUVmean: tumour vs. BPH 2.5 vs. 2.0 (p<0.001), tumour vs. inflammation 2.5 vs. 1.7 (p<0.001), tumour vs. healthy tissue 2.5 vs. 2.0 (p<0.001); W1, SUVmean: tumour vs. BPH 3.1 vs. 3.1 (p=0.771), tumour vs inflammation 3.1 vs. 2.2 (p=0.021), tumour vs. healthy tissue 3.1 vs. 2.5 (p<0.001)] as well as between high-grade and low/intermediate-grade tumours (W3, SUVmean: 2.6 vs. 2.1 (p=0.040); W1, SUVmean: 3.1 vs. 2.8 (p=0.173)). These differences were relevant to the peripheral zone, but not the central gland. Conclusion: Late-window [18F]Fluciclovine PET imaging shows promise for distinguishing between prostate tumours and benign tissue and for assessment of tumour aggressiveness

Combined 18F-Fluciclovine PET/MRI shows potential for detection and characterization of high-risk prostate cancer

The objective of this study is to investigate if quantitative imaging features derived from combined 18F-Fluciclovine Positron Emission Tomograpy (PET) / multiparametric Magnetic Resonance Imaging (MRI) show potential for detection and characterization of primary prostate cancer. Methods: Twenty-eight (28) patients diagnosed with high-risk prostate cancer underwent simultaneous 18F-Fluciclovine PET/MRI before radical prostatectomy. Volumes-of-interest (VOIs) of prostate tumors, benign prostatic hyperplasia (BPH) nodules, prostatitis, and healthy tissue were delineated on T2-weighted images using histology as a reference. Tumor VOIs were marked as high-grade (≥ Gleason Grade group 3) or not. MRI and PET features were extracted on the voxel and VOI-level. Partial least-squared discriminant analysis (PLS-DA) with double leave-one-patient-out cross validation was performed to classify tumor from benign tissue (BPH, prostatitis, healthy tissue) and high-grade tumor from other tissue (low-grade tumor, benign tissue). The performances of PET, MRI, and combined PET/MRI features were compared using the area under the receiver operating characteristic curve (AUC). Results: Voxel and VOI features were extracted from 40 tumor (26 high-grade), 36 BPH, 6 prostatitis, and 37 healthy tissue VOIs. PET/MRI performed better than MRI and PET for classification of tumor vs benign tissue (voxel: AUC 87%, 81%, and 83%; VOI: AUC 96%, 93%, and 93%, respectively) and high-grade tumor vs other tissue (voxel: AUC 85%, 79%, and 81%; VOI: AUC 93%, 93%, and 91%, respectively). T2-weighted MRI, diffusion-weighted MRI and PET features were most important for classification. Conclusion: Combined 18F-Fluciclovine PET/multiparametric MRI shows potential for improving detection and characterization of high-risk prostate cancer, in comparison to MRI and PET alone

Detection of recurrent prostate cancer with 18F-Fluciclovine PET/MRI

Objective: Simultaneous PET/MRI combines soft-tissue contrast of MRI with high molecular sensitivity of PET in one session. The aim of this prospective study was to evaluate detection rates of recurrent prostate cancer by 18F-fluciclovine PET/MRI. Methods: Patients with biochemical recurrence (BCR) or persistently detectable prostate specific antigen (PSA), were examined with simultaneous 18F-fluciclovine PET/MRI. Multiparametric MRI (mpMRI) and PET/MRI were scored on a 3-point scale (1-negative, 2-equivocal, 3-recurrence/metastasis) and detection rates (number of patients with suspicious findings divided by total number of patients) were reported. Detection rates were further stratified based on PSA level, PSA doubling time (PSAdt), primary treatment and inclusion criteria (PSA persistence, European Association of Urology (EAU) Low-Risk BCR and EAU High-Risk BCR). A detailed investigation of lesions with discrepancy between mpMRI and PET/MRI scores was performed to evaluate the incremental value of PET/MRI to mpMRI. The impact of the added PET acquisition on further follow-up and treatment was evaluated retrospectively. Results: Among patients eligible for analysis (n=84), 54 lesions were detected in 38 patients by either mpMRI or PET/MRI. Detection rates were 41.7% for mpMRI and 39.3% for PET/MRI (score 2 and 3 considered positive). There were no significant differences in detection rates for mpMRI versus PET/MRI. Disease detection rates were higher in patients with PSA≥1ng/mL than in patients with lower PSA levels but did not differ between patients with PSAdt above versus below 6 months. Detection rates in patients with primary radiation therapy were higher than in patients with primary surgery. Patients categorized as EAU Low-Risk BCR had a detection rate of 0% both for mpMRI and PET/MRI. For 15 lesions (27.8% of all lesions) there was a discrepancy between mpMRI score and PET/MRI score. Of these, 10 lesions scored as 2-equivocal by mpMRI were changed to a more definite score (n=4 score 1 and n=6 score 3) based on the added PET acquisition. Furthermore, for 4 of 10 patients with discrepancy between mpMRI and PET/MRI scores, the added PET acquisition had affected the treatment choice. Conclusion: Combined 18F-fluciclovine PET/MRI can detect lesions suspicious for recurrent prostate cancer in patients with a range of PSA levels. Combined PET/MRI may be useful to select patients for appropriate treatment, but is of limited use at low PSA values or in patients classified as EAU Low-Risk BCR, and the clinical value of 18F-fluciclovine PET/MRI in this study was too low to justify routine clinical use