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Objectives: To explore changes in bone mineral density (BMD) measured by DEXA and MRS fat fraction (FF), Dixon FF, and ADC in lower spinal vertebral bodies in men with prostate cancer treated with androgen deprivation therapy (ADT)., Methods: Twenty-eight men were enrolled onto a clinical trial. All received ADT. DEXA imaging was performed at baseline and 12 months. L-spine MRI was done at baseline and 6 months., Results: The number of patients who underwent DEXA, Dixon, ADC, and MRS at baseline/follow-up were 28/27, 28/26, 28/26, and 22/20. An increase in FF was observed from T11 to S2 (average 1 %/vertebra). There was a positive correlation between baseline MRS FF and Dixon FF (r = 0.85, p < 0.0001) and a negative correlation between MRS FF and ADC (r = -0.56, p = 0.036). Over 6 months, MRS FF increased by a median of 25 % in relative values (p = 0.0003), Dixon FF increased (p < 0.0001) and ADC values decreased (p = 0.0014). Men with >5 % BMD loss after 1 year had triple the percentage increase in MRS FF at 6 months (61.1 % vs. 20.9 %, p = 0.19)., Conclusions: Changes are observed on L-spine MRI after 6 months of ADT. Further investigation is warranted of MRS change as a potential predictive biomarker for later BMD loss., Key Points: • Spinal marrow fat fraction increases after 6 months of androgen deprivation therapy. • More inferior vertebral bodies tend to have higher fat fractions. • MRS fat fraction changes were associated with later changes in DEXA BMD.

Background: A prospective clinical trial was conducted to evaluate the feasibility of a novel approach to the treatment of patients with high risk prostate cancer (HRPC) through the use of a nomogram to tailor radiotherapy target volumes., Methods: Twenty seven subjects with HRPC were treated with a mildly hypofractionated radiotherapy regimen using image-guided IMRT technique between Jun/2013-Jan/2015. A set of validated prognostic factors were inputted into the Memorial-Sloan-Kettering Cancer Center (MSKCC) prostate cancer nomogram to estimate risk of loco-regional spread (LRS). The nomogram risk estimates for extra-capsular extension (ECE), seminal vesicles involvement (SVI), and pelvic lymph nodes involvement (LNI) were used to adapt radiotherapy treatment volumes based on a risk threshold of ≥15 % in all cases. A planning guide was used to delineate target volumes and organs at risk (OAR). Up to three dose levels were administered over 28 fractions; 70Gy for gross disease in the prostate +/- seminal vesicles (2.5Gy/fraction), 61.6Gy for subclinical peri-prostatic disease (2.2Gy/fraction) and 50.4Gy to pelvic nodes (1.8Gy/fraction). Data regarding protocol adherence, nomogram use, radiotherapy dose distribution, and acute toxicity were collected., Results: Nomogram use 100 % of patients were treated for ECE, 88.9 % for SVI, and 70.4 % for LNI. The three areas at risk of LRS were appropriately treated according to the study protocol in 98.8 % cases. The MSKCC nomogram estimates for LRS differed significantly between the time of recruitment and analysis. Contouring protocol compliance Compliance with the trial contouring protocol for up to seven target volumes was 93.0 % (159/171). Compliance with protocol for small bowel contouring was poor (59.3 %). Dose constraints compliance Compliance with dose constraints for target volumes was 97.4 % (191/196). Compliance with dose constraints for OAR was 88.2 % (285/323). Acute toxicity There were no grade 3 acute toxicities observed. 20/27 (74.1 %) and 6/27 (22.2 %) patients experienced a grade 2 genitourinary and gastrointestinal toxicity respectively., Conclusions: We have demonstrated the feasibility of this novel risk-adapted radiation treatment protocol for HRPC. This study has identified key learning points regarding this approach, including the importance of standardization and updating of risk quantification tools, and the utility of an observer to verify their correct use., Trial Registration: ClincialTrials.gov identifier NCT01418040 . Hunter New England Human Research Ethics Committee (HNEHREC) reference number 12/08/15/4.02.

Aim: To evaluate the potential of newly-developed, biocompatible iron oxide magnetic nanoparticles (MNPs) conjugated with J591, an antibody to an extracellular epitope of PSMA, to enhance MRI of prostate cancer., Materials & Methods: Specific binding to PSMA by J591-MNP was investigated in vitro. MRI studies were performed on orthotopic tumor-bearing NOD.SCID mice 2 h and 24 h after intravenous injection of J591-MNPs, or non-targeting MNPs., Results & Conclusion: In vitro, MNPs did not affect prostate cancer cell viability, and conjugation to J591 did not compromise antibody specificity and enhanced cellular iron uptake. Magnetic resonance contrast of tumors was increased in vivo using PSMA-targeting MNPs, but not by non-targeting MNPs. This provides proof-of-concept that PSMA-targeting MNPs have potential to enhance magnetic resonance detection/localization of prostate cancer.

Magnetic resonance microimaging was used to measure diffusion decay over an extended b-factor range in a formalin-fixed normal prostate sample and a Gleason pattern 3+4 cancer tissue sample. The coefficients of biexponential fits to diffusion decay data from 1600 voxels of dimension 160 × 160 × 160 μm(3) in each sample were correlated with underlying epithelial and stromal compartment partial volumes estimated from high-resolution apparent diffusion coefficient (ADC) data (40 × 40 × 40 μm(3) voxels) from the same tissue. In the normal tissue sample, the signal fractions of the low and high ADC components of the biexponential fits correlated linearly with partial volumes of epithelial tissue (R(2) = 0.6) and stromal tissue (R(2) = 0.5), respectively. Similar but weaker correlations were observed in the cancer sample. Epithelium-containing high spatial resolution voxels appeared to be composed of ∼60% low ADC and ∼40% high ADC component. Stromal voxels appeared to be composed of ∼20% low ADC and ∼80% high ADC component. This preliminary report suggests that distinctly different diffusion properties in microscopically adjacent cell types contribute to the multiexponential diffusion decay phenomenon in prostate tissue., (Copyright © 2011 Wiley Periodicals, Inc.)

MR microimaging at 16.4 T with 40-μm isotropic voxels was used to investigate compartmentation of water diffusion in formalin-fixed prostate tissue. Ten tissue samples (~ 28 mm(3) each) from five organs were imaged. The mean diffusivity of epithelial, stromal, and ductal/acinar compartments was estimated by two methods: (1) manual region of interest selection and (2) Gaussian fitting of voxel diffusivity histograms. For the region of interest-method, the means of the tissue sample compartment diffusivities were significantly different (P < 0.001): 0.54 ± 0.05 μm(2)/ms for epithelium-containing voxels, 0.91 ± 0.17 μm(2)/ms for stroma, and 2.20 ± 0.04 μm(2)/ms for saline-filled ducts. The means from the histogram method were also significantly different (P < 0.001): 0.45 ± 0.08 μm(2)/ms for epithelium-containing voxels, 0.83 ± 0.16 μm(2)/ms for stroma, 2.21 ± 0.02 μm(2)/ms for duct. Estimated partial volumes of epithelial, stromal, and ductal/acinar compartments in a "tissue only" subvolume of each sample were significantly different (P < 0.02) between cancer and normal tissue for all three compartments. It is concluded that the negative correlation between apparent diffusion coefficient and cancer Gleason grade observed in vivo results from an increase of partial volume of epithelial tissue and concomitant decrease of stromal tissue and ductal space., (Copyright © 2011 Wiley Periodicals, Inc.)

Prostate cancer detection using diffusion-weighted imaging is highly affected by the accuracy of the apparent diffusion coefficient (ADC) values in an image. Echo planar imaging (EPI) is a fast sequence commonly used for diffusion imaging but has inherent magnetic susceptibility and chemical shift artefacts associated. A diffusion sequence that is less affected by these artefacts is therefore advantageous. The half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequence was chosen. The diffusion sequences were compared in image quality, repeatability of the ADC value and the effect on the ADC value with varied b values. Eight volunteers underwent three scans of each sequence, on a 1.5-T Siemens system, using b values of 0, 150, 300, 450, 600, 750, 900 and 1000 s/mm(2). ADC maps were created to address the reproducibility of the ADC value when using two b values compared to eight b values. The ADC value using all b values with the HASTE sequence gave the best performance in all tested categories. Both sequences gave significantly different ADC mean values for two b values compared to when using eight b values (P<.05) suggesting larger error is present when using two b values. HASTE was shown to be an improvement over EPI in terms of repeatability, signal variation within a region of interest and standard deviation over the volunteer set. The improved accuracy of the ADC value in the HASTE sequence makes it potentially a more sensitive tumor detection technique., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Diffusion tensor microimaging was used to investigate the water diffusion properties of formalin-fixed prostate tissue at spatial resolution approaching the cellular scale. Diffusion tensor microimaging was performed at 16.4 T with 40 μm isotropic voxels. Diffusion tensor microimaging clearly demonstrated distinct microscopic diffusion environments and tissue architecture consistent with that seen on light microscopy of the same tissue. The most restricted diffusion environment is the secretory epithelial cell layer (voxel bulk mean diffusivity, D = 0.4 ± 0.1 × 10(-3) mm(2)/sec). Diffusion in the fibromuscular stromal matrix is relatively less restricted (D = 0.7 ± 0.1 × 10(-3) mm(2)/sec). In tumor tissue (Gleason pattern 4+4) distinct glandular and ductal structures are absent in the diffusion-weighted images and diffusivity is low (D = 0.5 ± 0.1 × 10(-3) mm(2)/sec). Distinct stromal and epithelial diffusion compartments are the most likely origin of biexponential diffusion decay observed in vivo., (Copyright © 2010 Wiley-Liss, Inc.)