Multisite MRI Intravoxel Incoherent Motion Repeatability and Reproducibility across 3 T Scanners in a Breast Diffusion Phantom: A BReast Intravoxel Incoherent Motion Multisite (BRIMM) Study.

BACKGROUND: Monoexponential apparent diffusion coefficient (ADC) and biexponential intravoxel incoherent motion (IVIM) analysis of diffusion-weighted imaging is helpful in the characterization of breast tumors. However, repeatability/reproducibility studies across scanners and across sites are scarce. PURPOSE: To evaluate the repeatability and reproducibility of ADC and IVIM parameters (tissue diffusivity (Dt ), perfusion fraction (Fp ) and pseudo-diffusion (Dp )) within and across sites employing MRI scanners from different vendors utilizing 16-channel breast array coils in a breast diffusion phantom. STUDY TYPE: Phantom repeatability. PHANTOM: A breast phantom containing tubes of different polyvinylpyrrolidone (PVP) concentrations, water, fat, and sponge flow chambers, together with an MR-compatible liquid crystal (LC) thermometer. FIELD STRENGTH/SEQUENCE: Bipolar gradient twice-refocused spin echo sequence and monopolar gradient single spin echo sequence at 3 T. ASSESSMENT: Studies were performed twice in each of two scanners, located at different sites, on each of 2 days, resulting in four studies per scanner. ADCs of the PVP and water were normalized to the vendor-provided calibrated values at the temperature indicated by the LC thermometer for repeatability/reproducibility comparisons. STATISTICAL TESTS: ADC and IVIM repeatability and reproducibility within and across sites were estimated via the within-system coefficient of variation (wCV). Pearson correlation coefficient (r) was also computed between IVIM metrics and flow speed. A P value <0.05 was considered statistically significant. RESULTS: ADC and Dt demonstrated excellent repeatability (<2%; <3%, respectively) and reproducibility (both <5%) at the two sites. Fp and Dp exhibited good repeatability (mean of two sites 3.67% and 5.59%, respectively) and moderate reproducibility (mean of two sites 15.96% and 13.3%, respectively). The mean intersite reproducibility (%) of Fp /Dp /Dt was 50.96/13.68/5.59, respectively. Fp and Dt demonstrated high correlations with flow speed while Dp showed lower correlations. Fp correlations with flow speed were significant at both sites. DATA CONCLUSION: IVIM reproducibility results were promising and similar to ADC, particularly for Dt . The results were reproducible within both sites, and a progressive trend toward reproducibility across sites except for Fp . LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

An improved model for prostate diffusion incorporating the results of Monte Carlo simulations of diffusion in the cellular compartment.

The purpose of this work was to refine a previously published model of prostate diffusion by incorporating improved estimates of cellular diffusivity obtained by Monte Carlo simulation. Stromal and epithelial cell size and intracellular volume fraction in different grades of cancer were determined from histological images. Diffusion in different mixtures of cells, corresponding to different tumor grades, was simulated and cellular apparent diffusion coefficient and kurtosis values determined. These values were incorporated into the previously published model of prostate diffusion and model predictions compared with values found in the literature. Stromal cell radius and intracellular volume fraction were 3.74 ± 0.96 µm and 13 ± 3% respectively in normal peripheral zone (PZ), and were similar in all grades of cancer. Epithelial cell radius and intracellular volume fraction were 3.40 ± 0.15 µm and 45 ± 5% respectively in normal PZ, rising to 4.75 ± 0.20 µm and 70 ± 8% in high grade cancer. Cellular apparent diffusion coefficient and kurtosis were 1.02 µm2 ms-1 and 0.58 respectively in normal PZ, and 0.61 µm2 ms-1 and 1.15 in high grade cancer (variation in simulation values are less than 0.1%). Agreement between model predictions and measurements were good, with a mean square error of 0.22 µm2 ms-1 . Incorporation of cellular diffusion coefficient and kurtosis values obtained by Monte Carlo simulation into a model of prostate diffusion gives good agreement with published results.

A monte carlo study of restricted diffusion: Implications for diffusion MRI of prostate cancer.

PURPOSE: Diffusion MRI is used frequently to assess prostate cancer. The prostate consists of cellular tissue surrounding fluid filled ducts. Here, the diffusion properties of the ductal fluid alone were studied. Monte Carlo simulations were used to investigate ductal residence times to determine whether ducts can be regarded as forming a separate compartment and whether ductal radius could determine the Apparent Diffusion Coefficient (ADC) of the ductal fluid. METHODS: Random walks were simulated in cavities. Average residence times were estimated for permeable cavities. Signal reductions resulting from application of a Stejskal-Tanner pulse sequence were calculated in impermeable cavities. Simulations were repeated for cavities of different radii and different diffusion times. RESULTS: Residence times are at least comparable with diffusion times even in relatively high grade tumors. ADCs asymptotically approach theoretical limiting values. At large radii and short diffusion times, ADCs are similar to free diffusion. At small radii and long diffusion times, ADCs are reduced toward zero, and kurtosis approaches a value of -1.2. CONCLUSIONS: Restricted diffusion in cavities of similar sizes to prostate ducts may reduce ductal ADCs. This may contribute to reductions in total ADC seen in prostate cancer. Magn Reson Med 77:1671-1677, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

A model describing diffusion in prostate cancer.

PURPOSE: Quantitative diffusion MRI has frequently been studied as a means of grading prostate cancer. Interpretation of results is complicated by the nature of prostate tissue, which consists of four distinct compartments: vascular, ductal lumen, epithelium, and stroma. Current diffusion measurements are an ill-defined weighted average of these compartments. In this study, prostate diffusion is analyzed in terms of a model that takes explicit account of tissue compartmentalization, exchange effects, and the non-Gaussian behavior of tissue diffusion. METHOD: The model assumes that exchange between the cellular (ie, stromal plus epithelial) and the vascular and ductal compartments is slow. Ductal and cellular diffusion characteristics are estimated by Monte Carlo simulation and a two-compartment exchange model, respectively. Vascular pseudodiffusion is represented by an additional signal at b = 0. Most model parameters are obtained either from published data or by comparing model predictions with the published results from 41 studies. Model prediction error is estimated using 10-fold cross-validation. RESULTS: Agreement between model predictions and published results is good. The model satisfactorily explains the variability of ADC estimates found in the literature. CONCLUSION: A reliable model that predicts the diffusion behavior of benign and cancerous prostate tissue of different Gleason scores has been developed. Magn Reson Med 78:316-326, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Minimization of errors in biexponential T2 measurements of the prostate.

PURPOSE: To determine the echo times that provide the greatest precision in measurements of prostate T2s. T2 relaxation time measurements in the prostate are complicated by the structure of prostate tissue, which consists of fluid-filled glands surrounded by epithelial and stromal cells. Since the glands are large relative to diffusion distances, there is little water exchange between the two compartments and T2s are biexponential. Because the relative size and characteristics of the two compartments change in prostate tumors, accurate measurement of the characteristics of each may provide useful information on tumor grade. MATERIALS AND METHODS: T2s were measured in a group of 25 men with biopsy-proven prostate cancer. Subjects were scanned at 3T with a 16-echo turbo-spin echo T2-mapping sequence. Normal prostate T2s were measured in areas showing no disease. Optimum echo times for measurement of normal prostate T2s were found by calculating the covariance matrix, which provides estimates of parameter variance. Echo times that minimize T2 variance were then found by searching over grids of different echo times. Optima for four to eight echo acquisitions were found. Optima were tested by Monte Carlo simulation. RESULTS: Fast and slow T2s were 60 msec and 360 msec, respectively. The fast signal fraction was 0.6. Optimum echo times were between 0 and 780 msec, depending on the number of echoes acquired. CONCLUSION: Use of optimum echo times can substantially improve the precision of biexponential T2 measurements. This optimization is anticipated to improve prostate cancer characterization using T2 measurements.