In Vivo Quantification of Water Diffusion, Stiffness, and Tissue Fluidity in Benign Prostatic Hyperplasia and Prostate Cancer

Abstract

Objectives Water diffusion, tissue stiffness, and viscosity characterize the biophysical behavior of tumors. However, little is known about how these parameters correlate in prostate cancer (PCa). Therefore, we paired tomoelastography of the prostate with diffusion-sensitive magnetic resonance imaging for the quantitative mapping of biophysical parameters in benign prostatic hyperplasia (BPH) and PCa. Materials and Methods Multifrequency magnetic resonance imaging elastography with tomoelastography processing was performed at 60, 70, and 80 Hz using externally placed compressed-air drivers. Shear-wave speed (SWS) and loss angle (φ) were analyzed as surrogate markers of stiffness and viscosity-related fluidity in the normal peripheral zone (PZ), hyperplastic transition zone (TZ), which is consistent with BPH, and PCa lesions. The SWS and φ were correlated with the normalized apparent diffusion coefficient (nADC). Results Thirty-nine men (median age/range, 67/49–88 years), 25 with BPH and 14 with biopsy-proven PCa, were prospectively enrolled in this institutional review board–approved study. The SWS in PCa (3.1 ± 0.6 m/s) was higher than in TZ (2.8 ± 0.3 m/s, P = 0.004) or tended to be higher than in PZ (2.8 ± 0.4 m/s, P = 0.025). Similarly, φ in PCa (1.1 ± 0.1 rad) was higher than in TZ (0.9 ± 0.2 m/s, P < 0.001) and PZ (0.9 ± 0.1 rad, P < 0.001), whereas nADC in PCa (1.3 ± 0.3) was lower than in TZ (2.2 ± 0.4, P < 0.001) and PZ (3.1 ± 0.7, P < 0.001). Pooled nADC was inversely correlated with φ (R = −0.6, P < 0.001) but not with SWS. TZ and PZ only differed in nADC (P < 0.001) but not in viscoelastic properties. Diagnostic differentiation of PCa from normal prostate tissues, as assessed by area under the curve greater than 0.9, was feasible using nADC and φ but not SWS. Conclusions Tomoelastography provides quantitative maps of tissue mechanical parameters of the prostate. Prostate cancer is characterized by stiff tissue properties and reduced water diffusion, whereas, at the same time, tissue fluidity is increased, suggesting greater mechanical friction inside the lesion. This biophysical signature correlates with known histopathological features including increased cell density and fibrous protein accumulation.

Causal contributors to tissue stiffness and clinical relevance in urology

“…SWE can provide information on tissue elasticity, but the combination of this technique with magnetic resonance can improve the detection of PCa 183 and provide guidance for more targeted biopsies rather than systematic ones, thus increasing the positive rate of PCa in targeted biopsies 177 , 184 . The biophysical signature of PCa, characterized by increased stiffness, reduced water diffusion, and increased mechanical fluidity of cancer tissue, correlates with increased cell density and fibrous protein accumulation 185 . SWE as well as tomoelastography with diffusion-weighted MRI have great potential for diagnosis, as they can provide quantitative maps of tissue mechanics.…”

Tomoelastography Based on Multifrequency MR Elastography for Prostate Cancer Detection: Comparison with Multiparametric MRI

“…was reported in one study to be higher in PCa than in normal PZ and TZ (24). The elevated fluidity might be associated with high blood vessel density because of angiogenesis (16,27) and increased intracellular fluid mobility of tumor cells because of the high cellularity of PCa tissue (24).…”

“…The elevated fluidity might be associated with high blood vessel density because of angiogenesis (16,27) and increased intracellular fluid mobility of tumor cells because of the high cellularity of PCa tissue (24). Increased cellularity may also explain the observed negative correlation between fluidity and apparent diffusion coefficient (ADC), as reported by Asbach et al (24), who used normalized ADC. Also, positive correlations between mechanical properties and lesion size implied that larger tumors might be stiffer and might behave more like fluid.…”

“…P values less than .05 were considered to indicate a statistically significant difference. Sample size was estimated to be 288 on the basis of data reported by Asbach et al (24) considering F test with three groups, population effect size of 0.3, power level of 0.9, significance level of .05, and the assumption that histopathologic analysis would be performed in 50% of the participants. Interreader agreement of PI-RADS version 2.1 was tested with k statistic.…”

Molecular MR Imaging of Prostate Cancer

“…The newer version leads to better reproducibility of the readers [62]. An improvement could be archieved by other parameters, such as MR proton spectroscop or MR elastography, which represents stiffness and tissue fluidity [63].…”