Sensitivity of magnetic resonance elastography to extracellular matrix and cell motility in human prostate cancer cell line-derived xenograft models.

Prostate cancer (PCa) is a significant health problem in the male population of the Western world. Magnetic resonance elastography (MRE), an emerging medical imaging technique sensitive to mechanical properties of biological tissues, detects PCa based on abnormally high stiffness and viscosity values. Yet, the origin of these changes in tissue properties and how they correlate with histopathological markers and tumor aggressiveness are largely unknown, hindering the use of tumor biomechanical properties for establishing a noninvasive PCa staging system. To infer the contributions of extracellular matrix (ECM) components and cell motility, we investigated fresh tissue specimens from two PCa xenograft mouse models, PC3 and LNCaP, using magnetic resonance elastography (MRE), diffusion-weighted imaging (DWI), quantitative histology, and nuclear shape analysis. Increased tumor stiffness and impaired water diffusion were observed to be associated with collagen and elastin accumulation and decreased cell motility. Overall, LNCaP, while more representative of clinical PCa than PC3, accumulated fewer ECM components, induced less restriction of water diffusion, and exhibited increased cell motility, resulting in overall softer and less viscous properties. Taken together, our results suggest that prostate tumor stiffness increases with ECM accumulation and cell adhesion - characteristics that influence critical biological processes of cancer development. MRE paired with DWI provides a powerful set of imaging markers that can potentially predict prostate tumor development from benign masses to aggressive malignancies in patients. STATEMENT OF SIGNIFICANCE: Xenograft models of human prostate tumor cell lines, allowing correlation of microstructure-sensitive biophysical imaging parameters with quantitative histological methods, can be investigated to identify hallmarks of cancer.

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

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.