Prostate tissue microstructure: Complementary assessment using multifrequency MR elastography and diffusion tensor imaging in ex vivo human prostate tissue.
Lynne E. Bilston1,2, Lauriane Jugé 1,3, and Roger Bourne4

1Neuroscience Research Australia, Randwick, NSW, Australia, 2Prince of Wales Clinical School, University of New South Wales, Kensington, NSW, Australia, 3School of Medical Sciences, University of New South Wales, Kensington, NSW, Australia, 4Discipline of Medical Radiation Sciences, Faculty of Health Sciences, University of Sydney, Lidcombe, NSW, Australia


MR elastography (MRE) and diffusion weighted imaging (DWI) techniques are sensitive to microstructural changes, as reflected in the tissue stiffness and water diffusion properties respectively. These results showed that mechanical and diffusion properties varied between fresh and fixed prostate tissue, but were not highly correlated with each other, suggesting that multifrequency MRE and DWI have the potential to be complementary imaging tools for tracking the alterations in soft tissue microstructure, such as those that occur in cancer and other diseases.


The best available prostate cancer imaging method, multi-parametric MRI1,2, is rapidly being adopted worldwide to assist targeted biopsy, risk stratification, and treatment selection. However the mpMRI protocol is still immature and has enormous potential for improvement. Prostate cancer is characterized by tissue structure changes that are often detectable by diffusion-weighted MRI (DWI), and potentially by MR elastography (MRE)3. MRE and DWI characterize different tissue structural parameters, and could provide complementary information, particularly in circumstances where the tissue undergoes changes that may alter mechanical parameters and diffusion concurrently. The aim of this study was to compare mechanical properties and diffusion parameters in fresh human prostate tissue and to assess the effects of formalin fixation.


This study was approved by the local human research ethics committee. One whole prostate was imaged, suspended on a rod inserted through the urethra4, immediately following surgery and again after formalin fixation for 48 hr and soaking in saline for 24 hr. MR imaging was performed on a preclinical MRI scanner (Bruker 94/20 Biospec), with a 72 mm volume coil.


A pulse-gradient spin-echo DWI sequence was used, with b-values 0 and 1600 s/mm2, δ/Δ = 5/20 ms, 6 gradient directions, TE/TR = 28/2000 ms; FOV 48×48 mm, matrix 32×32, slice thickness 2 mm, gap 2 mm.


MRE was performed using a spin echo MRE sequence3 TR/TE=1880/28 ms, matrix = 64x64, FOV = 64x64 mm, nine 1 mm thick axial slices, at 600, 800 and 1000 Hz using a custom-designed setup.

Anatomical Imaging:

T2-weighted images (TR/TE=3500/17 ms, RARE factor = 8, matrix 256x256, FOV=64x64 mm) were collected in matching geometry to visualise the anatomy of the prostate.


The fractional anisotropy (FA) and mean diffusivity (MD) were calculated from the diffusion data, and the shear modulus (G*) at each frequency was calculated using custom software5. Correlations between elastography and diffusion parameters were calculated using Matlab (r2013b).


Tissue shear modulus increased with frequency for both fresh (see Figure 1) and fixed tissue, consistent with the power-law typically observed in soft tissues. The fixed tissue was approximately 50kPa stiffer than the fresh tissue (Figure 2). G* was higher in the fibromuscular stroma anterior to the urethra than in the more glandular transition and peripheral zones. This difference was more marked in the fresh tissue and at higher frequency (Figure 2). Correlations between elastography parameters and diffusion parameters were weak (correlation coefficients are shown in Table 1). Sample correlation plots are shown in Figure 3 for diffusion parameters with the elastography data at 600 Hz.


Fixation of the prostate tissue substantially increased the tissue stiffness, but altered diffusion parameters to a lesser degree. The increased stiffness is likely a result of the chemical crosslinking between proteins in the tissue during fixation. This fixation did not appear to substantially alter the degree to which stiffness increased with frequency, possibly because the cross-linking that occurs during fixation with formalin does not greatly alter the fractality of the microstructure6. Diffusion and elastography parameters were only very weakly correlated, indicating these modalities provide complementary information about tissue microstructure.


The authors would like to thank Alice Hatt for her assistance in adapting the MRE setup for use on ex vivo prostate tissue. Lynne Bilston is supported by an NHMRC senior research fellowship.


1. Thompson, J.E., et al., Multiparametric Magnetic Resonance Imaging Guided Diagnostic Biopsy Detects Significant Prostate Cancer and could Reduce Unnecessary Biopsies and Over Detection: A Prospective Study. J. Urology, 2014. 192(1): p. 67-74.

2. Turkbey, B., et al., Prostate Cancer: Can Multiparametric MR Imaging Help Identify Patients Who Are Candidates for Active Surveillance? Radiology, 2013. 268(1): p. 144-152.

3. Sahebjavaher, R.S., et al., MR elastography and diffusion-weighted imaging of ex vivo prostate cancer: quantitative comparison to histopathology. NMR Biomed, 2015. 28(1): p. 89-100.

4. Bourne, R., et al., Effect of formalin fixation on biexponential modeling of diffusion decay in prostate tissue. Magn Res Med, 2013. 70(4): p. 1160-1166.

5. Sinkus, R., et al., Viscoelastic shear properties of in vivo breast lesions measured by MR elastography. Magn Reson Imaging, 2005. 23(2): p. 159-65.

6. Lambert, S., et. al., Bridging Three Orders of Magnitude: Multiple Scattered Waves Sense Fractal Microscopic Structures via Dispersion. Physical Review Letters, 2015. 115(9), 094301.


Figure 1. Representative images for fresh prostate tissue, showing T2W image, fractional anisotropy (FA), mean diffusivity (MD, in 10-3mm2/s), and shear modulus, G*(in kPa) at three frequencies (all plotted on the same colour scale).

Figure 2. Comparison of fresh (upper row) and fixed (lower row) prostate tissue. Diffusion parameters (MD, in 10-3mm2/s, and FA) are changed to a lesser degree than the tissue shear modulus(G*, in kPa), which increases substantially (right column).

Table 1. Correlation coefficients for correlation between MRE and diffusion parameters.

Figure 3. Sample correlation plots between diffusion parameters (MD, in 10-3mm2/s, upper row, and FA, lower row) and tissue shear modulus (G*, in kPa) at 600Hz, for fresh (left column) and fixed (right column) tissue.

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)