Beyond the Abstract - Biexponential diffusion decay in formalin-fixed prostate tissue: Preliminary findings, by Roger Bourne, PhD

BERKELEY, CA (UroToday.com) - In prostate disease, cancer volume is a well-established independent predictor of biochemical relapse in men who undergo surgery.

Cancer volume estimated by means of the determination of core involvement is a cornerstone of all active surveillance protocols for men with presumed low-grade, low-volume disease − perhaps the fastest growing cohort of men with clinically localised prostate cancer. One major limitation in the advice clinicians give patients who are potential candidates for active surveillance is the well-known discordance that exists between what is believed to be low-volume disease and the volume of disease found on final histological assessment of the specimen. Development of an imaging method whereby clinicians may accurately predict the "true" volume of disease in men with "low-volume" disease on biopsy would revolutionize the management of prostate cancer.

"...we suggest there is strong evidence that diffusion weighted MRI methods are highly sensitive to the microscopic tissue structure changes that define cancer and thus show potential for reliable prostate cancer volume assessment."

We believe MRI diffusion-weighted water imaging (DWI) may be an ideal candidate for this purpose because the free diffusion of water in tissue is known to be constrained by intra- and extracellular structures and cell walls. This property has been used extensively in the study of neural tissue, but has had only limited clinical application to diseases of glandular tissue such as prostate. Our diffusion MRI microscopy studies of formalin fixed prostate tissue suggest distinctly different water diffusion behaviours in the stroma, the epithelial layer, and in acini and ducts.[1] Changes in the relative partial volumes of these compartments most likely explain the recent clinical reports of a negative correlation between MRI-apparent diffusion coefficient (ADC) and prostate cancer Gleason grade.[2]

However, the single-parameter ADC estimate simplifies the potentially information-rich signal available from DWI. Preliminary clinical investigations of the way the diffusion weighted MRI signal decreases as the diffusion weighting increases suggest that a biexponential analysis may improve the accuracy of pathology assessment.[3,4] Our paper, Biexponential Diffusion Decay in Formalin Fixed Prostate Tissue,[5] looks at the biophysical basis of biexponential behaviour reported from clinical MRI. Although formalin fixation of tissue results in decreased water diffusivity due to protein cross-linking, we found that the relative diffusivities of the biexponential fit coefficients were very similar to those found in vivo. Most significantly, we found that the distinct differences in diffusivity of the epithelium and stroma, and changes in the relative partial volume of each, explained about 60% of the change in relative signal from the biexponential fit coefficients in normal glandular tissue. In the cancer sample we studied (Gleason 3+4), both high and low diffusivity components of the biexponential fit were significantly lower than for the normal glandular tissue – suggesting there are extensive microscopic tissue structure changes in the tumor tissue, rather than a simple proliferation of epithelial cells with ‘normal’ diffusion properties.

We have also used DWI to characterize the fibrous structure of stromal tissue and shown that fiber tracks mapped by diffusion tensor-based tractography match myocyte orientation seen on light microscopy of the same tissue.[6] After imaging multiple tissue samples we concluded that the microscopic heterogeneity of stromal fiber orientation meant that attempts to use low spatial resolution measures of diffusion anisotropy were likely to be unreliable – as has been the case so far in clinical MRI.

While the effects of formalin fixation on tissue diffusion properties require further characterization before these ex vivo studies can be directly related to current and potential clinical imaging methods, we suggest there is strong evidence that diffusion weighted MRI methods are highly sensitive to the microscopic tissue structure changes that define cancer and thus show potential for reliable prostate cancer volume assessment.

References:

  1. Bourne, R., et al., Microscopic Diffusivity Compartmentation in Formalin Fixed Prostate Tissue. Magnetic Resonance in Medicine, 2012: Early view. DOI 10.1002/mrm.22778.
  2. Vargas, H.A., et al., Diffusion-weighted Endorectal MR Imaging at 3 T for Prostate Cancer:Tumor Detection and Assessment of Aggressiveness. Radiology , 2011. 259(3): p. 775-784.
  3. Mulkern, R.V., et al., Biexponential characterization of prostate tissue water diffusion decay curves over an extended b-factor range. Magnetic Resonance Imaging , 2006. 24(5): p. 563-568.
  4. ShinMoto, H., et al., Biexponential apparent diffusion coefficients in prostate cancer. Magnetic Resonance Imaging , 2009. 27(3): p. 355-359.
  5. Bourne, R., et al., Biexponential Diffusion Decay in Formalin Fixed Prostate Tissue: Preliminary Findings. Magnetic Resonance in Medicine, 2012: Early view.. DOI: 10.1002/mrm.23291.
  6. Bourne, R., et al., Microscopic Diffusion Anisotropy in Formalin Fixed Prostate Tissue: Preliminary Findings. Magnetic Resonance in Medicine, 2012: p. Early view. DOI 10.1002/mrm.24179.

 

 


Written by:

Roger Bourne, PhD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

Senior Lecturer 

Discipline of Medical Radiation Sciences
Faculty of Health Sciences

The University of Sydney

75 East Street
Lidcombe, NSW 2141
 


 

Biexponential diffusion decay in formalin-fixed prostate tissue: Preliminary findings - Abstract

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