Microstructure Characterization of Bone Metastases from Prostate Cancer with Diffusion MRI: Preliminary Findings.

Colleen Bailey,Veronica A Morgan,Martin O Leach,David J Hawkes,Matthew R Orton,Daniel C Alexander,Eleftheria Panagiotaki,Nina Tunariu,David J Collins,Thorsten Feiweier

doi:10.3389/fonc.2018.00026

Abstract

To examine the usefulness of rich diffusion protocols with high b-values and varying diffusion time for probing microstructure in bone metastases. Analysis techniques including biophysical and mathematical models were compared with the clinical apparent diffusion coefficient (ADC). Four patients were scanned using 13 b-values up to 3,000 s/mm2 and diffusion times ranging 18-52 ms. Data were fitted to mono-exponential ADC, intravoxel incoherent motion (IVIM), Kurtosis and Vascular, extracellular, and restricted diffusion for cytometry in tumors (VERDICT) models. Parameters from the models were compared using correlation plots. ADC and IVIM did not fit the data well, failing to capture the signal at high b-values. The Kurtosis model best explained the data in many voxels, but in voxels exhibiting a more time-dependent signal, the VERDICT model explained the data best. The ADC correlated significantly (p < 0.004) with the intracellular diffusion coefficient (r = 0.48), intracellular volume fraction (r = -0.21), and perfusion fraction (r = 0.46) parameters from VERDICT, suggesting that these factors all contribute to ADC contrast. The mean kurtosis correlated with the intracellular volume fraction parameter (r = 0.26) from VERDICT, consistent with the hypothesis that kurtosis relates to cellularity, but also correlated weakly with the intracellular diffusion coefficient (r = 0.18) and cell radius (r = 0.16) parameters, suggesting that it may be difficult to attribute physical meaning to kurtosis. Both Kurtosis and VERDICT explained the diffusion signal better than ADC and IVIM, primarily due to poor fitting at high b-values in the latter two models. The Kurtosis and VERDICT models captured information at high b using parameters (Kurtosis or intracellular volume fraction and radius) that do not have a simple relationship with ADC and that may provide additional microstructural information in bone metastases.

Highlights

Bone metastases, the most common site of metastatic disease in prostate cancer, are associated with reduced quality of life and an increased risk of complications from bone weakness
This study explores the potential of microstructure characterization in bone metastases using a rich diffusion protocol with b-values up to 3,000 s/ mm2 and a range of diffusion times, fitting with a variety of diffusion models
This was consistent across all regions of interest (ROIs), as shown by the boxplots in Figure 2B, which demonstrate that apparent diffusion coefficient (ADC) and intravoxel incoherent motion (IVIM) models have much higher median ΔAIC across all voxels

Summary

Introduction

The most common site of metastatic disease in prostate cancer, are associated with reduced quality of life and an increased risk of complications from bone weakness. Histology is not generally feasible in bone and there are currently no imaging criteria for detecting benefit or improvement following therapy in osteoblastic bone metastases [1]. There is, a need for new imaging techniques and those sensitive to the tissue microstructure, such as the apparent diffusion coefficient (ADC), have shown promise in predicting response [2]. ADC is a relatively broad reflection of the tissue microstructure. Studies in other tumor types demonstrate that more advanced diffusion techniques can provide additional information. The inclusion of varying diffusion times reveals information about important length scales, such as the cell size and organization, as has been demonstrated in breast cancer [4]

Methods

Results

Conclusion