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Improved Prostate Cancer Diagnosis Using Hybrid Multi-Dimensional MRI - Beyond the Abstract

While prostate MRI is increasingly being used in the diagnosis of prostate cancer, histologic analysis after an invasive procedure (biopsies) remains the gold standard. The Gleason grading system looks at the tissue changes – mainly the changes in the glandular and tissue architecture. However, it is not feasible to image in-vivo at such high resolution using clinical MRI scanners to see these glandular structures or architectural changes. However, along with these tissue architecture changes, numerous studies have shown that there is a change in tissue composition with the presence and increasing Gleason grade of cancer.1,2 Furthermore, we know that these tissue components (stroma, epithelium and lumen) have distinct MRI properties (diffusion and T2 relaxometry) associated with each of these tissue components based on high field preclinical scanner (16T),3 which can be exploited to measure tissue composition changes non-invasively and diagnose prostate cancer. This is the basis of our technique Hybrid Multi-dimensional MRI (HM-MRI) that we have developed at the University of Chicago.

HM-MRI images the prostate over a larger imaging space by changing imaging parameters over multiple dimensions through echo time (T2 weighting) and b-values (diffusion weighting) and use our developed three-compartment prostate tissue model to measure fractional volumes of these tissue compositions non-invasively. Our initial feasibility work published in Radiology showed that it was feasible to measure these fractional volumes of stroma, epithelium, and lumen, and cancers are associated with increased epithelium volume (due to highly proliferating cancers cell that is epithelial in nature) and reduced stroma and lumen space.4

We validated our non-invasive tissue composition measures from MRI with 3 expert genitourinary pathologists in our work entitled “Histological validation of prostate tissue composition measurement using hybrid multi-dimensional MRI: agreement with pathologists' measures” which was recently published in Abdominal Radiology.5 Our recent work demonstrate that the tissue composition measured non-invasively using HM-MRI matches very closely with the reference standard results from the consensus of 3 expert pathologists. Axial HM-MRI was acquired on 3T MR scanners all combinations of echo times of 57, 70, 150, 200 ms and b-values of 0, 150, 750, 1500 s/mm2, and data were fitted using a 3-compartment signal model using our developed software to generate volumes for each tissue component (stroma, epithelium, lumen). Three experienced genitourinary pathologists independently as well as in consensus reviewed each histology image and provide an estimate of the percentage of epithelium and lumen for regions-of-interest corresponding to MRI. Agreement statistics were performed for tissue composition measured using HM-MRI and reference standard results from pathologists’ consensus. We showed that the agreement in tissue composition measurement using HM-MRI and consensus of pathologists is on par with the inter-raters (pathologists) agreement. This is a step towards ‘virtual pathology’. In addition, high diagnostic accuracy based on high area under the receiver operating characteristic curve using tissue composition measures from HM-MRI and pathologists suggests prostate cancer could be differentiated from benign tissue as indicated by increased epithelium and reduced luminal volume in prostate cancer compared to benign tissue.

We further validated our HM-MRI results with results from quantitative histology, showing that tissue composition measured by using HM-MRI had excellent correlation (Pearson correlation = 0.91) with quantitative histologic evaluation which was published in Radiology [6]. Most importantly a prospective validation of HM-MRI to guide prostate biopsy and in diagnosing cancer is currently underway in a registered clinical trial (ClinicalTrials.gov Identifier: NCT03585660). The initial results from our clinical trial were presented at RSNA 2020 that showed very promising results using HM-MRI as a standalone tool is slightly better than expert radiologists using conventional multiparametric MRI (mpMRI) in guiding biopsies to detect clinically significant prostate cancers. In another multi-reader study that recently concluded (Lee et al – provisionally accepted in Radiology) we showed that the performance of radiologists (3 of the 4 readers) improved using HM-MRI compared to mpMRI. In addition, the image interpretation time was reduced while using HM-MRI and had improved inter-radiologist agreement compared to mpMRI. Therefore, after these encouraging results, we are in the process of cross vendor testing and validation in a multi-center trial of HM-MRI.

In conclusion, these studies show that tissue composition measured non-invasively using HM-MRI demonstrates not only excellent correlation with reference standard measures from histology but also that HM-MRI can be used to improve the diagnosis of prostate cancer.

Written by: Aritrick Chatterjee, PhD1,2

  1. Department of Radiology, University of Chicago, Chicago, IL
  2. Center of Excellence in Prostate Imaging and Image Guided Therapy, University of Chicago, Chicago, IL

References:

  1. Chatterjee A, Watson G, Myint E, Sved P, McEntee M, Bourne R. Changes in Epithelium, Stroma, and Lumen Space Correlate More Strongly with Gleason Pattern and Are Stronger Predictors of Prostate ADC Changes than Cellularity Metrics. Radiology 2015; 277:751-762
  2. Langer DL, van der Kwast TH, Evans AJ, et al. Prostate tissue composition and MR measurements: investigating the relationships between ADC, T2, K(trans), v(e), and corresponding histologic features. Radiology 2010; 255:485-494
  3. Bourne RM, Kurniawan N, Cowin G, et al. Microscopic diffusivity compartmentation in formalin-fixed prostate tissue. Magn Reason Med 2012; 68:614-620
  4. Chatterjee A, Bourne RM, Wang S, et al. Diagnosis of Prostate Cancer with Noninvasive Estimation of Prostate Tissue Composition by Using Hybrid Multidimensional MR Imaging: A Feasibility Study. Radiology 2018; 287:864-873
  5. Chatterjee, A., Antic, T., Gallan, A.J. et al. Histological validation of prostate tissue composition measurement using hybrid multi-dimensional MRI: agreement with pathologists’ measures. Abdom Radiol (2021). https://doi.org/10.1007/s00261-021-03371-7
  6. Chatterjee A, Mercado C, Bourne R, et al. Validation of prostate tissue composition using Hybrid Multidimensional MRI: Correlation with histology. Radiology 2021. https://doi.org/10.1148/radiol.2021204459
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