Voxel Level Radiologic–Pathologic Validation of Restriction Spectrum Imaging Cellularity Index with Gleason Grade in Prostate Cancer

Abstract

Purpose: Restriction spectrum imaging (RSI-MRI), an advanced diffusion imaging technique, can potentially circumvent current limitations in tumor conspicuity, in vivo characterization, and location demonstrated by multiparametric magnetic resonance imaging (MP-MRI) techniques in prostate cancer detection. Prior reports show that the quantitative signal derived from RSI-MRI, the cellularity index, is associated with aggressive prostate cancer as measured by Gleason grade (GG). We evaluated the reliability of RSI-MRI to predict variance with GG at the voxel-level within clinically demarcated prostate cancer regions.Experimental Design: Ten cases were processed using whole mount sectioning after radical prostatectomy. Regions of tumor were identified by an uropathologist. Stained prostate sections were scanned at high resolution (75 mm/pixel). A grid of tiles corresponding to voxel dimensions was graded using the GG system. RSI-MRI cellularity index was calculated from presurgical prostate MR scans and presented as normalized z-score maps. In total, 2,795 tiles were analyzed and compared with RSI-MRI cellularity.Results: RSI-MRI cellularity index was found to distinguish between prostate cancer and benign tumor (t ¼ 25.48, P < 0.00001). Significant differences were also found between benign tissue and prostate cancer classified as low-grade (GG ¼ 3; t ¼ 11.56, P < 0.001) or high-grade (GG ! 4; t ¼ 24.03, P < 0.001). Furthermore, RSI-MRI differentiated between low and high-grade prostate cancer (t ¼ 3.23; P ¼ 0.003).Conclusions: Building on our previous findings of correlation between GG and the RSI-MRI among whole tumors, our current study reveals a similar correlation at voxel resolution within tumors. Because it can detect variations in tumor grade with voxel-level precision, RSI-MRI may become an option for planning targeted procedures where identifying the area with the most aggressive disease is important. Clin Cancer Res; 22(11); 2668-74. Ó2016 AACR.

Inflammation appears as high Prostate Imaging–Reporting and Data System scores on prostate magnetic resonance imaging (MRI) leading to false positive MRI fusion biopsy

“…A novel MRI acquisition protocol named restriction spectrum imaging (RSI) may be able to parse the signal of inflammation and cancer [15]. RSI-MRI in the prostate has specifically been shown to be more accurate than ADC values, improve tumor conspicuity, and alter signal between inflammation and cancer [16171819]. Other groups have investigated more efficient use of intravenous contrast enhancement techniques to distinguish aggressive tumors [20].…”

Voxel-level biological optimisation of prostate IMRT using patient-specific tumour location and clonogen density derived from mpMRI

“…Many studies applied a focal boost dose to sub-volumes identified as abnormal regions on quantitative images [ 7 , 14 , 50 , 60 ], including the FLAME-trial [ 37 ]. However, the use of sub-volumes means discretisation of tumour characteristics such as clonogen density and hypoxia, whereas typically these characteristics vary continuously throughout the gland [ 1 , 21 , 41 , 42 , 68 ]. In studies where voxel-level information was utilised, simple linear relationships between image intensities and doses were frequently assumed [ 3 , 14 , 60 ], or non-validated dose prescription functions were used [ 4 , 18 , 31 , 38 , 48 , 52 , 65 ].…”

Restriction spectrum imaging: An evolving imaging biomarker in prostate MRI

“…On a voxel‐by‐voxel basis, RSI CI was significantly different among benign (mean RSI cellularity index = 0.16), low grade (mean score = 1.15) and high grade disease (mean score = 1.52) with increasing cellularity index correlating to increasing Gleason grade. Thus RSI CI correlates with Gleason grade at the voxel level, reflecting variation within individual tumors …”

“…Thus RSI CI correlates with Gleason grade at the voxel level, reflecting variation within individual tumors. 55…”