GENITOURINARY IMAGING P rostate cancer (PCa) is the fourth most commonly diagnosed cancer and ranked eighth among the leading causes of cancer-related deaths worldwide (1). The aggressiveness of PCa is indicated by the Gleason score (GS), which is important for guiding management and predicting clinical outcome (2). Previous studies have demonstrated that GS is closely associated with pathologic characteristics in PCa. For instance, the proliferation of epithelial cells and tumor cells and reduced stroma and lumen volumes are hallmarks of high-risk PCa (3).Multiparametric MRI, especially diffusion MRI, plays an indispensable role, given its high sensitivity for PCa detection (4,5). The diffusion MRI-derived apparent diffusion coefficient (ADC) is traditionally considered to reflect the cellularity of tumors based on empirical observations (3). However, ADC is only an overall measure of the water diffusivity that is determined by multiple microstructural features, such as the intra-and extracellular space, cell size, permeability, and intrinsic diffusivity. More specific imaging markers for characterizing specific tumor microstructure are urgently needed for precise description of the pathologic characteristics of PCa.Progress in multidimensional diffusion MRI has enhanced our capacity to probe tissue microstructure by using different diffusion weightings (q-space) and varying diffusion times (t-space) (6), opening new avenues in PCa research (7-10). Particularly, the recent development of time-dependent diffusion MRI has demonstrated unique advantages in depicting cellular microstructures by characterizing the diffusion time dependence of restricted water diffusion and relating the diffusion time dependence to specific microstructural parameters (11,12). Background: Recently developed time-dependent diffusion MRI has potential in characterizing cellular tissue microstructures; however, its value in imaging prostate cancer (PCa) remains unknown. Purpose: To investigate the feasibility of time-dependent diffusion MRI-based microstructural mapping for noninvasively characterizing cellular properties of PCa and for discriminating between clinically significant PCa and clinically insignificant disease.
Materials and Methods:Men with a clinical suspicion of PCa were enrolled prospectively between October 2019 and August 2020. Time-dependent diffusion MRI data were acquired with pulsed and oscillating gradient diffusion MRI sequences at an equivalent diffusion time of 7.5-30 msec on a 3.0-T scanner. Time-dependent diffusion MRI-based microstructural parameters, including cell diameter, intracellular volume fraction, cellularity, and diffusivities, were estimated with a two-compartment model. These were compared for different International Society of Urological Pathology grade groups (GGs), and their performance in discriminating clinically significant PCa (GG .1) from clinically insignificant disease (benign and GG 1) was determined with a linear discriminant analysis. The fitted microstructural parameters were validate...