Prostate cancer (PCa) is the most common cancer, other than skin cancer, among American men. The accuracy of prostate MRI has improved over the past decade, partly relating to advances in scanner and receiver coil hardware. However, it has been the emergence of diffusion-weighted imaging (DWI) as a central component of prostate MRI acquisition and interpretation that has been crucial to MRI's current impact. Apparent diffusion coefficient (ADC) values derived from DWI are significantly associated with tumor aggressiveness shown in several studies (1-3). Overlap of metabolites is a major limitation in one-dimensional (1D) spectral-based single voxel MR Spectroscopy (MRS) and multivoxel-based MR spectroscopic imaging (MRSI). By combining echo-planar spectroscopic imaging (EPSI) with two-dimensional (2D) J resolved spectroscopic sequence (JPRESS), 2D spectra can be recorded in single (4) and multiple slices of prostate using five dimensional (5D) Echo-Planar J-Resolved Spectroscopic Imaging (EP-JRESI) (5). Compressed Sensing (CS) is a technique for accelerating the inherently slow data acquisition process, and is well suited for MRSI due to its intrinsic denoising effect. In this study, semi LASER (sLASER) based 5D EP-JRESI was used to quantitate changes in prostate metabolites (citrate (Cit), creatine (Cr), choline (Ch) and myoinositol (mI)) using compressed sensing reconstruction by minimizing total variation method and correlated with DWI findings.The NUS based 5D EP-JRESI sequence and the conventional DWI were evaluated in nine PCa patients (mean age 64.0 years) using a 3T MRI scanner (Siemens Medical Systems, Germany) using endorectal ‘receive’ coil. Axial DWI images were recorded using the single-shot echo planar imaging technique using the following imaging parameters: TR/TE= 2000/83 ms, 27cm FOV, 4-mm slice thickness, 0 mm intersection gap, 3 averages. Isotropic diffusion weighted images were obtained by using diffusion gradients with three b-values (0, 50 and 400 sec/mm²) along three directions of motion-probing gradients. In the 5D EP-JRESI data, CS reconstruction was then performed by solving the total variation minimization problem using the linearized Bregman iteration. The 5D EP-JRESI parameters were: FOV = 160x160x120 mm³, image matrix = 16x16x8, spectral width (F₂) = 1190 Hz, number of spectral points = 256, TE = 41ms, TR = 1.2s, Avg=1. For the second dimension (F₁), 64 increments with bandwidths of 1000Hz were used. Data acquisition included water-suppressed (WS) and non-water-suppressed (NWS) scans (20 mins). The NWS scan was used to perform eddy current and spectral phase correction. A 8X NUS scheme was imposed along the two spatial dimensions (k_y, k_z and t₁). Extractable individual voxel volume in prostate was 1.5 ml. The 5D EP-JRESI data acquired in the PCa patients were extracted and post-processed using a homebuilt MATLAB-based (The Mathworks, Natick, MA, USA) library of programs. The FWHM was approximately 18Hz observed in all the PCa patients. Eight patients were investigated using the 3T Prisma and one using the 3T Trio-Tim scanner. A p-value of <0.05 was considered significant.Fig.1 shows the ADC values of PCa patients in cancer and non-cancer regions. The mean and standard deviation (SD) ADC values were: 1.18 ±0.05 and 1.51 ±0.10-3 mm²/sec in cancer and unaffected regions. Significant changes observed between cancer and non-cancer regions (p<0.05). Using the NUS based 5D EP-JRESI data, 2D peaks due to Cit, Ch, Cr and mI, were quantified in cancer and non-cancer regions using the home-developed peak integration MATLAB code. Figs. 2 shows the (Ch+Cr)/Cit and (Ch+Cr)/mI of cancerous and non-cancerous regions processed using total variation method. The mean metabolite ratios and SD of (Ch+Cr)/Cit of cancer and non- cancerous regions processed using TV was: 0.379 ±0.094 and 0.228 ±0.69. Similarly (Ch+Cr)/mI was: 4.531 ±1.60 and 3.137 ±1.56. Fig.3 shows the Cit and Ch metabolites map of 65 year old PCa patient processed using 5D EP-JRESI data. Significant changes observed in (Ch+Cr)/Cit and (Ch+Cr)/mI in cancer and non-cancer regions. The metabolites ratios were inversely correlated with ADC values (p<0.05). In this study, we observed increased (Ch+Cr)/Cit and (Ch+Cr)/mI ratios in the cancer compared to non–cancer locations which agree with our earlier findings of slice based four dimensional (4D) EP-JRESI technique (4). Decrease in zinc is a prerequisite to the decrease in citrate level in prostate cancer (6). The osmoregulator myo-inositol is expressed in a variety of tissues, and its decrease was observed in PCa within human expressed prostatic secretions (EPS) using high resolution NMR (7).The advantage of compressed sensing based 5D EP-JRESI sequence is in recording short TE-based spectra from multiple regions of human prostate and it can be easily combined with DWI and other protocols. These pilot findings need further validation using larger cohorts.