The goal of this project is to determine the composition of the choline resonance and map it's spatial distribution in the human prostate prior to and after non-surgical therapy in order to investigate it's reliability as a sensitive, specific marker for cancer. The rationale for using 3-D MRSI for the follow-up of prostate cancer therapy is that currently available techniques (transrectal ultrasound, CT, MRI) cannot differentiate quiescent cells and necrotic debris from proliferating neoplastic cells, so an accurate assessment of residual or recurrent disease is lacking. The feasibility of this proposal is supported by recent studies which have demonstrated the potential of endorectal 1H localized spectroscopy to differentiate between normal, benign hyperplastic (BPH), malignant and necrotic tissues in the in situ human prostate. Using PRESS volume selection with 3-D phase encoding, we have demonstrated that it is possible to measure citrate and choline levels throughout the in situ normal and pathologic human prostate at a spatial resolution as small as 0.24 in 17 minutes, adding an overall 30 minutes to clinical MRI exams. In preliminary studies we have also observed changes in prostatic citrate and choline levels after cryosurgery that have correlated with clinical markers of therapeutic response. While our preliminary 3-D MRSI results so far correlate well with clinical findings, the identification of the components making up the observed choline resonance and correlation of changes in the composition of choline with disease progression or response to therapy would make a major contribution to our understanding of the biological significance of the abnormalities which we have observed. The goal of this project will be accomplished using quantitative high resolution (500 MHz) 1H spectroscopy of surgically removed tissues, or biopsy samples to determine the composition of the in vivo choline resonance. In the same patients, high resolution (0.24 cc) choline distributions will be determined using 3D MRSI and overlaid on high resolution magnetic resonance (MR) images acquired within the same exam. The volume in vivo 1H MRSI/MRI data will be correlated with the in vitro high resolution NMR results, step-sectioned histopathology of the surgically removed prostate, and histologic and cell cycling analysis of biopsy samples. We will determine the normal choline composition and distribution in the human Prostate and seminal vesicles by studying ten patients who are having their prostate surgically removed due to bladder cancer. We will determine the composition and distribution of choline in Cancer and BPH by studying thirty prostate cancer patients who are awaiting radical prostatectomy. These will include 10 poorly- differentiated, 10 moderately differentiated and 10 well differentiated cancers. Finally, we will determine whether significant levels of choline and citrate are present in necrotic tissue and whether the composition of the choline resonance in regions of residual cancer, BPH and normal tissues change after therapy in ten patients who undergo cryosurgery for prostate cancer. The proposed research will greatly enhance our ongoing clinical studies of prostate cancer therapy by providing a careful evaluation of the relationship between the level of the in vivo choline resonance, its composition and cancer prior to and after therapy.
