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MR imaging biomarkers for benign prostatic hyperplasia pharmacotherapy

by 1976- Jia, Guang

Abstract (Summary)
Benign prostatic hyperplasia (BPH) is a highly prevalent disease in older men and occurs in more than 50% of men aged 60 to 70 years. BPH results in prostate enlargement with bladder out ow obstruction. Treatment with a 5?-reductase inhibitor such as nasteride induces apoptosis in epithelial cells and leads to the reduction of prostate volume. However, pharmacologic treatment is not uniformly e ective in shrinking the prostate and in relieving symptoms, so the ability to predict how each patient will bene t best from varying pharmacotherapy is a question of great medical and economic importance. Finasteride is also used as a prophylaxis of BPH-associated hematuria and to reduce blood loss at surgical resection of the prostate. The important questions to be addressed include what is the optimum dose and how long should the patients be treated. An e ective non-invasive tool may be helpful to solve these questions by monitoring the changes in prostatic blood ow. Twenty-four male beagles with benign prostatic hyperplasia were enrolled in a drug trial and imaged at ve time points by magnetic resonance imaging (MRI). The capabilities of di erent MRI-based methodologies for measuring prostate volume were evaluated from anatomical MR images. The possibility of using pharmacokinetic parameters as a predictor of MRI prostate volume changes were evaluated and the use ii of DCE-MRI as a biologic marker of in-vivo changes in microcirculation in prostatic suburethral region was assessed. The segmented MRI prostate volume signi cantly correlated with post necropsy volume. The changes in prostate volume at the end of the treatment exhibited a signi cant linear correlation to the initial parenchymal Maximum Enhancement Ratio (MER) (p < 0.02) in the nasteride group. After completion of the therapeutic regiment, Tmax on prostatic suburethral area was signi cantly longer in the nasteride group compared to controls (p < 0.01), and the pharmacokinetic parameters amplitude A and exchange rate constant kep decreased 39% and 34% respectively in the nasteride group at the end of the treatment. In conclusion, MRI of prostate can supply important in-vivo biomarkers, such as organ volume and pharmacokinetic parameters, in the development of BPH pharmacotherapies such as 5?-reductase inhibitors. iii This is dedicated to the ones I love most: my parents and my wife Tanping iv
Bibliographical Information:

Advisor:

School:The Ohio State University

School Location:USA - Ohio

Source Type:Master's Thesis

Keywords:benign prostatic hyperplasia prostate biochemical markers

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