Development of Synchrotron Based Imaging Tools for Benign Prostatic Hyperplasia Using an Induced Canine Model
Date
2019-09-23
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
Type
Thesis
Degree Level
Masters
Abstract
Benign prostatic hyperplasia (BPH) is a disease that develops spontaneously in men and dogs, and the dog is an accepted model to study BPH in men. As the gland can also be the site of a malignant cancer, definitive diagnosis relies on histological evaluation of prostate tissue following an invasive biopsy. The use of a new imaging technique, synchrotron-based phase contrast computed tomography (PC-CT) for excised prostates shows great detail of the internal structure of the gland, comparable to that of low power histology. Considering this fact, our main objective was to induce BPH in dogs using a combination of hormones dihydrotestosterone (DHT) and estradiol and verify if PC-CT imaging of in situ prostate glands of live dogs allowed for improved non-invasive imaging details compared to conventional medical imaging modalities and early diagnosis of BPH. Two studies were conducted to achieve the objectives.
The first study involved the induction of BPH using intact male dogs with DHT and estradiol. The control group (n=3) received triolein carrier and the BPH induction group (n=3) received the hormone combination of DHT and estradiol (dissolved in triolein) injections three times/week for 35 weeks. Parameters that were assessed to diagnosis BPH were in vivo prostate volumes calculated using computed tomography (CT) images, volume of excised prostates determined using water displacement, 3D measurements of the excised gland, semen analysis, digital rectal exam (DRE), hormone analysis (estradiol, testosterone, DHT and canine prostate specific esterase CPSE), morphometric analysis and histological assessment of the tissue slides. The results showed that the gland volumes calculated both in vivo and ex vivo and the 3D measurements from BPH induction group were numerically higher than the control group. Sperm count decreased for all dogs but was reduced to zero or almost zero in the BPH induction group. The CPSE hormone analysis indicated that 1 dog from the treatment and 1 dog from the control group had BPH according to the manufacture’s defined threshold value. DHT hormone levels were higher for the induction group than controls throughout the entire study. This consequently affected the endogenous testosterone and estradiol, which were both decreased due to the negative feedback in the hypothalamic-pituitary-gonadal (HPG) axis. For DRE, prostates from all dogs were found to be enlarged in size by the end of the study and the histological diagnosis revealed that all dogs have a certain degree of BPH.
The second study involved the imaging of all six dogs with conventional non-invasive modalities (magnetic resonance imaging, MRI; CT; positron emission tomography, PET-CT; ultrasound, US; radiographs) plus the innovative PC-CT technique at the Canadian Light Source (CLS). None of these techniques resulted in images with the same level of fine detail as that obtained with previous PC-CT imaging of excised canine prostates. Comparisons among images from the various modalities determined that the best modality for the visualization of the internal structures of the prostate gland such as capsule, parenchyma, septa, lobe, urethra and cysts was MRI (T2), followed by US and CT. PC-CT images were comparable with PET-CT, allowing the visualization of the lobes and urethra filled with tracer.
In conclusion, all dogs developed BPH, either spontaneously (control group) or following induction (treatment group). Also, images of the in situ prostate gland of dogs were acquired for the first time at the CLS with the PC-CT technique. Although the quality and resolution was not as expected in comparison with PC-CT images of excised canine prostates, this technique shows promise and with additional study and development has the potential to become a useful diagnostic methodology.
Description
Keywords
BPH, PC-CT, DHT, estradiol, prostate gland, dog, CLS, synchrotron, in vivo imaging
Citation
Degree
Master of Science (M.Sc.)
Department
Small Animal Clinical Sciences
Program
Small Animal Clinical Sciences