<p>Prostate cancer (PCa) is the most common non-cutaneous cancer in men in the United States. Early detection of PCa is essential for improving treatment outcomes and survival rates. However, diagnosis of PCa at an early stage is challenged by the lack of an imaging method that can accurately visualize PCas. Because pathological processes change the mechanical properties of the tissue, elasticity imaging methods have the potential to differentiate PCas from other prostatic tissues. Acoustic radiation force impulse (ARFI) imaging is a relatively new elasticity imaging method that visualizes the local stiffness variations inside soft tissue.</p><p>The work presented in this dissertation investigates the feasibility of prostate ARFI imaging. Volumetric ARFI data acquisition and display methods were developed to visualize anatomic structures and pathologies in <italic>ex vivo </italic>human prostates. The characteristic appearances of various prostatic tissues in ARFI images were identified by correlating ARFI images with McNeal's zonal anatomy and the correlated histological slides, in which prostatic pathologies were delineated by a pathologist blinded to the ARFI images. The results suggest ARFI imaging is able to differentiate anatomic structures and identify suspicious PCa regions in the prostate.</p><p>To investigate the correlation between ARFI displacement amplitudes and the underlying tissue stiffness in the prostate ARFI images, the mechanical properties of prostatic tissues were characterized using a quantitative method, based upon shear wave elasticity imaging (SWEI). Co-registered ARFI and SWEI datasets were acquired in excised prostate specimens to reconstruct the shear moduli of prostatic tissues. The results demonstrated that variations in ARFI displacement amplitudes were inversely related to the underlying tissue stiffness; and the reconstructed shear moduli of prostatic tissues had good agreements with those reported in literature. The study suggests the matched ARFI and SWEI datasets provide complementary</p><p> information about tissue's elasticity. </p><p>To increase the efficiency of the data acquisition, a novel imaging sequence was developed to acquired matched ARFI-SWEI datasets without increasing the number of excitations compared to a conventional ARFI imaging sequence. Imaging parameters were analyzed both theoretically and experimentally. An analytical model was derived to quantify the fundamental accuracy limit in the reconstructed shear modulus, and demonstrated good agreement with the experimental data. The novel sequence was demonstrated in tissue-mimicking phantoms.</p><p>Finally, ARFI imaging sequences were developed in a transrectal probe, and ARFI images were presented from <italic>in vivo</italic> data acquired in patients under radical prostatectomy. The <italic>in vivo</italic> ARFI images demonstrated decreased contrast and resolution as compared to the matched <italic>ex vivo</italic> ARFI data. However, prostate anatomy and some PCa were successfully visualized in the <italic>in vivo</italic> ARFI images. Thus, we conclude that ARFI imaging has the potential to provide image guidance for locating cancerous regions during PCa diagnosis and treatment.</p> / Dissertation

published_or_final_version / Anatomy / Master / Master of Philosophy

Not available / text

Hyperthermia based cancer treatments delivered under various modalities have the potential to become an effective option to eradicate the disease, maintain functionality of infected organs, and minimize complications and relapse. Moreover, hyperthermia therapies are a form of minimally invasive cancer treatment which are key to improving the quality of life post-treatment. Many modalities are available for delivering the heat source. However, the ability to control the energy deposition to prevent damage to adjacent healthy tissue is a limiting factor in all forms of thermal therapies, including cryotherapy, microwave, radio-frequency, ultrasound, and laser. The application of a laser heat source under the guidance of real-time treatment data has the potential to provide unprecedented control over the temperature field induced within the biological domain. The computational infrastructure developed in this work combines a computational model of bioheat transfer based on a nonlinear version of the Pennes equation for heterogeneous media with the precise timing and orchestration of the real-time solutions to the problems of calibration, optimal control, data transfer, registration, finite element mesh refinement, cellular damage prediction, and laser control; it is an example of Dynamic-Data-Driven Applications System (DDDAS) in which simulation models interact with measurement devices and assimilates data over a computational grid for the purpose of producing high-fidelity predictions of physical events. The tool controls the thermal source, provides a prediction of the entire outcome of the treatment and, using intra-operative data, updates itself to increase the accuracy of the prediction. A precise mathematical framework for the real-time finite element solution of the problems of calibration, optimal heat source control, and goal-oriented error estimation applied to the equations of bioheat transfer is presented. It is demonstrated that current finite element technology, parallel computer architecture, data transfer infrastructure, and thermal imaging modalities are capable of inducing a precise computer controlled temperature field within a biological domain. The project thus addresses a set of problems falling in the intersection of applied mathematics, imaging physics, computational science, computer science and visualizations, biomedical engineering, and medical science. The work involves contributions in the three component areas of the CAM program; A, Applicable Mathematics; B, Numerical Analysis and Scientific Computing; and C, Mathematical modeling and Applications. The ultimate goal of this research is to provide the medical community a minimally invasive clinical tool that uses predictive computational techniques to provide the optimal hyperthermia laser treatment procedure given real-time, patient specific data. / text

Prostate-specific antigen (PSA) testing has caused a steep increase in the incidence of prostate cancer, especially the incidence of localised low risk disease. In order to decrease the overdiagnosis accompanied by PSA testing, analysis of inherited genetic variants have been suggested as potential tools for clinical assessment of disease risk. With the aim of minimizing overtreatment and postpone side-effects of curative treatment for low risk prostate cancer, active surveillance, a treatment strategy with initial surveillance and deferred radical prostatectomy at the time of progression has evolved.  The aim of this thesis was to study the validity of PSA (paper I) and inherited genetic variants (paper II) for early diagnosis of prostate cancer, to assess the extent of PSA testing in Sweden (paper III), and to study the safety of deferred radical prostatectomy in localised low to intermediate risk prostate cancer (paper IV). The study designs were i) case-control studies nested within the Västerbotten intervention project (paper I and II), ii) observational study in the Cancer Register of Sweden (paper III), and iii) observational study in the NPCR Follow-up study (paper IV). PSA had a high validity in predicting a prostate cancer diagnosis with an area under the receiver operating characteristics (ROC) curve of 0.86 (95% CI, 0.84 to 0.88). A combined test, including PSA, the ratio of free to total PSA, and 33 single nucleotide polymorphisms (SNPs) in a genetic risk score, increased the area under curve to 0.87 (95% CI, 0.85 to 0.89). The estimated uptake of PSA testing among men aged 55 to 69 years increased from zero to 56% between 1997 and 2007 and there were large variations in the uptake of PSA testing between counties in Sweden. After a median follow-up time of eight years there was no significant difference in presence of any one or more adverse pathology features or prostate cancer specific mortality after primary compared to deferred radical prostatectomy in localised low to intermediate risk prostate cancer. Results from these studies indicate that PSA and the hitherto identified SNPs are not suitable biomarkers in single-test prostate cancer screening. It is possible to estimate the uptake of PSA testing on a population level. Initial surveillance and deferred radical prostatectomy represent a feasible treatment strategy in localised low to intermediate risk prostate cancer.

Prostate cancer continues to be the most commonly diagnosed cancer among men. Brachytherapy has emerged as one of the definitive treatment options for early stage prostate cancer which entails permanent implantation of radioactive seeds into the prostate to eradicate the cancer with ionizing radiation. Successful brachytherapy requires the ability to perform dosimetry -which requires seed localization- during the procedure but such function is not available today. If dosimetry could be performed intraoperatively, physicians could implant additional seeds into the under-dosed portions of the prostate while the patient is still on the operating table. This thesis addresses the brachytherapy seed localization problem with introducing intensity based registration between transrectal ultrasound (TRUS) that shows only the prostate and a 3D seed model drawn from fluoroscopy that shows only the implanted seeds. The TRUS images are first filtered and compounded, and then registered to the seed model by using mutual information. A training phantom was implanted with 48 seeds and imaged. Various ultrasound filtering techniques were analyzed. The effect of false positives and false negatives in ultrasound was investigated by randomly masking seeds from the fluoroscopy volume or adding seeds to that in random locations. Furthermore, the effect of sparse and dense ultrasound data was analyzed by running the registration for ultrasound data with different spacing. The registration error remained consistently below clinical threshold and capture range was significantly larger than the initial guess guaranteed by the clinical workflow. This fully automated method provided excellent registration accuracy and robustness in phantom studies and promises to demonstrate clinically adequate performance on human data. / Thesis (Master, Electrical & Computer Engineering) -- Queen's University, 2008-09-27 12:35:16.691

High grade intraepithelial neoplasia (HGPIN) and atypical small acinar proliferation (ASAP) are two pathological lesions associated with prostate adenocarcinoma. HGPIN is an architectural finding, while ASAP is a term used to describe a lesion that cannot confidently be diagnosed as prostate adenocarcinoma. The mean incidence rate for HGPIN is 7.7% with a median of 5.2% and range of 0-24.6% and the cancer detection rate mean is 18.1%. The mean incidence rate for ASAP is 5.0% with a median of 4.4% and a range of 0.7-23.4%. The mean cancer detection rate is 40.2%. Currently, the incidence and cancer detection rates for HGPIN and ASAP for Winnipeg, Manitoba, have not been published. A retrospective study was conducted on all prostate biopsies collected from the Manitoba Cancer Care Prostate Centre (MCCPC) from 2008 and 2009. Prostate biopsies with a diagnosis of isolated HGPIN and or ASAP and no previous history of cancer were included in this study. In Winnipeg, Manitoba, from 2008-2009, the mean HGPIN incidence rate was 5.0% and the mean cancer detection rate was 46.1%. The mean ASAP incidence rate was 4.6% and the mean cancer detection rate of 48.2%. As a control, the cancer detection rate following a benign diagnosis was also calculated at 33.3%. The mean incidence and cancer detection rates for HGPIN and ASAP for Winnipeg, Manitoba are slightly lower than literature, but still fall within the published range. In addition, the mean ASAP cancer detection rate is similar to the cancer detection rate following a benign diagnosis indicating that, in our study, both a benign finding and a diagnosis of ASAP hold the same predictive value for cancer on a subsequent re-biopsy.

Messenger RNA (mRNA) posttranscriptional regulation has been implicated in the development and/or progression of several diseases including many types of cancer, rheumatoid arthritis, vascular disease, and Alzheimer's disease. Differential regulation of Androgen Receptor (AR) mRNA has been associated specifically with prostate cancer progression. In this thesis, molecular beacons were developed to allow for the detection of the expression and localization of AR mRNA in live prostate cancer cells. These beacons were then applied as a tool for studying how AR mRNA regulation is involved in prostate cancer growth and advancement. Two AR mRNA targeted beacons were designed and tested in solution and in live cells to determine their functionality. The beacon-based approach for AR mRNA detection was then optimized through the use of the two beacons in tandem and alteration of their backbone chemistry. A series of validation tests were performed on these beacons, including testing their abilities to: 1) produce a feasible localization pattern, 2) discriminate between AR positive (AR+) and AR negative (AR-) prostate cancer cell lines and 3) follow stimulus-induced changes in AR mRNA expression. Based on these results, a dual chimeric beacon approach was selected to determine the role of AR mRNA regulation in two systems that represent important stages in prostate cancer growth and progression: 1) hormone stimulation of androgen-dependent prostate cancer cells and 2) progression of androgen-dependent prostate cancer cells to the androgen-independent state. Our results suggest that changes in AR mRNA expression, organization, and localization may be indicative of molecular mechanisms involved in these critical transitions associated with prostate cancer progression. Taken together, this work provides a feasibility study for visualizing changes in AR mRNA state as a diagnostic measure for evaluating the aggressiveness of the disease and demonstrates the possible utility of therapeutically targeting AR mRNA regulation in order to prevent prostate cancer advancement.

Familial aggregation of prostate cancer has been demonstrated in studies conducted in a number of countries prior to the widespread adoption of prostate-specific antigen (PSA) testing for prostate cancer detection. PSA testing leads to over-diagnosis of asymptomatic disease that may not have become clinically significant within a man’s normal lifetime. This increase in the number of asymptomatic men diagnosed might alter the magnitude of familial risk estimates and the importance of a prostate cancer family history. (For complete abstract open document)

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.