Thesis (Ph. D.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.

Thesis (Ph. D.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.

Thesis (Ph.D.) - University of Queensland, 2006. / Includes bibliography.

This thesis describes the development of new magnetic resonance imaging (MRI) methods to characterize cardiac tissue with myocardial infarction (MI). Wall motion imaging (for visualizing myocardial contraction) and viability imaging (to identify MI) are two components of cardiac tissue characterization used for prognosis and treatment planning. MRI-based wall motion and viability methods are considered the gold standard in imaging, and characterization of MRI viability images has been correlated with inducibility for ventricular tachycardia (VT). However, viability imaging with MRI has limitations such as difficulty visualizing the blood-infarct border. Wall motion and viability images are acquired separately, each requiring cardiac gating and breath holds, leading to long scan times. A novel multi-contrast delayed enhancement (MCDE) sequence was developed that simultaneously acquires wall motion and viability images. In a patient study, the MCDE sequence was demonstrated to provide improved visualization of MI compared to the conventional inversion-recovery gradient echo (IR-GRE) sequence, particularly for small infarcts adjacent to the blood pool. MCDE images also provided accurate wall motion images that could be used to calculate the left ventricular ejection fraction. An image processing algorithm was developed to analyze MCDE images to segment and classify the infarct gray zone, which is hypothesized to represent heterogeneous infarct responsible for causing VT. In a study of 15 patients with MI, the MCDE-derived gray zone was shown to be less sensitive to image noise than the IR-GRE-derived gray zone, and did not require manual contours of the blood pool which contributes to additional variability in the IR-GRE gray zone analysis. Finally, a real-time delayed enhancement (RT-DE) method was developed to provide black-blood viability images without requiring cardiac gating or breath holds. RT-DE imaging was shown to have a high sensitivity for detecting MI in a study of 23 patients. The methods described in this thesis help expand the patient population that can undergo a cardiac viability exam and help improve the visualization of myocardial infarct. Further modifications in the pulse sequences to improve the temporal and spatial resolutions are proposed with the goal of predicting and guiding treatment of ventricular tachycardia resulting from myocardial infarct.

Prostate cancer is extremely prevalent, with shifting patient demographics leading to an increasing number of men balancing treatment efficacy with associated side-effects. Non-invasive characterization of disease – useful for guiding biopsy, to monitor disease progression during active surveillance, or for treatment planning of focal therapies – could have a significant impact on patient management. Through its excellent anatomic imaging capabilities and its ability to characterize physiologic properties, magnetic resonance imaging (MRI) has the potential to fulfill clinical goals; however, further improvements are necessary to maximize accuracy and impact. Thus, this thesis presents: 1) the development of a multi-parametric model to combine parameters derived from measurement of T2 relaxation, diffusion weighted imaging, and dynamic contrast-enhanced MRI to improve the discrimination between normal and malignant peripheral zone tissue; 2) determination of the impact that the presence of normal tissue within regions of tumour has on the measurement of apparent diffusion coefficient (ADC) and T2 relaxation in the peripheral zone; and 3) relationships between MRI measurement and underlying prostate tissue composition. A common patient cohort was used for all studies, with prostate cancer patients having in vivo MRI prior to prostatectomy followed by whole-mount histologic sectioning of the surgical specimens, facilitating the use of pathology as a gold-standard for all analyses. In the first study, the optimal multi-parametric model combines ADC, T2, and volume transfer constant (Ktrans) to yield the probability of malignancy for each voxel. Performance of the model is better than each single parameter, but not significantly so compared to ADC. The second study demonstrates that there is no difference in ADC and T2 between tumours containing significant portions of normal tissue and the surrounding normal tissue itself, indicating that full characterization of prostate cancer with MRI may be limited. Finally, by determining relationships between MRI parameters and tissue characteristics, the third study suggests mechanisms driving MR image appearance in the prostate, including the visualization of cancer. Taken together, this thesis presents potential improvements to prostate cancer imaging, and provides further insight into the interplay between the underlying histology and MRI.

Atherosclerotic plaque (AP) composition is an important factor influencing plaque rupture. Intraplaque hemorrhage (IPH) is a marker of complicated-plaque formation, responsible for many of the clinical manifestations of atherosclerotic disease. Magnetic resonance imaging (MRI) has emerged as a modality to image carotid AP. The in-vivo high-resolution MR imaging of carotid complicated-plaque forms the basis of this thesis. In the first part, Magnetic Resonance Imaging of Intraplaque Hemorrhage (MRIPH), an in-vivo high-spatial-resolution 3-dimensional MRI sequence specifically designed to depict complicated-plaque in the carotid arteries is described. MRIPH was applied, as compared with histologic analysis (gold standard), to demonstrate that T1-hyperintense intraplaque signal represented blood products. Strong agreement was seen between T1-hyperintensity and histologically-identified hemorrhage, with high sensitivity/specificity/positive- and negative-predictive values for T1-hyperintense detection of hemorrhage. While IPH increases plaque rupture risk, high degrees of calcification promote stability. Calcium can generate T1-hyperintensity in some gradient-echo (GRE) sequences. Therefore, distinction between these two components is crucial. In the second part, T1-hyperintensity in MRIPH was shown to be almost exclusively due to hemorrhage and not calcification by directly comparing in-vivo T1-hyperintensity with calcification in ex-vivo specimens imaged with microCT. T1- hyperintesity showed very good albeit inverse agreement with calcification and excellent agreement with lack of calcification as seen on microCT. IPH is thought to be the result of rupture/leakage of the vasa vasora. In the third part, we tested the hypothesis that if IPH were due to vasa vasorum rupture/leakage, the majority of the IPH would be associated with the adventitial rather than the luminal surface of the plaque. Deep (closer to vessel wall) and superficial (closer to vessel lumen) regions of complicated plaques were identified. Very good inter-rater agreement was seen for the location of IPH using MRIPH, with IPH being more frequently present in the deeper compared to superficial segments of the plaque. In summary, an in-vivo MR technique to detect IPH at high spatial-resolution in carotid complicated-plaque was developed; demonstrating T1-hyperintensity in MRIPH is the result of IPH and not calcification. The predilection of IPH for the deeper segments of the plaques suggests that IPH is due to vasa vasorum rupture/leakage.

Blood oxygen level dependent (BOLD) functional magnetic resonance imaging is a non-invasive technique used to trace changes in neural dynamics in reaction to mental activity caused by perceptual, motor or cognitive tasks. The BOLD response is a complex signal, a consequence of a series of physiological events regulated by increased neural activity. A method to infer from the BOLD signal onto underlying neuronal activity (hemodynamic inverse problem) is proposed in Chapter 2 under the assumption of a previously proposed mathematical model on the transduction of neural activity to the BOLD signal. Also, in this chapter we clarify the meaning of the neural activity function used as the input for an intrinsic dynamic system which can be viewed as an advanced substitute for the impulse response function. Chapter 3 describes an approach for recovering neural timing information (mental chronometry) in an object interaction decision task via solving the hemodynamic inverse problem. In contrast to the hemodynamic level, at the neural level, we were able to determine statistically significant latencies in activation between functional units in the model used. In Chapter 4, two approaches for regularization parameter tuning in a regularized-regression analysis are compared in an attempt to find the optimal amount of smoothing to be imposed on fMRI data in determining an empirical hemodynamic response function. We found that the noise autocorrelation structure can be improved by tuning the regularization parameter but the whitening-based criterion provides too much smoothing when compared to cross-validation. Chapter~5 illustrates that the smoothing techniques proposed in Chapter 4 can be useful in the issue of correlating behavioral and hemodynamic characteristics. Specifically, Chapter 5, based on the smoothing techniques from Chapter 4, seeks to correlate several parameters characterizing the hemodynamic response in Broca's area to behavioral measures in a naming task. In particular, a condition for independence between two routes of converting print to speech in a dual route cognitive model was verified in terms of hemodynamic parameters.

This thesis describes the development of new magnetic resonance imaging (MRI) methods to characterize cardiac tissue with myocardial infarction (MI). Wall motion imaging (for visualizing myocardial contraction) and viability imaging (to identify MI) are two components of cardiac tissue characterization used for prognosis and treatment planning. MRI-based wall motion and viability methods are considered the gold standard in imaging, and characterization of MRI viability images has been correlated with inducibility for ventricular tachycardia (VT). However, viability imaging with MRI has limitations such as difficulty visualizing the blood-infarct border. Wall motion and viability images are acquired separately, each requiring cardiac gating and breath holds, leading to long scan times. A novel multi-contrast delayed enhancement (MCDE) sequence was developed that simultaneously acquires wall motion and viability images. In a patient study, the MCDE sequence was demonstrated to provide improved visualization of MI compared to the conventional inversion-recovery gradient echo (IR-GRE) sequence, particularly for small infarcts adjacent to the blood pool. MCDE images also provided accurate wall motion images that could be used to calculate the left ventricular ejection fraction. An image processing algorithm was developed to analyze MCDE images to segment and classify the infarct gray zone, which is hypothesized to represent heterogeneous infarct responsible for causing VT. In a study of 15 patients with MI, the MCDE-derived gray zone was shown to be less sensitive to image noise than the IR-GRE-derived gray zone, and did not require manual contours of the blood pool which contributes to additional variability in the IR-GRE gray zone analysis. Finally, a real-time delayed enhancement (RT-DE) method was developed to provide black-blood viability images without requiring cardiac gating or breath holds. RT-DE imaging was shown to have a high sensitivity for detecting MI in a study of 23 patients. The methods described in this thesis help expand the patient population that can undergo a cardiac viability exam and help improve the visualization of myocardial infarct. Further modifications in the pulse sequences to improve the temporal and spatial resolutions are proposed with the goal of predicting and guiding treatment of ventricular tachycardia resulting from myocardial infarct.

Prostate cancer is extremely prevalent, with shifting patient demographics leading to an increasing number of men balancing treatment efficacy with associated side-effects. Non-invasive characterization of disease – useful for guiding biopsy, to monitor disease progression during active surveillance, or for treatment planning of focal therapies – could have a significant impact on patient management. Through its excellent anatomic imaging capabilities and its ability to characterize physiologic properties, magnetic resonance imaging (MRI) has the potential to fulfill clinical goals; however, further improvements are necessary to maximize accuracy and impact. Thus, this thesis presents: 1) the development of a multi-parametric model to combine parameters derived from measurement of T2 relaxation, diffusion weighted imaging, and dynamic contrast-enhanced MRI to improve the discrimination between normal and malignant peripheral zone tissue; 2) determination of the impact that the presence of normal tissue within regions of tumour has on the measurement of apparent diffusion coefficient (ADC) and T2 relaxation in the peripheral zone; and 3) relationships between MRI measurement and underlying prostate tissue composition. A common patient cohort was used for all studies, with prostate cancer patients having in vivo MRI prior to prostatectomy followed by whole-mount histologic sectioning of the surgical specimens, facilitating the use of pathology as a gold-standard for all analyses. In the first study, the optimal multi-parametric model combines ADC, T2, and volume transfer constant (Ktrans) to yield the probability of malignancy for each voxel. Performance of the model is better than each single parameter, but not significantly so compared to ADC. The second study demonstrates that there is no difference in ADC and T2 between tumours containing significant portions of normal tissue and the surrounding normal tissue itself, indicating that full characterization of prostate cancer with MRI may be limited. Finally, by determining relationships between MRI parameters and tissue characteristics, the third study suggests mechanisms driving MR image appearance in the prostate, including the visualization of cancer. Taken together, this thesis presents potential improvements to prostate cancer imaging, and provides further insight into the interplay between the underlying histology and MRI.

Atherosclerotic plaque (AP) composition is an important factor influencing plaque rupture. Intraplaque hemorrhage (IPH) is a marker of complicated-plaque formation, responsible for many of the clinical manifestations of atherosclerotic disease. Magnetic resonance imaging (MRI) has emerged as a modality to image carotid AP. The in-vivo high-resolution MR imaging of carotid complicated-plaque forms the basis of this thesis. In the first part, Magnetic Resonance Imaging of Intraplaque Hemorrhage (MRIPH), an in-vivo high-spatial-resolution 3-dimensional MRI sequence specifically designed to depict complicated-plaque in the carotid arteries is described. MRIPH was applied, as compared with histologic analysis (gold standard), to demonstrate that T1-hyperintense intraplaque signal represented blood products. Strong agreement was seen between T1-hyperintensity and histologically-identified hemorrhage, with high sensitivity/specificity/positive- and negative-predictive values for T1-hyperintense detection of hemorrhage. While IPH increases plaque rupture risk, high degrees of calcification promote stability. Calcium can generate T1-hyperintensity in some gradient-echo (GRE) sequences. Therefore, distinction between these two components is crucial. In the second part, T1-hyperintensity in MRIPH was shown to be almost exclusively due to hemorrhage and not calcification by directly comparing in-vivo T1-hyperintensity with calcification in ex-vivo specimens imaged with microCT. T1- hyperintesity showed very good albeit inverse agreement with calcification and excellent agreement with lack of calcification as seen on microCT. IPH is thought to be the result of rupture/leakage of the vasa vasora. In the third part, we tested the hypothesis that if IPH were due to vasa vasorum rupture/leakage, the majority of the IPH would be associated with the adventitial rather than the luminal surface of the plaque. Deep (closer to vessel wall) and superficial (closer to vessel lumen) regions of complicated plaques were identified. Very good inter-rater agreement was seen for the location of IPH using MRIPH, with IPH being more frequently present in the deeper compared to superficial segments of the plaque. In summary, an in-vivo MR technique to detect IPH at high spatial-resolution in carotid complicated-plaque was developed; demonstrating T1-hyperintensity in MRIPH is the result of IPH and not calcification. The predilection of IPH for the deeper segments of the plaques suggests that IPH is due to vasa vasorum rupture/leakage.