Research Plan

 

Cardiovascular Research

 

Background

The most important challenge in cardiovascular medicine at this time is accurate quantification of diagnostic measurements and treatment response, since this will ensure consistent outcomes across diagnostic platforms and hospitals. Magnetic Resonance Imaging (MRI) is becoming increasingly important for diagnosing and monitoring the treatment of cardiovascular disease. It is used to make functional measurements such as ventricular volume, ejection fraction, regurgitation volume and myocardial mass; myocardial strain analysis; myocardial ischemia and infarction; and assessment of myocardial viability and myocardial diseases like myocarditis. Higher field strengths, improved coil design and new imaging techniques have improved image quality and resolution so that it is possible to probe deeper into cardiac physiology, to study new areas such as cardiac remodeling and heart brain interactions. It is also now possible to monitor metabolic biomarkers and cellular biochemistry with Magnetic Resonance Spectroscopy (MRS). We develop MRI/MRS methods and post processing algorithms for quantitative measurement of cardiovascular function and physiological response to treatment.

 





Perfusion MRI

Myocardial Perfusion Quantification with exogenous contrast enhancement

Contrast enhanced First Pass MRI is used for quantitative assessment of myocardial perfusion. There has been significant progress in stress perfusion imaging and algorithms for quantification of myocardial perfusion. Currently, 2D slice projection imaging is performed rotationally about the long axis and along the short axis, but full coverage of the myocardium in not usually achieved. Full coverage is vital to the goal of early detection of perfusion defects. We use three dimensional (3D) Cardiac MRI to achieve full coverage and absolute perfusion quantification for early detection of myocardial perfusion defects.

 

Myocardial Perfusion Quantification with intrinsic contrast: BOLD, ASL, CEST

Gadolinium based contrast agents are not well tolerated by patients with kidney disease. Endogenous contrast mechanisms are increasingly necessary for use in patients who are clinically averse to exogenous contrast media. Arterial Spin Labeling (ASL) and Blood Oxygen Level Dependent (BOLD) contrast mechanisms are well established in brain MRI and are attractive methods for implementation in cardiac MRI. Recently, chemical exchange saturation transfer (CEST) has emerged as another promising intrinsic contrast mechanism that may be exploited in MRI. We refine these methods for quantitative measurement of myocardial perfusion.

 

Artifact Theory

Image artifacts are a constant reality in MRI and the development of artifact theory is necessary as the field progresses. The dark rim artifact (DRA) is one artifact that confounds contrast enhanced First Pass perfusion images at 1.5 Tesla, because the artifact can be mistaken for a perfusion defect or mask a defective region of myocardium. The origin of the DRA is not understood. We aim to establish the origin of the DRA and develop a theory for its existence by making artifact assessments, as well as T1 and T2 mapping of normal myocardium.

 



Magnetic Resonance Spectroscopy

Diabetes, Metabolic syndrome and Obesity related cardiovascular disease

Diabetes is associated with cardiovascular disease. In vivo assessment of magnetic resonance spectra from the myocardium in normal volunteers, diabetic patients and subjects with metabolic syndrome may reveal differences in metabolic profiles. Using proton and phosphorous spectroscopy along with principal component analysis (PCA) and simultaneous component analysis (SCA), these differences can be isolated and used to deduce biomarkers, which can be used to monitor the changes in cardiac metabolism associated with diabetes and its treatment. We use MRS to monitor the effectiveness of treatments that protect the heart in diabetics.

 

Hypertension

Magnetic resonance spectra from blood and myocardium in normal and hypertensive subjects may show metabolic biomarkers that change in responses to treatment for hypertension. We monitor metabolic changes in the cardiovascular system brought about by the treatments for hypertension.

 

Stem cell spectroscopy and Molecular imaging

Stem cell therapy carries the requirement to monitor and track anatomical and physiological changes as the stem cells become integrated into tissues. Tracking stem cells can be done with MRS through metabolic biomarkers, endogenous contrast mechanisms or exogenous contrast agents. We use MRS to establish the metabolic profile and identify biomarkers that can be used to track cardiac stem cells.

 


Cardiac Remodeling

The structure and blood flow characteristics of the heart undergo significant change as we age. One structural change involves the insertion angle of the aorta on the left ventricle. This is an important parameter which impacts the success of valve replacement surgery in some elderly patients, where the difficulty of this surgery correlates with increasing aortic angle. The changing aortic angle is also associated with spiral blood flow, which is thought to be associated with atherosclerosis. 3D MRI can be used to measure accurate and precise anatomy over several cardiac phases; while Phase Contrast (PC) MRI can be used for blood flow mapping. We determine the aortic angle and blood flow characteristics in normal volunteers.

 

Heart Brain Interaction

Psychological stress is associated with changes in heart rate, blood pressure and vascular tone and in extreme cases, can cause stress induced cardiomyopathy, but the mechanism is not understood. Using functional MRI, it is now possible to characterize the mechanism of the heart-brain interaction. We know that neurogenic control is mediated by both the sympathetic and parasympathetic components of the autonomic nervous system. Cardiovascular baroreceptor and chemoreceptor afferents are carried in the Vagus nerve, which terminate in the nucleus tractus solitarius (NTS) of the brainstem. The fibers involved in cardiovascular control then project to areas in the hypothalamus, amygdale, and insular cortex which have integrating function for the control of blood pressure, heart rate and vascular tone. Descending pathways pass through the brain stem back to the cardiovascular system where they form synapses directly onto cardiac and smooth muscle. Our goal is to establish the characteristics of the heart-brain interaction and to quantify the effect of psychological stress on myocardial perfusion in order to develop a psychological stress test for the heart.



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