Graham Wright

Research Synopsis

MR Characterization of Myocardial Pathophysiology following Acute Ischemic Events: In 1997, we demonstrated for the first time the relationship between characteristics of biexponential MR signal decay and the underlying oxygen state of muscle. This work has been developed toward characterization of myocardial hypoxia associated with perfusion deficits. A major step in this direction was our 2002 publication in Circulation, one of the top cardiac science journals, showing the relationship between MR signal changes in porcine myocardium and oxygen state in the cardiac veins. We also introduced and optimized an oxygen-sensitive SSFP method which yields improved sensitivity and the capacity for time-resolved oxygen studies. With colleagues in Chicago, this method proved sensitive to perfusion deficits in a canine model of coronary stenosis and is now being extended to patient studies. Meanwhile, myocardial relaxometry methods associated with the earlier work have been used to characterize physiological changes with stunning and following infarct in a porcine model. Our recent papers demonstrate, in this model, differential degrees of hemorrhage, inflammation, and microvascular obstruction in the tissue depending on severity of ischemia. Severity also impacts rate of resolution of these factors and subsequent extent of scar and ventricular remodeling. Parallel patient studies indicate similar behaviour, with evidence that diabetes is associated with greater inflammation and worse outcomes. These studies also suggest that various pharmaceutical and device interventions may hold promise in altering the course of this disease progression.

MR Characterization of Arrhythmogenic Substrate in the Heart: In 2007, we also introduced a new variant on myocardial wall motion and viability characterization with a gated inversion-recovery SSFP method yielding multiple images of varying T1 contrast across the cardiac cycle. This method appears more robust and more sensitive to the detection of small and heterogeneous infarcts particularly near the endocardial border than existing techniques. A real-time version also gives better performance in patients with arrhythmias or with difficulty in breath-holding. New quantitative analysis tools we introduced in association with this method yield more repeatable estimates of the extent of heterogeneous infarct, a measurement which reflects the risk of sudden cardiac death associated with complex arrhythmias, as demonstrated in a study following patients receiving implantable cardioverter defibrillators. Our recent preclinical experiments directly probing the electrical properties of MRI-identified heterogeneous infarct, combined with computational modeling suggests a potential causal link underlying this association. Finally, in the same preclinical model, we have demonstrated that MRI can help visualize at an acute stage ablative lesions aimed at eliminating the arrhythmogenic substrate (patent pending), holding the promise of more effective guidance of potentially curative therapies.

Real-time adaptive MRI for MR Angiography: In 1998, we introduced a novel method for establishing appropriate scan timing for contrast-enhanced MR angiography, a vascular mapping technique that has rapidly gained broad clinical use. This timing method, the subject of patent 6233475, was incorporated into an automated scan trigger that resulted in several major clinical publications with Dr. Farb and was used in over 1500 patient studies to date. Building on this platform, we have developed real-time adaptive methods for higher resolution coronary artery imaging, resulting in patents 6292683, 6675034, 6704593 and 7239136. In 2002, M. Sussman was a finalist for the I.I. Rabi Award based on this work. Most recently, G. Liu extended this work to develop a realtime method for monitoring the quiescent period in the heart (patent pending) aimed at improving the quality of MR coronary angiograms.

MR-Guided Cardiovascular Interventions: We have expanded real-time interactive visualization tools originally designed for vascular imaging as part of a larger cooperative effort with Stanford to establish a real-time MRI platform for cardiac applications (patent 6975751) which is now being commercialized by a Stanford spin-off (HeartVista) for wider clinical study. This platform is also central to our rapidly developing focus in MRI-guided electrophysiology and vascular interventions. As noted, above, this technology has facilitated direct correlation between MR-identified arrhythmogenic substrate and its electrical properties, as well as direct MR monitoring of ablations in heart tissue to eliminate such substrate. We have also developed novel technology to track devices and guidewires aimed at facilitating MR-guided crossing of chronic vascular blockages (patents 7505808 and EP 23344364). Related to this, we have developed unique tools (patent pending) to monitor potential heating of conductive devices in the body during MR scans to ensure that MR-guided interventions can be performed safely. We are now working with multiple companies aimed at moving these tools toward practical clinical use.