Myocardial Cavitation Enabled Therapy (MCET)

Hypertrophic cardiomyopathy (HCM), a common genetic cardiovascular disease, can lead to obstruction of the left ventricular outflow path, and result in sudden death.  Presently available treatments include open heart surgery (septal myectomy) and transcatheter septal ablation with alcohol. The less invasive ablation procedure has a high incidence of heart block requiring permanent pacemaker and of arrhythmia associated with scarring, and is not widely applied.

Myocardial contrast echocardiography (MCE) has enabled visualization of myocardial perfusion. High Mechanical Index (i.e., ultrasound intensity) MCE using intermittent destruction of contrast microbubbles (bioeffect) has been shown to lethally injure scattered cardiomyocytes in a focus volume. With this project we have created a safer, gentler method of cardiac tissue reduction for familial HCM by enhancing this bioeffect to therapeutic levels of myocardial reduction.

Our rapid progress thus far has succeeded in up to 21% debulking in the ultrasound focal region, while avoided potentially harmful premature contraction arrhythmias, reduced the initial swelling and minimized long term scarring.

Collaborators:  Douglas L. Miller, Ph.D. (UM Radiology), Gabe E. Ownes, M.D., Ph.D. (UM Pediatric Cardiology), William F. Armstrong, M.D. (UM Cardiology)

Quantitative Blood Volume Flow Assessment (Biomarker)

Stroke is a leading cause of death and serious long-term disability. Resulting cerebral ischemia is a concern and delivery of sufficient blood (and oxygen) to tissue at risk is paramount. Existing measures are either non-specific surrogate markers (e.g. blood pressure), are too invasive (e.g. jugular venous oximetry) or are unsuitable for bedside use (CT, MRI, PET). An inexpensive, non-invasive and accurate bedside tool for the measurement of blood delivery to the brain may be of potential value for Delayed Cerebral Ischemia (DCI) following aneurysmal Subarachnoid Hemorrhage (aSAH) as well as other cerebrovascular pathologies.

With our efforts in regard to blood volume flow (Q), we have created a quantitative non-invasive tool for reliably measuring blood flow (<10% error).  Our approach requires 3D ultrasound and uses Gauß's Theorem of surface integration (S) of velocity vectors (vi) and area elements (Ai). The relationship Q=v×A is invariant under angles α and β, since Q=v×A = (v∙cos(α))×(A/cos(α)). In other words the angle dependence of Q cancels.  Together with our unique and patented partial volume correction (wi), we can determine blood volume flow in vessels with limited beam sampling. 

Widespread clinical application is stimulated by our QIBA efforts in which we work with 6 companies and 8 laboratories to implement volume flow on current clinical ultrasound scanners for creating a new clinical biomarker.  Current in vivo studies include carotid, umbilical, hepatic and portal vein.  

A conventional duplex mode scan of the Internal Carotid Artery is shown below with B-mode and overlaid color flow (recorded with a GE 4DE7C array). This is a lateral-elevational image, also called the c-plane, where each voxel is equidistant from the scan array surface. In preliminary studies on 3D color flow we estimated volume flow in the CCA to within 4% of high resolution MRI phase contrast flow measurements.

Collaborators:  Jonathan M. Rubin, M.D., Ph.D. (UM Radiology), J. Brian Fowlkes, Ph.D. (UM Radiology)