Cardiovascular disease is the leading cause of death in patients with diabetes mellitus (DM), with atherosclerosis accounting for approximately 80% of the cases. Although the cause for the increased cardiovascular risk is multi-factorial, there is compelling evidence obtained from experimental models of DM suggesting that excessive myocardial lipid uptake may be contributory. This ectopic deposition of lipid, often stored as triacylglycerol (TAG) may directly cause myocardial damage and decreased function through a variety of mechanisms. However, accurate translation of these findings to humans with DM, requires an noninvasive imaging method that provides both accurate and reproducible measurements of myocardial tissue TAG. Currently, no such imaging method exists.
Primary Outcome Measures:
- optimizing the MRS measurement of TAG protocol devised from animal studies for respiratory and cardiac motion on a Siemens 1.5T human system [ Time Frame: 2 years ]
Secondary Outcome Measures:
- Measure the accuracy and reproducibility of the MRS method by comparing values of myocardial TAG obtained by MRS with biochemical quantification of TAG in biopsies [ Time Frame: 2 years ]
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||June 2009 (Final data collection date for primary outcome measure)
Procedure: Magnetic Resonance Spectroscopy
It is basically the same as an MRI. It is a noninvasive procedure that provides detailed body images on any plane.
Procedure: Endocardial Biopsy
This is a standard of care procedure that is already performed on heart transplant patients. This is a procedure that takes a biopsy (tissue sample) of the heart muscle.
Other Name: Heart Biopsy.
Because routine biopsy of the myocardium is not feasible, MRS is the most promising technique for the quantification of myocardial TAG. MRS is routinely used to precisely characterize metabolite concentrations in muscle and liver. 14-16 Studies such as monitoring the levels of deoxymyoglobin and real-time tracking of the postprandial accumulation of cellular lipids are examples of its diversity and potential.15,17,18 Generally, these studies suggest that the reproducibility of MRS is between 2 and 6%.18,19 In vivo cardiac MRS provides unique challenges because of the requirement to compensate for concurrent heart and lung motion. Using cardiac and respiratory gating to minimize motional artifacts, an initial validation study found a variation of 17% for sequential measurements, attributing the major error to residual motional effects. 20 Moreover, measurements were limited to the interventricular septum. Using navigator and cardiac gating appeared to give a slight, 4%, improvement, but this was a preliminary study and no validation was done.21 For a comprehensive clinical validation, other reproducibility factors must be addressed. Variations due to post-processing, coil placement and calibration, trigger reproducibility, internal versus external standard, shimming, and protocol sequence variables such as pulse quality, gradient strength, voxel size, relaxation time, echo time, and the number of scan repetitions are all known sources of reproducibility. 17,19,22-24 All of these variables must be characterized in order to achieve optimal inter- scanner and subject reproducibility along with accurate treatment tracking capability.