Fractional myocardial blood volume by ferumoxytol-enhanced MRI: Estimation of ischemic burden.

PURPOSE: To investigate model-fitted fractional myocardial blood volume (fMBV) derived from ferumoxytol-enhanced MRI as a measure of myocardial tissue hypoperfusion at rest. METHODS: We artificially induced moderate to severe focal coronary stenosis in the left anterior descending artery of 19 swine by percutaneous delivery of a 3D-printed coronary implant. Using the MOLLI pulse sequence, we acquired T1 maps at 3 T after multiple incremental ferumoxytol doses (0.0-4.0 mg/kg). We computed pixel-wise fMBV using a multi-compartmental modeling approach in 19 ischemic swine and 4 healthy swine. RESULTS: Ischemic myocardial segments showed a mean MRI-fMBV of 11.72 ± 3.00%, compared with 8.23 ± 2.12% in remote segments and 8.38 ± 2.23% in normal segments. Ischemic segments showed a restricted transvascular water-exchange rate (ki  = 15.32 ± 8.69 s-1 ) relative to remote segments (ki  = 17.78 [11.60, 26.36] s-1 ). A mixed-effects model found significant difference in fMBV (p = 0.002) and water-exchange rate (p < 0.001) between ischemic and remote myocardial regions after adjusting for biological sex and slice location. Analysis of fMBV as a predictor of impaired myocardial contractility using receiver operating characteristics showed an area under the curve of 0.89 (95% confidence interval [CI] 0.80, 0.95). An MRI-fMBV threshold of 9.60% has a specificity of 90.0% (95% CI 76.3, 97.2) and a sensitivity of 72.5% (95% CI 56.1, 83.4) for prediction of impaired myocardial contractility. CONCLUSIONS: Model-fitted fMBV derived from ferumoxytol-enhanced MRI can distinguish regions of ischemia from remote myocardium in a swine model of myocardial hypoperfusion.

Novel Percutaneous Approach for Deployment of 3D Printed Coronary Stenosis Implants in Swine Models of Ischemic Heart Disease.

Minimally invasive methods for creating models of focal coronary narrowing in large animals are challenging. Rapid prototyping using three-dimensionally (3D) printed coronary implants can be employed to percutaneously create a focal coronary stenosis. However, reliable delivery of the implants can be difficult without the use of ancillary equipment. We describe the use of a mother-and-child coronary guide catheter for stabilization of the implant and for effective delivery of the 3D printed implant to any desired location along the length of the coronary vessel. The focal coronary narrowing was confirmed under coronary cineangiography and the functional significance of the coronary stenosis was assessed using gadolinium-enhanced first-pass cardiac perfusion MRI. We showed that reliable delivery of 3D printed coronary implants in swine models (n = 11) of ischemic heart disease can be achieved through repurposing mother-and-child coronary guide catheters. Our technique simplifies the percutaneous delivery of coronary implants to create closed-chest swine models of focal coronary artery stenosis and can be performed expeditiously, with a low procedural failure rate.

3D-Printed Coronary Implants Are Effective for Percutaneous Creation of Swine Models with Focal Coronary Stenosis.

Reliable, closed-chest methods for creating large animal models of acute myocardial hypoperfusion are limited. We demonstrated the feasibility and efficacy of using magnetic resonance (MR)-compatible 3D-printed coronary implants for establishing swine models of myocardial hypoperfusion. We designed, manufactured, and percutaneously deployed implants in 13 swine to selectively create focal coronary stenosis. To test the efficacy of the implants to cause hypoperfusion or ischemia in the perfused territory, we evaluated regional wall motion, myocardial perfusion, and infarction using MR imaging. The overall swine survival rate was 85% (11 of 13). The implant retrieval rate was 92% (12 of 13). Fluoroscopic angiography confirmed focal stenosis. Cine and perfusion MRI showed regional wall motion abnormalities and inducible ischemia, respectively. Late gadolinium enhancement and histopathology showed no myocardial infarction. Our minimally invasive technique has promising applications for validation of new diagnostic methods in cardiac MR. Graphical abstract Our new minimally invasive, percutaneous method for creating swine models of acute focal coronary stenosis can be used for magnetic resonance imaging studies of myocardial ischemia. Comparable to existing methods in its efficacy and reliability, this rapid prototyping technique will allow researchers to more easily conduct translational cardiac imaging studies of coronary artery disease in large animal models.