Preliminary Baseline CEST CMR Measurements of Cardiac Energetics in Healthy Subjects (RF_FR_382)

Cardiovascular disease remains a leading cause of death worldwide, but novel cardiac MRI technologies may present a way to noninvasively evaluate cardiac function, improving diagnoses and subsequent therapeutic options. Chemical Exchange Saturation Transfer (CEST) is a CMR technique that allows for the measurement of in vivo metabolites of interest. Previous human studies using myocardial samples from heart transplants and 31P CMR spectroscopy of phosphocreatine have implicated creatine levels in heart failure. This study aims to preliminarily establish a baseline CEST-CMR measured creatine in healthy individuals as an assessment of metabolic activity in the heart.

Methods:

44 subjects (23 males and 21 females of mean ages 33.8 and 27.4, respectively) were screened against chronic diseases, including hypertension, hyperlipidemia, and cardiovascular disease. Cardiac CEST images were taken using Siemens PRISMA (13 females and 8 males) and CIMA (8 females and 15 males) scanners. From each subject, 31 images at varying ppm shifts were obtained. ImageJ was used to segment the interventricular septum of the heart for each image, from which mean gray values were measured. These values were fitted to a Z-spectrum curve. A creatine MTR asymmetry curve was created from the Z-spectrum and used to quantify creatine levels. An unpaired two-tailed t-test was used to analyze for differences between males and females. On the CIMA, a rigorous phantom scan was done with known creatine concentrations of 0 mmol to 50 mmol in increments of 10 mmol to validate the CEST protocol.

Results:

The phantom showed MTR asymmetry values that increased in correspondence to creatine solutions of increasing concentration, validating the CEST scan. We found that there is no significant difference between cardiac creatine levels in healthy male versus female individuals within the same scanner. The average MTR asymmetry creatine peak of females and males scanned in the PRISMA scanner were 0.1028 and 0.0857, respectively (p-value = 0.0884). The average creatine peak of females and males scanned in the CIMA scanner were 0.1826 and 0.1371, respectively (p-value = 0.0549). However, there was a significant difference found in average creatine levels measured between scanners (p-value < 0.0001). 

Conclusion:

This study provides a preliminary baseline CEST-CMR creatine MTR asymmetry in healthy individuals that can be compared in future studies assessing pathological states. In a small set of subjects, we showed no significant difference between males and females. Furthermore, we showed significant difference between two 3T scanners, suggesting a need to collect a normal group of CEST-CMR MTR asymmetry values for a given scanner. Future studies should apply the use of CEST in evaluating creatine levels and cardiac metabolic function in patients with heart failure, valvular disease, and other cardiovascular diseases.