Optimized CEST cardiovascular magnetic resonance for assessment of metabolic activity in the heart

Abstract

BackgroundPrevious studies have linked cardiac dysfunction to loss of metabolites in the creatine kinase system. Chemical exchange saturation transfer (CEST) is a promising metabolic cardiovascular magnetic resonance (CMR) imaging technique and has been applied in the heart for creatine mapping. However, current limitations include: (a) long scan time, (b) residual cardiac and respiratory motion, and (c) B0 field variations induced by respiratory motion. An improved CEST CMR technique was developed to address these problems.MethodsAnimals with chronic myocardial infarction (N = 15) were scanned using the proposed CEST CMR technique and a late gadolinium enhancement (LGE) sequence as reference. The major improvements of the CEST CMR technique are: (a) Images were acquired by single-shot FLASH, significantly increasing the scan efficiency. (b) All images were registered to reduce the residual motion. (c) The acquired Z-spectrum was analyzed using 3-pool-model Lorentzian-line fitting to generate CEST signal, reducing the impact of B0 field shifting due to respiratory motion. Feasibility of the technique was tested in a porcine model with chronic myocardial infarction. CEST signal was measured in the scar, border zone and remote myocardium. Initial studies were performed in one patient.ResultsIn all animals, healthy remote myocardial CEST signal was elevated (0.16 ± 0.02) compared to infarct CEST signal (0.09 ± 0.02, P < 0.001) and the border zone (0.12 ± 0.02, P < 0.001). For both animal and patient studies, the hypointense regions in the CEST contrast maps closely match the bright areas in the LGE images.ConclusionsThe proposed CEST CMR technique was developed to address long scan times, respiratory and cardiac motion, and B0 field variations. Lower CEST signal in bright region of the LGE image is consistent with the fact that myocardial infarction has reduced metabolic activity.

CEST MRI reveals a correlation between visceral fat mass and reduced myocardial creatine in obese individuals despite preserved ventricular structure and function

“…In the infarcted myocardium of large animals, resting creatine CEST contrast has been shown to be reduced by 50-70% compared with remote healthy myocardium. 28,29 While the reduction in creatine CEST contrast among obese adults in this study was below that observed in infarcted tissue in prior studies, it closely resembled the relative reduction in creatine CEST contrast in border zone tissue seen in miniature pigs by Zhou et al 29 However, the CEST contrast values measured in healthy controls in our study were lower than those observed in healthy myocardium in both prior studies, despite similar cardiomyocyte creatine concentrations between species. It is important to note differences in how the CEST-weighted images were acquired between studies.…”

“…Also, both prior studies were performed at field strengths of 3 T (versus 1.5 T in the current study) using single‐shot acquisitions. In the study performed by Zhou et al the use of single‐shot readouts enabled multiple points along a Z spectrum to be acquired in a single breath hold . In our preliminary studies, we observed significant motion artifacts when using a single‐shot readout to acquire an end‐diastolic frame, even when using a centric‐out encoding scheme.…”

“…In the study performed by Zhou et al the use of single-shot readouts enabled multiple points along a Z spectrum to be acquired in a single breath hold. 29 In our preliminary studies, we observed significant motion artifacts when using a single-shot readout to acquire an end-diastolic frame, even when using a centric-out encoding scheme. Importantly, if images are acquired serially with CEST preparation incremented from negative to positive offset frequencies in a single breath hold, then a bias at low positive offset frequencies may exist as the saturated myocardial magnetic moment following CEST preparation at 0 ppm results in lower steady state signal of subsequent images.…”

“…In addition, CEST enables imaging with higher sensitivity to creatine concentrations as compared with MRS techniques and can be performed with standard hardware. CEST imaging of myocardial creatine has been performed in infarcted large animal models and one patient with chronic myocardial infarction, with both studies revealing significantly reduced creatine CEST in infarcted tissue. In a prior study from our group, we observed attenuated cardiac creatine CEST contrast in obese mice fed a high fat diet despite preserved ventricular structure and systolic function .…”

Recent Advances in Cardiac Magnetic Resonance Imaging

“…The chemical exchange saturation transfer (CEST) technique has been developed to quantify metabolites and macromolecules 63)64)65). In a recent study, CEST was able to map the creatine distribution within the myocardium to evaluate the metabolic activity in an animal model,66) and an optimized in vivo cardiac CEST sequence that maps free creatine in myocardial tissue, with a markedly reduced scan time by 10-fold and improved motion registration and signal calculation, has been developed 67). The feasibility of the sequence has been tested against LGE imaging as a reference in a porcine myocardial infarction model, and the sequence has been applied in a patient with chronic myocardial infarction.…”