Determination of triglyceride in the human myocardium by magnetic resonance spectroscopy: reproducibility and sensitivity of the method

Abstract

-The primary aim of this investigation was to determine the reliability and sensitivity of 1 H magnetic resonance spectroscopy ( 1 H-MRS) as a method for quantifying myocardial triglyceride (TG) content in humans over time and in response to metabolic perturbations. Three separate experiments were designed to quantify myocardial TG content 1) over a 90-day period, 2) after a high-fat meal, and 3) after a 48-h fast. Proton spectra were collected from a 10 ϫ 20 ϫ 30-mm 3 voxel placed within the intraventricular septum, with measurements acquired at end-systole and end-expiration, using cardiac triggering and respiratory gating. Minimal variation was observed between myocardial TG content determined 90 days apart (r ϭ 0.98, CV ϭ 5%), whereas TG values were unaffected by a high-fat meal despite a significant twofold increase (P Ͻ 0.05) in serum TG. In contrast, myocardial TG content increased threefold (P Ͻ 0.05) after a 48-h fast despite a 25% reduction in serum TG. Body mass index was significantly related to myocardial TG (r ϭ 0.58, P Ͻ 0.05) and the change in myocardial TG after a 48-h fast (r 2 ϭ 0.60). 1 H-MRS is a reliable method for the determination of myocardial TG in humans and is relatively unaffected by the consumption of one high-fat meal but sensitive to changes following a prolonged fast. cardiac spectroscopy; cardiac imaging; lipotoxicity; prolonged fasting IN THE FACE OF AN OBESITY EPIDEMIC, the development of new technologies to predict the progression of obesity-related chronic disease has advanced dramatically in the past decade. Studies in animals reveal that an excessive deposition of triglyceride (TG) droplets in metabolically active tissues, such as the liver (8), skeletal muscle (10), and myocardium (3, 6, 25), impairs cellular function, predisposing animals to type 2 diabetes (9) and heart failure (3,6,25). In an effort to translate these studies into a clinical setting, researchers have relied on biopsy-derived quantification of TG or in vivo magnetic resonance spectroscopy (MRS) imaging to study the role of intracellular TG accumulation in the human liver (15, 21) and skeletal muscle (7,12,19) in the development of metabolic diseases. Impressively, results from studies using MRS of hepatic and muscle tissue mirror results obtained in animals (11,13,14,24), suggesting that intracellular TG may be a valuable biomarker for metabolic disease in humans. Unfortunately, the technology for measuring TG in the human myocardium is still not completely resolved.Until recently, the evaluation of myocardial TG in humans was limited to invasive biopsies, limiting the usefulness of intracellular TG as a biomarker for chronic disease in humans (16). We (20) and others (4, 5) have developed a proton MRS ( 1 H-MRS) technique similar to that used for skeletal muscle and hepatic tissue that quantifies intracellular TG in vivo in the beating human heart. Initial cross-sectional studies revealed that myocardial TG accumulated with increasing body mass and was related to cardiac structure and function in human...

Independent effects of circulating glucose, insulin and NEFA on cardiac triacylglycerol accumulation and myocardial insulin resistance in a swine model

“…Due to substrate competition [9], systemic and myocardial GU rates were low; the latter was inversely correlated with the increment in 3-OHB and NEFA levels. An increase in myocardial palmitate esterification and content was observed in the fasting group compared with the other groups, a finding consistent with studies in healthy and type 2 diabetic individuals [2,15,35]. These studies reported an increased myocardial TG content when lipolysis was induced by caloric restriction or a 48 h fasting period, unless acipimox was coadministered to counteract increasing NEFA levels [12].…”

“…Work in fasting dogs has demonstrated that elevated plasma NEFA concentrations, achieved by intralipid-heparin infusion, were associated with greater content and synthesis rates of myocardial TG compared with conditions with lower plasma NEFA, such as insulin or saline infusion [36]. In contrast, high-fat feeding does not change myocardial TG content in healthy subjects, despite notable increases in plasma TG and NEFA levels and an accumulation of liver fat [16,35]. Notably, insulin concentrations are low during caloric restriction or intralipid administration, while a high insulin in response to a high-fat diet may limit myocardial TG accumulation by suppressing the release of NEFA from adipose tissue and TG from the liver, which is consistent with our findings.…”

Assessment of epicardial fat volume and myocardial triglyceride content in severely obese subjects: relationship to metabolic profile, cardiac function and visceral fat

“…17,[19][20][21][22] Previous studies have shown that diabetic obese humans and rodents have elevated hepatic, myocellular and myocardial lipid content, and that treatment with pioglitazone leads to decreased hepatic and myocardial lipid together with improved insulin sensitivity. 23 Assessment of EF volume (EFV) and myocardial TG content (MTGC) has already been validated [24][25][26] with the emergence of non-invasive three-dimensional volumetric imaging techniques such as 3-T magnetic resonance imaging (MRI). This technique is also useful to address the relationship between excess myocardial lipids and impaired myocardial function.…”

Limits of a localized magnetic resonance spectroscopy assay for ex vivo myocardial triacylglycerol

“…Although a limit-based error analysis of the relaxation correction has been published [37], many studies report CV's based only on repeated acquisitions and do not include the uncertainty of the T 2 correction [5,8,9,12]. For species with comparatively long T 2 's, such as brain metabolites, the additional uncertainty is minor.…”

“…Localized magnetic resonance spectroscopy (LMRS), which uses gradient-enabled imaging systems, is increasingly used both in basic and clinical assays including qualitative and quantitative compositional, temperature, and pH measurements [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. Kreiss [16] summarized the main aspects of LMRS, including spectral artifacts, systematic errors, and general criteria for ensuring spectral quality.…”