Individuals interested in endogenous imaging of cardiac remodeling.To demonstrate the effects of myocardial hypertrophy on MT-weighted cardioCEST MRI.Cardiovascular disease is characterized by both increased interstitial fibrosis and extracellular volume, and by hypertrophic remodeling of individual cardiomyocytes. These structural changes are associated with increased risk of heart failure, arrhythmia, and sudden cardiac death. Techniques to characterize myocardial tissue remodeling with gadolinium are limited in populations with reduced renal function who are at increased risk for adverse cardiac events. The endogenous contrast mechanism of magnetization transfer (MT) is influenced by changes in tissue structure, and recently MT-weighted CMR approaches have shown promise in identifying cardiac fibrosis^(1,2,3). However, the impact of increased intracellular macromolecule concentration concomitant with hypertrophy on MT contrast remains unknown. In this study we use a murine model of chronic Angiotensin-II (AngII) stimulation to demonstrate that hypertrophy has little effect on MT contrast generated using cardiac chemical exchange saturation transfer (cardioCEST)⁽⁴⁾.Pulse Sequence: CEST encoding used a saturation pulse train of 88 spatially non-selective Gaussian pulses (flip angle= 270°, B1_average= 5.25μT, bandwidth= 200Hz, duration= 8.8ms, saturation frequency offsets= 6 and 15ppm). Four averages of one phase encoding step for each cardiac phase were acquired following each saturation train. A constant repetition time (TR) cine gradient echo sequence (TR/TE= 10.2/3.5 ms, flip angle= 10°) was used to encode CEST contrast into the steady state longitudinal magnetization. Data acquisition was prospectively triggered using combined ECG and respiratory waveforms. Dummy pulses were used to maintain steady state magnetization between heart beats in cases of heart rate variability and during respiratory motion. Images were acquired in 1 mid-ventricular short-axis slice with parameters: FOV= 25.6x25.6cm, Matrix= 192x192, slice thickness= 1mm. Animal Model: Adult male C57Bl/6 mice (n=12) received either constant infusion of AngII (1000ng/kg/min, BACHEM, n= 7) or saline (n= 5) via mini osmotic pump (Alzet, Cupertino, CA USA). MRI was performed prior to and 10 days after pump implantation, with anesthesia maintained using 1.25% isoflurane in oxygen and body temperature maintained using circulating thermostated water. Imaging: All imaging was performed on a 7T Bruker ClinScan (Bruker Biospin, Ettlingen, Germany) using a cylindrical volume coil for excitation and a 4-channel phased array surface coil for reception. A reference image (saturation offset= 333ppm, saturation flip angle= 1°) was acquired to normalize signal for the receiver coil profile (See Fig-1). Image Analysis: Following a manual registration protocol to account for slight changes in bed position between scans, the magnetization transfer ratio (MTR) was calculated on a pixel-wise basis as MTR(ω)= [(S_Ref-S(ω))/S_Ref]*100. Myocardial borders were traced manually and the MTR was averaged over the entire myocardium. Regions of interest were then drawn surrounding the left anterior descending artery (LADA), the posterior right ventricular insertion (RVI) point, the septum (Sept) and the lateral wall (LW). Histology: Immediately following post-treatment scanning, all mice were euthanized and hearts were isolated, fixed in formalin, sliced transversely at the imaging location and stained with picrosirius red. Sections from four AngII-treated mice and two saline-treated mice were also stained with wheat germ agglutinin (WGA). Images were digitized using a Nikon A1R confocal microscope at 10x magnification. A thresholding method as described by Beliveau et al⁽⁵⁾ was used to quantify the collagen volume fraction in the LAD, RVI, septum and lateral wall ROIs. Using the same ROIs, five mid-wall circumferentially oriented cardiomyocytes were selected in the WGA-stained sections to measure mean cross-sectional area (MCA) using ImageJ (NIH, Bethesda, Maryland USA).Angiotensin-II treatment provoked a perivascular pattern of fibrosis, however the collagen volume fraction was not significantly increased (AngII= 2.86% ± 0.9, Sal= 1.63% ± 0.3). Angiotensin-II treatment provoked a significant increase in MCA when compared to saline infusion (AngII= 4825μm² ± 717, Sal= 2372μm² ± 158, p= 0.01) (See Fig-2). Parametric maps (See Fig-1) reveal no significant changes in MTR at 6ppm in AngII-treated mice (30.8% ± 7.3) relative to saline-treated mice (27.2% ± 8.6) or pretreatment scans (25.8% ± 4.2) (See Fig-3). Linear regression revealed no correlation between regional MCA and MTR values (p= 0.943) (See Fig-4).Increased extracellular volume that is concomitant with myocardial fibrosis leads to a reduction in MT when compared to healthy myocardium. We examined whether cardiomyocyte hypertrophy, which is characterized by increased production of intracellular proteins, would impart an opposing MT effect. By using a mouse model of AngII induced hypertrophy that is largely absent of interstitial fibrosis, we demonstrated using a cardioCEST approach that cardiomyocyte hypertrophy does not significantly alter MT contrast.