No abstract

Using a new method of xenon laser-polarization that permits the generation of liter quantities of hyperpolarized 129Xe gas, the first 129Xe imaging results from the human chest and the first 129Xe spectroscopy results from the human chest and head have been obtained. With polarization levels of approximately 2%, cross-sectional images of the lung gas-spaces with a voxel volume of 0.9 cm3 (signal-to-noise ratio (SNR), 28) were acquired and three dissolved-phase resonances in spectra from the chest were detected. In spectra from the head, one prominent dissolved-phase resonance, presumably from brain parenchyma, was detected. With anticipated improvements in the 129Xe polarization system, pulse sequences, RF coils, and breathing maneuvers, these results suggest the possibility for 129Xe gas-phase imaging of the lungs with a resolution approaching that of current conventional thoracic proton imaging. Moreover, the results suggest the feasibility of dissolved-phase imaging of both the chest and brain with a resolution similar to that obtained with the gas-phase images.

The effect on micellar structure of changing the solvent from H20 to D20 for alkyltrimethylammonium bromide [C"TAB; C"TAB = C"H2^+1N(CH3)3Br, with = 12,14, and 16] has been examined. The energetics of micellization have been determined by measuring critical micelle concentrations by using surface tensiometry. The micellar structure has been elucidated through the use of small-angle neutron scattering (SANS). It was found that there is a solvent isotope effect that is small for C12TAB but increases with n. This effect is manifested mainly by an increase in aggregation number and is attributed to solventhydrocarbon interactions of the dissolved monomers. The fractional charge of the micelle is not altered by the isotopic composition of the solvent. C"TAB micelles are found to be drier than are micelles formed by the corresponding sodium alkyl sulfates, and this results in a larger solvent effect for the quaternary ammonium bromides.

No abstract

Background-The objective of this study was to noninvasively determine the effects of reperfused myocardial infarction (MI) on regional and global left-ventricular (LV) function 24 hours after MI in intact mice with contrast-enhanced cardiac MRI and a single, gradient-echo pulse sequence. Methods and Results-Twenty-three mice received baseline MRI scans followed by either 60 minutes of coronary occlusion (MI group, nϭ15) or thoracotomy without occlusion (sham group, nϭ8). Gadolinium-DTPA-enhanced magnetic resonance (MR) images were acquired 24 hours after surgery. Hearts were then excised for conventional infarct size determination via 2,3,5-triphenyl tetrazolium chloride (TTC) staining. In addition to infarct size, analysis of the MR images yielded left ventricular (LV) mass, LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV), LV ejection fraction (LVEF), cardiac output, and percent LV wall thickening (%WTh). Twenty-four hours after surgery, infarct size was 28.1Ϯ1.8% of LV mass by MRI and 27.5Ϯ1.7% by TTC (PϭNS). Bland-Altman analysis revealed close agreement between the results obtained by the 2 methods. MI had little effect on LVEDV but caused a 98% increase in LVESV (from 11.3 to 22.4 L, PϽ0.05), which resulted in a significant reduction in LVEF (from 70% to 37%, PϽ0.05). Compared with LV regional function at baseline, %WTh 24 hours after MI was significantly depressed, not only in infarcted myocardium but also in regions remote from the infarct zone. In contrast, sham-operated mice showed a small but significant increase in %WTh 24 hours after surgery (PϽ0.05). Conclusions-MRI can accurately assess both infarct size and cardiac function in intact mice early after large, reperfused MI, revealing the existence of contractile dysfunction in noninfarcted regions of the heart.

BackgroundChanges in energy substrate metabolism are first responders to hemodynamic stress in the heart. We have previously shown that hexose‐6‐phosphate levels regulate mammalian target of rapamycin (mTOR) activation in response to insulin. We now tested the hypothesis that inotropic stimulation and increased afterload also regulate mTOR activation via glucose 6‐phosphate (G6P) accumulation.Methods and ResultsWe subjected the working rat heart ex vivo to a high workload in the presence of different energy‐providing substrates including glucose, glucose analogues, and noncarbohydrate substrates. We observed an association between G6P accumulation, mTOR activation, endoplasmic reticulum (ER) stress, and impaired contractile function, all of which were prevented by pretreating animals with rapamycin (mTOR inhibition) or metformin (AMPK activation). The histone deacetylase inhibitor 4‐phenylbutyrate, which relieves ER stress, also improved contractile function. In contrast, adding the glucose analogue 2‐deoxy‐d‐glucose, which is phosphorylated but not further metabolized, to the perfusate resulted in mTOR activation and contractile dysfunction. Next we tested our hypothesis in vivo by transverse aortic constriction in mice. Using a micro‐PET system, we observed enhanced glucose tracer analog uptake and contractile dysfunction preceding dilatation of the left ventricle. In contrast, in hearts overexpressing SERCA2a, ER stress was reduced and contractile function was preserved with hypertrophy. Finally, we examined failing human hearts and found that mechanical unloading decreased G6P levels and ER stress markers.ConclusionsWe propose that glucose metabolic changes precede and regulate functional (and possibly also structural) remodeling of the heart. We implicate a critical role for G6P in load‐induced mTOR activation and ER stress.

Objectives We aimed to investigate the pathophysiology of peripheral arterial disease (PAD) by examining magnetic resonance imaging (MRI) and spectroscopic (MRS) correlates of functional capacity. Background Despite the high prevalence, morbidity, and cost of PAD, its pathophysiology is incompletely understood. Methods Eighty-five patients (age 68±10) with mild-to-moderate PAD (ankle brachial index (ABI) 0.69±0.14) had their most symptomatic leg studied by MRI/MRS. Percent wall volume in the superficial femoral artery was measured with black blood MRI. First-pass contrast-enhanced MRI calf muscle perfusion and 31P MRS phosphocreatine recovery time constant (PCr) were measured at peak exercise in calf muscle. All patients underwent MR angiography (MRA), treadmill testing with VO2 max measurement and a 6-minute walk test. Results Mean MRA index of number and severity of stenoses was 0.84±0.68 (normal, 0), % wall volume 74±11% (normal, 46±7%), tissue perfusion 0.039±0.015 sec−1 (normal, 0.065±0.013 sec−1), and PCr 87±54s (normal, 34±16s). MRA index, % wall volume, and ABI correlated with most functional measures. PCr was the best correlate of treadmill exercise time, whereas calf muscle perfusion was the best correlate of 6-minute walk distance. No correlation was noted between PCr and tissue perfusion. Conclusion Functional limitations in PAD are multifactorial. As measured by magnetic resonance imaging and spectroscopy, atherosclerotic plaque burden, stenosis severity, and tissue perfusion and energetics all play a role. However, cellular metabolism is uncoupled from tissue perfusion. These findings suggest a potential role for therapies that regress plaque, increase tissue perfusion, and/or improve cellular metabolism.

Background-The role of the angiotensin II type 2 receptor (AT 2 -R) in left ventricular (LV) remodeling may depend on the underlying stimulus. We hypothesized that cardiac AT 2 -R overexpression in transgenic (TG) mice would attenuate remodeling after myocardial infarction (MI). Methods and Results-Ten wild-type (WT) C57BL/6 mice and 12 TG mice that overexpress the AT 2 -R in the heart were studied by cardiac MRI at baseline and days 1, 7, and 28 post-MI induced by 1 hour of occlusion of the LAD followed by reperfusion. Short-axis imaging from apex to base was used to determine LV mass index, end-diastolic and end-systolic volume indices (EDVI, ESVI), regional wall thickness and thickening, and ejection fraction (EF). Gadolinium-DTPA was infused 20 minutes before day 1 imaging to assess infarct size. At baseline, heart rate, blood pressure, LV mass index, and EDVI were similar between groups.