The overall pattern of cardiac contraction depends on a spatial gradient of myosin regulatory light chain phosphorylation.

Evolution of the human heart has incorporated a variety of successful strategies for motion used throughout the animal kingdom. One such strategy is to add the efficiency of torsion to compression so that blood is wrung, as well as pumped, out of the heart. Models of cardiac torsion have assumed uniform contractile properties of muscle fibers throughout the heart. Here, we show how a spatial gradient of myosin light chain phosphorylation across the heart facilitates torsion by inversely altering tension production and the stretch activation response. To demonstrate the importance of cardiac light chain phosphorylation, we cloned a myosin light chain kinase from a human heart and have identified a gain-in-function mutation in two individuals with cardiac hypertrophy.

Mixed echo train acquisition displacement encoding with stimulated echoes: an optimized DENSE method for in vivo functional imaging of the human heart.

Mixed echo train acquisition displacement encoding with stimulated echoes (meta-DENSE) is a phase-based displacement mapping technique suitable for imaging myocardial function. This method has been optimized for use with patients who have a history of myocardial infarction. The total scan time is 12-14 heartbeats for an in-plane resolution of 2.8 x 2.8 mm2. Myocardial strain is mapped at this resolution with an accuracy of 2% strain in vivo. Compared to standard stimulated echo (STE) methods, both data acquisition speed and resolution are improved with inversion-recovery FID suppression and the meta-DENSE readout scheme. Data processing requires minimal user intervention and provides a rapid quantitative feedback on the MRI scanner for evaluating cardiac function. Published 2001 Wiley-Liss, Inc.

MRI of the human eye using magnetization transfer contrast enhancement.

PURPOSE: To determine the feasibility of using magnetization transfer contrast-enhanced magnetic resonance imaging (MRI) to track cataractous lens changes. METHODS: A fast spin-echo sequence was modified to include a magnetization transfer contrast (MTC) preparation pulse train. This consisted of twenty 8.5-msec sinc pulses, 1200 Hz upfield from the water resonance and 1.2-Hz power. The MTC preparation pulse was followed by acquisition through fast spin-echo imaging. The imaging parameters were number of excitations (NEX) = 1, echo time (TE) = 14 msec, recovery time (TR) = 2 sec, echo train length of eight echos, and a matrix size of 256 x 160. To reduce motion artifacts, the volunteers were asked to fixate on a blinking LED. Normal and MTC-enhanced images were acquired from normal volunteers and volunteers with nuclear or cortical cataracts. RESULTS: The eye was adequately imaged, with few motion artifacts appearing. The lens was well resolved, despite the short T(2). The cornea and ciliary body were also clearly visible. In the lens, resolution of the epithelium and cortex were enhanced with MTC. In addition, contrast-to-noise ratios were measured for each image. Examination of the contrast-to-noise ratio confirmed that MTC increased the contrast between the nucleus and cortex. Unenhanced MRIs showed significant differences between the cortex of normal volunteers and volunteers with cataracts. MTC-enhanced images improved the sensitivity to changes in the nucleus. CONCLUSIONS: In this preliminary study, we were able to use MTC-enhanced MRI to obtain high-contrast images of the human lens. Regular and enhanced MRIs detected statistically significant differences between normal and cataractous lenses.

In vivo (1)H double quantum filtered MRI of the human wrist and ankle.

Proton double quantum filtered (DQF) NMR imaging was applied in vivo to the human wrist and ankle with a clinical 1.5 T MR scanner. Water molecules having anisotropic motion were detected from tendons and ligaments. Images of Achilles tendon were obtained for a voxel size of 1.25 x 1.25 x 20 mm with three values of TR = 1.0, 0.5, and 0.2 sec, resulting in total acquisitions time of 17, 8.5, and 3.4 mins, respectively. Some degradation of the signal-to-noise ratio was observed at the shortest TR value and the contrast was significantly reduced due to SQ coherence leakage. The in vivo DQF images showed structure within the tendon that is otherwise not visible by conventional gradient-recalled echo (GRE) methods. Published 2000 Wiley-Liss, Inc.

A new class of contrast agents for MRI based on proton chemical exchange dependent saturation transfer (CEST).

It has been previously shown that intrinsic metabolites can be imaged based on their water proton exchange rates using saturation transfer techniques. The goal of this study was to identify an appropriate chemical exchange site that could be developed for use as an exogenous chemical exchange dependent saturation transfer (CEST) contrast agent under physiological conditions. These agents would function by reducing the water proton signal through a chemical exchange site on the agent via saturation transfer. The ideal chemical exchange site would have a large chemical shift from water. This permits a high exchange rate without approaching the fast exchange limit at physiological pH (6.5-7.6) and temperature (37 degrees C), as well as minimizing problems associated with magnetic field susceptibility. Numerous candidate chemicals (amino acids, sugars, nucleotides, heterocyclic ring chemicals) were evaluated in this preliminary study. Of these, barbituric acid and 5, 6-dihydrouracil were more fully characterized with regard to pH, temperature, and concentration CEST effects. The best chemical exchange site found was the 5.33-ppm indole ring -NH site of 5-hydroxytryptophan. These data demonstrate that a CEST-based exogenous contrast agent for MRI is feasible.

Effect of muscle action and metabolic strain on oxidative metabolic responses in human skeletal muscle.

A recent report suggests that differences in aerobic capacity exist between concentric and eccentric muscle action in human muscle (T. W. Ryschon, M. D. Fowler, R. E. Wysong, A. R. Anthony, and R. S. Balaban. J. Appl. Physiol. 83: 867-874, 1997). This study compared oxidative response, in the form of phosphocreatine (PCr) resynthesis rates, with matched levels of metabolic strain (i.e., changes in ADP concentration or the free energy of ATP hydrolysis) in tibialis anterior muscle exercised with either muscle action in vivo (n = 7 subjects). Exercise was controlled and metabolic strain measured by a dynamometer and (31)P-magnetic resonance spectroscopy, respectively. Metabolic strain was varied to bring cytosolic ADP concentration up to 55 microM or decrease the free energy of ATP hydrolysis to -55 kJ/mol with no change in cytoplasmic pH. PCr resynthesis rates after exercise ranged from 31.9 to 462.5 and from 21.4 to 405.4 micromol PCr/s for concentric and eccentric action, respectively. PCr resynthesis rates as a function of metabolic strain were not significantly different between muscle actions (P > 0.40), suggesting that oxidative capacity is dependent on metabolic strain, not muscle action. Pooled data were found to more closely conform to previous biochemical measurements when a term for increasing oxidative capacity with metabolic strain was added to models of respiratory control.

High-resolution strain analysis of the human heart with fast-DENSE.

Single breath-hold displacement data from the human heart were acquired with fast-DENSE (fast displacement encoding with stimulated echoes) during systolic contraction at 2.5 x 2.5 mm in-plane resolution. Encoding strengths of 0.86-1.60 mm/pi were utilized in order to extend the dynamic range of the phase measurements and minimize effects of physiologic and instrument noise. The noise level in strain measurements for both contraction and dilation corresponded to a strain value of 2.8%. In the human heart, strain analysis has sufficient resolution to reveal transmural variation across the left ventricular wall. Data processing required minimal user intervention and provided a rapid quantitative feedback. The intrinsic temporal integration of fast-DENSE achieves high accuracy at the expense of temporal resolution.

DENSE: displacement encoding with stimulated echoes in cardiac functional MRI.

Displacement encoding with stimulated echoes (DENSE) was developed for high-resolution myocardial displacement mapping. Pixel phase is modulated by myocardial displacement and data spatial resolution is limited only by pixel size. 2D displacement vector maps were generated for the systolic action in canines with 0.94 x 1.9 mm nominal in-plane resolution and 2.3 mm/pi displacement encoding. A radial strain of 0.208 was measured across the free left ventricular wall over 105 ms during systole. DENSE displacement maps require small first-order gradient moments for encoding. DENSE magnitude images exhibit black-blood contrast which allows for better myocardial definition and reduced motion-related artifacts.

Spatial localization with modified Fourier series windows. Application to the transmural 13C-nuclear magnetic resonance analysis of the in vivo myocardium.

RATIONALE AND OBJECTIVES: A modified Fourier Series Window (FSW) method is introduced that provides a simple, reasonably accurate, solution to spatial localization for layers in nuclear magnetic resonance (NMR) spectroscopy. This method was developed because signal originating from spins immediately adjacent to the coil plane can leak into standard FSW localized spectra obtained from more distal layers. METHODS: The B1 profile of the surface coil and a priori sample knowledge were used to generate modified FSW coefficients that largely compensate for contamination from proximal layers. These modified coefficients were used to acquire spatially localized spectra from a three-layered phantom containing inorganic phosphate, phosphocreatine, and pyrophosphate. Spatially localized spectra also were obtained from the open-chest canine myocardium. RESULTS: The modified Fourier Series Window approach was validated using a quality assurance phantom. This method was then applied to the transmural analysis of 13C-containing metabolites in the in vivo canine myocardium during 3-(13)C sodium pyruvate infusion (n = 10). In vivo NMR spectra were characterized by resonances corresponding to the C2, C3, and C4 carbons of glutamic acid and to endogenous triacyglycerides and surface lipids. A transmural trend in metabolites could be observed under these conditions. This trend, however, was likely to result from the interference of surface lipids in the epicardial layer. CONCLUSIONS: The authors demonstrate that the modified Fourier Series Window method can be applied in situations where signal-to-noise considerations limit the applicability of more sophisticated spatial localization methods. In addition, the authors report a slight gradient in the endogenous triacylglyceride resonance, which is likely to originate from the presence of surface lipids.

Alternate k-space sampling in EPI: compensation for T2* and adjustable T2 weighting.

In this work, preliminary results are described for a modification of the MBEST sampling scheme such that image resolution can be increased while preserving image contrast. In this new approach, a single spin-echo is used in sampling k-space. The basic idea relies on acquiring a conventional EPI image from the center of k-space and applying a pi pulse to permit the acquisition of the two outer edges of k-space. Using this new approach, it is possible to obtain an enhancement in EPI image resolution, while reducing the extent of T2* weighting. As a result, the resulting images possess reduced T2* contrast and suffer less signal loss from T2* effects such as spatial variations in susceptibility and field inhomogeneity.

3D echo planar imaging: application to the human head.

In this work, the authors present 3D images acquired from the human head using echo planar encoding for two of the three dimensions of k-space. The third dimension of k-space is filled by selecting and phase encoding a slab of spins as in conventional 3D steady state (GRASS based) acquisition regimens. Using this approach, a 128 x 64 x 64 3D data matrix could be obtained in 3.4-4.7 sec using effective TE values of 24 and 34 ms, respectively. High quality 3D images could be acquired once phase ghosts present on 2D images were minimized through proper adjustments of scanner hardware.

Water and fat MR imaging with chemical shift selective 3D steady state methods.

A new 3D acquisition regimen that enables the collection of conventional, water-suppressed, and fat-suppressed images with no increase in scan times compared with currently implemented 3D sequences is presented. The method is based on conventional 3D steady state with interleaved selective excitation of the fat resonance resulting in acquisition of a fat-based image during the TR period experienced by the water spins. This new sequence is relatively tolerant to susceptibility artifacts and results in excellent water-based images. Because the idea, which we propose, is independent of the type of steady-state imaging protocol utilized, it can be easily applied with regimens that are specifically tailored to enhance contrast.

Torque free asymmetric gradient coils for echo planar imaging.

In this work, we present a new torque-free asymmetric gradient coil that is capable of generating high quality axial, sagittal, and coronal echo planar images of the human head. This gradient set was calculated using the Biot-Savart law and least square approaches to optimize the field in the region of interest and to minimize net torques. The resulting structure has excellent shoulder-to-coil clearance and, as such, has the advantage of providing good patient access to the linear portion of the gradient while minimizing patient discomfort from claustrophobia.