Novel technique for cardiac electromechanical mapping with magnetic resonance imaging tagging and an epicardial electrode sock.

Near-simultaneous measurements of electrical and mechanical activation over the entire ventricular surface are now possible using magnetic resonance imaging tagging and a multielectrode epicardial sock. This new electromechanical mapping technique is demonstrated in the ventricularly paced canine heart. A 128-electrode epicardial sock and pacing electrodes were placed on the hearts of four anesthetized dogs. In the magnetic resonance scanner, tagged cine images (8-15 ms/frame) and sock electrode recordings (1000 Hz) were acquired under right-ventricular pacing and temporally referenced to the pacing stimulus. Electrical recordings were obtained during intermittent breaks in image acquisition, so that both data sets represented the same physiologic state. Since the electrodes were not visible in the images, electrode recordings and cine images were spatially registered with Gd-DTPA markers attached to the sock. Circumferential strain was calculated at locations corresponding to electrodes. For each electrode location, electrical and mechanical activation times were calculated and relationships between the two activation patterns were demonstrated. This method holds promise for improving understanding of the relationships between the patterns of electrical activation and contraction in the heart.

The evaluation of dielectric resonators containing H2O or D2O as RF coils for high-field MR imaging and spectroscopy.

Electromagnetic resonators consisting of low-loss dielectric material and/or metallic boundaries are widely used in microwave technologies. These dielectric resonators usually have high Q factors and well-defined field distributions. Magnetic resonance imaging was shown as a way of visualizing the magnetic field distribution of the resonant modes of these resonators, if the dielectric body contains NMR sensitive nuclei. Dielectric resonators have also been proposed as RF coils for magnetic resonance experiments. The feasibility of this idea in high-field MR is discussed here. Specifically, the dielectric resonances of cylindrical water columns were characterized at 170.7 MHz (4 T 1H Larmor frequency), and evaluated as NMR transmit and receive coils. The dielectric resonance of a cylindrical volume of D2O was used to image a hand at 170.7 MHz. This study demonstrated that MRI is an effective way of visualizing the magnetic field in dielectric structures such as a water cylinder, and can potentially be generalized to solid-state dielectric devices. The possible applications of dielectric resonators other than simple cylindrical volumes in MRI and MR solution spectroscopy at high field strengths are also discussed.

Radiofrequency shielding of surface coils at 4.0 T.

Because radiation loss associated with a radiofrequency (RF) coil increases as roughly the fourth power of the frequency, this loss mechanism may become important in high-field studies above 2.0 T. In this study, the contribution of radiation losses at 4.0 T were determined in a rectangular surface coil using an RF shield to modify the radiation losses. The effect of this shield was determined on coil Q, B1 distribution, and signal to noise as a function of distance between the coil and the shield. Phantoms and human tissue were evaluated to characterize the loss mechanisms. The results demonstrate a large radiation loss in the unshielded surface coil. However, the radiation losses in vivo were not dominant owing to a large inductive loss occurring from dielectric currents in the body at 170 MHz.

Simultaneous measurement of cerebral oxygen consumption and blood flow using 17O and 19F magnetic resonance imaging.

17O and 19F magnetic resonance (MR) imaging were used to determine simultaneously the concentrations of H2 17O and CHF3 in 0.8-cc voxels in the cat brain during inhalation of a gas mixture containing both 17O2 and CHF3. The arterial time course of CHF3 was determined by "on-line" mass spectrometer detection of expired CHF3, and the arterial time course of H2 17O was determined by 17O MR analysis of arterial samples withdrawn during the inhalation period. The brain data and the arterial data for the two tracers were combined to calculate the cerebral oxygen consumption (CMRO2) and the CBF. The protocol was repeated on seven cats, using pentobarbital anesthesia. The average values of CMRO2 and CBF for a 0.8-cc voxel in the parietal cortex were 1.5 +/- 0.5 mmol kg-1 min-1 and 38 +/- 15 ml 100 g-1 min-1, respectively. In individual animals the average uncertainty in CMRO2 and CBF, calculated from Monte Carlo approaches, was +/- 9%.

The design and test of a new volume coil for high field imaging.

A major problem in the development of high field (> 100 MHz) large volume (> 6000 cm3) MR coils is the interaction of the coil with the subject as well as the radiation loss to the environment. To reduce subject perturbation of the coil resonance modes, a volume coil that uses an array of freely rotating resonant elements radially mounted between two concentric cylinders was designed for operation at 170 MHz. Substantial electromagnetic energy is stored in the resonant elements outside the sample region without compromising the efficiency of the overall coil. This stored energy reduces the effect of the subject on the circuit and maintains a high Q, facilitating the tuning and matching of the coil. The unloaded Q of the coil is 680; when loaded with a head, it was 129. The ratio of 5.3 of the unloaded to loaded Q supports the notion that the efficiency of the coil was maintained in comparison with previous designs. The power requirement and signal-to-noise performance are significantly improved. The coil is tuned by a mechanism that imparts the same degree of rotation on all of the elements simultaneously, varying their degree of mutual coupling and preserving the overall coil symmetry. A thin radiofrequency shield is an integral part of the coil to reduce the radiation effect, which is a significant loss mechanism at high fields. MR images were collected at 4T using this coil design with high sensitivity and B1 homogeneity.

Nonglucose substrates increase glycogen synthesis in vivo in dog heart.

The effects of circulating nonglucose substrates on insulin-stimulated cardiac glycogen synthesis were studied in the dog heart in vivo using 13C-nuclear magnetic resonance (-NMR) and arteriovenous difference techniques. [1-13C]glycogen was monitored in hearts during an intravenous infusion of 20 mU/min insulin and glucose while [1-13C]glucose (10 mg/min) was infused into the left anterior descending coronary artery. When 1 mmol/min of lactate, pyruvate, or beta-hydroxybutyrate was added to the venous infusion, the measured rate of glycogen synthesis was increased, on average, sixfold. It was not increased further after a subsequent 10-min infusion of 5 micrograms/min epinephrine. Lactate extraction increased from 0.18 +/- 0.05 to 0.62 +/- 0.11 mumol.min-1.g wet wt-1 during lactate infusion, whereas glucose extraction did not change significantly (0.15 +/- 0.05 mumol.min-1.g wet wt-1 at 45 min of insulin and glucose infusion to 0.09 +/- 0.02 mumol.min-1.g wet wt-1 at 45 min of the lactate infusion). Therefore, the uptake and oxidation of circulating nonglucose substrates redirects the fate of extracted glucose from glycolysis to glycogen synthesis in the dog heart in vivo.

In vivo proton spectroscopy and spectroscopic imaging of [1-13C]-glucose and its metabolic products.

Metabolism of [1-13C]-glucose was studied in situ in cat brain using gradient-enhanced proton-detected heteronuclear spectroscopy. Proton detection of [1-13C]-glucose, [3-13C]-lactate, 4-[13C]-glutamine, 4-[13C]-glutamate and the combined signals 2-[13C]-glutamate/glutamine and 3-[13C]-glutamate/glutamine was achieved, despite the fact that some of the associated proton resonances are close to the water signal. Two-dimensional [1H-13C]-spectra demonstrate the possibility of in situ spectral assignment with 1H sensitivity and 13C resolution. Spectroscopic images of glucose and its metabolic products were also acquired, showing the possibility to study spatial dependence of metabolism.

Pyruvate and lactate metabolism in the in vivo dog heart.

Pyruvate increases the phosphorylation potential in perfused heart to a greater extent than the closely correlated substrate L-lactate. Therefore, metabolism of these compounds was studied in the myocardium of intact dogs. Phosphocreatine/ATP was increased 23% at 5.3 mM plasma pyruvate but was not significantly increased by lactate except at the highest concentration (17.5 mM in blood). Calculated [ADP] fell during pyruvate infusion from 51.5 +/- 2.0 to 38.6 +/- 3.3 microM but did not change significantly during lactate infusion. Intracellular free [Mg2+] fell from 705 +/- 53 to 498 +/- 30 microM at the highest pyruvate infusion and from 692 +/- 112 to 417 +/- 19 microM with lactate infusion. Extraction of both substrates was linear at low concentrations, reaching 0.56 mumol lactate.min-1.g wet wt-1 at 17.5 mM blood lactate and 0.58 mumol pyruvate.min-1.g wet wt-1 at 5.3 mM plasma pyruvate. Therefore, lactate uptake was almost five times lower than pyruvate uptake at similar concentrations. Elevated pyruvate (> 3 mM) resulted in almost complete inhibition of net lactate uptake. Infused [3-13C]lactate or -pyruvate gave rise to labeled glutamate and alanine in vivo, but labeled lactate was not visible when [3-13C]pyruvate was the substrate. The 13C enrichment of myocardial lactate was similar to alanine and acetyl CoA with infused [3-13C]lactate but was only one-half that of alanine and acetyl CoA when [3-13C]-pyruvate was the substrate, indicating a possible inhibition of lactate dehydrogenase.

Regulation of glycogen metabolism in canine myocardium: effects of insulin and epinephrine in vivo.

Myocardial glycogen synthesis and glucose, lactate, and oxygen extraction were measured in the hearts of anesthetized dogs during infusions of insulin and epinephrine. Glycogen was monitored in vivo using 13C-nuclear magnetic resonance during an infusion of [1-13C]glucose into the left anterior descending artery. Glycogen synthesis was observed during a venous infusion of insulin (1.8 microU.min-1.kg-1), and this newly synthesized glycogen was neither broken down nor was more glycogen synthesized during a subsequent epinephrine infusion (0.5 micrograms.min-1.kg-1). During recovery from epinephrine, glycogen synthesis occurred at 2.1 times the rate seen in the control period. Glycogen synthesis was not stimulated in the absence of epinephrine by control infusions of saline. Glucose uptake was increased by insulin during the control period (from 0.09 to 0.39 mumol.min-1.g-1), so that the combined extraction of glucose and lactate exceeded the requirement for oxidizable substrate calculated from oxygen consumption. The "excess" glucose (0.15 mumol.min-1.g wet wt-1) is presumably available for glycogen synthesis. During recovery from epinephrine, lactate uptake was increased over threefold. Because this additional lactate supplies most of the fuel required for oxidation, the excess glucose available for glycogen synthesis during this period was two times that seen before epinephrine (an average of 0.32 mumol.min-1.g wet wt-1 between 20 and 40 min postepinephrine). These data are consistent with the notion that glycogen synthesis can be activated in the heart without an accompanying increase in glucose uptake by providing an alternative substrate (i.e., lactate) for oxidation.

MRI contrast-dose relationship of manganese(III)tetra(4-sulfonatophenyl) porphyrin with human xenograft tumors in nude mice at 2.0 T.

Previously we reported that Mn(III)tetra(4-sulfonatophenyl) porphyrin, MnTPPS4, is a contrast agent which can effectively enhance tumor detection by MRI. By imaging 30 additional athymic nude mice bearing subcutaneous MCF-7 WT human breast carcinoma xenografts, we have extended dose-contrast relationships over a wide range of intraperitoneal (IP) doses ranging from 0.025 to 0.50 mmol/kg. The benefits of IP injection are higher possible doses on a volume basis and a reduction in toxicity versus IV administration. Full coronal cross-section images have been obtained on a 2-T spectrometer. Although individual tumor masses displayed different distribution patterns, reflective of their internal morphology, single doses of 0.10 mmol/kg or greater were necessary to produce a detectable effect. At a dose of 0.50 mmol/kg, marked enhancement was produced. Multiple small dosages administered over the course of several days before imaging did not produce increased enhancement. Preliminary results on the new porphyrin derivative, MnTPPS3, indicate that the ratio of the toxic dose to the effective dose may be adjustable to render this class of agents clinically useful.

Echo-planar imaging of diffusion and perfusion.

Use of the Stejskal-Tanner sequence for performing diffusion images in the human brain tends to be complicated by the presence of artifacts caused by voluntary or involuntary, sometimes pulsatile, motion. We describe the implementation of the technique of echo-planar diffusion imaging, which avoids these artifacts and allows reproducible quantitative values of the diffusion coefficient to be measured in vivo. The effects of perfusion are easily visible in a phantom containing a gel. The results for human brain show a significant "perfusion fraction" in grey matter, consistent with an extracellular, possibly microvascular, volume of about 10%.

Measurement of cerebral blood flow by volume-selective 19F NMR spectroscopy.

A stimulated echo sequence was used to obtain 19F NMR spectra from within a 4-ml voxel in a cat brain. The time dependence of the 19F NMR signal from an inert gas (CHF3) was used to calculate the blood flow in the voxel. The position of the voxel was selected using a 1H MR image.