Charles T. Wheeler

Utilizing MRI information to estimate F18-FDG distributions in rat flank tumors

This paper investigates the potential of magnetic resonance imaging (MRI) to improve the estimation of within-tumor variations in F18-FDG concentration. An image model is described for incorporating MRI images into positron emission tomography (PET) and single photon emission computed tomography (SPECT) radiotracer image reconstruction. The model promotes greater smoothing, of estimated radiotracer concentration, among nearby voxels that have more nearly similar MRI signals. R3230 mammary adenocarcinomas are grown on rat flanks. Autoradiography, histology, and T2-weighted MRI are used to demonstrate that the above image model accurately reflects true F18-FDG distributions in R3230 tumors. In vivo F18-FDG distributions are then reconstructed from PET projection data, with and without incorporating MRI. The F18-FDG images reconstructed with MRI show greater detail, and this additional detail is consistent with the results of the autoradiography and histology studies.

Measurements of hyperpolarized gas properties in the lung. Part III: 3He T1

Hyperpolarized 3He spin‐lattice relaxation was investigated in the guinea pig lung using spectroscopy and imaging techniques with a repetitive RF pulse series. T1 was dominated by interactions with oxygen and was used to measure the alveolar O2 partial pressure. In animals ventilated with a mixture of 79% 3He and 21% O2, T1 dropped from 19.6 sec in vivo to 14.6 sec after cardiac arrest, reflecting the termination of the intrapulmonary gas exchange. The initial difference in oxygen concentration between inspired and alveolar air, and the temporal decay during apnea were related to functional parameters. Estimates of oxygen uptake were 29 ± 11 mL min−1 kg−1 under normoxic conditions, and 9.0 ± 2.0 mL min−1 kg−1 under hypoxic conditions. Cardiac output was estimated to be 400 ± 160 mL min−1 kg−1. The functional residual capacity derived from spirometric magnetic resonance experiments varied with body mass between 5.4 ± 0.3 mL and 10.7 ± 1.1 mL. Magn Reson Med 45:421–430, 2001.

Effects of breathing and cardiac motion on spatial resolution in the microscopic imaging of rodents.

One can acquire high‐resolution pulmonary and cardiac images in live rodents with MR microscopy by synchronizing the image acquisition to the breathing cycle across multiple breaths, and gating to the cardiac cycle. The precision with which one can synchronize image acquisition to the motion defines the ultimate resolution limit that can be attained in such studies. The present work was performed to evaluate how reliably the pulmonary and cardiac structures return to the same position from breath to breath and beat to beat across the prolonged period required for MR microscopy. Radiopaque beads were surgically glued to the abdominal surface of the diaphragm and on the cardiac ventricles of anesthetized, mechanically ventilated rats. We evaluated the range of motion for the beads (relative to a reference vertebral bead) using digital microradiography with two specific biological gating methods: 1) ventilation synchronous acquisition, and 2) both ventilation synchronous and cardiac‐gated acquisitions. The standard deviation (SD) of the displacement was ≤100 μm, which is comparable to the resolution limit for in vivo MRI imposed by signal‐to‐noise ratio (SNR) constraints. With careful control of motion, its impact on resolution can be limited. This work provides the first quantitative measure of the motion‐imposed resolution limits for in vivo imaging. Magn Reson Med 53:858–865, 2005.

Fiber-optic stethoscope: A cardiac monitoring and gating system for magnetic resonance microscopy

A fundamental problem associated with using the conventional electrocardiograph (ECG) to monitor a subjects cardiac activity during magnetic resonance imaging (MRI) is the distortion of the ECG due to electromagnetic interference. This problem is particularly pronounced in MR microscopy (MRI of small animals at microscopic resolutions (< 0.03 mm3)) because the strong, rapidly‐switching magnetic field gradients induce artifacts in the animals ECG that often mimic electrophysiologic activity, impairing the use of the ECG for cardiac monitoring and gating purposes. The fiber‐optic stethoscope system offers a novel approach to measuring cardiac activity that, unlike the ECG, is immune to electromagnetic effects. The fiber‐optic stethoscope is perorally inserted into the esophagus of small animals to optically detect pulsatile compression of the esophageal wall. The optical system is shown to provide a robust cardiac monitoring and gating signal in rats and mice during routine cardiac MR microscopy. Magn Reson Med 47:314–321, 2002.

Extravascular extravasation of radiographic contrast media: Effects of conventional and low-osmolar agents in the rat thigh

We compared the damage resulting from intradermal injection of four commonly used radiographic contrast media in laboratory rats. Sixty percent meglumine diatrizoate (Reno M 60) and ioxaglate (Hexabrix) produced significantly more ulceration and crusting on gross inspection and more necrosis, edema, and hemorrhage on histologic evaluation than iopamidol 300 (Isovue) or 0.9% (normal) saline. Thirty percent meglumine diatrizoate (Reno M Dip) had an intermediate toxicity, resulting in significantly more visible swelling and more microscopically detected hemorrhage than iopamidol or saline, but less ulceration/crusting and necrosis than Reno M 60 and ioxaglate. Since the three contrast agents of similar osmolality produced different degrees of tissue damage, our results suggest that factors other than high osmolality are partially responsible for determining the severity of injuries from extravasated contrast media.

Magnetic resonance microscopy of toxic renal injury induced by bromoethylamine in rats

The alkylhalide 2-bromoethylamine hydrobromide (BEA) produces renal injury in rats that mimics analgesic-related renal injury in humans. Our purpose was to examine this injury, in vivo in rats, with magnetic resonance (MR) microscopy and correlate MR findings with findings from light microscopy of hematoxylin-eosin-stained sections. Rats (n = 48) were injected intravenously with BEA (150 mg/kg) or saline and imaged with MR 6, 48, and 336 hr later. The spin-spin relaxation time, T2, was measured from the cortex to the papilla. In other rats, we measured regional water content of the kidney. Renal injury was present 48 and 336 hr after BEA dosing based on increased renal organ weights, decreased urine specific gravity, and significant renal lesions (H & E). T2 was elevated in the inner stripe of the outer medulla in injured kidneys at 48 hr. The differences in T2 between cortex and outer medulla were also elevated 48 hr after BEA. In the inner medulla, there were no changes in T2 after BEA treatment. However, in all groups there were significant regional differences in T2. The value of T2 increased from outer to inner medulla and this gradient was directly correlated with water content. Thus, MR microscopy detected damage in the outer medulla after BEA injury but not the damage in the inner medulla. T2 appeared to reflect the water content in the different regions of the medulla. The noninvasive in vivo capability of MR microscopy, with its high sensitivity to tissue water, allows the toxicologist to monitor the progression and regression of toxic insult in the same animal. At present the technology is complicated. The precise and accurate measure of MR-sensitive parameters in live animals at microscopic resolution is difficult. However, as the technology matures, there will be significant improvements providing the toxicologist a unique in vivo tool.

Volumetric microCT system for in vivo microscopy

Two of the major barriers to improved image quality in microCT are the reduced signal to noise imposed by the smaller voxels and the effects of physiologic motion. The most direct approach to increase the signal to noise ratio (SNR) is to increase the flux. This is not possible in most of laboratory and commercial microCT systems that are currently in use. We adopted a design that allows the use of high instantaneous X-ray flux combined with synchronization to physiologic motion. High quality imaging of moving organs such as the heart or the lungs is directly dependent on appropriate gating techniques. For this purpose, we acquired X-ray projections using a flexible controller to enable sophisticated biological pulse sequences to minimize the effects of motion. This paper reports on the development of a volumetric microCT scanner dedicated to structural and functional phenotyping of the live mouse.

Effects of breathing motion on the spatial resolution in microscopic imaging techniques of rodents

Magnetic resonance microscopy is capable of producing high-resolution pulmonary images in live rodents by synchronizing the image acquisition across multiple breaths. The precision with which one can control motion will probably define the resolution limit that can be attained in such studies. This work was performed to evaluate how reliably the respiratory structures return to the same position from breath to breath each time data are acquired. Radio-opaque beads were surgically glued on the diaphragm of anesthetized, mechanically ventilated rats. Their range of motion (relative to a reference vertebral bead) was evaluated using digital micro-radiography with two specific biological pulse sequences: (1) ventilation synchronous acquisition, and (2) both ventilation synchronous and cardiac gated acquisition. The standard deviation of the displacement was on the order of, or less than 100 microns, which is comparable to the resolution limit for in vivo magnetic resonance imaging imposed by signal to noise constraints. With careful control of motion, its impact on resolution can be limited. This work provides the first quantitative measure of the motion imposed resolution limits for in vivo imaging.