Faculty Bibliography

PURPOSE: To examine, using blood oxygen level dependent (BOLD) MRI and EPR oximetry, the changes in oxygenation of intracranial tumors induced by carbogen breathing. MATERIALS AND METHODS: The 9L and CNS-1 intracranial rat tumor models were imaged at 7T, before and during carbogen breathing, using a multi-echo gradient-echo (GE) sequence to map R(2)*. On a different group of 9L tumors, tissue pO(2) was measured using EPR oximetry with lithium phthalocyanine as the oxygen-sensitive material. RESULTS: The average decline in R(2)* with carbogen breathing was 13 +/- 1 s(-1) in the CNS-1 tumors and 29 +/- 4 s(-1) in the 9L tumor. The SI vs. TE decay curves indicate the presence of multiple components in the tumor. Tissue pO(2) in the two 9L tumors measured was 8.6 +/- 0.5 and 3.6 +/- 0.6 mmHg during air breathing, and rose to 20 +/- 7 and 16 +/- 4 mmHg (mean +/- SE) with carbogen breathing. Significant changes were observed by 10 minutes, but changes in pO(2) and R(2)* continued in some subjects over the entire 40 minutes. CONCLUSION: EPR results indicate that glial sarcomas may be radiobiologically hypoxic. Both EPR and BOLD data indicate that carbogen breathing increases brain tumor oxygenation. These data support the use of BOLD imaging to monitor changes in oxygenation in brain tumors

Although shimming can improve static field inhomogeneity, local field imperfections induced by tissue susceptibility differences cannot be completely corrected and can cause substantial signal loss in gradient echo images through intravoxel dephasing. Dephasing increases with voxel size so that one simple method of reducing the effect is to use thin slices. Signal-to-noise ratio (SNR) can then be increased by averaging over the subslices to form the final, thick slice. We call this method subslice averaging or SSAVE. Alternatively, a range of different amplitude slice select rephase gradients can be used to compensate for different susceptibility induced gradient offsets. The final image can then be formed by combining individual images in a variety of ways: summation, summation of the squares of the images, forming the maximum intensity projection of the image set, and Fourier transformation followed by summation. We show here that, contrary to previous claims, the theoretical sensitivity (i.e., SNR divided by the square root of the imaging time) of all these alternative methods is very similar. However, performance time (i.e., minimum-imaging time) of the simplest method, SSAVE, is much shorter than that of alternatives. This is confirmed experimentally on phantoms and anesthetized mice. Magn Reson Med 45:470-476, 2001.

Huntingtin is an essential protein that with mutant polyglutamine tracts initiates dominant striatal neurodegeneration in Huntington's disease (HD). To assess the consequences of mutant protein when huntingtin is limiting, we have studied three lines of compound heterozygous mice in which both copies of the HD gene homolog (Hdh) were altered, resulting in greatly reduced levels of huntingtin with a normal human polyglutamine length (Q20) and/or an expanded disease-associated segment (Q111): Hdh(neoQ20)/Hdh(neoQ20), Hdh(neoQ20)/Hdh(null) and Hdh(neoQ20)/Hdh(neoQ111). All surviving mice in each of the three lines were small from birth, and had variable movement abnormalities. Magnetic resonance micro-imaging and histological evaluation showed enlarged ventricles in approximately 50% of the Hdh(neoQ20)/Hdh(neoQ111) and Hdh(neoQ20)/Hdh(null) mice, revealing a developmental defect that does not worsen with age. Only Hdh(neoQ20)/Hdh(neoQ111) mice exhibited a rapidly progressive movement disorder that, in the absence of striatal pathology, begins with hind-limb clasping during tail suspension and tail stiffness during walking by 3-4 months of age, and then progresses to paralysis of the limbs and tail, hypokinesis and premature death, usually by 12 months of age. Thus, dramatically reduced huntingtin levels fail to support normal development in mice, resulting in reduced body size, movement abnormalities and a variable increase in ventricle volume. On this sensitized background, mutant huntingtin causes a rapid neurological disease, distinct from the HD-pathogenic process. These results raise the possibility that therapeutic elimination of huntingtin in HD patients could lead to unintended neurological, as well as developmental side-effects

Blood oxygenation level-dependent (BOLD) magnetic resonance (MR) imaging is sensitive, in part, to the amount of paramagnetic deoxyhemoglobin in a voxel. This project was designed to determine whether there would be differences in the BOLD response between the hippocampus and other brain regions to acute hypoxia. R2* was quantified using a multi-echo gradient-echo sequence. The pyramidal CA1 region of the hippocampus showed a reduced response to changes in arterial oxygenation relative to cortex and basal ganglia and white matter. This difference may relate to the relative hypoxia sensitivity of the hippocampus. It also supports the premise that in functional MR imaging, the magnitude of the MR response to a stimulus may vary with the region of the brain.

A simple theoretical model was developed to compare the sensitivities (i.e., signal-to-noise ratios per unit imaging time) of two-dimensional (2D) multislice and 3D imaging sequences. The model shows that the sensitivities of 3D and 2D multislice MRI sequences are usually similar. Sensitivities are identical in T2-weighted sequences when the T(R)s of the two sequences are the same. In T1-weighted gradient-echo sequences, sensitivities are very similar when Ernst angle excitation is used and the T(R) of the 2D sequence is less than T1. The predictions of the model are confirmed in phantom and animal experiments

The mdx mouse has a genetically homologous disease to Duchenne muscular dystrophy in humans. The disease progression, however, is not accompanied by the same level of fatty infiltration and muscle degeneration as occurs in humans. Thus, the presence of histological/pathological changes in living mdx mice has been difficult to monitor. We quantified proton density and the T2 relaxation time of protons with a resolution of 195 x 195 x 1000 microm using multiecho magnetic resonance (MR) imaging at 7 Tesla. These relaxation data were correlated with water content in both muscle and brain of mdx and controls. No differences were observed in brain. The mdx muscles had increased water content and proton density and decreased T2 relative to controls. These data indicate that there are intrinsic changes in T2 (opposite to that which would be induced by fatty infiltration) and suggest that T2 imaging could be used to monitor progression and treatment in this animal model

RATIONALE AND OBJECTIVES: This study was designed to determine the relative influences of proton density versus collagen fiber orientation (through its influence on T2) in defining the layers of articular cartilage as seen in long-repetition-time magnetic resonance (MR) images. The authors mapped the T2 and proton densities of articular cartilage at 0 degree and 55 degrees with respect to the main magnetic field (B0) to determine the influence of T2 and water content on the normal laminar appearance of hyaline cartilage. MATERIALS AND METHODS: Six patellae of white-tailed deer were imaged at 7 T. T2 and proton densities were calculated from echo time versus signal intensity plots obtained with a multiecho, composite pulse sequence. Regions of interest in the radial and transitional zones were compared with the articular facets at 0 degree and 55 degrees relative to B0. Transmission electron microscopy was performed for correlation. RESULTS: At 0 degree, T2 was longer in the transitional than in the radial zone (29 vs 11 msec). AT 55 degrees, T2 increased in both radial and transitional zones, although the difference between the zones decreased (37 vs 29 msec). There was no difference in proton density between the two layers. CONCLUSION: Collagen fiber orientation, through T2 effects, is the dominant influence on the appearance of layers in hyaline cartilage in long-repetition-time MR images; proton density is not a major factor, and the collagen fiber orientation in the transitional zone is not totally random

An optimization scheme was developed for gradient echo imaging using a half-birdcage RF coil at 7 T to obtain maximal contrast between gray and white matter in the spinal cord of rodents. This optimization was combined with microimaging techniques to obtain in vivo pixel sizes of 78 x 78 x 700 microm. These techniques can be implemented in an in vivo study to investigate the myelin structure within the white matter of the rodent spinal cord