Faculty Bibliography

An animal model was developed to monitor [K(+)] in the brain using partial K(+) replacement with Rb(+) and (87)Rb MRI. Fifty-one rats were given 0-80 mM of RbCl in the drinking water for up to 90 days. Focal cerebral ischemia was produced in 15 of the animals. Na, K, and Rb content in precision-guided submilligram samples of cortical brain were determined by emission flame photometry. Multinuclear (87)Rb/(23)Na/(1)H MRI was performed on phantoms and rats at 3T using a twisted projection imaging (TPI) scheme for (87)Rb/(23)Na, and custom-built surface or parallel cosine transmit/receive coils. Brain [Rb(+)] was safely brought up to 17-25 mEq/kg within 2-3 weeks of feeding. The characteristic patterns of [K(+)] decrease (with a sharp drop at 3-4 hr of ischemia) and [Na(+)] increase (at a rate of 31%/hr) observed previously in animals without Rb/K substitution were reproduced in ischemic cortex. The Rb/(Rb+K) ratio increased over time in ischemic areas (R = 0.91, P < 0.001), suggesting an additional index of ischemia progression. Preliminary (87)Rb MRI gave an estimate of 20-25 mEq Rb/kg brain weight (N = 2). In conclusion, brain Rb(+) is detectable by (87)Rb MRI and does not significantly interfere with ion dynamics in ischemic brain, which enables (87)Rb MRI studies of K(+) in ischemia.

Triple quantum (TQ) sodium MRI techniques with clinically acceptable 18-min data acquisition times were demonstrated in vivo in a nonhuman primate model of focal brain ischemia. Focal brain ischemia was induced in four animals using embolization coils to occlude the posterior cerebral artery, and a balloon catheter to occlude the middle cerebral artery. A statistically significant increase (P < 0.001) in the TQ sodium MRI signal intensity in the ischemic hemisphere relative to the contralateral hemisphere was seen at all time points in all four animals. This increased TQ sodium MRI signal intensity was demonstrated as early as 0.6 hr after the onset of ischemia. The TQ sodium MRI hyperintensity corresponded to the anatomical location of the ischemic cortex, as indicated by the registration of the TQ imaging data with anatomical proton MRI data. The results demonstrate that early after the onset of ischemia, there was an increase in the TQ signal intensity in the ischemic hemisphere, and a negligible change in the single quantum (SQ) signal intensity

An extension of the "UNaliasing by Fourier encoding the Overlaps using the temporaL Dimension" (UNFOLD) method to the excitation domain (XUNFOLD) is presented to improve the temporal resolution of multishot tailored RF (TRF) pulses. Multishot three-dimensional TRF pulses were designed to produce a time series of images with periodically aliased excitation profiles. The XUNFOLD method is shown to remove the excitation profile aliasing from the dynamic imaging data by filtering in the temporal frequency dimension. The technique is demonstrated to improve the temporal resolution of simulated functional MRI (fMRI) activation in a time series of brain images.

This study examined whether the severity of cerebral white matter abnormalities (evident on MR images as white matter hyperintensities (WMH)) was related to the cognitive performance of 141 high-functioning older adults. The elderly showed the typical age decrement on measures of processing speed, working memory, and inhibition; however WMH severity was significantly related only to processing speed. The strength of this relationship was, however, influenced by the educational level of the participants, such that processing speed was more associated with WMH severity in less-educated than in well-educated participants. This is consistent with recent concepts of cognitive reserve, but does raise a question as to the underlying source of the cognitive decrement found in the sort of well-educated elders typically used in cognitive-aging studies.

The pathology associated with late-stage dementia in human immunodeficiency virus (HIV) infection has been studied extensively. Neuropathological examination has demonstrated abundant activation and infection of macrophages/microglia termed HIV encephalitis. For obvious reasons, less is known regarding the neuropathology of minor cognitive impairment seen in earlier stages of HIV infection. The authors examined the utility of the peripheral benzodiazepine receptor ligand PK11195 in positron emission tomography (PET) imaging to assess microglial/macrophage activation in the brains of HIV-infected subjects with minor neurocognitive impairment in a cross-sectional study of 12 HIV infected individuals and 5 age-matched noninfected controls. Subjects were given a battery of neuropsychological tests in addition to assessing CD4 T-cell count and peripheral viremia followed by contrast enhanced magnetic resonance imaging (MRI) and PET with [15O]H2O followed by [11C](R)-PK11195. Two of the six neurocognitively impaired HIV-infected subjects demonstrated plasma viral breakthrough, whereas only one of six nonimpaired individuals demonstrated plasma viral load near the limits of detection. MRI demonstrated no abnormal enhancement and although atrophy was more prominent in impaired subjects, it was also present though to a lesser extent in nonimpaired subjects. None of the 12 HIV-infected subjects demonstrated increased retention of [11C](R)-PK11195 in the brain parenchyma compared to the 5 controls. These results suggest that either [11C](R)-PK11195 PET assessment is insensitive to the degree of macrophage activation in HIV-associated minor neurocognitive impairment or macrophage activation is not the pathological substrate of this neurological condition.

A new k-space direct matrix inversion (DMI) method is proposed here to accelerate non-Cartesian SENSE reconstructions. In this method a global k-space matrix equation is established on basic MRI principles, and the inverse of the global encoding matrix is found from a set of local matrix equations by taking advantage of the small extension of k-space coil maps. The DMI algorithm's efficiency is achieved by reloading the precalculated global inverse when the coil maps and trajectories remain unchanged, such as in dynamic studies. Phantom and human subject experiments were performed on a 1.5T scanner with a standard four-channel phased-array cardiac coil. Interleaved spiral trajectories were used to collect fully sampled and undersampled 3D raw data. The equivalence of the global k-space matrix equation to its image-space version, was verified via conjugate gradient (CG) iterative algorithms on a 2x undersampled phantom and numerical-model data sets. When applied to the 2x undersampled phantom and human-subject raw data, the decomposed DMI method produced images with small errors (< or = 3.9%) relative to the reference images obtained from the fully-sampled data, at a rate of 2 s per slice (excluding 4 min for precalculating the global inverse at an image size of 256 x 256). The DMI method may be useful for noise evaluations in parallel coil designs, dynamic MRI, and 3D sodium MRI with fixed coils and trajectories.

This article presents a small-flip-angle, three-dimensional tailored RF pulse that excites thin slices with an adjustable quadratic in-plane spatial variation. The quadratic spatial variation helps to compensate for the loss in image uniformity using a volume coil at 3 T due to the wavelike properties of the RF field. The pulse is based on a novel "fast-kz" design that uses a series of slice-select subpulses along kz and phase encoding "blips" along kx-ky. The method is demonstrated by acquiring a series of 5-mm-thick T2-weighted images of the human brain at 3 T using pulses 4.8 ms in length with a 45 degrees flip angle.

BACKGROUND AND PURPOSE: Thrombolytic therapy with intravenous tPA must be administered within 3 hours after stroke onset. However, stroke onset time cannot be established in 20% to 45% of potential patients. We propose that the rate of increase of the brain concentration of sodium ([Na+]br) after stroke, monitored using sodium MRI in a rat model of cortical ischemia, is linear in each individual animal, can locate the ischemic region, and can be used to estimate onset time. METHODS: After induction of focal cortical ischemia in rats under isoflurane anesthesia, [Na+]br time course maps were acquired continuously on a 3 T whole body scanner from 2 to 7 hours after occlusion followed by T2-weighted proton images. Microtubule-associated protein-2 immunostained brain sections were used to verify the location of the infarct. RESULTS: The ischemic region identified with microtubule-associated protein-2 corresponded to the region of maximum [Na+]br increase (P<0.001; n=5), and all of the animals demonstrated high linearity. [Na+]br increased at a mean rate of 25+/-4.7%/h in ischemic tissue (P=0.013) but not in normal cortex (1.0+/-1.1%/h; P=0.42). The mean onset time error was 1+/-4 minutes (n=4). CONCLUSIONS: These results of sodium MRI show that the region of maximum [Na+]br increase corresponds to the ischemic region. Although [Na+]br increases at a different rate in each animal, the increase is linear, and, therefore, onset time can be estimated. These findings suggest that this method can be used as a ticking clock to estimate time elapsed after vascular occlusion.

Osteoarthritis (OA) is a leading cause of disability worldwide. Magnetic resonance imaging (MRI), with its unique ability to image and characterize soft tissue non-invasively, has proven valuable in assessing cartilage in OA. The development of new, fast imaging methods with high contrast show promise to improve the magnetic resonance (MR) evaluation of this disease. In addition to morphologic MRI methods, MRI contrast mechanisms under development may reveal detailed information about the physiology of cartilage. It is anticipated that these and other MRI techniques will play an increasingly important role in assessing the success or failure of therapies for OA. On December 5 and 6, 2002, OMERACT (Outcome Measures in Rheumatology Clinical Trials) and OARSI (Osteoarthritis Research Society International) held a workshop in Bethesda, MD aiming at providing a state-of-the-art review of imaging outcome measures for OA of the knee to help guide scientists and pharmaceutical companies in the use of MRI in multi-site studies of OA. Applications of MRI were initially reviewed by a multidisciplinary, international panel of expert scientists and physicians from academia, the pharmaceutical industry and regulatory agencies. The findings of the panel were then presented to a wider group of participants for open discussion. The following report summarizes the results of these discussions with respect to novel MRI pulse sequences for evaluating articular cartilage of the knee in OA and notes any additional advances that have been made since.

Triple quantum filtered sodium MRI techniques have been recently demonstrated in vivo. These techniques have been previously advocated as a means to separate the sodium NMR signal from different physiological compartments based on the differences between their relaxation rates. Among the different triple quantum coherence transfer filters, the three-pulse coherence transfer filter has been demonstrated to be better suited for human imaging than the traditional four-pulse implementation. While the three-pulse structure has distinct advantages in terms of RF efficiency, the lack of a refocusing pulse in the filter introduces an increased dependence on the main magnetic field inhomogeneities, which can sometimes lead to significant signal loss. In this paper, we characterize these dependencies and introduce a method for their compensation through the acquisition of a B(0) map and the use of a modified phase cycling scheme.