Faculty Bibliography

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.

The dynamics of spin 3/2 systems is analyzed using the density matrix theory of relaxation. By using the superoperator formalism, an algebraic formulation of the density matrix's evolution is obtained, in which the contributions from free relaxation and RF application are easily factored out. As an intermediate step, an exact form for the propagator of the density matrix for a spin 3/2 system, in the presence of static quadrupolar coupling, inhomogeneous static magnetic field, and relaxation is demonstrated. Using this algebraic formulation, exact expressions for the behavior of the density matrix in the classical one-, two-, and three-pulse experiments are derived. These theoretical formulas are then used to illustrate the bias introduced on the measured relaxation parameters by the presence of large spatial variations in the B0 and B1 fields. The theoretical predictions are easily evaluated through simple matrix algebra and the results agree very well with the experimental observations. This approach could prove useful for the characterization of the spatial variations of the signal intensity in multiple quantum-filtered sodium MRI experiments.

This work presents a small tip-angle 3D tailored RF slab-select pulse for reducing the B1 field inhomogeneity at 3T. The compensated slice profile was determined from a B1 inhomogeneity map. SNR improvement and degree of artifact reduction were evaluated in a NiCl2 doped phantom and human brains. The technique was found to reduce inhomogeneities as large as 30% of the peak image magnitude in all three spatial directions in the brain using a standard head coil.

This chapter demonstrates the use of sodium magnetic resonance imaging (MRI) as a noninvasive, in vivo means to assess metabolic changes that ensue from loss of cell ion homeostasis due to cell death in the brain. The chapter is organized in two sections. In the first section, the constraints imposed on the imaging methods by the nuclear magnetic resonance (NMR) properties of the sodium ion are discussed and strategies for avoiding their potential limitations are addressed. The second section illustrates the use of sodium MRI for monitoring focal brain ischemia in permanent and temporary primate models of endovascular middle cerebral artery occlusion

BACKGROUND: Skeletal muscle lipid is associated with obesity and type 2 diabetes and may be altered by diet, physical activity, and weight loss. OBJECTIVE: We explored the utility of magnetic resonance imaging (MRI) for quantifying the lipid concentration of muscle tissue in vivo. DESIGN: Fat-selective MR images of the lower leg were taken in 8 normal-weight [body mass index (in kg/m(2)) < or = 24.9] and 8 obese (body mass index > 29.9) subjects to obtain spatial maps of lipid signal intensity within muscle tissue. Fast-spiral-sequence (echo time = 5.6-13.8 ms, repetition time = 1 s, 8 interleaves) MRI scans were conducted at 3.0 T by using an extremity transmit-receive coil. Lipid concentrations within muscle were determined from manually drawn regions of interest in the tibialis anterior (TA), soleus, and medial head of the gastrocnemius (MHG) muscle groups. RESULTS: There was extremely good agreement (mean R(2) = 0.985) between the fat signal intensity and the actual lipid concentration of standards containing 2.5, 5.0, and 10.0 g lipid/dL, which were placed on the subject's leg during each scan. The lipid content of both the soleus (2.99 +/- 0.37 g/dL) and the MHG (3.80 +/- 0.68 g/dL) was higher (P < 0.05) than that of the TA (1.83 +/- 0.28 g/dL). Lipid content was more than two-fold higher (P < 0.05) in the MHG of obese subjects (5.48 +/- 1.18 g/dL) than in the MHG of normal-weight subjects (2.54 +/- 0.47 g/dL), but did not differ significantly in the TA or soleus. CONCLUSIONS: MRI can be used to quantify lipid within human muscle tissue. MRI can also be used to detect differences in muscle lipid content among various muscle groups and between normal-weight and obese subjects.

For many years, neurosurgeons and otolaryngologic surgeons have used the fibrin glue product Tisseel to repair skull-base spinal fluid leaks and to help secure repairs following anterior cranial-base surgery. Despite the widespread use, the potential focal cerebral toxicity of this fibrin glue has never been investigated. We studied the safety of Tisseel applied directly to neural tissue (brain parenchyma, cervical cord, and C3-C6 spinal roots) of 6 monkeys (Macaca nemestrina) to determine if any underlying biochemical injury would occur. Another 3 animals that served as controls received saline rather than Tisseel. We found that median nerve electroencephalographic tracings and somatosensory evoked potentials in the experimental and control animals were identical. Likewise, cerebrospinal fluid indicators of neuronal or brain injury, inflammatory responses, and infection were negative in both groups. Finally, there were no significant differences between the two groups with respect to edema volumes and apparent diffusion coefficient values. We conclude that Tisseel does not induce an apparent inflammatory response or abnormal neurophysiologic or histologic response within 5 days of its application when it is applied directly to the brain parenchyma or onto the cervical spinal cord.

HIV infection in humans and simian immunodeficiency virus (SIV) infection in macaques result in encephalitis in approximately one-quarter of infected individuals and is characterized by infiltration of the brain with infected and activated macrophages. 1-(2-chlorphenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxamide (PK11195) is a ligand specific for the peripheral benzodiazepine receptor abundant on macrophages and is expressed in low levels in the noninfected brain. We hypothesized that positron-emission tomography (PET) with the carbon-11-labeled, R-enantiomer form of PK11195 ([(11)C](R)-PK11195) could image brain macrophages and hence the development of encephalitis in vivo. [(11)C](R)-PK11195 binding was assessed in the brain using PET in 11 SIV infected macaques, six of which showed increased binding in vivo. Postmortem examination of the brain in these six macaques demonstrated encephalitis, while macaques that did not show an increase in [(11)C](R)-PK11195 binding did not develop SIV encephalitis. Brain tissue from SIV encephalitic macaques also showed increased [(3)H](R)-PK11195 binding compared with binding in nonencephalitic macaques. Increased PK11195 binding in vivo and in postmortem brain tissue correlated with abundance of macrophages but not astrocytes. Our results suggest that PET [(11)C](R)-PK11195 imaging can detect the presence of macrophages in SIV encephalitis in vivo and may be useful to predict the development of HIV encephalitis and in studies of the pathogenesis and treatment of HIV dementia.

We address the development of triple-quantum-filtered sodium MRI as a non-invasive surrogate measure for cell proliferation in brain tumors. We demonstrate that through careful consideration of the theoretical description of the signal, triple-quantum-filtered sodium images of adequate signal-to-noise ratio (SNR) can be acquired in clinically acceptable imaging times.