S.J. Blackband

A three-dimensional digital atlas database of the adult C57BL/6J mouse brain by magnetic resonance microscopy

A comprehensive three-dimensional digital atlas database of the C57BL/6J mouse brain was developed based on magnetic resonance microscopy images acquired on a 17.6-T superconducting magnet. By using both manual tracing and an atlas-based semi-automatic segmentation approach, T2-weighted magnetic resonance microscopy images of 10 adult male formalin-fixed, excised C57BL/6J mouse brains were segmented into 20 anatomical structures. These structures included the neocortex, hippocampus, amygdala, olfactory bulbs, basal forebrain and septum, caudate-putamen, globus pallidus, thalamus, hypothalamus, central gray, superior colliculi, inferior colliculi, the rest of midbrain, cerebellum, brainstem, corpus callosum/external capsule, internal capsule, anterior commissure, fimbria, and ventricles. The segmentation data were formatted and stored into a database containing three different atlas types: 10 single-specimen brain atlases, an average brain atlas and a probabilistic atlas. Additionally, quantitative group information, such as variations in structural volume, surface area, magnetic resonance microscopy image intensity and local geometry, were computed and stored as an integral part of the database. The database augments ongoing efforts with other high priority strains as defined by the Mouse Phenome Database focused on providing a quantitative framework for accurate mapping of functional, genetic and protein expression patterns acquired by a myriad of technologies and imaging modalities.

MR microscopy of multicomponent diffusion in single neurons.

This study examines multicomponent diffusion in isolated single neurons and discusses the implications of the results for macroscopic water diffusion in tissues. L7 Aplysia neurons were isolated and analyzed using a 600 MHz Bruker wide‐bore instrument with a magnetic susceptibility‐matched radiofrequency microcoil. Using a biexponential fit, the apparent diffusion coefficients (ADCs) from the cytoplasm (with relative fraction) were 0.48 ± 0.14 × 10−3 mm2s−1 (61 ± 11%) for the fast component, and 0.034 ± 0.017 × 10−3 mm2s−1 (32 ± 11%) for the slow component (N = 10). Diffusion in the nucleus appears to be primarily monoexponential, but with biexponential analysis it yields 1.31 ± 0.32 × 10−3 mm2s−1 (89 ± 6%) for the fast component and 0.057 ± 0.073 × 10−3 mm2s−1 (11 ± 6%) for the slow (N = 5). The slow component in the nucleus may be explained by cytoplasmic volume averaging. These data demonstrate that water diffusion in the cytoplasm of isolated single Aplysia neurons supports a multiexponential model. The ADCs are consistent with previous measurements in the cytoplasm of single neurons and with the slow ADC measurement in perfused brain slices. These distributions may explain the multiple compartments observed in tissues, greatly aiding the development of quantitative models of MRI in whole tissues. Magn Reson Med 46:1107–1112, 2001.

Oscillating and pulsed gradient diffusion magnetic resonance microscopy over an extended b‐value range: Implications for the characterization of tissue microstructure

Oscillating gradient spin‐echo (OGSE) pulse sequences have been proposed for acquiring diffusion data with very short diffusion times, which probe tissue structure at the subcellular scale. OGSE sequences are an alternative to pulsed gradient spin echo measurements, which typically probe longer diffusion times due to gradient limitations. In this investigation, a high‐strength (6600 G/cm) gradient designed for small‐sample microscopy was used to acquire OGSE and pulsed gradient spin echo data in a rat hippocampal specimen at microscopic resolution. Measurements covered a broad range of diffusion times (TDeff = 1.2–15.0 ms), frequencies (ω = 67–1000 Hz), and b‐values (b = 0–3.2 ms/μm2). Variations in apparent diffusion coefficient with frequency and diffusion time provided microstructural information at a scale much smaller than the imaging resolution. For a more direct comparison of the techniques, OGSE and pulsed gradient spin echo data were acquired with similar effective diffusion times. Measurements with similar TDeff were consistent at low b‐value (b < 1 ms/μm2), but diverged at higher b‐values. Experimental observations suggest that the effective diffusion time can be helpful in the interpretation of low b‐value OGSE data. However, caution is required at higher b, where enhanced sensitivity to restriction and exchange render the effective diffusion time an unsuitable representation. Oscillating and pulsed gradient diffusion techniques offer unique, complementary information. In combination, the two methods provide a powerful tool for characterizing complex diffusion within biological tissues. Magn Reson Med 69:1131–1145, 2013.

Quantitative measurement of neurodegeneration in an ALS–PDC model using MR microscopy

Exposure to cycad (Cycas micronesica K.D. Hill) toxins via diet has been shown to induce neurodegeneration in vivo that mimics the progressive neurological disease, amyotrophic lateral sclerosis--parkinsonism dementia complex (ALS--PDC). In previous studies, specific cortical and subcortical cell loss was measured with conventional stained sections. In the present study, magnetic resonance (MR) microscopy was used to examine neurodegeneration in three dimensions (3D) in isolated intact brains and spinal cords. Mice were fed washed cycad for 2 months and showed progressive motor deficits resembling human ALS--PDC. CNS tissue was imaged at 17.6 T. T2* scans were acquired on both spinal cord and brain samples with an isotropic resolution of 41 microm. Through MR volumetrics, cycad-fed mice showed significantly decreased volumes in lumbar spinal cord gray matter, substantia nigra, striatum, basal nucleus/internal capsule, and olfactory bulb. Cortical measurements of conventionally stained sections revealed that cycad-fed mice also showed decreased cortical thickness. These results show that MR microscopy (MRM) is sensitive enough to measure degeneration in this early stage model of a progressive neurological disease with strong correlations to behavioral deficits and histological results and may be applicable in vivo to the same model. Similar analysis may be used in the future as a diagnostic aid in tracking the early progression of neurological disorders in preclinical human subjects.

Nuclear magnetic resonance imaging measurements of water diffusion in the perfused hippocampal slice during N-methyl-d-aspartate-induced excitotoxicity

Significant changes in the apparent diffusion coefficient of water are observed in nuclear magnetic resonance images of patients with acute ischemic stroke. However, the underlying mechanisms of these apparent diffusion coefficient changes are still unresolved. To analyse possible mechanisms, this study applies nuclear magnetic resonance imaging on a 14.1 Tesla narrow-bore magnet to quantitatively study water diffusion in individually perfused brain slices following exposure to N-methyl-D-aspartate excitotoxicity. The results indicate that brain slices have at least two distinct diffusing water compartments with apparent diffusion coefficients of 0.96+/-0.10x10(-3) mm2/s and 0.06+/-0.01x10(-3) mm2/s. When excitotoxicity was induced with N-methyl-D-aspartate, there was a significant decrease in the fraction of the fast diffusing water component in the slices (P<0.001). However, neither apparent diffusion coefficient changed significantly. Prior treatment with dizocilpine maleate (MK-801) depressed the effects of N-methyl-D-aspartate (P<0.01, ANOVA). The results demonstrate brain slice compartmental changes resulting from direct receptor stimulation and provide evidence for tissue water redistribution as an important mechanism for changes in apparent diffusion coefficient seen in clinical magnetic resonance imaging. The brain slice preparation affords a well-controlled method to study the mechanisms of tissue nuclear magnetic resonance contrast, bridging the gap between basic nuclear magnetic resonance studies and clinical magnetic resonance imaging. The brain slice model also offers a new way to test the utility of potential anti-stroke drugs using high field nuclear magnetic resonance imaging.

Intermolecular multiple quantum coherences at high magnetic field: the nonlinear regime.

Experiments have been carried at magnetic-field strengths of 9.4, 14.1, and 17.6 T to explore the evolution of intermolecular multiple quantum coherences in the nonlinear regime where the system evolves for times that are much greater than the characteristic time of action of the long-range dipolar field, tau(d). The results show the expected Bessel function form of the recorded signal as a function of time of evolution, with evident zeros and sign changes. As expected, the rate of signal evolution increases at higher-field strengths as a result of the increased equilibrium magnetization. A numerical method for calculating the evolution of magnetization under the action of the distant dipolar field, relaxation, and diffusion that is based on Fourier analysis of the magnetization distribution has been applied to the correlated two-dimensional spectroscopy revamped by asymmetric z-gradient echo detection sequence in the nonlinear regime and shown to produce results that are in good agreement with experimental data acquired at different magnetic fields and rates of spatial modulation. Experiments and simulations have also been used to explore the evolution of magnetization in a mixture of two interacting spin species in the nonlinear regime.

High resolution MR microimaging of neuronal tissue at 17.6 T

The evolution of magnetic resonance instruments to higher field strengths mandates continued improvement in associated RF technologies. Coil design, gradients and amplifiers must not only be optimized to the sample of interest but must meet the concomitant challenges of increased operating frequencies at higher magnetic fields. Using one of the first 17.6 T wide-bore MR instruments equipped for both imaging and high resolution spectroscopy, a variety of biological samples have been examined. In this report, we describe some of the recent applications of this 750 MHz instrument to microimaging and microspectroscopy, with particular focus on the necessary RF hardware developments required at greatly increased resolutions. Predominately through the optimization of RF coils, maximum image resolutions of less than 10 /spl mu/m have been achieved from research-relevant, biological samples.