Aaron S. Field

Diffusion Tensor Imaging of the Brain

SummaryDiffusion tensor imaging (DTI) is a promising method for characterizing microstructural changes or differences with neuropathology and treatment. The diffusion tensor may be used to characterize the magnitude, the degree of anisotropy, and the orientation of directional diffusion. This review addresses the biological mechanisms, acquisition, and analysis of DTI measurements. The relationships between DTI measures and white matter pathologic features (e.g., ischemia, myelination, axonal damage, inflammation, and edema) are summarized. Applications of DTI to tissue characterization in neurotherapeutic applications are reviewed. The interpretations of common DTI measures (mean diffusivity, MD; fractional anisotropy, FA; radial diffusivity, Dr; and axial diffusivity, Da) are discussed. In particular, FA is highly sensitive to microstructural changes, but not very specific to the type of changes (e.g., radial or axial). To maximize the specificity and better characterize the tissue microstructure, future studies should use multiple diffusion tensor measures (e.g., MD and FA, or Da and Dr).

White matter tractography using diffusion tensor deflection

Diffusion tensor MRI provides unique directional diffusion information that can be used to estimate the patterns of white matter connectivity in the human brain. In this study, the behavior of an algorithm for white matter tractography is examined. The algorithm, called TEND, uses the entire diffusion tensor to deflect the estimated fiber trajectory. Simulations and imaging experiments on in vivo human brains were performed to investigate the behavior of the tractography algorithm. The simulations show that the deflection term is less sensitive than the major eigenvector to image noise. In the human brain imaging experiments, estimated tracts were generated in corpus callosum, corticospinal tract, internal capsule, corona radiata, superior longitudinal fasciculus, inferior longitudinal fasciculus, fronto‐occipital fasciculus, and uncinate fasciculus. This approach is promising for mapping the organizational patterns of white matter in the human brain as well as mapping the relationship between major fiber trajectories and the location and extent of brain lesions. Hum. Brain Mapping 18:306–321, 2003.

Deactivation of Sensory-Specific Cortex by Cross-Modal Stimuli

Visual and auditory cortices traditionally have been considered to be modality-specific. Thus, their activity has been thought to be unchanged by information in other sensory modalities. However, using functional magnetic resonance imaging (fMRI), the present experiments revealed that ongoing activity in the visual cortex could be modulated by auditory information and ongoing activity in the auditory cortex could be modulated by visual information. In both cases, this cross-modal modulation of activity took the form of deactivation. Yet, the deactivation response was not evident in either cortical area during the paired presentation of visual and auditory stimuli. These data suggest that cross-modal inhibitory processes operate within traditional modality-specific cortices and that these processes can be switched on or off in different circumstances.

Probiotic helminth administration in relapsing–remitting multiple sclerosis: a phase 1 study

Background: Probiotic treatment strategy based on the hygiene hypothesis, such as administration of ova from the non-pathogenic helminth, Trichuris suis, (TSO) has proven safe and effective in autoimmune inflammatory bowel disease. Objective: To study the safety and effects of TSO in a second autoimmune disease, multiple sclerosis (MS), we conducted the phase 1 Helminth-induced Immunomodulatory Therapy (HINT 1) study. Methods: Five subjects with newly diagnosed, treatment-naive relapsing–remitting multiple sclerosis (RRMS) were given 2500 TSO orally every 2 weeks for 3 months in a baseline versus treatment control exploratory trial. Results: The mean number of new gadolinium-enhancing magnetic resonance imaging (MRI) lesions (n-Gd+) fell from 6.6 at baseline to 2.0 at the end of TSO administration, and 2 months after TSO was discontinued, the mean number of n-Gd+ rose to 5.8. No significant adverse effects were observed. In preliminary immunological investigations, increases in the serum level of the cytokines IL-4 and IL-10 were noted in four of the five subjects. Conclusion: TSO was well tolerated in the first human study of this novel probiotic in RRMS, and favorable trends were observed in exploratory MRI and immunological assessments. Further investigations will be required to fully explore the safety, effects, and mechanism of action of this immunomodulatory treatment.

Characterization of Cerebral White Matter Properties Using Quantitative Magnetic Resonance Imaging Stains

The image contrast in magnetic resonance imaging (MRI) is highly sensitive to several mechanisms that are modulated by the properties of the tissue environment. The degree and type of contrast weighting may be viewed as image filters that accentuate specific tissue properties. Maps of quantitative measures of these mechanisms, akin to microstructural/environmental-specific tissue stains, may be generated to characterize the MRI and physiological properties of biological tissues. In this article, three quantitative MRI (qMRI) methods for characterizing white matter (WM) microstructural properties are reviewed. All of these measures measure complementary aspects of how water interacts with the tissue environment. Diffusion MRI, including diffusion tensor imaging, characterizes the diffusion of water in the tissues and is sensitive to the microstructural density, spacing, and orientational organization of tissue membranes, including myelin. Magnetization transfer imaging characterizes the amount and degree of magnetization exchange between free water and macromolecules like proteins found in the myelin bilayers. Relaxometry measures the MRI relaxation constants T1 and T2, which in WM have a component associated with the water trapped in the myelin bilayers. The conduction of signals between distant brain regions occurs primarily through myelinated WM tracts; thus, these methods are potential indicators of pathology and structural connectivity in the brain. This article provides an overview of the qMRI stain mechanisms, acquisition and analysis strategies, and applications for these qMRI stains.

Diffusion tensor eigenvector directional color imaging patterns in the evaluation of cerebral white matter tracts altered by tumor

To categorize the varied appearances of tumor‐altered white matter (WM) tracts on diffusion tensor eigenvector directional color maps.

Dietary caffeine consumption modulates fMRI measures.

Caffeine is the most widely used stimulant in the world. The stimulant effects of caffeine are mediated through its antagonistic properties on neuronal adenosine receptors. In addition, caffeine blocks neurovascular adenosine receptors and decreases cerebral perfusion. Although the effects of caffeine on blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging measures are extremely important, there are few studies addressing this issue in the literature. Because chronic caffeine use causes an upregulation of adenosine receptors, the differential effects of caffeine in low and high users is of particular interest. The present study was designed to test the hypothesis that caffeine has differential effects on the BOLD signal in high and low caffeine users. We demonstrated that the BOLD signal change in visual cortex was significantly greater in high users than in low users in the presence of caffeine. In addition, the magnitude of the BOLD signal was significantly correlated with caffeine consumption. We propose that the outcome observed here was due to an upregulation of adenosine receptors in high users, resulting in differential contributions of the neural and vascular effects of adenosine in the two study populations.

Test-retest reproducibility of quantitative CBF measurements using FAIR perfusion MRI and acetazolamide challenge.

The reproducibility of quantitative cerebral blood flow (CBF) measurements using MRI with arterial spin labeling and acetazolamide challenge was assessed in 12 normal subjects, each undergoing the identical experimental procedure on two separate days. CBF was measured on a 1.5T scanner using a flow‐sensitive alternating inversion recovery (FAIR) pulse sequence, performed both at baseline and 12 min after intravenous administration of acetazolamide. T1 was measured in conjunction with the FAIR scan in order to calculate quantitative CBF. The CBF maps were segmented to separate gray matter (GM) from white matter (WM) for region‐of‐interest (ROI) analyses. Post‐ acetazolamide CBF values (ml/100 g/min, mean ± SD) of 87.5 ± 12.5 (GM) and 46.1 ± 10.8 (WM) represented percent increases of 37.7% ± 24.4% (GM) and 40.1% ± 24.4% (WM). Day‐to‐day differences in baseline CBF were −1.7 ± 6.9 (GM) and –1.4 ± 4.7 (WM) or, relative to the mean CBF over both days for each subject, −2.5% ± 11.7% (GM) and −3.8% ± 13.6% (WM) Day‐ to‐day differences in absolute post‐ACZ CBF increase were −2.5 ± 6.8 (GM) and 2.7 ± 9.4 (WM) or, relative to the mean CBF increase over both days for each subject, –4.7% ± 13.3% (GM) and 9.1% ± 26.2% (WM). Thus, FAIR‐ based CBF measurements show satisfactory reproducibility from day to day, but with sufficient variation to warrant caution in interpreting longitudinal data. The hemispheric asymmetry of baseline CBF and post‐acetazolamide CBF increases varied within a narrower range and should be sensitive to small changes related to disease or treatment. Magn Reson Med 47:921–928, 2002.

Diffusion tensor imaging in cerebral tumor diagnosis and therapy.

Diffusion-weighted MR images and their analysis using the tensor model open up many new possibilities for tissue characterization, surgical planning, and treatment follow-up in patients with cerebral neoplasms. These possibilities are only just beginning to be fully explored. This article reviews the physical principles underlying diffusion tensor imaging (DTI); the various postprocessing methods available for DTI data in the context of tumor imaging; the commonly encountered patterns of tumor-related alteration to cerebral white matter, as depicted by directionally encoded color maps; and the current state of the art in DTI-based tumor diagnosis and treatment planning.

A Calorie-Restricted Diet Decreases Brain Iron Accumulation and Preserves Motor Performance in Old Rhesus Monkeys

Caloric restriction (CR) reduces the pathological effects of aging and extends the lifespan in many species, including nonhuman primates, although the effect on the brain is less well characterized. We used two common indicators of aging, motor performance speed and brain iron deposition measured in vivo using MRI, to determine the potential effect of CR on elderly rhesus macaques eating restricted (n = 24; 13 males, 11 females) and standard diets (n = 17; 8 males, 9 females). Both the CR and control monkeys showed age-related increases in iron concentrations in globus pallidus (GP) and substantia nigra (SN), although the CR group had significantly less iron deposition in the GP, SN, red nucleus, and temporal cortex. A diet × age interaction revealed that CR modified age-related brain changes, evidenced as attenuation in the rate of iron accumulation in basal ganglia and parietal, temporal, and perirhinal cortex. Additionally, control monkeys had significantly slower fine motor performance on the Movement Assessment Panel, which was negatively correlated with iron accumulation in left SN and parietal lobe, although CR animals did not show this relationship. Our observations suggest that the CR-induced benefit of reduced iron deposition and preserved motor function may indicate neural protection similar to effects described previously in aging rodent and primate species.