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Mapping neuronal activity noninvasively is a key requirement for in vivo human neuroscience. Traditional functional magnetic resonance (MR) imaging, with a temporal response of seconds, cannot measure high-level cognitive processes evolving in tens of milliseconds. To advance neuroscience, imaging of fast neuronal processes is required. Here, we show in vivo imaging of fast neuronal processes at 100-ms time scales by quantifying brain biomechanics noninvasively with MR elastography. We show brain stiffness changes of ~10% in response to repetitive electric stimulation of a mouse hind paw over two orders of frequency from 0.1 to 10 Hz. We demonstrate in mice that regional patterns of stiffness modulation are synchronous with stimulus switching and evolve with frequency. For very fast stimuli (100 ms), mechanical changes are mainly located in the thalamus, the relay location for afferent cortical input. Our results demonstrate a new methodology for noninvasively tracking brain functional activity at high speed.

Cell-therapy was proposed to be a promising tool in case of death or impairment of specific cell types. Correct identification of implanted cells became crucial when evaluating the success of transplantation therapy. Various methods of cell labeling have been employed in previously published studies. The use of intrinsic signaling of green fluorescent protein (GFP) has led to a well known controversy in the field of cardiovascular research. We encountered similar methodological pitfalls after transplantation of GFP-transfected embryonic stem cells into rat brains following traumatic brain injury (TBI). As the identification of implanted graft by intrinsic autofluorescence failed, anti-GFP labeling coupled to fluorescent and conventional antibodies was needed to visualize the implanted cells. Furthermore, different cell types with strong intrinsic autofluorescence were found at the sites of injury and transplantation, thus mimicking the implanted stem cells. GFP-positive stem cells were correctly localized, using advanced histological techniques. The activation of microglia/macrophages, accompanying the transplantation post TBI, was shown to be a significant source of artefacts, interfering with correct identification of implanted stem cells. Dependent on the strategy of stem cell tracking, the phagocytosis of implanted cells as observed in this study, might also impede the interpretation of results. Critical appraisal of previously published data as well as a review of different histological techniques provide tools for a more accurate identification of transplanted stem cells., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Dramatic cerebral responses following brain injury (TBI) comprise inflammation, cell death, and modulation of trophic factor release. These cerebral modulations might induce and/or attenuate acute neuronal damage. Here, we investigated the effect of tissue extract derived from healthy (HBE) or injured rat brain (TBE) on the differentiation of cultured embryonic stem cells in vitro. Rats were sacrificed at t = 45 minutes following lateral fluid-percussion injury and extracts of cerebral tissue were prepared from 4-6 healthy or injured rat brain hemispheres. Murine embryonic stem cells (CGR8) cultured in serum-free medium were then conditioned for a week with HBE or TBE. Omission of serum from the culture medium induced neural differentiation of CGR8 stem cells, as indicated by a significant time dependent down-regulation of oct-4 with a concomitant upregulation of nestin after 7 days. In parallel cell loss was observed that seemed to be largely due to apoptotic cell death. In TBE treated cells, on the other hand, a significant amplification of apoptotic cell death, enhancement of nestin and MAP2 expression and marked morphological changes such as axonal-like outgrowth was observed within 3 days of conditioning. Treatment of stem cells with HBE resulted in less pronounced neuronal differentiation processes. Axonal-like outgrowth was not observed. Our data suggest that during the early acute phase of traumatic injury the cerebral environment is disposed to detrimental as well as potent protective signals that seem to rapidly induce neurogenic processes., (Copyright © 2010 S. Karger AG, Basel.)

Objective: There is a growing literature on the relationship between low serum B-vitamins, elevated homocysteine, and cognitive impairment; however, few studies have examined radiological markers of associated neuropathology in geropsychiatry inpatients. The authors examined the relationship of homocysteine, folate, and vitamin B12 with magnetic resonance imaging (MRI) markers of neuropathology., Methods: In this archival study, authors reviewed the MRIs and medical records of 34 inpatients in a geriatric psychiatry unit. Patients were selected if folate, B12, and/or homocysteine levels had been assessed and if the appropriate clinical MRIs were performed (19 men; mean age, 75 years). Patients with schizophrenia or current substance dependence were excluded. The relationships between MRI volume measures, white-matter hyperintensity (WMH) grade, and serum concentrations of folate, B12, and homocysteine were analyzed, using age-adjusted Pearson correlations., Results: Homocysteine was related to WMH grade, but not brain-volume measures. Folate was associated with hippocampus and amygdala, and negatively associated with WMH. B12 level was not statistically associated with any brain measure., Conclusions: Elevated homocysteine and low folate were associated with radiological markers of neuropathology. Since no patient had clinically deficient folate, it may be important to rethink what defines functionally significant micronutrient deficiency and explore what this means in different age- and health-status groups. Larger samples will be needed to assess interactions between homocysteine, micronutrients, and other neuropathology risk factors.

Objective: Our objective was to evaluate a new scanning method, MR line scan diffusion imaging, and assess the apparent diffusion coefficient in the brains of healthy subjects and stroke patients., Subjects and Methods: Line scan diffusion imaging without cardiac gating or head restraints was implemented on low- (0.5 T) and medium- (1.5 T) field-strength scanners with conventional hardware. Diffusion-weighted images were obtained in six healthy subjects and eight stroke patients. Unidirectional diffusion encoding was used for fast localization of stroke lesions. For further characterization, orthogonal diffusion encoding was applied, and the trace of the apparent diffusion coefficient was calculated. Single-shot diffusion-weighted echoplanar imaging served as the reference standard. For healthy subjects, imaging was repeated four times on each scanner. Mean and relative precision of the apparent diffusion coefficient trace values were calculated for each pixel. In stroke lesions and adjacent normal tissue, apparent diffusion coefficient trace values were determined., Results: In the 108 scans obtained, line scan diffusion imaging proved to be robust, virtually free of artifact (independent of slice location and orientation), reproducible, and rapid for localization of a stroke. Scan time for 14 slices at 7-mm thickness was 8 min at 0.5 T and 7 min at 1.5 T. Image qualities with line scan diffusion imaging and single-shot diffusion-weighted echoplanar imaging were comparable. At 1.5 T, precision was essentially the same for line scan diffusion imaging (4.3%) and echoplanar imaging (4.7%). With line scan diffusion imaging at 0.5 T and 1.5 T, normal paraventricular apparent diffusion coefficient trace values averaged 0.71 microm2/msec, and with echoplanar imaging these values averaged 0.69 microm2/msec. In acute lesions apparent diffusion coefficient trace values were low, and in chronic lesions these values were high., Conclusion: Line scan diffusion imaging on low- and medium-field-strength MR scanners equipped with conventional hardware was reliable and practical for measuring brain apparent diffusion values, which can be applied to the early diagnosis, and hence timely management, of stroke.

A novel line scan diffusion imaging sequence (LSDI) is introduced. LSDI is inherently insensitive to motion artifacts and high quality diffusion maps of the brain can be obtained rapidly without the use of head restraints or cardiac gating. Results from a stroke study and abdominal diffusion images are presented. The results indicate that it is feasible to use the LSDI technique for clinical evaluation of acute ischemic stroke. In contrast to echo-planar diffusion imaging, LSDI does not require modified gradient hardware and can be implemented on conventional scanners. Thus, LSDI should dramatically increase the general availability of robust clinical diffusion imaging.

A retrospective analysis of clinical imaging using 2DFT SSFP at 0.14 T is presented. The technique's potential for tissue characterization and its utility for clinical diagnosis were tested by both in vitro measurements of various tissues and in vivo clinical images. Different pulse angles not only influenced image contrast, but also helped characterize lesions, particularly those containing fat. In addition, the pulse angle changed the signal from venous flow perpendicular to the imaged slice. The slow flow sensitivity of the 2DFT SSFP technique was demonstrated in the detection of CSF motion. Rapid SSFP offers flow sensitivity and adequate lesion detecting ability, along with high patient throughput.

Using a rapid Fourier SSFP imaging technique, which is sensitive to slow flow (approximately 1 mm/sec) in the plane of the image, we obtained 135 brain MRI examinations. The CSF flow/motion patterns were mapped by two images with orthogonal in plane flow sensitivity directions. Analysis showed significant deviations from the "normal" pattern in ventricular enlargements because of obstruction (no evidence of CSF flow/motion) or in normal pressure hydrocephalus (complex, intensive flow pattern in lateral ventricles) suggesting a diagnostic potential for this fast imaging technique.

The addition of a spin-lock preparatory sequence to a Carr-Purcell-Meiboom-Gill (CPMG) imaging sequence provides a method which allows an accurate and simple comparison of T1p and T2 contrast. Sagittal and axial brain images, produced with the application of a three pulse preparatory spin-lock sequence prior to a sixteen-echo CPMG imaging sequence, are compared with images acquired without the spin-lock sequence. The CPMG sequence uses non-selective refocusing pulses. Therefore, observed echo signals accurately reflect T2 relaxation. This allows a convenient method for assessing the degree to which T1p and T2 contrast differ. The spin-lock CPMG (SL-CPMG) images were acquired with a spin-locking field amplitude of 0.4 G and resemble heavily T2-weighted images at 0.15 T. Quantitative analyses of signal intensities from edema and normal brain tissue confirm the qualitative observations. This in vivo method should prove useful for determining when the additional RF power deposition associated with spin-locking techniques will provide an alternate form of tissue contrast than that available from additional echo collection.