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Perinatal hypoxia affects normal neurological development and can lead to motor, behavioral and cognitive deficits. A common acute treatment for perinatal hypoxia is oxygen resuscitation (hyperoximia), a controversial treatment. Magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI), was performed in a P7 rat model of perinatal hypoxia to determine the effect of hyperoximia. These studies were performed on two groups of animals: 1) animals which were subjected to ischemia followed by hypoxia (HI), and 2) HI followed by hyperoximic treatment (HHI). Lesion volumes on high resolution MRI and DTI derived measures, fractional anisotropy (FA), mean diffusivity (MD), and axial and radial diffusivities (lambda(l) and lambda(t), respectively) were measured in vivo one day, one week, and three weeks after injury. Most significant differences in the MRI and DTI measures were found at three weeks after injury. Specifically, three weeks after HHI injury resulted in significantly larger hyperintense lesion volumes (95.26 +/- 50.42 mm(3)) compared to HI (22.25 +/- 17.62 mm(3)). The radial diffusivity lambda(t) of the genu of corpus callosum was significantly larger in HHI (681 +/- 330 x 10(-6) mm(2)/sec) than in HI (486 +/- 96 x 10(-6) mm(2)/sec). Over all, most significant differences in all the DTI metrics (FA, MD, lambda(t), lambda(l)) at all time points were found in the corpus callosum. Our results suggest that treatment of perinatal hypoxia with normobaric oxygen does not ameliorate, but exacerbates damage., ((c) 2009 Wiley-Liss, Inc.)

Diffusion tensor imaging (DTI) has the potential to reveal disruption of white matter microstructure in chronically injured spinal cords. We quantified fractional anisotropy (FA) and mean diffusivity (MD) to demonstrate retrograde Wallerian degeneration (WD) of cranial corticospinal tract (CST) in cervical spinal cord injury (SCI). Twenty-two patients with complete cervical SCI in the chronic stage were studied with DTI along with 13 healthy controls. Mean FA and MD values were computed for midbrain, pons, medulla, posterior limb of internal capsule, and corona radiata. Significant reduction in the mean FA and increase in MD was observed in the cranial CST in patients with SCI compared with controls, suggesting retrograde WD. Statistically significant inverse FA and MD changes were noted in corona radiata, indicating some restoration of spared white matter tracts. Temporal changes in the DTI metrics suggest progressing degeneration in different regions of CST. These spatiotemporal changes in DTI metrics suggest continued WD in injured fibers along with simultaneous reorganization of spared white matter fibers, which may contribute to changing neurological status in chronic SCI patients.

Perinatal hypoxia is a major cause of neurodevelopmental deficits. Neuronal migration patterns are particularly sensitive to perinatal hypoxia/ischemia and are associated with the clinical deficits. The rat model of hypoxia/ischemia at P7 mimics that of perinatal injury in humans. Before assessing the effects of postnatal injury on brain development, it is essential to determine the normal developmental trajectories of various brain structures in individual animals. In vivo longitudinal diffusion tensor imaging (DTI) was performed from postnatal day 0 (P0) to P56 on Wistar rats. The DTI metrics, mean diffusivity (MD), fractional anisotropy (FA), axial (lambdal) and radial (lambdat) diffusivities, were determined for four gray matter and eight white matter structures. The FA of the cortical plate and the body of corpus callosum decreased significantly during the first 3 weeks after birth. The decrease in the cortical plate's FA value was associated mainly with an increase in lambdat. The initial decrease in FA of corpus callosum was associated with a significant decrease in lambdal. The FA of corpus callosum increased during the rest of the observational period, which was mainly associated with a decrease in lambdat. The FA of gray matter structures, hippocampus, caudate putamen, and cortical mantle did not show significant changes between P0 and P56. In contrast, the majority of white matter structures showed significant changes between P0 and P56. These temporal changes in the DTI metrics were related to the neuronal and axonal pruning and myelination that are known to occur in the developing brain.

Diffusion tensor imaging (DTI) has the potential to provide important information about the integrity of white matter tracts in injured spinal cord tissue. It is thought that DTI-based transverse diffusivity (lambda(t)) reflects the state of myelin, whereas longitudinal diffusivity (lambda(l)) reflects axonal integrity. However, this has not been established in spinal cord injury (SCI). Therefore, we performed quantitative histologic analysis on 4- and 8-week post-SCI rodent spinal cords that had received a moderately severe injury at the T7 level and correlated the histology with lambda(t) and lambda(l) measured in vivo. Using antibodies specific to myelin and axonal process (i.e., neurofilament), the percent area of expression was determined in the dorsal, ventral, and lateral white matter from both rostral and caudal regions away from the epicenter of the injury site. The results suggest a positive correlation between lambda(t) and demyelination in many but not all regions. However, these studies failed to establish a correlation between lambda(l) and axonal damage. These results suggest that caution must be exercised in interpreting the DTI metrics in terms of tissue pathology in SCI., ((c) 2007 Wiley-Liss, Inc.)

Functional MRI (fMRI) on spinal cord-injured rodents at 4 and 8 weeks post injury (PI) is described. The paradigm for fMRI, based on electrical stimulation of rat paws, was automated using an in-house designed microprocessor-based controller that was interfaced to a stimulator. The MR images were spatially normalized to the Paxinos and Watson atlas using publicly available digital images of the cryosections. In normal uninjured animals, the activation was confined to the contralateral somatosensory cortex. In contrast, in injured animals, extensive activation, which included structures such as ipsilateral cortex, thalamus, hippocampus, and the caudate putamen, was observed at 4 and 8 weeks PI. Quantitative cluster analysis was carried out to calculate the volumes and centers of activation in individual brain structures. Based on this analysis, significant increase in activation between 4 and 8 weeks was observed only in the ipsilateral caudate putamen and thalamus. These studies suggest extensive and ongoing brain reorganization in spinal cord-injured animals., (Copyright 2006 Wiley-Liss, Inc.)

In vivo longitudinal diffusion tensor imaging (DTI) of rodent spinal cord injury (SCI) was carried out over a period of eight weeks post-injury. A balanced, rotationally invariant, alternating gradient polarity icosahedral diffusion encoding scheme was used for an unbiased estimation of the DTI metrics. The fractional anisotropy (FA), diffusivities along (longitudinal), and perpendicular (transverse) to the fiber tracts, were estimated for the ventral, dorsal, and lateral white matter. In all the three regions, the DTI metrics were observed to be significantly different in injured cords relative to the uninjured controls close to the epicenter of the injury. However, these differences gradually disappeared away from the epicenter. The spatio-temporal changes in the DTI metrics showed a recovery pattern that is region specific. Although the temporal trends in the tissue recovery in rostral and caudal sections seem to be similar, overall the DTI metrics were observed to be closer to the normal tissue values in the caudal relative to the rostral sections (rostral-caudal asymmetry).

Diffusion tensor imaging (DTI) was performed on 15 fresh spontaneously or therapeutically aborted normal fetuses and five term infants at different gestational ages. Regional cortical fractional anisotropy (FA) values were observed to increase with gestational age (GA) from 15 to 28 weeks, followed by a decrease through 36 weeks. The early increase in the cortical FA value, which has never been reported before, is consistent with neuronal migration from the germinal matrix. A statistically significant inverse correlation between GA and the FA values in the germinal matrix was observed (r = -0.81, P = 0.004). In addition, there was a significant difference in the FA values in the right and left frontal cortices (P = 0.007, sign test), suggesting cortical lateralization during the early stage of development. Our studies suggest that the DTI-estimated anisotropy could be useful in following neuronal migration, cortical maturation, and associated changes in the germinal matrix during early brain development.

Pathological changes were followed longitudinally with in vivo magnetic resonance imaging (MRI) and behavioral studies in experimental spinal cord injury (SCI). MRI-observed pathology was correlated with histology. On MRI, the cavitated regions of the injured cord were gradually filled with viable tissue between two and 8 weeks postinjury, and a concomitant improvement was observed in the neurobehavioral scores. By weeks 3-6, on MRI, the gray matter (GM) returned in the segments caudal, but not rostral, to the injury site. The corresponding histological sections revealed motor neurons as well as other nuclei in the gray matter immediately caudal to the epicenter, but not at the site of injury, suggesting neuronal recovery in perilesioned areas. The neuronal and neurological recovery appeared to occur about the same time as neovasculature that was reported on the contrast-enhanced MRI, suggesting a role for angiogenesis in recovery from SCI. The role of angiogenesis in neuronal recovery is further supported by the immunohistochemical observation of greater bromodeoxyuridine uptake by blood vessels near the lesion site compared with uninjured cords.