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Diffusion Kurtosis Imaging (DKI) provides quantifiable information on the non-Gaussian behavior of water diffusion in biological tissue. Changes in water diffusion tensor imaging (DTI) parameters and DKI parameters in several white and grey matter regions were investigated in a mild controlled cortical impact (CCI) injury rat model at both the acute (2 hours) and the sub-acute (7 days) stages following injury. Mixed model ANOVA analysis revealed significant changes in temporal patterns of both DTI and DKI parameters in the cortex, hippocampus, external capsule and corpus callosum. Post-hoc tests indicated acute changes in mean diffusivity (MD) in the bilateral cortex and hippocampus (p < 0.0005) and fractional anisotropy (FA) in ipsilateral cortex (p < 0.0005), hippocampus (p = 0.014), corpus callosum (p = 0.031) and contralateral external capsule (p = 0.011). These changes returned to baseline by the sub-acute stage. However, mean kurtosis (MK) was significantly elevated at the sub-acute stages in all ipsilateral regions and scaled inversely with the distance from the impacted site (cortex and corpus callosum: p < 0.0005; external capsule: p = 0.003; hippocampus: p = 0.011). Further, at the sub-acute stage increased MK was also observed in the contralateral regions compared to baseline (cortex: p = 0.032; hippocampus: p = 0.039) while no change was observed with MD and FA. An increase in mean kurtosis was associated with increased reactive astrogliosis from immunohistochemistry analysis. Our results suggest that DKI is sensitive to microstructural changes associated with reactive astrogliosis which may be missed by standard DTI parameters alone. Monitoring changes in MK allows the investigation of molecular and morphological changes in vivo due to reactive astrogliosis and may complement information available from standard DTI parameters. To date the use of diffusion tensor imaging has been limited to study changes in white matter integrity following traumatic insults. Given the sensitivity of DKI to detect microstructural changes even in the gray matter in vivo, allows the extension of the technique to understand patho-morphological changes in the whole brain following a traumatic insult.

Previously, magnetic resonance spectroscopy studies of alterations in cerebral metabolite concentration during functional activation have been focused on phosphocreatine using 31P MRS and lactate using 1H MRS with controversial results. Recently, significant improvements on the spectral resolution and sensitivity of in vivo spectroscopy have been made at ultrahigh magnetic field strength. Using highly resolved localized short-TE 1H MRS at 11.7 T, we report metabolic responses of rat somatosensory cortex to forepaw stimulation in alpha-chloralose-anesthetized rats. The phosphocreatine/creatine ratio was found to be significantly decreased by 15.1 +/- 4.6% (mean +/- SEM, P < 0.01). Lactate remained very low (approximately

Peripheral neuropathy often manifests clinically with symptoms of mechanical and cold allodynia. However, the neuroplastic changes associated with peripheral neuropathic pain and the onset and progression of allodynic symptoms remain unclear. Here, we used a chronic neuropathic pain model (spared nerve injury; SNI) to examine functional and metabolic brain changes associated with the development and maintenance of mechanical and cold hypersensitivity, the latter which we assessed both behaviorally and during a novel acetone application paradigm using functional MRI (fMRI). Female Sprague–Dawley rats underwent SNI (n = 7) or sham (n = 5) surgery to the left hindpaw. Rats were anesthetized and scanned using a 7 T MRI scanner 1 week prior to (pre-injury) and 4 (early/subchronic) and 20 weeks (late/chronic) post-injury. Functional scans were acquired during acetone application to the left hindpaw. 1 H magnetic resonance spectroscopy was also performed to assess SNI-induced metabolic changes in the anterior cingulate cortex (ACC) pre- and 4 weeks post-injury. Mechanical and cold sensitivity, as well as anxiety-like behaviors, were assessed 2 weeks pre-injury, and 2, 5, 9, 14, and 19 weeks post-injury. Stimulus-evoked brain responses (acetone application to the left hindpaw) were analyzed across the pre- and post-injury time points. In response to acetone application during fMRI, SNI rats showed widespread and functionally diverse changes within pain-related brain regions including somatosensory and cingulate cortices and subcortically within the thalamus and the periaqueductal gray. These functional brain changes temporally coincided with early and sustained increases in both mechanical and cold sensitivity. SNI rats also showed increased glutamate within the ACC that correlated with behavioral measures of cold hypersensitivity. Together, our findings suggest that extensive functional reorganization within pain-related brain regions may underlie the development and chronification of allodynic-like behaviors.

A new single-shot echo-planar imaging (EPI) sequence with interleaved z-shim and optimized compensation for susceptibility-induced signal loss is proposed in this paper. Experiments on human brain demonstrated that the new method is able to regain signal dropout in brain areas with severe susceptibility-induced local gradients, while its image acquisition speed is comparable to that of conventional single-shot EPI techniques. Significant signal-to-noise ratio improvements were demonstrated in the ventral prefrontal and lateral temporal lobes with the new technique compared to a conventional EPI. Brain activation experiments with a bilateral finger-tapping task were performed with intentionally introduced local gradients near the left sensorimotor cortex, by a small gadolinium (Gd)-doped bottle placed on the left side of the head. The results of the functional experiments showed that the interleaved z-shim EPI sequence effectively recovered the signal loss caused by the Gd-doped bottle and reliably detected activation signals in bilateral sensorimotor regions, while the activation signals on the left side diminished considerably in a conventional EPI technique. The new technique, with the capability of reducing susceptibility artifacts and rapid scanning speed, may be particularly useful for event-related functional MRI experiments in the base of the brain, which are of great importance in neuropsychiatric studies.

A perfusion-based event-related functional MRI method for the study of brain activation is presented. In this method, cerebral blood flow (CBF) was measured using a recently developed multislice arterial spin-labeling (ASL) perfusion imaging method with rapid spiral scanning. Temporal resolution of the perfusion measurement was substantially improved by employing intertrial subtraction and stimulus-shifting schemes. Perfusion and blood oxygenation level-dependent (BOLD) signals were obtained simultaneously by subtracting or adding the control and labeled images, respectively, in the same data sets. The impulse response function (IRF) of perfusion during brain activation was characterized for multiple stimulus durations and compared to the simultaneously acquired BOLD response. The CBF response curve preceded the BOLD curve by 0.21 s in the rising phase and 0.64 s in the falling phase. Linear additivity of the CBF and BOLD responses was assessed with rapidly repeated stimulations within single trials, and departure from linearity was found in both responses, characterized as attenuated amplitude and delayed rising time. Event-related visual and sensorimotor activation experiments were successfully performed with the new perfusion technique.

METHODS MRI experiments were done on a 1.5T GE-LX2 scanner on normal subjects. Cerebral perfusion was measured with a modified multislice perfusion imaging technique in which pulsed arterial spin-labeling was combined with a fast spiral scan (10). Temporal resolution was improved by using inter-trial subtraction and stimulus shifting (9). In the perfusion sequence, gradient-echo signals were acquired with TI =1.2s, TE=22ms, and TR =2s. The echo time was chosen to allow for detection of perfusion and BOLD signals simultaneously. Perfusion and BOLD signals were obtained by subtracting or adding the control and labeled perfusion images respectively in the same data sets. Brain activation experiments were performed with black-white flashing checkerboard (8Hz) presented with a back projector. Multiple stimuli were presented within single trials to address the linearity of the impulse response of the brain perfusion. Four types of stimuli were used in the experiments, as shown in Fig.1. In experiment I, a visual stimulus of Is duration was delivered at the start of each trial. In experiment II, two stimuli (1s duration) with a interval of 2s were delivered. In experiment III, three stimuli (1s duration) with intervals of 2s were delivered. In experiment IV, two stimuli (1s duration) with a interval of 5s were delivered. Inter-stimulus interval (ISI) was 18s, and 48 trials were acquired, in all experiments.