Decreased resting functional connectivity after traumatic brain injury in the rat.

Traumatic brain injury (TBI) contributes to about 10% of acquired epilepsy. Even though the mechanisms of post-traumatic epileptogenesis are poorly known, a disruption of neuronal networks predisposing to altered neuronal synchrony remains a viable candidate mechanism. We tested a hypothesis that resting state BOLD-fMRI functional connectivity can reveal network abnormalities in brain regions that are connected to the lesioned cortex, and that these changes associate with functional impairment, particularly epileptogenesis. TBI was induced using lateral fluid-percussion injury in seven adult male Sprague-Dawley rats followed by functional imaging at 9.4T 4 months later. As controls we used six sham-operated animals that underwent all surgical operations but were not injured. Electroencephalogram (EEG)-functional magnetic resonance imaging (fMRI) was performed to measure resting functional connectivity. A week after functional imaging, rats were implanted with bipolar skull electrodes. After recovery, rats underwent pentyleneterazol (PTZ) seizure-susceptibility test under EEG. For image analysis, four pairs of regions of interests were analyzed in each hemisphere: ipsilateral and contralateral frontal and parietal cortex, hippocampus, and thalamus. High-pass and low-pass filters were applied to functional imaging data. Group statistics comparing injured and sham-operated rats and correlations over time between each region were calculated. In the end, rats were perfused for histology. None of the rats had epileptiform discharges during functional imaging. PTZ-test, however revealed increased seizure susceptibility in injured rats as compared to controls. Group statistics revealed decreased connectivity between the ipsilateral and contralateral parietal cortex and between the parietal cortex and hippocampus on the side of injury as compared to sham-operated animals. Injured animals also had abnormal negative connectivity between the ipsilateral and contralateral parietal cortex and other regions. Our data provide the first evidence on abnormal functional connectivity after experimental TBI assessed with resting state BOLD-fMRI.

Where fMRI and electrophysiology agree to disagree: corticothalamic and striatal activity patterns in the WAG/Rij rat.

The relationship between neuronal activity and hemodynamic changes plays a central role in functional neuroimaging. Under normal conditions and in neurological disorders such as epilepsy, it is commonly assumed that increased functional magnetic resonance imaging (fMRI) signals reflect increased neuronal activity and that fMRI decreases represent neuronal activity decreases. Recent work suggests that these assumptions usually hold true in the cerebral cortex. However, less is known about the basis of fMRI signals from subcortical structures such as the thalamus and basal ganglia. We used WAG/Rij rats (Wistar albino Glaxo rats of Rijswijk), an established animal model of human absence epilepsy, to perform fMRI studies with blood oxygen level-dependent and cerebral blood volume (CBV) contrasts at 9.4 tesla, as well as laser Doppler cerebral blood flow (CBF), local field potential (LFP), and multiunit activity (MUA) recordings. We found that, during spike-wave discharges, the somatosensory cortex and thalamus showed increased fMRI, CBV, CBF, LFP, and MUA signals. However, the caudate-putamen showed fMRI, CBV, and CBF decreases despite increases in LFP and MUA signals. Similarly, during normal whisker stimulation, the cortex and thalamus showed increases in CBF and MUA, whereas the caudate-putamen showed decreased CBF with increased MUA. These findings suggest that neuroimaging-related signals and electrophysiology tend to agree in the cortex and thalamus but disagree in the caudate-putamen. These opposite changes in vascular and electrical activity indicate that caution should be applied when interpreting fMRI signals in both health and disease from the caudate-putamen, as well as possibly from other subcortical structures.

Neuroimaging biomarkers of epileptogenesis.

Much progress has been made in the field studying the process of epileptogenesis via neuroimaging techniques. Conventional imaging methods include magnetic resonance imaging with morphometric analysis, magnetic resonance spectroscopy and positron emission tomography. Newer network-based methods such as diffusion tensor imaging and functional magnetic resonance imaging with resting functional connectivity are being developed and applied to clinical use. This review provides a brief summary of the major human and animal studies in both partial and generalized epilepsies that demonstrate the potential of these imaging modalities to serve as biomarkers of epileptogenesis.

The role of diffusion-weighted imaging in the differential diagnosis of intracranial cystic mass lesions: a report of 147 lesions.

BACKGROUND: The objective of this study is to evaluate the sensitivity and specificity of DWI in differentiating brain abscesses from other intracranial cystic lesions. METHODS: One hundred fifteen patients with 147 cystic lesions (mean age, 26.4 year) were prospectively studied with DWI on a 1.5-T magnetic resonance imaging. Lesions appearing hyperintense on DWI with the ADC values of lower than 0.9 +/- 0.13 x 10(-3) mm(2)/s (mean +/- SD) were considered as brain abscess, whereas hypointense lesions on DWI with the ADC values 2.2 +/- 0.9 x 10(-3) mm(2)/s were categorized as nonabscess cystic lesions. RESULTS: Ninety-three of 97 brain abscess lesions were hyperintense on DWI, with significantly low (P = .0001) ADC value (0.87 +/- 0.05 x 10(-3) mm(2)/s) (mean +/- SEM), compared with 48 nonabscess lesions (2.89 +/- 0.05 x 10(-3) mm(2)/s). Four of 97 brain abscess lesions in 65 patients were false negative, and 2 of 50 nonabscess lesions in 50 patients were false positive for the diagnosis of brain abscess. The ADC value of the tumor cysts (2.9 +/- 0.05 x 10(-3) mm(2)/s) was significantly lower (P = .02) compared with benign cysts and neurocysticercosis (3.2 +/- 0.05 x 10(-3) mm(2)/s) among nonabscess group. The sensitivity of DWI for the differentiation of brain abscesses from nonabscesses was 96%; specificity, 96%; positive predictive value, 98%; negative predictive value, 92%; and accuracy of the test, 96%. CONCLUSIONS: Diffusion-weighted imaging has high sensitivity and specificity for the differentiation of brain abscess from other nonabscess intracranial cystic lesions.

Analysis of microbial etiology and mortality in patients with brain abscess.

OBJECTIVES: Despite the technological advancements in diagnostic and neurosurgical procedures, brain abscess continues to remain a potentially fatal central nervous system infection. In a prospective study we determined the predisposing factors and the microbiological profile of brain abscess. We also analyzed the mortality in patients with the type of infections identified. METHODS: Over a period of 8 years (1997-2004), aspirated pus from 118 patients with brain abscess was directly inoculated into BACTEC PLUS+ aerobic and BACTEC PLUS+ anaerobic media immediately after collection and subcultured on solid media as appropriate. Predisposing factors, if any, were recorded in all patients. Mortality of patients during hospital stay was correlated with the type of infections identified. RESULTS: Predisposing factors were identified in 94 (79.7%) patients, otogenic infection being the most common (37/118; 31.4%). Microorganisms were demonstrated in 96 (81.4%) patients, by culture in 89 (75.4%) patients and by Gram stain in 7 (5.9%) additional cases. A total of 105 organisms were isolated - 67 (63.8%) aerobes, 32 (30.5%) anaerobes, 5 (4.8%) mycobacteria and 1 (0.9%) fungus. Viridans streptococci (23.8%), Staphylococcus aureus (14.3%), Bacteroides fragilis group/species and Peptostreptococcus species (10.5% each) were the common isolates. Overall mortality was 14.4%; patients with Gram-negative infections had higher mortality than Gram-positive infections (6/20; 30% vs. 6/63; 9.5%; P=0.02). CONCLUSIONS: Culture of pus immediately after aspiration in an automated system yields good results. Gram stain coupled with culture can guide the neurosurgeons better to treat their patients more rationally. Patients with Gram-negative infections need special attention in terms of management because of high mortality rate.

Cytotoxic edema is responsible for raised intracranial pressure in fulminant hepatic failure: in vivo demonstration using diffusion-weighted MRI in human subjects.

It is not clear whether cerebral edema in fulminant hepatic failure is predominantly vasogenic or cytotoxic, though cytotoxic edema due to astrocyte swelling is more likely. Diffusion-weighted magnetic resonance imaging can differentiate vasogenic from cytotoxic edema. We performed diffusion-weighted imaging in patients with fulminant hepatic failure to clarify the issue by measuring apparent diffusion coefficient, which quantifies movement of water molecule across cell membrane. Seven patients with fulminant hepatic failure underwent conventional and diffusion-weighted magnetic resonance imaging. Apparent diffusion coefficient was measured in four cortical areas and 12 deep white and gray matter regions in both cerebral hemispheres. Thirteen healthy subjects served as controls. The apparent diffusion coefficient values in patients and controls were compared using Wilcoxon signed rank test. Two patients who survived underwent repeat imaging using same protocol. Patients with FHF had significantly lower apparent diffusion coefficient in all cortical and deep white and gray matter regions of interest compared to controls (p < 0.001), suggesting cytotoxic cell swelling. In two survivors with repeat imaging, one showed complete resolution while the changes persisted in the other, suggesting ischemic injury. Cerebral edema in fulminant hepatic failure is predominantly due to cytotoxic edema.