Sensitive Detection of Infratentorial and Upper Cervical Cord Lesions in Multiple Sclerosis with Combined 3D FLAIR and T2-Weighted (FLAIR3) Imaging.

BACKGROUND AND PURPOSE: Infratentorial and spinal cord lesions are important for diagnosing and monitoring multiple sclerosis, but they are difficult to detect on conventional MR imaging. We sought to improve the detection of infratentorial and upper cervical cord lesions using composite FLAIR3 images. MATERIALS AND METHODS: 3D T2-weighted FLAIR and 3D T2-weighted images were acquired in 30 patients with MS and combined using the FLAIR3 formula. FLAIR3 was assessed against 3D T2-FLAIR by comparing the number of infratentorial and upper cervical cord lesions per subject using the Wilcoxon signed rank test. Intrarater and interrater reliability was evaluated using the intraclass correlation coefficient. The number of patients with and without ≥1 visible infratentorial/spinal cord lesion on 3D T2-FLAIR versus FLAIR3 was calculated to assess the potential impact on the revised MS diagnostic criteria. RESULTS: Compared with 3D T2-FLAIR, FLAIR3 detected significantly more infratentorial (mean, 4.6 ± 3.6 versus 2.0 ± 1.8, P < .001) and cervical cord (mean, 1.58 ± 0.94 versus 0.46 ± 0.45, P < .001) lesions per subject. FLAIR3 demonstrated significantly improved interrater reliability (intraclass correlation coefficient = 0.77 [95% CI, 0.63-0.87] versus 0.60 [95% CI, 0.40-0.76] with 3D T2-FLAIR, P = .019) and a tendency toward a higher intrarater reliability (0.86 [95% CI, 0.73-0.93] versus 0.79 [95% CI, 0.61-0.89], P = .23). In our cohort, 20%-30% (47%-67%) of the subjects with MS had ≥ 1 infratentorial (cervical cord) lesion visible only on FLAIR3. CONCLUSIONS: FLAIR3 provides higher sensitivity than T2-FLAIR for the detection of MS lesions in infratentorial brain parenchyma and the upper cervical cord.

Examination of preliminary behavioral and effective connectivity findings from treatment response to citalopram in cocaine use disorder: A dynamic causal modeling study.

We sought effective (directional) connectivity parameters associated with response to citalopram in cocaine use disorder (CUD) by conducting a functional magnetic resonance imaging (fMRI) experiment with participants diagnosed with CUD (n = 13) and matched healthy controls (HC; n = 17). CUD participants showed a positive correlation between bilateral DLPFC-to-putamen effective connectivity and treatment effectiveness score. These preliminary results support further investigation of prefrontal-striatal interactions in response to treatment in CUD.

On the stability of carbon sequestration in an anisotropic horizontal porous layer with a first-order chemical reaction.

Carbon dioxide (CO2) sequestration in deep saline aquifers is considered to be one of the most promising solutions to reduce the amount of greenhouse gases in the atmosphere. As the concentration of dissolved CO2 increases in unsaturated brine, the density increases and the system may ultimately become unstable, and it may initiate convection. In this article, we study the stability of convection in an anisotropic horizontal porous layer, where the solute is assumed to decay via a first-order chemical reaction. We perform linear and nonlinear stability analyses based on the steady-state concentration field to assess neutral stability curves as a function of the anisotropy ratio, Damköhler number and Rayleigh number. We show that anisotropy in permeability and solutal diffusivity play an important role in convective instability. It is shown that when solutal horizontal diffusivity is larger than the vertical diffusivity, varying the ratio of vertical to horizontal permeabilities does not significantly affect the behaviour of instability. It is also noted that, when horizontal permeability is higher than the vertical permeability, varying the ratio of vertical to horizontal solutal diffusivity does have a substantial effect on the instability of the system when the reaction rate is dominated by the diffusion rate. We used the Chebyshev-tau method coupled with the QZ algorithm to solve the eigenvalue problem obtained from both the linear and nonlinear stability theories.

DTI correlates of cognition in conventional MRI of normal-appearing brain in patients with clinical features of subacute combined degeneration and biochemically proven vitamin B(12) deficiency.

BACKGROUND AND PURPOSE: Vitamin B12 deficiency may cause neural injury that results in cognitive deficits. The main purpose of our study was to evaluate morphometric and microstructural changes in the brain and relate them to cognition in subacute combined degeneration of the spinal cord and patients with biochemically deficient vitamin B12. MATERIALS AND METHODS: Fifty-one patients were recruited and underwent nerve-conduction velocity tests and routine hematologic examinations. Serum vitamin B12 and homocystine levels were also measured. All patients and 46 age- and sex-matched controls underwent cervical spine and brain MR imaging along with cognition tests. MR imaging included conventional scans and DTI. Voxel-based morphometry was performed for determining the WM and GM volumes, based on T1-weighted images. DTI measures that included fractional anisotropy, ADC, radial diffusivity, and axial diffusivity were determined by using tract-based statistics. RESULTS: None of the patients showed any abnormality on conventional MR imaging. No significant changes in GM and WM volumes were observed in patients compared with controls. Significant reductions in the fractional anisotropy and an increase in ADC and radial diffusivity values were observed in multiple brain regions in patients compared with controls. These changes were confirmed on the region-of-interest analysis. Neuropsychological scores were significantly different in patients compared with controls and showed significant correlation with fractional anisotropy and radial diffusivity in a few brain regions. CONCLUSIONS: Microstructural changes are seen in WM regions on DTI in patients with vitamin B12 deficiency and correlate with cognition scores. DTI can be used for objective assessment of microstructural changes in the brain in vitamin B12 deficiency.

Role of diffusion tensor imaging as an independent predictor of cognitive and language development in extremely low-birth-weight infants.

BACKGROUND AND PURPOSE: Diffusion tensor imaging at term can predict later development of cerebral palsy. Less is known about its ability to independently predict cognitive and language development in extremely preterm infants. The goals of the study were to investigate the following: 1) whether regional DTI measures at term-equivalent age in extremely low-birth-weight infants (birth weight, ≤1000 g) are predictive of Bayley III developmental scores at 18- to 22-months' corrected age, and 2) to compare white matter microstructural development at term and neurodevelopmental outcomes of extremely low-birth-weight infants with healthy term controls. MATERIALS AND METHODS: Fractional anisotropy and mean diffusivity in 7 vulnerable cerebral regions were measured in 42 extremely low-birth-weight and 16 term infants with high-quality DTI scans. The Bayley mental scale score (average of cognitive and language scale scores) was the primary outcome of interest with individual scores serving as secondary outcomes. Multiple linear regression modeling was used to identify the incremental ability of DTI measures to predict Bayley scores over known predictors. RESULTS: Compared with healthy term infants, extremely low-birth-weight infants exhibited significantly higher mean diffusivity and lower fractional anisotropy in 6 of 7 regions. At 18- to 22-months' corrected age, 39 extremely low-birth-weight infants (93%) and 14 term infants (88%) had undergone neurodevelopmental assessments. Although not statistically significant, extremely low-birth-weight infants averaged 7-9 points lower on Bayley subtests than term controls. In multivariable analyses, centrum semiovale mean diffusivity was a significant predictor of mental and language scale scores, and subventricular zone fractional anisotropy was a significant predictor of cognitive scale scores. A 10% increase in centrum semiovale mean diffusivity was associated with a 4.6 (95% CI, 1.6-7.6) point lower mental scale score (adjusted R(2) = 0.341, P = .001). CONCLUSIONS: In our extremely low-birth-weight cohort, DTI was an independent predictor of later cognitive and language development.

Understanding epileptogenesis in calcified neurocysticercosis with perfusion MRI.

OBJECTIVES: Calcified cysticercus larva with perilesional abnormality is thought to be responsible for seizures in patients with neurocysticercosis (NCC). However, it is not well understood why some calcified cysts are associated with seizures even without perilesional abnormality. METHODS: The study group consists of 30 subjects from an ongoing survey for disease burden estimation of a swine farming community who had a single calcified lesion without any perilesional abnormality with or without presentation of seizures. Each group consisted of 15 patients with calcified cysts and was labeled as asymptomatic and symptomatic. We performed dynamic contrast-enhanced (DCE) MRI on all these subjects and determined serum matrix metalloproteinase-9 (MMP-9) levels and MMP-9 gene polymorphisms. RESULTS: DCE-MRI-derived rate transfer constant (k(ep)) and serum MMP-9 levels showed significant differences between symptomatic and asymptomatic subjects. We observed an increase in the MMP-9 levels, k(ep), and the volume transfer coefficient (k(trans)) in these lesions. We also observed a significant increase in MMP-9 (R279Q) gene polymorphism in symptomatic subjects compared with asymptomatic and control subjects. CONCLUSIONS: Perilesional inflammation, which varies from symptomatic to asymptomatic subjects, can be quantified using DCE-MRI in calcified cysticercosis and may help distinguish these 2 groups with similar imaging findings. The observed increase in k(ep) with serum MMP-9 levels suggests that the former may serve as a biomarker of MMP-9 levels in these subjects. The significant MMP-9 (R279Q) gene polymorphism in symptomatic subjects might explain the differences in the observed DCE-MRI indices between symptomatic and asymptomatic subjects.

Composite MRI scores improve correlation with EDSS in multiple sclerosis.

BACKGROUND: Quantitative measures derived from magnetic resonance imaging (MRI) have been widely investigated as non-invasive biomarkers in multiple sclerosis (MS). However, the correlation of single measures with Expanded Disability Status Scale (EDSS) is poor, especially for studies with large population samples. OBJECTIVE: To explore the correlation of MRI-derived measures with EDSS through composite MRI scores. METHODS: Magnetic resonance images of 126 patients with relapsing-remitting MS were segmented into white and gray matter, cerebrospinal fluid, T2-hyperintense lesions, gadolinium contrast-enhancing lesions, T1-hypointense lesions ('black holes': BH). The volumes and average T2 values for each of these tissues and lesions were calculated and converted to a z-score (in units of standard deviation from the mean). These z-scores were combined to construct composite z-scores, and evaluated against individual z-scores for correlation with EDSS. RESULTS: Composite scores including relaxation times of different tissues and/or volumetric measures generally correlated more strongly with EDSS than individual measures. The maximum observed correlation of a composite with EDSS was r = 0.344 (p < 0.0001), which is an improvement over the highest-performing single MRI measure (BH; r = 0.298, p < 0.001). CONCLUSION: Z-transformation permits construction of composite scores including volumetric and T2-relaxation measures. Inclusion of multiple MRI measures in the composite can provide a broader characterization of the disease process, resulting in more robust correlations with EDSS.

Aquaporins in spinal cord injury: the janus face of aquaporin 4.

Although malfunction of spinal cord water channels (aquaporins, AQP) likely contributes to severe disturbances in ion/water homeostasis after spinal cord injury (SCI), their roles are still poorly understood. Here we report and discuss the potential significance of changes in the AQP4 expression in human SCI that generates glial fibrillary acidic protein (GFAP)-labeled astrocytes devoid of AQP4, and GFAP-labeled astroglia that overexpress AQP4. We used a rat model of contusion SCI to study observed changes in human SCI. AQP4-negative astrocytes are likely generated during the process of SCI-induced replacement of lost astrocytes, but their origin and role in SCI remains to be investigated. We found that AQP4-overexpression is likely triggered by hypoxia. Our transcriptional profiling of injured rat cords suggests that elevated AQP4-mediated water influx accompanies increased uptake of chloride and potassium ions which represents a protective astrocytic reaction to hypoxia. However, unbalanced water intake also results in astrocytic swelling that can contribute to motor impairment, but likely only in milder injuries. In severe rat SCI, a low abundance of AQP4-overexpressing astrocytes was found during the motor recovery phase. Our results suggest that severe rat contusion SCI is a better model to analyze AQP4 functions after SCI. We found that AQP4 increases in the chronic post-injury phase are associated with the development of pain-like behavior in SCI rats, while possible mechanisms underlying pain development may involve astrocytic swelling-induced glutamate release. In contrast, the formation and size of fluid-filled cavities occurring later after SCI does not appear to be affected by the extent of increased AQP4 levels. Therefore, the effect of therapeutic interventions targeting AQP4 will depend not only on the time interval after SCI or animal models, but also on the balance between protective role of increased AQP4 in hypoxia and deleterious effects of ongoing astrocytic swelling.

Normobaric hyperoximia increases hypoxia-induced cerebral injury: DTI study in rats.

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.

3D MPRAGE improves classification of cortical lesions in multiple sclerosis.

BACKGROUND: Gray matter lesions are known to be common in multiple sclerosis (MS) and are suspected to play an important role in disease progression and clinical disability. A combination of magnetic resonance imaging (MRI) techniques, double-inversion recovery (DIR), and phase-sensitive inversion recovery (PSIR), has been used for detection and classification of cortical lesions. This study shows that high-resolution three-dimensional (3D) magnetization-prepared rapid acquisition with gradient echo (MPRAGE) improves the classification of cortical lesions by allowing more accurate anatomic localization of lesion morphology. METHODS: 11 patients with MS with previously identified cortical lesions were scanned using DIR, PSIR, and 3D MPRAGE. Lesions were identified on DIR and PSIR and classified as purely intracortical or mixed. MPRAGE images were then examined, and lesions were re-classified based on the new information. RESULTS: The high signal-to-noise ratio, fine anatomic detail, and clear gray-white matter tissue contrast seen in the MPRAGE images provided superior delineation of lesion borders and surrounding gray-white matter junction, improving classification accuracy. 119 lesions were identified as either intracortical or mixed on DIR/PSIR. In 89 cases, MPRAGE confirmed the classification by DIR/PSIR. In 30 cases, MPRAGE overturned the original classification. CONCLUSION: Improved classification of cortical lesions was realized by inclusion of high-spatial resolution 3D MPRAGE. This sequence provides unique detail on lesion morphology that is necessary for accurate classification.

Early postnatal development of rat brain: in vivo diffusion tensor imaging.

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.

In vivo demonstration of neuroinflammatory molecule expression in brain abscess with diffusion tensor imaging.

BACKGROUND AND PURPOSE: Neuroinflammatory molecules, including tumor necrosis factor-alpha, interleukin1-beta, lymphocyte function associated molecule-1, and intercellular cell adhesion molecule-1 contribute to the development of brain abscess. We hypothesized that the high fractional anisotropy (FA) in the brain abscess cavity reflects the upregulation of these neuroinflammatory molecules. MATERIALS AND METHODS: Diffusion tensor imaging (DTI) was performed in 24 patients with brain abscess and Staphylococcus aureus-treated as well as nontreated Jurket cell lines (at 4 time points: 1, 24, 48, and 72 hours). Neuroinflammatory molecules were quantified from the brain abscess cavity aspirate of the patients as well as from the heat-killed S aureus-treated and nontreated cell lines and correlated with DTI measures. RESULTS: The DTI-derived FA strongly correlated with the presence of neuroinflammatory molecules in the pus as well as in S aureus-treated cell lines; no such correlation was observed in nontreated cell lines. CONCLUSIONS: These data indicate that neuroinflammatory molecules confer high diffusion anisotropy inside the brain abscess cavity. We propose that increased FA reflects upregulated inflammatory response in brain abscess.

Longitudinal magnetic resonance spectroscopic imaging of primary progressive multiple sclerosis patients treated with glatiramer acetate: multicenter study.

Multicenter proton magnetic resonance spectroscopic imaging (MRSI) studies were performed on 58 primary progressive multiple sclerosis (PPMS) patients from four centers for investigating the efficacy of glatiramer acetate (GA) treatment. These patients were drawn from 943 subjects who participated in the PROMiSe trial. In these MRSI studies, patients were followed over a period of 3 years. MRSI data were acquired by all the centers using the same pulse sequence, and spectral analysis was performed at a single site using a customized analysis software package. Quantitative metabolite ratios, N-acetyl aspartate (NAA)/creatine (Cr) and choline (Cho)/Cr, were compared between GA-treated and placebo-treated PPMS patients. There was no significant difference in metabolite ratios between GA-treated and placebo-treated patients. The difference in metabolite ratios between the normal-appearing tissues (NAT) and lesion-containing regions (LCR) in GA treated patients was not significantly different from placebo treated patients. Strong lipid resonances, even in the absence of lesions, were observed on MRSI data in both gray matter and white matter in placebo- and GA-treated PPMS patients. No significant difference in number of patients with lipids between the two groups over a period of 3 years was found.

Improved identification of intracortical lesions in multiple sclerosis with phase-sensitive inversion recovery in combination with fast double inversion recovery MR imaging.

BACKGROUND AND PURPOSE: Accurate detection and classification of purely intracortical lesions in multiple sclerosis (MS) are important in understanding their role in disease progression and impact on the clinical manifestations of the disease. However, detection of these lesions with conventional MR imaging remains a challenge. Although double inversion recovery (DIR) has been shown to improve the sensitivity of the detection of cortical lesions, this sequence has low signal-to-noise ratio (SNR), poor delineation of lesion borders, and is prone to image artifacts. We demonstrate that intracortical lesions can be identified and classified with greater confidence by the combination of DIR with phase-sensitive inversion recovery (PSIR) images. MATERIALS AND METHODS: A total of 16 subjects with MS were included in this study. DIR, PSIR, and fluid-attenuated inversion recovery (FLAIR) images were acquired and inspected by 3 experts, with identification of lesions by consensus. PSIR and DIR images were jointly used to classify lesions as purely intracortical, mixed gray-white matter, and juxtacortical. The difference in the number of lesions detected in each category was compared between combined PSIR and DIR and conventional FLAIR. RESULTS: PSIR consistently allowed a clearer classification and delineation of lesions. Combined PSIR and DIR images showed a 337% improvement in the total number of lesions detected compared with FLAIR alone. Detection of intracortical lesions was improved by 417% compared with FLAIR. Detection of mixed gray-white matter and juxtacortical lesions was improved by 396% and 130%, respectively, compared with FLAIR. CONCLUSION: Reliable detection and classification of intracortical lesions in MS are greatly improved by combined use of PSIR and DIR.

High-resolution vascular imaging of the rat spine using liposomal blood pool MR agent.

BACKGROUND AND PURPOSE: High-resolution, vascular MR imaging of the spine region in small animals poses several challenges. The small anatomic features, extravascular diffusion, and low signal-to-noise ratio limit the use of conventional contrast agents. We hypothesize that a long-circulating, intravascular liposomal-encapsulated MR contrast agent (liposomal-Gd) would facilitate visualization of small anatomic features of the perispinal vasculature not visible with conventional contrast agent (gadolinium-diethylene-triaminepentaacetic acid [Gd-DTPA]). METHODS: In this study, high-resolution MR angiography of the spine region was performed in a rat model using a liposomal-Gd, which is known to remain within the blood pool for an extended period. The imaging characteristics of this agent were compared with those of a conventional contrast agent, Gd-DTPA. RESULTS: The liposomal-Gd enabled acquisition of high quality angiograms with high signal-to-noise ratio. Several important vascular features, such as radicular arteries, posterior spinal vein, and epidural venous plexus were visualized in the angiograms obtained with the liposomal agent. The MR angiograms obtained with conventional Gd-DTPA did not demonstrate these vessels clearly because of marked extravascular soft-tissue enhancement that obscured the vasculature. CONCLUSIONS: This study demonstrates the potential benefit of long-circulating liposomal-Gd as a MR contrast agent for high-resolution vascular imaging applications.

Assessment of white matter damage in subacute sclerosing panencephalitis using quantitative diffusion tensor MR imaging.

BACKGROUND AND PURPOSE: Subacute sclerosing panencephalitis (SSPE), a rare progressive degenerative disease, is caused by persistent infection with a defective measles virus. The correlation between the clinical staging and MR imaging is usually poor. The aim of the study was to investigate the role of diffusion tensor imaging (DTI) in the early detection of white matter damage in SSPE in the presence of normal findings on conventional imaging. METHODS: DTI was performed in 21 patients in stage II SSPE and 10 age/sex-matched healthy controls. Fractional anisotropy (FA) and mean diffusivity (MD) values were calculated in the periventricular white matter, corpus callosum, and posterior limb of the internal capsule in patients with normal and abnormal findings on conventional imaging as well as healthy controls. RESULTS: The patients were grouped into those with normal (n = 11) and abnormal (n = 10) findings on conventional imaging for the purpose of quantitative DTI analysis. Abnormal- and normal-appearing white matter on T2-weighted images showed significantly decreased FA values in all the regions compared with those in healthy controls. MD values were significantly increased in the periventricular white matter region of the frontal and parietooccipital lobe in patients with normal as well as abnormal findings on conventional imaging compared with those in healthy controls. CONCLUSION: DTI detects early white matter abnormalities that may have significant therapeutic implication, even in the presence of normal findings on conventional imaging, in patients with SSPE.

Diffusion tensor imaging in polymicrogyria: a report of three cases.

INTRODUCTION: Polymicrogyria (PMG), a neuronal migration disorder, commonly manifests as a seizure disorder. The aim of this study was to look for the abnormalities in the underlying white matter using diffusion tensor imaging (DTI) that appeared normal on conventional magnetic resonance imaging (MRI) in patients with PMG. METHODS: DTI was performed in three patients with PMG and eight age- and sex-matched healthy controls. Fractional anisotropy (FA) and mean diffusivity (MD) values were calculated for the cortex and adjoining subcortical white matter in both controls and patients. RESULTS: We observed a significantly decreased mean FA value with no significant change in the MD value in subcortical white matter underlying polymicrogyric cortex (FA = 0.23+/-0.04, MD = 1.0+/-0.05 x 10(-3) mm(2)/s) as compared to both contralateral (FA = 0.32+/-0.04, MD = 1.0+/-0.05 x 10(-3) mm(2)/s) and normal control (FA = 0.32+/-0.04, MD = 1.0+/-0.06 x 10(-3) mm(2)/s) white matter. Significantly increased MD and decreased FA values were also observed in the polymicrogyric cortex (FA = 0.08+/-0.01, MD = 1.2+/-0.10 x 10(-3) mm(2)/s) as compared to normal contralateral (FA = 0.12+/-0.04, MD = 1.1+/-0.09 x 10(-3) mm(2)/s) and normal control (FA = 0.12+/-0.01, MD = 1.1+/-0.09 x 10(-3) mm(2)/s) cortex. CONCLUSION: Significantly decreased FA values with no change in MD values in the subcortical white matter subjacent to polymicrogyric cortex reflect microstructural changes in the white matter probably due to the presence of ectopic neurons.

Serial quantitative diffusion tensor MRI of the term neonates with hypoxic-ischemic encephalopathy (HIE).

AIM: To determine the altered pattern of fractional anisotropy (FA) and mean diffusivity (MD) change in brain parenchyma in serially studied neonates with mild or moderate hypoxic ischemic injury (HIE) within 7 days after birth and again at the age of three months. METHODS: Serial diffusion tensor imaging (DTI) was performed at two-time points in term neonates with mild (n = 7) and moderate (n = 10) HIE and age/sex-matched controls (n = 7). Neurodevelopmental outcome was assessed at the time of the 2nd study. RESULTS: On comparing FA and MD changes over time using two-way analysis of variance between neonates with HIE and controls, we observed significant differences in age-related FA increase (p < 0.05) in anterior limb of internal capsule and periventricular white matter of parietal, occipital, and temporal lobes. Significant differences in age-related MD decrease (p < 0.05) was observed in the caudate nuclei, and temporal white matter among these groups. Significant positive correlation was observed between neurodevelopmental outcome and FA. CONCLUSION: The results suggest that abnormal FA and MD values help in early and more accurate assessment of microstructural damage in HIE that may have predictive value for long-term neurofunctional outcome in these neonates.

Pilot study to examine the effect of antibiotic therapy on MRI outcomes in RRMS.

This trial examined the safety and possible MRI and clinical effects of anti-chlamydial antibiotic therapy in relapsing-remitting MS (RRMS). Newly diagnosed MS patients were selected to participate if they showed Chlamydia pneumoniae gene in their CSF and had one or more enhancing lesions on brain magnetic resonance imaging (MRI). After a 4-month run in phase of monthly MRI, patients were randomized to receive rifampin (300 mg twice daily) and azithromycin (500 mg every other day) for 6 months or placebo (PBO). Patients then had monthly MRI on therapy and two additional scans on months 12 and 14. Lumbar punctures were repeated between months 7 and 8 and within 2 weeks of termination of the study. Data on 4 patients on treatment and 4 on PBO were available for analysis. The primary outcome measure of showing a beneficial effect on enhancing lesions was not met. However, there was a significant difference in brain parenchymal fraction loss favoring those patient receiving antibiotics compared with PBO (p< or =0.02). Three of the four patients on antibiotic therapy cleared the organism from the CSF by month 12; in the PBO group one patient cleared the organism. The reduction in atrophy in patients receiving antibiotics must be viewed with caution, due to the small number of patients studied.

A pharmacokinetic model for quantitative evaluation of spinal cord injury with dynamic contrast-enhanced magnetic resonance imaging.

A multicompartment pharmacokinetic model was proposed to quantitatively describe the distribution of the contrast agent gadopentetate-dimeglumine (Gd) in an experimental spinal cord injury (SCI). Concentration of Gd was measured in different compartments with in vivo dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the acute phase of injury. The concentration data for each rat was fitted to the model to estimate transfer rates between different compartments. The results indicate: 1) lack of uptake of Gd in normal cord tissue, 2) rapid exchange of Gd between plasma and cerebrospinal fluid in both normal and injured cord tissues, and 3) slower uptake of Gd in injured cord. With this approach, it is possible to quantify the integrity of the blood-spinal cord barrier (BSCB) in vivo, evaluate the pathobiology of injured cord, assess the efficacy of interventions, and monitor the progression of injury with postinjury time.