DTI of chronic spinal cord injury in children without MRI abnormalities (SCIWOMR) and with pathology on MRI and comparison to severity of motor impairment.

STUDY DESIGN: This investigation was a cohort study that included: 36 typically developing (TD) children and 19 children with spinal cord lesions who underwent spinal cord MRI. OBJECTIVES: To investigate diffusion tensor imaging (DTI) cervical and thoracic spinal cord changes in pediatric patients that have clinically traumatic and non-traumatic spinal cord injury (SCI) without MR (SCIWOMR) abnormalities. SETTING: Thomas Jefferson University, Temple University, Shriners Hospitals for Children all in Philadelphia, USA. METHODS: 36 TD children and 19 children with spinal cord lesions that represent either a chronic traumatic acquired SCI or chronic non-traumatic SCI (≥6 months post injury), age range, 6-16 years who underwent cervical and thoracic spinal cord MRI in 2014-2017. Additionally DTI was correlated to clinical American Spinal Injury Association Impairment Scale (AIS). RESULTS: Both SCIWOMR and MRI positive (+) groups showed abnormal FA and RD DTI values in the adjacent MRI-normal appearing segments of cephalad and caudal spinal cord compared to TD. The FA values demonstrated perilesional abnormal DTI findings in the middle and proximal segments of the cephalad and caudal cord in the SCIWOMR AIS A/B group compared to SCIWOMR AIS C/D group. CONCLUSIONS: We found DTI changes in children with SCIWOMR with different causes of spinal lesions. We also investigated the relationship between DTI and clinical AIS scores. This study further examined the potential diagnostic value of DTI and should be translatable to adults with spinal cord lesions.

Application of Color Transformation Techniques in Pediatric Spinal Cord MR Images: Typically Developing and Spinal Cord Injury Population.

The purpose of this study was to evaluate an improved and reliable visualization method for pediatric spinal cord MR images in healthy subjects and patients with spinal cord injury (SCI). A total of 15 pediatric volunteers (10 healthy subjects and 5 subjects with cervical SCI) with a mean age of 11.41 years (range 8-16 years) were recruited and scanned using a 3.0T Siemens Verio MR scanner. T2-weighted axial images were acquired covering entire cervical spinal cord level C1 to C7. These gray-scale images were then converted to color images by using five different techniques including hue-saturation-value (HSV), rainbow, red-green-blue (RGB), and two enhanced RGB techniques using automated contrast stretching and intensity inhomogeneity correction. Performance of these techniques was scored visually by two neuroradiologists within three selected cervical spinal cord intervertebral disk levels (C2-C3, C4-C5, and C6-C7) and quantified using signal to noise ratio (SNR) and contrast to noise ratio (CNR). Qualitative and quantitative evaluation of the color images shows consistent improvement across all the healthy and SCI subjects over conventional gray-scale T2-weighted gradient echo (GRE) images. Inter-observer reliability test showed moderate to strong intra-class correlation (ICC) coefficients in the proposed techniques (ICC > 0.73). The results suggest that the color images could be used for quantification and enhanced visualization of the spinal cord structures in addition to the conventional gray-scale images. This would immensely help towards improved delineation of the gray/white and CSF structures and further aid towards accurate manual or automatic drawings of region of interests (ROIs).

Segmentation of corpus callosum using diffusion tensor imaging: validation in patients with glioblastoma.

BACKGROUND: This paper presents a three-dimensional (3D) method for segmenting corpus callosum in normal subjects and brain cancer patients with glioblastoma. METHODS: Nineteen patients with histologically confirmed treatment naïve glioblastoma and eleven normal control subjects underwent DTI on a 3T scanner. Based on the information inherent in diffusion tensors, a similarity measure was proposed and used in the proposed algorithm. In this algorithm, diffusion pattern of corpus callosum was used as prior information. Subsequently, corpus callosum was automatically divided into Witelson subdivisions. We simulated the potential rotation of corpus callosum under tumor pressure and studied the reproducibility of the proposed segmentation method in such cases. RESULTS: Dice coefficients, estimated to compare automatic and manual segmentation results for Witelson subdivisions, ranged from 94% to 98% for control subjects and from 81% to 95% for tumor patients, illustrating closeness of automatic and manual segmentations. Studying the effect of corpus callosum rotation by different Euler angles showed that although segmentation results were more sensitive to azimuth and elevation than skew, rotations caused by brain tumors do not have major effects on the segmentation results. CONCLUSIONS: The proposed method and similarity measure segment corpus callosum by propagating a hyper-surface inside the structure (resulting in high sensitivity), without penetrating into neighboring fiber bundles (resulting in high specificity).

Clinical Utility of Diffusion Tensor Imaging as a Biomarker to Identify Microstructural Changes in Pediatric Spinal Cord Injury.

Background: Lack of clarity about the neurological consequence of spinal cord injury (SCI) in children causes speculation about diagnoses, recovery potential, and treatment effectiveness. Diffusion tensor imaging (DTI) has shown promising results as a biomarker to evaluate spinal cord integrity at a microstructural level. Objectives: To look at the difference between pediatric participants with and without SCI to determine which DTI metrics best categorize spinal cord tissue damage and to correlate DTI metrics with two clinical measures: Capabilities of the Upper Extremity Test (CUE-T) and Spinal Cord Independence Measure version III (SCIM-III). Methods: This single-site, prospective study included pediatric participants with SCI (n = 26) and typically developed (TD) control subjects (n = 36). All participants underwent two magnetic resonance imaging (MRI) scans on a 3T MR scanner. Participants with SCI also completed the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), CUE-T, and SCIM-III outcomes measures. Results: This study found significant strength of association between fractional anisotropy (FA) and upper extremity muscle strength (UEMS) in participants with SCI. Most DTI parameters showed a significant difference between participants with SCI and TD participants and a moderate correlation with the CUE-T total score. Regional effects on group differences were found to be significant. Conclusion: This study demonstrates the strength of association between DTI parameters and clinical measures in the pedantic SCI population. It illustrates DTI as a potential biomarker of SCI location and severity in the pediatric SCI population.

Tumor vascular leakiness and blood volume estimates in oligodendrogliomas using perfusion CT: an analysis of perfusion parameters helping further characterize genetic subtypes as well as differentiate from astroglial tumors.

The purpose of this study was to determine the usefulness of perfusion CT (PCT) parameters particularly blood volume and neovascular permeability estimates (permeability surface area-product, PS) in the evaluation of oligodendrogliomas (OG), correlation with genetic subtypes of OGs (with or without loss of heterozygosity/LOH on 1p/19q) as well as comparison of perfusion parameters of OGs with astroglial tumors. Pre-operative PCT done in 21 patients with OGs was retrospectively correlated with our previously published PCT data for 32 patients with astroglial neoplasms (Jain R et al., AJNR Am J Neuroradiol 29:694-700, 2008). All OGs were also analyzed for genetic subtypes of with or without LOH. PCT parameters PS and cerebral blood volume (CBV) were obtained for the entire lesion and a statistical analysis done to correlate various histopathological variants. Low grade OGs (n = 13) showed slightly lower CBV (1.42 vs. 1.72 ml/100 g; P value 0.391) and PS (0.56 vs. 0.95 ml/100 g/min; P value 0.099) as compared to high grade OGs (n = 8), though not statistically significant. LOH positive OGs (n = 13) showed higher mean CBV (1.59 vs. 1.45; P value 0.712) and slightly lower PS (0.68 vs. 0.75; P value 0.718) as compared to LOH negative OGs (n = 8), although not statistically significant. Low grade OGs (n = 13) showed higher mean CBV 1.42 ml/100 g as compared to low grade astroglial tumors (n = 8) 0.95 ml/100 g (P value = 0.08), however no statistically significant difference was noted for PS (0.56 vs. 0.52 ml/100 g/min, P value 0.695). Statistically significant differences were observed in CBV and PS values of high grade OGs and high grade astroglial tumors with the high grade glial tumors showing higher mean CBV (2.79 vs. 1.72; P value 0.03) as well as higher PS (2.37 vs. 0.95; P value < 0.01), however this difference was not significant if only comparing grade III OGs with grade III astroglial tumors. PCT perfusion parameters including PS values do not help grade OGs despite showing a trend for higher CBV and PS in higher grade OGs. Similarly LOH positive OGs also showed slightly higher CBV, but again failed to reach any statistically significant level. Low grade OGs showed slightly higher CBV as compared to low grade astroglial tumors, whereas higher grade OGs showed significantly lower PS values as compared to higher grade astroglial tumors despite showing high CBV.

Correlation of DTI metrics in the wall and cavity of brain abscess with histology and immunohistochemistry.

Diffusion tensor imaging (DTI) was performed in eight patients with brain abscess (BA). The aim of this study was to see the difference in the relationship between intercellular cell adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) expression and DTI metrics measured in vivo in the wall and cavity of BA and its possible explanation vis-à-vis histology and immunohistochemistry. Neuroinflammatory molecules (NMs) were quantified from BA cavity aspirate of the patients and quantitative immunohistochemical analysis was performed for ICAM-1 and LFA-1 in the BA wall, showing maximal positive staining and correlated with DTI metrics. The fractional anisotropy (FA) significantly increased while mean diffusivity and spherical anisotropy significantly decreased in the BA wall compared to the BA cavity. In the BA wall, FA and linear anisotropy (CL) showed a significant positive correlation with ICAM-1 and LFA-1 expression whereas FA and planar anisotropy positively correlated with NMs quantified from aspirated pus respectively. Higher FA values in the BA wall compared to BA cavity, even when ICAM-1 and LFA-1 were expressed only in the macrophages and not in the collagen fibers, suggests that a combination of both concentric layers of collagen fibers as well as neutrophils and macrophages provide structural orientation and are responsible for increased FA. In the BA wall, increased CL was found compared to the cavity, indicating the presence of concentrically laid collagen fibers responsible for the diffusion of water molecules in the direction parallel to the collagen fibers. We conclude that in the BA, different mechanisms are operative for the changes in the DTI metrics in the wall and cavity; these conclusions are validated by histology and immunohistochemistry.

Predicting survival in glioblastomas using diffusion tensor imaging metrics.

PURPOSE: To retrospectively correlate various diffusion tensor imaging (DTI) metrics in patients with glioblastoma multiforme (GBM) with patient survival analysis and also degree of tumor proliferation index determined histologically. MATERIALS AND METHODS: Thirty-four patients with histologically confirmed treatment naive GBMs underwent DTI on a 3.0 Tesla (T) scanner. Region-of-interest was placed on the whole lesion including the enhancing as well as nonenhancing component of the lesion to determine the various DTI metrics. Kaplan-Meier estimates and Cox proportional hazards regression methods were used to assess the relationship of DTI metrics (minimum and mean values) and Ki-67 with progression free survival (PFS). To study the relationship between DTI metrics and Ki-67, Pearson's correlation coefficient was computed. RESULTS: Univariate analysis showed that patients with fractional anisotropy (FA)(mean) ≤ 0.2, apparent diffusion coefficient (ADC)(min) ≤ 0.6, planar anisotropy (CP)(min) ≤ 0.002, spherical anisotropy (CS)(mean) > 0.68 and Ki-67 > 0.3 had lower PFS rate. The multivariate analysis demonstrated that only CP(min) was the best predictor of survival in these patients, after adjusting for age, Karnofsky performance scale and extent of resection. No significant correlation between DTI metrics and Ki-67 were observed. CONCLUSION: DTI metrics can be used as a sensitive and early indicator for PFS in patients with glioblastomas. This could be useful for treatment planning as high-grade gliomas with lower ADC(min), FA(mean), CP(min), and higher CS(mean) values may be treated more aggressively.

Treatment induced necrosis versus recurrent/progressing brain tumor: going beyond the boundaries of conventional morphologic imaging.

Brain tumor patients undergo various combinations therapies, leading to very complex and confusing imaging appearances on follow up MR imaging and hence, differentiating recurrent or progressing tumors from treatment induced necrosis or effects has always been a challenge in neuro-oncologic imaging. This particular topic has become more relevant these days because of the advent of newer anti-angiogenic and anti-neoplastic chemotherapeutic agents as well as use of salvage radiation therapy. Various clinically available functional imaging modalities can provide additional physiologic and metabolic information about the tumors which could be useful in identifying viable tumor from treatment induced necrosis and hence, can guide treatment planning. In this review we will discuss various functional neuro-imaging modalities, their advantages and limitations and also their utility in treatment planning.

Serial changes in diffusion tensor imaging metrics of corpus callosum in moderate traumatic brain injury patients and their correlation with neuropsychometric tests: a 2-year follow-up study.

OBJECTIVE: To assess longitudinally the severity of diffuse axonal injury in the corpus callosum in patients with moderate traumatic brain injury (TBI) through quantitative diffusion tensor imaging and to correlate these changes with neuropsychometric tests (NPT) at 6 and 24 months after injury. DESIGN: Prospective longitudinal study. PARTICIPANTS: Sixteen patients with TBI and 17 age/sex-matched healthy controls. METHODS: Patients underwent magnetic resonance imaging at 3 time points: within 2 weeks (range = 5-14 days), 6 months, and 24 months after injury. NPT could be performed only at 6 and 24 months. RESULTS: In patients with TBI, a significant increase in fractional anisotropy (FA) values in genu as well as an insignificant decrease in radial diffusivity (RD) and mean diffusivity values in genu and splenium were observed over time, respectively. FA, RD, and mean diffusivity values continued to be abnormal in patients compared with controls at the end of 2 years. Although some NPT scores improved over time in these patients, these were still significantly impaired compared with controls. CONCLUSIONS: FA and RD indices appear to be surrogate markers of microstructural alterations in patients over time and correlate significantly with some of the NPT scores. The recovery in these indices associated with recovery in neurocognitive deficits suggests that these indices may be used as an objective marker for residual injury in these patients.

Correlation of diffusion tensor imaging with histology in the developing human frontal cerebrum.

Transient early cerebral laminar organization resulting from normal developmental events has been revealed in human beings through histology and imaging studies. DTI studies have postulated that the fractional anisotropy (FA)-based differentiation of different laminar structures reflects both differing cellular density over the glial fibers and fiber alignment in respective regions. The aim of this study was to correlate FA values in these transient zones with histology. Brain DTI was performed on 50 freshly aborted human fetuses with gestational ages (GA) ranging from 12 to 42 weeks. Regions of interest were placed on the cortical plate, subplate, intermediate and germinal matrix (GMx) zones of the frontal lobe to quantify FA values. Glial fibrillary acidic protein (GFAP), neurofilament (NF) and neuron-specific enolase (NSE) immunohistochemical analyses were performed for the cortical plate, intermediate zone and GMx. In the cortical plate, a significant positive correlation was observed between FA values and percentage area of GFAP expression in fetuses

Understanding development and lateralization of major cerebral fiber bundles in pediatric population through quantitative diffusion tensor tractography.

Region of interest based morphometric diffusion tensor imaging analysis, has been used extensively for the assessment of age-related changes in human brain, is limited to two dimensions and does not reflect the whole fiber bundle; however, diffusion tensor tractography (DTT) offers an overall view of individual fiber bundle in three-dimensional spaces. Quantitative DTT was performed on 51 healthy subjects of pediatric age range and young adults to compare age-related fractional anisotropy (FA) changes in corpus callosum, sensory and motor pathways, limbic tracts [cingulum (CNG) and fornix (Fx)], and superior and inferior longitudinal fascicules. In corpus callosum, inferior longitudinal fascicules, limbic tracts (CNG and Fx), sensory pathways, and motor pathways, an initial sharp increase in FA was observed up to the age of 2 y followed by a gradual increase up to 21 y. In superior longitudinal fascicules, sharp increase in FA was observed up to 3 y followed by a gradual increase. The FA value of the left CNG (p = 0.01, sign test) was observed to be significantly greater than that of the right CNG. We conclude that white matter fiber tracts mature with age and can be assessed by using DTT that may greatly improve our understanding of the human brain development.

Region-specific maturation of cerebral cortex in human fetal brain: diffusion tensor imaging and histology.

INTRODUCTION: In this study, diffusion tensor imaging (DTI) and glial fibrillary acidic protein (GFAP) immunohistochemical analysis in different cortical regions in fetal brains at different gestational age (GA) were performed. METHODS: DTI was performed on 50 freshly aborted fetal brains with GA ranging from 12 to 42 weeks to compare age-related fractional anisotropy (FA) changes in different cerebral cortical regions that include frontal, parietal, occipital, and temporal lobes at the level of thalami. GFAP immunostaining was performed and the percentage of GFAP-positive areas was quantified. RESULTS: The cortical FA values in the frontal lobe peaked at around 26 weeks of GA, occipital and temporal lobes at around 20 weeks, and parietal lobe at around 23 weeks. A significant, but modest, positive correlation (r = 0.31, p = 0.02) was observed between cortical FA values and percentage area of GFAP expression in cortical region around the time period during which the migrational events are at its peak, i.e., GA < or = 28 weeks for frontal cortical region and GA < or = 22 weeks for rest of the lobes. CONCLUSIONS: The DTI-derived FA quantification with its GFAP immunohistologic correlation in cortical regions of the various lobes of the cerebral hemispheres supports region-specific migrational and maturational events in human fetal brain.

Comparative evaluation of corpus callosum DTI metrics in acute mild and moderate traumatic brain injury: its correlation with neuropsychometric tests.

PRIMARY OBJECTIVE: To look for differences in vulnerability of corpus callosum (CC) in patients of mild and moderate traumatic brain injury (TBI) in the acute stage using quantitative diffusion tensor imaging (DTI) and to correlate these with neuropsychometric tests (NPT) done at 6 months post-injury. RESEARCH DESIGN, METHODS AND PROCEDURES: Conventional MRI, DTI and NPT were performed on 83 patients (moderate TBI, n = 57; mild TBI, n = 26) within 5-14 days after TBI. Thirty-three age- and sex-matched healthy controls were also included for comparison. RESULTS: Significantly decreased fractional anisotropy (FA) in genu and splenium; significantly increased radial diffusivity (RD) values in genu, midbody and splenium with significant increase in mean diffusivity (MD) and a decrease in axial diffusivity (AD) only in genu, respectively, in patients with moderate TBI compared to healthy controls were observed. However, in moderate TBI, significantly decreased FA was found only in genu compared to mild TBI. Moderate TBI showed poor NPT scores compared to mild TBI, but this did not reach statistical significance. CONCLUSIONS: It is concluded that DTI abnormalities in the regions of CC were more in patients with moderate TBI compared to mild TBI and this was associated with relatively poor neuropsychological outcome 6 months post-injury.

Diffusion Tensor Imaging Assessment of Regional White Matter Changes in the Cervical and Thoracic Spinal Cord in Pediatric Subjects.

There are no studies to date,describing changes in the diffusion tensor imaging (DTI) metrics of the white matter (WM) regions of the entire cervical and thoracic spinal cord (SC) remote from the lesion in pediatric spinal cord injury (SCI) subjects. The purpose of this study was to determine whether DTI at sites cephalad and caudal to a lesion provides measures of cord abnormalities in children with chronic SCI. A retrospective study included 10 typically developing subjects (TD) and 10 subjects with chronic SCI who underwent SC imaging in 2014-2017. Axial diffusion tensor images using an inner field of view DTI sequence were acquired to cover the entire cervical and thoracic SC. Regions of interest were drawn on the SC WM: right and left lateral (motor), ventral (motor), and dorsal (sensory) tracts. To detect differences in DTI metrics between TD and SCI of the cord, a one way analysis of variance with pooled t test was performed. A stepwise regression analysis was performed to assess the correlation between DTI metrics and clinical scores. In motor and sensory tracts, fractional anisotropy (FA) and axial diffusivity (AD) were significantly decreased in the proximal segments of the caudal cord. In motor tracts cephalad to the lesion, FA was significantly decreased whereas AD was significantly increased in the proximal segment; however, AD was decreased in the distal and middle segments. International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) total score was significantly correlated with FA and AD of the motor and sensory tracts cephalad to the lesion. This study demonstrates that FA and AD have the potential to be sensitive biomarkers of the full extent of cord injury and might be useful in detecting remote injuries to the SC and in guiding new treatments.

Retrograde Wallerian degeneration of cranial corticospinal tracts in cervical spinal cord injury patients using diffusion tensor imaging.

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.

Comparative evaluation of the cerebral and cerebellar white matter development in pediatric age group using quantitative diffusion tensor imaging.

Age-dependent changes in the normal cerebral white matter have been reported; however, there is no study on normal cerebellar white matter maturation in developing brain using diffusion tensor imaging (DTI). We performed DTI in 21 children who had normal neurological assessment along with no evidence of any abnormality on imaging. The aim of this study was to compare the age-related changes in fractional anisotropy (FA) and mean diffusivity (MD) quantified from cerebral white matter (splenium and genu of the corpus callosum and posterior limb of the internal capsule) and cerebellar white matter (middle cerebellar peduncles, superior cerebellar peduncles, and inferior cerebellar peduncles) regions in healthy children ranging in age from birth to 132 months. Log-linear regression model showed best fit to describe the age-related changes in FA and MD both for cerebral and cerebellar white matter. In cerebral white matter, an initial sharp increase in FA was observed up to the age of 24 months followed by a gradual increase up to 132 months. In cerebellar white matter, sharp increase in FA was observed up to 36 months, which then followed a gradual increase. However, MD showed a sharp decrease in cerebral white matter up to 24 months followed by a more gradual decrease thereafter, while in cerebellar white matter after an initial decrease (6 months), it followed a stable pattern. This study provides normative database of brain white matter development from neonates to childhood. This quantitative information may be useful for assessing brain maturation in patients with developmental delay of the cerebral and cerebellar white matter.

Diffusion tensor imaging in the developing human cerebellum with histologic correlation.

Diffusion tensor imaging was performed on 24 freshly aborted human fetuses with gestational age ranging from 20 to 37 weeks to observe age-related fractional anisotropy changes in cerebellar cortex and cerebellar white matter. Quantitative immunohistochemical analysis was performed for glial fibrillary acidic protein in each fetus molecular layer of cerebellar cortex and myelin basic protein expression was quantified in myelinated areas of the middle cerebellar peduncles. The cerebellar cortical fractional anisotropy reached its peak value at 28 weeks, and then decreased gradually until 37 weeks. The time course of glial fibrillary acidic protein expression paralleled that of fractional anisotropy in the cerebellar cortex from 20 weeks of gestation upto the gestational age at which the fractional anisotropy reached its peak value (28 weeks). In the middle cerebellar peduncles, the fractional anisotropy increased continuously upto 37 weeks of gestational age and showed a significant positive correlation with myelin basic protein immunostained fibers. The fractional anisotropy quantification can be used to assess the migrational and maturation changes during the development of the human fetal cerebellum supported by the immunohistochemical analysis.

DTI derived indices correlate with immunohistochemistry obtained matrix metalloproteinase (MMP-9) expression in cellular fraction of brain tuberculoma.

We performed in vivo diffusion tensor imaging (DTI) in a total of 33 patients with brain tuberculomas (BT). Thirteen of them had surgical excision of the lesion as it was clinically indicated, and in these samples matrix metalloproteinase-9 (MMP-9) expression was quantified. We correlated the results of DTI indices like fractional anisotropy (FA), mean diffusivity (MD), linear anisotropy (CL), planar anisotropy (CP) and spherical anisotropy (CS) with MMP-9 expression. In addition, the remaining 20 patients had serial DTI studies while on specific anti-tuberculous drug therapy and DTI indices in these patients were quantified. The FA, CL and CP significantly decreased while MD and CS significantly increased in BT compared to normal white matter. The FA, CL and CP showed negative correlation with MMP-9 while CS correlated positively. In serial follow-up studies in 20 patients FA, CL and CP showed significant increase while CS decreased significantly over time. We conclude that DTI indices show strong correlation with MMP-9 and these may be used as a surrogate marker of MMP-9 expression in BT. In addition, these indices may be of value in assessing the therapeutic response in patients with BT who are treated only with specific anti-tuberculous drugs.

Cerebral diffusion tensor imaging and in vivo proton magnetic resonance spectroscopy in patients with fulminant hepatic failure.

BACKGROUND AND AIM: Cerebral edema is a major complication in patients with fulminant hepatic failure (FHF). The aim of this study was to evaluate the metabolite alterations and cerebral edema in patients with FHF using in vivo proton magnetic resonance spectroscopy (MRS) and diffusion tensor imaging, and to look for its reversibility in survivors. METHODS: Ten FHF patients along with 10 controls were studied. Five of the 10 patients who recovered had a repeat imaging after three weeks. N-acetylaspartate, choline (Cho), glutamine (Gln), glutamine/glutamate (Glx), and myoinositol ratios were calculated with respect to creatine (Cr). Mean diffusivity (MD) and fractional anisotropy (FA) were calculated in different brain regions. RESULTS: Patients exhibited significantly increased Gln/Cr and Glx/Cr, and reduced Cho/Cr ratios, compared to controls. In the follow-up study, all metabolite ratios were normalized except Glx/Cr. Significantly decreased Cho/Cr were observed in deceased patients compared to controls. In patients, significantly decreased MD and FA values were observed in most topographical locations of the brain compared to controls. MD and FA values showed insignificant increase in the follow-up study compared to their first study. CONCLUSIONS: We conclude that the Cho/Cr ratio appears to be an in vivo marker of prognosis in FHF. Decreased MD values suggest predominant cytotoxic edema may be present. Persistence of imaging and MRS abnormalities at three weeks' clinical recovery suggests that metabolic recovery may take longer than clinical recovery in FHF patients.

Evaluation of mannitol effect in patients with acute hepatic failure and acute-on-chronic liver failure using conventional MRI, diffusion tensor imaging and in-vivo proton MR spectroscopy.

AIM: To evaluate the effect of an intravenous bolus of mannitol in altering brain metabolites, brain water content, brain parenchyma volume, cerebrospinal fluid (CSF) volume and clinical signs in controls and in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF), by comparing changes in conventional magnetic resonance imaging (MRI), in vivo proton magnetic resonance spectroscopy (PMRS) and diffusion tensor imaging (DTI) before and after its infusion. METHODS: Five patients each with ALF and ACLF in grade 3 or 4 hepatic encephalopathy and with clinical signs of raised intracranial pressure were studied along with five healthy volunteers. After baseline MRI, an intravenous bolus of 20% mannitol solution was given over 10 min in controls as well as in patients with ALF and ACLF. Repeat MRI for the same position was acquired 30 min after completing the mannitol injection. RESULTS: No statistically significant difference was observed between controls and patients with ALF and ACLF in metabolite ratios, DTI metrics and brain volume or CSF volume following 45 min of mannitol infusion. There was no change in clinical status at the end of post-mannitol imaging. CONCLUSION: The osmotic effect of mannitol did not result in significant reduction of brain water content, alteration in metabolite ratios or any change in the clinical status of these patients during or within 45 min of mannitol infusion.