Diffusion tensor tractography and neuropsychological assessment in patients with vitamin B12 deficiency.

INTRODUCTION: Structural imaging of the brain does not demonstrate any changes in a vast majority of patients with vitamin B12 deficiency, even in advanced stages. In this study, we aimed to assess and correlate the functional integrity of the brain fiber tracts using diffusion tensor tractography with neuropsychological examination in patients with vitamin B12 deficiency. METHODS: The study was conducted at two tertiary care centers. Thirty-two patients with vitamin B12 deficiency were enrolled and subjected to diffusion tensor tractography, as an extension of diffusion tensor imaging, and neuropsychological assessment. Tests of significance were done to detect changes, pre- and post-vitamin B12 supplementation in the diffusivity parameters (fractional anisotropy and mean diffusivity) and the neuropsychological test scores. RESULTS: Statistically significant changes were observed in the diffusivity parameters and the neuropsychological test scores between the controls and the patients with vitamin B12deficiency in the pre- and post-treatment phases. CONCLUSIONS: This is the first study to evaluate the diffusion tensor tractography (DTT) parameters in the light of clinical neuropsychological assessment in patients with vitamin B12 deficiency. Utilization of DTT parameters may antedate structural changes and may quantify the neurocognitive deficits.

T2*-weighted MR angiography substantially increases the detection of hemorrhage in the wall of brain abscess: implications in clinical interpretation.

INTRODUCTION: The purpose of the present study was to identify the true prevalence of hemorrhage in the abscess using T2*-weighted angiography (SWAN) imaging and to study its influence on diffusion tensor imaging (DTI) metrics. METHODS: Fifteen patients of brain abscess underwent conventional, SWAN, and DT imaging on a 3-T MRI followed by its confirmation with histology. DTI metrics were quantified by region-of-interest analysis on hemorrhagic and non-hemorrhagic regions of the abscess wall. Prussian blue staining was performed on excised abscess walls to confirm hemorrhage on histology. RESULTS: Eleven of 15 patients showed evidence of hemorrhage on both Prussian blue staining as well as SWAN imaging. Fractional anisotropy (FA) and linear anisotropy (CL) values were significantly higher, while spherical anisotropy was significantly lower in hemorrhagic compared to non-hemorrhagic regions of the abscess wall. CONCLUSION: Hemorrhage in the abscess wall is a common feature and may not always indicate neoplasm. The presence of intracellular iron in addition to concentrically laid collagen fibers may have synergistic effect on FA and CL values in the abscess wall. Inclusion of SWAN to MRI protocol will define the true prevalence of hemorrhage in brain abscess.

Diffusion Tensor and Dynamic Contrast-Enhanced Magnetic Resonance Imaging Correlate with Molecular Markers of Inflammation in the Synovium.

Objectives: It is difficult to capture the severity of synovial inflammation on imaging. Herein we hypothesize that diffusion tensor imaging (DTI) derived metrics may delineate the aggregation of the inflammatory cells and expression of inflammatory cytokines and dynamic contrast-enhanced (DCE) imaging may provide information regarding vascularity in the inflamed synovium. Patients and methods: Patients with knee arthritis (>3-months duration) underwent conventional (T2-weighted fast spin echo and spin echo T1-weighted images) as well as DTI and DCE MRI and thereafter arthroscopic guided synovial biopsy. DCE and DTI metrics were extracted from the masks of the segments of the inflamed synovium which enhanced on post-contrast T1-weighted MRI. These metrics were correlated with immunohistochemistry (IHC) parameters of inflammation on synovium. Statistical analysis: Pearson's correlation was performed to study the relationship between DTI- and DCE-derived metrics, IHC parameters, and post-contrast signal intensity. Linear regression model was used to predict the values of IHC parameters using various DTI and DCE derived metrics as predictors. Results: There were 80 patients (52 male) with mean age 39.78 years and mean disease duration 19.82 months. Nineteen patients had tuberculosis and the rest had chronic undifferentiated monoarthritis (n = 31), undifferentiated spondyloarthropathy (n = 14), rheumatoid arthritis (n = 6), osteoarthritis (n = 4), reactive arthritis (n = 3), ankylosing spondylitis (n = 2), and juvenile idiopathic arthritis (n = 1). Fractional anisotropy (FA), a metric of DTI, had significant correlation with number of immune cells (r = 0.87, p < 0.01) infiltrating into the synovium and cytokines (IL-1ß, r = 0.55, p < 0.01; TNF-α, r = 0.42, p < 0.01) in all patients and also in each group of patients and adhesion molecule expressed on these cells in all patients (CD54, r = 0.51, p < 0.01). DCE parameters significantly correlated with CD34 (blood flow, r = 0.78, p < 0.01; blood volume, r = 0.76, p < 0.01) in each group of patients, a marker of neo-angiogenesis. FA was the best predictor of infiltrating inflammatory cells, adhesion molecule and proinflammatory cytokines. Amongst the DCE parameters, blood volume, was best predictor of CD34. Conclusion: DTI and DCE metrics capture cellular and molecular markers of synovial inflammation in patients with chronic inflammatory arthritis.

Serum proinflammatory cytokines correlate with diffusion tensor imaging derived metrics and 1H-MR spectroscopy in patients with acute liver failure.

Hyperammonemia and inflammation are major contributing factors in the development of cerebral edema (CE) in acute liver failure (ALF). Aim of this study was to look for the relationship between proinflammatory cytokines with diffusion tensor imaging (DTI) derived metrics and (1)H-MR spectroscopy ((1)H-MRS) derived Glutamate/Glutamine (Glx). Fourteen patients with ALF and 14 age/sex matched controls were included in this study. All subjects had undergone clinical, biochemical, MR imaging and (1)H-MRS studies. Serum proinflammatory cytokines (IL-6 and TNF-α), blood ammonia level and Glx were computed for independent t-test and Pearson correlation. Serum proinflammatory cytokines, blood ammonia level and brain Glx were significantly increased in ALF patients as compared to controls. Blood ammonia level and Glx showed significant positive correlation with proinflammatory cytokines. Spectroscopy voxel derived spherical anisotropy (CS) showed positive correlation with Glx while mean diffusivity (MD) showed negative correlation. Proinflammatory cytokines showed positive correlation with CS and negative correlation with MD in various brain regions including spectroscopy voxel. Significant correlation of Glx, CS and MD with proinflammatory cytokines suggests that both DTI derived metrics and (1)H-MRS measure the synergistic effect of hyperammonemia and proinflammatory cytokines and may be used as non-invasive tools for understanding the pathogenesis of CE in ALF.

Serial diffusion tensor imaging to characterize radiation-induced changes in normal-appearing white matter following radiotherapy in patients with adult low-grade gliomas.

PURPOSE: The aim of this study was to ascertain whether diffusion tensor imaging (DTI) metrics fractional anisotropy (FA), mean diffusivity (MD), linear case (CL), planar case (CP), spherical case (CS)-can characterize a threshold dose and temporal evolution of changes in normal-appearing white matter (NAWM) of adults with low-grade gliomas (LGGs) treated with radiation therapy (RT). METHODS AND MATERIALS: Conventional and DTI imaging were performed before RT in 5 patients and subsequently, on average, at 3 months (n = 5), 8 months (n = 3), and 14 months (n = 5) following RT for a total of 18 examinations. Isodose distribution at 5-Gy intervals were visualized in all the slices of fluid attenuated inversion recovery (FLAIR) and the corresponding DTI images without diffusion sensitization (b0DTI). The latter were exported for relative quantitative analysis. RESULTS: Compared to pre-RT values, FA and CL decreased, whereas CS increased at 3 and 8 months and recovered partially at 14 months for the dose bins >55 Gy and 50-55 Gy. For the 45 50 Gy bin, the FA and CL decreased with an increase in CS at 3 months; no further change was seen at 8 or 14 months. For the >55 Gy and 50-55 Gy bins, CP decreased and MD increased at 3 months and returned to baseline at 8 months following RT. CONCLUSION: Radiation-induced changes in NAWM can be detected at 3 months after RT, with changes in FA, CL, and CS (but not CP or MD) values seen at a threshold dose of 45-50 Gy. A partial recovery was evident by 14 months to regions that received doses of 50-55 Gy and >55 Gy, thus providing an objective measure of radiation effect on NAWM.

Evaluation of cerebral white-matter micro-structural alterations in patients with medically refractory epilepsy using diffusion tensor tractography.

INTRODUCTION: Diffusion tensor tractography (DTT) is a newer magnetic resonance imaging (MRI) technique that helps in evaluation of white matter. Presurgical planning with tractography may be valuable for evaluation of white matter tracts and their relationship with epileptogenic focus and for evaluation of cortical fibres around the epileptogenic zone. METHODS: This study was carried out on 33 patients diagnosed with medically refractory epilepsy (males, 27; females, 6) with a mean age of 31.93 (range: 19-50) years. Twenty age and sex matched controls were also included. DTT evaluation was done using a 3.0 TexlaMRI scanner. Single-shot spin-echo echo-planar imaging (with 32-different diffusion gradient directions) was acquired for reconstruction of the white matter tracts. Diffusion metrics within fibre bundles that were reconstructed by a continuous fibre-track algorithm were compared between groups. RESULTS: Patients had either partial seizures (21 patients; simple partial, complex partial or secondarily generalized seizure) or generalized seizures (12 patients; tonic clonic, tonic or myoclonic). Out of the 33 patients, 23 patients were classified into the lesional group and the rest into the non-lesional group. The lesions observed on conventional MRI included focal gliosis, hippocampal sclerosis, post-hypoxic encephalopathy, calcification and post-traumatic cavitation, in various parts of the brain. Significant differences were observed in terms of fractional anisotropy and mean diffusivity values amongst controls and patients, as well as on the lesional and non-lesional side of the brain; patients with a normal conventional imaging showed fractional anisotropy and mean diffusivity changes as well. CONCLUSION: We conclude that widespread diffusion abnormalities occur in the white matter tracts on the side of lesion as well as distant from the epileptic focus.

Thiamine deficiency related microstructural brain changes in acute and acute-on-chronic liver failure of non-alcoholic etiology.

BACKGROUND & AIMS: Mammillary body atrophy in alcoholic liver disease usually indicates thiamine deficiency. The purpose of this study was to explore the relationship among blood thiamine, mammillary bodies, major fiber bundle fractional anisotropy, and volume changes with diffusion tensor tractography in patients with acute and acute-on-chronic liver failure of non-alcoholic etiology. METHODS: Blood thiamine, mammillary bodies, fiber bundle fractional anisotropy and volume of major fiber tracts were quantified from acute and acute-on-chronic liver failure patients and compared with healthy controls. In 7 acute liver failure patients, follow-up study was done after clinical recovery at 5 weeks. RESULTS: Blood thiamine, mammillary bodies and fornix volume, and fornix fiber bundle fractional anisotropy were significantly decreased as compared to controls. Blood thiamine showed significant positive correlation with mammillary bodies' volume only. On follow-up study, acute liver failure patients showed significant reversibility only in blood thiamine level and mammillary bodies' volume. CONCLUSIONS: Mammillary bodies' volume changes are primarily a consequence of thiamine deficiency, which may secondarily result in microstructural changes in the fornix. These observable changes are known to be specific and may be reversible with restoration of blood thiamine level. These imaging changes may be used as imaging biomarker of thiamine deficiency in these patients in future.

Differentiation of infective from neoplastic brain lesions by dynamic contrast-enhanced MRI.

INTRODUCTION: It is not always possible to differentiate infective from neoplastic brain lesions with conventional MR imaging. In this study, we assessed the utility of various perfusion indices in the differentiation of infective from neoplastic brain lesions. METHODS: A total of 103 patients with infective brain lesions (group I, n=26) and neoplastic brain lesions (high-grade glioma, HGG, group II, n=52; low-grade glioma, LGG, group III, n=25) underwent dynamic contrast-enhanced MR imaging. The perfusion indices, including relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), transfer coefficient (k(trans)) and leakage (v(e)), were calculated and their degree of correlation with immunohistologically obtained microvessel density (MVD) and vascular endothelial growth factor (VEGF) determined. The rCBV was corrected for the leakage effect. Discriminant analysis for rCBV, rCBF, k(trans) and v(e) was performed to predict the group membership of each case and post hoc analysis was performed to look for group differences. RESULTS: The rCBV, rCBF, k(trans), v(e), MVD and VEGF were significantly different (P<0.001) between the three groups. Discriminant analysis showed that rCBV predicted 73.1% of the infective lesions, 84.6% of the HGG and 72.0% of the LGG. The rCBF classified 86.5% of the HGG, 80.0% of the LGG and 65.4% of the infective lesions. The k(trans) discriminated 98.1% of the HGG, 76.0% of the LGG and 88.5% of the infective lesions correctly. The v(e) classified 98.1% of the HGG, 76.0% of the LGG and 84.6% the infective lesions. The rCBV was correlated significantly with MVD and VEGF, while the correlation between k(trans) and MVD was not significant. CONCLUSION: Physiological perfusion indices such as k(trans) and v(e) appear to be useful in differentiating infective from neoplastic brain lesions. Adding these indices to the current imaging protocol is likely to improve tissue characterization of these focal brain mass lesions.