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Purpose: To modify the generalized tracer kinetic model (GTKM) by introducing an additional tissue uptake leakage compartment in extracellular extravascular space (LTKM). In addition, an implicit determination of voxel-wise local arterial input function (AIF) C p( t) was performed to see whether these changes help in better discrimination between low- and high-grade glioma using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). Materials and Methods: The modified model (LTKM) was explored and fitted to the concentration-time curve C( t) of each voxel, in which the local AIF C p( t) could be estimated by a time invariant convolution approximation based on a separately measured global AIF C a( t). A comparative study of tracer kinetic analysis was performed on 184 glioma patients using DCE-MRI data on 1.5T and 3T MRI systems. Results: The LTKM analysis provided more accurate pharmacokinetic parameters as evidenced by their relative constancy with respect to the length of concentration-time curve used. In addition, LTKM with local AIF resulted in improved discrimination between low-grade and high-grade gliomas. Conclusion: LTKM with local AIF provides more accurate estimation of physiological parameters and improves discrimination between low-grade and high-grade gliomas as compared with GTKM. J. Magn. Reson. Imaging 2013;38:677-688. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

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. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose To correlate dynamic contrast-enhanced (DCE) MRI derived perfusion indices with immunohistochemically obtained vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in a cellular fraction of brain tuberculomas (BT). Materials and Methods Thirteen BT patients underwent DCE MRI. Perfusion indices (cerebral blood volume [CBV], transfer coefficient [ktrans] and leakage [ve]) maps were generated for the quantitative analysis. The CBV was corrected for the leaky blood-brain barrier (BBB). The relative CBV (rCBV), ktrans, and ve were calculated by placing 10 regions of interest (ROIs) showing the highest values in the lesion. The percentage area of VEGF and percentage area of MMP-9 and microvessel density (MVD) were quantified from 10 fields per lesion with maximal expression of the excised BT. Pearson correlation analysis between physiological indices and quantitative VEGF, MMP-9, and MVD was performed for each ROI. Results The average value of rCBV, ktrans, ve, VEGF, MMP-9, and MVD were 3.53 ± 0.37, 2.04 ± 0.40 min−1, 0.71 ± 0.09, 12.51 ± 2.56, 18.09 ± 2.06, 10.87 ± 1.99, respectively. The ktrans ( r = 0.918, P < 0.001) and ve ( r = 0.899, P < 0.001) showed significant correlation with MMP-9, while rCBV correlated significantly with MVD ( r = 0.962, P < 0.001) and VEGF ( r = 0.868, P < 0.001). Conclusion We conclude that the expression of MMP-9, a marker of BBB disruption and disease activity in BT correlates with DCE-derived ktrans and thus has the potential to be used as its surrogate marker. J. Magn. Reson. Imaging 2008;28:588-597. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

High fractional anisotropy (FA) usually reflects the orientation and integrity of white matter (WM) fibers. Other regions of increased FA have been described, such as brain abscesses, developing cortex, and areas of hemorrhage. It may not be possible to differentiate true fibers from the pseudofibers found inside an abscess cavity on the basis of FA and mean diffusivity (MD). The aim of this study was to differentiate true WM fibers from pseudo WM tracts inside the abscess cavity using geometrical diffusion tensor imaging metrics [linear anisotropy (CL), planar anisotropy (CP), and spherical anisotropy (CS)]. Diffusion tensor imaging was performed in 42 patients with brain abscess and 10 age/sex-matched controls. Automated segmentation using Java-based software divided the abscess cavity into two sub-regions with FA < 0.20 and FA ≥ 0.20. Quantitation was carried out on the sub-regions of the abscess cavity with FA ≥ 0.20. In healthy controls, regions of interest were placed on the corpus callosum, posterior limb of the internal capsule, and periventricular and subcortical WM. Significantly increased CP values were observed inside the abscess cavity compared with various normal WM regions. Significantly increased FA and CL values were observed in the abscess cavity compared with subcortical WM only. However decreased FA and CL values were observed in the cavity compared with the corpus callosum, posterior limb of the internal capsule, and periventricular WM. The 95% confidence intervals of means for the abscess cavity were well separated from those for WM in the case of CL and CP; however, they overlapped in the case of FA, MD, and CS. High CP with low CL inside the abscess cavity suggests that the shape of the diffusion tensor is predominantly planar, whereas it is linear in WM tracts. These geometrical indices may have advantages over FA for differentiating true from pseudo WM tracts inside the abscess cavity. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose To understand the biological basis of possible mechanisms responsible for increased fractional anisotropy (FA) in different stages of hemorrhage and hemorrhagic brain lesions. Materials and Methods A total of 19 patients with cerebral hemorrhage (CH), five patients with hemorrhagic infarct (HI), and nine patients with hemorrhagic brain tumor (HBT) were prospectively evaluated with diffusion tensor imaging (DTI) and the FA and mean diffusivity (MD) was quantified. Ex vivo DTI of blood clot and histology of the blood clot and HBT were performed to interpret the temporal changes in the DTI metrics. Results High FA (>0.20) with low MD in the acute and early subacute stage and low FA (<0.20) with increased MD in the late subacute and chronic stage of CH and HI were observed. HBT showed high FA with low MD at all stages. In CH and HI, a significant reduction in FA ( P < 0.001) with increased MD ( P < 0.001) was seen in the late subacute and chronic stages compared to the acute and early subacute stages, normal white matter (NWM), and HBT. In HBT, there was no significant statistical difference in the FA values between different stages. Histology of HBT and ex vivo blood clot showed structural organization of intact red blood cells (RBCs) with fibrin mesh where the FA values were high compared to normal tissue region that is devoid of blood. Conclusion Intact RBCs entangled within fibrin mesh appear to be responsible for high FA in hemorrhagic brain lesions. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Purpose To compare the signal intensity on the fluid attenuated inversion recovery (FLAIR) sequence and magnetization transfer ratios (MTRs) for the differentiation of abscesses from non-abscess cystic brain lesions, and to correlate these MR parameters with the viscosity, viable cell density and total protein concentration of the cystic fluid. Materials and Methods Signal intensity on FLAIR and MTRs from the cystic cavity of lesions were calculated from 33 patients (brain abscess ( N = 12) and non-abscess ( N = 21)). The fluid from the lesion was aspirated at the time of surgery, and the viscosity, viable cell density, and total protein concentration were measured. Results Signal intensity on FLAIR correlated significantly with the total protein concentration in abscess (r = 0.60, P < 0.05) and non-abscess lesions (r = 0.41, P < 0.05). However, there was no significant difference ( P > 0.05) in the FLAIR signal intensity of the abscess (318.8 ± 75) and non-abscess group (258 ± 47). The MTR of the brain abscesses (13 ± 0.95) was significantly higher ( P < 0.05) than that of the non-abscess group (3.5 ± 0.3). A significant correlation was observed between MTR and viscosity (r = 0.75, P < 0.05), total protein concentration (r = 0.60, P < 0.05), and cell density (r = 0.70, P < 0.05) in brain abscess, and viscosity (r = 0.81, P < 0.05) and total protein concentration (r = 0.41, P < 0.05) in non-abscess lesions. Conclusion It is possible to differentiate brain abscesses from non-abscess cystic lesions using MT imaging. The MTR correlates significantly with the viscosity, viable cell density, and total protein concentration in brain abscess, and with viscosity and total protein concentration in non-abscess lesions. FLAIR signal intensity correlates significantly only with the total protein concentration in abscess and non-abscess lesions. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Restricted diffusion in brain abscess is assumed to be due to a combination of inflammatory cells, necrotic debris, viscosity, and macromolecules present in the pus. We performed diffusion-weighted imaging (DWI) on 41 patients with proven brain abscesses (36 pyogenic and five tuberculous), and correlated the apparent diffusion coefficient (ADC) from the abscess cavity with viable cell density, viscosity, and extracellular-protein content quantified from the pus. On the basis of the correlation between cell density and ADC in animal tumor models and human tumors in the literature, we assumed that the restricted ADC represents the cellular portion in the abscess cavity. We calculated restricted and unrestricted lesion volumes, and modeled cell density over the restricted area with viable cell density per mm3 obtained from the pus. The mean restricted ADC in the cavity (0.65 ± 0.01 × 10-3 mm2/s) correlated inversely with restricted cell density in both the pyogenic (r = −0.90, P = <0.05) and tuberculous (0.60 ± 0.04 × 10-3 mm2/s, r = −0.94, P = <0.05) abscesses. We conclude that viable cell density is the main biological parameter responsible for restricted diffusion in brain abscess, and it is not influenced by the etiological agents responsible for its causation. Magn Reson Med, 2005. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Purpose: The main objective of this study was to use diffusion tensor imaging (DTI) to search and quantify the extent of abnormality beyond the obvious lesions seen on the T2 and fluid-attenuation inversion recovery (FLAIR) magnetic resonance images in patients with chronic traumatic brain injury (TBI) with and without epilepsy. Methods: DTI was performed on 23 chronic TBI patients (with late posttraumatic epilepsy, n = 14; without epilepsy, n = 9) and 11 age-matched controls. The ratios of fractional anisotropy (FA) and mean diffusivity (MD) between the regions of interest beyond the T2/FLAIR-visualized abnormality and the corresponding contralateral normal-appearing region were calculated. FA and MD ratios were compared for relative changes in these parameters among the TBI subjects with and without epilepsy and controls. Tissue volumes exhibiting abnormalities on DTI also were measured in these patients. Results: The mean regional FA ratio was significantly lower, whereas the mean regional MD value was higher in patients with TBI compared with controls. The mean regional FA ratio was significantly lower in TBI patients with epilepsy (0.57 ± 0.059) than in those without epilepsy (0.68 ± 0.039). Although the regional MD ratio was higher in TBI patients with epilepsy (1.15 ± 0.140) relative to those without epilepsy (1.09 ± 0.141), the difference did not reach statistical significance. The tissue volume with low FA value also was found to be higher in TBI patients with epilepsy than without. Conclusions: Severity of injury as predicted by the DTI-derived increased volume of microstructure damage is associated with delayed posttraumatic epilepsy in TBI patients. These findings could be valuable in predicting epileptogenesis in patients with chronic TBI. [ABSTRACT FROM AUTHOR]

The Achromobacter fischeri nitrite reductase used in the preserver studies was monodisperse as judged by ultracentrifugation and disc-gel electrophoresis. The native enzyme has an average molecular weight of 80000 as determined by the Archibald approach-to-equilibrium method, disc-gel electrophoresis and from a combination of hydrodynamic properties. The sedimentation and diffusion coefficients are 5.25 S and 60.5 µm² s-1 respectively, frictional ratio (///0) 1.25, and Stokes' radius 3.49 nm. Nitrite reductase does not dissociate in the presence of 6 M guanidine-HCl or 6 M urea. The enzyme however splits into two physically indistingiushable subunits upon treatment with 6 M guanidine-HCl, in combination with 1% 2-mercaptoethanol or 1% sodium dodecylsulfate and 1% 2-mercaptoethanol. In both the systems the subunit molecular weight has been found to be approximately 39000. Methionine is the sole N-terminal residue detected. These results indicate that Achromobacter nitrite reductase is composed of two subunits of equivalent size which are covalently bonded by a disulfide bridge. [ABSTRACT FROM AUTHOR]