Rishi Awasthi

Discriminant analysis to classify glioma grading using dynamic contrast-enhanced MRI and immunohistochemical markers.

IntroductionThe purpose of the present study was to look for the possible predictors which might discriminate between high- and low-grade gliomas by pooling dynamic contrast-enhanced (DCE)-perfusion derived indices and immunohistochemical markers.MethodsDCE-MRI was performed in 76 patients with different grades of gliomas. Perfusion indices, i.e., relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), permeability (ktrans and kep), and leakage (ve) were quantified. MMP-9-, PRL-3-, HIF-1α-, and VEGF-expressing cells were quantified from the excised tumor tissues. Discriminant function analysis using these markers was used to identify discriminatory variables using a stepwise procedure. To look for correlations between immunohistochemical parameters and DCE metrics, Pearsons correlation coefficient was also used.ResultsA discriminant function for differentiating between high- and low-grade tumors was constructed using DCE-MRI-derived rCBV, kep, and ve. The form of the functions estimated are “D1 = 0.642 × rCBV + 0.591 × kep − 1.501 × ve − 1.550” and “D2 = 1.608 × rCBV + 3.033 × kep + 5.508 × ve − 8.784” for low- and high-grade tumors, respectively. This function classified overall 92.1% of the cases correctly (89.1% high-grade tumors and 100% low-grade tumors). In addition, VEGF expression correlated with rCBV and rCBF, whereas MMP-9 expression correlated with kep. A significant positive correlation of HIF-1α with rCBV and VEGF expression was also found.ConclusionDCE-MRI may be used to differentiate between high-grade and low-grade brain tumors non-invasively, which may be helpful in appropriate treatment planning and management of these patients. The correlation of its indices with immunohistochemical markers suggests that this imaging technique is useful in tissue characterization of gliomas.

Magnetic‐Nanoparticle‐Doped Carbogenic Nanocomposite: An Effective Magnetic Resonance/Fluorescence Multimodal Imaging Probe

A novel and facile approach is developed to synthesize a magnetic nanoparticle (iron oxide)-doped carbogenic nanocomposite (IO-CNC) for magnetic resonance (MR)/fluorescence imaging applications. IO-CNC is synthesized by thermal decomposition of organic precursors in the presence of Fe(3) O(4) nanoparticles with an average size of 6 nm. IO-CNC shows wavelength-tunable fluorescence properties with high quantum yield. Magnetic studies confirm the superparamagnetic nature of IO-CNC at room temperature. IO-CNC shows MR contrast behavior by affecting the proton relaxation phenomena. The measured longitudinal (r(1) ) and transverse (r(2) ) relaxivity values are 4.52 and 34.75 mM(-1) s(-1) , respectively. No apparent cytotoxicity is observed and the nanocomposite shows a biocompatible nature. In vivo MR studies show both T(1) and T(2) * contrast behavior of the nanocomposite. Fluorescence imaging indicates selective uptake of IO-CNC by macrophages in spleen.

Diffusion Tensor MR Imaging in Children with Pantothenate Kinase−Associated Neurodegeneration with Brain Iron Accumulation and Their Siblings

BACKGROUND AND PURPOSE: It has been reported that iron concentration influences DTI metrics in deep gray matter nuclei. We hypothesized that increased FA in the deep gray nuclei may indicate abnormal iron accumulation in patients with PKAN and their siblings. MATERIALS AND METHODS: Seven patients with the characteristic “eye-of-the-tiger sign,” their 5 siblings, and 5 age-matched controls were prospectively studied. One-way ANOVA with Bonferroni post hoc multiple comparisons was used to compare DTI metrics (FA and MD) among subject groups in the putamen, CN, GP, SN, and ALIC. In addition, hypointense and hyperintense regions of the eye-of-the-tiger sign were segmented, and their DTI metrics were compared. In the patient group, the values of DTI metrics in hypointense regions were also compared with those of the ALIC. RESULTS: A significant increase in FA values of the GP and SN from controls to the patient group to siblings was observed. In the GP, MD values were significantly higher in patients compared with controls and siblings. The patients showed significantly increased FA with decreased MD in hypointense compared with hyperintense regions of the eye-of-the-tiger sign. No difference in FA values were observed between the ALIC and hypointense regions of the eye-of-the-tiger sign in patients. CONCLUSIONS: High FA values in siblings of patients with PKAN suggest the presence of abnormal iron in deep gray matter nuclei, even in the absence of its demonstration on T2*-weighted GRE.

Dynamic contrast-enhanced (DCE) derived transfer coefficient (ktrans) is a surrogate marker of matrix metalloproteinase 9 (MMP-9) expression in brain tuberculomas.

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).

Comparative evaluation of 3-dimensional pseudocontinuous arterial spin labeling with dynamic contrast-enhanced perfusion magnetic resonance imaging in grading of human glioma.

Introduction The study was performed to compare dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) with 3-dimensional (3D) pseudocontinuous arterial spin labeling (PCASL) MRI in gliomas with an aim to see whether arterial spin labeling (ASL)–derived cerebral blood flow (CBF) values can be used as an alternative to DCE-MRI for its grading. Materials and Methods Sixty-four patients with glioma (37 male; mean age, 43 years; 38 high grade and 26 low grade) underwent 3D-PCASL and DCE-MRI. The DCE indices (relative cerebral blood volume, rCBV; relative CBF, rCBF; permeability, ktrans and kep; and leakage, ve) and ASL (absolute and rCBF) values were quantified from the tumors. Student independent t test was used to compare ASL and DCE-MRI indices. Pearson correlation was used to see correlation between DCE- and ASL-derived CBF values in tumor and normal parenchyma. Results On Student t test, neither ASL-derived absolute CBF (P = 0.78) nor rCBF (P = 0.12) values were found to be significantly different in 2 groups, whereas DCE indices except ve were significantly higher in high-grade gliomas. Arterial spin labeling–derived rCBF values weakly correlated with DCE-derived rCBF values, whereas these did not show correlation in normal grey (P = 0.12, r = 0.2) and white (P = 0.26, r = 0.14) matter regions. Conclusions Three-dimensional pseudocontinuous arterial spin labeling does not appear to be a reliable technique in the current form and may not be a suitable replacement for DCE in grading of glioma.

Dynamic contrast-enhanced magnetic resonance imaging-derived kep as a potential biomarker of matrix metalloproteinase 9 expression in patients with glioblastoma multiforme: a pilot study.

Objective To look for the association of tissue matrix metalloproteinase 9 (MMP-9) expression with dynamic contrast-enhanced magnetic resonance imaging and to see whether these can prognosticate patients with glioblastoma multiforme (GBM). Methods Forty-seven patients with GBM underwent dynamic contrast-enhanced magnetic resonance imaging to look for association of its indices with tissue MMP-9 expression using Pearson correlation. Kaplan-Meier survival analysis was performed to study the survival pattern for low-, medium-, and high-tissue MMP-9 expression and kep values. Results Among perfusion indices, kep, ktrans, and ve significantly correlated with MMP-9 expression. Matrix metalloproteinase 9 expression was found to be best estimated by kep using a quadratic model. The 1-year survival in low-, medium-, and high-tissue MMP-9 and kep groups were 59%, 45%, and 7%, and 59%, 33%, and 15%, respectively. Conclusion The association of kep and MMP-9 expression with survival suggests that kep may be used as imaging biomarker of GBM progression and its prognostication.

Subcompartmentalization of extracellular extravascular space (EES) into permeability and leaky space with local arterial input function (AIF) results in improved discrimination between high- and low-grade glioma using dynamic contrast-enhanced (DCE) MRI

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) Cp(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).

T1-Weighted Dynamic Contrast-Enhanced MR Evaluation of Different Stages of Neurocysticercosis and Its Relationship with Serum MMP-9 Expression

BACKGROUND AND PURPOSE: Epileptogenesis in NCC is associated with perilesional inflammation and disruption in BBB. We quantified BBB in different stages of NCC by using DCE-MR imaging to look for the differences in perfusion indices and to correlate these indices with serum MMP-9 expression. MATERIALS AND METHODS: DCE-MR imaging along with conventional MR imaging was performed in 57 single cysticercous brain lesions to quantify the kep, Ktrans, and ve around the lesions, which were in different stages of evolution. There were 6 lesions in the vesicular stage and 17 lesions each in the colloidal, granular-nodular, and calcified stages. Serum MMP-9 was quantified from all patients, whereas perfusion indices were quantified from all stages except for the vesicular stage. RESULTS: We observed significant differences among the 3 stages of NCC in serum MMP-9 expression as well as DCE-derived kep values. In addition, kep showed a strongly significant positive correlation with MMP-9 expression when modeled with the individual stage of the disease as well as with all stages when pooled together. Other DCE-derived hemodynamic and pharmacokinetic parameters showed inconsistent differences with each stage of the disease. The correlation of DCE-derived parameters with serum MMP-9 expression and edema volume also showed inconsistency with the stage of the disease. CONCLUSIONS: We conclude that kep correlates best with serum MMP-9 expression among the pharmacokinetic indices and most closely represents the degree of BBB breakdown, which is highest in the colloidal stage and lowest in the calcified stage. kep may be used as a noninvasive image biomarker of BBB breakdown in different stages of NCC.

Comparative evaluation of dynamic contrast-enhanced perfusion with diffusion tensor imaging metrics in assessment of corticospinal tract infiltration in malignant glioma.

Objective: To compare dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) with diffusion tensor imaging (DTI) for predicting tumor infiltration in a conventional MRI normal-appearing internal capsule adjacent to the tumor in patients with glioblastoma multiforme. Methods: Thirty patients with glioblastoma multiforme underwent a neurological examination for motor assessment, DCE MRI, and DTI. On fused DCE and DTI images, regions of interest were placed on the normal-appearing internal capsule and the corresponding region of the contralateral internal capsule. These patients were pooled into group 1 (improved after surgery, n = 9) and group 2 (did not improve after surgery, n = 21) on the basis of motor strength. The DTI and perfusion metrics were statistically analyzed to look for a predictor of motor functionality. Results: Multivariate logistic regression analysis showed only cerebral blood volume to be the predictor of improvement in motor functionality after surgery (P = 0.043). Conclusions: We conclude that cerebral blood volume appears to be the predictor of motor functionality after surgery and may indirectly suggest tumor infiltration, whereas DTI helps to precisely localize the fiber tracts.

Apparent Diffusion Coefficient with Higher b-Value Correlates Better with Viable Cell Count Quantified from the Cavity of Brain Abscess

BACKGROUND AND PURPOSE: DWI by using higher b-values provides tissue diffusivity with less T2 shinethrough effect. VCD in the abscess cavity correlates with ADC values. The purpose of this study was to investigate which b-value−derived ADC correlates better with VCD. MATERIALS AND METHODS: Thirty patients with brain abscess underwent conventional MR imaging and DWI with b = 1000, 2000, and 3000 s/mm2 on a 3T MR imaging scanner. ADC values were quantified by placing regions of interest inside the abscess cavity in all sections where the lesion was apparent on coregistered ADC maps derived from different b-values. VCD was measured on pus aspirated. RESULTS: An increase in b-value was associated with a decrease in ADC values in normal parenchyma as well as in the abscess cavity. The most significant negative correlation of VCD was observed with b = 3000 s/mm2 (r = −0.98, P = .01). CONCLUSIONS: VCD in the abscess cavity can be best assessed at b = 3000 s/mm2 secondary to the reduction in the T2 shinethrough effect. DWI with b = 3000 s/mm2 is of promising value in the assessment of the therapeutic response of brain abscess.