Biomedical subjects
Publications and source records attributed to Rakesh K Gupta.
Complete cerebellar agenesis is a very rare entity, which occurs during the early period of embryogenesis and is usually associated with severe motor dysfunction. We report a case of complete cerebellar agenesis with complete corpus callosum agenesis diagnosed on magnetic resonance imaging (MRI). These anomalies were also associated with rudimentary pons.
The presence of large number of false lesion classification on segmented brain MR images is a major problem in the accurate determination of lesion volumes in multiple sclerosis (MS) brains. In order to minimize the false lesion classifications, a strategy that combines parametric and nonparametric techniques is developed and implemented. This approach uses the information from the proton density (PD)- and T2-weighted and fluid attenuation inversion recovery (FLAIR) images. This strategy involves CSF and lesion classification using the Parzen window classifier. Image processing, morphological operations, and ratio maps of PD- and T2-weighted images are used for minimizing false positives. Contextual information is exploited for minimizing the false negative lesion classifications using hidden Markov random field-expectation maximization (HMRF-EM) algorithm. Lesions are delineated using fuzzy connectivity. The performance of this algorithm is quantitatively evaluated on 23 MS patients. Similarity index, percentages of over, under, and correct estimations of lesions are computed by spatially comparing the results of present procedure with expert manual segmentation. The automated processing scheme detected 80% of the manually segmented lesions in the case of low lesion load and 93% of the lesions in those cases with high lesion load.
Taenia solium infection is a zoonotic disease and swine is the natural intermediate host. Till date no literatures have described clinical signs in swine indicative of brain involvement by cysticerci. In the present study we describe such clinical signs of porcine neurocysticercosis (NCC). These signs were excessive salivation, excessive blinking and tearing, and subconjunctival nodule. A total of 30 swine (18 with 2 or all 3 clinical signs and 12 without any sign) underwent magnetic resonance imaging (MRI). All 18 swine with above signs had NCC on MRI along with variable involvement of other organs that were subsequently confirmed by ex vivo MRI, necropsy and histopathology, while none of the 12 animals without any sign had NCC. As development of a porcine NCC model has proved difficult, we propose that naturally infected swine can be identified on the basis of these clinical signs and thus used as a model for further research on NCC.
OBJECTIVES: Despite the technological advancements in diagnostic and neurosurgical procedures, brain abscess continues to remain a potentially fatal central nervous system infection. In a prospective study we determined the predisposing factors and the microbiological profile of brain abscess. We also analyzed the mortality in patients with the type of infections identified. METHODS: Over a period of 8 years (1997-2004), aspirated pus from 118 patients with brain abscess was directly inoculated into BACTEC PLUS+ aerobic and BACTEC PLUS+ anaerobic media immediately after collection and subcultured on solid media as appropriate. Predisposing factors, if any, were recorded in all patients. Mortality of patients during hospital stay was correlated with the type of infections identified. RESULTS: Predisposing factors were identified in 94 (79.7%) patients, otogenic infection being the most common (37/118; 31.4%). Microorganisms were demonstrated in 96 (81.4%) patients, by culture in 89 (75.4%) patients and by Gram stain in 7 (5.9%) additional cases. A total of 105 organisms were isolated - 67 (63.8%) aerobes, 32 (30.5%) anaerobes, 5 (4.8%) mycobacteria and 1 (0.9%) fungus. Viridans streptococci (23.8%), Staphylococcus aureus (14.3%), Bacteroides fragilis group/species and Peptostreptococcus species (10.5% each) were the common isolates. Overall mortality was 14.4%; patients with Gram-negative infections had higher mortality than Gram-positive infections (6/20; 30% vs. 6/63; 9.5%; P=0.02). CONCLUSIONS: Culture of pus immediately after aspiration in an automated system yields good results. Gram stain coupled with culture can guide the neurosurgeons better to treat their patients more rationally. Patients with Gram-negative infections need special attention in terms of management because of high mortality rate.
Brain water may increase in hepatic encephalopathy (HE). Diffusion tensor imaging was performed in patients with cirrhosis with or without HE to quantify the changes in brain water diffusivity and to correlate it with neuropsychological (NP) tests. Thirty-nine patients with cirrhosis, with minimal (MHE) or overt HE, were studied and compared to 18 controls. Mean diffusivity (MD) and fractional anisotropy (FA) were calculated in corpus callosum, internal capsule, deep gray matter nuclei, periventricular frontal, and occipital white matter regions in both cerebral hemispheres. The MD and FA values from different regions in different groups were compared using analysis of variance and Spearman's rank correlation test. In 10 patients with MHE, repeat studies were performed after 3 weeks of lactulose therapy to look for any change in MD, FA, and NP scores. Significantly increased MD was found with insignificant changes in FA in various regions of brain in patients with MHE or HE compared with controls, indicating an increase in interstitial water in the brain parenchyma without any microstructural changes. A significant correlation was found between MD values from corpus callosum, internal capsule, and NP test scores. After therapy, MD values decreased significantly and there was a corresponding improvement in NP test scores. Further analysis showed that MD values were different for different grades of minimal or overt HE. In conclusion, the increase in MD with no concomitant changes in FA in cirrhosis with minimal or early HE indicates the presence of reversible interstitial brain edema.
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.
PURPOSE: To detect lesion-related focal Wallerian degeneration (WD) changes in different segments of the corpus callosum (CC) in patients with large middle cerebral arterial (MCA) territory stroke using diffusion tensor imaging (DTI). MATERIALS AND METHODS: Eight patients underwent DTI scans at three different time points: six to eight weeks, 10-12 weeks, and beyond six months of stroke onset. Eight healthy age-matched controls were also scanned using the same protocol at three different time points. Region-of-interest (ROI) analysis was performed on seven segments of the CC to determine the fractional anisotropy (FA), mean diffusivity (MD), and corresponding callosal cross-sectional areas. RESULTS: On repeated-measures analysis of variance (ANOVA), a significant reduction in the FA values was observed from the first to the third study compared to controls, reflecting temporal degeneration in the rostrum, genu, rostral body, anterior midbody, and splenium of the CC. However, a significant temporal elevation in MD values was observed in only the rostral body and anterior midbody of the CC. This was associated with a significant region-specific reduction in the cross-sectional areas at time points beyond six months, and appears to be consistent with the loss of callosal structural components due to interruption of the cortico-callosal fibers secondary to WD. CONCLUSION: These results indicate that cortico-callosal topographical changes exhibit a significant temporal decline in observed FA values that is suggestive of cortico-callosal WD in patients with large MCA territory stroke.
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.
We describe for the first time an unusual location and clinical presentation of medulloepithelioma, a rare embryonal tumor. A 5-year-old child presented with sudden onset of bilateral hearing loss. On imaging, the lesion appeared to be extra axial and was located in the right cerebello-pontine (CP) angle, extending into middle fossa along the trigeminal ganglion and in front of the brain stem into the opposite CP angle. It did not show any enhancement following contrast administration and had restricted diffusion on diffusion-weighted imaging, simulating an epidermoid. However, in vivo localized proton MR spectroscopy revealed a creatine peak dominated by a large choline resonance, peak of glycine with lactate/lipid and invisible N-acetylaspartate suggestive of a neoplastic lesion and not an epidermoid. Only subtotal resection could be performed and the patient had a stormy post-operative course due to extensive dissemination of the disease.
A technique that involves minimal operator intervention was developed and implemented for identification and quantification of black holes on T1-weighted magnetic resonance images (T1 images) in multiple sclerosis (MS). Black holes were segmented on T1 images based on grayscale morphological operations. False classification of black holes was minimized by masking the segmented images with images obtained from the orthogonalization of T2-weighted and T1 images. Enhancing lesion voxels on postcontrast images were automatically identified and eliminated from being included in the black hole volume. Fuzzy connectivity was used for the delineation of black holes. The performance of this algorithm was quantitatively evaluated on 14 MS patients.
Diffusion tensor imaging (DTI) was performed on 15 fresh spontaneously or therapeutically aborted normal fetuses and five term infants at different gestational ages. Regional cortical fractional anisotropy (FA) values were observed to increase with gestational age (GA) from 15 to 28 weeks, followed by a decrease through 36 weeks. The early increase in the cortical FA value, which has never been reported before, is consistent with neuronal migration from the germinal matrix. A statistically significant inverse correlation between GA and the FA values in the germinal matrix was observed (r = -0.81, P = 0.004). In addition, there was a significant difference in the FA values in the right and left frontal cortices (P = 0.007, sign test), suggesting cortical lateralization during the early stage of development. Our studies suggest that the DTI-estimated anisotropy could be useful in following neuronal migration, cortical maturation, and associated changes in the germinal matrix during early brain development.
The role of neuroendoscopy in patients of tuberculous meningitis with hydrocephalus (TBMH) is not yet established. We present details of endoscopic morphology, and analyze outcome of Neuroendoscopy performed in 28 patients (15 males and 13 females, average age 23 years) of TBMH in last 2.5 years. Endoscopic procedures performed included endoscopic third ventriculostomy (ETV) alone (n=19), ETV with monroplasty (n=2), and septostomy (n=2), ETV with decompression/biopsy of tuberculoma (n=2) and with abscess drainage (n=1). Outcome was assessed on the basis of clinico-radiological improvement, need for external shunt and complications. Outcome was satisfactory in 14 (50%), acceptable in five (18%) and unsatisfactory in nine (32%) patients. Overall, 19 (68%) patients benefited from endoscopic intervention. Cerebrospinal fluid (CSF) leak (n=2) and per-operative bleeding (n=1) were the only complications encountered. Endoscopy appears to be helpful in a considerable number of patients with TBMH, and should be considered as the first surgical option for CSF diversion surgery in these patients. External shunt should be reserved for those who fail the endoscopic CSF diversion.
PURPOSE: To determine the feasibility of a statistical classification strategy (SCS) and the identity of metabolites of bacterial and host origins that potentially contributed to the most discriminatory regions of magnetic resonance (MR) spectra from Staphylococcus aureus abscesses of biopsy material from controls, gliomas, and staphylococcal abscesses. MATERIALS AND METHODS: Human and animal study received ethics committee approval, and informed patient consent was obtained. A rat model of S aureus brain abscess was developed. Histologic and microbiologic examination was performed to assess abscess development 3-4, 6-8, and 10-15 days after initiation. Metabolite profiles in pus (n = 62) and controls (n = 37) were characterized with ex vivo MR spectroscopy and compared with data from rat gliomas (n = 27). SCS, optimal region selection, and development of pairwise classifiers allowed MR spectra of abscesses (n = 42, day 6-8) to be distinguished from those of glioblastoma multiforme and controls. MR spectroscopy profiles of pus from animal abscesses were compared with in vivo MR spectra from patients with staphylococcal brain abscesses (n = 7, aged 6-67 years) and ex vivo pus MR spectra from patients with S aureus abscesses. RESULTS: Histologically confirmed abscesses were present 6-8 days after stereotactic injection of S aureus in 42 of 47 rats (89%). MR spectra of abscesses and glioblastoma multiforme in the animal model were similar. Typical metabolites of abscesses due to anaerobe bacteria (acetate, succinate, amino acids) were not detectable in S aureus abscesses in rats or humans. MR spectroscopic findings from controls, abscesses, and gliomas were distinguished by means of SCS with an accuracy of 99%. Analysis of the most discriminatory regions with two-dimensional correlation spectra indicated that glutamine and/or glutamate and aspartate potentially contributed to successful classification. CONCLUSION: S aureus is detectable in abscesses with a non-culture-based method in an animal model.
Expression of the bacterial luciferase (lux) system in mammalian cells would culminate in a new generation of bioreporters for in vivo monitoring and diagnostics technology. Past efforts to express bacterial luciferase in mammalian cells have resulted in only modest gains due in part to low overall expression of the bacterial genes. To optimize expression, we have designed and synthesized codon-optimized versions of the luxA and luxB genes from Photorhabdus luminsecens. To evaluate these genes in vivo, stable HEK293 cell lines were created harboring wild type luxA and luxB (WTA/WTB), codon-optimized luxA and wild type luxB (COA/WTB), and codon-optimized versions of both luxA and luxB genes (COA/COB). Although mRNA levels within these clones remained approximately equal, LuxA protein levels increased significantly after codon optimization. On average, bioluminescence levels were increased by more than six-fold [5x10(5) vs 2.9x10(6) relative light units (RLU)/mg total protein] with the codon-optimized luxA and wild type luxB. Bioluminescence was further enhanced upon expression of both optimized genes (2.7x10(7) RLU/mg total protein). These results show promise toward the potential development of an autonomous light generating lux reporter system in mammalian cells.
PURPOSE: To investigate the utility of whole-brain diffusion tensor imaging (DTI) in elucidating the pathogenesis of multiple sclerosis (MS) using the normal-appearing white matter (NAWM) of the corpus callosum (CC) as a marker of occult disease activity. MATERIALS AND METHODS: A high signal-to-noise ratio (SNR) and optimized entire brain DTI data were acquired in 26 clinically-definite relapsing and remitting multiple sclerosis (RRMS) patients and 32 age-matched healthy adult controls. The fractional anisotropy (FA) values of seven functionally distinct regions in the normal-appearing CC were compared between patients and controls. RESULTS: This study indicates that 1) there was a gender-independent FA heterogeneity of the functionally specialized CC segments in normal volunteers; 2) FA in the MS group was significantly decreased in the anterior (P=0.0039) and posterior (P=0.0018) midbody subdivisions of the CC, possibly due to a reduction of small-caliber axons; and 3) the FA of the genu of the CC was relatively intact in the MS patients compared to the healthy age-matched controls (P=0.644), while the splenium showed an insignificant trend of reduced FA values (P=0.248). The decrease in FA in any of the CC subdivisions did not correlate with disease duration (DD) or the expanded disability status scale (EDSS) score. CONCLUSION: The preliminary results are consistent with published histopathology and clinical studies on MS, but not with some published DTI reports. This study provides insights into the pathogenesis of MS, and the role played by compromised axonal integrity in this disease.
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 mm(3) obtained from the pus. The mean restricted ADC in the cavity (0.65 +/- 0.01 x 10(-3) mm(2)/s) correlated inversely with restricted cell density in both the pyogenic (r = -0.90, P = <0.05) and tuberculous (0.60 +/- 0.04 x 10(-3) mm(2)/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.
Restricted diffusion is noted in a large number of non-stroke conditions including tuberculoma. The purpose of this study was to demonstrate spectrum of diffusion weighted imaging (DWI) abnormalities in tuberculomas and tuberculous abscess and to distinguish these from degenerating neurocysticercosis. Seventy tuberculomas and tuberculous abscesses in 30 patients were categorized in three groups depending on the intensity in the core of the lesion on T2 weighted images. Mean apparent diffusion coefficient (ADC) was calculated from the core as well as from the wall of the lesions. Forty-five lesions of neurocysticercosis in different stage of evolution in 12 patients were also included for comparison. The mean ADC value from the core of the T2 hypointense lesions was significantly higher compared to the wall ((1.24+/-0.32)x10(-3) and (1.06+/-0.15)x10(-3)mm(2)/s, respectively), while mean ADC value from the core of mildly T2 hyperintense lesions was significantly lower compared to the wall ((0.80+/-0.08)x10(-3) and (1.08+/-0.13)x10(-3)mm(2)/s, respectively). Truly T2 hyperintense lesions were divided into two subgroups, tuberculomas and tuberculous abscesses; ADC values from the core and the wall of these lesions were (0.74+/-0.13)x10(-3), (0.61+/-0.08)x10(-3) and (1.03+/-0.14)x10(-3), (1.08+/-0.14)x10(-3)mm(2)/s, respectively, and was significantly lower in core as compared to the wall. However, there was no significant difference between ADC values of the tuberculous abscess and the hyperintense tuberculomas. Vesicular and degenerating stages of cysticercus cysts from the core showed ADC values of (1.66+/-0.29)x10(-3) and (1.51+/-0.23)x10(-3)mm(2)/s, respectively, and were significantly higher than the core of all groups of tuberculomas and tuberculous abscess. We conclude that addition of DWI to routine imaging protocol may help in differentiation of tuberculous lesions from degenerating cysticercus granuloma.
Capabilities of diffusion-weighted (DW) and magnetization transfer (MT) imaging are well established for tissue characterization in various pathologies individually. However, the effect of suppression of macromolecules on applying MT pulse on signals associated with DW imaging and resulting change in the apparent diffusion coefficient (ADC) of water molecules has not been demonstrated previously. In the present study, we have performed DW echo planar imaging (EPI) with and without MT preparation pulse to see the effect of macromolecular signal suppression on ADC. A total of 10 normal volunteers and 20 patients with different intracranial cystic lesions [abscesses (n=10), cystic tumors (n=5), arachnoid cysts (n=5)] were subjected to DW imaging (b=0 and 1000 s/mm(2)) with and without MT saturation pulse. Analysis of region of interest (ROI) from different areas of white matter in normal volunteers and in the wall and cavity of cystic lesions in patients was carried out for calculating the ADC values. We found a significant increase (P<.05) in the ADC values in brain parenchyma and cavity of those intracranial cystic lesions having considerable amount of proteins after the application of MT preparation pulse except for arachnoid cysts. This is due to the size of the macromolecules present in the normal and abnormal tissue. Our studies suggest that this technique is likely to give a novel image contrast and may be of value in improving the tissue specificity in pathologies associated with variable macromolecular size.