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Chemical exchange saturation transfer (CEST) MRI is a non-invasive molecular imaging technique with potential applications in pre-clinical and clinical studies. Applications of amide proton transfer-weighted (APT-w), glutamate-weighted (Glu-w) and creatine-weighted (Cr-w) CEST, among others, have been reported. In general, CEST data are acquired at multiple offset-frequencies. In reported studies, different offset-frequency step sizes and interpolation methods have been used during B 0 inhomogeneity correction of data. The objective of the current study was to evaluate the effects of different step sizes and interpolation methods on CEST value computation. In the current study, simulation (Glu-w, Cr-w and APT-w) and experimental data from the brain were used. Experimental CEST data (Glu-w) were acquired from human volunteers at 7 T and brain tumor patients (APT-w) at 3 T. During B 0 inhomogeneity correction, different interpolation methods (polynomial [degree-1, 2 and 3], cubic-Hermite, cubic-spline and smoothing-spline) were compared. CEST values were computed using asymmetry analysis. The effects of different step sizes and interpolation methods were evaluated using coefficient of variation (CV), normalized mean square error (nMSE) and coefficient of correlation parameters. Additionally, an optimum interpolation method for APT-w values was selected based upon fitting accuracy, T-test, receiver operating characteristic analysis, and its diagnostic performance in differentiating low-grade and high-grade tumors. CV and nMSE increase with an increase in step size irrespective of the interpolation method (except for cubic-Hermite and cubic-spline). The nMSE of Cr-w and Glu-w CEST values were least for polynomial (degree-2 and 3). The quality of Glu-w CEST maps became coarse with the increase in step size. There was a significant difference (P < .05) between low-grade and high-grade tumors using polynomial interpolation (degree-1, 2 and 3); however, linear interpolation outperforms other methods for APT-w data, providing the highest sensitivity and specificity. In conclusion, depending upon the saturation parameters and field strength, optimization of step size and interpolation should be carried out for different CEST metabolites/molecules. Glu-w, Cr-w and APT-w CEST data should be acquired with a step size of between 0.2 and 0.3 ppm. For B 0 inhomogeneity correction, polynomial (degree-2) should be used for Glu-w and Cr-w CEST data at 7 T and linear interpolation should be used for APT-w data at 3 T for a limited frequency range., (© 2021 John Wiley & Sons, Ltd.)

Background: Radiomics in neuroimaging has gained momentum as a noninvasive prediction tool not only to differentiate between types of brain tumors, but also to create phenotypic signatures in neurological and neuropsychiatric disorders. However, there is currently little understating about the robustness and reproducibility of radiomic features in a baseline normative population., Purpose: To investigate the intra- and interscanner reproducibility, spatial robustness, and sensitivity of radiomics on fluid attenuation inversion recovery (FLAIR) images, which are widely used in neuro-oncology investigations., Study Type: Retrospective., Population: Three separate datasets of healthy controls: 1) 87 subjects (age range 12-64 years), 2) intrascanner three timepoints, four subjects, and 3) interscanner, eight subjects at three different sites., Field Strength/sequence: T 2 -weighted FLAIR at 1.5T and 3.0T., Assessment: Spatial variance across lobes, and their relation with age/gender, intra- and inter-scanner reproducibility (with and without site harmonization) of radiomics., Statistical Tests: Analysis of variance (ANOVA), interclass correlation (ICC), coefficient of variation (CoV), Bland-Altman analysis., Results: Analysis of data revealed no differences between genders; however, multiple radiomic features were highly associated with age (P < 0.05). Spatial variability was also evaluated where only 29.04% gray matter and 38.7% white matter features demonstrated an ICC >0.5. Furthermore, the results demonstrated intra-scanner reliability (ICC >0.5); however, inter-scanner reproducibility was poor, with ICC < 0.5 for 82% gray matter and 78.5% white matter features. The inter-scanner reliability improved (ICC < 0.5 for 39.67% gray matter and 38% white matter features) using site-harmonization techniques., Data Conclusion: These findings suggest that, accounting for age, spatial locations in radiomics-based analysis and use of intersite radiomics harmonization is crucial before interpreting these features for pathological inference. Level of Evidence 3. Technical Efficacy Stage 1. J. MAGN. RESON. IMAGING 2021;53:394-407., (© 2020 International Society for Magnetic Resonance in Medicine.)

Purpose: T1-contrast and T2-flair images of magnetic resonance imaging (MRI) are commonly fused with computed tomography (CT) and used for delineation of postoperative residual tumor and bed after surgery in patients with glioblastoma multiforme (GBM). Our prospective study was aimed to see the feasibility of incorporating perfusion MRI in delineation of brain tumor for radiotherapy planning and its implication on treatment volumes., Methods: Twenty-four patients with histopathologically proven GBM were included in the study. All patients underwent radiotherapy planning with a contrast CT scan. In addition to radiotherapy (RT) planning protocol, T1-perfusion MRI was also done in all patients in the same sitting. Perfusion imaging was processed on the in-house-developed JAVA-based software. The images of CT and MRI were sent to the iPlan planning system (Brainlab AG, GmbH) using a Digital Imaging and Communications in Medicine - Radiation Therapy (DICOM-RT) protocol. A structure of gross tumor volume (GTV)-perfusion (GTV-P) was delineated based only on the MRI perfusion images. Subsequently, GTV-P and GTV were fused together to make GTV-summated (GTV-S). Using existing guidelines, GTV-S was expanded to form clinical target volume-summated (CTV-S) and planning target volume-summated (PTV-S). The increment in each of the summated volumes as compared to baseline volume was noted. The common overlap volume (GTVO) between GTV and GTV-P was calculated using intersection theory (GTV n GTV-P = GTVO [Overlap])., Results: Mean ± standard deviation (cc) for GTV, GTV-P, and GTVO was 46.3 ± 33.4 cc (range: 5.2 cc-108.0 cc), 26.0 ± 26.2 (range: 6.6 cc-10.3.0 cc), and 17.5 ± 22.3 cc (range: 10.0 cc-92 cc), respectively. Median volume (cc) for GTV, GTV-P, and GTVO was 40.8 cc, 17.2 cc, and 8.0 cc, respectively. Mean absolute and relative increments from GTV to that of GTV-S were 8.5 ± 8.2 cc and 27.2 ± 30.9%, respectively. Average CTV volume (cc) was 230.4 ± 115.3 (range: 80.8 cc-442.0 cc). Mean and median CTV-S volumes were 262.0 ± 126.3 cc (range: 80.8 cc-483.0 cc) and 221.0 cc, respectively. The increment in the mean CTV volume (with respect to CTV created from GTV-S) was 15.2 ± 15.9%. Mean and median PTV volumes created on the summated CTV were 287.1 ± 134.0 cc (range: 118.9 cc-576.0 cc) and 258.0 cc, respectively. Absolute and relative increments in PTV volume, while incorporating the perfusion volume, were 31.3 ± 28.9 cc and 12.5 ± 13.3%, respectively. Out of the total of 24 patients, perfusion scanning did not do any increment in GTV in five patients., Conclusions: Our study is the first to present the feasibility and the outcome of contouring on perfusion imaging and its overlay on regular MRI images. The implications of this on long-term outcome and control rates of glioblastoma patients need to be seen in future studies., Competing Interests: None

Purpose: To evaluate the role of amide proton transfer-weighted (APT-w) magnetic resonance imaging (MRI) in differentiating neoplastic and infective mass lesions using different contrast normalizations, region of interest (ROI) selection, and histogram analysis., Procedures: Retrospective study included 32 treatment-naive patients having intracranial mass lesions (ICMLs): low-grade glioma (LGG) = 14, high-grade glioma (HGG) = 10, and infective mass lesions = 8. APT-w MRI images were acquired along with conventional MRI images at 3 T. APT-w contrast, corrected for B 0 -field inhomogeneity, was computed and optimized with respect to different types of normalizations. Different ROIs on lesion region were selected followed by ROI analysis and histogram analysis. Statistical analysis was performed using Shapiro-Wilk's test, t tests, ANOVA with Tukey's post hoc test, and receiver operation characteristic (ROC) analysis., Results: ICMLs showed significantly (p < 0.01) higher APT-w contrast in lesion compared with contralateral side. There was a substantial overlap between mean APT-w contrast of neoplastic and infective mass lesions as well as among different groups of ICMLs irrespective of ROI selection and normalizations. APT-w contrast (using type 4 normalization: normalized with reference signal at negative offset frequency and APT-w contrast in normal-appearing white matter) reduced variability of APT-w contrast across different subjects, and overlap was less compared with other types of normalizations. There was a significant difference (p < 0.05) between neoplastic and infective mass lesions using t test for different histogram parameters of type 4 normalized APT-w contrast. ANOVA with post hoc showed significant difference (p < 0.05) for different histogram parameters of APT-w contrast (Type 4 normalization) between LGG and HGG, LGG, and infective mass lesion. Histogram parameters such as standard deviation, mean of top percentiles, and median provided improved differentiation between neoplastic and infective mass lesions compared with mean APT-w contrast. A greater number of histogram parameters of type 4 normalized APT-w contrast corresponding to active lesion region can significantly differentiate between ICMLs than other types of normalizations and ROIs., Conclusions: APT-w contrast using type 4 normalization and active lesion region (ROI-2) should be used for studying APT. APT-MRI should be combined with other MRI techniques to further improve the differential diagnosis of ICMLs.

Proton MRS ( 1 H MRS) provides noninvasive, quantitative metabolite profiles of tissue and has been shown to aid the clinical management of several brain diseases. Although most modern clinical MR scanners support MRS capabilities, routine use is largely restricted to specialized centers with good access to MR research support. Widespread adoption has been slow for several reasons, and technical challenges toward obtaining reliable good-quality results have been identified as a contributing factor. Considerable progress has been made by the research community to address many of these challenges, and in this paper a consensus is presented on deficiencies in widely available MRS methodology and validated improvements that are currently in routine use at several clinical research institutions. In particular, the localization error for the PRESS localization sequence was found to be unacceptably high at 3 T, and use of the semi-adiabatic localization by adiabatic selective refocusing sequence is a recommended solution. Incorporation of simulated metabolite basis sets into analysis routines is recommended for reliably capturing the full spectral detail available from short TE acquisitions. In addition, the importance of achieving a highly homogenous static magnetic field (B 0 ) in the acquisition region is emphasized, and the limitations of current methods and hardware are discussed. Most recommendations require only software improvements, greatly enhancing the capabilities of clinical MRS on existing hardware. Implementation of these recommendations should strengthen current clinical applications and advance progress toward developing and validating new MRS biomarkers for clinical use., (© 2019 International Society for Magnetic Resonance in Medicine.)

Background: Perilesional gliosis is an important substrate for seizures in patients harboring a calcified neurocysticercosis (NCC) lesion and magnetic resonance imaging (MRI) is useful for evaluating gliosis., Aims: The purpose of this study was to evaluate the usefulness of double-inversion recovery (DIR) sequence for identifying perilesional gliosis., Settings and Design: Hospital-based cross-sectional study., Methods and Materials: Forty-five patients with seizures were included in this study and a total of 88 calcified lesions identified on susceptibility weighted imaging (SWI) were evaluated on 3D-fluid attenuating inversion recovery (FLAIR), 3D-DIR, and 3D-postcontrast T1-weighted imaging on a 3T MRI for the presence of perilesional signal changes/enhancement. Perilesional signal was rated on a semiquantitative scale from grade 0 to 2 by independent raters., Statistical Analysis Used: Friedman, Wilcoxon signed rank, and Kappa tests were used., Results: 3D-DIR sequence performed better than both 3D-FLAIR and postcontrast 3D-T1W sequences as more number of lesions showed perilesional signal change on DIR sequence. DIR sequence showed perilesional signal abnormality in 24 lesions in which 3D-FLAIR was normal, whereas in another 18 lesions, it demonstrated perilesional signal changes better than 3D-FLAIR. In only three lesions, FLAIR was found to be superior to DIR sequence, whereas postcontrast T1W images showed rim enhancement in five cases where no perilesional signal change was seen on FLAIR/DIR sequences., Conclusions: Combining 3D-DIR with 3D-FLAIR, and postcontrast 3D-T1W sequences is beneficial for evaluation of calcified NCC lesions and 3D-DIR sequence is better than other two sequences for perilesional signal abnormalities., Competing Interests: None

Delayed brain development in perinatally HIV-infected children may affect the functional brain activity and subsequently cognitive function. The current study evaluated the functional brain activity in HIV-infected children by quantifying the amplitude of low frequency fluctuations (ALFF) and functional connectivity (FC). Additionally, correlation of ALFF and FC with cognitive measures was performed. Twenty-six HIV-infected children and 20 control children underwent neuropsychological (NP) assessment and resting-state functional magnetic resonance imaging (rs-fMRI). ALFF and FC maps were generated and group differences were analyzed using two-sample t-test. Furthermore, ALFF and FC showing significant group differences were correlated with NP scores using Pearson's correlation. Significantly lower ALFF in the left middle temporal gyrus, precentral and post central gyrus was observed in HIV-infected children compared to controls. FC was significantly reduced in the right inferior parietal, vermis, middle temporal and left postcentral regions, and significantly increased in the right precuneus, superior parietal and left middle frontal regions in HIV-infected children as compared to control. HIV-infected children showed significantly lower NP scores in various domains including closure, exclusion, memory, verbal meaning, quantity and hidden figure than controls. These waning cognitive functions were significantly associated with changes in ALFF and FC in HIV-infected children. The findings suggest that abnormal ALFF and FC may responsible for cognitive deficits in HIV-infected children. ALFF and FC in association with cognitive evaluation may provide a clinical biomarker to evaluate functional brain activity and to plan neurocognitive intervention in HIV-infected children undergoing standard treatment., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Solitary calcified neurocysticercosis is a common cause of seizures in the developing countries. Factors responsible for seizure recurrence in patients with solitary calcified neurocysticercosis are not known. We evaluated the clinical, neuroimaging and biochemical predictors of seizure recurrence., Methods: This was a prospective observational study. Patients with new-onset seizures and a solitary calcified neurocysticercosis were included. Patients were evaluated clinically; baseline electroencephalography and magnetic resonance imaging of brain were done for all patients.. The patients were followed for 1year. Seizure recurrence was defined as the recurrence of an episode of seizure at least 1 week after the initiation of the anti-epileptic drugs., Results: Fifty-four patients with a mean age of 20.43±7.34years were included. Thirteen patients developed seizure recurrence during the follow-up period. On univariate analysis, status epilepticus at presentation (p=0.025), size of the lesion >10mm (p=0.015), presence of perilesional edema (p<0.001) and scolex (p=0.033) were significantly associated with seizure recurrence. On multivariate analysis, only presence of perilesional edema (p=0.018, odds ratio=12.122, 95% confidence interval 1.521-96.639) was an independent predictor of seizure recurrence., Conclusion: Status epilepticus at presentation is associated with an increased risk of seizure recurrence. Neuroimaging features like presence of perilesional edema and scolex can similarly predict seizure recurrence. These neuroimaging features can serve as potential surrogate markers to define therapy in these patients. The findings of our study might be helpful in stratifying patients with a higher risk of seizure recurrence, especially those who may require a more aggressive management., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Pediatric HIV patients often suffer with neurodevelopmental delay and subsequently cognitive impairment. While tissue injury in cortical and subcortical regions in the brain of adult HIV patients has been well reported there is sparse knowledge about these changes in perinatally HIV infected pediatric patients. We analyzed cortical thickness, subcortical volume, structural connectivity, and neurocognitive functions in pediatric HIV patients and compared with those of pediatric healthy controls. With informed consent, 34 perinatally infected pediatric HIV patients and 32 age and gender matched pediatric healthy controls underwent neurocognitive assessment and brain magnetic resonance imaging (MRI) on a 3 T clinical scanner. Altered cortical thickness, subcortical volumes, and abnormal neuropsychological test scores were observed in pediatric HIV patients. The structural network connectivity analysis depicted lower connection strengths, lower clustering coefficients, and higher path length in pediatric HIV patients than healthy controls. The network betweenness and network hubs in cortico-limbic regions were distorted in pediatric HIV patients. The findings suggest that altered cortical and subcortical structures and regional brain connectivity in pediatric HIV patients may contribute to deficits in their neurocognitive functions. Further, longitudinal studies are required for better understanding of the effect of HIV pathogenesis on brain structural changes throughout the brain development process under standard ART treatment.

Background and Aims: Minimal hepatic encephalopathy (MHE) is the mildest form of hepatic encephalopathy (HE) and is characterized by deficits in neurocognitive performance without any clinical symptoms of HE. In the current study, we aim to evaluate and compare the neurocognitive, biochemical, and brain magnetic resonance (MR) imaging changes between patients with cirrhotic MHE and extrahepatic portal vein obstruction (EHPVO) MHE., Methods: Thirty-three cirrhotic and 14 EHPVO patients were diagnosed with MHE and were included in the analysis along with 24 normal healthy volunteers. All subjects underwent MR imaging including diffusion tensor imaging and proton MR spectroscopy ( 1 H-MRS) followed by cognitive assessments, critical flicker frequency (CFF) measurements, quantification of blood ammonia, and serum proinflammatory cytokine levels., Results: We observed abnormal neurocognitive functions and CFF measurements in both cirrhotic MHE and EHPVO MHE patients as compared with controls. Significantly increased blood ammonia, serum proinflammatory cytokines (IL-6, TNF-α) level, mean diffusivity in multiple brain sites, 1 H-MRS derived glutamate/glutamine (Glx)/creatine (Cr), and significantly decreased 1 H-MRS derived myo-inositol/Cr were observed in both cirrhotic MHE and EHPVO MHE compared with those of controls. Choline/Cr level was significantly decreased in cirrhotic MHE as compared with controls and EHPVO MHE., Conclusions: Cirrhotic MHE showed more severe changes on mean diffusivity in multiple brain sites and inflammation as compared with EHPVO MHE. This study confirms that there are significant difference in neurocognitive, biochemical, and MR profile between cirrhotic MHE and EHPVO MHE, which may help to understand the pathophysiologies of these two types of MHE and may contribute to improve their clinical managements., (© 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction: The resting state functional MRI (rsfMRI) approach is useful to explore the brain's functional organization in health and disease conditions. In this study, using rsfMRI the alteration in brain due to vitamin B12 deficiency and reversibility of these alterations following therapy was studied., Methods: Thirteen patients with clinical and biochemical evidence of vitamin B12 deficiency were recruited in this study. Fifteen age and sex matched healthy controls were also included. Patients and controls were clinically evaluated using neuropsychological test (NPT). The analysis was carried out using regional homogeneity (ReHo) and low frequency oscillations (LFO) of BOLD signals in resting state. Six patients were also evaluated with rsfMRI and NPT after 6 weeks replacement therapy., Results: ReHo values in patients with vitamin B12 deficiency were significantly lower than controls in the entire cerebrum and the brain networks associated with cognition control, i.e., default mode, cingulo-opercular and fronto-parietal network. There was no significant difference using LFO and it did not show significant correlations with NPT scores. ReHo showed significant correlation with NPT scores. All the 6 patients showed increase in ReHo after replacement therapy., Conclusion: We conclude that brain networks associated with cognition control are altered in patients with vitamin B12 deficiency, which partially recover following six weeks of replacement therapy. This is the first study to evaluate the rsfMRI in the light of clinical neuropsychological evaluation in patients. rsfMRI may be used as functional biomarker to assess therapeutic response in vitamin B12 deficiency patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Acute-on-chronic liver failure (ACLF) is a form of liver disease with high short-term mortality. ACLF offers considerable potential to affect the cortical areas by significant tissue injury due to loss of neurons and other supporting cells. We measured changes in cortical thickness and metabolites profile in ACLF patients following treatment, and compared it with those of age matched healthy volunteers., Methods: For the cortical thickness analysis we performed whole brain high resolution T1-weighted magnetic resonance imaging (MRI) on 15 ACLF and 10 healthy volunteers at 3T clinical MR scanner. Proton MR Spectroscopy ((1)H MRS) was also performed to measure level of altered metabolites. Out of 15 ACLF patients 10 survived and underwent follow-up study after clinical recovery at 3 weeks. FreeSurfer program was used to quantify cortical thickness and LC- Model software was used to quantify absolute metabolites concentrations. Neuropsychological (NP) test was performed to assess the cognitive performance in follow-up ACLF patients compared to controls., Results: Significantly reduced cortical thicknesses in multiple brain sites, and significantly decreased N-acetyl aspartate (NAA), myo-inositol (mI) and significantly increased glutamate/glutamine (glx) metabolites were observed in ACLF compared to those of controls at baseline study. Follow-up patients showed significant recovery in cortical thickness and Glx level, while NAA and mI were partially recovered compared to baseline study. When compared to controls, follow-up patients still showed reduced cortical thickness and altered metabolites level. Follow-up patients had abnormal neuropsychological (NP) scores compared to controls., Conclusions: Neuronal loss as suggested by the reduced NAA, decreased cellular density due to increased cerebral hyperammonemia as supported by the increased glx level, and increased proinflammatory cytokines and free radicals may account for the reduced cortical thickness in ACLF patients. Presence of reduced cortical thickness, altered metabolites and abnormal NP test scores in post recovery subjects as compared to those of controls is associated with incomplete clinical recovery. The current imaging protocol can be easily implemented in clinical settings to evaluate and monitor brain tissue changes in patients with ACLF during the course of treatment.

Albendazole is the drug of choice for Taenia solium infection. Concomitant administration of steroid has been advocated to avoid adverse reactions to albendazole therapy in neurocysticercosis. Some T. solium cysticerci (larvae) respond to albendazole therapy while others do not and the reasons remain unexplained. We hypothesise that the immune response differs between treatment responder and non-responder cysticerci and this may determine the outcome. Twenty swine naturally infected with T. solium were purchased from the market and the infection was confirmed by magnetic resonance imaging. Swine were divided into two groups; swine in group 1 were treated with albendazole and those in group 2 were treated with albendazole plus steroid (prednisolone). All the animals underwent follow-up MRIs at 6 and 12 weeks after start of therapy and were then sacrificed. Tissues surrounding the cysticerci were collected and studied for the expression of different cytokines by reverse transcriptase PCR and ELISA. Albendazole therapy was found to be more effective in parasite killing than albendazole plus steroid (94.11% versus 70.96%, P=0.011). Albendazole therapy provoked a pro-inflammatory, Th1 (IFN-γ) and pleiotropic (IL-6) cytokine response around the dead cysticerci. Despite a heavy parasite burden in the brain, all the pigs treated with albendazole plus steroid survived. In this group of animals, a mixed pro-inflammatory Th1, Th2 (IL-4) and regulatory cytokine (IL-10) response was associated with responder cysticerci. Further, Th2 and regulatory cytokine responses were associated with non-responder cysticerci., (Copyright © 2015 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.)

Introduction: Vitamin B12 deficiency may cause neural tissue damage. Even in advanced stages, conventional imaging of brain usually appears normal in vitamin B12 deficient patients. The aim of this study was to assess the structural and functional changes in brain of patients with vitamin B12 deficiency before and after six weeks of vitamin B12 supplementation using diffusion tensor imaging and pseudo-continuous arterial spin labelling (PCASL)., Methods: MR imaging including DTI and PCASL and neuropsychological tests (NPT) were performed in 16 patients with vitamin B12 deficiency and 16 controls before and after 6weeks of therapy. Cerebral blood flow (CBF) derived from PCASL and DTI indices was calculated in brain of patients with vitamin B12 deficiency and controls., Results: Patient with vitamin B12 deficiency showed altered neuropsychological scores and altered CBF as well as fractional anisotropy (FA) values in various brain regions as compared with controls. Both CBF values and neuropsychological scores showed complete reversibility at 6weeks post therapy. Though FA values showed significant recovery, it failed to show complete recovery., Conclusion: Our results suggest that micro-structural recovery lags behind functional recovery in patients with vitamin B12 deficiency following therapy and CBF change may be used as an early predictor of complete recovery in patients with B12 deficiency., (Copyright © 2015. Published by Elsevier Inc.)

Background and Purpose: Studies of brain tumors have identified altered tissue metabolism and water diffusion in MRI normal appearing tissue regions. In this retrospective study the relationship of these imaging measures with tumor grade in gliomas was investigated., Methods: MR spectroscopic imaging of whole brain and mean diffusivity (MD) measurements were obtained in subjects with untreated glioma and from normal control subjects. Mean metabolite values for N-acetylaspartate (NAA), total creatine (Cre), and total choline (Cho) were obtained in gray- and white-matter regions for the hemisphere contralateral to the tumor location, and MD values were obtained from contralateral normal-appearing white matter. Analyses tested for differences in mean values between subject groups while accounting for age., Results: Analysis demonstrated increased NAA/Cre and MD, and decreased Cho/NAA for all tumor grades relative to control values. Differences between tumor grades were also observed for NAA, NAA/Cre, and Cho/NAA. Abnormal values of water diffusion were also observed, but with only a weak association between alterations in diffusion and tissue metabolites., Conclusions: This study supports previous observations of altered tissue metabolism and water diffusion in normal-appearing white matter while additionally finding differences of metabolite values in gray matter and an association with tumor grade., (Copyright © 2013 by the American Society of Neuroimaging.)

Purpose: Magnetic resonance (MR) imaging and computed tomography (CT) are used almost exclusively in radiation therapy planning of glioblastoma multiforme (GBM), despite their well-recognized limitations. MR spectroscopic imaging (MRSI) can identify biochemical patterns associated with normal brain and tumor, predominantly by observation of choline (Cho) and N-acetylaspartate (NAA) distributions. In this study, volumetric 3-dimensional MRSI was used to map these compounds over a wide region of the brain and to evaluate metabolite-defined treatment targets (metabolic tumor volumes [MTV])., Methods and Materials: Volumetric MRSI with effective voxel size of ∼1.0 mL and standard clinical MR images were obtained from 19 GBM patients. Gross tumor volumes and edema were manually outlined, and clinical target volumes (CTVs) receiving 46 and 60 Gy were defined (CTV46 and CTV60, respectively). MTVCho and MTVNAA were constructed based on volumes with high Cho and low NAA relative to values estimated from normal-appearing tissue., Results: The MRSI coverage of the brain was between 70% and 76%. The MTVNAA were almost entirely contained within the edema, and the correlation between the 2 volumes was significant (r=0.68, P=.001). In contrast, a considerable fraction of MTVCho was outside of the edema (median, 33%) and for some patients it was also outside of the CTV46 and CTV60. These untreated volumes were greater than 10% for 7 patients (37%) in the study, and on average more than one-third (34.3%) of the MTVCho for these patients were outside of CTV60., Conclusions: This study demonstrates the potential usefulness of whole-brain MRSI for radiation therapy planning of GBM and revealed that areas of metabolically active tumor are not covered by standard RT volumes. The described integration of MTV into the RT system will pave the way to future clinical trials investigating outcomes in patients treated based on metabolic information., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Tuberculosis (TB) has shown a resurgence in nonendemic populations in recent years and accounts for 8 million deaths annually in the world. Central nervous system involvement is one of the most serious forms of this infection, acting as a prominent cause of morbidity and mortality in developing countries. The rising number of cases in developed countries is mostly attributed to factors such as the pandemic of acquired immunodeficiency syndrome and increased migration in a globalized world. Mycobacterium TB is responsible for almost all cases of tubercular infection in the central nervous system. It can manifest in a variety of forms as tuberculous meningitis, tuberculoma, and tubercular abscess. Spinal infection may result in spondylitis, arachnoiditis, and/or focal intramedullary tuberculomas. Timely diagnosis of central nervous system TB is paramount for the early institution of appropriate therapy, because delayed treatment is associated with severe morbidity and mortality. It is therefore important that physicians and radiologists understand the characteristic patterns, distribution, and imaging manifestations of TB in the central nervous system. Magnetic resonance imaging is considered the imaging modality of choice for the study of patients with suspected TB. Advanced imaging techniques including magnetic resonance perfusion and diffusion tensor imaging may be of value in the objective assessment of therapy and to guide the physician in the modulation of therapy in these patients.

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., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Infection of the central nervous system can be life-threatening and hence requires early diagnostic support for its optimal management. Routine definitive laboratory diagnostic tests can be time-consuming and delay definitive therapy. Noninvasive imaging modalities have established themselves in the diagnosis of various neurologic diseases. In this article, a pragmatic review of the current role of magnetic resonance spectroscopy in the diagnosis and management of intracranial infections is addressed., (Copyright © 2013 Elsevier Inc. All rights reserved.)

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 imaging (DTI) was performed on 25 patients with neurocysticercosis (NCC). The aim of this study was to investigate the changes in DTI measures during the evolutionary course of NCC lesions from vesicular to calcified stage in the brain. DTI measures were quantified from the NCC lesions of all patients. On the basis of conventional imaging findings, NCC lesions were classified into vesicular, vesicular colloidal, granular nodular and calcified stages. Significant inverse correlation was observed between the evolutionary stage of NCC lesion and mean diffusivity (MD; r=-0.748, P<0.001) and spherical anisotropy (CS; r=-0.585, P<.001) values. Significant direct correlations were observed between evolutionary stages of NCC lesion and mean fractional anisotropy (FA; r=0.575, P<0.001), linear anisotropy (CL; r=0.478, p<0.001) and planar anisotropy (CP; r=0.561, p<0.001) values. Successive decrease in MD values calculated from NCC lesions was observed, moving from vesicular to granular nodular stage. On FA, CL and CP maps, a significant increase in signal intensity value was observed in calcified as compared to other stages. We conclude that DTI measures may indicate the evolutionary changes in NCC from vesicular to calcified stage., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The study was aimed to test the feasibility of utilizing an algorithmically determinable stable fiber mass (SFM) map obtained by an unsupervised principal eigenvector field segmentation (PEVFS) for automatic delineation of 18 white matter (WM) tracts: (1) corpus callosum (CC), (2) tapetum (TP), (3) inferior longitudinal fasciculus (ILF), (4) uncinate fasciculus (UNC), (5) inferior fronto-occipital fasciculus (IFO), (6) optic pathways (OP), (7) superior longitudinal fasciculus (SLF), (8) arcuate fasciculus (AF), (9) fornix (FX), (10) cingulum (CG), (11) anterior thalamic radiation (ATR), (12) superior thalamic radiation (STR), (13) posterior thalamic radiation (PTR), (14) corticospinal/corticopontine tract (CST/CPT), (15) medial lemniscus (ML), (16) superior cerebellar peduncle (SCP), (17) middle cerebellar peduncle (MCP) and (18) inferior cerebellar peduncle (ICP). Diffusion tensor imaging (DTI)-derived fractional anisotropy (FA) and the principal eigenvector field have been used to create the SFM consisting of a collection of linear voxel structures which are grouped together by color-coding them into seven natural classes to provide PEVFS signature segments which greatly facilitate the selection of regions of interest (ROIs) for fiber tractography using just a single mouse click, as compared with a manual drawing of ROIs in the classical approach. All the 18 fiber bundles have been successfully reconstructed, in all the subjects, using the single ROIs provided by the SFM approach, with their reproducibility characterized by the fact that the ROI selection is user independent. The essentially automatic PEVFS method is robust, efficient and compares favorably with the classical ROI methods for diffusion tensor tractography (DTT)., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Neurocysticercosis (NCC) is the most frequent parasitic infection of the central nervous system caused by the larvae of Taenia solium. The prevalence of NCC is obscured due to variations in the methods used for epidemiological studies and often asymptomatic manifestation. The present study was conducted on 595 apparently healthy individuals belonging to the pig farming community of northern India to estimate the prevalence of asymptomatic NCC and to evaluate risk factors based on questionnaires. Diagnosis of NCC was based on neuroimaging, immunological and epidemiological criteria. Asymptomatic NCC was detected in 90 (15.1%) of 595 individuals. The evaluation of risk factors showed that age >15 years (P=0.001), intake of raw vegetables (P=0.025) and undercooked pork (P=0.005), lack of safe drinking water (P=0.003), inadequate drainage system (P=0.049), no separate place for pigs (P≤0.001), NCC related active epilepsy in the family (P≤0.001) were significantly associated with asymptomatic NCC. The present study shows high prevalence of asymptomatic NCC in pig farming community of northern India. Further, asymptomatic NCC is associated with most variables of poor socio-economic parameters., (Copyright © 2011 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Minimal hepatic encephalopathy (MHE) and hyperammonemia are seen in patients with extrahepatic portal venous obstruction (EHPVO). Inflammation has been shown to play an important role in the pathogenesis of hepatic encephalopathy in cirrhotics. This study assessed serum pro-inflammatory cytokines and their correlation with hyperammonemia, (1)H-magnetic resonance (MR) spectroscopy-derived brain glutamine, and diffusion tensor imaging (DTI)-derived metrics in patients with EPHVO, with and without MHE., Methods: Neuropsychological tests, DTI, (1)H-MR spectroscopy, and estimation of blood ammonia and pro-inflammatory cytokines (tumor necrosis factor-α[TNF-α] and interleukin-6 [IL-6]) were done in 20 patients with EHPVO and eight healthy controls., Results: Pro-inflammatory cytokines (TNF-α and IL-6), blood ammonia, brain glutamine, and mean diffusivity were increased in both patient groups, as compared to controls. Patients with MHE (n-12) had significantly higher TNF-α, IL-6, blood ammonia, brain glutamine, and mean diffusivity, signifying brain edema, than controls. A significant, positive correlation was seen between TNF-α and IL-6 and between blood ammonia and TNF-α, IL-6, and brain glutamine. Significant, positive correlations of TNF-α, IL-6, and blood ammonia with mean diffusivity values were seen in various brain regions, including spectroscopy voxel-derived mean diffusivity., Conclusion: Patients with extrahepatic portal vein obstruction have inflammation and hyperammonemia made evident by higher blood TNF-α, IL-6, ammonia, and brain glutamine levels. A significant correlation between hyperammonemia, pro-inflammatory cytokines, and cerebral edema on DTI in various brain regions suggests that both these factors play a role in the pathogenesis of MHE in these patients., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Purpose: Spina bifida cystica (SBC) is a group of neurodevelopmental defects caused by improper neural tube closure, which may be responsible for deficits in cognitive functions. The purpose of this study was to examine changes in normal appearing deep gray and white matter brain regions in SBC patients compared with controls through diffusion tensor imaging (DTI) and correlate these changes with neuropsychometric tests., Methods: Conventional magnetic resonance imaging and neuropsychometric tests were performed on 13 patients and ten controls. DTI-derived fractional anisotropy (FA) and mean diffusivity (MD) were quantified in different brain regions in controls and patients., Results: Significantly decreased FA was observed in caudate nuclei, putamen, genu, splenium, and increased FA was found in middle cerebellar peduncle (MCP) in patients compared with controls. We observed significantly increased MD in genu and splenium. However, increased MD was found in fornix of patients compared with controls. Majority of neuropsychological tests were found to be significantly impaired and some of these showed significant correlation with DTI metrics in genu, splenium, and MCP in these patients., Conclusions: We conclude that DTI metrics are significantly abnormal in deep gray matter nuclei, genu, splenium, and MCP in SBC patients and may provide microstructural basis for neuropsychological abnormalities in these patients.

This study aimed to demonstrate age-related and gender-related changes in diffusion tensor imaging (DTI) indices of deep grey matter (GM) nuclei of the normal human brain. DTI was performed on 142 subjects (age: 10-52 years). Regions of interest were placed on the caudate nucleus (CN), putamen, globus pallidus, frontal white matter (WM), occipital WM, anterior and posterior limb of internal capsule, genu of the corpus callosum and splenium in all participants. The quadratic regression model was used to describe age-related and gender-related changes in DTI indices for GM and WM. We observed increased fractional anisotropy (FA) values with age up to adulthood in GM, and a rise up to the third decade of life followed by a decrease in FA for WM. We observed higher FA values in males compared to females in CN and all WM regions. Decreased mean diffusivity with age was observed in GM and WM irrespective of gender. This normative data may be valuable in the diagnosis of neurodegenerative diseases., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Rationale and Objectives: To demonstrate the correlation of proinflammatory cytokines (PCs), intercellular adhesion molecule (sICAM-1), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) in CSF of tuberculous meningitis (TBM) patients with magnetic resonance imaging (MRI) including diffusion tensor imaging (DTI) and also to look for the changes in imaging parameters after antitubercular treatment (ATT) in these patients., Materials and Methods: Forty patients with TBM (median age, 27.7 years) and 30 age-/sex-matched controls were included in this study. PCs were quantified from the CSF of TBM patients at the time of hospital admission (baseline). MRI including DTI was performed at the time of baseline study and 6 months after ATT., Results: Significant positive correlation of PCs with fractional anisotropy (FA) values and post-contrast signal intensity (PCSI) collected from cerebral cortical regions was observed in TBM patients. A significant positive correlation of FA values with PCSI was also observed at both time points in patient groups. At baseline study significantly high FA values were observed in patients compared to controls. Significantly decreased FA values and PCSI were observed in the patients after 6 months of ATT compared to the baseline study., Conclusions: Results of this study suggest that the DTI-derived anisotropy have the potential to delineate meningeal inflammation and it may be used in assessment of therapeutic response in TBM patients as an additional method to conventional imaging., (Copyright 2010 AUR. Published by Elsevier Inc. All rights reserved.)

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.

Purpose: To evaluate T(2)-relaxation changes in patients with minimal hepatic encephalopathy (MHE) using T(2) relaxometry and to correlate T(2) values with brain metabolites evaluated using 2D magnetic resonance spectroscopy (MRS)., Materials and Methods: Eight MHE patients and 13 healthy subjects were evaluated using T(2) relaxometry, and eight patients and nine healthy subjects underwent 2D MRS in right frontal and left occipital regions. Whole-brain T(2)-relaxation maps were compared between MHE and control subjects using analysis-of-covariance, with age and gender included as covariates. T(2) values derived from the right frontal and left occipital lobes were correlated with the metabolite ratios., Results: Multiple brain regions including anterior and mid cingulate cortices, right anterior and left posterior insular cortices, right prefrontal, medial frontal, and right superior temporal cortices showed significantly increased T(2) values in MHE patients compared to control subjects. MRS showed significantly increased ratios of glutamine/glutamate (Glx) and decreased ratios of myo-inositol, taurine, choline, and myo-inositol/choline (mICh) with respect to creatine (Cr&#95;d) in patients compared to controls. Frontal Glx/Cr&#95;d showed significantly positive correlation with T(2) values., Conclusion: MHE patients showed significantly increased T(2) values in multiple brain regions reflecting increased free water content and T(2) values in frontal lobe correlated with the increased Glx/Cr&#95;d ratio.

Aim: To compare changes in apparent diffusion coefficient (ADC) in neonatal meningitis using serial diffusion-weighted imaging (DWI)., Method: Thirty neonates with meningitis and 12 age/sex-matched controls were studied using DWI. ADC was quantified by placing region of interest(s) on periventricular white matter during acute illness and again at 21 days. Three groups of patients were studied: those with normal findings on both conventional MRI and DWI, those with abnormal DWI only and those with abnormal conventional MRI as well as DWI. Neurodevelopment assessment was performed in controls and patients at 3 months using Indian adaptation of Bayley scales of infant development (BSID) kit., Results: Patients with neonatal meningitis with normal imaging (n = 8) showed no significant difference in ADC compared to controls. Patients showing abnormality only on DWI (n = 10) and on both conventional magnetic resonance imaging (MRI) as well as DWI (n = 12) had significantly reduced ADC (p = 0.001) than controls at baseline study. Follow-up study showed no significant differences in ADC in controls compared to any patient group. Significantly reduced neurodevelopmental scores were observed in patient groups compared to controls., Conclusion: We conclude that quantitative ADC may detect meningitis-induced hypoxia early in brain parenchyma, which may be associated with abnormal motor and mental development.

Diffuse axonal injury (DAI) that follows traumatic brain injury (TBI) is thought to be a major contributor to neurocognitive dysfunction that sometimes follows TBI. Conventional magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and neuropsychological tests (NPT) were performed on 38 TBI patients [hemorrhagic DAI (H-DAI, n=8), non-hemorrhagic (Nh-DAI, n=7), with no apparent DAI on conventional MRI (NA-DAI, n=23)] with a Glasgow Coma Scale score ranging between 9 and 13. The fractional anisotropy (FA) and mean diffusivity (MD) were quantified from different regions of the corpus callosum (CC), and peri-ventricular white matter (PWM) within 5-14 days and 6 months following TBI. Patients in all three groups showed decreased FA in the anterior limb of the internal capsule (ALIC) and the posterior limb of the internal capsule (PLIC), while the genu of the CC showed a decrease in the H-DAI group during the early period following TBI that persisted 6 months later, which appeared to be consistent with axonopathy. In patients without abnormalities on conventional MRI and DTI in the initial phase, a significant decrease in FA and increase in MD were observed in a few regions of the CC at 6 months, which was suggestive of demyelination/gliosis. The changes in FA and MD in the CC and PWM at 6 months follow-up showed significant correlation with some of the NPT performed in the three groups. DTI demonstrates axonopathy in the acute stage, as well as at secondary stages, at 6 months post-injury in the CC and PWM in regions of normal-appearing white matter on conventional MRI.

Background and Aims: Acute-on-chronic liver failure (ACLF), acute liver failure (ALF) and chronic liver disease (CLD) are common forms of liver failure and present with similar clinical profiles. The aim of this study was to compare brain metabolite alterations in all the three groups of patients with controls, using in vivo proton magnetic resonance spectroscopy (MRS), and to look for any significant differences in metabolites that may help in differentiating between these three conditions., Methods: Nine patients with ACLF, 10 with ALF, 10 patients with CLD and 10 age-matched controls were studied. The relative concentrations of N-acetylaspartate (NAA), choline (Cho), glutamine/glutamate (Glx) and myoinositol (mI) with respect to creatine (Cr) were measured., Results: ACLF (3.07+/-0.72), ALF (4.39+/-1.25) and CLD (3.15+/-0.69) patients exhibited significantly increased Glx/Cr ratios compared with controls (2.14+/-0.42). The NAA/Cr ratio was significantly decreased in both ACLF (mean=0.84+/-0.28) and CLD (mean=0.97+/-0.21) patients as compared with that in controls (mean=1.24+/-0.20). No significant difference among ALF, ACLF and CLD patients was noted in the Cho/Cr ratios. ACLF patients showed significantly lower mI/Cr and Glx/Cr ratios compared with the ALF group., Conclusion: In vivo proton MRS-derived cerebral metabolite alterations in hepatic encephalopathy owing to ALF are significantly different from the one owing to ACLF and CLD; these may be due to the differences in the pathogenesis of these two overlapping clinical conditions.

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.

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 > or = 0.20. Quantitation was carried out on the sub-regions of the abscess cavity with FA > or = 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.

Colloidal and calcified cysts are considered responsible for seizure in neurocysticercosis (NCC); however, calcified cysts have also been reported in asymptomatic individuals. We carried out a MRI-based study in a rural pig farming community of North India to detect the various stages, locations and numbers of the cyst in asymptomatic individuals and compared them with symptomatic NCC cases to see its association with occurrence of seizures. A total of 107 asymptomatic family members of 29 symptomatic NCC confirmed cases were evaluated clinically, immunologically and by neuroimaging for NCC. MRI-based staging of the parasite was done in both groups, and compared to look for the differences, if any. Thirty-one (29.0%) asymptomatic family members of symptomatic cases were diagnosed to have NCC. There was no difference in proportion of colloidal/degenerating and calcified stages of the parasite between symptomatic and asymptomatic groups; however, significantly higher proportion of the asymptomatic populations had vesicular stage of the parasite (P=0.029). Our findings show that a large number of individuals harboring different stages of cysticerci in their brain remain symptoms free and question the belief that the degenerating/calcified stages of the parasite are primarily responsible for seizure occurrence in NCC.

Purpose: To prospectively perform a direct measurement of fractional anisotropy (FA) and mean diffusivity (MD) in cortical lesions of patients with multiple sclerosis (MS)., Materials and Methods: The study was approved by the institutional review board and was HIPAA compliant; informed consent was obtained. Magnetic resonance (MR) images, including double inversion-recovery (DIR), phase-sensitive inversion-recovery (PSIR), and diffusion-tensor images, were acquired from nine MS patients with cortical lesions (five women, four men; median age, 47 years) and nine age- and sex-matched volunteer control subjects. Following nonlinear elastically constrained image registration for aligning diffusion-weighted images to DIR images, maps of FA and MD were computed for each subject. Cortical lesions were identified on DIR images and validated by using PSIR images. The diffusion-tensor imaging maps were then overlaid on the coregistered DIR images, and mean FA and MD values were measured in regions of interest drawn on the cortical lesions. Differences between normal gray matter (GM) and cortical lesions were evaluated by using the generalized estimating equation. FA and MD histograms of whole brain and GM (global analysis) in healthy control subjects and MS patients were also computed for comparison with those in previously published studies., Results: FA and MD values were significantly higher in cortical lesions compared with similar regions in healthy control subjects. Histogram peak FA was significantly decreased and peak MD was significantly increased in patients relative to control subjects., Conclusion: DIR and PSIR combined with nonlinear image registration allowed direct focal measurement of FA and MD in cortical lesions., ((c) RSNA, 2008.)

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.

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., ((c) 2006 Wiley-Liss, Inc.)

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.

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.

Objective: This study was performed to evaluate the role of diffusion-weighted imaging (DWI) in the diagnosis of Japanese encephalitis (JE) and to look for any relationship of the apparent diffusion coefficient (ADC) values with duration of the illness., Methods: We performed DWI in fourteen patients of JE. T2 weighted (T2W) and DWI were compared for number and location of lesions in all patients. Based on imaging patients were divided in three groups: group 1 (n=9) showing more lesions on DWI compared with T2W images, group 2 (n=3) with equal number of lesions on T2W and DWI and group 3 (n=2) with lesions more pronounced on T2W than DWI. ADC values were computed for all the lesions. The time interval between onset of neurologic signs/symptoms and MRI were charted and correlated with ADC values., Results: DWI was helpful in making early diagnosis of JE by showing characteristic involvement of bilateral thalami in four patients. Nine out of fourteen patients showed additional lesions on DWI. ADC from lesions in groups I, II and III measured 0.648 +/- 0.099 x 10 mm/s, 0.739 +/- 0.166 x 10 mm/s and 1.123 +/- 0.185 x 10 mm/s respectively. The ADC from the lesions in group 1 was significantly lower compared with group 2 (P value <0.05) while it was higher in group 3 lesions compared with the other two groups. There was a significant direct correlation of ADC values with the disease duration in these cases (r=0.847, P <0.01)., Conclusions: DWI is helpful in early diagnosis and characterization of the duration of the lesions in JE.

Purpose: To examine whether all the histopathologically seen features of cysticercus cysts excised from brain of swine naturally infected with neurocysticercosis during its evolution are actually visible on magnetic resonance imaging (MRI)., Materials and Methods: Five swine naturally infected with cerebral cysticercosis were subjected to fast spin-echo (SE) T2, SE T1, fluid attenuated inversion recovery imaging, T1-weighted magnetization transfer (MT), and postcontrast T1-weighted MT sequences on MRI. These animals were sacrificed after imaging and ex vivo imaging of the intact excised brain using the same imaging protocol was also performed. Grossing of these brains was done similar to the ex vivo imaging planes. Numeral density and external appearance of each cyst and scolex were evaluated on each pulse sequence. Amount of pericystic edema, if present, was also assessed. On histopathology, cellular characteristics, inflammatory response, and the extent of edema, if present, in the brain parenchyma around the cysts were graded. Cysts were categorized into viable, early, and late degenerated on histopathology. The MRI features of each cyst were correlated with their histopathologic findings., Results: Out of 31 cysts, eight were found to be viable, 13 early degenerated, and 10 late degenerated on histopathology. T2-weighted imaging demonstrated all the cysts while T1-weighted imaging showed 97% of the cysts. Scolex was seen in 90.3% and 93.5% of the cysts on T2- and T1-weighted images, respectively. Minimal edema (grade I) and inflammation in degenerating cysts present on histopathology was not visible on MRI. All but one of eight degenerated cysts, which showed enhancement on postcontrast MRI, had edema on imaging as well as on histopathology., Conclusion: T2-weighted MRI demonstrated all the cysts that were visible on histopathology. Non-enhancement of some of the degenerated cysts along with absence of edema on MRI is likely to underestimate the staging of neurocysticercosis evolution, and these early degenerating cysts may be misdiagnosed as in viable stage., (Copyright 2004 Wiley-Liss, Inc.)

Neuroanatomical changes have been identified in patients diagnosed with late-life major depressive disorder (MDD) compared with controls. These primarily comprise a decrease in focal brain volumes and an increase in MRI-determined high intensity lesions that are largely confined to the white matter. The physiological status of normal-appearing white matter in patients with MDD remains unknown. Magnetization transfer (MT) is a relatively new neuroimaging technique that permits us to examine the biophysical characteristics of specific brain regions. Using MT, we studied eight patients with late-life MDD and eight non-depressed controls. MT ratios (MTR), which reflect the integrity of the macromolecular protein pool, were ascertained in normal-appearing white matter and subcortical nuclei. Patients had significantly lower MTRs in the genu and splenium of the corpus callosum, the right caudate nucleus and putamen, and the occipital white matter compared with controls. The findings indicate that the structure of the macromolecular protein matrix may be compromised in normal-appearing white matter and critical subcortical nuclei in patients with late-life major depression. These changes may provide important substrates to mood disorders and have implications for neuronal connectivity and its role in the pathophysiology of late-life depression.

Neurocysticercosis (NCC) is the most frequent parasitic disease of central nervous system. In our earlier study, we had observed creatine [(creatine + phosphocreatine); (tCr)] on ex vivo proton MR spectroscopy (1H MRS) in some of the cysticercus cyst fluid samples obtained from swine's brain parenchyma. In current study, swine brains of freshly slaughtered animals naturally infected with NCC were subjected to ex vivo magnetic resonance (MR) imaging on a 1.5Tesla MR system. Cysticercus cysts (n = 12) were removed from these brains and were labeled depending upon presence or absence of edema around cysts as observed on imaging. Cysticercus cyst fluid (100 microl) was subjected to different 1H MRS experiments and results were compared with histopathological examinations to look for any relationship between tCr and parameters like quantification of musculature, and cellular infiltration in wall of the parasite. Histopathology of cyst wall was categorized into two groups based on cellular characteristics and the amount of musculature. Grade I cysts (n = 5) with no or minimal inflammation and large amount of musculature showed tCr on 1H MRS. However, grade II cysts (n = 7) with profuse inflammation and less amount of musculature in the cyst wall lacked tCr. Higher amount of musculature in grade I cysts was associated with higher concentration of tCr in the cyst fluid (r2 = 0.93, P = 0.007). Creatine appears to be a marker of innocuous and viable NCC.

Purpose: To examine the relationships between the damaged macromolecular pool seen on magnetization transfer (MT) imaging and cerebral metabolic changes recorded by magnetic resonance spectroscopy (MRS), in frontal white and gray matter regions of late-life MDD patients., Materials and Methods: MT imaging and MRS were performed on eight patients with late-life MDD and eight age-matched healthy controls. MT ratios were calculated using the on-resonance and off-resonance images. Correlations were computed between MT ratios and the ratios of several metabolites, including choline (Cho), myo-inositol (mI), N-acetylaspartate (NAA), and N-acetylaspartylglutamate (NAAG), to creatine (Cr)., Results: Statistically significant correlations were found in white matter between the MT ratios and mI/Cr (r = -0.90, N = 7, P = 0.016), and between the MT ratios and (NAA + NAAG)/Cr (r = -0.89, N = 8, P = 0.007). No significant correlations were found in gray matter or between the MT ratios and NAA/Cr or Cho/Cr in white matter., Conclusion: Changes in the white matter macromolecular protein pool, observed as reduced MT ratios, may be related to changes in the mI and the total NAA pools. These findings may have implications for the pathophysiology of late-life major depression., (Copyright 2003 Wiley-Liss, Inc.)

Traumatic brain injury (TBI) is one of the commonest causes of morbidity and mortality in the developed countries with posttraumatic epilepsy and functional disability being its major sequelae. The purpose of this study was to test the hypothesis whether the normal appearing adjacent gray and white matter regions on T2 and T1 weighted magnetization transfer (MT) weighted images show any abnormality on quantitative imaging in patients with TBI. A total of 51 patients with TBI and 10 normal subjects were included in this study. There were significant differences in T2 and MT ratio values of T2 weighted and T1 weighted MT normal appearing gray matter regions adjacent to focal image abnormality compared to normal gray matter regions in the normal individuals as corresponding contralateral regions of the TBI patient's group (p < 0.05). However the adjoining normal appearing white matter quantitative values did not show any significant change compared to the corresponding contralateral normal white matter values. We conclude that quantitative T2 and MT ratio values provide additional abnormality in patients with TBI that is not discernable on conventional T2 weighted and T1 weighted MT imaging especially in gray matter. This additional information may be of value in overall management of these patients with TBI.

Although Japanese Encephalitis (JE) and Wilson's disease (WD) are different entities, MR findings in both these conditions are quite similar. The purpose of this retrospective study was to find out the similarities and differences between JE and WD on MR imaging. The study group comprised 25 proven cases of JE and 10 cases of WD. Spin echo (SE) TI- and T2-weighted imaging was performed on a 1.5-T MR system. Fourteen of these 35 cases (10 JE, 4 WD) were also examined using T1-weighted magnetization transfer (MT) SE sequence before and after contrast administration. Although both JE and WD showed similar topographical distribution of lesions, predominant involvement of the basal ganglia and thalami, there were some differences. Brain stem lesion was more frequent for WD than for JE, and posteromedial part of the thalami was spared in WD. The lesion characteristics were also different between both; in WD mixed intensity in the basal ganglia and hyperintense linear rim at the peripheral putamen was observed frequently, whereas hyperintense basal ganglia on T2-weighted images, subacute hemorrhage in the thalami and meningeal enhancement were seen only in the patients with JE. These characteristic lesion criteria may help in differentiation of JE from WD on MR imaging.