Clinical Utility of Diffusion Tensor Imaging as a Biomarker to Identify Microstructural Changes in Pediatric Spinal Cord Injury.

Background: Lack of clarity about the neurological consequence of spinal cord injury (SCI) in children causes speculation about diagnoses, recovery potential, and treatment effectiveness. Diffusion tensor imaging (DTI) has shown promising results as a biomarker to evaluate spinal cord integrity at a microstructural level. Objectives: To look at the difference between pediatric participants with and without SCI to determine which DTI metrics best categorize spinal cord tissue damage and to correlate DTI metrics with two clinical measures: Capabilities of the Upper Extremity Test (CUE-T) and Spinal Cord Independence Measure version III (SCIM-III). Methods: This single-site, prospective study included pediatric participants with SCI (n = 26) and typically developed (TD) control subjects (n = 36). All participants underwent two magnetic resonance imaging (MRI) scans on a 3T MR scanner. Participants with SCI also completed the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), CUE-T, and SCIM-III outcomes measures. Results: This study found significant strength of association between fractional anisotropy (FA) and upper extremity muscle strength (UEMS) in participants with SCI. Most DTI parameters showed a significant difference between participants with SCI and TD participants and a moderate correlation with the CUE-T total score. Regional effects on group differences were found to be significant. Conclusion: This study demonstrates the strength of association between DTI parameters and clinical measures in the pedantic SCI population. It illustrates DTI as a potential biomarker of SCI location and severity in the pediatric SCI population.

DTI of chronic spinal cord injury in children without MRI abnormalities (SCIWOMR) and with pathology on MRI and comparison to severity of motor impairment.

STUDY DESIGN: This investigation was a cohort study that included: 36 typically developing (TD) children and 19 children with spinal cord lesions who underwent spinal cord MRI. OBJECTIVES: To investigate diffusion tensor imaging (DTI) cervical and thoracic spinal cord changes in pediatric patients that have clinically traumatic and non-traumatic spinal cord injury (SCI) without MR (SCIWOMR) abnormalities. SETTING: Thomas Jefferson University, Temple University, Shriners Hospitals for Children all in Philadelphia, USA. METHODS: 36 TD children and 19 children with spinal cord lesions that represent either a chronic traumatic acquired SCI or chronic non-traumatic SCI (≥6 months post injury), age range, 6-16 years who underwent cervical and thoracic spinal cord MRI in 2014-2017. Additionally DTI was correlated to clinical American Spinal Injury Association Impairment Scale (AIS). RESULTS: Both SCIWOMR and MRI positive (+) groups showed abnormal FA and RD DTI values in the adjacent MRI-normal appearing segments of cephalad and caudal spinal cord compared to TD. The FA values demonstrated perilesional abnormal DTI findings in the middle and proximal segments of the cephalad and caudal cord in the SCIWOMR AIS A/B group compared to SCIWOMR AIS C/D group. CONCLUSIONS: We found DTI changes in children with SCIWOMR with different causes of spinal lesions. We also investigated the relationship between DTI and clinical AIS scores. This study further examined the potential diagnostic value of DTI and should be translatable to adults with spinal cord lesions.

Diffusion Tensor Imaging Assessment of Regional White Matter Changes in the Cervical and Thoracic Spinal Cord in Pediatric Subjects.

There are no studies to date,describing changes in the diffusion tensor imaging (DTI) metrics of the white matter (WM) regions of the entire cervical and thoracic spinal cord (SC) remote from the lesion in pediatric spinal cord injury (SCI) subjects. The purpose of this study was to determine whether DTI at sites cephalad and caudal to a lesion provides measures of cord abnormalities in children with chronic SCI. A retrospective study included 10 typically developing subjects (TD) and 10 subjects with chronic SCI who underwent SC imaging in 2014-2017. Axial diffusion tensor images using an inner field of view DTI sequence were acquired to cover the entire cervical and thoracic SC. Regions of interest were drawn on the SC WM: right and left lateral (motor), ventral (motor), and dorsal (sensory) tracts. To detect differences in DTI metrics between TD and SCI of the cord, a one way analysis of variance with pooled t test was performed. A stepwise regression analysis was performed to assess the correlation between DTI metrics and clinical scores. In motor and sensory tracts, fractional anisotropy (FA) and axial diffusivity (AD) were significantly decreased in the proximal segments of the caudal cord. In motor tracts cephalad to the lesion, FA was significantly decreased whereas AD was significantly increased in the proximal segment; however, AD was decreased in the distal and middle segments. International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) total score was significantly correlated with FA and AD of the motor and sensory tracts cephalad to the lesion. This study demonstrates that FA and AD have the potential to be sensitive biomarkers of the full extent of cord injury and might be useful in detecting remote injuries to the SC and in guiding new treatments.

Characterization of spinal cord diffusion tensor imaging metrics in clinically asymptomatic pediatric subjects with incidental congenital lesions.

STUDY DESIGN: Retrospective study. OBJECTIVES: To perform quantitative DTI measurements of the entire cervical and thoracic spinal cord (SC) in typically developing (TD) pediatric subjects with incidental findings of syringomyelia or hydromyelia on conventional MRI and in a TD population without any abnormalities. SETTING: USA. METHODS: 26 TD recruited as part of large SC DTI study, four of these had incidental findings. Axial DTI images were acquired on 3T MR scanner to cover the cervical and thoracic SC. We performed group analysis of DTI values in the cord above and below the MR-defined lesion. For single-subject analysis, the cord above and below the lesion was compared to average values of TD population. A standard least squares regression model was used to compare DTI parameters fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) between TD population and subjects with hydromyelia and syringomyelia. A p value of 0.05 was used for statistical significance. RESULTS: In group analysis, MD and AD were significantly different in cord above the lesion in subjects with hydromyelia and syringomyelia (n = 4) compared to TD population (n = 22). For single-subject analysis, DTI parameters were significantly different in cord above the syringomyelia and below the syringomyelia; MD, AD, and RD were significantly different. A subject with hydromyelia showed significant difference in FA below the lesion. CONCLUSIONS: This study demonstrates that DTI has the potential to be used as an imaging biomarker to evaluate SC above and below the congenital lesion in syringohydromyelia subjects.

Age related diffusion and tractography changes in typically developing pediatric cervical and thoracic spinal cord.

Background and objective: Diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) are two techniques that can measure white matter integrity of the spinal cord. Recently, DTI indices have been shown to change with age. The purpose of this study is (a) to evaluate the maturational states of the entire pediatric spinal cord using DTI and DTT indices including fractional anisotropy (FA), mean diffusivity (MD), mean length of white matter fiber tracts and tract density and (b) to analyze the DTI and DTT parameters along the entire spinal cord as a function of spinal cord levels and age. Method: A total of 23 typically developing (TD) pediatric subjects ranging in age from 6 to 16 years old (11.94 ±â€¯3.26 (mean ±â€¯standard deviation), 13 females and 10 males) were recruited, and scanned using 3.0 T MR scanner. Reduced FOV diffusion tensor images were acquired axially in the same anatomical location prescribed for the T2-weighted images to cover the entire spinal cord (C1-mid L1 levels). To mitigate motion induced artifacts, diffusion directional images were aligned with the reference image (b0) using a rigid body registration algorithm performed by in-house software developed in Matlab (MathWorks, Natick, Massachusetts). Diffusion tensor maps (FA and MD) and streamline deterministic tractography were then generated from the motion corrected DTI dataset. DTI and DTT parameters were calculated by using ROIs drawn to encapsulate the whole cord along the entire spinal cord by an independent board certified neuroradiologist. These indices then were compared between two age groups (age group A = 6-11 years (n = 11) and age group B = 12-16 years (n = 12)) based on similar standards and age definitions used for reporting spinal cord injury in the pediatric population. Standard least squared linear regression based on a restricted maximum likelihood (REML) method was used to evaluate the relationship between age and DTI and DTT parameters. Results: An increase in FA (group A = 0.42 ±â€¯0.097, group B = 0.49 ±â€¯0.116), white matter tract density (group A = 368.01 ±â€¯236.88, group B = 440.13 ±â€¯245.24) and mean length of fiber tracts (group A = 48.16 ±â€¯20.48 mm, group B = 60.28 ±â€¯23.87 mm) and a decrease in MD (group A = 1.06 ±â€¯0.23 × 10-3 mm2/s, group B = 0.82 ±â€¯0.24 × 10-3 mm2/s) were observed with age along the entire spinal cord. Statistically significant increases have been shown in FA (p = 0.004, R2 = 0.57), tract density (p = 0.0004, R2 = 0.58), mean length of fiber tracts (p < 0.001, R2 = 0.5) and a significant decrease has been shown in MD (p = 0.002, R2 = 0.59) between group A and group B. Also, it has been shown DTI and DTT parameters vary along the spinal cord as a function of intervertebral disk and mid-vertebral body level. Conclusion: This study provides an initial understanding of age related changes of DTI values as well as DTT metrics of the spinal cord. The results show significant differences in DTI and DTT parameters which may result from decreasing water content, myelination of fiber tracts, and the thickening diameter of fiber tracts during the maturation process. Consequently, when quantitative DTI and DTT of the spinal cord is undertaken in the pediatric population an age and level matched normative dataset should be used to accurately interpret the quantitative results.

Application of Color Transformation Techniques in Pediatric Spinal Cord MR Images: Typically Developing and Spinal Cord Injury Population.

The purpose of this study was to evaluate an improved and reliable visualization method for pediatric spinal cord MR images in healthy subjects and patients with spinal cord injury (SCI). A total of 15 pediatric volunteers (10 healthy subjects and 5 subjects with cervical SCI) with a mean age of 11.41 years (range 8-16 years) were recruited and scanned using a 3.0T Siemens Verio MR scanner. T2-weighted axial images were acquired covering entire cervical spinal cord level C1 to C7. These gray-scale images were then converted to color images by using five different techniques including hue-saturation-value (HSV), rainbow, red-green-blue (RGB), and two enhanced RGB techniques using automated contrast stretching and intensity inhomogeneity correction. Performance of these techniques was scored visually by two neuroradiologists within three selected cervical spinal cord intervertebral disk levels (C2-C3, C4-C5, and C6-C7) and quantified using signal to noise ratio (SNR) and contrast to noise ratio (CNR). Qualitative and quantitative evaluation of the color images shows consistent improvement across all the healthy and SCI subjects over conventional gray-scale T2-weighted gradient echo (GRE) images. Inter-observer reliability test showed moderate to strong intra-class correlation (ICC) coefficients in the proposed techniques (ICC > 0.73). The results suggest that the color images could be used for quantification and enhanced visualization of the spinal cord structures in addition to the conventional gray-scale images. This would immensely help towards improved delineation of the gray/white and CSF structures and further aid towards accurate manual or automatic drawings of region of interests (ROIs).

Reduced Field of View Diffusion Tensor Imaging and Fiber Tractography of the Pediatric Cervical and Thoracic Spinal Cord Injury.

The aim of this study is to assess the utility and effectiveness of diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) of the entire pediatric cervical and thoracic spinal cord toward discrimination of typically developing (TD) controls and subjects with spinal cord injury (SCI). A total of 43 pediatric subjects, including 23 TD subjects ranging in age from 6 to 16 years old and 20 subjects with SCI ranging in age from 7 to 16 years, were recruited and scanned using a 3.0 Tesla magnetic resonance scanner. Reduced field of view diffusion tensor images were acquired axially to cover the entire spinal cord across two slabs. For DTI analysis, motion correction was performed by coregistration of the diffusion-weighted images to the reference image (b0). Streamline deterministic tractography results were generated from the preprocessed data. DTI and DTT parameters of the whole cord, including fractional anisotropy (FA), mean diffusivity (MD), tract length, and tract density, were calculated, averaged across the whole spinal cord, and compared between the TD and SCI groups. Statistically significant decreases have been shown in FA (TD = 0.46 ± 0.11; SCI = 0.37 ± 0.09; p < 0.0001) and tract density (TD = 405.93 ± 243.84; SCI = 268.90 ± 270.34; p < 0.0001). However, the mean length of tracts and MD did not show significant differences. When investigating differences in DTI and DTT parameters above and below the injury site, it was shown that the FA and tract density in patients with cervical SCI decreased significantly in the thoracic region. An identical trend was observed in the cervical region for patients with thoracic SCI as well. When comparing TD and SCI subjects, FA and tract density were the most sensitive parameters in detecting functional changes of the spinal cord in chronic pediatric SCI. The results show that both DTI and DTT have the potential to be imaging biomarkers in the diagnosis of SCI.

Identification of ghost artifact using texture analysis in pediatric spinal cord diffusion tensor images.

PURPOSE: Ghost artifacts are a major contributor to degradation of spinal cord diffusion tensor images. A multi-stage post-processing pipeline was designed, implemented and validated to automatically remove ghost artifacts arising from reduced field of view diffusion tensor imaging (DTI) of the pediatric spinal cord. METHOD: A total of 12 pediatric subjects including 7 healthy subjects (mean age=11.34years) with no evidence of spinal cord injury or pathology and 5 patients (mean age=10.96years) with cervical spinal cord injury were studied. Ghost/true cords, labeled as region of interests (ROIs), in non-diffusion weighted b0 images were segmented automatically using mathematical morphological processing. Initially, 21 texture features were extracted from each segmented ROI including 5 first-order features based on the histogram of the image (mean, variance, skewness, kurtosis and entropy) and 16s-order feature vector elements, incorporating four statistical measures (contrast, correlation, homogeneity and energy) calculated from co-occurrence matrices in directions of 0°, 45°, 90° and 135°. Next, ten features with a high value of mutual information (MI) relative to the pre-defined target class and within the features were selected as final features which were input to a trained classifier (adaptive neuro-fuzzy interface system) to separate the true cord from the ghost cord. RESULTS: The implemented pipeline was successfully able to separate the ghost artifacts from true cord structures. The results obtained from the classifier showed a sensitivity of 91%, specificity of 79%, and accuracy of 84% in separating the true cord from ghost artifacts. CONCLUSION: The results show that the proposed method is promising for the automatic detection of ghost cords present in DTI images of the spinal cord. This step is crucial towards development of accurate, automatic DTI spinal cord post processing pipelines.

Magnetic resonance spectroscopy for detection of choline kinase inhibition in the treatment of brain tumors.

Abnormal choline metabolism is a hallmark of cancer and is associated with oncogenesis and tumor progression. Increased choline is consistently observed in both preclinical tumor models and in human brain tumors by proton magnetic resonance spectroscopy (MRS). Thus, inhibition of choline metabolism using specific choline kinase inhibitors such as MN58b may be a promising new strategy for treatment of brain tumors. We demonstrate the efficacy of MN58b in suppressing phosphocholine production in three brain tumor cell lines. In vivo MRS studies of rats with intracranial F98-derived brain tumors showed a significant decrease in tumor total choline concentration after treatment with MN58b. High-resolution MRS of tissue extracts confirmed that this decrease was due to a significant reduction in phosphocholine. Concomitantly, a significant increase in poly-unsaturated lipid resonances was also observed in treated tumors, indicating apoptotic cell death. MRI-based volume measurements demonstrated a significant growth arrest in the MN58b-treated tumors in comparison with saline-treated controls. Histologically, MN58b-treated tumors showed decreased cell density, as well as increased apoptotic cells. These results suggest that inhibition of choline kinase can be used as an adjuvant to chemotherapy in the treatment of brain tumors and that decreases in total choline observed by MRS can be used as an effective pharmacodynamic biomarker of treatment response.

The Corpus Callosum Wallerian Degeneration in the Unilateral Brain Tumors: Evaluation with Diffusion Tensor Imaging (DTI).

PURPOSE: The purpose of this study was to evaluate whether DTI could demonstrate the water diffusivity changes in the corpus callosum (CC), which were not visible on the morphologic imaging in patients with glioblastoma multiforme (GBM) and brain metastases with no midline CC infiltration. MATERIALS AND METHODS: Twenty-seven patients with treatment naïve unilateral GBM and eleven patients with a solitary brain metastasis with no midline CC infiltration underwent DTI. Ten controls with normal brain MRI were also included. Based on the tensors, the principal diffusion directions, the anisotropy values, and the prior information about the diffusivity pattern in CC, a similarity measure was proposed. Subsequently, the CC was automatically divided into the Witelson subdivisions. RESULTS: We observed significantly decreased fractional anisotropy values in all the regions of CC in the patients with GBM and metastases as compared to those in the controls. The mean diffusivity values showed a significant increase in all the regions of CC, except the splenium in patients with GBM and the isthmus in the patients with metastases, as compared to that in the controls respectively. CONCLUSION: In conclusion, DTI is more sensitive than the morphologic MR imaging in the evaluation of changes within the CC, in brain tumours which do not infiltrate the CC. However, these changes of the DTI metrics in the CC are due to a Wallerian degeneration rather than a tumour infiltration, as was shown by our results, as similar changes were seen in the GBM as well as the non-infiltrating metastases patients.

Segmentation of corpus callosum using diffusion tensor imaging: validation in patients with glioblastoma.

BACKGROUND: This paper presents a three-dimensional (3D) method for segmenting corpus callosum in normal subjects and brain cancer patients with glioblastoma. METHODS: Nineteen patients with histologically confirmed treatment naïve glioblastoma and eleven normal control subjects underwent DTI on a 3T scanner. Based on the information inherent in diffusion tensors, a similarity measure was proposed and used in the proposed algorithm. In this algorithm, diffusion pattern of corpus callosum was used as prior information. Subsequently, corpus callosum was automatically divided into Witelson subdivisions. We simulated the potential rotation of corpus callosum under tumor pressure and studied the reproducibility of the proposed segmentation method in such cases. RESULTS: Dice coefficients, estimated to compare automatic and manual segmentation results for Witelson subdivisions, ranged from 94% to 98% for control subjects and from 81% to 95% for tumor patients, illustrating closeness of automatic and manual segmentations. Studying the effect of corpus callosum rotation by different Euler angles showed that although segmentation results were more sensitive to azimuth and elevation than skew, rotations caused by brain tumors do not have major effects on the segmentation results. CONCLUSIONS: The proposed method and similarity measure segment corpus callosum by propagating a hyper-surface inside the structure (resulting in high sensitivity), without penetrating into neighboring fiber bundles (resulting in high specificity).

Quantification of age- and gender-related changes in diffusion tensor imaging indices in deep grey matter of the normal human brain.

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.

Tumor vascular leakiness and blood volume estimates in oligodendrogliomas using perfusion CT: an analysis of perfusion parameters helping further characterize genetic subtypes as well as differentiate from astroglial tumors.

The purpose of this study was to determine the usefulness of perfusion CT (PCT) parameters particularly blood volume and neovascular permeability estimates (permeability surface area-product, PS) in the evaluation of oligodendrogliomas (OG), correlation with genetic subtypes of OGs (with or without loss of heterozygosity/LOH on 1p/19q) as well as comparison of perfusion parameters of OGs with astroglial tumors. Pre-operative PCT done in 21 patients with OGs was retrospectively correlated with our previously published PCT data for 32 patients with astroglial neoplasms (Jain R et al., AJNR Am J Neuroradiol 29:694-700, 2008). All OGs were also analyzed for genetic subtypes of with or without LOH. PCT parameters PS and cerebral blood volume (CBV) were obtained for the entire lesion and a statistical analysis done to correlate various histopathological variants. Low grade OGs (n = 13) showed slightly lower CBV (1.42 vs. 1.72 ml/100 g; P value 0.391) and PS (0.56 vs. 0.95 ml/100 g/min; P value 0.099) as compared to high grade OGs (n = 8), though not statistically significant. LOH positive OGs (n = 13) showed higher mean CBV (1.59 vs. 1.45; P value 0.712) and slightly lower PS (0.68 vs. 0.75; P value 0.718) as compared to LOH negative OGs (n = 8), although not statistically significant. Low grade OGs (n = 13) showed higher mean CBV 1.42 ml/100 g as compared to low grade astroglial tumors (n = 8) 0.95 ml/100 g (P value = 0.08), however no statistically significant difference was noted for PS (0.56 vs. 0.52 ml/100 g/min, P value 0.695). Statistically significant differences were observed in CBV and PS values of high grade OGs and high grade astroglial tumors with the high grade glial tumors showing higher mean CBV (2.79 vs. 1.72; P value 0.03) as well as higher PS (2.37 vs. 0.95; P value < 0.01), however this difference was not significant if only comparing grade III OGs with grade III astroglial tumors. PCT perfusion parameters including PS values do not help grade OGs despite showing a trend for higher CBV and PS in higher grade OGs. Similarly LOH positive OGs also showed slightly higher CBV, but again failed to reach any statistically significant level. Low grade OGs showed slightly higher CBV as compared to low grade astroglial tumors, whereas higher grade OGs showed significantly lower PS values as compared to higher grade astroglial tumors despite showing high CBV.

Predicting survival in glioblastomas using diffusion tensor imaging metrics.

PURPOSE: To retrospectively correlate various diffusion tensor imaging (DTI) metrics in patients with glioblastoma multiforme (GBM) with patient survival analysis and also degree of tumor proliferation index determined histologically. MATERIALS AND METHODS: Thirty-four patients with histologically confirmed treatment naive GBMs underwent DTI on a 3.0 Tesla (T) scanner. Region-of-interest was placed on the whole lesion including the enhancing as well as nonenhancing component of the lesion to determine the various DTI metrics. Kaplan-Meier estimates and Cox proportional hazards regression methods were used to assess the relationship of DTI metrics (minimum and mean values) and Ki-67 with progression free survival (PFS). To study the relationship between DTI metrics and Ki-67, Pearson's correlation coefficient was computed. RESULTS: Univariate analysis showed that patients with fractional anisotropy (FA)(mean) ≤ 0.2, apparent diffusion coefficient (ADC)(min) ≤ 0.6, planar anisotropy (CP)(min) ≤ 0.002, spherical anisotropy (CS)(mean) > 0.68 and Ki-67 > 0.3 had lower PFS rate. The multivariate analysis demonstrated that only CP(min) was the best predictor of survival in these patients, after adjusting for age, Karnofsky performance scale and extent of resection. No significant correlation between DTI metrics and Ki-67 were observed. CONCLUSION: DTI metrics can be used as a sensitive and early indicator for PFS in patients with glioblastomas. This could be useful for treatment planning as high-grade gliomas with lower ADC(min), FA(mean), CP(min), and higher CS(mean) values may be treated more aggressively.

A diffusion tensor imaging study of deep gray and white matter brain maturation differences between patients with spina bifida cystica and healthy controls.

The aim of this study was to use diffusion tensor imaging (DTI) to identify differences in the maturation of deep gray matter (GM) and white matter (WM) between patients with spina bifida cystica (SBC) (n=29) with normal-appearing brains on conventional MRI, and age-matched and sex-matched healthy control participants (n=33). Changes in DTI metrics were calculated using a log-linear regression model. We observed increasing fractional anisotropy (FA) with age in the occipital, fornix, cingulum and middle cerebellar peduncles and decreasing FA with age in the genu and splenium of the corpus callosum (CC) and caudate nuclei in patients compared to controls. Increasing FA values in some of the WM structures probably represent faulty WM maturation, whereas decreasing FA values in the CC represents changes secondary to the affected WM fibers contributing to the CC. DTI changes in deep GM and WM in the absence of any abnormality on conventional MRI might provide the basis for cognitive decline in these patients.

Treatment induced necrosis versus recurrent/progressing brain tumor: going beyond the boundaries of conventional morphologic imaging.

Brain tumor patients undergo various combinations therapies, leading to very complex and confusing imaging appearances on follow up MR imaging and hence, differentiating recurrent or progressing tumors from treatment induced necrosis or effects has always been a challenge in neuro-oncologic imaging. This particular topic has become more relevant these days because of the advent of newer anti-angiogenic and anti-neoplastic chemotherapeutic agents as well as use of salvage radiation therapy. Various clinically available functional imaging modalities can provide additional physiologic and metabolic information about the tumors which could be useful in identifying viable tumor from treatment induced necrosis and hence, can guide treatment planning. In this review we will discuss various functional neuro-imaging modalities, their advantages and limitations and also their utility in treatment planning.

Serial changes in diffusion tensor imaging metrics of corpus callosum in moderate traumatic brain injury patients and their correlation with neuropsychometric tests: a 2-year follow-up study.

OBJECTIVE: To assess longitudinally the severity of diffuse axonal injury in the corpus callosum in patients with moderate traumatic brain injury (TBI) through quantitative diffusion tensor imaging and to correlate these changes with neuropsychometric tests (NPT) at 6 and 24 months after injury. DESIGN: Prospective longitudinal study. PARTICIPANTS: Sixteen patients with TBI and 17 age/sex-matched healthy controls. METHODS: Patients underwent magnetic resonance imaging at 3 time points: within 2 weeks (range = 5-14 days), 6 months, and 24 months after injury. NPT could be performed only at 6 and 24 months. RESULTS: In patients with TBI, a significant increase in fractional anisotropy (FA) values in genu as well as an insignificant decrease in radial diffusivity (RD) and mean diffusivity values in genu and splenium were observed over time, respectively. FA, RD, and mean diffusivity values continued to be abnormal in patients compared with controls at the end of 2 years. Although some NPT scores improved over time in these patients, these were still significantly impaired compared with controls. CONCLUSIONS: FA and RD indices appear to be surrogate markers of microstructural alterations in patients over time and correlate significantly with some of the NPT scores. The recovery in these indices associated with recovery in neurocognitive deficits suggests that these indices may be used as an objective marker for residual injury in these patients.

Correlation of DTI metrics in the wall and cavity of brain abscess with histology and immunohistochemistry.

Diffusion tensor imaging (DTI) was performed in eight patients with brain abscess (BA). The aim of this study was to see the difference in the relationship between intercellular cell adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) expression and DTI metrics measured in vivo in the wall and cavity of BA and its possible explanation vis-à-vis histology and immunohistochemistry. Neuroinflammatory molecules (NMs) were quantified from BA cavity aspirate of the patients and quantitative immunohistochemical analysis was performed for ICAM-1 and LFA-1 in the BA wall, showing maximal positive staining and correlated with DTI metrics. The fractional anisotropy (FA) significantly increased while mean diffusivity and spherical anisotropy significantly decreased in the BA wall compared to the BA cavity. In the BA wall, FA and linear anisotropy (CL) showed a significant positive correlation with ICAM-1 and LFA-1 expression whereas FA and planar anisotropy positively correlated with NMs quantified from aspirated pus respectively. Higher FA values in the BA wall compared to BA cavity, even when ICAM-1 and LFA-1 were expressed only in the macrophages and not in the collagen fibers, suggests that a combination of both concentric layers of collagen fibers as well as neutrophils and macrophages provide structural orientation and are responsible for increased FA. In the BA wall, increased CL was found compared to the cavity, indicating the presence of concentrically laid collagen fibers responsible for the diffusion of water molecules in the direction parallel to the collagen fibers. We conclude that in the BA, different mechanisms are operative for the changes in the DTI metrics in the wall and cavity; these conclusions are validated by histology and immunohistochemistry.

Magnetic resonance imaging in central nervous system tuberculosis.

Tuberculosis (TB) in any form is a devastating disease, which in its most severe form involves the central nervous system (CNS), with a high mortality and morbidity. Early diagnosis of CNS TB is necessary for appropriate treatment to reduce this morbidity and mortality. Routine diagnostic techniques involve culture and immunological tests of the tissue and biofluids, which are time-consuming and may delay definitive management. Noninvasive imaging modalities such as computed tomography (CT) scan and magnetic resonance imaging (MRI) are routinely used in the diagnosis of neurotuberculosis, with MRI offering greater inherent sensitivity and specificity than CT scan. In addition to conventional MRI imaging, magnetization transfer imaging, diffusion imaging, and proton magnetic resonance spectroscopy techniques are also being evaluated for better tissue characterization in CNS TB. The current article reviews the role of various MRI techniques in the diagnosis and management of CNS TB.

Understanding development and lateralization of major cerebral fiber bundles in pediatric population through quantitative diffusion tensor tractography.

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.