Pratik Mukherjee

Agenesis of the corpus callosum: genetic, developmental and functional aspects of connectivity.

Agenesis of the corpus callosum (AgCC), a failure to develop the large bundle of fibres that connect the cerebral hemispheres, occurs in 1:4000 individuals. Genetics, animal models and detailed structural neuroimaging are now providing insights into the developmental and molecular bases of AgCC. Studies using neuropsychological, electroencephalogram and functional MRI approaches are examining the resulting impairments in emotional and social functioning, and have begun to explore the functional neuroanatomy underlying impaired higher-order cognition. The study of AgCC could provide insight into the integrated cerebral functioning of healthy brains, and may offer a model for understanding certain psychiatric illnesses, such as schizophrenia and autism.

Extent of Microstructural White Matter Injury in Postconcussive Syndrome Correlates with Impaired Cognitive Reaction Time: A 3T Diffusion Tensor Imaging Study of Mild Traumatic Brain Injury

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) may be a useful index of microstructural changes implicated in diffuse axonal injury (DAI) linked to persistent postconcussive symptoms, especially in mild traumatic brain injury (TBI), for which conventional MR imaging techniques may lack sensitivity. We hypothesized that for mild TBI, DTI measures of DAI would correlate with impairments in reaction time, whereas the number of focal lesions on conventional 3T MR imaging would not. MATERIALS AND METHODS: Thirty-four adult patients with mild TBI with persistent symptoms were assessed for DAI by quantifying traumatic microhemorrhages detected on a conventional set of T2*-weighted gradient-echo images and by DTI measures of fractional anisotropy (FA) within a set of a priori regions of interest. FA values 2.5 SDs below the region average, based on a group of 26 healthy control adults, were coded as exhibiting DAI. RESULTS: DTI measures revealed several predominant regions of damage including the anterior corona radiata (41% of the patients), uncinate fasciculus (29%), genu of the corpus callosum (21%), inferior longitudinal fasciculus (21%), and cingulum bundle (18%). The number of damaged white matter structures as quantified by DTI was significantly correlated with mean reaction time on a simple cognitive task (r = 0.49, P = .012). In contradistinction, the number of traumatic microhemorrhages was uncorrelated with reaction time (r = −0.08, P = .71). CONCLUSION: Microstructural white matter lesions detected by DTI correlate with persistent cognitive deficits in mild TBI, even in populations in which conventional measures do not. DTI measures may thus contribute additional diagnostic information related to DAI.

Q-ball reconstruction of multimodal fiber orientations using the spherical harmonic basis.

Diffusion tensor imaging (DTI) accurately delineates white matter pathways when the Gaussian model of diffusion is valid. However, DTI yields erroneous results when diffusion takes on a more complex distribution, as is the case in the brain when fiber tracts cross. High angular resolution diffusion imaging (HARDI) overcomes this limitation of DTI by more fully characterizing the angular dependence of intravoxel diffusion. Among the various HARDI methods that have been proposed, QBI offers advantages such as linearity, model independence, and relatively easy implementation. In this work, reconstruction of the q‐ball orientation distribution function (ODF) is reformulated in terms of spherical harmonic basis functions, yielding an analytic solution with useful properties of a frequency domain representation. The harmonic basis is parsimonious for typical b‐values, which enables the ODF to be synthesized from a relatively small number of noisy measurements and thus brings the technique closer to clinical feasibility from the standpoint of total imaging time. The proposed method is assessed using Monte Carlo computer simulations and compared with conventional q‐ball reconstruction using spherical RBFs. In vivo results from 3T whole‐brain HARDI of adult volunteers are also provided to verify the underlying mathematical theory. Magn Reson Med, 2006.

Diffusion Tensor MR Imaging and Fiber Tractography: Theoretic Underpinnings

SUMMARY: In this article, the underlying theory of clinical diffusion MR imaging, including diffusion tensor imaging (DTI) and fiber tractography, is reviewed. First, a brief explanation of the basic physics of diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) mapping is provided. This is followed by an overview of the additional information that can be derived from the diffusion tensor, including diffusion anisotropy, color-encoded fiber orientation maps, and 3D fiber tractography. This article provides the requisite background for the second article in this 2-part review to appear next month, which covers the major technical factors that affect image quality in diffusion MR imaging, including the acquisition sequence, magnet field strength, gradient amplitude and slew rate, and multichannel radio-frequency coils and parallel imaging. The emphasis is on optimizing these factors for state-of-the-art DWI and DTI based on the best available evidence in the literature.

Diffusion tensor imaging: serial quantitation of white matter tract maturity in premature newborns.

Magnetic resonance diffusion tensor imaging (DTI) enables the discrimination of white matter pathways before myelination is evident histologically or on conventional MRI. In this investigation, 14 premature neonates with no evidence of white matter abnormalities by conventional MRI were studied with DTI. A custom MR-compatible incubator with a novel high sensitivity neonatal head coil and improved acquisition and processing techniques were employed to increase image quality and spatial resolution. The technical improvements enabled tract-specific quantitative characterization of maturing white matter, including several association tracts and subcortical projection tracts not previously investigated in neonates by MR. Significant differences were identified between white matter pathways, with earlier maturing commissural tracts of the corpus callosum, and deep projection tracts of the cerebral peduncle and internal capsule exhibiting lower mean diffusivity (Dav) and higher fractional anisotropy (FA) than later maturing subcortical projection and association pathways. Maturational changes in white matter tracts included reductions in Dav and increases in FA with age due primarily to decreases in the two minor diffusion eigenvalues (lambda2 and lambda3). This work contributes to the understanding of normal white matter development in the preterm neonatal brain, an important step toward the use of DTI for the improved evaluation and treatment of white matter injury of prematurity.

Diffusion tensor MR imaging and fiber tractography: technical considerations.

SUMMARY:This second article of the 2-part review builds on the theoretic background provided by the first article to cover the major technical factors that affect image quality in diffusion imaging, including the acquisition sequence, magnet field strength, gradient amplitude, and slew rate as well as multichannel radio-frequency coils and parallel imaging. The sources of many common diffusion image artifacts are also explored in detail. The emphasis is on optimizing these technical factors for state-of-the-art diffusion-weighted imaging and diffusion tensor imaging (DTI) based on the best available evidence in the literature. An overview of current methods for quantitative analysis of DTI data and fiber tractography in clinical research is also provided.

Diffusion tensor imaging of mild traumatic brain injury.

Mild traumatic brain injury (mTBI) remains a challenge to accurately assess with conventional neuroimaging. Recent research holds out the promise that diffusion tensor imaging (DTI) can be used to predict recovery in mTBI patients. Unlike computed tomography or conventional magnetic resonance imaging, DTI is sensitive to microstructural axonal injury, the neuropathology that is thought to be most responsible for the persistent cognitive and behavioral impairments that often occur after mTBI. Through the use of newer DTI analysis techniques such as automated region of interest analysis, tract-based voxel-wise analysis, and quantitative tractography, researchers have shown that frontal and temporal association white matter pathways are most frequently damaged in mTBI and that the microstructural integrity of these tracts correlates with behavioral and cognitive measures. Future longitudinal DTI studies are needed to elucidate how symptoms and the microstructural pathology evolve over time. Moving forward, large-scale investigations will ascertain whether DTI can serve as a predictive imaging biomarker for long-term neurocognitive deficits after mTBI that would be of value for triaging patients to clinical trials of experimental cognitive enhancement therapies and rehabilitation methods, as well as for monitoring their response to these interventions.

Quantitative diffusion tensor MRI fiber tractography of sensorimotor white matter development in premature infants.

Diffusion tensor MRI (DTI) fiber tracking is the first non-invasive and in vivo technique for the delineation and quantitation of specific white matter pathways. In this study, quantitative fiber tracking was used to assess the structural development of the motor tract and somatosensory radiation in premature human newborns. These pathways are unmyelinated in the youngest premature infants and begin to myelinate during late preterm maturation. Previous studies have only been able to delineate parts of these pathways that could be manually outlined in 2D based on anatomical landmarks. Furthermore, these previous studies could not separate motor and sensory regions. A high-sensitivity neonatal head coil was employed in conjunction with an MR-compatible incubator to perform high-resolution imaging of the premature infant brain. The motor and somatosensory tracts were successfully delineated with 3D DTI fiber tracking in 37 exams of preterm newborns between 28 and 43 weeks gestational age. Both streamline deterministic and probabilistic methods were employed to perform quantitative fiber tractography. Tract-specific measurements of diffusion parameters including fractional anisotropy, directionally averaged diffusivity, and eigenvalues were obtained from the motor and sensory pathways. Using both deterministic and probabilistic fiber tracking, all tract-specific diffusion parameters were found to be significantly correlated with age and the motor tracts were found to have higher anisotropy and lower diffusivity than the sensory pathway. By segmenting the 3D fiber tracks by slice, measurements from different axial levels of the brain were found to vary with region and age. In summary, deterministic and probabilistic DTI fiber tracking methods were used to quantify the developmental changes of motor and somatosensory pathways in premature infants.

Focal Lesions in Acute Mild Traumatic Brain Injury and Neurocognitive Outcome: CT versus 3T MRI

Mild traumatic brain injury (mTBI) is associated with long-term cognitive deficits. This study compared the detection rate of acute post-traumatic focal lesions on computed tomography (CT) and 3T (Tesla) magnetic resonance (MR) imaging with neurocognitive outcomes. Adults (n = 36; age range, 19-52 years) with a single episode of mTBI (Glasgow Coma Scale 13-15, as well as loss of consciousness and post-traumatic amnesia) were prospectively enrolled and had CT within 24 h of injury and 3T MR within 2 weeks of injury. The CT and MR scans were reviewed by two neuroradiologists who were blinded to clinical information. Twenty-eight of these mTBI subjects and 18 matched healthy volunteers also underwent serial neurocognitive testing. Of the 36 mTBI cases, intraparenchymal lesions were detected in 18 CT and 27 acute MR exams, consisting of hemorrhagic traumatic axonal injury (TAI) (eight CT, 17 MR), non-hemorrhagic TAI (zero CT, four MR), and cerebral contusions (13 CT, 21 MR). Mild TBI patients had significantly worse performance on working memory tasks than matched controls at the acute time point (<2 weeks), and at 1 month and at 1 year post-injury; yet there was no significant correlation of imaging findings with working memory impairment. In conclusion, 3T MR detected parenchymal lesions in 75% of this mTBI cohort with loss of consciousness and post-traumatic amnesia, a much higher rate than CT. However, the CT and 3T MR imaging findings did not account for cognitive impairment, suggesting that newer imaging techniques such as diffusion tensor imaging are needed to provide biomarkers for neurocognitive and functional outcome in mTBI.

Development of a robust method for generating 7.0 T multichannel phase images of the brain with application to normal volunteers and patients with neurological diseases.

The increased susceptibility effects and high signal-to-noise ratio at 7.0 T enable imaging of the brain using the phase of the magnetic resonance signal. This study describes and evaluates a robust method for calculating phase images from gradient-recalled echo (GRE) scans. The GRE scans were acquired at 7.0 T using an eight-channel receive coil at spatial resolutions up to 0.195 x 0.260 x 2.00 mm. The entire 7.0 T protocol took less than 10 min. Data were acquired from forty-seven subjects including clinical patients with multiple sclerosis (MS) or brain tumors. The phase images were post-processed using a fully automated phase unwrapping algorithm that combined the data from the different channels. The technique was used to create the first phase images of MS patients at any field strength and the first phase images of brain tumor patients above 1.5 T. The clinical images showed novel contrast in MS plaques and depicted microhemorrhages and abnormal vasculature in brain tumors with unsurpassed resolution and contrast.