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Chugani D.C.,Wayne State University | Chugani D.C.,Translational Imaging Laboratory
Biomarkers in Medicine

The purpose of this paper is to discuss the mechanisms of α-[ 11C]methyl-L-tryptophan (AMT) PET as an in vivo biomarker for detection of epileptogenic cortex. AMT was originally designed as a tracer to measure the serotonin synthesis rate. This tracer was first applied in patients with medically refractory epilepsy in an attempt to detect changes in serotonin synthesis based upon reports of increased serotonergic innervation in cortical specimens obtained following epilepsy surgery. The first group of epilepsy patients undergoing AMT PET scans were patients with tuberous sclerosis complex. Studies of brain tissue subsequent to epilepsy surgery in these patients with tuberous sclerosis complex implicated the kynurenine pathway of tryptophan metabolism as a primary mechanism of increased brain tissue retention of AMT in epileptogenic brain regions, rather than alterations in serotonin synthesis. Kinetic analyses of AMT in brain tumors indicate changes in tryptophan transport and tissue retention in other pools as well. These studies indicate that AMT PET may be a biomarker of immune activation in the epileptogenic process. © 2011 Future Medicine Ltd. Source

Jeong J.-W.,Wayne State University | Jeong J.-W.,Translational Imaging Laboratory | Chugani H.T.,Wayne State University | Chugani H.T.,Translational Imaging Laboratory | And 2 more authors.
Journal of Magnetic Resonance Imaging

Purpose To explore whether diffusion-weighted imaging (DWI) can localize specific segments of primary motor areas in children with Sturge-Weber syndrome (SWS), this study investigated the corticospinal tract (CST) between precentral gyrus (PCG) and posterior limb of internal capsule (PIC). Materials and Methods DWI was performed on 32 healthy children and seven children with unilateral SWS affecting the sensorimotor area variably. A hierarchical dendrogram was applied to find PCG-segments uniquely connected to PIC-segments. The resulting PCG-clusters were used to image primary motor pathways in DWI and find metabolic abnormalities of primary motor areas in positron emission tomography (PET) scans. Results In healthy children, five PCG-clusters were found to have unique CST courses, corresponding to CST segments of mouth/lip, fingers, and leg/ankle primary motor areas determined by functional magnetic resonance imaging (fMRI). In children with SWS, reduced streamlines in these PCG clusters were highly correlated with glucose-hypometabolism on PET (R2 = 0.2312, P = 0.0032). Impaired CST segment corresponding to finger movements correlated with severity of hand motor deficit. Conclusion The presented method can detect impaired CST segments corresponding to specific motor functions in young children who cannot cooperate for fMRI. This approach can be clinically useful for a noninvasive presurgical evaluation of cortical motor areas in such children. J. Magn. Reson. Imaging 2013;38:1152-1161. © 2013 Wiley Periodicals, Inc. Copyright © 2013 Wiley Periodicals, Inc. Source

Jeong J.-W.,Wayne State University | Jeong J.-W.,Translational Imaging Laboratory | Asano E.,Wayne State University | Asano E.,Translational Imaging Laboratory | And 4 more authors.
Human Brain Mapping

As a new tool to quantify primary motor pathways and predict postoperative motor deficits in children with focal epilepsy, the present study utilized a maximum a posteriori probability (MAP) classification of diffusion weighted imaging (DWI) tractography combined with Kalman filter. DWI was performed in 31 children with intractable focal epilepsy who underwent epilepsy surgery. Three primary motor pathways associated with "finger," "leg," and "face" were classified using DWI-MAP classifier and compared with the results of invasive electrical stimulation mapping (ESM) via receiver operating characteristic (ROC) curve analysis. The Kalman filter analysis was performed to generate a model to determine the probability of postoperative motor deficits as a function of the proximity between the resection margin and the finger motor pathway. The ROC curve analysis showed that the DWI-MAP achieves high accuracy up to 89% (finger), 88% (leg), 89% (face), in detecting the three motor areas within 20 mm, compared with ESM. Moreover, postoperative reduction of the fiber count of finger pathway was associated with postoperative motor deficits involving the hand. The prediction model revealed an accuracy of 92% in avoiding postoperative deficits if the distance between the resection margin and the finger motor pathway seen on preoperative DWI tractography was 19.5 mm. This study provides evidence that the DWI-MAP combined with Kalman filter can effectively identify the locations of cortical motor areas even in patients whose motor areas are difficult to identify using ESM, and also can serve as a reliable predictor for motor deficits following epilepsy surgery. © 2013 Wiley Periodicals, Inc. Source

Jeong J.-W.,Childrens Hospital of Michigan | Jeong J.-W.,Wayne State University | Jeong J.-W.,Translational Imaging Laboratory | Asano E.,Childrens Hospital of Michigan | And 8 more authors.
Magnetic Resonance in Medicine

The independent component analysis (ICA) tractography method has improved the ability to isolate intravoxel crossing fibers; however, the accuracy of ICA is limited in cases with voxels in local clusters lacking sufficient numbers of fibers with the same orientations. To overcome this limitation, the ICA was combined with a ball-stick model (BSM) ["ICA+BSM"]. An ICA approach is applied to identify crossing fiber components in voxels of small cluster, which are maximally independent in orientation. The eigenvectors of these components are numerically optimized via the subsequent BSM procedure. Simulation studies for two or three crossing fibers demonstrate that ICA+BSM overcomes the limitation of the original ICA method by refining regional ICA solutions in diffusion measurement of a single voxel. It shows 2°-5° of angular errors to isolate two or three fibers, providing a better recovery of simulated fibers compared with ICA alone. Human studies show that ICA+BSM achieves high anatomical correspondence of corticospinal tracts compared with postmortem corticospinal histology, yielding 92.2% true positive detection including both lateral and medial projections, compared with 84.1% for ICA alone. This study demonstrates that the intravoxel crossing fiber problem in clinical diffusion MRI may be sorted out more efficiently by combining ICA with BSM. © 2012 Wiley Periodicals, Inc. Source

Jeong J.-W.,Wayne State University | Jeong J.-W.,Translational Imaging Laboratory | Chugani D.C.,Wayne State University | Chugani D.C.,Translational Imaging Laboratory | And 5 more authors.

Neuropathological studies have demonstrated decreased Purkinje cells in cerebellar cortex and changes in the dentate nucleus of the cerebellum, the projection target for the Purkinje cells, in autistic spectrum disorders (ASD). The dentatorubrothalamic tract is formed by efferents from the dentate nucleus projecting toward the red nucleus with axon collaterals to this nucleus and continuing to innervate the ventral lateral and ventral anterior nuclei of the thalamus. In the current study, we assessed whether the dentatorubrothalamic tract is altered in ASD using Q-ball imaging (QBI). The QBI tractography was performed in 13 children with high functioning ASD (HFA), 11 children with low functioning ASD (LFA), and 14 typically developing children (TD). Regions of interest in dentate nucleus and red nucleus in both hemispheres were objectively placed to sort bilateral dorsal-rostral (DR), dorsal-caudal (DC), ventral-rostral (VR), and ventral-caudal (VC) portions of the dentatorubrothalamic pathway. Group differences in fractional anisotropy (FA), axial diffusivity, radial diffusivity, and fiber volume of individual pathways were analyzed. Significantly reduced FA was found in children with LFA and HFA, compared to the TD group in tracts originating in all four subdivisions of the right dentate nucleus. Tract-based morphometry (TBM) analysis demonstrated significant reductions of FA in caudal midbrain (p<0.0001), dorsal-caudal dentate (p00.0013), and ventral-caudal dentate (p00.0061) on the right in the LFA group. The FA values in TBM segments of right VR and VC pathways were significantly correlated with communication skills in the combined HFA/ LFA group, while there was a significant correlation found between TBM segments of right DR pathway and daily living skills (r00.76; p00.004). Decreased white matter integrity in dorsal portions of the dentatorubrothalamic tract may be related to motor features in ASD, while changes in the ventral portions are related more to communication behavior. © Springer Science+Business Media, LLC 2012. Source

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