Guo Liang Yang

Computer-aided stereotactic functional neurosurgery enhanced by the use of the multiple brain atlas database

Introduces a computer-aided atlas-based functional neurosurgery methodology and describes NeuroPlanner, a software system which supports it. NeuroPlanner provides four groups of functions: (1) data-related for data reading, interpolation, reformatting, and image processing; (2) atlas-related for multiple atlases reading, atlas-to-data global and local registrations, two way anatomical indexing, and multiple labeling in two and three dimensions; (3) atlas data exploration-related for three-dimensional (3 D) display and real-time manipulation of cerebral structures, continuous navigation, two-dimensional (2-D), triplanar, 3-D presentations, and 2-D interaction in four views; and (4) neurosurgery-related for targeting, trajectory planning, mensuration, simulating the insertion of microelectrode, and simulating therapeutic lesioning. All operations, excluding atlas and data reading, are real time. The combined anatomical index of the multiple brain atlas database containing complementary 2-D and 3-D atlases has about 1000 structures per hemisphere, and over 400 sulcal patterns. Neurosurgical planning with mutually preregistered multiple brain atlases in all three orthogonal orientations is novel. The approach is validated with 24 intraoperative and postoperative datasets for thalamotomies, thalamic stimulations, pallidotomies, and pallidal stimulations. Its potential benefits include increased accuracy of target definition, reduced time of the surgical procedure by decreasing the number of tracts, facilitated planning of more sophisticated trajectories, lowered cost by reducing the number of microelectrodes used, reduced surgical complications, and the extra degree of confidence given to the neurosurgeon.

White matter abnormalities in first-episode schizophrenia: a combined structural MRI and DTI study.

This study examined white matter volume change and integrity jointly in patients with first-episode schizophrenia using an empirically derived region of interest approach and novel Diffusion Tensor Imaging (DTI) geometric indices. Structural images from 103 individuals comprising of 39 patients with first-episode schizophrenia and 64 healthy controls were examined for regions of white matter volume change using voxel-based morphometry (VBM). These regions were then further interrogated for group differences employing geometric indices in addition to fractional anisotropy (FA).VBM analyses revealed that patients with first-episode schizophrenia had lower white matter volume in the right temporal-occipital region (p<0.005) corresponding to the inferior longitudinal fasciculus. Further analyses of diffusion anisotropy in the right temporal-occipital region revealed lower planar anisotropy, and higher linear anisotropy (p=0.012) in patients. FA in the implicated region was also found to be correlated with severity of delusions (r=0.47, p=0.004).We confirmed previous findings of lower white matter volume in the region of inferior longitudinal fasciculus. The presence of changes in geometric diffusion indices in the implicated white matter region suggested that pathophysiological processes which underlie cerebral white matter volume reduction may not be reflected by changes in FA. Further research is needed to better understand the nature of these white matter changes and its progression in schizophrenia over time.

Cortical and subcortical white matter abnormalities in adults with remitted first-episode mania revealed by Tract-Based Spatial Statistics

OBJECTIVES Abnormalities of brain white matter have been noted in structural magnetic resonance imaging and diffusion tensor imaging (DTI) studies of bipolar disorder, but there are fewer investigations specifically examining white matter integrity early in the course of illness. In this study, we employed DTI to elucidate white matter changes in adult patients with remitted first-episode mania and hypothesized that first-episode mania was associated with decreased fractional anisotropy in cortical (frontal) and subcortical (thalamus, striatum) white matter as well as white matter tracts (cingulum, corpus callosum). METHODS Diffusion tensor images were acquired from 16 patients with remitted first-episode mania and 16 healthy controls matched for age, gender, handedness, and years of education. Fractional anisotropy and radial and axial diffusivities were analyzed using Tract-Based Spatial Statistics. RESULTS Patients had lower fractional anisotropy and higher radial diffusivity in the left anterior frontal white matter, right posterior thalamic radiation, left cingulum, and bilateral sagittal striatum. In addition, increased radial diffusivity was found in the left corpus callosum. CONCLUSION Our findings highlighted that white matter abnormalities were present by the time of remission of first-episode mania. The widespread occurrence of these white matter abnormalities both in first-episode mania and chronic bipolar disorder suggested that disruption of white matter cortical-subcortical networks as well as projection, associative, and commissural tracts is a hallmark of the illness.

Medical Image Resource Center-making electronic teaching files from PACS

A picture archive and communications system (PACS) is a rich source of images and data suitable for creating electronic teaching files (ETF). However, the potential for PACS to support nonclinical applications has not been fully realized: at present there is no mechanism for PACS to identify and store teaching files; neither is there a standardized method for sharing such teaching images. The Medical Image Resource Center (MIRC) is a new central image repository that defines standards for data exchange among different centers. We developed an ETF server that retrieves digital imaging and communication in medicine (DICOM) images from PACS, and enables users to create teaching files that conform to the new MIRC schema. We test-populated our ETF server with illustrative images from the clinical case load of the National Neuroscience Institute, Singapore. Together, PACS and MIRC have the potential to benefit radiology teaching and research.

Corpus callosum morphology in first-episode and chronic schizophrenia: combined magnetic resonance and diffusion tensor imaging study of Chinese Singaporean patients

BACKGROUND Abnormalities in the corpus callosum have been reported in patients with schizophrenia for over 30 years but the influence of inter-individual differences and illness characteristics remains to be fully elucidated. AIMS To examine the influence of individual and illness characteristics on the corpus callosum in Chinese Singaporean patients with schizophrenia. METHOD Using magnetic resonance and diffusion tensor imaging, mean corpus callosum area, volume and fractional anisotropy were investigated in 120 Chinese Singaporean patients (52 with chronic and 68 with first-episode schizophrenia) and compared with data from 75 matched healthy controls. RESULTS Both area and volume were significantly reduced in patients relative to controls but no significant differences in corpus callosum existed between genders in either patients or controls. Differences in area and volume of the corpus callosum were greatest in patients whose condition was chronic relative to patients with a first episode and controls. Anterior callosum in patients, regardless of chronicity, was no different to that of controls. CONCLUSIONS Morphological abnormalities in the corpus callosum may increase with illness progression.

Three-Dimensional Interactive and Stereotactic Human Brain Atlas of White Matter Tracts

We present a human brain atlas of white matter (WM) tracts containing 40 major tracts, which is three-dimensional (3D), segmented, labeled, interactive, stereotactic and correlated to structure and vasculature. We consider: 1) WM accuracy by correlating WM tracts to underlying neuroanatomy and quantifying them; 2) balance between realism and completeness by processing a sequence of track volumes generated for various parameters with the increasing track number to enable a tract “shape convergence”. MPRAGE and DTI in 64 directions of the same subject were acquired on 3 Tesla. The method has three steps: DTI-MPRAGE registration, 3D tract generation from DTI, to WM reconstruction from MPRAGE to parcellation into 17 components. 82 track volumes were generated for a wide spectrum of parameter values: Fractional Anisotropy threshold in [0.0125, 0.55] and trajectory angle lower than 45°,60°,65°,70°,75°,80°,85°,90°. For each tract, a sequence of track volumes was processed to create/edit contours delineating this tract to achieve its shape convergence. The parcellated tracts were grouped into commissures, associations, projections and posterior fossa tracts, and labeled following Terminologia Anatomica. To facilitate that, a dedicated tract editor is developed which processes multiple track volumes, handles tracts in three representations (tracks, contours, envelopes); provides editing/visualization simultaneously on axial, coronal, sagittal planes; enables tract labeling and coloring; and provides numerous tools (track counting, smoothing and length thresholding; representation conversion and saving; structural atlas support). A stereotactic tract atlas along with parcellated WM was developed to explore in real-time any individual tract or their groups along with surrounding neuroanatomy.

Increased body mass index makes an impact on brain white-matter integrity in adults with remitted first-episode mania

BACKGROUND Obesity is increasingly prevalent in bipolar disorder (BD) but data about the impact of elevated body mass index (BMI) on brain white-matter integrity in BD are sparse. Based on extant literature largely from structural magnetic resonance imaging (MRI) studies, we hypothesize that increased BMI is associated with decreased fractional anisotropy (FA) in the frontal, temporal, parietal and occipital brain regions early in the course of BD. METHOD A total of 26 euthymic adults (12 normal weight and 14 overweight/obese) with remitted first-episode mania (FEM) and 28 controls (13 normal weight and 15 overweight/obese) matched for age, handedness and years of education underwent structural MRI and diffusion tensor imaging scans. RESULTS There are significant effects of diagnosis by BMI interactions observed especially in the right parietal lobe (adjusted F(1,48) = 5.02, p = 0.030), occipital lobe (adjusted F(1,48) = 10.30, p = 0.002) and temporal lobe (adjusted F(1,48) = 7.92, p = 0.007). Specifically, decreased FA is found in the right parietal (F(1,48) = 5.864, p = 0.023) and occipital lobes (F(1,48) = 4.397, p = 0.047) within overweight/obese patients compared with normal-weight patients with FEM. Compared with overweight/obese controls, decreased FA is observed in right parietal (F(1,48) = 6.708, p = 0.015), temporal (F(1,48) = 10.751, p = 0.003) and occipital (F(1,48) = 9.531, p = 0.005) regions in overweight/obese patients with FEM. CONCLUSIONS Our findings suggest that increased BMI affects temporo-parietal-occipital brain white-matter integrity in FEM. This highlights the need to further elucidate the relationship between obesity and other neural substrates (including subcortical changes) in BD which may clarify brain circuits subserving the association between obesity and clinical outcomes in BD.

ARVCF Genetic Influences on Neurocognitive and Neuroanatomical Intermediate Phenotypes in Chinese Patients With Schizophrenia

OBJECTIVE There are notable similarities between velocardiofacial syndrome and schizophrenia in terms of neurocognitive deficits and brain structural abnormalities. These similarities have supported the role of the armadillo repeat gene deleted in velocardiofacial syndrome (ARVCF) as a susceptibility gene in schizophrenia. This study investigated the relationships between haplotypes of the ARVCF gene and specific intermediate phenotypes in schizophrenia. We hypothesized that ARVCF gene haplotypes influence caudate nucleus volume, fractional anisotropy, and neurocognitive functioning in schizophrenia. METHOD Between May 2006 and November 2009, 200 Chinese participants (125 patients with DSM-IV diagnosis of schizophrenia and 75 controls) were genotyped using blood samples, and a subset of 166 participants (99 patients with DSM-IV diagnosis of schizophrenia and 67 controls) underwent structural magnetic resonance imaging, diffusion tensor imaging, and completed neuropsychological testing. RESULTS The haplotype T-G-A-T-T-G-G-C-T-G-T (ARVCF-Hap1) was significantly associated with fractional anisotropy of the caudate nucleus and executive functioning in patients. Specifically, patients with more copies of ARVCF-Hap1 have lower white matter integrity in caudate nucleus (P = .0008) and greater perseverative errors (P = .00003) on the Wisconsin Card Sorting Test. A trend of lower caudate volume (P = .015) in patients with more copies of ARVCF-Hap1 was also observed. CONCLUSIONS These findings are consistent with known ARVCF gene effects on neurodevelopment in terms of cellular arrangement, migration, and intracellular signaling involving the striatum and may involve interactions with other brain networks such as prefrontal cortex, and they underscore the importance of imaging-genetic studies to elucidate the genetic influences underlying intermediate phenotypes in complex neurobehavioral disorders.

CACNA1C genomewide supported psychosis genetic variation affects cortical brain white matter integrity in Chinese patients with schizophrenia

OBJECTIVE Recent genomewide association studies have implicated the calcium channel, voltage-dependent, L type, alpha 1C subunit (CACNA1C) genetic variant in schizophrenia, which is associated with functional brain changes and cognitive deficits in healthy individuals. However, the impact of CACNA1C on brain white matter integrity in schizophrenia remains unclear. On the basis of prior evidence of CACNA1C-mediated changes involving cortical brain regions, we hypothesize that CACNA1C risk variant rs1006737 is associated with reductions of white matter integrity in the frontal, parietal, and temporal regions and cingulate gyrus. METHOD A total of 160 Chinese participants (96 DSM-IV-diagnosed patients with schizophrenia and 64 healthy controls) were genotyped by using blood samples and underwent structural magnetic resonance imaging and diffusion tensor imaging scans from 2008 to 2012. Two-way analysis of covariance was employed to examine CACNA1C-related genotype effects, diagnosis effects, and genotype × diagnosis interaction effects on fractional anisotropy (FA) of relevant brain regions. RESULTS Significant diagnosis-genotype interactions were observed (left frontal lobe mean FA: F₁,₁₅₆ = 6.22, P = .014; left parietal lobe mean FA: F₁,₁₅₆ = 7.14, P = .008; left temporal lobe mean FA: F₁,₁₅₆ = 8.37, P = .004). Compared with patients who were A carriers, patients who were G homozygotes had lower mean FA in the left frontal lobe (F₁,₉₃ = 2.504, P = .014), left parietal lobe (F₁,₉₃ = 2.37, P = .020), and left temporal lobe (F₁,₉₃ = 3.01, P = .003), with standardized effect sizes of -1.43, -1.3, and -1.0, respectively. CONCLUSIONS CACNA1C risk variant rs1006737 affects cortical white matter integrity in schizophrenia. Further imaging genetic investigations on the mediating effect of CACNA1C in schizophrenia can uncover brain circuitries involved in schizophrenia and suggest potential novel targets for intervention.

GRIN2B Gene and Associated Brain Cortical White Matter Changes in Bipolar Disorder: A Preliminary Combined Platform Investigation

Abnormalities in glutamate signaling and glutamate toxicity are thought to be important in the pathophysiology of bipolar disorder (BD). Whilst previous studies have found brain white matter changes in BD, there is paucity of data about how glutamatergic genes affect brain white matter integrity in BD. Based on extant neuroimaging data, we hypothesized that GRIN2B risk allele is associated with reductions of brain white matter integrity in the frontal, parietal, temporal, and occipital regions and cingulate gyrus in BD. Fourteen patients with BD and 22 healthy controls matched in terms of age, gender and handedness were genotyped using blood samples and underwent diffusion tensor imaging. Compared to G allele, brain FA values were significantly lower in BD patients with risk T allele in left frontal region (P = 0.001), right frontal region (P = 0.002), left parietal region (P = 0.001), left occipital region (P = 0.001), right occipital region (P < 0.001), and left cingulate gyrus (P = 0.001). Further elucidation of the interactions between different glutamate genes and their relationships with such structural, functional brain substrates will enhance our understanding of the link between dysregulated glutamatergic neurotransmission and neuroimaging endophenotypes in BD.