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Featured researches published by Song Lai.


Developmental Disabilities Research Reviews | 2009

Structural and Functional Neuroimaging in Klinefelter (47,XXY) Syndrome: A Review of the Literature and Preliminary Results from a Functional Magnetic Resonance Imaging Study of Language

Kyle J. Steinman; Judith L. Ross; Song Lai; Allan L. Reiss; Fumiko Hoeft

Klinefelter (47,XXY) syndrome (KS), the most common form of sex-chromosomal aneuploidy, is characterized by physical, endocrinologic, and reproductive abnormalities. Individuals with KS also exhibit a cognitive/behavioral phenotype characterized by language and language-based learning disabilities and executive and attentional dysfunction in the setting of normal general intelligence. The underlying neurobiologic mechanisms are just now beginning to be elucidated through structural and functional neuroimaging. Here, we review the literature of structural and functional neural findings in KS identified by neuroimaging and present preliminary results from a functional magnetic resonance imaging study examining brain activity during a verb generation task in KS.


Investigative Ophthalmology & Visual Science | 2013

Evidence for widespread structural brain changes in glaucoma: a preliminary voxel-based MRI study.

Alice L. Williams; John Lackey; Sheryl S. Wizov; Tao Ming Thomas Chia; Srinivas Gatla; Mark L. Moster; Robert C. Sergott; George L. Spaeth; Song Lai

PURPOSE To investigate structural brain changes in patients with glaucoma. METHODS High-resolution T1-weighted anatomical brain magnetic resonance images (MRI) were collected in 15 patients with glaucoma of varying severity and in 15 age-, race-, and sex-matched controls. Exclusion criteria included neurological disease, another disorder which could affect the visual field, and a score of less than 25 on the mini-mental status examination. The scans were analyzed with an automatic volumetric MRI technique to measure the volumes of 93 structures in each brain. Analyses of covariance with age as a covariate were carried out to identify structures that differed significantly between the two groups (i.e., glaucoma versus normal control). The volumes of all brain structures in the group of 15 glaucoma patients were also correlated with clinical measures of disease severity. Linear multivariate regression analyses were conducted to determine the significance of these relationships. RESULTS Five structures differed significantly between the two groups (P < 0.05). These structures included the right and left inferior occipital gyri and the right middle occipital gyrus, right inferior temporal gyrus, and right occipital lobe white matter. Interestingly, all of these structures were larger in the glaucoma group than in the control group. Within the group of glaucoma patients, 38% of all brain structures had independent associations between decreasing volume and more severe disease in multivariate regression analysis. CONCLUSIONS These results suggest that patients with glaucoma undergo widespread and complex changes in cortical brain structure and that the extent of these changes correlates with disease severity.


The Journal of Neuroscience | 2011

Neuroanatomical Phenotype of Klinefelter Syndrome in Childhood: A Voxel-Based Morphometry Study

Daniel M. Bryant; Fumiko Hoeft; Song Lai; John Lackey; David P. Roeltgen; Judith L. Ross; Allan L. Reiss

Klinefelter syndrome (KS) is a genetic disorder characterized by a supernumerary X chromosome. As such, KS offers a naturally occurring human model for the study of both X-chromosome gene expression and androgen on brain development. Previous neuroimaging studies have revealed neuroanatomical variations associated with KS, but have differed widely with respect to subject inclusion criteria, including mosaicism, pubertal status, and history of testosterone replacement therapy (TRT), all factors likely to influence neurodevelopment. We conducted a voxel-based morphometry study of regional gray and white matter (GM and WM, respectively) volumes in 31 KS males (mean age, 9.69 ± 1.70 years) and 36 typically developing (TD) male controls (10.99 ± 1.72 years). None of the participants with KS had received TRT, and all were prepubertal and had nonmosaic 47,XXY karyotypes. After controlling for age, males with KS showed trends (0.05 < p < 0.10) for significantly reduced total gray matter volume (TGMV) and total white matter volume (TWMV), relative to TD males. After controlling for TGMV and age, the KS group had significantly increased sensorimotor and parietal-occipital GM and significantly reduced amygdalar, hippocampal, insular, temporal, and inferior frontal GM relative to TD controls. After controlling for TWMV and age, the KS group had significantly increased left parietal WM as well as significantly reduced frontal and temporal WM. These findings are indicative of a characteristic prepubertal neuroanatomical phenotype that may be associated with cognitive-behavioral features of KS. This work offers new insight into the relationships among X-chromosome gene expression, neuroanatomy, and cognitive-behavioral functions impaired in KS, including language and attention.


Developmental Medicine & Child Neurology | 2012

Sex chromosomes and the brain: a study of neuroanatomy in XYY syndrome

Daniel M. Bryant; Fumiko Hoeft; Song Lai; John Lackey; David P. Roeltgen; Judith L. Ross; Allan L. Reiss

Aim  To assess global and regional brain matter variations associated with XYY syndrome by comparison with Klinefelter syndrome and typical development.


Biopolymers | 2008

Design of (Gd-DO3A)n-Polydiamidopropanoyl-Peptide Nucleic Acid-d(Cys-Ser-Lys-Cys) Magnetic Resonance Contrast Agents

Nariman V. Amirkhanov; Ivan Dimitrov; Armin W. Opitz; Kaijun Zhang; John Lackey; Christopher A. Cardi; Song Lai; Norman J. Wagner; Mathew L. Thakur; Eric Wickstrom

We hypothesized that chelating Gd(III) to 1,4,7-tris(carboxymethylaza)cyclododecane-10-azaacetylamide (DO3A) on peptide nucleic acid (PNA) hybridization probes would provide a magnetic resonance genetic imaging agent capable of hybridization to a specific mRNA. Because of the low sensitivity of Gd(III) as an magnetic resonance imaging (MRI) contrast agent, a single Gd-DO3A complex per PNA hybridization agent could not provide enough contrast for detection of cancer gene mRNAs, even at thousands of mRNA copies per cell. To increase the Gd(III) shift intensity of MRI genetic imaging agents, we extended a novel DO3An-polydiamidopropanoyl (PDAPm) dendrimer, up to n = 16, from the N-terminus of KRAS PNA hybridization agents by solid phase synthesis. A C-terminal D(Cys-Ser-Lys-Cys) cyclized peptide analog of insulin-like growth factor 1 (IGF1) was included to enable receptor-mediated cellular uptake. Molecular dynamic simulation of the (Gd-DO3A-AEEA)16-PDAP4-AEEA2-KRAS PNA-AEEA-D(Cys-Ser-Lys-Cys) genetic imaging nanoparticles in explicit water yielded a pair correlation function similar to that of PAMAM dendrimers, and a predicted structure in which the PDAP dendron did not sequester the PNA. Thermal melting measurements indicated that the size of the PDAP dendron included in the (DO3A-AEEA)n-PDAPm-AEEA2-KRAS PNA-AEEA-D(Cys-Ser-Lys-Cys) probes (up to 16 Gd(III) cations per PNA) did not depress the melting temperatures (Tm) of the complementary PNA/RNA hybrid duplexes. The Gd(III) dendrimer PNA genetic imaging agents in phantom solutions displayed significantly greater T1 relaxivity per probe (r1 = 30.64 +/- 2.68 mM(-1) s(-1) for n = 2, r1 = 153.84 +/- 11.28 mM(-1) s(-1) for n = 8) than Gd-DTPA (r1 = 10.35 +/- 0.37 mM(-1) s(-1)), but less than that of (Gd-DO3A)32-PAMAM dendrimer (r1 = 771.84 +/- 20.48 mM(-1) s(-1)) (P < 0.05). Higher generations of PDAP dendrimers with 32 or more Gd-DO3A residues attached to PNA-D(Cys-Ser-Lys-Cys) genetic imaging agents might provide greater contrast for more sensitive detection.


Ajidd-american Journal on Intellectual and Developmental Disabilities | 2010

Atypical Functional Brain Activation During a Multiple Object Tracking Task in Girls With Turner Syndrome: Neurocorrelates of Reduced Spatiotemporal Resolution

Elliott A. Beaton; Joel Stoddard; Song Lai; John Lackey; Jianrong Shi; Judith L. Ross; Tony J. Simon

Turner syndrome is associated with spatial and numerical cognitive impairments. We hypothesized that these nonverbal cognitive impairments result from limits in spatial and temporal processing, particularly as it affects attention. To examine spatiotemporal attention in girls with Turner syndrome versus typically developing controls, we used a multiple object tracking task during functional magnetic resonance (fMRI) imaging. Participants actively tracked a target among six distracters or passively viewed the animations. Neural activation in girls with Turner syndrome during object tracking overlapped with but was dissimilar to the canonical frontoparietal network evident in typically developing controls and included greater limbic activity. Task performance and atypical functional activation indicate anomalous development of cortical and subcortical temporal and spatial processing circuits in girls with Turner syndrome.


Magnetic Resonance in Medicine | 2009

Phase labeling using sensitivity encoding: data acquisition and image reconstruction for geometric distortion correction in epi.

Udomchai Techavipoo; Thomas Leist; Song Lai

Geometric distortion caused by magnetic field inhomogeneity is generally an inevitable tradeoff for fast MRI acquisitions using echo‐planar imaging. Most of the existing distortion‐correction techniques require separate scans for field maps in order to correct the distortion contained in a measurement. A drawback of these current techniques is that the field map scans and the measurement can capture different patient positions, which invalidates the stationary condition. A new method was developed in this work to correct geometric distortion by using local phase shifts derived directly from the measurement itself, without the need of extra field map scans. This self‐sufficient method takes advantage of parallel imaging and k‐space trajectory modification to produce multiple images from a single acquisition. The measurement is also used to derive sensitivity maps for parallel imaging reconstruction. The derived phase shifts are retrospectively applied to the measurement for correction of geometric distortion in the measurement itself. The proposed method was successfully demonstrated using experimental data from a phantom and a human brain. Magn Reson Med, 2009.


Journal of Magnetic Resonance Imaging | 2009

Toward a practical protocol for human optic nerve DTI with EPI geometric distortion correction

Udomchai Techavipoo; Annette F. Okai; John Lackey; Jianrong Shi; Michael A. Dresner; Thomas Leist; Song Lai

To develop a practical protocol for diffusion tensor imaging (DTI) of the human optic nerve with echo planar imaging (EPI) geometric distortion correction.


Biochemical Society Transactions | 2007

Receptor-mediated internalization of chelator-PNA-peptide hybridization probes for radioimaging or magnetic resonance imaging of oncogene mRNAs in tumours

Xiaobing Tian; Atis Chakrabarti; Nariman V. Amirkhanov; Mohan R. Aruva; Kaijun Zhang; Christopher A. Cardi; Song Lai; Mathew L. Thakur; Eric Wickstrom

Early external detection of cancer gene activity might enable early treatment of cancer and might reduce cancer mortality. We hypothesized that oncogene mRNA overexpressed at thousands of copies per malignant cell in a zone of transformed cells could be imaged externally by scintigraphic imaging, PET (positron emission tomography) or MRI (magnetic resonance imaging) with PNA (peptide nucleic acid) hybridization probes that include chelators for metal cations and a cyclized peptide analogue of IGF-1 (insulin-like growth factor 1), D(Cys-Ser-Lys-Cys), to mediate internalization by IGF1R (IGF-1 receptor) overexpressed on cancer cells. We observed that human MCF7 breast cancer cells that overexpress IGF1R efficiently internalized fluorescein-chelator-PNA-D(Cys-Ser-Lys-Cys) to the cytoplasm, but not with D(Cys-Ala-Ala-Cys). Scintigraphic imaging of MCF7 xenografts in immunocompromised mice revealed that CCND1 and MYC [(99m)Tc]chelator-PNA-D(Cys-Ser-Lys-Cys) probes yielded xenograft. PET imaging with [(64)Cu]chelator-PNA-D(Cys-Ser-Lys-Cys) yielded stronger signals. Scintigraphic imaging of human AsPC1 pancreas cancer xenografts with [(99m)Tc]chelator-KRAS PNA-D(Cys-Ser-Lys-Cys) yielded strong xenograft signals. Stronger xenograft image intensities were obtained by PET imaging of [(64)Cu]chelator-KRAS PNA-D(Cys-Ser-Lys-Cys). MRI required extension of chelator-polydiamidopropanoate dendrimers from the N-termini of the PNA probes to increase the number of contrast paramagnetic gadolinium (III) cations per probe. These results provide a basis for detection of oncogene activity in tissues from outside the body by hybridization with metal-chelator-PNA-peptides that are selectively internalized by cancer cells.


Genes, Brain and Behavior | 2014

Brain morphology in children with 47,XYY syndrome: a voxel- and surface-based morphometric study

Jean-François Lepage; David S. Hong; Mira Raman; Matthew Marzelli; David P. Roeltgen; Song Lai; Judith L. Ross; Allan L. Reiss

The neurocognitive and behavioral profile of individuals with 47,XYY is increasingly documented; however, very little is known about the effect of a supernumerary Y‐chromosome on brain development. Establishing the neural phenotype associated with 47,XYY may prove valuable in clarifying the role of Y‐chromosome gene dosage effects, a potential factor in several neuropsychiatric disorders that show a prevalence bias toward males, including autism spectrum disorders. Here, we investigated brain structure in 10 young boys with 47,XYY and 10 age‐matched healthy controls by combining voxel‐based morphometry (VBM) and surface‐based morphometry (SBM). The VBM results show the existence of altered gray matter volume (GMV) in the insular and parietal regions of 47,XYY relative to controls, changes that were paralleled by extensive modifications in white matter (WM) bilaterally in the frontal and superior parietal lobes. The SBM analyses corroborated these findings and revealed the presence of abnormal surface area and cortical thinning in regions with abnormal GMV and WMV. Overall, these preliminary results demonstrate a significant impact of a supernumerary Y‐chromosome on brain development, provide a neural basis for the motor, speech and behavior regulation difficulties associated with 47,XYY and may relate to sexual dimorphism in these areas.

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John Lackey

Thomas Jefferson University

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Jianrong Shi

Thomas Jefferson University

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Judith L. Ross

Thomas Jefferson University

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Thomas Leist

Thomas Jefferson University

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Eric Wickstrom

Thomas Jefferson University

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Fumiko Hoeft

University of California

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