Structural and Functional imaging approaches Advanced imaging technology affords a detailed understanding of altered brain function in the developmental disabilities as well as a means with which to test therapies. The molecular biology revolution has revealed a myriad of genotypes that affect brain development. Neuroimaging permits us to characterize phenotypes that associate with particular mutations. The combination of multiple imaging modalities - MRI, MEG, CT, PET and SPECT - offers a unique regional profiling of disease. Imaging has several distinct advantages: 1. Imaging is non-invasive. 2. Imaging offers regional (spatially-localized) assessment of structural, physiological, functional and biochemical aspects of brain tissue. Although a single modality cannot offer this broad characterization, spatially registered integration of MRI, CT, SPECT and PET information can provide an """"""""imaging"""""""" phenotype, or profile. Combined with the temporal and spectral informafion from MEG, this """"""""phenotype"""""""" can be extended to 5-dimensions. 3. It allows whole-body screening for potential toxicifies and side effects as well as non-local spread. 4.The """"""""Imaging"""""""" phenotype can be quantified in each of its domains to provide objective indices of disease progression and response to therapy. Such quantificafion may be volumetric (e.g. region size), morphologic (e.g. encapsulated vs. infiltrative, stellate tumor) or parametric along physiological axes (such as fracfional tissue blood volume, microvascular permeability or rate of glucose metabolism). 5. Use of imaging criteria as """"""""inclusion criteria"""""""" for preclinical (and by extension clinical) trials will improve the homogeneity of the sample populafion and speed up the drug evaluafion process as well as providing an objective criterion or set of criteria for patient stratification/selection for treatment. 6.Imaging is translational. MRI, CT, SPECT and PET can be performed in human preclinical and clinical trials. The same biomarkers can be used in humans as were established in the animal models. Furthermore, imaging may provide eariy evidence of biological response. Conversely a non-responding patient can be identified at an eariier stage and management can be altered. 7. Preclinical imaging is ethically appropriate, thus minimizing use of laboratory animals. Preclinical imaging can use a serial design. This has many advantages: (i) By using each mouse as its own """"""""control"""""""", it is not necessary to know the precise rate of disease progression. Consequently, small differences in the response of a cohort can be identified without assuming a cohort mean, (ii) Statistical power is Improved. For example, a paired t test can be used to screen for tumor volume post-treatment, (ili) Non-invasive imaging discloses disease prior to onset of symptomatology, (iv) individual differences within a cohort can be studied, thereby reflecting patient variability.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Center Core Grants (P30)
Project #
5P30HD026979-25
Application #
8723676
Study Section
Special Emphasis Panel (ZHD1-MRG-C)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
25
Fiscal Year
2014
Total Cost
$177,032
Indirect Cost
$43,867
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Yerys, Benjamin E; Herrington, John D; Satterthwaite, Theodore D et al. (2017) Globally weaker and topologically different: resting-state connectivity in youth with autism. Mol Autism 8:39
Chapman, Kimberly A; Ostrovsky, Julian; Rao, Meera et al. (2017) Propionyl-CoA carboxylase pcca-1 and pccb-1 gene deletions in Caenorhabditis elegans globally impair mitochondrial energy metabolism. J Inherit Metab Dis :
Monnerie, Hubert; Romer, Micah; Jensen, Brigid K et al. (2017) Reduced sterol regulatory element-binding protein (SREBP) processing through site-1 protease (S1P) inhibition alters oligodendrocyte differentiation in vitro. J Neurochem 140:53-67
Yerys, Benjamin E; Nissley-Tsiopinis, Jenelle; de Marchena, Ashley et al. (2017) Evaluation of the ADHD Rating Scale in Youth with Autism. J Autism Dev Disord 47:90-100
Glauser, Tracy A; Holland, Katherine; O'Brien, Valerie P et al. (2017) Pharmacogenetics of antiepileptic drug efficacy in childhood absence epilepsy. Ann Neurol 81:444-453
Hanamura, Kenji; Washburn, Halley R; Sheffler-Collins, Sean I et al. (2017) Extracellular phosphorylation of a receptor tyrosine kinase controls synaptic localization of NMDA receptors and regulates pathological pain. PLoS Biol 15:e2002457
Chen, Yong; Bang, Sookhee; McMullen, Mary F et al. (2017) Neuronal Activity-Induced Sterol Regulatory Element Binding Protein-1 (SREBP1) is Disrupted in Dysbindin-Null Mice-Potential Link to Cognitive Impairment in Schizophrenia. Mol Neurobiol 54:1699-1709
White, Rachel S; Bhattacharya, Anup K; Chen, Yong et al. (2016) Lysosomal iron modulates NMDA receptor-mediated excitation via small GTPase, Dexras1. Mol Brain 9:38
Herrington, John D; Miller, Judith S; Pandey, Juhi et al. (2016) Anxiety and social deficits have distinct relationships with amygdala function in autism spectrum disorder. Soc Cogn Affect Neurosci 11:907-14
Mlynarski, Elisabeth E; Xie, Michael; Taylor, Deanne et al. (2016) Rare copy number variants and congenital heart defects in the 22q11.2 deletion syndrome. Hum Genet 135:273-85

Showing the most recent 10 out of 311 publications