Krabbe Disease is an inherited neurodegenerative disease that is rapidly progressive and fatal within 2 years. It is caused by galactocerebrosidase enzyme deficiency (GALC) that results in disruption of myelin metabolism. Once the myelin sheath is destroyed, severe degeneration of mental and motor skills ensue. Umbilical cord transplantation (UCBT) is the only treatment available and is only successful if the patient is treated before symptoms appear. This study will examine the potential for Diffusion Tensor Imaging to be used prognostically for urgent treatment decisions, and as a marker of disease progression associated with motor disability after UCBT. We propose to develop a quantitative method to objectively identify presymptomatic white matter tract abnormalities in at-risk newborns who should receive immediate treatment. This approach will be a key component of a population screening program that identifies babies with low galactocerebrosidase where a family history cannot confirm the diagnosis of infantile Krabbe Disease.
Specific Aims : 1) In a prospective study of over 100 babies with low galactocerebrosidase enzyme, determine if DTI can identify which of these newborns will develop infantile Krabbe Disease, 2) To assess how corticospinal white matter tract myelination progresses in the first 24 months of life in infants with low galactocerebrosidase who do not develop infantile Krabbe Disease, 3) To determine, among transplanted children, whether long- term motor function can be predicted by baseline DTI fractional anisotropy measurements. The new knowledge acquired can be immediately translated into clinical practice by correlating DTI measures with disease severity, expected rate of progression and clinical outcomes. The measure has the potential to be validated as a surrogate marker of diseases progression when evaluating the efficacy of new treatments. PUBLIC HEALTH NARRATIVE: Krabbe disease is an inherited neurodegenerative disease that is fatal if untreated within 2 years. Umbilical cord transplantation (UCBT) is only successful if the patient is treated before symptoms appear. This study will examine the potential for Diffusion Tensor Imaging to be used prognostically for treatment decisions, and as a marker of disease progression associated with motor disability after UCBT.
|Escolar, M L; Kiely, B T; Shawgo, E et al. (2017) Psychosine, a marker of Krabbe phenotype and treatment effect. Mol Genet Metab 121:271-278|
|Zuccoli, Giulio; Narayanan, Srikala; Panigrahy, Ashok et al. (2015) Midbrain morphology reflects extent of brain damage in Krabbe disease. Neuroradiology 57:739-45|
|Gupta, A; Poe, M D; Styner, M A et al. (2015) Regional differences in fiber tractography predict neurodevelopmental outcomes in neonates with infantile Krabbe disease. Neuroimage Clin 7:792-8|
|Sharma, Anuja; Fletcher, P Thomas; Gilmore, John H et al. (2014) PARAMETRIC REGRESSION SCHEME FOR DISTRIBUTIONS: ANALYSIS OF DTI FIBER TRACT DIFFUSION CHANGES IN EARLY BRAIN DEVELOPMENT. Proc IEEE Int Symp Biomed Imaging 2014:559-562|
|Martin, Holly R; Poe, Michele D; Provenzale, James M et al. (2013) Neurodevelopmental outcomes of umbilical cord blood transplantation in metachromatic leukodystrophy. Biol Blood Marrow Transplant 19:616-24|
|Farzinfar, Mahshid; Oguz, Ipek; Smith, Rachel G et al. (2013) Diffusion imaging quality control via entropy of principal direction distribution. Neuroimage 82:1-12|
|Farzinfar, Mahshid; Li, Yin; Verde, Audrey R et al. (2013) DTI Quality Control Assessment via Error Estimation From Monte Carlo Simulations. Proc SPIE Int Soc Opt Eng 8669:1667549|
|Csapo, Istvan; Davis, Brad; Shi, Yundi et al. (2013) Longitudinal image registration with temporally-dependent image similarity measure. IEEE Trans Med Imaging 32:1939-51|
|Gupta, Aditya; Toews, Matthew; Janardhana, Ravikiran et al. (2013) Fiber feature map based landmark initialization for highly deformable DTI registration. Proc SPIE Int Soc Opt Eng 8669:|
|Sharma, Anuja; Fletcher, P Thomas; Gilmore, John H et al. (2013) SPATIOTEMPORAL MODELING OF DISCRETE-TIME DISTRIBUTION-VALUED DATA APPLIED TO DTI TRACT EVOLUTION IN INFANT NEURODEVELOPMENT. Proc IEEE Int Symp Biomed Imaging 2013:684-687|
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