Children with hydrocephalus (HCP) may suffer from significant brain injury resulting in concomitant functional and cognitive deficits. Even though shunt surgery can greatly reduce the morbidity and mortality associated with this condition, the potential injury related to pre-operative increased intracranial pressure and the post-operative variability in motor and neurocognitive outcomes are poorly understood. Long term prognosis for these patients remains multi-factorial and uncertain. The overall goal is to use diffusion tensor imaging (DTI) to establish white matter (WM) integrity as a non-invasive biomarker to quantify in vivo injury and post-treatment recovery in children with HCP.
The specific aims of the proposal are: (1) to quantify WM damage by comparing the anisotropic diffusion properties between children with congenital HCP and age-matched normal children;(2) to quantify WM recovery by comparing anisotropic diffusion properties in children with congenital HCP before and after the shunt surgery;and to establish the correlation between the post-shunt WM integrity and the motor and cognitive functional outcomes;(3) to define the relation between WM abnormality based on DTI with the outcome measures confounded by shunt revisions. DTI will be performed on 72 children (Age 0-3 yrs) with congenital HCP before shunt surgery and post-operatively at 3 months, 12 months, and 24 months. DTI metrics will be calculated in major WM regions of interest. Motor and general cognitive functions will be tested at the same four time points. Comparison with a matched group of normal children will enable us to quantify WM abnormalities based on DTI in children with HCP and assess the effect of surgery at various post-operative stages. We will also assess the impact of shunt revisions on the degree of WM recovery. Motor and cognitive deficits and recovery will be correlated to imaging data to provide a prognostic measure based on WM integrity in the clinical management. At the study conclusion, the derived data will improve our understanding of the change seen in WM integrity before and after treatment for HCP during a period of WM maturation. By defining the relationship of motor and neurocognitive developmental outcomes to the DTI measures of WM integrity, the study will contribute a new approach to the prognosis and longitudinally assessment of children treated for HCP.

Public Health Relevance

This study will establish the WM anisotropic diffusion property derived from DTI as a marker for in vivo white matter damage and its course of recovery in children with hydrocephalus. It will allow us to have a better understanding of the variability in the outcomes and provide a non-invasive and quantifiable means to predict these outcomes. The knowledge to be gained from the present study will also provide a solid basis for assessing treatment effect and for planning on additional therapeutic interventions, to improve the long-term outcomes to an individual's development.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Medical Imaging Study Section (MEDI)
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Hirtz, Deborah G
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Cincinnati Children's Hospital Medical Center
United States
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Mangano, Francesco T; Altaye, Mekibib; McKinstry, Robert C et al. (2016) Diffusion tensor imaging study of pediatric patients with congenital hydrocephalus: 1-year postsurgical outcomes. J Neurosurg Pediatr 18:306-19
Yuan, Weihong; Meller, Artur; Shimony, Joshua S et al. (2016) Left hemisphere structural connectivity abnormality in pediatric hydrocephalus patients following surgery. Neuroimage Clin 12:631-639
Yuan, Weihong; Harpster, Karen; Jones, Blaise V et al. (2016) Changes of White Matter Diffusion Anisotropy in Response to a 6-Week iPad Application-Based Occupational Therapy Intervention in Children with Surgically Treated Hydrocephalus: A Pilot Study. Neuropediatrics 47:336-40
Akbari, S Hassan A; Limbrick Jr, David D; McKinstry, Robert C et al. (2015) Periventricular hyperintensity in children with hydrocephalus. Pediatr Radiol 45:1189-97
Ragan, Dustin K; Cerqua, Jonathon; Nash, Tiffany et al. (2015) The accuracy of linear indices of ventricular volume in pediatric hydrocephalus: technical note. J Neurosurg Pediatr 15:547-51
Yuan, Weihong; Holland, Scott K; Shimony, Joshua S et al. (2015) Abnormal structural connectivity in the brain networks of children with hydrocephalus. Neuroimage Clin 8:483-92
Akbari, S Hassan A; Holekamp, Terrence F; Murphy, T Martin et al. (2015) Surgical management of complex multiloculated hydrocephalus in infants and children. Childs Nerv Syst 31:243-9
Masino, Susan A; Ruskin, David N (2013) Ketogenic diets and pain. J Child Neurol 28:993-1001
Yuan, W; McKinstry, R C; Shimony, J S et al. (2013) Diffusion tensor imaging properties and neurobehavioral outcomes in children with hydrocephalus. AJNR Am J Neuroradiol 34:439-45
Masino, Susan A; Kawamura Jr, Masahito; Cote, Jessica L et al. (2013) Adenosine and autism: a spectrum of opportunities. Neuropharmacology 68:116-21

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