We are developing a suite of new computational methods to predict disposition of therapeutic agents directly injected into brain parenchyma. Our broad purpose is to develop a systems approach to site-specific delivery for brain diseases. We expect use in device design and selection, animal and pre-clinical testing, pre-operative planning, intra-operative controlled delivery, and post-operative monitoring. This fast track application aims to create (i) methods to validate models via in-vivo imaging (in Phase I), and (ii) a software product that can be used for predicting spatial distribution of intra-parenchymally injected molecules (in Phase II).
The specific aims i n Phase I are: (1) investigate MRI methods that can accurately assess the concentration of contrast agents in tissue when increase of water content and tissue edema can make quantitation difficult; and (2) propose methods to assess the resistance of brain tissue to the flow of injected fluid, including preferred directions of flow. Successful completion will enable assay of molecules in tissue in vivo for research. This will therefore have value well beyond the other aim, namely to provide the basis for validating software which will be developed in Phase II to serve as a critical pre-operative planning tool for all such deliveries in clinical practice.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
4R44NS043105-02
Application #
6790727
Study Section
Special Emphasis Panel (ZRG1-SSS-E (02))
Program Officer
Jacobs, Tom P
Project Start
2003-09-30
Project End
2004-08-31
Budget Start
2003-09-30
Budget End
2004-08-31
Support Year
2
Fiscal Year
2003
Total Cost
$419,027
Indirect Cost
Name
Image-Guided Neurologics, Inc.
Department
Type
DUNS #
City
Baltimore
State
MD
Country
United States
Zip Code
21210
Macauley, Shannon L; Roberts, Marie S; Wong, Andrew M et al. (2012) Synergistic effects of central nervous system-directed gene therapy and bone marrow transplantation in the murine model of infantile neuronal ceroid lipofuscinosis. Ann Neurol 71:797-804
Roberts, Marie S; Macauley, Shannon L; Wong, Andrew M et al. (2012) Combination small molecule PPT1 mimetic and CNS-directed gene therapy as a treatment for infantile neuronal ceroid lipofuscinosis. J Inherit Metab Dis 35:847-57
Raghavan, Raghu; Brady, Martin (2011) Predictive models for pressure-driven fluid infusions into brain parenchyma. Phys Med Biol 56:6179-204
Macauley, Shannon L; Pekny, Milos; Sands, Mark S (2011) The role of attenuated astrocyte activation in infantile neuronal ceroid lipofuscinosis. J Neurosci 31:15575-85
Cooper, Jonathan D (2010) The neuronal ceroid lipofuscinoses: the same, but different? Biochem Soc Trans 38:1448-52
Wong, Andrew M S; Rahim, Ahad A; Waddington, Simon N et al. (2010) Current therapies for the soluble lysosomal forms of neuronal ceroid lipofuscinosis. Biochem Soc Trans 38:1484-8
Kielar, Catherine; Wishart, Thomas M; Palmer, Alice et al. (2009) Molecular correlates of axonal and synaptic pathology in mouse models of Batten disease. Hum Mol Genet 18:4066-80
Macauley, Shannon L; Wozniak, David F; Kielar, Catherine et al. (2009) Cerebellar pathology and motor deficits in the palmitoyl protein thioesterase 1-deficient mouse. Exp Neurol 217:124-35
Raghavan, Raghu; Brady, Martin L; Rodriguez-Ponce, Maria Inmaculada et al. (2006) Convection-enhanced delivery of therapeutics for brain disease, and its optimization. Neurosurg Focus 20:E12