This is a request for supplemental funds under PAR-04-140 to promote the clinical resident research experience of S. Scott Lollis, MD, a 2nd year resident in Nuerosurgery at Dartmouth-Hitchcock Medical Center, through studies of neuroimaging of hydrocephalus (HC). The parent grant, Advanced Magnetic Resonance Elastography (PI: KD. Paulsen, PhD), has the long term goal of understanding the mechanical properties of tissue to determine their relevance in diagnosing and characterizing pathology with Magnetic Resonance Elastography (MRE) which provides a unique method for their non-invasive, spatially-resolved measurement in vivo. The requested supplement frames the research hypothesis that MRE produces a unique imaging signature for HC that distinguishes the disease from cerebral atrophy (CA) which cannot be differentiated with currently available MR imaging studies.The .clinical management of HC - a disease estimated to afflict 1.5% of the population annually - is confounded by the inability to differentiate it from other neurological conditions such as CA. When correctly diagnosed, the success rate for remedy of HC condition is high and is achieved through open-cranium surgical intervention to place shunts to resume control of CSF (cerebral spinal fluid) drainage. CA, on the other hand, does not benefit from such intervention. The difficulty is that CA appears indistinguishable from HC on MR studies and patients with the two conditions present very similar neurological symptoms. The clinical dilemma is whether to operate since HC is readily remedied via ventriculoperitoneal shunts whereas CA has no known surgical treatment (it is estimated that up to one-third of such surgeries performed annually are non-beneficial as a result of imperfect patient selection.) To test the hypothesis that MRE produces a unique imaging signature for HC that distinguishes the disease from CA, animal studies will be completed in a feline model involving MRE of normal brain, HC and CA. The one-year effort will culminate in the development of a clinical protocol that will be used to translate the work into feasibility testing in humans in the future.
The specific aims of the project are to: (1) conduct a series of MRE exams in feline subjects with normal brain and HC sufficient to detect a statistically valid difference in average shear modulus in the region of interest between the 2 groups, (2) develop a new feline model for CA which induces a pathological response similar to that observed in humans but without causing an increase in intracranial pressure and conduct a series of MRE exams to evaluate differences in the MRE signature of this group relative to those in Aim #1, and (3) develop a clinical protocol for delivery of MRE exams in patients presenting with either normal or HC symptoms as determined from standard MR imaging studies and, time permitting, conduct a small pilot series of exams in consenting subjects to determine if the animal findings can be reproduced in humans.
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| Pattison, A J; Lollis, S S; Perrinez, P R et al. (2010) Time-harmonic magnetic resonance elastography of the normal feline brain. J Biomech 43:2747-52 |
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