Development and Early Clinical Evaluation of Noninvasive MRI Measurement of ICP

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DESCRIPTION (provided by applicant): This bioengineering-radiology-neurosurgery partnership aims to further develop and test the clinical utility of a novel method for non-invasive measurement of intracranial compliance (ICC) and intracranial pressure (ICP). These important neurophysiologic parameters are measured using dynamic magnetic resonance imaging (MRI) of blood and cerebrospinal fluid (CSF) flows to and from the brain. The feasibility of this new technique is demonstrated using phantoms, computer simulations, non-human primate animal model, healthy volunteers, and small number of patients. Noninvasive quantification of these parameters is potentially important for improved diagnosis and treatment of several neurological problems. In this proposal we aim to demonstrate the potential clinical utility of a noninvasive ICC measurement to study a relatively common and poorly understood neurological problem, Chiari Malformations (CM) (associated with downward displacement of the cerebellar tonsils into the spinal canal). Some evidence suggests that ICC plays an important role in the pathophysiology of this disorder. However, because of increased risk of brain herniation associated with invasive ICC measurements in these patients, intracranial compliance has not been measured previously. Noninvasive ICC measurement in CM may help explain the pathophysiology and will potentially improve the diagnosis and treatment of this debilitating disorder. Moreover, since MRI is already used to diagnose CM, it would be practical to add the additional scan to obtain the ICC measurement noninvasively. While intracranial compliance quantifies the ability of the intracranial compartment to accommodate increase in volume (e.g., brain swelling) without a large increase in pressure, it is ICP that is more widely used clinically. Our MRI-based measurement of ICP relies on the inverse relationship between ICC and ICP. We propose further validations of a strong linear correlation we found between MR-ICP and invasively measured ICP in 9 patients. The proposed validations are an essential step before the method can become clinically acceptable and the potentially high diagnostic value of a noninvasive MR-ICP can be assessed in other neurological problems. The developmental components of the proposal aim at improving the MRI data acquisition scheme and at shortening overall scan time, primarily for increased measurement reliability by multiple sampling of ICP and for allowing dynamic measurements of ICP. The proposed developmental work also aims to improve measurements of total cerebral blood flow (tCBF), a byproduct of the MR-ICP measurement, by normalizing for the subject's total brain tissues volumes and weights. Preliminary results demonstrated lesser inter-individual variability of the normalized tCBF measurement.