Thursday, May 16, 2024
5/16/2024
Summary: Chiari malformation Type I (CM) is a serious neurological disorder characterized by the cerebellar tonsillar position located below the foramen magnum (tonsillar ectopia). The “crowding” that occurs near the foramen magnum causes compression on the cerebellum and brainstem and disrupts the natural flow of cerebrospinal fluid. To further complicate matters, 3% of children and 1% of adults are shown to have tonsillar ectopia on a radiology report, but just 300,000 individuals (0.08%) are diagnosed with CM in the US. Thus, there are greater than 10 times more individuals with radiographic evidence of tonsillar ectopia than individuals that actually have a diagnosis of CM. As such, surgeons and patients are dissatisfied with the current radiological measurement as a diagnostic criterion. Approximately 20,000 CM patients are evaluated each year for surgery in the US from which half receive surgical decompression of the posterior fossa with the goal of creating more space around the cerebellar tonsils. While the majority of CM patients have reported improvement in quality of life after surgery, this improvement is not consistent across different symptoms. The significance of the situation even got the attention of Congress, which in 2009 directed NINDS to, “encourage aggressive measures toward advanced engineering and imaging analysis to an objective diagnostic test for CM.” Static anatomical measurements alone are NOT adequate to diagnose CM. The combination of altered brain anatomy with altered CSF motion and dynamic brain tissue strain during the cardiac cycle likely work together to cause CM symptoms. Thus, understanding the relationship between biomechanical and disease severity measures would lead to an objective diagnostic test for CM. The goal of the proposed study is to obtain novel MR-based dynamic biomechanical measures before decompression surgery and determine their relationship with disease severity measures. We hypothesize that these biomechanical measures are correlated with disease severity measures. Furthermore, these biomechanical measures may reflect the underlying pathophysiology associated with CM, and serve as a better prognostic indicator than the standard methods that are currently being used clinically. Our group has developed several novel MR image-processing techniques that provide in-vivo subject-specific biomechanical measures of 1) resistance to CSF motion, 2) brain tissue strain, and 3) brain morphometrics. In a different group of CM patients, we have examined disease severity measures including DTI, cognitive function, and symptomology. Preliminary results have demonstrated these biomechanical and disease severity measures to be significantly different in CM subjects compared to healthy controls. However, these measures need to be acquired on the same patient population in order to determine their precise relationship. We will obtain biomechanical and disease severity measures in 50 adult CM patients before surgery. This study will provide an understanding of the importance of biomechanical measures in the pathophysiology of CM that may lead to better clinical diagnostic testing for CM.
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