Novel MR Image Processing as an Objective Diagnostic Test for Chiari Malformation - 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.
