Increased Hindbrain Motion in Chiari Malformation I Patients Measured Through 3D Amplified MRI (3D aMRI)

Chiari Malformation type 1 (CM-I) is a neurological disorder characterized by morphological defects such as excessive cerebral tonsils herniation and vast associated symptomatology. Given that these structural defects cannot explain the underlying symptomatology, and might result in misdiagnosis, in this work, we studied the brain’s intrinsic motion to better understand the mechanisms of CM-I. We acquired 3D cine MRI of 14 healthy and 14 CM-I subjects and used 3D amplified MRI (3D aMRI) to visualize and measure the brain’s intrinsic motion during the cardiac cycle. We observed that the regional brain motion in CM-I was significantly higher than the healthy subjects, with anterior-posterior (AP) and superior-inferior (SI) displacements in cerebral tonsils and medulla having the highest differences between the healthy and CM-I (∽45% ∽73% increased motion in the CM-I group). The motion of the cerebellum, and brainstem in AP directions (∽42% and ∽31% increased motion in the CM-I group, respectively), followed by the motion of the cerebral tonsils and medulla in medial-lateral (ML) directions were other significant differences found between the two groups (∽16% increased motion in the CM-I group). Additionally, for the CM-I subjects, we measured morphological parameters including the tonsil herniation, ratio of neural tissue in the foramen magnum, and 4 th ventricle volume. We then used the morphometrics and brain’s intrinsic motion to analyze the symptomatology of the CM-I patients and their surgical outcomes. Interestingly, we found the ratio of neural tissue in the foramen to be directly correlated with the SI motion of the tonsils ( r = 0.58). We also found the tonsil herniation to be directly correlated with the AP motion of the tonsils ( r = 0.61), and AP and ML motions of the medulla ( r = 0.66, and r = 0.57). Additionally, we found the ML motion of the tonsils to be the only indicator of the surgical outcome ( AUC = 0.95), in which subjects with higher motion had an improved outcome. Although we did not observe a significant correlation between the brains motion and morphometrics on the CM-I symptoms due to our small sample size, illustrative cases increase our hope for the development of a future tool based on the brain biomechanics. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was supported by NIH Grant No. 1R21NS111415-01 and partially by NSF Grant No. CMMI-1953323. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: IRB of Icahn School of Medicine at Mount Sinai gave ethical approval for this work (IRB-18-01303). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors