Non-invasive Optical Spectroscopy-based Biomarker for Evaluating Intracranial Compliance in Chiari Malformation Patients

Introduction: Chiari malformations (CMs) are characterized by cerebellar tonsillar descent leading to abnormal cerebrospinal fluid dynamics and hindbrain crowding at the foramen magnum. Intracranial compliance (ICC) has been suggested to be pathologically decreased in CM. Previous work has shown that diminished ICC can be identified through the decreased amplitude ratio of the percussion peak (P1) to the tidal peak (P2) in pulsatile intracranial pressure (ICP) waveforms. However, invasive ICP sensors are associated with risks such as infection and hemorrhage. Instead, cerebral blood flow (CBF) waveforms, which share a similar morphology to ICP waveforms, can be measured non-invasively and serve as a biomarker for ICC monitoring. Specifically, we hypothesize that a lower P1/P2 ratio in CBF waveforms is seen in untreated CMs relative to controls.

Methods: Diffuse correlation spectroscopy (DCS), a non-invasive optical modality that uses fluctuations in near-infrared light to measure changes in microvasculature CBF, was performed on 10 CM patients and 10 healthy controls. In each case, the DCS probe was placed on the forehead while the patient was in the supine position for 9 minutes. Data was collected approximately 1-week pre-operatively and 2-weeks post-operatively in CM patients. P1/P2 ratios were calculated from DCS-derived pulsatile CBF waveforms. Additionally, a nonhuman primate hydrocephalus model was used to compare the similarity of P1/P2 in invasive ICP waveforms with non-invasive CBF waveforms.

Results: In the nonhuman primate, P1/P2 measured with the invasive ICP monitor was highly correlated to P1/P2 measured with CBF waveforms (R=0.86), thus validating the similarity in morphology. In CM patients, P1/P2 was significantly lower in pre-operative patients compared to healthy subjects (p=0.01). Additionally, P1/P2 was found to increase after decompression surgery (p=0.05) and was no longer significantly different from healthy subjects (p=0.90).

Conclusion : Abnormal ICC as measured via non-invasive CBF waveforms may be an effective biomarker for symptomatic CM and adequate post-operative decompression.