Non-invasive biomarkers for spontaneous intracranial hypotension (SIH) through phase-contrast MRI

Abstract

Background and objective: Spontaneous intracranial hypotension (SIH) is an underdiagnosed disease. To depict the accurate diagnosis can be demanding; especially the detection of CSF-venous fistulas poses many challenges. Potential dynamic biomarkers have been identified through non-invasive phase-contrast MRI in a limited subset of SIH patients with evidence of spinal longitudinal extradural collection. This study aimed to explore these biomarkers related to spinal cord motion and CSF velocities in a broader SIH cohort.

Methods: A retrospective, monocentric pooled-data analysis was conducted of patients suspected to suffer from SIH who underwent phase-contrast MRI for spinal cord and CSF velocity measurements at segment C2/C3 referred to a tertiary center between February 2022 and June 2023. Velocity ranges (mm/s), total displacement (mm), and further derivatives were assessed and compared to data from the database of 70 healthy controls.

Results: In 117 patients, a leak was located (54% ventral leak, 20% lateral leak, 20% CSF-venous fistulas, 6% sacral leaks). SIH patients showed larger spinal cord and CSF velocities than healthy controls: e.g., velocity range 7.6 ± 3 mm/s vs. 5.6 ± 1.4 mm/s, 56 ± 21 mm/s vs. 42 ± 10 mm/s, p < 0.001, respectively. Patients with lateral leaks and CSF-venous fistulas exhibited an exceptionally heightened level of spinal cord motion (e.g., velocity range 8.4 ± 3.3 mm/s; 8.2 ± 3.1 mm/s vs. 5.6 ± 1.4 mm/s, p < 0.001, respectively).

Conclusion: Phase-contrast MRI might become a valuable tool for SIH diagnosis, especially in patients with CSF-venous fistulas without evidence of spinal extradural fluid collection.

Keywords: CSF flow; CSF–venous fistula; Phase-contrast MRI; Spinal cord motion; Spontaneous intracranial hypotension.

Fig. 1

Examples of MRI sequences and MRI processing among patients with SIH—top row with sagittal 3D T2 SPACE of the cervical spine, without (middle) and with segmentation (blue = CSF, left, orange = spinal cord, right side). The axial images are phase images with and without automated segmentation. Through-plane axial measurements at C2/C3 (red line) encode velocities in head–feet direction (arrows). At the bottom, acquired velocities in mm/s (y-axis) are plotted over one standardized heartbeat (x-axis). Measurements start with the R-peak of the ECG. Each colored line indicates a different individual. The arrows within the time-resolved plots indicate the peak-to-peak velocity amplitude = velocity range in the craniocaudal direction

Fig. 2

Clinical data of patients with confirmed spinal CSF leaks, n = 117, spinal longitudinal extradural collection (SLEC). Patients with CSF–venous fistulas were older than patients with ventral or lateral leaks (p < 0.001, p = 0.001, respectively) and showed higher Bern scores (p > 0.082)

Fig. 3

Boxplots of velocity ranges (top) and adjusted velocity ranges (bottom) in healthy participants (green) and SIH patients (blue) stratified by leak type

Fig. 4

Receiver operating characteristics of spinal cord motion analysis at the segment C2/C3 in SIH patients with confirmed CSF–venous fistulas. The area under the curve (AUROC) for all spinal cord data is > 0.744, maximum is reached by measurements of the velocity range adjusted to age and sex: 0.83 in patients with CSF–venous fistula