Technical Note: Quantification of blood‐spinal cord barrier permeability after application of magnetic resonance‐guided focused ultrasound in spinal cord injury
Chloe G. Cross, Allison Payne, Gregory W. J. Hawryluk, Riley Haag‐Roeger, Rahul Cheeniyil, Dalton Brady, Henrik Odéen, Satoshi Minoshima, Donna J. Cross, Yoshimi Anzai
Abstract
PURPOSE: To demonstrate that magnetic resonance-guided focused ultrasound (MRgFUS) facilitates blood-spinal cord barrier (BSCB) permeability and develop observer-independent MRI quantification of BSCB permeability after MRgFUS for spinal cord injury (SCI). METHODS: Noninjured Sprague-Dawley rats (n = 3) underwent MRgFUS and were administered Evans blue post-MRgFUS to confirm BSCB opening. Absorbance was measured by spectrophotometry and correlated with its corresponding image intensity. Rats (n = 21) underwent T8-T10 laminectomy and extradural compression of the spinal cord (23g weighted aneurysm-type clip, 1 min). The intervention group (n = 11) was placed on a preclinical MRgFUS system, administered microbubbles (Optison, 0.2 mL/kg), and received 3 MRgFUS sonications (25 ms bursts, 1 Hz pulses for 3 min, 3 acoustic W, approximately 1.0-2.1 MPa peak pressure as measured via hydrophone). The sham group (n = 10) received equivalent procedures with no sonications. T1w MRI was obtained both pre- and post-MRgFUS BSCB opening. Spinal cords were segmented manually or semiautomatically and a Pearson correlation with P ≤ 0.001 was used to correlate the two segmentation methods. MRgFUS sonication and control regions intensity values were evaluated with a paired t-test with a P ≤ 0.01. RESULTS: Semiautomatic segmentation reduced computational time by 95% and was correlated with manual segmentation (Pearson = 0.92, P < 0.001, n = 71 regions). In the noninjured rat group, Evans blue absorbance correlated with image intensity in the MRgFUS and control regions (Pearson = 0.82, P = 0.02, n = 6). In rats that underwent the SCI procedure, an increase in signal intensity in the MRgFUS targeted region relative to control was seen in all SCI rats (10.65 ± 12.4%, range: 0.96-43.9%, n = 11, P = 0.002). SCI sham MRgFUS revealed no change (0.63 ± 0.52%, 95% CI 0.320.95, n = 10). This result was significant between both groups (P = 0.003). CONCLUSION: The implemented semiautomatic segmentation procedure improved data analysis efficiency. Quantitative methods using contrast-enhanced MRI with histological validation are sensitive for detection of blood-spinal cord barrier opening induced by magnetic resonance-guided focused ultrasound.