Noninvasive blood–brain barrier integrity mapping in patients with high-grade glioma and metastasis by multi–echo time–encoded arterial spin labeling

Abstract

Purpose: In brain tumors, disruption of the blood–brain barrier (BBB) indicates malignancy. Clinical assessment is qualitative; quantitative evaluation is feasible using the K2 leakage parameter from dynamic susceptibility contrast MRI. However, contrast agent–based techniques are limited in patients with renal dysfunction and insensitive to subtle impairments. Assessing water transport times across the BBB (Tex) by multi-echo arterial spin labeling promises to detect BBB impairments noninvasively and potentially more sensitively. We hypothesized that reduced Tex indicates impaired BBB. Furthermore, we assumed higher sensitivity for Tex than dynamic susceptibility contrast–based K2, because arterial spin labeling uses water as a freely diffusible tracer. Methods: We acquired 3T MRI data from 28 patients with intraparenchymal brain tumors (World Health Organization Grade 3 & 4 gliomas [n = 17] or metastases [n = 11]) and 17 age-matched healthy controls. The protocol included multi-echo and single-echo Hadamard-encoded arterial spin labeling, dynamic susceptibility contrast, and conventional clinical imaging. Tex was calculated using a T2-dependent multi-compartment model. Areas of contrast-enhancing tissue, edema, and normal-appearing tissue were automatically segmented, and parameter values were compared across volumes of interest and between patients and healthy controls. Results: Tex was significantly reduced (−20.3%) in contrast-enhancing tissue compared with normal-appearing gray matter and correlated well with |K2| (r = −0.347). Compared with healthy controls, Tex was significantly lower in tumor patients' normal-appearing gray matter (Tex,tumor = 0.141 ± 0.032 s vs. Tex,HC = 0.172 ± 0.036 s) and normal-appearing white matter (Tex,tumor = 0.116 ± 0.015 vs. Tex,HC = 0.127 ± 0.017 s), whereas |K2| did not differ significantly. Receiver operating characteristic analysis showed a larger area under the curve for Tex (0.784) than K2 (0.604). Conclusion: Tex is sensitive to pathophysiologically impaired BBB. It agrees with contrast agent–based K2 in contrast-enhancing tissue and indicates sensitivity to subtle leakage.