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

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 (T_ex) by multi-echo arterial spin labeling promises to detect BBB impairments noninvasively and potentially more sensitively. We hypothesized that reduced T_ex indicates impaired BBB. Furthermore, we assumed higher sensitivity for T_ex 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. T_ex 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: T_ex 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, T_ex was significantly lower in tumor patients' normal-appearing gray matter (T_ex,tumor = 0.141 ± 0.032 s vs. T_ex,HC = 0.172 ± 0.036 s) and normal-appearing white matter (T_ex,tumor = 0.116 ± 0.015 vs. T_ex,HC = 0.127 ± 0.017 s), whereas |K₂| did not differ significantly. Receiver operating characteristic analysis showed a larger area under the curve for T_ex (0.784) than K₂ (0.604).

Conclusion: T_ex is sensitive to pathophysiologically impaired BBB. It agrees with contrast agent-based K₂ in contrast-enhancing tissue and indicates sensitivity to subtle leakage.