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Arterial Spin Labeling-Derived Fractional Tumor Burden as a Primary Biomarker for Differentiating Recurrent Tumor
Rafail Christodoulou1, Elham Rahimy1, Erqi Liu Pollom1
1From the Division of Neuroimaging and Neurointervention, Department of Radiology (R.C., M.I.), Radiation Oncology (E.R., E.L.P., S.S.), Neurosurgery (M.H.G.), Division of Neuro-Oncology, Department of Neurology (S.N.), Stanford Brain Tumor Center (E.R., E.L.P., M.H.G., S.N., S.S., M.I.), Stanford University, Stanford, CA.
Background And Purpose:
Differentiating recurrent tumor from radiation necrosis after stereotactic radiosurgery remains a challenge with conventional MRI. Fractional tumor burden, a voxel-level perfusion biomarker originally developed using DSC-MRI, characterizes intralesional perfusion heterogeneity and has demonstrated good performance and improved interrater agreement in diagnostic interpretations over conventional perfusion metrics. We evaluated arterial spin labeling-derived fractional tumor burden for distinguishing tumor recurrence from radiation necrosis in treated brain metastases.
Materials And Methods:
This retrospective study included 86 patients with 102 brain metastases (68 radiation necrosis, 34 tumor) evaluated with arterial spin labeling-MRI after stereotactic radiosurgery. Ground truth was based on histopathology or clinico-radiologic follow-up. The primary endpoint was fractional tumor burden-high voxel percentage (absolute and normalized). Secondary endpoints included fractional tumor burden-low, mean CBF, maximum CBF, and delta T1. Absolute CBF thresholds of ≤50 and ≥80 mL/100 g/min and normalized thresholds of ≤1.0 and ≥1.4 were defined a priori from prior histopathology-informed data. Diagnostic performance was assessed by receiver operating characteristic analysis and DeLong testing. Between-group comparisons used Mann-Whitney U tests; generalized linear mixed-effects models assessed logistic regression.
Results:
Normalized fractional tumor burden-high demonstrated good discrimination of tumor from radiation necrosis, with area under the curve 0.81 (95% CI 0.71-0.90), sensitivity 0.79 (95% CI 0.63-0.94), specificity 0.74 (95% CI 0.61-0.86), PPV 0.60 (95% CI 0.43-0.77), and NPV 0.88 (95% CI 0.77-0.96), numerically outperforming absolute fractional tumor burden-high (area under the curve 0.75; 95% CI 0.66-0.84), although the difference was not significant (P = 0.22). Secondary arterial spin labeling-derived metrics demonstrated comparable performance (area under the curves = 0.79-0.83). Normalized fractional tumor burden-high significantly outperformed delta T1 (change in area under the curve = 0.19; 95% CI 0.05-0.31; P = 0.004). Logistic regression confirmed a monotonic association between normalized fractional tumor burden-high and tumor probability (OR = 1.62 per 10% increase; 95% CI 1.33-2.38; P = 0.001).
Conclusions:
Arterial spin labeling-derived fractional tumor burden-high provides good lesion-level differentiation between recurrent brain metastases and radiation necrosis after stereotactic radiosurgery, performing comparably to conventional CBF metrics. The voxel-level approach offers a clinically interpretable perfusion biomarker suitable for post-treatment response assessment.
