Relationship between radiation dose and microbleed formation in patients with malignant glioma

BACKGROUND: Cranial irradiation is associated with long-term cognitive changes. Cerebral microbleeds (CMBs) have been identified on susceptibility-weighted MRI (SWI) in patients who have received prior cranial radiation, and serve as radiographic markers for microvascular injury thought to contribute to late cognitive decline. The relationship between CMB formation and radiation dose has not previously been quantified. METHODS: SWI was performed on 13 patients with stable WHO grade III-IV gliomas between 2 and 4 years after chemoradiotherapy to 60 Gy. The median age at the time of treatment was 41 years (range 25 – 74 years). CMBs were identified as discrete foci of susceptibility on SWI that did not correspond to vessels. CMB density for low (<30 Gy), median (30–45 Gy), and high (>45 Gy) dose regions was computed. RESULTS: Twelve of 13 patients exhibited CMBs. The number of CMBs was significantly higher for late (>3 years from treatment) compared to early (<3 years) timepoints (early median 6 CMBs; late median 27 CMBs; p = 0.001), and there were proportionally more CMBs at lower doses for late scans (p = 0.006). 88% of all CMBs were observed in regions receiving at least 30 Gy, but the CMB density within medium and high dose regions was not significantly different (p = 0.33 and p = 0.9, respectively, for early and late time points). CONCLUSIONS: CMBs predominantly form in regions receiving at least 30 Gy, but form in lower dose regions with longer follow-up. We do not observe a clear dose–response relationship at doses above 30 Gy. These findings provide important information to assess the risk of late microvascular sequelae from cranial irradiation.