MRI-Based Prediction of Macrovascular Causes of Intracerebral Hemorrhage: The MACRO Score

Abstract

Background and objectives: Although most spontaneous intracerebral hemorrhages (ICHs) are due to cerebral small vessel diseases (SVDs), between 1 in 7 and 1 in 10 are due to a macrovascular cause. Rapid diagnosis has important therapeutic and prognostic implications but sometimes requires digital subtraction angiography (DSA), an invasive procedure which cannot be performed in all patients. MRI provides optimal sensitivity for markers of SVD but was not included in previous risk stratification scores. We aimed to create and validate a risk stratification score for macrovascular causes of ICH including MRI findings to guide diagnosis and further investigations.

Methods: We pooled data from 2 large observational study cohorts (London/United Kingdom and Graz/Austria) of consecutive patients with ICH who had brain MRI and at least 1 angiographic modality within 90 days of symptom onset. The primary outcome was a macrovascular cause of ICH (arteriovenous malformation/dural arteriovenous fistula, aneurysm, cavernoma, or cerebral venous thrombosis), with the diagnosis based on neurovascular multidisciplinary meetings. Using lasso logistic regression, we built the MRI Assessment of the Causes of intRacerebral haemOrrhage (MACRO) score to assess the probability of a macrovascular cause. We performed internal validation using bootstrapping and external validation in an independent cohort (Bern/Switzerland).

Results: We included 1,043 patients with ICH (mean age 66 years, 42% female), 78 of whom had a macrovascular cause (7.5%). The final score includes age (0-39, 40-69, or ≥70), location of ICH (lobar, deep, or infratentorial), and SVD markers on MRI (≥1 microbleed, ≥1 lacune, presence of cortical superficial siderosis, or white matter hyperintensities using the Fazekas scale). The MACRO score showed an optimism-adjusted c-statistic of 0.90 (95% CI 0.88-0.93), superior to existing CT-based scores (p < 0.001). In external validation, the c-statistic was 0.87 (95% CI 0.80-0.94). MACRO scores ≥6 (59.5% of patients) indicated a very low risk of a macrovascular cause (0.2%), while scores ≤2 (9% of patients) indicated a high risk (48.9%).

Discussion: The MRI-based MACRO score shows excellent performance in predicting the likelihood of macrovascular causes of spontaneous intracerebral hemorrhage, making it useful in guiding further investigations. Important limitations include the observational study design and the performance of DSA in a minority of patients.

Figure 1. Study Flowchart (Derivation Cohort)

ICH = intracerebral hemorrhage.

Figure 2. MRI to Assess ICH Etiology (MACRO) Score

Observed risk categories are color-coded as <1% (green), 1%–5% (yellow), 5%–10% (orange), and >10% (red). Higher MACRO scores indicate a lower risk of a macrovascular cause. The overall proportion of patients with a macrovascular cause per MACRO score is reported, as well as the observed risk of detecting a macrovascular cause after initial CT angiography and after both MRI and CT angiography showing no evidence of a macrovascular cause. *CT or MR angiography. ICH = intracerebral hemorrhage; MACRO = MRI Assessment of the Causes of intRacerebral haemOrrhage.

Figure 3. Neuroimaging Examples Showing Included Patients With Different Risks of a Macrovascular Cause

(A) Patient in their fifties with cerebellar ICH (A.a). SWI and FLAIR sequences (A.b/A.c) showed no evidence of cerebral small vessel disease (MACRO score 1, indicating a high risk of a macrovascular cause). In dynamic MR angiography, a small AVM originating from the left posterior inferior cerebellar artery was suspected, which was confirmed on DSA (A.d). (B) Patient in their forties with a parietal lobar ICH (B.a). SWI shows several cerebral microbleeds in a mixed distribution (B.b), as well as confluent white matter hyperintensities and several lacunes (B.c/B.d). This patient had a MACRO score of 7, indicating a very low risk of a macrovascular cause. DSA and repeat MRI did not show any evidence of a macrovascular cause for the ICH. DSA = digital subtraction angiography; FLAIR = fluid-attenuated inversion recovery; ICH = intracerebral hemorrhage; MACRO = MRI Assessment of the Causes of intRacerebral haemOrrhage.

Figure 4. ROC Curves for Different Macrovascular Risk Scores in the Derivation Cohort of Patients With Spontaneous Intracerebral Haemorrhage

ICH = intracerebral hemorrhage; MACRO = MRI Assessment of the Causes of intRacerebral haemOrrhage; ROC = receiver operating characteristic; SICH = spontaneous ICH.