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Increased extracellular free water content is associated with cerebral microbleed severity in patients with cerebral

Jingjing Deng1,2, Lu Chen1,2, Li Huang1,2

  • 1Department of Radiology, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.

Medicine
|May 19, 2026
PubMed

Insights

Increased extracellular free water (FW) is linked to more severe cerebral microbleeds (CMB) in patients with cerebral small vessel disease (CSVD). This finding highlights FW as a potential imaging biomarker for CSVD progression.

Area of Science:

  • Neurology
  • Radiology
  • Biomarkers

Background:

  • Cerebral small vessel disease (CSVD) is a common condition affecting the brain's small blood vessels.
  • Cerebral microbleeds (CMB) are a hallmark of CSVD and are associated with increased risk of stroke and cognitive decline.
  • Extracellular free water (FW) is an imaging marker that may reflect tissue damage in the brain.

Purpose of the Study:

  • To investigate the association between extracellular free water (FW) content and the severity of cerebral microbleeds (CMB) in patients with CSVD.
  • To determine if FW is an independent predictor of CMB burden in CSVD patients.

Main Methods:

  • 159 patients with CSVD underwent multimodal MRI, including diffusion tensor imaging (DTI) for FW quantification and susceptibility-weighted imaging (SWI) for CMB assessment.
  • Patients were grouped by CMB burden: none, mild (1-2 CMB), and extensive (≥3 CMB).
  • Spearman correlation and multivariate linear regression analyses were used to assess the relationship between FW and CMB severity, adjusting for clinical factors.

Main Results:

  • 53 patients (33.3%) had CMB. A significant positive correlation was found between FW values and CMB burden (R=0.511, P<0.001).
  • FW, age, sex, hypertension, and white matter hyperintensity (WMH) volume differed significantly across CMB groups (P<0.05).
  • Extracellular FW was independently associated with CMB severity after adjusting for age, hypertension, and WMH volume (P<0.05).

Conclusions:

  • Increased extracellular free water content is independently associated with the presence and severity of cerebral microbleeds in patients with CSVD.
  • FW may serve as a valuable imaging biomarker for assessing CMB burden and potentially predicting disease progression in CSVD.
Keywords:
cerebral microbleedscerebral small vessel diseasediffusion tensor imagingfree watersusceptibility-weighted imaging

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