Correlations in post-mortem imaging-histopathology studies of sporadic human cerebral small vessel disease: A systematic review

Neuropathol Appl Neurobiol. 2021 Dec;47(7):910-930. doi: 10.1111/nan.12737. Epub 2021 Jun 15.


Aims: Sporadic human cerebral small vessel disease (SVD) commonly causes stroke and dementia but its pathogenesis is poorly understood. There are recognised neuroimaging and histopathological features. However, relatively few studies have examined the relationship between the radiological and pathological correlates of SVD; better correlation would promote greater insight into the underlying biological changes.

Methods: We performed a systematic review to collate and appraise the information derived from studies that correlated histological with neuroimaging-defined SVD lesions. We searched for studies describing post-mortem imaging and histological tissue examination in adults, extracted data from published studies, categorised the information and compiled this narrative.

Results: We identified 38 relevant studies, including at least 1146 subjects, 342 of these with SVD: 29 studies focussed on neuroradiological white matter lesions (WML), six on microinfarcts and three on dilated perivascular spaces (PVS) and lacunes. The histopathology terminology was diverse with few robust definitions. Reporting and methodology varied widely between studies, precluding formal meta-analysis. PVS and 'oedema' were frequent findings in WML, being described in at least 94 and 18 radiological WML, respectively, in addition to myelin pallor. Histopathological changes extended beyond the radiological lesion margins in at least 33 radiological WML. At least 43 radiological lesions not seen pathologically and at least 178 histological lesions were not identified on imaging.

Conclusions: Histopathological assessment of human SVD is hindered by inconsistent methodological approaches and unstandardised definitions. The data from this systematic review will help to develop standardised definitions to promote consistency in human SVD research.

Keywords: cerebral small vessel disease; neuroimaging; neuropathology; radiology; systematic review; vascular dementia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Aged
  • Aged, 80 and over
  • Autopsy / methods
  • Brain / blood supply*
  • Brain / pathology
  • Cerebral Small Vessel Diseases / pathology*
  • Female
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Neuroimaging* / methods
  • Stroke / pathology*
  • Stroke / physiopathology