Elsevier

The Lancet Neurology

Volume 12, Issue 8, August 2013, Pages 822-838
The Lancet Neurology

Position Paper
Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration

https://doi.org/10.1016/S1474-4422(13)70124-8Get rights and content

Summary

Cerebral small vessel disease (SVD) is a common accompaniment of ageing. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. SVD can present as a stroke or cognitive decline, or can have few or no symptoms. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive deficits, physical disabilities, and other symptoms of neurodegeneration. Terminology and definitions for imaging the features of SVD vary widely, which is also true for protocols for image acquisition and image analysis. This lack of consistency hampers progress in identifying the contribution of SVD to the pathophysiology and clinical features of common neurodegenerative diseases. We are an international working group from the Centres of Excellence in Neurodegeneration. We completed a structured process to develop definitions and imaging standards for markers and consequences of SVD. We aimed to achieve the following: first, to provide a common advisory about terms and definitions for features visible on MRI; second, to suggest minimum standards for image acquisition and analysis; third, to agree on standards for scientific reporting of changes related to SVD on neuroimaging; and fourth, to review emerging imaging methods for detection and quantification of preclinical manifestations of SVD. Our findings and recommendations apply to research studies, and can be used in the clinical setting to standardise image interpretation, acquisition, and reporting. This Position Paper summarises the main outcomes of this international effort to provide the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE).

Introduction

Neurodegenerative diseases such as Alzheimer's disease commonly coexist with cerebrovascular disease in older people. Cerebral small vessel disease (SVD) is the most common vascular cause of dementia, a major contributor to mixed dementia, and the cause of about a fifth of all strokes worldwide.1, 2 Alzheimer's disease and SVD share risk factors3, 4 and both lead to cognitive decline and dementia;5, 6, 7 the clinical differentiation of Alzheimer's disease from vascular cognitive impairment or vascular dementia is increasingly recognised to be blurred.8

Signs of SVD on conventional MRI include recent small subcortical infarcts, white matter magnetic resonance (MR) hyperintensities, lacunes, prominent perivascular spaces, cerebral microbleeds, and atrophy.2 However, the terms for and definitions of these lesions have varied substantially between studies.9, 10 For example, our systematic review identified 1144 instances of 50 different terms used to describe white matter hyperintensities in 940 papers; in some cases, two different terms were used in the same paper (table 1; appendix). This amount of variation inhibits cross-study comparisons and is a barrier to research on risk factors, pathophysiology, pathological correlations, and clinical consequences of these lesions. Indeed, the same lesions are classified differently across studies—eg, different definitions have resulted in small cavities being classified as perivascular spaces or lacunes.9 Interpretation of data from many reports is hampered by the variable consequences of acute SVD and related lesions and the convergence of lesions with different causes but similar late appearances on MRI (figure 1). Use of more standard terminology, definitions, and methods for image acquisition and analysis across research centres would remove a major barrier to progress. Furthermore, such standardisation could be used in clinical practice to improve diagnosis and better understand the cause of cognitive impairment in elderly patients.

Neuroimaging consensus standards for classification of SVD were first proposed by the US National Institute of Neurological Disorders and Stroke and the Canadian Stroke Network as part of the development of standards for research on vascular cognitive impairment.11 Subsequently, a scientific statement from the American Heart Association incorporated neuroimaging evidence for SVD or stroke as part of the criteria for probable vascular mild cognitive impairment and dementia, and included a class 2 recommendation for neuroimaging as part of the clinical investigation of vascular cognitive impairment.12 However, neither of these guidelines provide comprehensive recommendations for the many forms of SVD seen on neuroimaging, and neither include advances in understanding the pathophysiology and measurement of SVD, which are changing rapidly.

Our international effort builds on previous initiatives and aims to provide clear, rigorous, evidence-based, and easy-to-apply definitions and terminology for the structural neuroimaging features of SVD that avoid presumption of mechanisms of pathogenesis. We include examples to help improve the standard use, minimum advisory standards for image acquisition, standards for analysis of imaging data on SVD and related features, and scientific reporting standards to improve clarity of publications on SVD.

Although this Position Paper focuses on the most common manifestations of SVD, other vascular lesions, such as ischaemic or haemorrhagic stroke, subarachnoid haemorrhage, subdural haematoma, and vascular malformations unrelated to SVD, can also contribute to cognitive impairment and dementia, especially after stroke. We provide a description of their features and neuroimaging recommendations in the appendix.

This Position Paper summarises the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE). Our main aim is to recommend standards for research with MRI; however, many of the principles also apply to research with CT, and the standards might also facilitate a more consistent approach to identification of manifestations of SVD on neuroimaging in clinical practice.

Section snippets

Methods

In 2011, the UK Medical Research Council (London, UK), the German Centre for Neurodegenerative Disease (DZNE, Bonn Germany), and the Canadian Institutes of Health Research (Ottawa, ON, Canada) issued a call for proposals under a funding concordat of the Centres of Excellence in Neurodegeneration (COEN), which aimed to accelerate progress in understanding the pathogenesis of neurodegeneration.13 This initiative provided funding for a working group of experts to establish standards for

Context

Clinically evident recent small subcortical infarcts, commonly called lacunar strokes or lacunar syndrome, cause about 25% of all ischaemic strokes (figure 2). Occasionally, a recent asymptomatic small subcortical infarct is identified by chance on imaging,14, 15 and is referred to as a silent cerebral infarct. By contrast, for as yet unknown reasons, in up to 30% of patients, symptomatic lacunar stroke syndromes seem not to be accompanied by visible small subcortical infarcts,16 indicating

Image acquisition

If no contraindications are known, MRI, rather than CT, is preferred for research and routine clinical use because it has higher sensitivity and specificity for detecting most manifestations of SVD (table 2). A field strength of 3·0 T might be preferred, but images from modern 1·5 T MRI scanners are often of a similarly high definition,80 and are therefore acceptable; 1·5 T systems are also more widely available than 3·0 T systems, an important consideration for multicentre studies. Imaging

Future developments and challenges

Advances in the technology for imaging, as well as in novel protocols for image acquisition and post-processing, have improved imaging of the various manifestations of SVD. These advances have the potential to help explain the role of SVD in neurodegenerative disease and to identify new mechanisms of disease. Examples of promising technology are advances in small-artery imaging with ultra-high-field strength MRI (>3·0 T), diffusion tensor imaging of detailed structural connectivity,

Conclusions

Our neuroimaging standards for SVD are intended to harmonise current disparate terminology and analysis methods. We encourage other researchers to use these standards. They could provide a useful introduction to the principles of neuroimaging in SVD, which could help investigators to incorporate measurement of SVD into studies of neurodegenerative diseases or the pathological basis of ageing. These standards should allow cross-study comparisons of findings, accelerating the translation of new

References (111)

  • M Dichgans et al.

    Prevention of vascular cognitive impairment

    Stroke

    (2012)
  • C Brayne et al.

    Neuropathological correlates of dementia in over-80-year-old brain donors from the population-based Cambridge City over-75s cohort (CC75C) study

    J Alzheimers Dis

    (2009)
  • FE Matthews et al.

    Epidemiological pathology of dementia: attributable-risks at death in the Medical Research Council Cognitive Function and Ageing Study

    PLoS Med

    (2009)
  • Cognitive function and ageing study (MRC CFAS)

    Lancet

    (2001)
  • JA Schneider et al.

    Mixed brain pathologies account for most dementia cases in community-dwelling older persons

    Neurology

    (2007)
  • GM Potter et al.

    Wide variation in definition, detection, and description of lacunar lesions on imaging

    Stroke

    (2010)
  • YC Zhu et al.

    Silent brain infarcts: a review of MRI diagnostic criteria

    Stroke

    (2011)
  • V Hachinski et al.

    National Institute of Neurological Disorders and Stroke–Canadian Stroke Network vascular cognitive impairment harmonization standards

    Stroke

    (2006)
  • PB Gorelick et al.

    Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association

    Stroke

    (2011)
  • A united approach to vascular disease and neurodegeneration

    Lancet Neurol

    (2012)
  • DW Kang et al.

    New ischemic lesions coexisting with acute intracerebral hemorrhage

    Neurology

    (2012)
  • D Chowdhury et al.

    Are multiple acute small subcortical infarctions caused by embolic mechanisms?

    J Neurol Neurosurg Psychiatry

    (2004)
  • FN Doubal et al.

    Characteristics of patients with minor ischaemic strokes and negative MRI: a cross sectional study

    J Neurol Neurosurg Psychiatry

    (2011)
  • GM Potter et al.

    Counting cavitating lacunes underestimates the burden of lacunar infarction

    Stroke

    (2010)
  • F Moreau et al.

    Cavitation after acute symptomatic lacunar stroke depends on time, location, and MRI sequence

    Stroke

    (2012)
  • S Koch et al.

    Imaging evolution of lacunar stroke–leukoariosis or lacune?

    Neurology

    (2011)
  • GA Donnan et al.

    The stroke syndrome of striatocapsular infarction

    Brain

    (1991)
  • CM Fisher

    Lacunar infarcts—a review

    Cerebrovasc Dis

    (1991)
  • M Santos et al.

    Differential impact of lacunes and microvascular lesions on poststroke depression

    Stroke

    (2009)
  • P Choi et al.

    Silent infarcts and cerebral microbleeds modify the associations of white matter lesions with gait and postural stability: population-based study

    Stroke

    (2012)
  • DA Snowdon et al.

    Brain infarction and the clinical expression of Alzheimer disease. The Nun Study

    JAMA

    (1997)
  • CL Franke et al.

    Residual lesions on computed tomography after intracerebral hemorrhage

    Stroke

    (1991)
  • SE Vermeer et al.

    Incidence and risk factors of silent brain infarcts in the population-based Rotterdam Scan Study

    Stroke

    (2003)
  • WT Longstreth et al.

    Lacunar infarcts defined by magnetic resonance imaging of 3660 elderly people. The Cardiovascular Health Study

    Arch Neurol

    (1998)
  • S Debette et al.

    The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis

    BMJ

    (2010)
  • AA Gouw et al.

    Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations

    J Neurol Neurosurg Psychiatry

    (2011)
  • KF de Laat et al.

    Loss of white matter integrity is associated with gait disorders in cerebral small vessel disease

    Brain

    (2011)
  • BG Windham et al.

    Covert neurological symptoms associated with silent infarcts from midlife to older age: the Atherosclerosis Risk in Communities study

    Stroke

    (2012)
  • M Saini et al.

    Silent stroke: not listened to rather than silent

    Stroke

    (2012)
  • D Inzitari et al.

    Changes in white matter as determinant of global functional decline in older independent outpatients: three year follow-up of LADIS (leukoaraiosis and disability) study cohort

    BMJ

    (2009)
  • VC Hachinski et al.

    Leukoaraiosis

    Arch Neurol

    (1987)
  • H Pollock et al.

    Perivascular spaces in the basal gangli of the human brain: their relationship to lacunes

    J Anat

    (1997)
  • S Groeschel et al.

    Virchow-Robin spaces on magnetic resonance images: normative data, their dilatation, and a review of the literature

    Neuroradiology

    (2006)
  • FN Doubal et al.

    Enlarged perivascular spaces on MRI are a feature of cerebral small vessel disease

    Stroke

    (2010)
  • RM Kwee et al.

    Virchow-Robin spaces at MR imaging

    Radiographics

    (2007)
  • YC Zhu et al.

    Severity of dilated Virchow-Robin spaces is associated with age, blood pressure, and MRI markers of small vessel disease: a population-based study

    Stroke

    (2010)
  • AM MacLullich et al.

    Enlarged perivascular spaces are associated with cognitive function in healthy elderly men

    J Neurol Neurosurg Psychiatry

    (2004)
  • J Poirier et al.

    Cerebral lacunae. A proposed new classification

    Clin Neuropathol

    (1984)
  • LA Heier et al.

    Large Virchow-Robin spaces: MR-clinical correlation

    AJNR Am J Neuroradiol

    (1989)
  • TF Patankar et al.

    Dilatation of the Virchow-Robin space is a sensitive indicator of cerebral microvascular disease: study in elderly patients with dementia

    AJNR Am J Neuroradiol

    (2005)
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