Table 4: Reporting MR imaging changes of presumed vascular ...



Supplementary Web Appendix:

Table A1. Expanded summary of terms used to describe MR changes of presumed vascular origin: recent small subcortical infarcts, lacunes of presumed vascular origin, cerebral microbleeds.

Delphi principle used to develop the consensus document

Literature search methods and terms

Further details of recommendations for image analysis of SVD features on neuroimaging

Other vascular lesions that may be relevant to neurodegeneration

Figure A1. Overlap between lesion types

Figure A2: Recent small subcortical infarction (illustrating size in different planes).

Figure A3. Periventricular and deep WMH. EES suggestion example

Figure A4. WMH appearance on T1w MPRAGE and T2 - EES suggestion example

Figure A5. PVS example

References

Table A1: Expanded summary of terms used to describe recent small subcortical infarcts, lacunes of presumed vascular origin and cerebral microbleeds: Data were derived from structured literature search; for methodology see Supplementary Text

|Term |Variants of use of term |Use of term in titles and abstract |

| | |Total No.* |% |

|Recent small subcortical infarcts and lacunes of presumed of vascular origin | | |

|lacunar infarct(s) |hyperacute lacunar infarct; isolated lacunar infarct; old lacunar infarcts; silent cerebral lacunar |127 |26% |

| |infarcts; subclinical lacunar infarct(s); subcortical lacunar infarct(s); symptomatic lacunar | | |

| |infarct(s); acute lacunar infarct(s); silent lacunar infarct(s); | | |

|lacunar infarction(s) |acute cerebral lacunar infarction; brain lacunar infarction; cerebral lacunar infarction; chronic |77 |15% |

| |cerebral lacunar infarction; old lacunar infarctions; subclinical cerebral lacunar infarction; | | |

| |subclinical lacunar infarction; silent lacunar infarction; acute lacunar infarction | | |

|lacunar stroke(s) |acute ischemic lacunar stroke; asymptomatic lacunar stroke; lacunar stroke subtype; |60 |12% |

|subcortical infarct(s) |acute small subcortical infarctions; acute subcortical infarct(s); small, deep subcortical infarct; |50 |10% |

| |silent subcortical infarct; small subcortical infarct(s) | | |

|lacune(s) |hyperintense lacune; medial pontine lacune(s); old lacunes; silent lacune(s); symptomatic lacunes; |50 |10% |

| |vascular lacune(s) | | |

|lacunar syndrome(s) |lacunar syndrome of presumed ischemic origin; lacunar syndrome stroke; lacunar syndrome with |27 |5.5% |

| |infarction; pontine lacunar syndromes; clinical lacunar syndrome; | | |

|silent brain infarct(s) |silent brain infarction(s) |25 |5% |

|subcortical stroke(s) |Subcortical infarction, subcortical cystic infarcts |23 |4.5% |

|lacunar lesion(s) |cerebral lacunar lesions; deep lacunar lesions; subcortical lacunar lesions; symptomatic lacunar |20 |4% |

| |lesion(s); asymptomatic lacunar lesions | | |

|other |Small vessel disease stroke, small deep infarct, perforator territory infarct, lacunar arteriopathy, |36 |7% |

| |etc | | |

| | | | |

|cerebral microbleeds | | | |

|microbleed |cerebral microbleed (M), brain M, chronic M, silent cerebral M, silent T2* cerebral M, asymptomatic M |294 |76 |

|microhemorrhage/microhaemorrhage |Cerebral microhemorrhage |78 |20 |

|dot-like hemosiderin spot |dot-like hemosiderin deposition, dotlike hemosiderin spots |7 |2 |

|other |cerebral iron deposits, hypointensities in susceptibility-weighted images, microsusceptibility change,|8 |2 |

| |punctate iron source, lesions on T2*-weighted gradient-echo imaging, low signal brain lesion on | | |

| |T2*-weighted gradient echo imaging, foci of signal loss on gradient-echo T2*-weighted MR images, | | |

| |amyloid-related imaging abnormality-hemorrhage | | |

*Number of instances term was mentioned at least once in the abstract or in the title. The total number of instances was N=495 in a sample of 454 abstracts for recent small subcortical infarcts and lacunes of presumed vascular origin and N=387 in a sample of 370 abstracts for cerebral microbleeds.

Delphi principle used to develop the consensus document

The Delphi method is a structured communication technique, originally developed as a systematic, interactive prediction method, which relies on a panel of experts (references in ). We used the principle of the Delphi approach, adapted for face-to-face meetings:

We used a systematic, transparent, democratic approach, as unbiased as possible, with random allocation of participants to groups throughout. We convened a panel of experts known for their expertise in SVD and other forms of dementia and neurodegeneration such as Alzheimer’s disease. We aimed to identify experts from all major continents within funder criteria and budget limitations. We held two workshops and worked remotely in between. Writing group chairs were selected to chair SVD topic groups that were not their particular feature of interest to avoid strongly held views distorting the consensus.

First workshop, Edinburgh, March 2012:

• A series of questions were posed about each SVD feature to all present, to: summarise current definitions, terminology, image acquisition, image analysis and standards for reporting studies of SVD imaging features; propose consensus terms; and identify outstanding issues and points of contention that would impede consensus;

• Next, the group was split randomly into two subgroups with each subgroup discussing a specific SVD feature; this process was repeated twice in order to discuss each of the six SVD features of interest (each participant contributed to three SVD feature discussions);

• The results of these focussed discussions were then fed back to all participants and discussed;

• Contentious points were flagged for further discussion;

Participants were then randomly assigned to one topic writing group, with a chair, to prepare the draft text of their topic section. Gaps in the group were identified and additional experts identified to fill those gaps. The drafts were circulated prior to the second workshop. Six additional independent expert advisors were identified to attend the second workshop and independently critique the proposed standards.

Second workshop, Munich, November 2012:

• The draft statements were presented to all participants, discussed and consensus agreed.

• The independent expert advisors provided critique and suggestions for improvement.

• All participants, including those who were unable to attend the second workshop, provided written feedback and commented on the draft

Thereafter a revised draft of the consensus statement was circulated for comment and, after a further iteration, final sign off.

Literature search methods and terms

We searched the literature using the Pubmed search engine from Jan 1 1980 to April 17 2012, run on April 18 2012, restricted to human studies published in English (search terms see below) to cover the six SVD components.  

The MeSH terms "cerebral small vessel disease" and "vascular dementia" were used to ensure potentially relevant articles, and the MeSH terms "lacunar stroke" and "leukoaraiosis" were used where relevant. All terms were exploded. 

We adjusted the sensitivity and specificity of the terms to optimise the number of hits while verifying that known relevant articles were included. For most lesions this produced a manageable number of hits (2000). After an initial run, several additional terms were added to the search for terms related to acute and chronic lacunar lesions. The final search terms and their initial yields are as follows: 

Recent small subcortical infarcts and lacuness – yields 2303 articles: 

(Lacun* OR deep infarct* OR subcortical infarct* OR deep stroke* OR subcortical stroke* OR silent stroke* OR silent brain infarct* OR small vessel infarct* or small vessel stroke* OR lacunar stroke OR microinfarct* or microscopic infarct* OR etat crible) AND (brain OR cerebr* OR lacunar stroke OR cerebral small vessel disease OR vascular dementia OR stroke) AND (MRI OR computed tomography).

 

WMH - yields 967 articles

((White matter hyperintens*) OR (white matter lesion*) OR (white matter disease*) OR (white matter change*) OR (leukoaraiosis)) AND ((leukoaraiosis) OR (cerebral small vessel disease) OR (vascular dementia)) AND (MRI OR computed tomography)

Perivascular spaces - yields 256 articles

((Perivascular space*) OR (Virchow Robin) OR (Virchow-Robin)) AND (brain OR cerebr* OR leukoaraiosis OR cerebral small vessel disease OR vascular dementia) AND (MRI)

Microbleeds - yields 367 articles

((microbleed*) OR (microhemorrhag*) OR (microhaemorrhag*) OR ((“dot-like”) AND (suscept* OR hemosid*))) AND (brain OR cerebr* OR cerebral small vessel disease OR vascular dementia) AND (MRI)

 

Atrophy - yields 464 articles

(Atrophy OR brain volum* OR cerebral volum* OR volume loss) AND (leukoaraiosis OR cerebral small vessel disease OR lacunar stroke OR vascular dementia) AND (MRI OR computed tomography)

Note: expanding the search to include "dementia" and "Alzheimer's" as well as "vascular dementia" yields many more articles, 3,203

  

We distributed the search results to the work group chairs for use in formulating their recommendations.

Additionally, for four of the lesions, we performed an analysis of the frequency of terms. For recent small subcortical infarcts and lacunes there were 2303 potentially relevant abstracts identified. Two reviewers (KS, FD) evaluated 641/2303 (28%): the first 480 consecutive abstracts and every 10th abstract thereafter, which yielded 142 terms for small deep infarcts (not including 17 terms that had been identified in previous work3) giving a total of 159 terms. Amongst these the commonest were lacunar infarcts (127), lacunar infarctions (77), lacunar strokes (60) lacunes (50) and subcortical (50). “Small deep infarcts” occurred 10 times and there were more than 100 terms that have been used to describe lacunes of presumed vascular origin.

For WMH and microbleeds, one reviewer (EES) performed a similar analysis. For WMH, There were a total of 1,144 instances of 50 different terms for WMH used in the 920 abstracts identified in the literature search. The number of instances is greater than the number of abstracts because in some cases 2 different terms for WMH were used in the same abstract. Generally the terms were grouped around 5 major "families"--in order, leukoaraiosis (including mis-spellings), white matter lesions (and derivatives), WMH, leukoencephalopathy (mostly from older CADASIL literature) and white matter disease.

For CMBs, there were a total of 387 instances of 20 different terms for MB used in the 370 abstracts reviewed. ‘Microbleed’ was by far the most frequent, with "cerebral microbleed" appearing more commonly than "brain microbleed".

These results are summarised in main manuscript Table 1 (WMH) and Supplementary Table 1 (recent SSI and lacunes of presumed vascular origin).

 

Further details of recommendations for image analysis of SVD features on neuroimaging

Recent small subcortical infarcts: Visual assessment of acute small deep brain infarcts on DWI and structural sequences is the reference standard for image analysis of acute small deep brain infarcts at present. Observers should be trained in brain imaging interpretation and specifically in how to recognise acute infarcts. Various schemes have been described for classifying lesion location, size, shape, visibility on different sequences, etc, for quantification of acute as well as established SVD lesions in research (examples available at bric.ed.ac.uk/imageanalysis).1 Points to consider in image analysis include recording the shape (eg ovoid, or tubular running the length of a perforating arteriole) (Supplementary figure 2). Lesion location should be specified (centrum semiovale; corona radiata, basal ganglia; thalamus, internal capsule, external capsule, optic radiation, cerebellum, brain stem). Multiplicity of acute lesions should be described. A small proportion of acute symptomatic lacunar lesions are accompanied by other acute lesions, the appearance of which indicates that they occurred simultaneously or at least within a few days. Multiplicity might suggest a proximal embolic source,2,3 although other mechanisms might also cause such appearances.4,5 Acute lesion volume may be a useful measure in future but the reliability and optimal method has not yet been fully explored.

Lacunes of presumed vascular origin: Image analysis of lacunes is very dependent on visual scoring; although lacune volume can be measured, there is as yet no established computational analysis approach. It is important to distinguish lacunes from PVS, given the likely difference in aetiology. This is poorly done at present;6 but might improve with a proposed size boundary of 3mm or more for lacunes and ................
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