Microinfarcts

a new small artery disease of the brain?

JM Wardlaw Chair of Applied Neuroimaging Head of Neuroimaging Sciences University of Edinburgh

Microinfarcts: Definition
Microscopic not visible to the naked eye minute foci with neuronal loss, gliosis, pallor, or cysts sharply delineated microscopic ischemic lesions accompanied by cellular death or tissue necrosis, often associated with gliosis and cavitation

cavitated

Cortical noncavitated

Brundel et al JCBFM 2012;32:425-36; Smith et al TLN 2012;11:272-82

Microinfarcts: Location
All brain regions Preponderance for cortex (mostly examined cortex) Possibly more in borderzone regions Many studies did not compare regions directly

Brundel et al JCBFM 2012;32:425-36; Smith et al TLN 2012;11:272-82

Microinfarcts: Size
Little consensus:
microscopic, or 50 m to 400 m to a few mm classed as microinfarcts

Cystic ones may be larger?

Brundel et al JCBFM 2012;32:425-36; Smith et al TLN 2012;11:272-82

Microinfarcts: Prevalence
24% in 1229 non-demented older control subjects, range 2.5 43%1 Two large neuropathology databases, aged 652
National Alzheimers Co-ordinating Centre (6189) Adult Changes in Thought (219) Microinfarcts common 19.7% and 16% ? More common in men than women (21 vs 18.5%)

Increase in prevalence in AD: 43% in 409 patients in 8 studies,1 More common in VaD: 62% in 87 patients in 6 studies1
1Brundel et al JCBFM 2012;32:425-36; 2Longstreth Alz Dis Assoc Dis 2009;23:291

Microinfarcts: Prevalence

Percent of patients with microinfarcts in NACC and ACT neuropathology databases combined, total n=6408
Longstreth Alz Dis Assoc Disorders 2009;23:291-4

Microinfarcts: Cognition

Microinfarcts increase risk of dementia: OR 2.31 95% CI 1.40-3.82 Prevalence of microinfarcts in subjects with and without dementia in community-based cohorts, all-cause mortality, prospective assessment in life. Microinfarcts more than double the risk of dementia

Smith et al TLN 2012;11:272-282

Microinfarcts: Risk factors

Age

Hypertension mixed results possibly in patients

<80 but not >80 years no clear gender bias in other studies

Microinfarcts: Pathology
cerebral amyloid angiopathy arteriolosclerosis CADASIL co-exist with degenerative pathologies

Smith et al TLN 2012;11:272-282

Microinfarcts and Imaging

Microscopic so hard to see on routine 1.5 or 3T MR unless very bright signal cysts or areas of rarefaction cortex ?some PVS might be microinfarcts

Microinfarcts and Macroscopic Findings

Strong association with macroscopic features: Nat AD Coord Centre: Macroinfarcts WMH Haemorrhage OR 4.4 2.6 2.0 95% CI (3.8-5.2) (2.1, 3.3) (1.6, 2.6)

Adult Changes in Thought: Macroinfarcts 2.9

(1.4, 6.3)

Longstreth Alz Dis Assoc Disorders 2009;23:291-4

Microinfarcts and Macroscopic Findings

Some small DWI +ve lesions in patients with haemorrhage Some small DWI lesions in patients with nonhaemorrhagic SVD

Kimberley Neurology 2009;72:1230, Smith et al TLN 2012;11:272-282

Microinfarcts in CADASIL
53 year old male Progressive cognitive decline age 40 First stroke age 50 MRI high volume of lacunar lesions, WMH, BMB all above median Second stroke age 53 Died six months later
Jouvent et al Stroke 2011;42:27-10

Microinfarcts in CADASIL
High res Low res

In vivo

Post mortem

Jouvent et al Stroke 2011;42:27-10

7T MRI
In 6 brains of patients dying with AD, found 6 lesions of which 5 were confirmed as microinfarcts on histology

Donor brain scanned PM with macro and microscopic findings

Van Veluw et al JCBFM 2012;33:322-9

7T MRI
In 22 older independent subjects mean age 683 years scanned in vivo: found 15 probable microinfarcts in 6 subjects

Possible microinfarct 76 yrs male. FLAIR (top, 0.8x0.8x0.8mm) T2 (below 0.7x0.7x0.7mm)

Van Veluw et al JCBFM 2012;33:322-9

7T MRI
In 22 older independent subjects mean age 683 years scanned in vivo: found 15 probable microinfarcts in 6 subjects

66 year female. FLAIR (left 0.8x0.8x0.8) T2 (middle 0.7x0.7x0.7), T1 (right 1x1x1)

Van Veluw et al JCBFM 2012;33:322-9

microvascular lesions on 7T MRI: small acute infarcts

FLAIR 0.80x0.80x0.80 mm3

Van Biessels

7T MRI
Hyperintense on FLAIR and T2, hypointense on T1 Detectable if:
>0.5mm diam ex vivo >1mm at clinical resolution ex and in vivo

Van Veluw et al JCBFM 2012;33:322-9

1.5T MRI

91 year old subject in Lothian 1921 Birth Cohort

Microinfarcts
Common with advancing age Association with macroscopic and microscopic SVD, CAA and CADASIL Less defined association with usual vascular risk factors Visible with close scrutiny even at 1.5T (at least three are..)

Microinfarcts
Future directions Closer in-vivo PM histopath correlation Distribution Risk factors Tighten up on macroscopic imaging associations Terminology. Distinct? Or just a tiny vessel version of what we see already?

Microinfarcts and SADB?

Simply a question of scale