Cerebral Microbleeds

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Definition

  • cerebral microbleeds (CMBs) or cerebral microhemorrhages are characterized by hemosiderin deposits caused by small hemorrhages and may serve as a radiologic biomarker of small vessel disease (SVD)
    • black lesions on blood-sensitive MRI sequences (GRE T2* or SWI images)
  • often found incidentally; the prevalence increases with age
    • general population ∼ 10-15%   (Sveinbjornsdottir, 2008)
    • 6.5% of the individuals aged 45-50 years
    • up to 40% of the population > 80 years    [Poels, 2009]
    • incidence of CMBs in AD is 20-43%; in vascular dementia, it is up to 85%!   [Seo, 2007]
  • microhemorrhages are associated with:
    • older age (prevalence increasing significantly after the age of 75)
    • hypertension
    • smoking
    • white matter disease and lacunar stroke
    • previous ischemic stroke or intracerebral hemorrhage (ICH)
    • COVID-19 leukoencephalopathy (mostly in critically ill patients) (Agarwal, 2020)
  • a high number of microbleeds is associated with an increased risk of:
  • increased risk of progression is common in:

Cerebral microbleeds and the risk of hemorrhage

  • the risk of ICH increases with the number of CMBs
    • ≥ 10 CMBs – OR for ICH 5.5!
    • according to the CROMIS-2 trial, the risk of bleeding in patients with CMBs is 9.8/1000 vs. 2.6/1000 patient-years (adjusted hazard ratio 3·67, 95% CI 1·27–10·60) [Wilson, 2018]
  • the risk of ICH is up to 5%/year in cases with multiple lobar CMBs [Van Etten, 2014]
    • ≥ 5 CMBs = OR for ICH 2.8
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black round or ovoid lesion with blooming on GRE/SWI

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black round or ovoid lesion with blooming on GRE/SWI

devoid of signal hyperintensity on T1- or T2-weighted sequences

at least half surrounded by brain parenchyma

distinct from other potential mimics such as iron/calcium deposits, bone, or vessel flow voids

clinical history, excluding traumatic diffuse axonal injury (DAI)

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at least half surrounded by brain parenchyma

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distinct from other potential mimics such as iron/calcium deposits, bone, or vessel flow voids

clinical history, excluding traumatic diffuse axonal injury (DAI)

 

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Classification

  • subcortical (mainly caused by arteriolopathy)  → Binswanger’s disease
  • cortical (mostly caused by CAA – with an increased risk of lobar hemorrhage)  
  • combined (combination of CAA and arteriolosclerosis or rather arteriolosclerosis alone) [Jung, 2020]

Radiographic features of hypertensive angiopathy

  • cerebral microbleeds (predominantly in the deep grey nuclei and brainstem)
  • subcortical infarcts (lacunar) in the deep grey nuclei, white matter, and brainstem
  • dilated perivascular spaces in the basal ganglia
  • white matter hyperintensities and hyperintensities in the deep grey nuclei and brainstem on T2

Test

  • cerebral microbleeds (predominantly in the deep grey nuclei and brainstem)

Diagnostic evaluation

  • detectable only on specific sequences, such as gradient-recalled echo (GRE) and susceptibility-weighted imaging (SWI)
    • microbleeds are inapparent on other MRI sequences and CT
  • black, round, or oval lesions measuring 2-5 mm in diameter, associated with a blooming artifact, which overestimates the size of the lesions

Greenberg’s criteria (Roob, 1999)

  • black round or ovoid lesion with blooming on GRE/SWI
  • devoid of signal hyperintensity on T1- or T2-weighted sequences
  • at least half surrounded by brain parenchyma
  • distinct from other potential mimics such as iron/calcium deposits, bone, or vessel flow voids
  • clinical history, excluding traumatic diffuse axonal injury (DAI)

Radiographic features of hypertensive angiopathy

  • both techniques are used to detect blood products and calcifications due to their sensitivity to local susceptibility effects
  • T2*-weighted gradient-echo (GRE) sequences operate in 2D multi-slice mode, using relatively long TR’s, low flip angles, and relatively long TE’s
  • modern susceptibility-weighted imaging (SWI) methods are based on GRE sequences but include numerous enhancements for improved differentiation between paramagnetic (hemorrhage) and diamagnetic (calcification) substances
  • SWI is superior to GRE (particularly in the diagnosis of traumatic brain injury and microvascular angiopathy)
  • however, SWI sequences take longer than standard GRE and are more susceptible to motion artifacts

Radiographic features of hypertensive angiopathy

It is a “susceptibility artifact” caused by paramagnetic substances

  • hemosiderin
    • cavernous malformation Cavernous malformation in the right thalamus
    • old hemorrhages, microbleeds Cortical and subcortical microbleeds
    • SAH (even small superficial)
    • diffuse axonal injury (DAI)  Diffuse axonal injury (DAI)
    • superficial siderosis
    • older thrombus
      • detection of cerebral venous thrombosis (CVT)   Cord sign indicating venous thrombosis (GRE)
      • excessive blooming from hemosiderin is an unfavorable predictor of recanalization Blooming artifact indicating left MCA thrombosis  [Chen, 2015]
  • calcification
  • metals
    • PKAN (Pantothenate Kinase-Associated Neurodegeneration) PKAN with typical "tiger eyes" in T2 sequence
  • gas
    • air embolism  Air embolism via jugular venous catheter (MR SWI)
  • due to the artifact, SWI is highly sensitive in detecting even small lesions, particularly those associated with hemorrhage or mineralization

TEST POPUP

Differential Diagnosis

  • calcium and iron deposits (calcium is hyperdense on the CT scan)   PKAN “eye-of-the-tiger” - bilateral central hyperintense areas within a hypointense region in the medial globus pallidus (T2 a GRE)  PKAN “eye-of-the-tiger” - bilateral central hyperintense areas within a hypointense region in the medial globus pallidus (T2)
    • diseases with an accumulation of iron  → see here
  • flow void from veins or small arteries on the cross-section  Subcortical CMB and artery cross section (green arrow)
    • follow the continuum of the vessel on adjacent slices
  • cavernous malformation (cavernoma)  Cerebral cavernous malformation with a typical popcorn appearance
  • malignant melanoma metastases   The malignant melanoma
    • T1 – hyperintense (due to bleeding and/or the presence of melanin) 
    • T2 – hypointense
    • T1 C+ – diffuse or ring-like saturation
    • T2*- hypointense
  • pneumocephalus and gas embolism   Tohle je test
  • metallic emboli from mechanical heart valve (very rare) 

Management

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CMBs and thrombolysis

CMBs and anticoagulation therapy

CMBs and antiplatelet therapy

  • the risk of symptomatic intracranial hemorrhage (sICH) may increase after thrombolytic therapy in patients with cerebral microbleeds (CMBs)
  • CMBs < 10  ⇒  IVT seems safe (AHA/ASA 2019 IIa/B-NR)
  • CMBs > 10 ⇒ IVT carries a higher risk of ICH; the expected benefit of treatment must outweigh the risk ⇒ consider IVT in patients with a severe stroke
    • a small study retrospectively found a slightly increased risk (3%) of bleeding in patients with microbleeds on GRE [Fiehler, 2007]
    • an increased risk of bleeding is associated with CAA as a cause of microbleeds
  • MRI screening is not recommended to assess CMB burden before making a treatment decision regarding IVT

test text

  • no definitive guidelines exist for antiplatelet use in patients with CMBs
  • single antiplatelet therapy – seems a safe and beneficial approach (RESTART trial subanalysis) [Salman, 2019]
  • dual antiplatelet therapy (DAPT) – individual risk-benefit analysis is crucial (DAPT is acceptable after recent stenting, etc.)

Radiographic features of hypertensive angiopathy

  • cerebral microbleeds (predominantly in the deep grey nuclei and brainstem)
  • subcortical infarcts (lacunar) in the deep grey nuclei, white matter, and brainstem
  • dilated perivascular spaces in the basal ganglia
  • white matter hyperintensities and hyperintensities in the deep grey nuclei and brainstem on T2

Test

  • cerebral microbleeds (predominantly in the deep grey nuclei and brainstem)

Test2

CMBs and thrombolysis

CMBs and anticoagulation therapy

CMBs and antiplatelet therapy

  • the risk of symptomatic intracranial hemorrhage (sICH) may increase after thrombolytic therapy in patients with cerebral microbleeds (CMBs)
  • CMBs < 10  ⇒  IVT seems safe (AHA/ASA 2019 IIa/B-NR)
  • CMBs > 10 ⇒ IVT carries a higher risk of ICH; the expected benefit of treatment must outweigh the risk ⇒ consider IVT in patients with a severe stroke
    • a small study retrospectively found a slightly increased risk (3%) of bleeding in patients with microbleeds on GRE [Fiehler, 2007]
    • an increased risk of bleeding is associated with CAA as a cause of microbleeds
  • MRI screening is not recommended to assess CMB burden before making a treatment decision regarding IVT

test text

  • no definitive guidelines exist for antiplatelet use in patients with CMBs
  • single antiplatelet therapy – seems a safe and beneficial approach (RESTART trial subanalysis) [Salman, 2019]
  • dual antiplatelet therapy (DAPT) – individual risk-benefit analysis is crucial (DAPT is acceptable after recent stenting, etc.)
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