Cerebrovascular Disease

Stroke (sudden loss of neurologic function) from infarction (80%), haemorrhagic (20%), infection, tumour or postictal. Transient ischaemic attack (TIA) is symptoms lasting <24hrs (usually <15min), warning sign for infarction in weeks-months. TIA incorrect clinical diagnosis in 25% (may be completed infarct, ICH, migraine, seizure), 1/3 have later infarction (20% within 1/12) or have infarct on DWI (despite resolution of Sx).

The brain receives 15% of resting cardiac output, 20% of total body oxygen consumption. Hypoxia is low blood oxygen, ischaemia is transient or permanent interruption of circulation. May be global or focal. Metabolic depletion of energy causes inappropirate release of excitatory neurotransmitters eg glutamate, initiating cell damage from excessive influx of calcium through receptors. This may initiate a cascade of injury, with resulting cell death (mostly necrosis). The surrounding at-risk penumbra may undergo apoptosis.

Ischaemic Stroke

Perfusion reduced long enough to cause necrosis. Grey matter is more susceptible, receiving 3-4x more blood than white matter. Haemorrhagic/red infarction has multiple or confluent petechial haemorrhages, typically after reperfusion of emboli. Nonhaemorrhagic/pale/bland/anaemic infarcts are usually from thrombosis. TOAST trial subtypes of acute infarct:

  • Large artery atherosclerosis (most) – Thrombosis or emboli of carotid bifurcation, origin of MCA, ends of basilar a. May cause progressive stenosis and thrombosis or fragmentation and distal embolisation. Higher risk with systemic hypertension, diabetes etc. Benefit from carotid endarterectomy when carotid narowed >50-70% or <1.5mm (CBF reduction doesn’t occur until ~90% due to autoregulation), complete occlusion may become protective.
  • Cardioemboli (15-20%) – Higher rate of recurrence, highest 1/12 mortality. Mostly MCA territory. Shower embolisation in fat embolisation, causing widespread haemorrhagic lesions in white matter. High risks include mechanical valve, AF, LA/LV thrombus, sick sinus syndrome, MI <4/52, dilated cardiomyopathy, akinetic LV segment, atrial myxoma, infective endocarditis. Medium risks include MV prolapse/calcification/stenosis, atrial septal aneurysm, patent foramen ovale (paradoxical emboli), atrial flutter, lone AF, tissue valve, nonbacterial endocarditis, CHF, hypokinetic LV segment, MI 4-6/52 old.
  • Small vessel occlusion (lacune) <15mm
  • Other aetiology – Vasculitidies, migraine headache, systemic/metabolic events (eg anoxia/hypoxia), vasospasm. More common in younger patients in absence of cadiovascular risk factors. Vunerable areas sensitive to hypoxia/hypotension include Ammon’s horn (CA-1), globus pallidus, amygdala (anterior choroidal-PCA watershed), cerebellar Purkinje cells, occipital lobes.
  • Undetermined aetiology (25%)

Phases of infarct:

  • Hyperacute (0-6hrs) – Vascular insufficiency and cytotoxic oedema. NCCT sensitivity ~50%, CTA adds 10% in sensitivity, CTA/CTP adds 20-30% (ie 70-80% sensitivity). Initial hypodensity or loss of grey-white differentiation after 3-6hrs (grey becomes isodense to white esp cortical ribbon sign, loss of basal ganglia) due to reduced CBV, hence the earlier this occurs the worse the prognosis (profound perfusion defect). This is exaggerated on CTA. High T2/FLAIR is initially subtle, confined to grey matter. High DWI/low ADC seen within minutes (light-bulb sign) from cytotoxic oedema and intracellular viscosity, reversible in <5%. DWI may partially return to normal at 8-16hrs (partial recovery of cellular function).
    • Vascular occlusion may be seen as hyperdense artery sign on CT (can see most of the time when slice thickness <2.5mm), or lack of flow void on T2WI. On gradient normal flow seen as intraluminal low signal with adjacent high signal due to flow effect along phase-encoding direction; acute clot causes marked intraluminal low signal with blooming. Nonenhancement on CTA/MRA/angiography is initially over a larger area than the actual occlusion, which may fill in around the thrombus on delayed imaging. Chronic occlusion or very slow flow causes iso/high T1 and high T2/FLAIR. Clot dissolves within first few days.
    • Failure of membrane pumps within 5min causes efflux of K+; and influx of Ca2+, Na+ and water, causing cellular/cytotoxic oedema. Calcium activates intracellular enzymes, lysing organelles and precipitating proteins causing cell lysis, release of vasoactive substances and excitatory amino acites compromising adjacent cells. Small component of vasogenic odema when there is loss of integrity of the more resistant capillary endothelial cells.
  • Acute (6hrs-3days) – Cytotoxic and vasogenic oedema. Neuronal damage and death increases, endovascular cells are damaged with breakdown of BBB. May have RBC leak, but haemorrhage absent or mild. Leptomeningeal collaterals may dilate. Rate of vasogenic oedema milder and takes longer if there is no reperfusion. Hypodensity, iso/low T1, high T2 with well-defined smooth/convex borders. Lacunar infarcts difficult to distinguish from chronic, may have convex ill-defined margins. Mass effect with sulcal effacement. No parenchymal enhancement. DWI peaks at ~48hrs. Penumbra persists or reduces in size as infarct enlarges.
  • Early subacute (1.5-5days) – Reperfusion. Blood flow reestablishes after 24-72hrs as clots are lysed or break up, leptomeningeal collaterals are prominent. New ‘leaky’ vessels grow into area by day 3-4. Reestablishment of flow may cause rapid oedema and haemorhage. Haemorrhagic transformation peaks at 48hrs, small amounts seen in most (on pathological specimens). Microbleeds imply vascular fragility and increased risk of haemorrhage and future infarct. Vasogenic oedema increases (high ADC, may cause transtentorial or subfalcine herniation in malignant infarct), cytotoxic oedema (low ADC) reduces. Mild streaky gyral hyperdensity from reperfused cortex or haemorrhage, margins indistinct. Parenchyma starts to enhance, typically gyriform (or peripheral in basal ganglia infarcts). T1 reduces and T2 increases. DWI usually persists (may reduce), but ADC less hypointense. May have Wallerian degeneration with mild T2 and mass effect in ipsilateral cerebral peduncle and pons.
  • Late subacute (5-14days) – Resolving oedema and early healing. Oedema resorbs with resulting more defined borders, infiltration of macrophages and glial cells to remove dead tissue. Tissue becomes gelatinous and friable. Haemorrhage at this stage is uncommon. ‘Fogging effect’ – reduced oedema and accumulation of proteins balance each other and appear near normal on CT (this is not seen on MR). Parenchymal enhnacement increases, may be bizzare and appear like neoplasm or inflammation. ADC increases and DWI may be high due to T2 shine-through.
  • Chronic (>2weeks) – Healing. Dead neuronal tissue replaced by gliosis and cystic degeneration/encephalomalacia. Lacunar infarcts become small fluid-filled cavities with surrounding gliosis. On FLAIR there is central low signal with surrounding high T2 (cf chronic ischaemic change with no central hypointensity and perivascular spaces with no peripheral high signal). Volume loss with sulcal enlargement and ex-vacuo dilatation of ventricle, concave margins. Oedema or mass effect beyond 1/12 excludes simple ischaemia, may be recurrent infarction or tumour. Wallerian degeneration with atrophy of ipsilateral cerebral peduncle and ventral pons. Hypodensity is now most marked in subcortical white matter with relative cortical hyperdensity. Cortical (pseudo-)laminar necrosis is band-like death of cells with relative preservation adjacent to meninges, may be high T1. Mild enhancement usually resolves by 3 weeks, may persist for up to 2 months. Pia and arachnoid are not affected, and don’t contribute to healing process.

Perfusion scans (CTP or MRP) – Cine imaging of first pass of contrast injection every sec for ~45sec, then at longer intervals for up to 90sec. Time attenuation curves are generated for arterial (ROI over eg A2/contralateral M2 orthoganal to scan plane), venous (eg ROI over superior sag sinus/torcula/trans sinus), and each pixel. Venous outflow function/VOF/curve occurs 1-2seconds after arterial input function/AIF/curve. MTT/CBV/CBV/TTP parametric colour maps calculated with red high and blue low values. Normally perfusion is symmetrical with higher CBF and CBV in grey matter. CTP is not as useful in the posterior fossa due to beam hardening artefact, relatively small size of infarcts (which may not be detectable on CTP), ocular lenses included in cine image acquisition (increased risk of cataracts).

  • Mean transit time (MTT) is the average transit time of blood moving through a given volume of brain (sec). Calculated by mathematical deconvolution of each pixel wrt AIF.
  • Cerebral blood volume (CBV) is the volume of blood moving through given volume of brain (mL/100g) which includes ateries/arterioles, capillaries, venules/veins. Calculated by dividing AUC of the pixel by arterial ROI AUC. However, relies on intact BBB, and is overestimated when there is leak of contrast (eg infection/inflammation, tumour). With ischaemia CBV may initially increased due to vasodilatation, then reduce with infarct.
  • Cerebral blood flow is volume of blood moving through given volume of brain per unit time (mL/100g/min). Calculated by CBF = CBV/MTT or max slope of curve. With infarcts initially MTT increases, with autoregulation causing vasodilatation and increasing CBV to maintain CBF; once maximum CBV reached then any increase in MTT reduces CBF.
  • Time to peak (TTP) is the time from start of contrast injection to maximal enhancement (sec).

CTA to identify vessel occlusions, stenoses, dissections. Presence of peripheral pial collateral vessels is a good prognostic indicator. Source images can also be reviewed to detect lack of enhancement in the microvascularture of infarcted brain cortex (but this tends to over-estimate the size of the infarct).

  • Infarct core when CBV reduced, very low CBF, area of change of C-CT or DWI positive. Irreversible neuronal death. However, not all CT/DWI/CBV lesions are irreversible. CTP tends to overestimate core when compared to DWI.
  • Ischaemic penumbra (brain at risk) when CBF reduced, MTT increased, DWI usually normal. Identified by subtracting out areas of abnormal DWI (diffusion-perfusion mismatch) or areas of predicted infarct core (CBV-MTT perfusion mismatch). Over minutes the infarct core expands to fill the ischaemic penumbra.
  • Normal CBF is 20-50 mL/100g/min.

The larger the core the more disability the patient will have, however this does not predict the result of reperfusion therapy (which penumbra would predict). Generally those <7hrs onset or small core, NIHSS >10, APSECTS > 5 and ICA or M1 occlusion tend to be treated. Outside of these criteria it depends on centre and case-by-case basis eg may be worth retrieving M2 clot if NIHSS is >10, lower NIHSS with ICA/M1 occlusion. Matched areas of infarction and abnormal perfusion should not be treated, since there is no tissue to salvage; ischaemic penumbras >20% of infarcted areas tend to be treated.

Other patterns and ptifalls:

  • The VOI for AIF needs to be placed on a vessel running perpendicular to scan plane to reduce patial voluming artefact. Due to larger size this is not as important for VOF. Inaccurate placement or poor enhancement in these vessels will result in invalid perfusion maps. Changes may mimick global hypoperfusion.
  • Imaging field of view not including the infarcted region of brain (eg posterior fossa) – need to correlate with clinical suspicion.
  • Chronic small vessel ischaemic change with reduce CBV and CBF., but no changes in MTT
  • Mature infarct will appear as low CBV – but will usually be apparent as old on the C-CT
  • Black/null pixels in the region of infarcts due to no/very little contrast flow in the region.
  • Small lacunar infarcts may be missed due to low resolution of calculated CTP maps
  • Proximal stenoses may cause chronic hypoperfusion of supplying territories with prolonged MTT, variable CBF/CBV changes. Difficult to distinguish from acute ischaemia, slow collateral flow or combination of these. May also overestimate penumbra. Need to correlate with CTA.
  • Seizure with show hyperperfusion in ictal regions
  • Postischaemic hyperperfusion – restoration of flow/perfusion pressure to a region previously affected by severe iscaehmia (spontaneous or therapeutic recanalisation). Causes increased CBV and CBF
  • Vasospasm may prolong MTT, reduce CBF

Administration of IV tPA improves outcome (~30% re-perfusion rate) when given within 3-4.5hrs and penumbra >20% of infarct; contraindications include haemorrhage, mass, structural abnormality, >1/3 of MCA territory (or ASPECTS score ≤ 7), T-occlusion of distal ICA and proximal MCA+ACA. Note that there is no incresaed risk of symptomatic haemorrhage in patients with <5 chronic microhaemorrhages (on MRI SWI/T2*); unknown with >5. CTA/CTP imaging should not delay administration of IV tPA; this can be administered or prepared before further imaging (‘time is brain’). Intra-arterial treatment (esp clot retrieval) can extend therapeutic window up to 8hrs in anterior circulation, 24hrs in posterior circulation; in combination with IV tPA can result in up to 100% re-perfusion rate. Haemorrhagic complications are more common when early signs of large infarcts are present including loss of grey-white differentiation, low attenuation in basal ganglia, poor definition of the insula.

Assessment of Cerebrovascular Reserve

Proximal stenoses may reduce distal arterial perfusion pressure, compensated by auto-regulation (vasodilatation esp in the acute setting) and collateral circulation. Cerebrovascular reserve (ability to further vasodilate) is reduced, hence is at risk of ischaemia during times of stress. however the degree of stenosis does not accurately predict the degree of compromise. CT perfusion before and ~20min after acetazolamide (carbonic anyhydrase inhibitor causing short-term cerebral arteriole vasodilatation; 1000mg IV) may help to determine this reserve. If vessels are already maximally dilated (reserve already fully utilised) there will be no further vasodilatation, and in areas of haemodynamic imparment decrease in CBF, prolonged MTT. CBV will generally increase everywhere.


May be diffuse (hypoxic-ischaemic), multifocal (vasculitis, emboli) or focal (single embolism or thrombus). Anterior circulation ischaemia causes visual changes, aphasia, sensorimotor deficits. Posterior (vertebrobasilar) circulation ischaemia causes syncopy, ataxia, cranial nerve abnormalities, homonymous visual field deficits, facial symptoms (contralateral to body symptoms).

  • ICA may affect MCA or watershed zones between, amaurosis fugax (transient monocular blindness from opthalmic aartery occlusion). Complete occlusions may be assymptomatic if there are well-developed collaterals. ACA territory usually spared due to AComm. Combined ACA/MCA (holohemispheric) infarcts are rare, usually fatal.
    • ACA (5%) – Pure ACA rare, usually from intrinsic disease (diabetes, HTN, vasospasm, vasculitis, severe subfalcine herniation) rather than emboli. Medial lenticulostriate (supply rostral basal ganglia; recurrent artery of Heubner – caudate head/anteroinferior internal capsule, putamen, globus pallidus, hypothalamus, optic chiasm) may cause motor aphasia, facial weakness, disturbance in mood and judgement. Pericallosal branches (corpus callosum) cause interhemispheric disconnection syndromes. Hemispheric branches (medial frontal and parietal lobes) cause preferential contralateral leg weakness; bilateral may cause incontinence or akinetic mutism (awake but apathetic).
    • MCA (65%) – If there are good cortical collaterals then infarct may be confined (at least initially) to basal ganglia and insula. Lateral lenticulostriate branches (supply most basal ganglia: putamen, lateral globus pallidus, superior internal capsule and adjacent corona radiata, most caudate) cause contralateral muscle tone abnormalities (globus pallidus/putamen), pure or mixed sensory/motor deficits (internal capsule/corona radiata), subtle contralateral homonymous hemianopsia (lateral geniculate nucleus), rarely conduction aphasia (inablity to repeat/read aloud; arcuate fasciculus between Wernicke to Broca speech areas). Hemispheric branches include anterior temporal artery (anterolateral tip), operculofrontal (frontal lobe), central sulcus arteries (motor and sensory strips), posterior parietal artery (parietal lobe), angular artery (posterolateral pariental, lateral occipital), posterior temporal artery (most temporal lobe, visual radiations -> contralateral homonymous hemianopia). Insular is furthest from potential collateral supply, hence most susceptible. Brocca area in rostral MCA branches of dominant hemisphere causes motor aphasia. Wernicke areas posterior dominant hemisphere causes receptive aphasia. Homunculus of precentral/motor cortex from inner/medial to lateral: toes, ankle, knee, hip, trunk, shoulder, elbow, wrist, fingers, thumb, neck, brow, eyelid, nares, lips, tongue, larynx. Nondominant posterior MCA infarcsts commonly cause bizarre visiospatial abnormalities or neglect.
    • Anterior choroidal artery – Hippocampus, posterior limb internal capsule, lateral aspect of lateral ventricles just anterior to the atrium.
  • Vertebral artery – Atherosclerosis common at origins, cervical narrowing from compressive uncovertebral osteophytes. Rapid rotation may stretch the vertebrals at C1-2 causing dissection. Angioplasty/stenting reserved for severe medically refractory cases.
  • Basilar artery – Occlusion usually rapidly fatal (infarction of cardiorespiratory centre in medulla). 1/3 of basilar occlusions present subacute ‘not quite right’, before becoming fatal. Needs urgent intervension, ie after confirmation with CTA, do not delay treatment by investigating further with MRI.
    • Brainstem perforating arteries – Focal brainstem infarction with cranial nerve dysfunction, ataxia, somnolence, crossed motor/sensory deficits. Paramidline, unilateral, tubular on transverse images, respects midline and extends to ventral surface (cf central or diffuse from metabolic or hypertensive haemorrhages). Large/multiple pontine lesions may cause ‘locked in’ state (quadriparesis with intact cognition).
    • PCA (10-15%)- Perforating arteries to midbrain (loss of pupillary reflex/quadrigeminal plate, impaired upgaze/CN3, somnolence/reticular activating formation) and thalamus (contralateral sensory loss). Posterior choroidal arteries (choroid plexus 3rd/lat ventricles, pineal gland) rarely cause symptoms due to rich collaterals via choroid plexus. Cortical branches include inferior temporal (inferomedial; memory deficit, severe when bilateral), parieto-occipital (superior occipital gyrus), calcarine artery (visual cortex of occipital lobe, homonymous hemianopsia).
  • Cerebellar arteries – HA, vertigo, nausea, vomiting, ipsilateral ataxia. 85% ischaemic, 15% primary haemorrhages. Haemorrhages and infarctions with significant mass effect are surgical emergencies requiring posterior fossa decompression as there may be superior vermis (through tentorium) or tonsillar/inferior vermis herniation. Cerebellar swelling may be rapid (3hrs-10days after event), occuring if infarction >1/3 of cerebellum, basilar artery occlusion, embolus with reperfusion or massive SCA infarct. May cause hydrocephalus.
    • Superior cerebellar artery (SCA) – Superior vermis, middle and superior cerebellar peduncles, superolateral hemispheres. Most embolic.
    • AICA – Anteromedial cerebellum, occasionally middle cerebellar peduncle. Ipsilateral limb ataxia, nausea, vomiting, dizziness, HA.
    • PICA – Dorsolateral medulla, inferior vermis, posterolateral hemispheres. AICA-PICA loop – ff PICA large, ipsilateral AICA usually small (and vice versa). Ipsilatearl ataxia, nausea, vomiting, dizziness, HA. Lateral medulla insults cause Wallenberg syndrome (ataxia, facial numbness, Horner syndrome, dysphagia, dysarthria).
  • Watershed (borderzone) infarction – Transient global hypoperfusion from cardiac arrest, massive bleeding, anaphylaxis, GA, carotid occlusion/stenosis unmasked by hypotension.
    • Cortical watershed zone – String of deep white matter lesions (rosary bed sign) or damage extending from ‘corners’ of upper lateral ventricles in frontal lobe (ACA/MCA) and posterior parietal (MCA/PCA). Weakness isolated to upper arms (man-in-a-barrel syndrome), cortical blindness, memory loss.
    • Deep watershed zone – Basal ganglia between perforator arteries inferiorly and deep end arteries from superiorly.

Haemorrhagic Transformation

Reperfusion into infarcted capillary beds may cause gross or microscopic haemorrahge in 1/2, with contribution from loss of vascular autoregulation, anticoagulation or thrombolytics. Some have HA, but commonly asymptomatic (tissue already dysnfunctional). Confined to territory of infarcted vessel (cf disrespect to vascular boundaries), intraventricular extension is uncommon. Peak 1-2/7. Serpinginous patchy/discontinuous line of petechial blood following gyral countour (dense, high T1). Tx controversial, some continue anticoagulants if an embolic source is confirmed. Gross haemorrhage may be indistinguishable from primary haematoma, tends to occur earlier. Catastrophic haemorrhage may follow thrombolysis esp if treatment is delayed or baseline CT shows extensive oedema.

Small Vessel Ischaemia

Unidentified bright objects (‘UBO’s, age-related white matter changes small-vessel ischaemic change, senescent change, leukoaraiosis, microangiopathic leukoencephalopathy, subcortical atrteriosclerotic encephalopathy) – Histological axonal atrophy with diminished myelin (myelin pallor). Usually longstanding HTN causing arteriosclerosis and lipohyalinosis of vessels thus narrowing and thrombosis. Small ischaemic lesions in deep white matter (long penetrating end arteries). Usually spares grey matter, subcortical ‘U’ fibres, central corpus callosum, medulla, midbrain and cerebellar peduncles due to collateral supply (cf MS). Usually asymptomatic. Small T2 foci scattered throughout brains of older patients. ?Abnormal or from normal aging. If multiple, may lead to Binswanger disease. May be subclinical precipitant leading to amyloid deposition and Alzheimer disease.

Lacunes (15-20% of strokes) – Similar aetiology as age-related white matter change, but are <15mm infarcts generally in basal ganglia, upper 2/3 putamina (above the anterior commisure cf Virchow-Robin spaces below). TIAs precede in 60%. Commonly lentiform nucleus (37%), pons (16%), thalamus (14%), caudate (10%) and internal capsule/corona radiata (10%). Internal capsule lacunes may cause major deficit. Anterior limb usually silent. Posterior limb (genu/med->lat: head->arm->leg HAL) may cause severe sensory, motor or mixed abormalities, genu may disrupt speech production or swallowing (usually only when bilateral). Etat lacunaire – multiple lacunar infarcts. Affected vessels may be associated with widening of perivascular spaces (etat crible).

In younger patients nonspecific punctate white matter lesions (small high T2) may reflect hypercoagulable conditions, vasculitis, cardiogenic emboli (patent foramen ovale, valvular vegetation), no known aetiology (gliotic residue of remote unspecified insult ?postviral). Hypercoagulable states include homocystinaemia, antiphospholipid syndrome (causes miscarriages), factor V Leiden, prothrombin gene mutation, antithrombin deficiency, protein C/S deficiency.


  • Ependymitis granularis – Normal 7-10mm high T2 along tips of frontal horns. Subependymal loose axonal network with low myelin count, allowing transependymal flow of CSF.
  • Senescent periventricular hyperintensity – With age T2 intensity along enire length of lateral ventricles, normal.
  • Enlarged perivascular spaces (Virchow-Robin spaces, etat crible) – CSF enveloped by pia around perforating vessels, central semiovale, common medial temporal lobe, inferior 1/3 putamen and thalamus (lenticulostriate arteries cf lacunes in upper 2/3). Follow CSF signal with high T2 and iso- on PD and FLAIR. Most are bilaterally symmetric 1-3mm but may be up to 5mm, all age-groups, but increase in size and frequency with age.

Venous Infarction

Uncommon, usually younger patients with HA, sudden focal deficits, seizures. Increased risk with hypercoagulable state, pregnancy, infection (from scalp, face, middle ear, sinus), dehydration, meningitis, direct invasion from tumour. Any dural sinus or cortical vein; most commonly transverse, superior sagittal, cavernous sinuses. Occluded outflow causes stasis, deoxygenation, neuronal death. Continued perfusion into damaged vessels may cause haemorrhage in deep cortical/subcortical regions. Rounded (cf wedge shaped arterial), may spare overlying cortex, might not conform to an arterial territory. Emtpy delta sign – filling defect in superior sagittal sinus seen at 1-4/52 (not acute or chronic); but is normal in 10%. Best seen on spin-echo and MR venography with absent flow voids.

Global Cerebral Hypoxia/Ischaemia

(Diffuse ischaemic/hypoxic encephalopathy). Anoxia when there is near-complete absence of oxygen in blood for >5min, hypoxia with partial prolonged hyoxaemia. Neurons are the most sensitive, followed by glia (oligodendrocytes, astrocytes).

  • Anoxia from cardiac arrest, prolonged seizure, strangulation/hanging, near-drowning, smoke/carbon monoxide inhalation. Metabolically active areas most affected including globus pallidi, Ammon’s horn (dentate nucleus and hipopcampus esp CA1), Purkinje cells of cerebellum. Loss of deep grey-white differentiation may not be apparant for 12-24hrs (cf hyperactue infarction), as CBV is maintained. Cytotoxic oedema with high DWI seen earlier on MRI at ~3hrs. Eventually causes basal ganglia and hippocampal atrophy.
  • Carbon monoxide binds to Hb preventing oxygen binding. Changes most marked in bilateral globus pallidi. Delayed postanoxic encephalopathy in 3% after 2-3 weeks causes high T2 in corpus callosum, subcortical U fibres and internal/external capsules; with low T2 thalamus and putamen.
  • Prolonged hypoxia damages portions furthest from the heart at watershed zones (esp ACA/MCA sickled shaped), but more diffuse than typical watershed infarct. Relative sparing of basal ganglia and hippocampi. Subsequent diffuse cerebral oedema with loss of grey-white differentation and corresponding DWI. Involvement of some layers of cortex with preservation of others causing pseudolaminar necrosis.
  • Severe anoxia/hypoxia causes diffuse oedema, sulcal effacement, raised intracranial pressure with tonsillar herniation then complete cessation of CBF (brain death). Vessels around COW and falx/tent remain relatively hyperdense.
  • Brain death – Irreversible cessation of all cerebral and brain stem functions. Absent spontaneous respirations, no brainstem reflexes, flat serial EEG. Absent radionuclide perfusion uptake (SPECT Tc99 HMPAO). Absent cerebral blood flow on MRA or CTA.

When intracranial pressure increases above 25mmHg cascade of decompensation and eventually brain death will occur. Decompressive craniectomy does not significantly improve neurological outcome and will not reverse damage already done. However, it will reduce the mortality rate (saving patients but leaving many with severe disability).

Intracranial Haemorrhage

MRI (FLAIR and GRE T2*) is more sensitive than CT, even in the hyperacute phase (despite earlier opinions).

Foci of intracranial susceptibility artifact (blood products or calcification) may be deep (usually hypertension), lobar/peripheral (CAA) or random (cavernomas, neurocystercercosis).

CT temporal changes – Timing variable depending of size, recurrence (esp SDH), mixed blood and fluid (eg SAH), cause (eg tumoural) and location. Fluid-fluid levels suggest active bleeding (esp if swirling present) or absence of coagulation (eg heparin, warfarin). Focal extravasation of contrast (‘dot sign’) suggest active bleeding, ie haematoma growth.

  • Freshly extravasated blood is slightly dense (except severely anaemic patients). Blood has HU of 50-60 (cf brain 30-40).
  • <72hrs density increases as serum is extruded, clot forms and retracts (equivalent of higher haematocrit).
  • Vasogenic oedema increases to max at 5 days. Extensive oedema <12hrs raises tumour, infection or prior haemorrhage.
  • >72hrs density reduces centripetally (‘melting ice cube’) due to change in structure of haemoglobin, RBC lysis with dilution and digestion of blood products by macrophages. Haematoma eventually becomes hypodense.
  • 6 days to 6 weeks smooth peripheral rim enhancement of intraparenchymal haemorrhages due to breakdown of BBB from toxic/inflammatory effects.
  • >2months small intraparenchymal haemorrhages may be invisible. Less atrophy than haemorrhagic infarcts or contusions as it tends to displace rather than destroy tissue. May have subtle marginal dense haemosiderin or dystrophic calcification.

MRI interactions with iron – Changes in T1 relaxation only occurs within angstroms, whereas changes to T2 occur mm away.

  • Proton-electron dipole-diple interaction (PEDDI) – Paramagnetic methaemoglobin has strong local field; when water is close enough (3 Ã…=angstrom or 0.3nm) spin transition is induced hence shortened T1 and T2; effect greater with T1WI with high signal. This is independent to field strength.
  • Susceptibility effects – Intracellular paramagnetic metHb, deoxyhaemoglobin and haemosiderin is able to set up local field gradient (susceptibility) cf protons outside, hence faster precession. Water diffusing across membranes each experience different amounts of this gradient, hence greater phase incoherence and low T2/T2*. Effect is greater with longer TE due to greater time for diffusion, and sequences with no dephasing pulse (susceptibility weighted SWI eg GRE, EPI/b0DWI). Effect is dependent on field strength, greater with lower strength.
  • Restricted or increased diffusion occurs in and adjacent to haematomas from various causes at different ages. Susceptibility effects will also alter DWI signal.

MRI temporal changes:

  • Hyperacute (<3-6hrs) – Oxyhaemoglobin blood has no unpaired electrons, diamagnetic. Early clot formation without retraction, hence highly proteinaceous cellular fluid, hence mildly high T1, high T2. Venous blood at peripheries of haematoma has higher deoxyhaemoglobin (paramagnetic) causing susceptibility hence slightly reduced T2 (esp SWI). Mild adjacent vasogenic oedema.
  • Acute (6-72hrs) – Predominately deoxyhaemoglobin with paramagnetic Fe2+ (4 unpaired electrons), but water molecules prevented from approaching close enough to cause proton-electron dipole-dipole interaction (PEDDI). Clot retraction reduces water (esp centrally), and supsceptibility of paramagnetic Fe cause mildly low T1 and low T2*. Rate of conversion to deoxyhaemoglomin is dependent on local pH and oxygen tension, may be delayed when surrounded by oxyen-rich CSF, occurs peripheral -> central. Increasing surrounding high T2 vasogenic oedema.
  • Early subacute (3-7 days) – Intracellular deoxyhaemoglobin oxidises to methaemoglobin (ferric Fe3+, 5 unpaired electrons, paramagnetic) from periphery -> central via several mechanisms, irreversible conversion as the normal RBC enzyme which converts metHb back to deoxyhaemoglomin is not working. Water molecules can approach Fe, allowing PEDDI with marked shortening of T1 (high T1). Susceptibility causes low T2*. Increasing surrounding oedema.
  • Late subacute (7-14 days) – Lysis of blood cells increases access of methaemoglobin to free water; the more dilute the extracellular metHb the more T2 approaches CSF. Susceptibility resolves due to loss of local field inhomogeneity, revealing the ‘true’ high T2 of the haematoma/oedema. Areas of low T2 correspond to retracted clot with intact RBC membranes. High T1 from PEDDI. Peripheral oedema and mass effect start to reduce.
  • Chronic (>2 weeks) – Fe ingested by macrophages and oxidated in lysosomes creating intracellular haemosiderin and ferritin (insoluble Fe3+, superparamagnetic with ~2000 Fe molecules, rust-coloured). This causes significant susceptibily, low on all sequences and blooming on SWI. Starts at the periphery. Insoluble avoiding interaction with water hence no PEDDI and low T1. Haematoma progressively shrinks. Surrounding oedema and mass effect completely resolves. Haemosiderin-laden macrophages quickly enter the bloodstrem in nonneuronal tissues and areas where the BBB is destroyed (eg tumour). In areas of BBB preservation/restoration haemosiderin/ferritin is trapped permanently within brain parenchyma. Recurrent or large SAH (brain tumours, trauma, weepy granulation tissue, amyloid angiopathy) causes diffuse haemosiderin deposition on brain surface (superficial haemosiderosis/siderosis). Small haematomas and deep grey matter bleeds cause peripheral low signal cleft (haemosiderin slit). Large haematomas, haemorrhagic infarcts and contusions cause encephalomalacia with marginal/gyral low signal. Petechial haemorrhages (HTN, amyloid angiopathy, DAI, multiple cavernous malformations, capillary telangiectasia, radiation) produce foci only seen on SWI.

Subarachnoid Haemorrhage (SAH)

From aneurysm rupture (most), AVM of brain or spinal cord, vascular malformation of dura, marked thrombocytopaenia or other severe coagulopathy, vessel injury ± aneurysm/AVM (from drugs including cocaine, trauma, dissection). Typically sudden severe HA. Detection difficult if small or delayed (sensitivity 66% at 3/7, usually not seen at 1/52) in which case lumbar puncture (RBC or xanthochromia) is more sensitive. Haemorrhage is diluted and doesn’t tend to clot (CSF has anticlotting mechanism), lower deoxyhaemoglobin (CSF has relatively high oxygen tension). If bleed is brisk and large may form clot with mass effect and evolves but doesn’t form haemosiderin; might not be seen on FLAIR if acute low T2 but easily seen on T2WI. Most sensitive areas include interpeduncular fossa, posterior occipital horns, also layers in sulci. On MRI subtlely high T1 (‘dirty CSF’), high on FLAIR (much more sensitive than CT, but nonspecific with DDx: inflammatory/neoplastic disease, metallic particles, pure oxygen during MRI as O2 is paramagnetic, pulsation artifact in skull base). On CT may be isodense with lack of CSF hypodensity in basal cisterns, sylvian fissures, anterior interhemispheric fissure, sulcal spaces; making temporal horns and anterior 3rd ventricles stand out.

Siderosis (haemosiderin deposition of leptomenininges, subpia and cranial nerves) from chronic recurrent SAH (not in a single aneurysmal SAH even if large as is cleared before conversion to haemosiderin), eg postoperative granulation tissue, chronic low-grade neoplasms, vascular malformations, CAA, recurrent trauma, bleeding diatheses. Haemosiderin is neurotoxic, causing symptoms. CN8 is particularly sensitive to haemosiderin, causing sensorineural hearing loss.

Traumatic SAH is usually associated with parenchymal or other extra-axial haematoma. Extensive basal SAH without other parenchymal/extra-axial haemorrhage (DDx aneurysm) is uncommon, usually from traumatic dissection (esp vertebral), basal skull fractures (dissection of ICA, proximal MCA). Small amount of SAH in interpeduncular cistern is common and benign with no clinical significance.

Parenchymal Haemorrhage

Primary intraparenchymal haemorrhages have higher initial mortality, but fewer deficits on recovery (tends to tear and displace tissue) than infarcts. Resolving haematomas/infarcts show subacute phase enhancement, vascular capsule. Chronic oral anticoagulation increases risk of bleed by 8x. Pts >60yo tend to have HTN, haemorrhagic infarct or CAA; younger patients usually have an underlying vascular anomaly, venous thrombosis or vasculopathy. May be basal ganglia/thalamus (ganglionic haemorrhage) or lobar haemorrhage.

  • Hypertensive haemorrhage (50%) – Damage of small perforating arteries -> lipohyalinosis -> fibrinoid necrosis (previously thought to be microaneurysms). May be associated with minute Charcot-Bouchard microaneurysms <300μm. Causes 15% of mortality in those with chronic HTN. Commonly basal ganglia (putamen in 50-60%), thalamus, brainstem, cerebellum, lobar subcortical white matter (controversial ?coexisting CAA). After 24-36hrs haemorrhage may enlarge, increasing oedema and mass effect. Usually associated old lacular infarcts, old petechial/slit haemorrhages (deep grey matter, posterior fossa, subcortical; slit-like caviy surrounded by brownish discolouration), chronic small vessel ischaemic change. Usually chronic HTN, but may be seen in acute HTN eg sympathomimetics (cocaine, amphetamines), dialysis, fluid overload.
    • Hypertensive encephalopathy – Malignant HTN with diffuse cerebral dysfunction. Brain oedema ± herniations. Petechial and fibrinoid necrosis of arterioles in grey and white matter.
  • Cerebral amyloid angiopathy (CAA, congophilic angiopathy) – Amyloid deposits (takes up Congo red dye, yellow/apple-green birefringence) in media and adventitia of small and medium sized vessels limited to cortical and leptomeningeal arterioles/capillaries, replacing normal vessel constituents esp elastic lamina -> microaneurysms and fibrinoid degeneration, vascular fragility. Not associated with systemic vascular amyloidosis or HTN; but is associated with brain parenchymal deposits (Alzheimer disease, same beta amyloid), Down syndrome, chronic traumatic encephalopathy, late postradiation necrosis, CJD. Usually elderly with 10% in 60s, >50% in 90s; rarely <55yo. Usually lobar esp frontal and parietal; rarely in cerebellum, white matter, basal ganglia or brain stem; occasionally SAH and SDH. May be recurrent in same location or multiple simultaneous, widespread multifocal cortical/subcortical microbleeds on T2*. May require follow-up scan to exclude haemorrhagic metastases. Almost all have extensive chronic small vessel ischaemic change with sparing of subcortical U fibres.
    • Inflammatory amyloid angiopathy (Amyloid beta related angiitis ABRA) – Rare, overlapping features with PACNS. Can cause multifocal patchy white matter T2 hyperteinsity.
  • Tumours cause 1-2% of bleeds, from necrosis, vascular invasion and/or neovascularity. Most are grade III/IV including glioblastoma, pituitary adenomas, craniopharyngiomas, haemangioblastomas, DNET, ependymomas, metastases (lung, breast, thyroid, melanoma, choriocarcinoma, RCC). Often recurrent over days-weeks. Tends to be more complex and heterogeneous, delayed irregular evolution (?intratumoral hypoxia), lesion enhancement in acute phase (DDx AVM), more prominent oedema which is earlier than expected and persists >1/52, haemosiderin ring absent/incomplete/delayed (benign haematoma ring develops at 2-3/52). Follow-up in 3-6/52 if findings are ambiguous.
  • Haemorrhagic infarcts tend to be in a vascular distribution, infrequently significant mass effect, less confluent, some contrast enhancement (breakdown of BBB), usually no intraventricular extension.

Carotid and Vertebral Dissection

Carotid artery dissection more common than vertebral. Intimal tear with intramural haematoma causing stenosis, occlusion or pseudoaneurysm. May re-enter true lumen with resolution of clot creating false lumen. Usually extracranial, may involve intracranial. Most from trauma (penetrating or rapid neck turning/hyperextension, often mild with symptoms developing over hours/days), occasionally from HTN, FMD, connective tissue disease, migraine HA, coughing, violent sneezing, vomiting, intubation/ventilation, respiratory infection. Symptoms include infarct (usually emboli rather than occlusion), neck pain, compression of adjacent sympathetic nerves (Horner syndrome). Tx anticoagulation to prevent recurrent emboli, most heal spontaneously. Aneurysms require stenting.

On angiography extracranial ICA dissection casues smooth tapering to a pointed occlusion, long asymmetric narrowing (occasionally spiralling = string sign), double lumen with intimal flap (rare, true lumen usually smaller), pseudoaneurysm. Vertebral artery dissection is less specific with occlusion/stenosis (usually ~C5 where there is maximal neck rotation). On MRI intramural haematoma is typically high T1, low/high T2 (usually 3-7/7 old). Target sign – expanded high T1 artery wall with small low signal true lumen, better seen on FS to eliminate periarterial fat. High signal IMH may mimic flow on MRA, but tends to be less intense and amorphous.

Intracranial Venous Thrombosis

Symptoms are nonspecific, variable, protean; including HA, seizures, papilloedema, regional venous infarcts and parenchymal haemorrhages, intracranial HTN/coma/death. Mostly young women and children, increased risk with hormones (OCP, pregnancy, postnatal/puerperium, steroids), prothrombotic haematological conditions (protein S deficiency, polycythaemia), local factors (trauma/fractures, infection, tumour), systemic illness (dehydration, sepsis, hypercoagulability), idiopathic (12.5%). May lead to dural AV fistula, pseudotumour cerebri (benign idiopathic intracranial hypertension). Most start in dural venous sinus, may progress to other sinuses or cortical veins, deep venous system (in children). May resolve spontaneously or after treatment with rapid resolution.

Acute clot is hyperdense and expansile (NECT, DDx polycythaemia esp normal in newborns and common minimal perinatal paratentorial haemorrhage) in dural venous sinus and/or cortical vein (cord sign). Clot becomes isodense/hypodense with resolution of expansion, hence impossible to see on NECT. On CE nonenhancing clot with empty delta sign. On MR clot has same temporal sequence as haemorrahge but slower progression and no haemosiderin formation. May have loss of flow void, but signal may be seen if vessel is oblique or along plane of image. Acute clot is similar to flowing blood but marked low SWI with blooming. Expanded sinus with convex lateral walls. CTV and PC/TOF MRV are more sensitive; but on TOF subacute high T1 clot may mimic flow, hence should also perform PC. Enhanced MRV and CTV usually eliminates artifact from slow or turbulent flow. Arachnoid granulations are focal filling defects usually with CSF high T2 (cf focal thrombi). Chronically occluded sinuses are small, may have partial recanalisation with irregular narrowings and focal occlusions, dilated collateral cortical veins. Thick enhancement of tentorium or falx.


  • Focal subcortical haemorrhage. Appears more acute than intravenous clot as it develops later.
  • SAH, SDH.
  • Focal/diffuse oedema causing mass effect and increased diffusion. On CT impossible to distinguish from infarction.
  • Venous infarction with diffusion restriction, occasionally reverse (cf arterial infarct).

Vascular Anomalies and Malformations

Vascular malformations are classified into AVMs, cavernous malformations (cavernomas), capillary telangiectasias and venous angiomas (DVA). Occult cerebrovascular malformations – small, unable to distinguish between telangectasia, cavernous malformation or small thrombosed AVM. May have small calcification on CT. On MR focal heterogeneous (acute/subacute blood) with surrounding low T2 (haemosiderin).

Cerebral Aneurysm

Saccular/berry (most common) are acquired, not congenital as previously thought but ?underlying defect in media, aetiology remains unknown. The sac is made of thickened hyalinised intimi and adventitia, lacks muscular wall and elastic lamina. 90% are at branching points from damage of endothelium -> thinning of tunica media, fragmentation of internal elastica. 2% of population. Increased risk with family history (7-20% in 1st degree relatives), smoking, HTN, rapid increase in BP (eg cocaine), binge drinking, ADPKD, Ehlers-Danlos, NF1, Marfan syndrome, FMD, aortic coarctation. 15-20% have multiple aneurysms. Peak age 50yo, M>F until postmenopausal F>M. Those >3-5mm are at risk of bleeding, but most ruptured aneurysms are smaller (during acute growth may bleed or stabilise); increase in size with time indicates instability. Unruptured aneurysms may cause unilateral 3rd nerve palsy (PComm), cavernous sinus syndrome (ICA/parasellar), optic chiasm syndrome (bitemporal field defect, AComm). 85% from anterior COW, 15% posterior; 40% AComm, 20% supraclinoid ICA (origins of PComm, ACh, opthalmic), 30% MCA (usually M1/2 junction, clot may expand sylvian fissure mimicing intraparenchymal bleed), 5% vertebrobasilar (basilar tip, PICA, SCA; may only see blood in 4th ventricle esp PICA). Risk of rupture 1.3%/yr, increasing with size with 50%/yr at >10mm. 1/3 of ruptures from acute increase in intracranial pressure (eg straining). 25-50% mortality, 1/3 of survivors have major deficit. Often improve within minutes. If untreated 20% rebleed within 2/52, 40% within 6/12 then 2% per year, with rerupture higher risk of mortality. Cx of bleeding include obstructive hydrocephalus (almost all have some degree), vasospasm, infarct (from raised ICP or vasospasm). The thicker the SAH or IVH/parenchymal extension, the higher grade and worse prognosis. The offending aneurysm is usually the largest, most irregular, focal mass effect, adjacent clot, vasospasm, or has change on serial exams. Characteristics of the aneurysm include size (giant >25mm), neck morphology (narrow/broad based), shape/contour (multilobed/irregular or focal outpouching = Murphy’s tit indicates previous and higher risk of rebleed), wall thickness (intramural/intraluminal bleeds), relationship to vessels/branching, vasospasm, neck/wall calcification (difficult to clip), normal variation of COW. DDx infundibulum (dilated origin with branch vessel from apex), vascular loop. MRA not as sensitive as CTA, but usually detects those >3mm, reasonable for screening. No aneurysm seen in 10% of spontaneous SAH due to vasospasm, or aneurysm filled with clot. Catheter angiography of all intracranial vessels should be done within 1/52 as clotted aneurysms almost always rebleed. DDx SAH from spinal canal (eg AVM/AVF) or benign nonaneurysmal perimesencephalic SAH (from rich venous plexus posterior to clivus; younger M>F, ?related to coitus, doesn’t recur but need to exclude basilar tip aneurysm with follow-up angiogram).

Other types of aneurysms:

  • Fusiform/atherosclerotic – Diffuse long segment, mostly distal vertebral, basilar, proximal MCA. From severe atherosclerosis, dissection, vasculopathies, congenital (collagen disorders, NF1).
  • Infectous(/mycotic) aneurysm – Pseudoaneurysm from infection breakdown or arterial wall. Most are from from septic emboli, usually multiple, small in distal vessels esp MCA branches. Few are from direct spread of infection. 60% fusiform, 40% saccular. High risk of rupture. Rapidly progressive. Stenosis of parent vessel. Vessel becomes very fragile, most of the time treatment usually requires vessel sacrifice.
  • Pseudoaneurysm – Rare, traumatic with haematoma confined by adventitia or surrounding tissues (true aneurysms bound by all 3 layers). Usually causes infarction rather than haemorrhage.
  • Dissecting aneurysm – May cause infarction (due to narrowing a the vessel) or SAH. Blowout/aneurysm of the false sac with narrowing of the true lumen.
  • High-flow AVMs – Within feeding vessels or nidus.
  • Serpentine giant aneurysm – giant aneurysm esp MCA, with a serpiginous tract extending through the aneurysm, separate in and ouflow.
  • Neoplastic – From tumour emboli and growth through vessel wall.

Tx surgical clipping and/or coil embolisation. Early treatment allows more aggressive treatment for vasospasm. Rebleed after Tx more likely extends into parenchyma as aneurysm adherent to brain (scar tissue). Vasospasm (focal or diffuse) usually 3/7 after initial bleed and may persist/worsen, may cause infarct; Tx 3H’s: HTN, hypervolaemia and haemodilution. Post-treatment follow-up with MRA (endovascular coils), CTA (surgical clipping), or catheter angiography.

Arteriovenous Malformation (AVM)

Congenital tangle of dilated feeding artery(s) connected directly to draining veins (usually much larger than aa) via nidus/core (cluster of entangled loops without capillaries). Most common posterior MCA territory. May have supply from multiple vascular territories, including dural aa (esp superficial posterior fossa). Separated by gliotic tissue, often had previous haemorrhage. M:F 2:1, tend to only become symptomatic 10-30yo with seizure or haemorrhage. May cause heart failure in newborn esp vein of Galen. 2% associated with Wyburn-Mason syndrome (retinal, cutaneous, mandibular and brainstem vascular malformations), Klippel-Trenaeunay-Weber (hemihypertrophy angiomatosis of extremity and brain), Sturge-Weber, HHT (Osler-Weber-Rendu, AD, mucocutaneous telangiectasias and visceral AVMs, 5-10% have cerebral AVM where 1/2 are multiple, usually small and cortical). Supratentorial in 80-90%. Cause haemorrhage or seizures. 2-4% annual risk of bleeding, double/triple in first year after initial bleed, 1% annual risk of mortality. >50% have nidal or feeding aa aneursym with increased risk of haemorrhage. Steal phenomenon Рblood diverted to AVM with hypoperfusion of normal brain causing neurological Sx, seizures, parenchymal loss. Adjacent gliosis from chronic ischaemia or haemorrhage. Vessels mildly hyperdense due to blood pool effect with serpentine, punctate or irregular m̩lange configuration. May have curvilinear or speckled calcification. Artifacts in phase-encoding direction. Susceptibility from prior haemorrhage with haemosiderin. Marked enhancement, enlarged feeding aa and draining vv well beyond nidus. Angiography for determining feeding vessels. Just after bleed may be difficult to see due to compression from haematoma or spontaenous obliteration, hence repeat angiography may be needed. Tx embolisation (cure rate only 20% if used alone), surgery, radiosurgery (<30mm). Cx of Tx with extensive steal is brain swelling or haemorrhage due to perfusion pressure breakthrough (marked haemodynamic changes), hence may need staged treatment.

Vein of Galen malformations – AVM often presenting in infancy with hydrocephalus (almost always present, rapidly enlarging head), seizures, high output heart failure. Direct fistula of choroidal aa from thalamoperforate branches of basilar and proximal PCAs. Markedly enlarged vein of Galen (actually median prosencephalic vein) or basal vein of Rosenthal, enlarged dural sinuses. Cx IVH, dural sinus thrombosis, atrophic brain, delayed development (ischaemia from chronic steal). Poor prognosis without treatment, worse with younger age. Tx endovascular occlusion. DDx pial AVM causing dilated vein of Galen (older patients, hydrocephalus usually not present).

Capillary Telangiectasia

Microscopic dilated thin-walled channels separated by relatively normal brain parenchyma. Usually small (<30mm), solitary, incidental. Usually pons, may be elsewhere. Rarely associated with HHT, may occur after radiotherapy. Most don’t haemorrhage. Typically isodense/intense on unenhanced CT/MR, small nodular enhancement, focal slight low signal on SWI. Almost always asymptomatic. Lacks progression, no oedema. No Tx.


(Cavernous angioma/haemangioma/malformation). Thin-walled sinusoidal immature venous channels without intervening normal brain tissue (cf capillary telangiectasias). May be acquired (radiotherapy, DVAs) or congenital AD (multiple in 10-20%). More common than telangiectasias. Commonly cerebellum, pons, subcortical regions. Usually asymptomatic, may haemorrhage (usually small) causing seizure or focal deficit. CT and angiography usually normal unless associated with DVA. MR reticulated mildly enhancing lesion with extensive dark haemosiderin rim on all sequences esp SWI, staining adjacent parenchyma. Haemorrhage of varying ages in and adjacent, occasionally dystrophic calcification. Lacks mass effect unless haemorrhage. If large may have central heterogeneity in popcorn pattern. Most small, may be large with hemic cysts. Areas of high T1 or oedema suggest acute/subacute haemorrhage. Recurrent bleeds may require excision or radiosurgery.

Cavernoma of the cavernous sinus is T2 hyperintense, enhances. Soft tumour without narrowing the ICA (cf meningioma).

Developmental Venous Anomaly (DVA)

(Venous angioma, varix). Congenital, 3% of population. Network of dilated medullary veins converging radially to large vein draining to ventricular or cortical surface. ?From prenatal occlusion of draining vein with large collateral veins. Commonly associated with cavernoma. On unenhanced scan isodense/intense (flow too slow to cause flow void). On enhanced scan small veins (amorphous enhancement in venules) coalesce on surface of brain with draining veins traversing through white matter to subependymal region; vice versa for deep lesions. Caput medusa DVAs drain from different angles to a single large vein. Occasionally large, draining most of a cerebral hemisphere. DVA is compensatory drainage for region of brain and treatment may cause venous infarct, hence reserved for life-threatening haemorrhage.

Dural Arteriovenous Fistula (dAVF)

(Dural AVM). Acquired from dural sinus thrombosis -> sudden recanalisation -> direct communication with small dilated aa in sinus wall/dura -> raised sinus pressure -> impaired outflow from adjacent brain with venous backpressure -> dilated cortical veins, parenchymal haemorrhage, SAH, venous infarction, ‘tight brain’, elevated ICP (pseudotumour cerebri, idiopathic intracranial hypertension). Occasionally may cause progressive dementia from chronic hypoperfusion. Increased risk of Cx with DAVFs in deep venous system, retrograde venous flow, venous aneurysms, stenotic channels where blood must drain, complex lesions. Sigmoid sinus most common, may cause tinnitus, bruit. Carotid-cavernous fistulas cause enlargement of the cavernous sinus, superior opthlamic vein, stranding of intraorbital fat, enlarged extraocular mm, proptosis, glaucoma. Slow flow fistulas may resovle spontaneously, aided by intermittent ipsilateral carotid artery compression. May cause CN3/4/6 palsies from venous compression (esp CN6 in Dorello’s canal). MRV/CTV may show regions of stenosis or focal occlusions. On catheter angiography ECA or CCA injection shows dilated meningeal aa, fistula and delayed filling of cortical veins. Tx embolisation, stenting of venous sinus, carotid massage to allow sinus thrombosis. The mortality of dAVF is defined by the degree of elevation in venous pressure, ie adequacy of venous drainage.

Ethmoidal dAVF (anterior cranial fossa dAVF) – fistula between ophthalmic artery and dural venous sinus. Typical haemorrhage pattern right frontal extending to floor anterior cranial fossa +/- subdural/SAH.



Onset is usually subacute. Uncommon. Pattern of vasculitis on imaging is more commonly due to RCVS or intracranial atherosclerosis. Gold standard investigation is catheter angiography (10% false negative due to small aa and arteriole involvement). CTA and MRA cannot detect 2nd and 3rd degree branches abnormal except 3T MRA. CT and MR perfusion studies may show no perfusion abnormalily hence exclude vasculitis. Final diagnosis often requires biopsy (vessels, meninges, parenchyma, skin/nerve/muscle, random temporal artery). Variable infarcts. Parenchymal and superficial SAH from distal arterial disease.


  • FMD – Cervical ICA and vertebrals
  • GCA – Especially superficial temporal artery

Skull base to Circle of Willis:

  • Moyamoya
  • Basal cistern meningitis – COW and basilar artery. Arterial constrictions and spasm. Bacterial meningitis uncommon. Chronic granulomatous meningitis (eg TB) causes stenoses/occlusions slowly creating a moyamoya pattern, but also involves posterior circulation. May affect perforating aa causing basal ganglia and thalamic infarcts. Communicating hydrocephalus also common.
  • Sickle cell – Cerebrovascular disease in 5-17%, higher in children. Stasis and ischaemia in vasa vasorum -> intimal and medial hyperplasia -> narrowings and occlusions of ICA, proximal ACA and MCA. Collaterals develop similar to moyamoya. Posterior circulation usually spared. Contrast may precipitate a sickle cell crisis, hence requires reducing HbS to <20% prior to the study, O2 and warming blanket. High T2 foci from small vessel sludging and occlusion, indistinguishable from MS.
  • Cocaine abuse – Rare

Secondary and tertiary vessels (‘cerebral vasculitis’) – Circumferential tapered stenoses with intervening normal/enlarged regions, typically multiple territories. May cause focal parenchymal haemorrhage, superficial SAH, cortical infarcts (typically distal portions with deep structures less commonly involved).

  • Inflammatory granulomatous diseases
    • Primary angiitis of the CNS (PACNS, granulomatous angiitis of the nervous system) – Elevated ESR. Small distal cerebral aa and vv infiltrated with lymphocytes, giant cells, mononuclear cells. Subacute presentation, may be rapidly progressive with mortality in 25%. Changes involving basal ganglia, cortex +/- subcortical WM, cerebellum, meninges. Patchy T2 signal change, enhancement (punctate, linear or gyriform). Vessel wall enhancement is smooth concentric, long,Multiple bilateral supratentorial infarcts esp deep white matter. May cause haemorrhage.
    • Granulomatosis with polyangiitis (Wegener granulomatosis) – Necrotising systemic vasculitis of kidneys, respiratory tracts, brain. Thought to be a variant of PACNS. Peak 30s-40s, M slightly >F. Positive c-ANCA (anti-neutrophil cytoplasmic antibody).
    • Amyoid beta related angiitis of the CNS (ABRA, inflammatory CAA)
    • Polyarteritis nodosa – Necrotising inflammation of small and medium aa with late CNS involvement. Immune-mediated, 30% hepatitis B surface antigen positive. Aneurysms uncommon in CNS (cf renal and splanchnic vessels).
    • Neurosarcoidosis – Rarely CNS vasculitis with invasion of walls. May also involve veins.
    • Bercet’s disease
  • Infection – Herpes zoster, TB, fungal, neurosyphilis
  • Drugs – Cocaine, amphetamines, ephedrine
  • Pregnancy/perinatal/COCP – Oedema or spasm of vessel wall.
  • Atherosclerosis – Especially diabetes, HTN. Stenoses usually asymmetric and irregular.
  • Vasospasm – Eg SAH usually more diffuse narrowing with no intervening normal vessel calibre, centred at bifurcations.
  • Intravascular lymphoma (lymphomatoid granulomatosis, neoplastic angioendotheliosis) – Malignant lymphoma confined to intracranial vessels causing medium vessel occlusions.

Small vessels – Imaging studies almost always normal apart from deep grey, white mater and subcortical infarcts (tend to be irregular-parallel periventricular cf MS).

  • Collagen vascular disease – SLE, anti-cardiolipin and anti-phospholipid syndromes. Tends to cause perivascular inflammation of endothelial proliferation rather than true vasculitis. Vasculitis is rare; more commmonly cardioembolic infarcts
  • Radiation vasculopathy – Endothelial degeneration, intimal fibrosis, fibroblastic proliferation of media occuring months-years after therapy. In severe cases may also involve secondary and tertiary aa.
  • Migraine headache – White matter T2 foci in 10-25% of patients with migraines, usually few, subcortical frontal lobes ?due to spasm of small aa from migraine attacks. Rarely hemiplegic migraine with ACA or MCA infarct, increased risk with CADASIL and women with auras.
  • HIV encephalitis
  • Susac’s syndrome

Intracranial atherosclerosis is common, particular middle-older age. Multifocal narrowings predominantely vertebrobasilar, ICAs, M1 segments. Can get inflammatory change with active atherosclerosis with wall enhancement.

Reversible Cerebral Vasoconstriction Syndrome (RCVS)

Sudden onset headache. Can be idiopathic or secondary (eg pregnancy, multiple different therapeutic and recreational drugs). 10% of RCVS also have PRES. Multiple vessel narrowings, initially involving distal vessels then proximal. Occasionaly involves extracranial ICA. Maximal vasoconstriction is at the time of the headache. Usually resolves within 10 days, otherwise by definition will resolve within 3 months. Haemorrhage may occur at presentation, infarcts may occur at presentation or later. Should not be treated with steroids (compared to vasculitis).

Reversible multifocal intracranial stenoses (RMIS) is a subtype of RCVS where arterial stenoses persist longer than 3 months.

Fibromuscular Dysplasia (FMD)

Etiology unknown. F:M 4:1, mean age 50yo. DDx atherosclerosis, catheter vasospasm, standing waves.

  • Type 1 (most common) – Fibrous and muscular thickening of esp media causing narrowing. Thinning and disruption of internal elastic lamina causes saccular dilatations with string of beads appearance.
  • Type 2 – Unifocal/multifocal tubular stenoses.
  • Type 3 – Lesions confined to portion of arterial wall.

Involves cervicocephalic aa in 30% esp ICA (esp 20mm distal to bifurcation at C2), vertebral a, commonly multiple vessels (bilateral ICA in 60%). Intracranial FMD rare. Cx dissection, cavernous-carotid fistula. Higher risk of intracranial aneurysms ?pseudoaneurysms.

Giant Cell Arteritis (GCA)

(Temporal arteritis). Most >70yo, F>M. Associated with polymyalgia rheumatica in 40%. Involves media of vessels esp superficial temporal arteries scattered along vessel. Intracranial involvement rare. Visual loss and headache, tenderness/swelling, jaw claudication.

Moyamoya Disease

Idiopathic, linked to genetic defect, ?epiphenomenon of other proximal stenosis vasculopathies (NF with ICA stenoses, radiation, atherosclerosis, sickle cell). Mostly Japanese. In children (most) course is progressive with ischaemia (TIAs, stroke); adults intraparenchymal and SAH. Eventually develops dementia. Obliterative arteriopathy (progressive stenosis then occlusion) of supraclinoid ICA and 1st-order branches. Extensive collaterals including dural vessels, pericallosal from PCA, deep perforating lenticulostriate arteries. Dilated irregular perforating arteries causes puff of smoke appearance (Japanese = moyamoya) and curvilinear hyperdensities/low T1/T2 (pathognomonic). Multiple basal ganglia, cortical and subcortical infarcts, basal ganglia haemorrhage, SAH, atrophy.


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