Stroke &Imaging

• Stroke is a leading cause of mortality and morbidity in the developed world. The goals of an imaging evaluation for acute stroke are to establish a diagnosis as early as possible and to obtain accurate information about the intracranial vasculature and brain perfusion for guidance in selecting the appropriate therapy. A comprehensive evaluation may be performed with a combination of computed tomography (CT) or magnetic resonance (MR) imaging techniques. Unenhanced CT can be performed quickly, can help identify early signs of stroke, and can help rule out hemorrhage. CT angiography and CT perfusion imaging, respectively,can depict intravascular thrombi and salvageable tissue indicated by a penumbra. These examinations are easy to perform on most helical CT scanners and are increasingly used in stroke imaging protocols to decide whether intervention is necessary. While acute infarcts may be seen early on conventional MR images, diffusion-weighted MR imaging is more sensitive for detection of hyperacute ischemia. Gradient-echo MR sequences can be helpful for detecting a hemorrhage.

• The status of neck and intracranial vessels can be evaluated with MR angiography, and a mismatch between findings on diffusion and perfusion MR images may be used to predict the presence of a penumbra. The information obtained by combining various imaging techniques may help differentiate patients who do not need intravenous or intraarterial therapy from those who do, and may alter clinical outcomes.

• acute cerebral ischemia may result in a central irreversibly infarcted tissue core surrounded by a peripheral region of stunned cells that is called a penumbra .Evoked potentials in the peripheral region are abnormal, and the cells have ceased to function, but this region is potentially salvageable with early recanalization .

• A penumbra can be evaluated both on CT images (on which it is evidenced by a discrepancy in perfusion parameters) and on MR images (on which it is indicated by a mismatch between diffusion and perfusion parameters). The presence of a penumbra has important implications for selection of the appropriate therapy and prediction of the clinical outcome. Intravenous thrombolytic treatment is not typically administered to patients with acute stroke beyond the conventional 3-hour period after the onset of symptoms, because such treatment results in an increased risk of hemorrhage . However, the results of recent studies have demonstrated that intravenous thrombolytic therapy may benefit patients who are carefully selected according to findings of a diffusion or perfusion mismatch or a penumbra at imaging

• •Posterior Inferior Cerebellar Artery (PICA in blue)• The PICA territory is on the inferior occipital surface of the cerebellum and is in equilibrium

with the territory of the AICA in purple, which is on the lateral side (1). • The larger the PICA territory, the smaller the AICA and viceversa. • •Superior Cerebellar Artery (SCA in grey)• The SCA territory is in the superior and tentorial surface of the cerebellum.

• •Branches from vertebral and basilar artery• These branches supply the medulla oblongata (in blue) and the pons (in green). • •Anterior Choroideal artery (AchA in blue))• The territory of the AChA is part of the hippocampus, the posterior limb of the internal capsule

and extends upwards to an area lateral to the posterior part of the cella media.

• •Lenticulo-striate arteries • The lateral LSA' s (in orange) are deep penetrating arteries of the middle cerebral artery (MCA).• Their territory includes most of the basal ganglia.• The medial LSA' s (indicated in dark red) arise from the anterior cerebral artery (usually the A1-

segment).• Heubner's artery is the largest of the medial lenticulostriate arteries and supplies the

anteromedial part of the head of the caudate and anteroinferior internal capsule.

• •Anterior cerebral artery (ACA in red)• The ACA supplies the medial part of the frontal and the parietal lobe and the anterior portion

of the corpus callosum, basal ganglia and internal capsule. • •Middle cerebral artery (MCA in yellow)• The cortical branches of the MCA supply the lateral surface of the hemisphere, except for the

medial part of the frontal and the parietal lobe (anterior cerebral artery), and the inferior part of the temporal lobe (posterior cerebral artery).

• The deep penetrating LSA-branches are discussed above. • •Posterior cerebral artery (PCA in green)• P1 extends from origin of the PCA to the posterior communicating artery, contributing to the

circle of Willis. • Posterior thalamoperforating arteries branch off the P1 segment and supply blood to the

midbrain and thalamus.• Cortical branches of the PCA supply the inferomedial part of the temporal lobe, occipital pole,

visual cortex, and splenium of the corpus callosum.

Watershed Infarcts• Watershed infarcts occur at the border zones

between major cerebral arterial territories as a result of hypoperfusion.

• There are two patterns of border zone infarcts:

• 1.Cortical border zone infarctions• Infarctions of the cortex and adjacent

subcortical white matter located at the border zone of ACA/MCA and MCA/PCA

• 2.Internal border zone infarctions• Infarctions of the deep white matter of the

centrum semiovale and corona radiata at the border zone between lenticulostriate perforators and the deep penetrating cortical branches of the MCA or at the border zone of deep white matter branches of the MCA and the ACA.

• On the left three consecutive CT-images of a patient with an occlusion of the right internal carotid artery.

• The hypoperfusion in the right hemisphere resulted in multiple internal border zone infarctions.

• This pattern of deep watershed infarction is quite common and should urge you to examine the carotids.

• On the left images of a patient who has small infarctions in the right hemisphere in the deep borderzone (blue arrowheads) and also in the cortical borderzone between the MCA- and PCA-territory (yellow arrows).

• There is abnormal signal in the right carotid (red arrow) as a result of occlusion.

• In patients with abnormalities that may indicate borderzone infarcts, always study the images of the carotid artery to look for abnormal signal

Cerebral Venous territory

• On the left the CT nicely demonstrates the dense thrombosed transverse sinus (yellow arrow). The FLAIR image demonstrates the venous infarction in the temporal lobe.

• The clinical presentation of thrombosis of the deep cerebral venous system are severe dysfunction of the diencephalon, reflected by coma and disturbances of eye movements and pupillary reflexes. Usually this results in a poor outcome. However, partial syndromes without a decrease in the level of consciousness or brainstem signs exist, which may lead to initial misdiagnoses.

• Deep cerebral venous system thrombosis is an underdiagnosed condition when symptoms are mild and should be suspected if the patient is a young woman, if the lesions are within the basal ganglia or thalamus and especially if they are bilateral.

• On the left images of a patient with deep cerebral vein thrombosis. Notice the bilateral infarctions in the basal ganglia .

CT Early signs of ischemia• CT has the advantage of being

available 24 hours a day and is the gold standard for hemorrhage.

• Hemorrhage on MR images can be quite confusing.

• On CT 60% of infarcts are seen within 3-6 hrs and virtually all are seen in 24 hours.

• The overall sensitivity of CT to diagnose stroke is 64% and the specificity is 85%.

• In the table on the left the early CT-signs of cerebral infarction are listed.

• Hypoattenuation on CT is highly specific for irreversible ischemic brain damage if it is detected within first 6 hours (1).

• Patients who present with symptoms of stroke and who demonstrate hypodensity on CT within first six hours were proven to have larger infarct volumes, more severe symptoms, less favorable clinical courses and they even have a higher risk of hemorrhage.

• Therefore whenever you see hypodensity in a patient with stroke this means bad news.

• No hypodensity on CT is a good sign.

• Obscuration of the lentiform nucleus

• Obscuration of the lentiform nucleus, also called blurred basal ganglia, is an important sign of infarction.

• It is seen in middle cerebral artery infarction and is one of the earliest and most frequently seen signs (2).

• The basal ganglia are almost always involved in MCA-infarction.

• Insular Ribbon sign

• This refers to hypodensity and swelling of the insular cortex.

• It is a very indicative and subtle early CT-sign of infarction in the territory of the middle cerebral artery.

• This region is very sensitive to ischemia because it is the furthest removed from collateral flow.

• It has to be differentiated from herpes encephalitis.

• Dense MCA sign

• This is a result of thrombus or embolus in the MCA.

• On the left a patient with a dense MCA sign.• On CT-angiography occlusion of the MCA is

visible.

• Hemorrhagic infarcts

• 15% of MCA infarcts are initially hemorrhagic• Hemorrhage is most easily detected with CT,

but it can also be visualized with gradient echo MR-sequences.

• First look at the images on the left and try to detect the abnormality.

• The findings in this case are very subtle.

• There is some hypodensity in the insular cortex on the right, which is the area we always look at first.

• In this case it is suggestive for infarction, but sometimes in older patients with leukencephalopathy it can be very difficult.

• A CTA was performed

• CT Perfusion (CTP)• With CT and MR-diffusion we can get a good impression

of the area that is infarcted, but we cannot preclude a large ischemic penumbra (tissue at risk).

• With perfusion studies we monitor the first pass of an iodinated contrast agent bolus through the cerebral vasculature.

• Perfusion will tell us which area is at risk.• Approximately 26% of patients will require a perfusion

study to come to the proper diagnosis. The limitation of CT-perfusion is the limited coverage.

• Studies were performed to compare CT with MRI to see how much time it took to perform all the CT studies that were necessary to come to a diagnosis.

• It was demonstrated that Plain CT, CTP and CTA can provide comprehensive diagnostic information in less than 15 minutes, provided that you have a good team.

• In the case on the left first a non-enhanced CT was performed.

• If there is hemorrhage, then no further studies are necessary.

• In this case the CT was normal and a CTP was performed, which demonstrated a perfusion defect.

• A CTA was subsequently performed and a dissection of the left internal carotid was demonstrated.

• On PD/T2WI and FLAIR infarction is seen as high SI.

• These sequences detect 80% of infarctions before 24 hours.

• They may be negative up to 2-4 hours post-ictus!

• On the left T2WI and FLAIR demonstrating hyperintensity in the territory of the middle cerebral artery.

• Notice the involvement of the lentiform nucleus and insular cortex.

• High signal on conventional MR-sequences is comparable to hypodensity on CT.

• It is the result of irreversible injury with cell death.

• So hyperintensity means BAD news: dead brain.

• Diffusion Weighted Imaging (DWI)

• DWI is the most sensitive sequence for stroke imaging.• DWI is sensitive to restriction of Brownian motion of

extracellular water due to imbalance caused by cytotoxic edema.

• Normally water protons have the ability to diffuse extracellularly and loose signal.

• High intensity on DWI indicates restriction of the ability of water protons to diffuse extracellularly.

• First look at the images on the left and try to detect the abnormality.

• Then continue reading.

• The findings in this case are very subtle.• There is some hypodensity and swelling in

the left frontal region with effacement of sulci compared with the contralateral side.

• You probably only notice these findings because this is an article about stroke and you would normally read this as 'no infarction'.

• Now continue with the DWI images of this patient.

• When we look at the DWI-images it is very easy and you don't have to be an expert radiologist to notice the infarction.

• This is why DWI is called 'the stroke sequence'

• Pseudo-normalization of DWI• This occurs between 10-15 days.• The case on the left shows a

normal DWI.• On T2WI there is may be some

subtle hyperintensity in the right occipital lobe in the vascular territory of the posterior cerebral artery.

• The T1WI after the administration of Gadolinium shows gyral enhancement indicating infarction.

• First it was thought that everything that is bright on DWI is dead tissue.

• However now there are some papers suggesting that probably some of it may be potentially reversible damage.

• If you compare the DWI images in the acute phase with the T2WI in the chronic phase, you will notice that the affected brain volume in DWI is larger compared to the final infarcted area (respectively 62cc and 17cc).

• Perfusion MR Imaging

• Perfusion with MR is comparable to perfusion CT.

• A compact bolus of Gd-DTPA is delivered through a power injector.

• Multiple echo-planar images are made with a high temporal resolution.

• T2* gradient sequences are used to maximize the susceptibility signal changes.

• The area with abnormal perfusion can be dead tissue or tissue at risk.

• Combining the diffusion and perfusion images helps us to define the tissue at risk, i.e. the penumbra.

• On the DWI there is a large area with restricted diffusion in the territory of the right middle cerebral artery.

• Notice also the involvement of the basal ganglia.

• There is a perfect match with the perfusion images, so this patient should not undergo any form of thrombolytic therapy.

CNS Vasculitis &

MRI

Characterization of CNS Vasculitis

• Vasculitis of the CNS is characterized by the size of the affected vessel, as illustrated in Fig. Determining size and location of the predominantly affected vessels is useful to obtain an optimal tissue biopsy and establish appropriate treatment . Large artery vasculitis usually responds well to steroids alone,while small and medium-sized vessel vasculitis respond better to a combination of cytotoxic agents and steroids. Therefore, a clear understanding of the size of the vessels involved and the pathophysiologic mechanisms are useful for the treatment decision.

• Digital subtraction catheter angiography and brain biopsy are the diagnostic foundations in establishing the diagnosis. However, angiography has a false-negative rate of 20–30%, as small arteries with a diameter of less than 100–200 μm are beyond the limit of resolution of digital subtraction angiography . Good-quality MR angiography can demonstrate stenosis or occlusion of large to middle-sized arteries,but the resolution is not sufficient to detect abnormalities of small arteries.

• MR imaging, on other hand, is sensitive to detect gray and white matter lesions in CNS vasculitis, but the appearance of these lesions is usually not specific .

• Whether the lesions on MR imaging are reversible or irreversible depends on the severity of ischemia and seems to be related to size and location of the vessels involved. Occlusion or stenosis involving large, medium or small arteries mainly results in infarction,whereas lesions involving arterioles, capillaries,venules or veins predominantly cause vasogenic edema or gliosis.

• DW imaging can be useful to differentiate an acute or subacute infarction from vasogenic edema or gliosis,which is important both for choice of treatment and to predict the long-term prognosis.

• Multifocal and multiphasic ischemia are some of the characteristic sequelae of CNS vasculitis.DW imaging can differentiate the phases of cerebral infarction as hyperacute, acute, subacute or chronic.

• The hyperacute phase of an infarction usually has a decreased apparent diffusion coefficient (ADC) and a normal or subtle increase in signal intensity on T2-weighted or fluid-attenuated inversion-recovery (FLAIR) images. The acute phase has a decreased ADC with hyperintensity on T2-weighted images. In the subacute phase, ADC values are normalized; in the chronic phase, DW imaging shows hypointensity with increased ADC.

CNS VASCULITIS

NONINFECTIOUSNecrotizing VasculitidesPACNS (primary angiitis of the central nervoussystem)Polyarteritis nodosaGiant cell arteritisTakayasu's arteritisWegener's granulomatosisLymphomatoid granulomatosisNeurosarcoidosisVasculitis Associated with Collagen Vascular DiseasesSystemic lupus erythematosusSclerodermaRheumatoid arthritisSjogren's syndromeDrug-Related VasculitisOthersSusac's syndrome (retinocochleocerebralvasculopathy)Behcet's syndromeSneddon syndromeEales diseaseDegos disease (malignant atrophic papillosis)INFECTIOUSHaemophilus influenzaeSyphilisTuberculosisHerpes ZosterHIVOther

Primary Angiitis of the CentralNervous System

• Primary angiitis of the central nervous system (PACNS), also known as noninfectious granulomatous angiitis of the central nervous system or granulomatous angiitis of the nervous system, affects parenchymal and leptomeningeal vessels of the central nervous system with a predilection for small arteries and arterioles (200 to 500 mm in diameter). It strikes middle-aged persons with complaints of headache and signs of focal or global neurologic dysfunction. This can be a rapidly progressive disease and is frequently fatal. The sedimentation rate is elevated in more than two thirds of patients, and cerebrospinal fluid (CSF) demonstrates elevated protein and pleocytosis in more than 80% of cases.

• Primary angitis of the central nervous system tends to affect small to medium sized vessels of the brain parenchyma and meninges,but can affect vessels of any size. Angiography typically shows a “string-of-beads” appearance, but it has a false-negative rate of 20–30% . Brain and meningeal biopsies are diagnostic in only 50–72% of patients with primary angitis of the central nervous system

• The vasculitis process results in multiple regions of deep white matter infarction, hemorrhage, or tumor like masses that may be easily imaged on MR. Lesions are usually multiple and supratentorial, involving both hemispheres.

• Lesions detected on MR have a positive angiographic correlation; however, not all lesions seen angiographically have positive MR findings. Angiography is more sensitive than MR at detecting vessel involvement.

• Magnetic resonance imaging findings in primary angitis of the central nervous system are highly variable,ranging from multiphasic cerebral infarction,vasogenic edema and gliosis, to hemorrhage and leptomeningeal enhancement . The lesions caused by occlusion of large or medium-sized arteries affect the cortical or deep gray matter. If the vessels involved are small, MR imaging may show discrete or diffuse lesions in the deep or subcortical white matter. On follow-up MR imaging, the lesions may change with regard to number and size, and they may even disappear. DW imaging is useful in differentiating an acute or subacute infarction from reversible vasogenic edema and can demonstrate multiphasic infarctions.Prompt diagnosis is important, as primary angitis of the central nervous system is often fatal if not treated with aggressive immunosuppression

Giant Cell (Temporal) Arteritis• The criteria of the American College of

Rheumatology for the diagnosis of giant cell arteritis include at least three of the following: (1) age at disease onset >50 years, (2) new onset of headache, (3)claudication of jaw or tongue, (4) tenderness of the temporal artery on palpation or decreased pulsation, (5) erythrocyte sedimentation ratio >50 mm/h and(6) temporal artery biopsy showing vasculitis with multinucleated giant cells.

• Giant cell arteritis is probably a T cell-mediated vasculitis and it can affect medium to large arteries.

• The superficial temporal, vertebral and ophthalmic arteries are more commonly involved than the internal carotid arteries,while the intracranial arteries are rarely involved .Abrupt and irreversible visual loss is the most dramatic complication of giant cell arteritis,while a TIA and stroke are rare (7%),but when present most often involve the vertebrobasilar territory. Steroids are effective, and giant cell arteritis is usually self-limited and rarely fatal.

Takayasu’s Arteritis (Aortitis Syndrome)

• Takayasu’s arteritis is a primary arteritis of unknown cause but probably also related to T cell mediated inflammation. Takayasu’s arteritis commonly affects large vessels including the aorta and its major branches to the arms and the head. It is more commonly seen in Asia and usually affects young women. Pulseless upper extremities and hypertension are the common clues to suggest the diagnosis.

• Most patients are treated with steroids alone to reduce the inflammation. The prognosis is relatively good and 90% of patients are still alive after 10 years.

• TIA or stroke is rare but can occasionally occur in severe cases with significant stenosis of arteries supplying the CNS.

Polyarteritis Nodosa (PeriarteritisNodosa

• Polyarteritis nodosa is a multisystem disease characterized by necrotizing inflammation of the small and medium size arteries with CNS involvement occurring late in the disease in more than 45% of cases. The CNS manifestations include encephalopathy, seizures, and focal deficits. It is an immune-mediated disease with about 30% of patients having hepatitis B surface antigen. The diagnosis is confirmed by nerve, muscle, or kidney biopsy, which demonstrates multiple small aneurysms or arteritis. Polyarteritis is closely related to allergic angiitis and granulomatosis (Churg-Strauss) disease and a polyangiitis overlap syndrome (combination of Churg-Strauss and polyarteritis nodosa).

• Imaging findings include cortical or subcortical infarction as well as nonspecific high intensity T2WI lesions in the white matter. Intracranial hemorrhage (SAH,intraparenchymal) and vascular dissection have been reported.Aneurysms, which are common in the renal and splanchnic vessels, are unusual in the CNS.

• Wegener Granulomatosis• This granulomatous necrotizing systemic vasculitis affects

the kidneys, upper and lower respiratory tracts, but can affect the brain producing stroke, visual loss, and other cranial nerve problems. The peak incidence is in the fourth to fifth decade with a slight male predominance.

• The vasculitis affects small and medium-size arteries and veins while sparing larger vessels. High intensity abnormalities on T2WI occur in about 28% of cases. History plus positive c-ANCA tests help make thediagnosis.

Collagen Vascular Diseases• Behçet’s disease is a multisystem vasculitis of unknown origin. It

is especially common in Middle Eastern and Mediterranean countries. CNS involvement has been described in 4–49% of cases [6]. The parenchymal distribution of lesions, especially at the mesodiencephalic junction (46%) supports small vessel vasculitis involving both the arterial and venous systems; mainly venules. The lesions are occasionally reversible on MRI, which mainly represents vasogenic edema,which is why DW imaging is useful in distinguishing them from infarction . The treatment is usually a combination of cytotoxic agents and steroids. In other types of collagen diseases,such as scleroderma or rheumatoid arthritis,involvement of the CNS is very rare.

Vasculopathy of the CNS

• Vasculopathy is caused by a wide variety of underlying conditions such as degenerative, metabolic, inflammatory,embolic, coagulative and functional disorders . This presentation focuses on vasculopathies that mimic vasculitis, but have no inflammation in the wall of the blood vessel

Spectrum of CNS vasculopathy

Systemic Lupus Erythematosus

• Involvement of the CNS occurs in 14–75% of patients with systemic lupus erythematosus (SLE). Pathologically,microinfarcts and small vessel vasculopathy are the most common.Vasculopathy affects predominantly the arterioles and capillaries, resulting in vessel tortuosity, vascular hyalinization, endothelial proliferation and perivascular inflammation or gliosis.

• True vasculitis is very rare (0–7%). This vasculopathy may be related to both acute inflammation and ischemia [28]. In recent reports, the mechanism of vasculopathy in CNS involvement of SLE has been attributed to intravascular activation of a complement,which leads to adhesion between neutrophils and/or platelets and endothelium, resulting in leukothrombosis in the microvasculature (Shwartzman phenomenon)

• In this vasculopathy, despite widespread microvascular occlusions, parenchymal damage is minimal and potentially reversible. Sibbit et al. reported that up to 38% of CNS lesions in SLE were potentially reversible on MR imaging [30]. MR angiography and conventional angiography may provide additional information concerning vascular abnormalities.

• DW imaging shows primarily two patterns of parenchymal lesions with acute or subacute CNS symptoms: one is an acute or subacute infarction,and the other is vasogenic edema with or without microinfarcts .CNS involvement in SLE is also due to associated uremia, hypertension, infection, Libman–Sacks endocarditis, and corticosteroid or immunosuppressive therapy.

• On T2WI, high signal is recognized in the white matter,sometimes in a vascular distribution but also involving cortical and subcortical areas, particularly in the occipital region. Such high-intensity regions have been reported in a symmetric distribution in young female patients with diffuse C S lupus. Periventricular white matter appears to be relatively spared even in patients with diffuse C S lupus, which may differentiate it from multiple sclerosis, where there is a predilection for periventricular lesions. Atrophy is commonly found in these patients,related either to the encephalopathy itself or to the effect of steroid treatment. Data suggest that some lesions may evolve within a 7- to 10-day course in patients with rapidly changing neurologic symptoms and that certain lesions may be responsive to steroid therapy.Subarachnoid hemorrhage and intraparenchymal hemorrhage have also been reported in C S lupus. The presence of saccular and fusiform aneurysms has also been observed.

Thank you for your attention