Cerebral Revascularization Imaging 

Updated: Aug 24, 2016
  • Author: Jeffrey P Kochan, MD; Chief Editor: James G Smirniotopoulos, MD  more...
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Presentation of Stroke

Types of Stroke

Stroke is defined as the damage to the brain and the resultant neurologic deficits that occur when the blood supply to a given area of the brain is lost. Stroke, however, is not a single process. Instead, it may be the result of 1 or more of the following processes: thrombotic stroke, embolic stroke, hemorrhagic stroke, and reversible ischemic stroke (see the images below).

Hyperdensity in the left temporal parietal region Hyperdensity in the left temporal parietal region consistent with an acute parenchymal hemorrhage with intraventricular depression.
Technetium-99m single-photon emission CT (SPECT) i Technetium-99m single-photon emission CT (SPECT) images of a stroke resulting from occlusion of the right internal carotid artery. Note the significant decrease in uptake throughout virtually the entire right cerebral hemisphere.

Thrombotic stroke

A thrombotic stroke occurs when plaque and clots form locally on the wall of a cerebral artery, leading to a progressive narrowing of the arterial lumen until it becomes completely occluded.

Embolic stroke

An embolic stroke occurs when a clot and/or plaque becomes dislodged from the heart or walls of the extracranial arteries that supply the brain (eg, carotid artery bifurcation) and are carried by arterial blood flow into the brain. Once it reaches the brain, the embolus lodges in a small-diameter vessel, creating a blockage. The image below demonstrates the appearance of an acute embolic stroke on a computed tomography (CT) scan.

The most common appearance of an acute thromboembo The most common appearance of an acute thromboembolic stroke is a normal computed tomography (CT) scan. The earliest finding that might be detected is an asymmetric hyperattenuating cerebral artery that corresponds to the neurologic deficit. The hyperattenuated area in the suprasellar cistern and left sylvian represents an intraluminal clot secondary to either local thrombosis or embolus. This has been referred to as the "hyperdense middle cerebral artery sign."

Hemorrhagic stroke

A hemorrhagic stroke occurs when a blood vessel in the head ruptures, reducing blood flow to all or part of the brain. Aneurysms tend to rupture into the subarachnoid space overlying the surface of the brain. In this instance, injury to the brain results from a sudden and severe elevation in intracranial pressure. If high enough, this pressure leads to compression of both the arteries and veins, thus reducing the amount of arterial blood that can reach the brain and the amount of venous blood that can leave it.

A hemorrhagic stroke may also occur as a result of direct hemorrhage into the brain caused by the rupture of smaller, deeper blood vessels within the brain itself. This mechanism is referred to as parenchymal hemorrhage, or primary intracerebral hemorrhage. The most common causes of parenchymal hemorrhage include trauma, hypertension, and drug abuse.

Reversible ischemic stroke

A transient ischemic attack (TIA) occurs when a small thromboembolus occludes a small distal artery. The cessation of blood flow to the affected area of the brain is temporary, either because the small clot spontaneously breaks down and blood flow is re-established or because collateral vessels bypass the occluded segment before irreversible damage occurs. Although the deficits may resolve completely, the event should be considered an early warning sign of stroke. Early treatment of the conditions that can trigger a TIA may prevent a more devastating and permanent loss of brain function.

Silent Injuries

On the basis of a study of 43 patients with high-grade, asymptomatic carotid stenosis, Capoccia et al concluded that silent injuries following CAS can be assessed using a combination of biochemical marker measurements of brain damage, neuropsychometric testing, and diffusion-weighted imaging (DWI). [1] They found that silent injuries from carotid revascularization could be evaluated using DWI, the Mini–Mental State Examination (MMSE) test, and serum-level measurements for neuron-specific enolase (NSE) and S100beta protein (biochemical markers for cerebral injury).

In the study, carotid revascularization was accomplished using either endarterectomy (20 patients) or stenting (23 patients). Postoperatively, the number of new subcortical lesions found on DWI, the decline in MMSE scores, and the S100beta and NSE levels were greater in patients treated with stenting than in those who underwent endarterectomy.



The IV tissue plasminogen activator (tPA) protocol does not specify any imaging study other than the initial nonenhanced CT examination. There is no provision in the protocol requiring that an occluded vessel be identified. Few patients present within the required 3 hours, and of those that do, time to perform any additional imaging is rarely available. Some institutions can provide rapid access to MRI, which can lend additional information as to the distribution of the ischemia. [2, 3]

Magnetic resonance angiography (MRA) can be used to confirm a suspected vessel occlusion but offers little in the planning of therapy (see the image below). The physician should seriously consider whether the time invested in additional imaging is worth the risk to the patient, particularly if thrombolytic therapy may be delayed.

Magnetic resonance angiogram (MRA) demonstrates co Magnetic resonance angiogram (MRA) demonstrates complete occlusion of the left internal carotid artery. Faint signal intensity in the M1 segment of the left middle cerebral artery represents a thrombus.

Most of the information needed to determine a patient’s candidacy for thrombolytic therapy and to predict the outcome should first be culled from a focused neurologic examination, the patient’s history, and the results of the initial nonenhanced CT. An MRI performed concurrently with thrombolytic or anticoagulant therapy may lay the foundation for newer, faster techniques that may someday replace CT as the first line of imaging. Because MRI can have logistical drawbacks, CT is the most appropriate imaging modality for the assessment of acute stroke. The inclusion of a perfusion study adds only a few more minutes to the routinely performed nonenhanced CT scan. As with MRI, dynamic imaging with CT is performed to observe the transit of a contrast agent through the tissue. [4, 5, 6, 7, 8]

As with magnetic resonance perfusion-weighted imaging (PWI), semiquantitative assessment can be performed by calculating the time to peak (TTP) enhancement and the mean transit time (MTT) (see the image below). The MTT represents the length of time the contrast material stays in the tissue, and it is approximated by the full width of the contrast agent transit curve at half the height of the enhancement peak. The MTT is more accurately assessed by using arterial input deconvolution methods. The total amount of contrast agent that ultimately travels into the tissue, a measure of the cerebral blood volume (CBV), is estimated from the area under the contrast agent transit curve.

Cerebral perfusion, as related to perfusion MRI (G Cerebral perfusion, as related to perfusion MRI (Graph A) and CT perfusion imaging (Graph B). Graph A shows the effect of a bolus injection of a paramagnetic contrast agent, such as a gadolinium-based agent, as it passes through a single voxel as a function of time. Paramagnetic susceptibility results in decreased signal intensity in the sampled area of brain. Graph B shows a similar but inverted response on CT perfusion study with the transit of iodinated contrast material through a sample, resulting in increased attenuation.

CT scanning

The first radiographic evidence of a stroke appears with imaging of the edema that develops in the area of ischemic brain. In most instances, this edema does not become apparent on CT scans until after the first 5-6 hours, depending on the degree to which the affected vessel is narrowed and supplied by collateral perfusion. Therefore, for a patient to be considered a candidate for the IV tPA protocol, the CT findings should be normal. If an infarct identified on CT is correlated with a clinical event that precedes the current event by more than 3 months and if it differs in neurologic presentation, the patient may still be considered a candidate for IV tPA therapy. Findings suggestive of neoplasm or hemorrhage exclude the patient from thrombolytic therapy. Occasionally, an isolated hyperattenuating cerebral artery is the only abnormality seen on the initial CT, and this finding is usually correlated with the neurologic deficit observed. [9, 10, 7, 8]

Correlation of imaging findings

On occasion, a new stroke may result from the extension of an old infarct. It may be difficult to determine the duration of the deficit from the history provided by an unaccompanied, obtunded, or aphasic patient. In this instance, a comparison of the CT and MRI findings might aid in decision making.

On CT scans, a chronic infarct appears as a well-defined area of decreased attenuation equivalent to that of the CSF in the ventricles. On proton density– and T2-weighted MRIs, a chronic infarct has the signal intensity characteristics of CSF. A comparison of the CT and MRI findings could help to identify a chronic infarct as the cause of a stroke, and could help determine whether or not the patient requires acute intervention. The appearance of a chronic infarct on 3 different imaging modalities is demonstrated in the image below.

(Image A) The CT scan shows a chronic infarct as a (Image A) The CT scan shows a chronic infarct as a well-defined area of decreased attenuation equivalent to that of the cerebrospinal fluid (CSF) in the ventricles. (Image B) On the T2-weighted MRI, a chronic infarct has the signal intensity characteristics of CSF, whereas an acute infarct may be less intense than CSF. (Image C)The diffusion-weighted MRI shows a chronic infarct as a region of hypointensity.

On CT scans, a subacute infarct (see the image below) appears as a less well-defined hypoattenuation within 5-6 hours of the onset. A subacute infarct appears as a region of moderate hyperintensity on T2-weighted and fluid-attenuated inversion-recovery (FLAIR) MRIs. An acute infarct may be less intense than CSF. DWI shows a chronic infarct as a region of hypointensity, whereas an acute infarct is shown as hyperintense. To date, DWI is the most sensitive imaging technique for identifying an acute stroke, as DWI can detect these changes earlier than any other modality. [6]

Subacute infarct appears as a hypodensity on a CT Subacute infarct appears as a hypodensity on a CT scan (Image A) obtained within 5-6 hours of onset and as a region of hyperintensity on a T2-weighted MRI (Image B), on a fluid-attenuated inversion recovery (FLAIR) MRI (Image C), and on a diffusion-weighted MRI (Image D).

Diffusion and perfusion MRI

Diffusion and perfusion MRIs are potentially useful in selecting patients most likely to benefit from arterial or IV thrombolysis (see Mechanism of injury and patient selection, below). Ultrafast imaging with echo-planar imaging (EPI) perfusion/diffusion sequences can identify stroke with a high degree of confidence because this technique depicts changes associated with blood flow disruption at the cellular level. The microscopic changes in flow can be detected in advance of an infarction (see the images below). [4, 5, 6]

Perfusion MRIs. Perfusion MRIs.
Perfusion MRIs. Perfusion MRIs.

The combination of diffusion and perfusion MRI provides a vivid representation of the ischemic core and penumbra. Diffusion abnormalities represent the ischemic core, whereas in most cases, a perfusion deficit represents potentially reversible ischemic tissue. The presence of a perfusion abnormality in the absence of a diffusion abnormality can define a potentially salvageable injury.

Diffusion is a random motion occurring on a microscopic scale. Nuclear magnetic resonance has been used to measure the diffusion coefficients of various materials by applying magnetic field gradients. This principle is also applied in DWI to produce an image of the brain with diffusion contrast.

The use of EPI techniques allows for the acquisition of a complete diffusion-weighted study of the whole brain in less than 2 minutes. Randomly moving spins are dephased by the gradient pulses and lose their signal. Stationary spins are completely rephased with no loss of signal. For example, the signal loss from CSF is greater than the signal loss from brain parenchyma because the diffusion of water within CSF is greater than the diffusion of water in the brain parenchyma.

A change in the diffusion coefficient can be discerned shortly after the complete cessation of blood flow to a region of the brain; however, the reason for this change is unknown and is a subject of research.

One popular hypothesis attributes the alteration to a diminished delivery of oxygen and glucose to the brain tissue, resulting in cessation of the cellular adenosine triphosphate–dependent ionic pumps. A failure to maintain ionic equilibrium induces a net flux of water from the extracellular space into the intracellular space, a phenomenon known as cytotoxic edema. The diffusion coefficient of intracellular water is less than its extracellular coefficient, likely because the movement of water is restricted by the large number of intracellular structures. This change in the ratio of intracellular water to extracellular water results in an overall apparent decrease in the diffusion of water.

PWI can be performed in a variety of ways, with single-photon emission CT (SPECT), positron emission tomography (PET), CT, or MRI. One of the most effective techniques in dynamic contrast-enhanced MRI is to take advantage of the speed of EPI.

The objective is to measure the signal change caused by the passage of a bolus of paramagnetic contrast material through the brain. The passage of intravascular contrast material produces a relative decrease in brain signal intensity caused by changes in intravascular magnetic susceptibility from the high concentration of contrast. The cortical gray matter darkens, followed by darkening of the white matter. When the circulation through the brain concludes, the parenchymal signal intensity reverts to baseline.

The image below demonstrates the effect of the passage of contrast material through a single voxel as a function of time. Three common modes of analysis include calculating maps of relative cerebral blood flow (rCBF), calculating maps of relative cerebral blood volume (rCBV), and determining the tissue MTT (tMTT). Qualitatively, the rCBV is proportional to the area under the signal intensity–versus-time curve. The tMTT may be estimated as the time during which one half of the area under the signal intensity–versus-time curve is washed out. The rCBF can be calculated as a ratio of rCBV divided by tMTT.

Cerebral perfusion, as related to perfusion MRI (G Cerebral perfusion, as related to perfusion MRI (Graph A) and CT perfusion imaging (Graph B). Graph A shows the effect of a bolus injection of a paramagnetic contrast agent, such as a gadolinium-based agent, as it passes through a single voxel as a function of time. Paramagnetic susceptibility results in decreased signal intensity in the sampled area of brain. Graph B shows a similar but inverted response on CT perfusion study with the transit of iodinated contrast material through a sample, resulting in increased attenuation.

Three common patterns are seen with perfusion/diffusion MRI in the evaluation of patients with acute stroke: (1) DWI abnormality without a perfusion deficit, (2) DWI abnormality with a matching PWI abnormality, and (3) DWI abnormality with a corresponding but larger PWI abnormality.

Although the cause of an ischemic injury may have resolved by the time imaging scans are taken, a diffusion abnormality might persist without an associated perfusion deficit (pattern 1). Subsequent initiation of autothrombolysis by the body’s own mechanisms can result in the restoration of flow, preventing further ischemic damage but without reversing the damage already done.

The second pattern, a DWI abnormality with a matching perfusion abnormality, usually results in an infarct that is slightly larger than the original DWI abnormality. In this situation, reperfusion to the most severely injured area has not occurred by the time of imaging. An increase in the volume of the infarct often occurs over the next several days. One hypothesis for this phenomenon is based on the production of excitotoxic chemicals by the infarcted tissue. Observation suggests that the therapeutic window for the prevention of further brain injury may last for several days. As the infarct evolves, the DWI defect converts from a hyperintense focus to a hypointense defect.

The third and most common pattern occurs if therapeutic intervention is not undertaken, in which case the DWI abnormality often increases in size to approximate the perfusion abnormality.

A note about gadolinium

Gadolinium-based contrast agents have been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness.

Nuclear medicine SPECT

Nuclear medicine SPECT (seen in the image below) is not usually indicated in the workup of acute stroke, but it can provide additional insight about the distribution of ischemia when the conventional imaging findings (those of the CT and MRI scans) do not correlate with clinical observations. SPECT, however, was developed in the early 1960s, and it was more widely used before the introduction of MRI.

Technetium-99m single-photon emission CT (SPECT) i Technetium-99m single-photon emission CT (SPECT) images of a stroke resulting from occlusion of the right internal carotid artery. Note the significant decrease in uptake throughout virtually the entire right cerebral hemisphere.

Under normal circumstances, SPECT perfusion images in patients without CNS disease show bilaterally symmetric activity. Activity is greatest from the cortex along the convexity of the frontal, temporal, parietal, and occipital lobes and in the regions of the basal ganglia and thalamus. Structures containing white matter and CSF have less activity.

SPECT and PET are used to acquire information about the concentration of radionuclides in body tissues. As in CT, SPECT imaging involves the rotation of a photon detector array around the patient’s head to acquire data from multiple angles. In SPECT, the emission source (eg, injected radionuclide) is inside the patient’s head, whereas in CT, the emission source is outside the body.

SPECT provides better image quality than planar (2-dimensional) imaging because focal sources of activity are not superimposed; therefore, the signal-to-noise ratio is increased. Although the resolution and sensitivity of SPECT do not equal those of PET, the greater availability of SPECT radiopharmaceuticals, the use of mathematical reconstruction algorithms to increase resolution, and the practical and economic aspects of SPECT instrumentation make this modality more attractive to most institutions for clinical studies of the brain in the subacute to chronic settings.

SPECT imaging differs from PET in resolution and sensitivity. Radionuclides used for SPECT imaging emit a single photon, usually about 140 keV, whereas PET results from the emission of 2 high-energy 511-keV photons.

Spatial resolution and image quality are dependent on the total number of unscattered photons recorded by the detector. Because only a single photon is emitted from the radionuclides used for SPECT, a collimator is used when acquiring the image data. A collimator has a lower detection efficiency than PET. In PET, additional collimation is not required because the pair of detected photons (gamma rays) travel along parallel lines. In PET, as many as 500 noncollimated detectors may be used, whereas in SPECT, only 1 or 3 collimated detectors are used.

SPECT images are acquired 10-30 minutes after the injection of 20 mCi of technetium-99m (99mTc) hexamethylpropyleneamine oxime (HMPAO) or 99mTc exametazime (Ceretec; Amersham), or 30-60 minutes after the injection of 99mTc ethyl cysteinate dimer (ECD) (Neurolite; DuPont). These agents are unique in that first-pass extraction in the brain is high, with little redistribution.

Patients must remain still during the study, which usually lasts 20-30 minutes. Most state-of-the-art imaging systems are designed to reduce head motion and patient discomfort. The patient's eyes and ears may be covered during the scan to reduce outside stimulants, which can alter cerebral blood flow and/or metabolism.

SPECT images are generated by using multidetector-row or rotating gamma camera systems that record photons emitted by tracers taken up by the brain. The high collection efficiency of the multidetector-row system makes rapid scanning possible. SPECT perfusion images of the brain can be obtained with a spatial resolution of 10 mm in the section plane. The multidetector-row system is, therefore, the preferred tool for studies requiring higher spatial resolution, regional quantification, or rapid sequential imaging.

The rotating gamma camera is preferred for routine clinical imaging because of its wider availability and because it can be used for other types of tomographic and nontomographic imaging. The major limitation of rotating gamma camera tomography is its relatively poor sensitivity. Gamma cameras have been designed with multiple detectors to improve instrument sensitivity. Three- and four-head cameras provide greater spatial resolution of 6-10 mm, compared with 14-17 mm for single-head systems (without increasing the examination time).

Reconstructions can be obtained at any angle, including the axial, coronal, and sagittal planes. Scanning angles can be matched to those obtained with CT or MRI to facilitate image comparisons. SPECT images can be merged with MRIs and CT scans, creating a single image for anatomic and functional correlation. Three-dimensional volumetric and surface-rendered images add perspective and facilitate the localization and sizing of lesions.

A radiotracer accumulates in different areas of the brain proportional to the rate of delivery of the blood to that volume of brain tissue. Therefore, the radiotracer measures cerebral perfusion. Accumulation of the radiotracer within the brain is measured in milliliters per minute per 100 g, whereas the flow of blood in vessels is measured in milliliters per minute.

As in magnetic resonance PWI, perfusion SPECT results are also calculated as rCBF, provided that (1) the injected isotope is freely diffusible from the blood pool into the brain, (2) the brain extracts all or nearly all of the available isotope from the blood, and (3) the isotope remains fixed within the brain without redistribution.


Angiography is not indicated in the IV protocol for stroke; however, it is essential in the intra-arterial protocol to identify the occluded vessel and the possible origin of the thromboembolus (see the image below). Typically, the embolus arises from the carotid bifurcation (in anterior circulation strokes) or from the vertebral artery origins or vertebrobasilar junction (in posterior circulation strokes). [11]

Images in a 47-year-old woman with a sudden onset Images in a 47-year-old woman with a sudden onset of left hemiplegia, which occurred while she was in the ICU. She was excluded from the intravenous tissue-type plasminogen activator (tPA) protocol because she had recently undergone heart-lung transplantation. Image A is an angiogram of the right internal carotid artery that demonstrates an occlusion of the right middle cerebral artery. Image B shows that flow in the right middle cerebral artery is reestablished at 28 minutes during a selective infusion of urokinase into the right middle cerebral artery. The patient recovered her former neurologic function while she was on the angiography table.

Angiographic results can also be of some prognostic value. A patient with a complete occlusion of the carotid terminus and middle cerebral artery is less likely to completely recover his or her neurologic function if significant collateral perfusion is not identified from the anterior or posterior cerebral arteries to the ipsilateral middle cerebral artery. Conversely, the identification of collateral perfusion may imply a more significant recovery, even if therapy is offered closer to the 6-hour limit of the intra-arterial protocol. [5, 11, 8]

Angiography has also been useful in identifying venous occlusive disease as the underlying etiology of neurologic deficits.