Cerebral Revascularization and Imaging

Cerebral revascularization is surgery that restores blood flow to the brain, decreasing the chance of stroke or other damage to brain tissue. Revascularization is performed to treat several conditions that reduce blood flow to the brain. Such conditions include moyamoya disease, carotid artery disease, and atherosclerosis of the cerebral arteries. Each of these conditions puts the brain at risk of cerebral ischemia or ischemic stroke. Each condition may also cause transient ischemic attacks (TIAs). In addition, the delicate new vessels that are formed as part of MMD are at risk for leaking into the brain and causing hemorrhagic stroke. ^[1]

Revascularization may also be performed to bypass a damaged artery. For example, it is sometimes done to route blood past an aneurysm. The danger posed by an aneurysm is that blood might leak or burst out through the weak area, causing a hemorrhagic stroke. Some aneurysms cannot be treated by standard procedures that clip them shut or seal them off. In these cases, a revascularization procedure can provide an alternative blood flow path. The section of the artery with the aneurysm can then be completely shut down, safely preventing hemorrhagic stroke. ^[1]

A bypass may also be necessary when a skull base tumor becomes entangled with one of the major arteries that enter the brain. Removing the tumor may require removal of part of the artery. A bypass provides an alternative route for blood flow, allowing safe removal of the tumor. ^[1]

Cerebral vascular insufficiency, typically caused by extracranial or intracranial steno-occlusive disease (any arterial occlusion or severe extracranial or intracranial stenosis in symptomatic arterial territory), is the leading cause of ischemic stroke. Surgical treatment options for cerebral vascular insufficiency due to intracranial steno-occlusive disease include cerebral revascularization procedures such as extracranial-to-intracranial (EC-IC) bypass and endarterectomy; endovascular treatment options include angioplasty with or without stent placement and mechanical thrombectomy. ^[2]

In a systematic review of effects of revascularization on cognitive outcomes in patients with intracranial steno-occlusive disease, review authors examined existing literature on intracranial steno-occlusive disease, including intracranial atherosclerosis and MMD, to determine the extent and quality of evidence for the effect of revascularization on cognitive performance. They concluded that effects of revascularization on cognitive performance in intracranial steno-occlusive disease remain uncertain due to limitations in existing studies. Additional well-designed randomized trials and observational studies are needed to determine if revascularization can arrest or reverse cognitive decline in these patients. ^[3]

Authors of a retrospective review of revascularization procedures performed most often for patients with recurrent stroke who were receiving optimal medical therapy and received a diagnosis of cerebrovascular steno-occlusion found that no further strokes or ischemic events were observed long term, and that graft patency remained high, at 95%. They concluded that cerebral revascularization may be done safely at high-volume cerebrovascular centers for high-risk patients for whom optimal medical therapy has failed, and that further research must be done to develop an improved method of risk stratification for patients with symptomatic atherosclerotic cerebrovascular steno-occlusive disease to determine which patients may benefit from intervention. Given the high risk of recurrent stroke in some patients and the fact that for some patients, medical therapy fails, surgical revascularization may offer the best method of ensuring good long-term outcomes with manageable up-front risks. ^[4]

Stroke is defined as damage to the brain and resultant neurologic deficits that occur when the blood supply to a given area of the brain is lost. Stroke, however, is not a singular process. It may occur as the result of 1 or more of the following processes: thrombotic stroke, embolic stroke, hemorrhagic stroke, and reversible ischemic stroke.

(See images below.)

Thrombotic stroke

A thrombotic stroke occurs when plaque and clots are formed locally on the wall of a cerebral artery, leading to 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 from the walls of the extracranial arteries that supply the brain (eg, carotid artery bifurcation) and is 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 shows an acute embolic stroke on computed tomography [CT] scan.)

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 sudden and severe elevation in intracranial pressure. If high enough, this pressure can lead to compression of both 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 the result of direct hemorrhage into the brain caused by 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. 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 patients with conditions that can trigger a TIA may prevent a more devastating and permanent loss of brain function.

Silent stroke

Although an overt stroke causes obvious symptoms such as weakness in one arm or speech problems that last longer than a day, a covert or silent stroke is not obvious except on brain scans such as magnetic resonance imaging (MRI). The NeuroVISION study has provided important insights into the development of vascular brain injury after surgery, which contribute to mounting evidence showing the importance of vascular health for cognitive function. ^[5]

Canadian researchers from the NeuroVISION study led by P.J. Devereaux reported that “silent” covert strokes are actually more common than overt strokes in people 65 years of age and older who undergo surgery. They found that 1 in 14 people older than 65 years who underwent elective, noncardiac surgery had a silent stroke, suggesting that as many as 3 million people in this age category globally suffer a covert stroke after surgery each year. All patients received an MRI within 9 days of surgery to look for imaging evidence of silent stroke. The research team followed patients for 1 year after surgery to assess their cognitive capabilities. They found that people who had a silent stroke after surgery were more likely to experience cognitive decline, perioperative delirium, overt stroke, or TIA within 1 year compared to those who did not have a silent stroke. ^[5]

The first radiographic evidence of a stroke appears with imaging of edema that develops in the area of the ischemic brain. In most instances, this edema does not become apparent on computed tomography (CT) scans until after the first 5 to 6 hours, depending on the degree to which the affected vessel is narrowed and is supplied by collateral perfusion.

Alteplase is a tissue plasminogen activator (tPA) that is used for management of acute myocardial infarction (MI), acute ischemic stroke, and pulmonary embolism. ^[6]  The intravenous (IV) tPA protocol does not specify any imaging study other than the initial nonenhanced CT examination. No provision in the protocol requires that an occluded vessel be identified. Few patients present within the required time, and among those who do, time to perform additional imaging is rarely available. Some institutions can provide rapid access to magnetic resonance imaging (MRI), which can lend additional information as to ischemia distribution. ^{[7, 8]}

For a patient to be considered a candidate for the IV tPA protocol, 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 initial CT; this finding is usually correlated with the neurologic deficit observed. ^{[9, 10, 11, 12]}

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 results of the initial nonenhanced CT. Magnetic resonance imaging 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 assessment of acute stroke. 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. ^{[9, 10, 13, 14, 15]}

Ischemic stroke is the second leading cause of mortality and disability in the western world. Revascularization interventions are the cornerstone of acute treatment for patients with this pathology and must be administered as soon as possible after the patient’s arrival for treatment. The latest guidelines from the American Heart Association (AHA)/American Stroke Association (ASA) call for tissue plasminogen activator (tPA) treatment within 4.5 hours of symptom onset and recommend endovascular treatment within 6 hours of symptom onset. Advanced neuroimaging methods with perfusion studies are a fundamental tool in patient selection. ^[16]

Radiologic perfusion imaging techniques (ie, MRI perfusion, CT perfusion, and single-photon emission CT [SPECT]) have been used to assess and quantify the effects of revascularization on brain hemodynamics. Nevertheless, these techniques cannot determine the selective contribution of a bypass artery to brain perfusion. Flat-detector CT (FD CT) is an effective method for selectively visualizing perfused brain areas of direct and indirect bypasses and for obtaining volumetric measurements of the bypass. ^[17]

Digital subtraction angiography (DSA) is considered the gold standard for diagnosing moyamoya disease (MMD). Because of its high spatial and temporal resolution, DSA plays an irreplaceable role in assessing steno-occlusion of the terminal internal carotid artery (ICA) and the patency of anastomosis. Moreover, DSA is the best choice for observing establishment of collateral circulation, which is crucial for treatment decisions and evaluation of neo-angiogenesis status after surgery. However, DSA is not recommended for pediatric patients or for patients in poor condition, because of its invasiveness and time consumption and the need for anesthesia. ^[18]

The most accurate diagnostic modality for assessing bypass efficacy has yet to be determined. An imaging modality combining digital subtraction angiography (DSA) with flat-detector (FD) imaging has become available and has proved its value in the practice of interventional neuroradiology. This technique when used in the postoperative setting allows more precise evaluation in terms of bypass patency and dynamics. ^[17]

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

(See the image below.)

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, comparison of CT and MRI findings might aid decision making.

On CT scans, a chronic infarct appears as a well-defined area of decreased attenuation equivalent to that of cerebrospinal fluid (CSF) in the ventricles. On proton density– and T2-weighted MRI, a chronic infarct has the signal intensity characteristics of CSF. Comparison of CT and MRI findings could facilitate identification of a chronic infarct as the cause of stroke and could help the clinician determine whether or not the patient requires acute intervention.

(A chronic infarct is shown on 3 different imaging modalities below.)

On CT scans, a subacute infarct appears as a less well-defined hypoattenuation within 5 to 6 hours of onset. A subacute infarct appears as a region of moderate hyperintensity on T2-weighted and fluid-attenuated inversion-recovery (FLAIR) MRI. An acute infarct may be less intense than CSF. Diffusion-weighted imaging (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 acute stroke, as DWI can detect these changes earlier than any other modality. ^[15]

(See the image below.)

Advanced computed tomography imaging techniques

Flat-detector CT (FD CT) is an effective method for selectively visualizing perfused brain areas of direct and indirect bypasses and for obtaining volumetric measurements of the bypass. Flat-detector CT is a promising imaging tool for evaluating brain perfusion anatomy after direct and indirect revascularization procedures and for grading and comparing the vascular contributions of bypass arteries and/or burr holes. The main advantages of this technique are that it can be easily implemented in the angiography suite as an add-on tool to conventional angiography, and it can demonstrate exact supply areas in a 3-dimensional (3D) view of individual bypass or burr hole arteries. The clinical significance of this study for individual patients is that thanks to this technique, postoperative evaluation in terms of bypass patency and dynamics is now possible, which enables comparison of different types of bypass procedures for research purposes. Further research is warranted to explore the role of FD CT perfusion scanning for bypass patients and for neurovascular patients. ^[17]

Computed tomography angiography (CTA)  can clearly show the circle of Willis, as well as the anterior, middle, and posterior cerebral arteries and their main branches, providing an important diagnostic basis for occlusive vascular lesions. Because of its short acquisition time and fast image postprocessing, CTA is the first choice in emergency cases. ^[18]

Computed tomography perfusion (CTP) offers the advantages of short acquisition time and high spatial resolution, so it is generally the first choice for measuring changes in cerebral hemodynamics after surgery. Among parameters extracted from the time intensity curve, changes in TTP and MTT are the most sensitive ones in the early postoperative period, followed by cerebral blood flow (CBF), which is also a matter of great concern to surgeons. Cerebral blood flow is closely related to bypass patency and can directly reflect the degree of blood suppy recovery. The change in cerebral blood volume is complicated and is affected by the ability of different automatic regulation processes involving arterial, capillary, venous, and parenchymal components. ^[18]  

Advanced magnetic resonance imaging techniques

Diffusion and perfusion MRIs are potentially useful in selecting patients most likely to benefit from arterial or IV thrombolysis. 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. Microscopic changes in flow can be detected in advance of an infarction. ^{[13, 14, 15]}

(See the images below.)

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 diffusion-weighted imaging (DWI) to produce an image of the brain with diffusion contrast.

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

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

One popular hypothesis attributes the alteration to diminished delivery of oxygen and glucose to brain tissue, resulting in cessation of cellular adenosine triphosphate–dependent ionic pumps. 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 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 water diffusion.

Perfusion-weight magnetic resonance imaging (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 involves taking advantage of the speed of EPI.

The objective is to measure the signal change caused by passage of a bolus of paramagnetic contrast material through the brain. 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; this is followed by darkening of the white matter. When circulation through the brain concludes, the parenchymal signal intensity reverts to baseline.

Three common modes of analysis include calculating maps of relative cerebral blood flow (rCBF), calculating maps of relative cerebral blood volume (rCBV), and determining tissue MTT (tMTT). Qualitatively, rCBV is proportionate to the area under the signal intensity-versus-time curve. Tissue MTT 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 the ratio of rCBV divided by tMTT.

(The image below shows the effect of passage of contrast material through a single voxel as a function of time.)

Three common patterns are seen with perfusion/diffusion MRI for evaluation of patients with acute stroke: (1) diffusion-weighted imaging (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 ischemic injury may have resolved by the time imaging scans are taken, the first pattern shows that a diffusion abnormality might persist without an associated perfusion deficit. Subsequent initiation of autothrombolysis by the body’s own mechanisms can result in restoration of flow, preventing further ischemic damage 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 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 infarcted tissue. Observation suggests that the therapeutic window for 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 when therapeutic intervention is not undertaken, in which case the DWI abnormality is often increased in size to approximate the perfusion abnormality.

Magnetic resonance angiography (MRA) provides a noninvasive, radiation-free alternative to DSA and CTA for evaluating bypass patency and can be used to measure arterial caliber to predict the development of surgical collaterals. Among MRA techniques, 3-dimensional time-of-flight magnetic resonance angiography (3D TOF-MRA) is the most commonly used technique for cerebral artery imaging, with high spatial resolution and signal-to-noise ratio (SNR), as well as very thin slice thickness. ^[18]

Magnetic resonance angiography can be used to confirm suspected vessel occlusion but offers little that can help to guide treatment planning. The physician should seriously consider whether time invested in additional imaging is worth the risk to the patient, particularly if thrombolytic therapy may be delayed.

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.

Intracranial vessel wall imaging (IVWI) is an adjunct to conventional MRA and has great potential for morphologic assessment of revascularization in moyamoya disease (MMD). Based on high-resolution MRI, IVWI has proved effective in differentiating MMD from intracranial atherosclerotic stenosis. More research is needed to evaluate the value of IVWI in differentiating ischemic or hemorrhagic stroke caused by MMD. ^[18]

Ultrahigh field intensity MRI is a promising neuroimaging technique for evaluating MMD, especially risk of hemorrhage. ^[18]

Fluid-attenuated inversion-recovery MRI (FLAIR-MRI) showing a decrease in the “ivy sign”—leptomeningeal high signal intensity—after surgery suggests that this is related to improvement in cerebral hemodynamics and clinical symptoms; a de novo “ivy sign” may predict early postoperative cerebral hyperperfusion syndrome. ^[18]

Dynamic susceptibility contrast (DSC) MRI is currently one of the magnetic resonance perfusion imaging techniques most used by neurosurgeons. Dynamic susceptibility contrast MRI can help the clinician in selecting candidates for MMD intervention and can predict outcomes and risks of surgery. Disadvantages include the need for a contrast agent, insufficient quantitative reliability, and long resolution time. ^[18]

Arterial spin labeling (ASL) MRI uses magnetically labeled inflowing blood as an endogenous tracer to estimate brain perfusion at the tissue level; this is especially suitable for pediatric patients with MMD. Overall, ASL-MRI is a promising noninvasive alternative for evaluating hemodynamics of MMD when nuclear medical imaging methods are not available, but its limitations such as weak signal intensity, low image resolution, and poor repeatability keep it from becoming a standalone imaging method for clinical cerebral perfusion assessments. ^[18]

Blood oxygen level–dependent functional magnetic resonance imaging (BOLD-fMRI) is a brain mapping technique that uses deoxyhemoglobin in the blood vessels as an endogenous contrast agent to produce functional activation maps. BOLD-fMRI is widely used to monitor cerebrovascular reserve and neurovascular coupling changes and to assess surgical efficacy following revascularization. BOLD-fMRI holds future potential in becoming a routine examination for preoperative and postoperative evaluation of patients with MMD, especially pediatric patients. However, how to improve the stability and repeatability of BOLD imaging is a major concern in clinical practice. ^[18]

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 they were 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 single-photon emission computed tomography (SPECT) is considered the reference standard technique for cerebral blood flow (CBF) perfusion assessments. ^[18]  SPECT is not usually indicated in the workup of acute stroke, but it can provide additional insight about the distribution of ischemia when conventional imaging findings (those of CT and MRI scans) do not correlate with clinical observations. SPECT was developed in the early 1960s, and it was more widely used before the introduction of MRI.

(See the SPECT images below.)

Under normal circumstances, SPECT perfusion images in patients without central nervous system (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 regions of the basal ganglia and thalamus. Structures containing white matter and CSF have less activity.

Positron emission tomography (PET) is considered the standard functional imaging method for quantifying metabolic processes that are relevant to MMD vascular functionalities after bypass surgery. However, PET is limited by its general clinical unavailability, high cost, and lengthy measurement time. ^[18]

SPECT and PET are used to acquire information about concentrations of radionuclides in body tissues. As in CT, SPECT imaging involves 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 image data are acquired. A collimator has 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 to 30 minutes after injection of 20 mCi of technetium-99m (^99mTc) hexamethylpropyleneamine oxime (HMPAO) or ^99mTc exametazime (Ceretec; Amersham), or 30 to 60 minutes after 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 to 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 via 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 spatial resolution of 10 mm in the section plane. Therefore, the multidetector-row system is 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 it has 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 to 10 mm, compared with 14 to 17 mm for single-head systems (without increased 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 MRI and CT scans, creating a single image for anatomic and functional correlation. Three-dimensional volumetric and surface-rendered images add perspective and facilitate localization and sizing of lesions.

A radiotracer accumulates in different areas of the brain proportionate to the rate of delivery of 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 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 available isotope from the blood, and (3) the isotope remains fixed within the brain without redistribution.

Ultrasonography

Transcranial color-coded duplex sonography (TCCS) can provide real-time quantitative information on donor and recipient arteries. This is an ideal imaging tool for monitoring graft flow postoperatively. ^[18]

Intraoperative ultrasonography (IVUS) allows quick detection of graft patency revision of problematic grafts, thus greatly improving the success rate of surgeries. ^[18]

Transcranial Doppler (TCD) is commonly used for monitoring intracranial ischemic disease because it is noninvasive, quick, bedside, and cheap. ^[18]

Contrast-enhanced ultrasonography (CEUS) is a promising imaging technique for visualizing microvascular circulation and brain perfusion, providing qualitative and semiquantitative information. Contrast-enhanced ultrasonography has been used to assess neurosurgical conditions such as intracranial tumors, arteriovenous malformations, and aneurysms. ^[18]

Fluorescence imaging

Indocyanine green and sodium fluorescein imaging agents are commonly used for intraoperative fluorescence imaging. Intraoperative fluorescence imaging provides semiquantitative regional hemodynamic alterations and can be used to identify patients at high risk of transient neurologic events, thus allowing adjustments to perioperative treatment. ^[18]

Angiography

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. Typically, the embolus arises from the carotid bifurcation (in anterior circulation strokes) or vertebral artery origins or from the vertebrobasilar junction (in posterior circulation strokes). ^[19]

(See image below.)

Angiographic results can also be of some prognostic value. A patient with 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, identification of collateral perfusion may imply more significant recovery, even if therapy is offered closer to the 6-hour limit of the intra-arterial protocol. ^{[10, 14, 19]}

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

Intraoperative dual-image video angiography (DIVA) used with Doppler ultrasonography during extracranial-to-intracranial (EC-IC) bypass surgery was described in an analytic study in which the study authors concluded that hemodynamic recovery after cerebrovascular bypass brings about a better outcome in ischemic stroke. The result of surgery improves with proper selection of patients with hemodynamic impairment (in stage 2). With various modalities such as intraoperative Doppler and DIVA, improved surgical techniques may aid in reduction of complications and may improve clinical outcomes. ^[20]

Indocyanine green videoangiography (ICG-VA) is a near-infrared range fluorescent marker used for intraoperative real-time assessment of flow in cerebrovascular surgery. Given its high spatial and temporal resolution, ICG-VA has been widely established as a useful technique for performing a qualitative analysis of graft patency during revascularization procedures. In addition, this fluorescent modality can provide valuable qualitative and quantitative information regarding cerebral blood flow within the bypass graft and in the territories supplied. Digital subtraction angiography (DSA) is considered to be the gold standard diagnostic modality for postoperative bypass graft patency assessment. However, this technique is time and labor intensive and is an expensive interventional procedure. In contrast, ICG-VA can be performed intraoperatively with no significant addition to total operative time and, when used correctly, can accurately show acute occlusion. Such time-sensitive ischemic injury detection is critical for re-establishment of flow through direct surgical management. In addition, ICG has an excellent safety profile, with few adverse events reported in the literature. ^[21]

Updated guidelines from the American Heart Association (AHA) and the American Stroke Association (ASA) have extended the time limit on mechanical clot removal from 6 hours to up to 24 hours in select patients. The new guidelines recommend thrombectomy in eligible patients 6-16 hours after a stroke. They also broaden the eligibility criteria by allowing patients who are ineligible for IV tPA to undergo mechanical thrombectomy within 6 hours. ^{[6, 22]}

Patients should be considered for thrombectomy in less than 6 hours after stroke onset if they have a large clot in one of the large vessels at the base of the brain and meet the following criteria:

• Pre-stroke modified Rankin Scale (mRS) score of 0 to 1
• Causative occlusion of the internal carotid artery or middle cerebral artery segment 1 (M1)
• Age over 18 years
• National Institutes of Health Stroke Scale score ≥6
• Alberta Stroke Program Early CT score ≥6.

The AHA/ASA has also issued guidelines for reduction of stroke risk specifically in women. These gender-specific recommendations include the following:

• A stroke risk score should be developed specifically for women.
• Women with a history of high blood pressure before pregnancy should be considered for low-dose aspirin and/or calcium supplement treatment to reduce the risk of preeclampsia.
• Blood pressure medication may be considered for pregnant women with moderately high blood pressure (150-159 mm Hg/100-109 mm Hg), and pregnant women with severe high blood pressure (160/110 mm Hg or above) should be treated.
• Women should be screened for high blood pressure before they start to use birth control pills because of increased risk of stroke.
• Women with migraine headaches with aura should be encouraged to quit smoking to reduce the risk of stroke.
• Women over age 75 should be screened for atrial fibrillation.

Evaluating and managing stroke in patients with COVID-19

Because patients with COVID-19 infection are at high risk of developing acute stroke, an international panel of stroke experts from 18 countries issued a set of recommendations for managing acute ischemic stroke patients with suspected or confirmed infection with the virus. Recommendations include the following:

• Due to the high rate of mortality among COVID-19 patients who have multiple organ dysfunction/failure, a Sequential Organ Failure Assessment (SOFA) score may be helpful in devising a treatment plan.
• It is reasonable to perform chest computed tomography (CT) and/or radiography to identify radiologic abnormalities suggestive of COVID-19 infection.
• It is important to take into account risk factors for contrast-induced nephropathy due to the high rate of renal insufficiency in patients with COVID-19.
• Tests for assessing coagulation profile such as thromboelastography and serum concentration of D-dimers may be considered as needed.
• A stringent policy is required to select acute ischemic stroke patients for mechanical thrombectomy.
• If intubation is needed, the procedure should be performed in a negative-pressure room with teams of experienced clinicians wearing protective gear and using video-guided laryngoscopy. A tracheobronchial specimen may be taken at this time to confirm suspected COVID-19 infection.
• Parameters from the SIESTA (Sedation vs Intubation for Endovascular Stroke TreAtment) trial should be used if intubation and mechanical ventilation are performed to ascertain that there is no decrease in blood pressure or abnormal blood gases uring the procedure.