Identifying The Vascular Lesion

Ischemic stroke occurs because of impairments in microvascular perfusion of affected brain tissue. However, the vascular event that results in impaired perfusion often occurs in a macroscopically visible vessel. Imaging studies that can study these vessels provide several kinds of important information to the stroke neurologist. First, by definitively demonstrating a vascular lesion that could be responsible for ischemic symptoms, vascular imaging can help to cement the diagnosis of an acute ischemic stroke, especially when DWI is not available and other studies are equivocal or negative. Second, the location of the vascular lesion conveys important prognostic information. In general, vascular lesions that involve larger, more proximal arteries that serve larger volumes of tissues cause infarcts that result in more severe neurologic deficits and a greater likelihood of hemorrhagic transformation. Finally, vascular imaging can be essential in guiding therapy. Intra-arterial thrombolysis or mechanical clot disruption can be undertaken only if a sufficiently proximal arterial lesion can be identified. Even when only intravenous thrombolysis is considered, vascular imaging helps to predict the likelihood of successful throm-bolysis, as well as the likelihood of severe injury if thrombolysis is not attempted.

Catheter Angiography

Catheter angiography is the oldest vascular imaging technique, and although it remains the gold standard for vascular imaging, it is seldom used diagnostically in the acute stroke setting. In this technique, the patient is brought to an operating room-like fluoroscopy suite and sedated. A catheter is inserted into a femoral artery and is then fluoroscopically guided into the aortic arch. The catheter is then advanced into one of the carotid or vertebral arteries, and a radio-opaque, iodine-based contrast material is injected, while high-resolution images of the neck or brain are acquired at a rate of several frames per second.

Catheter angiography provides exquisite image detail and can visualize vessels as small as 0.1 mm in diameter, considerably smaller than those seen by CT- and MR-based vascular imaging techniques. Catheter angiography also provides high temporal resolution, which can help to distinguish arteries from veins and to detect prolonged intravascular stasis of blood.

Despite its advantages, diagnostic catheter angiography is now almost never performed for evaluation of acute stroke in institutions that have access to modern CT and MR scanners. There are several reasons for this. Catheter angiography requires the presence of highly trained angiographers, technologists, and sometimes anesthesiologists, some of whom may not be immediately available at all times of the day. It is a relatively time-consuming technique, and it may unacceptably delay the initiation of therapy in the acute stroke patient. The iodinated contrast used for catheter angiography can result in nephrotoxicity and allergic reactions, which are discussed in the next section. Also, catheter angiography is a highly invasive and somewhat risky procedure. Complications may occur if atherosclerotic plaques are dislodged from the aorta during catheter passage or if small thrombi form on the tip of the catheter and travel into the brain. The rate of neurologic complications related to cerebral angiography is approximately 0.5-4%. Most of these are transient, with permanent neurologic deficits occurring in only 0.1-0.5% of patients who undergo an angiogram.42

CT Angiography

CT angiography (CTA) is a technique that provides high-resolution vascular images using the same CT scanners that are used for conventional CT imaging and the same iodine-based contrast agents that are used for catheter angiography and conventional contrast-enhanced CT. CTA is much less invasive than catheter angiography, as it involves injection of a bolus of contrast agent through a standard intravenous catheter in a peripheral vein, rather than into a centrally placed arterial catheter. CT images of the head and neck are obtained and are carefully timed to acquire images as the contrast material passes through the arteries (Fig. 2.3). Many CTA protocols also allow for excellent visualization of cervico-cranial venous structures.

The amount of contrast material required for CTA is comparable to that used for conventional contrast-enhanced CT imaging. The amount of scanning time required for a CTA examination of the head and neck, such as is usually performed for acute

FIGURE 2.3 CT angiography. CTA is performed by acquiring axial CT images while an intravenously injected bolus of contrast material passes through the arteries. In one such image (a), portions of the contrast-filled right and left middle cerebral arteries (RMCA, LMCA) are clearly seen, as well as the right internal carotid artery (RICA) and basilar artery (BA). Note that major venous structures, including the superior sagittal sinus (SSS), are also seen. CTA images are often combined to form projections, such as image (b), which shows abrupt cutoff of one of the two middle cerebral artery divisions (large arrow) due to embolic occlusion. There is also irregular narrowing of the other division (small arrows). Another projection of CTA images of the neck from the same examination (c) shows the bifurcation of the left common carotid artery (single long arrow) into the external and internal (single short arrow) carotid arteries. The latter is acutely occluded due to dissection. Note the internal jugular vein (double arrows) passing close to the carotid arteries.

FIGURE 2.3 CT angiography. CTA is performed by acquiring axial CT images while an intravenously injected bolus of contrast material passes through the arteries. In one such image (a), portions of the contrast-filled right and left middle cerebral arteries (RMCA, LMCA) are clearly seen, as well as the right internal carotid artery (RICA) and basilar artery (BA). Note that major venous structures, including the superior sagittal sinus (SSS), are also seen. CTA images are often combined to form projections, such as image (b), which shows abrupt cutoff of one of the two middle cerebral artery divisions (large arrow) due to embolic occlusion. There is also irregular narrowing of the other division (small arrows). Another projection of CTA images of the neck from the same examination (c) shows the bifurcation of the left common carotid artery (single long arrow) into the external and internal (single short arrow) carotid arteries. The latter is acutely occluded due to dissection. Note the internal jugular vein (double arrows) passing close to the carotid arteries.

stroke patients, varies depending on the scanner being used. With a 16-slice CT scanner, less than 30 seconds of imaging time is typically needed, allowing the examination to occur during a single breath-hold, which reduces motion artifacts related to breathing. Thirty-two- and 64-slice scanners allow for even faster imaging, while using even less contrast material.

CTA offers many attractive features that have made it a very widely used technique in acute stroke imaging. As discussed above, CT scanners are widely available, and emergency patients can usually be brought to and from a scanner with minimal delay. CT scanners, unlike MRI scanners, allow for metallic equipment to be brought safely into the scanner room, allowing for easier monitoring of potentially unstable acute stroke patients, most notably those receiving intravenous recombinant tissue-plasminogen activator (rt-PA). The speed of the CTA technique also makes CTA images relatively resistant to degradation by artifact related to patient motion, which is a significant problem when scanning acute stroke patients who may be neurologi-cally impaired, critically ill, or uncooperative. Although CTA does not usually offer catheter angiography's ability to show the movement of blood from arteries to veins over time and cannot show tiny blood vessels with the same spatial resolution provided by catheter angiography, CTA does produce vascular images with detail greater than that of other vascular imaging techniques such as magnetic resonance angiography (MRA). Furthermore, emerging CTA techniques may potentially allow for serial imaging of limited parts of the neurovascular anatomy, with tracking of the passage of contrast material from large arteries into veins.

CTA suffers from only a few disadvantages that weigh against these desirable attributes. Chief among them is the fact that CTA requires injection of iodine-based contrast material. Iodinated contrast is nephrotoxic and may result in transient or permanent renal failure, particularly in patients whose renal function is already impaired. The incidence and severity of contrast-induced nephropathy is low when adequate renal function is confirmed by means of prescan serum creatinine measurement43 or preferably computation of the glomerular filtration rate. However, waiting for laboratory values to become available may unacceptably delay diagnosis and treatment in the acute stroke setting. Although drugs such as sodium bicarbonate and N-acetylcysteine have advanced the prevention of contrast-induced nephropathy in patients with impaired renal function, the mainstay of prevention remains adequate pre- and postcontrast hydration.

Besides impairment of renal function, injection of iodinated contrast triggers allergic adverse reactions in some patients. Some studies have reported that the incidence of such reactions is between 4.9% and 8.02% when high-osmolar ionic contrast agents are used.44 However, the reported incidence of adverse reactions is much lower when nonionic monomeric contrast agents are used, falling to 0.59% in one study, with only 0.01% of patients suffering severe reactions.45 In another study, the incidence of adverse reactions to nonionic contrast agents was 3.13%, with 0.04% of reactions classified as severe.46

With modern multislice scanners and optimized protocols,47 CTA images can provide excellent visualization of the primary intracranial arteries (i.e., the proximal anterior, middle, and posterior cerebral arteries), their smaller secondary branches (e.g., the superior and inferior divisions of the MCA, and the pericallosal and callosomarginal arteries), and often even smaller tertiary branches. In one study of 44 acute stroke patients who were intra-arterial thrombolysis candidates and who underwent both CTA and catheter angiography studies, CTA was 98.4% sensitive and 98.1% specific in detecting occlusion of large intracranial arteries.48

Besides establishing the diagnosis of stroke, CTA can help to determine an acute stroke patient's prognosis by determining whether vascular lesions are in large primary intracranial arteries, where they tend to cause more widespread ischemic damage, or in smaller secondary and tertiary arteries. In one study of 74 acute stroke patients who were subsequently treated by intravenous or intra-arterial thrombolysis, the presence of a "carotid T lesion,'' in which an embolus occludes the top of the internal carotid artery and extends into the middle and anterior cerebral arteries, was a better predictor of early death than hypodensity more than one third of the (MCA) territory, which is often taken to be an indicator of advanced early injury and poor prognosis.49 In that study, catheter angiography rather than CTA was used to identify the vascular lesion. Another study, which used CTA, found that occlusion of a large intracranial artery was one of the two factors that independently predicted poor outcome in acute stroke patients (the other was poor initial neurologic status).50

At the other extreme are those acute stroke patients who have no visible arterial occlusion whatsoever, presumably because their infarcts were due to lesions in small arteries that cannot be imaged, or because an embolus in a large proximal artery has broken up spontaneously. Several studies (again using catheter angiogra-phy rather than CTA) have shown that such patients generally enjoy relatively favorable outcomes.51,52

Besides merely predicting outcome, CTA plays a critical role in directing acute therapy by detecting occlusion of proximal intracranial arteries that are accessible by endovascular microcatheterization and therefore may be treated by intra-arterial thrombolysis or mechanical clot disruption. Indeed, studies using both catheter angiography and CTA suggest that proximal occlusions should be treated with intra-arterial rather than or in addition to intravenous thrombolysis, if possible, because intravenous thrombolysis is less effective in treating proximal lesions than in treating distal ones.6,53,54

Finally, besides visualizing blood vessels, CTA images may be more useful than NCCT in evaluating the brain parenchyma. In CTA, not only large vessels but also the microvasculature becomes opacified by contrast-containing blood. Therefore, in CT images used for CTA (sometimes called CTA source images or CTA-SI), hypo-perfused brain tissue may become visibly hypodense, and CTA-SI allows for more sensitive detection of acute stroke than CT.55-57 In one study, CTA-SI increased the utility of the ASPECTS metric in predicting the clinical outcomes of acute stroke patients.58 Under idealized clinical scanning conditions,59 CTA-SI can theoretically measure regional cerebral blood volume, thereby helping to identify tissue that may be irreversibly destined for infarction (see discussion of cerebral perfusion below).

Magnetic Resonance Angiography

MRA describes any of the several MRI techniques that are used to depict arteries. These can be divided into contrast-based techniques and noncontrast-based techniques.

There are two widely used noncontrast-based MRA techniques: time-of-flight (TOF) MRA and phase contrast (PC) MRA. The physical principles underlying both techniques are far more complicated than those underlying catheter angiogra-phy and CTA and are beyond the scope of this chapter. Both are unlike other vascular imaging techniques used in acute stroke, in that they are completely noninvasive, requiring no exogenous contrast material whatsoever, thereby obviating concerns regarding contrast allergies and contrast-induced nephropathy (Fig. 2.4). Unlike catheter angiography and CTA, MRI uses no ionizing radiation. Like catheter angiography (but not CTA), both TOF and PC MRA can be used to demonstrate the direction of blood flow, which can be helpful in assessing the direction of flow in a vessel providing collateral perfusion or in situations such as suspected subclavian steal. Additionally, PC MRA can quantitatively measure the velocity of flow, an ability shared only by ultrasound, a modality that is usually not used in acute stroke. All of these features represent potential advantages of noncontrast-based MRA over CTA.

However, noncontrast-based MRA suffers from several disadvantages. First among these are the logistical difficulties involved in moving an acute stroke patient to and from an MRI scanner, which have been discussed above. TOF and PC MRA are relatively time consuming, requiring approximately 3-8 minutes to produce images of either the cervical or intracranial arteries. Also, MRA images are more

FIGURE 2.4 Noncontrast MR angiography. A noncontrast MRA examination of the head was performed in a patient with suspected acute stroke, resulting in axial images like that seen on the left, which shows portions of the patient right and left middle cerebral arteries (RMCA, LMCA), the right internal carotid artery (RICA), the right posterior cerebral artery (RPCA), and the right posterior communicating artery (Pcom). Like CTA images, MRA images are often combined to yield projections such as the one on the right, in which the internal carotid (ICA), middle cerebral (MCA), and anterior cerebral (ACA) arteries are more clearly visualized by computationally removing the arteries of the posterior circulation.

FIGURE 2.4 Noncontrast MR angiography. A noncontrast MRA examination of the head was performed in a patient with suspected acute stroke, resulting in axial images like that seen on the left, which shows portions of the patient right and left middle cerebral arteries (RMCA, LMCA), the right internal carotid artery (RICA), the right posterior cerebral artery (RPCA), and the right posterior communicating artery (Pcom). Like CTA images, MRA images are often combined to yield projections such as the one on the right, in which the internal carotid (ICA), middle cerebral (MCA), and anterior cerebral (ACA) arteries are more clearly visualized by computationally removing the arteries of the posterior circulation.

sensitive to degradation by patient motion than are CTA images, and this represents a significant disadvantage in imaging the acute stroke patient. Finally, both TOF and PC rely on rapid, coherent motion of water molecules in blood to make arteries visible in MRA images. Therefore, these techniques often show artifactually diminished or absent blood flow when there is turbulent flow in a stenotic segment of an artery or slow flow distal to a stenosis. This problem, in combination with relatively inferior spatial resolution, makes TOF and PC prone to overestimating the degree of stenosis in a narrowed vessel.

MRA can also be performed with a contrast agent, using a technique that is conceptually similar to that used for CTA (Fig. 2.5). Essentially, Tl-weighted images of the head or neck are obtained during the intravascular transit of an intravenously injected bolus of a gadolinium-based contrast material. The technique is more technically demanding than noncontrast MRA, because image acquisition must be timed to coincide with arterial enhancement. In depicting arteries, contrast-enhanced MRA relies not on the motion of water molecules, but instead on the distribution of the contrast agent. Therefore, contrast-enhanced MRA is less likely than noncontrast MRA to overestimate stenosis in regions of slow or turbulent

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