Timely CTA improves stroke treatment odds
Perfusion imaging offers alternative to traditional angiography for cerebral infarcts
By: Rick W. Obray and Kieran J. Murphy, M.D.
More than 700,000 people in the U.S. suffer a stroke each year,1-2 of which approximately 80% are ischemic and 20% are hemorrhagic.3 Historically, little could be done to reduce the morbidity and mortality associated with stroke, but new treatment strategies, such as thrombolysis therapy, have been shown to improve patient outcomes.4-11
Advances in CT have led to the development of CT angiography (CTA) and CT perfusion (CTP). These minimally invasive imaging modalities are rapidly developing into powerful tools for the diagnosis and treatment of both ischemic and hemorrhagic stroke.2-20 They hint of a future in which diagnostic catheter angiography may be virtually eliminated, and only therapeutic procedures will be invasive.
Only 3% of the 500,000 people in the U.S. who suffer an acute ischemic stroke each year3 receive acute treatment. Patients shown to benefit from thrombolytic therapy are those experiencing an acute stroke involving occlusion of the middle cerebral artery (MCA),21-23 those in whom an initial CT does not demonstrate extended infarct signs as delineated by Hacke et al,4 those with efficient collateral circulation,4,24 and those with efficient collateral circulation and moderate to severe persisting neurological deficit for less than three hours.4,6,11,25-27
Both CTA and CTP use high-speed spiral CT scanning and 3D volumetric reconstruction software to create various types of images following injection of intravenous contrast solution. CTA provides 3D vascular delineation similar to other noninvasive techniques as well as visualization of adjacent nonvascular soft tissue. It also offers rapid volume acquisition, limited reconstruction artifact, and scan completion during the period of peak intravascular contrast enhancement.
Using CTA, it is often possible to see filling defect in a vessel as a result of contrast displacement by clot or thrombus. CTA's sensitivity for detecting flow abnormality in vessels in the circle of Willis is at least 89% compared with digital subtraction angiography (DSA),28 and CTA does not carry DSA's risk of complications of up to 5% or its risk of permanent stroke of up to 0.5%.29-32 CTA has been reported to provide accurate estimation of cerebral blood flow, allowing for determination of the cerebral ischemic penumbra,17,19,20,33 and has also been shown to be equivalent to perfusion- and diffusion-weighted MRI in identification of the areas of the brain in acute stroke patients that might benefit from thrombolytic therapy.20
At Johns Hopkins, 2640 interventional neuroradiology procedures are performed annually, including 500 neurointerventional procedures. Our very busy stroke program admits roughly 1000 patients at two separate hospitals every year. These numbers place demands on CT for high volumes, flawless system reliability, accuracy, and speed. The accompanying case studies are examples of how CTA and CTP are being used in the treatment of acute ischemic stroke and illustrate their increasing importance as a readily available diagnostic tool.
CT CEREBRAL PERFUSION (CBP) STUDY
In conventional x-ray CT studies, morphological information is obtained by plain CT and dynamic information concerning blood flow around and within lesions is obtained by contrast dynamic CT. The recent introduction of high-speed multidetector CT is expected to further increase the range of applications for contrast dynamic CT. Regional cerebral perfusion studies have conventionally been performed using xenon-CT, in which nonradioactive Xe gas is inhaled and serves as contrast medium. The Xe gas passes through the blood-brain barrier (BBB), which is a characteristic of the capillary blood vessels in the brain, and enters the brain tissues. Xe gas studies thus permit regional cerebral blood flow reaching the brain tissues to be determined with a high degree of accuracy.
Unlike Xe gas, iodinated contrast media that are commonly employed in contrast CT studies cannot pass through the BBB and, therefore, do not accurately reflect intracerebral capillary blood flow. In Xe-CT studies, the contrast medium runs through the large vessels, passes through the capillary blood vessels, and enters the brain tissues (Figure 1). CT studies employing iodinated contrast medium, on the other hand, visualize only the flow of contrast medium through the blood vessels. Such flow should properly be referred to as "perfusion" and must be differentiated from blood flow actually reaching the brain tissues.
Perfusion is defined as the blood volume running through the capillary blood vessels per unit time per unit volume of brain tissue, expressed in units of mL/min/100 mL brain tissue. In addition, the cerebral blood volume (CBV)-the distribution of blood volume per unit brain tissue-and the mean transit time (mtt, in seconds) of the contrast medium are also employed. Cerebral blood flow (CBF), CBV, and mtt are useful for evaluating patients with ischemic cerebrovascular disease, for identifying the presence or absence of enlarged peripheral blood vessels, and for assessing blood flow rates.
The term perfusion imaging has lately been used in discussions of imaging modalities such as MRI, but CT perfusion studies provide more accurate information than MRI. The use of gadolinium in MRI permits measurement of various physiological parameters such as blood volume in the capillary blood vessels in the brain tissues (CBV), mtt of contrast medium running through the capillary vessels, and CBF. With the exception of the mtt, these parameters are expressed only as relative values in MRI studies, while CT permits absolute values to be obtained for each parameter. Because these parameters do not reflect cerebral function or metabolism, this method cannot properly be referred to as functional imaging or metabolic imaging.
In measuring perfusion, iodinated contrast medium is injected intravenously and passes through the heart and lungs to the cerebral arteries, the capillary blood vessels in the brain tissues, and then the cerebral veins. In normal brain tissues, the contrast medium remains within the capillary blood vessels.
Figure 1 shows how contrast medium runs through the brain tissues. Dynamic CT images following the course of contrast medium were obtained to measure the changes in CT values (i.e., the time-density curve [TDC]) in the pixels in the cerebral artery (square region of interest on the left), in the pixels in the brain tissues including capillary blood vessels (square ROI at the center), and in the pixels in the cerebral vein (square ROI on the right). The obtained TDCs are the Ca(t), Ci(t), and Csss(t) curves, respectively.
When contrast medium that runs through a cerebral artery with a density of "a" and a total volume of "V" enters the capillary blood vessels, the density remains constant, and the total volume of flow equals the volume of the capillary blood vessels in the tissues (density = a, total volume = Vi). All of the contrast medium reconverges in the vein, resulting in a density of "a" and a total volume of "V." The complicated network of capillary blood vessels in the brain tissues is responsible for the differences in the transit time.
The transit time can be obtained from the Ca(t) and Ci(t) curves as the mtt. The blood volume (mL) per unit brain tissue can be calculated from the total volume of contrast medium in the tissues (Vi) and the density of the contrast medium in the large artery (a), Vi/a. The values for a and Vi can be obtained from the Ca(t) and Ci(t) curves, respectively, where Vi = area under the Ci(t) curve and a = area under the Ca(t) curve. The CBF can be obtained as blood volume (mL) per unit brain tissue per mtt. CBF = Vi/a/mtt.
When Xe is used, the inhaled gas is taken up and eliminated in the following route: pulmonary vein, heart, cerebral arteries, capillary blood vessels, brain tissues, cerebral veins, heart, and lungs. As it follows this route, the Xe gas passes through the BBB and enters the brain tissues. In addition, because Xe has a large atomic number and a high x-ray absorption rate, the CT value is increased in proportion to the Xe concentration. This enhancement effect causes changes in CT values in dynamic scanning, permitting regional CBF reaching the brain tissues to be evaluated with a high degree of accuracy.
PRINCIPLES OF MDCT CBP
Dynamic CT is employed to measure the time-density curve in the cerebral artery, Ca(t), and the time-density curve in tissues including capillary blood vessels, Ci(t), when the contrast medium runs through the cerebral artery and then through the capillary blood vessels in the brain tissues. The passage of contrast medium through the capillary blood vessels can be evaluated quantitatively by using Ca(t) and Ci(t) as the input function and the output function, respectively, and then obtaining the transfer function (deconvolution method). The transfer function of normal capillary blood vessels in the brain is a simple rectangle, and it can therefore be readily determined by fitting all the interslice data in selective dynamic CT.
The mtt of contrast medium can be obtained from this transfer function. After the contrast medium is injected into a vein, it passes through the heart and lungs, resulting in a time lag in the time-density curve of the brain tissues, Ci(t). These effects can be eliminated by referring to the time-density curve for the cerebral artery, Ca(t), obtained immediately before the contrast medium enters the brain tissues. In addition, the blood volume in the brain tissues can be calculated from the area under the curve (time quadrature) of the time-density curves Ca(t) and Ci(t). At this time, compensation is required to correct for differences in the percent volume of cells in the blood (hematocrit) between large blood vessels and peripheral blood vessels.
NEUROIMAGING CTA PROTOCOLS
All of the images shown in the accompanying case studies were acquired on four- and eight-slice CT scanners capable of 0.5-sec rotation and 0.5-mm slice thickness. Acquisition parameters vary depending on the region imaged and scanner capabilities. Optimal vascular enhancement is essential and is best performed with a power injector infusing nonionic contrast through a 20- or 22-gauge IV catheter at a rate of approximately 3 cc/sec. Although an empirically determined delay can result in good studies, contrast monitoring using fluoroscopic bolus tracking and visual or automated triggering offers much more reliable results when imaging a broad patient population.
Coverage in the craniocaudal distance is related to table speed and scan time. Within the allowable time, increased coverage can be obtained by increasing table speed (greater pitch). Isotropic voxels of 0.5 mm avoid spatial resolution loss in the reconstructed nonaxial images and overcome beam hardening issues. Unnecessarily fast table speeds can be avoided by restricting the volume of interest or by a larger detector array. See the table for a summary of the CTA acquisition parameters.
Our image postprocessing is conducted on the console or is offloaded to a separate workstation. Both 2D and 3D reconstructions are typically generated. Two-D axial images at 0.5-mm resolution can be reconstructed at 0.3-mm intervals to help assess the degree of vessel narrowing. Nonaxial and 3D images provide a familiar presentation format and relationships to anatomic landmarks, including the carotid bifurcation, angle of mandible, anterior clinoid process, and circle of Willis. At our institution, volume rendering techniques are used for all neurovascular CT angiograms.
CTA IN INTRACEREBRAL HEMORRHAGIC STROKE
About 150,000 people in the U.S. suffer a hemorrhagic stroke each year, with more than half of these representing intracerebral hemorrhage.34 The resulting morbidity is significant, and the 30-day mortality rate is greater than 35%.34-36 Current treatment strategies attempt to reduce intracranial pressure and maintain adequate perfusion of the brain.34,37 Several studies have suggested that minimally invasive techniques using thrombolysis followed by aspiration of intracerebral hematomas are safe, effective, and may improve patient outcomes.38-41
CTA is a powerful tool in the evaluation of these patients because it provides information regarding the source and location of hemorrhagic stroke noninvasively. It has been shown to be an effective modality for depicting ruptured and unruptured aneurysms greater than 3 mm, and it has relatively good sensitivity for detecting aneurysms less than 3 mm.42 A large study of the sensitivity and specificity of CTA compared with catheter angiography is needed.
MR. OBRAY is a medical student and DR. MURPHY is director of interventional neuroradiology at Johns Hopkins Hospital in Baltimore.
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Case study 1
CTA confirms stent patency
55-year-old woman with fibromuscular dysplasia and left middle cerebral artery stroke. Patient was treated via stenting of her left internal carotid artery. CTA was then performed as a follow-up test. CTA through the stent gives surprising detail of the lumen. The absence of metal artifact allows evaluation of the device, vessel, and flow. In this patient, no stent collapse is seen and the vessel distal to the stent appears free of disease. Catheter angiography is the gold standard for evaluation of these patients but requires complex patient management issues such as admission and conversion from Coumadin to heparin. The use of CTA eliminates the need for DSA and the risks associated with it.
Case study 2
Imaging guides proper treatment course
75-year-old woman with left MCA occlusion, diffuse disease, and a left MCA stroke. Patient was treated with bilateral vertebral and bilateral carotid stenting. In all, a total of five stents were placed: two in the right internal carotid artery, one in the left carotid, and one in each vertebral artery. Patency of the stented vessels can be clearly evaluated, due to the lack of artifact. There was no need to stop anticoagulation and add the risk of additional stroke.
