Stroke || Computed Tomography–Based Evaluation of Cerebrovascular Disease

45 Computed Tomography–Based Evaluation of Cerebrovascular DiseaseIMANUEL DZIALOWSKI, VOLKER PUETZ, RÜDIGER VON KUMMER

This chapter studies the clinical efficacy of computed tomography (CT) in patients with acute ischemic or

hemorrhagic stroke. We will discuss noncontrast CT (NCT) as well as CT angiography (CTA) and CT perfusion imag-ing (CTP) for acute stroke. Because of the differing prog-nosis between anterior and posterior circulation ischemic strokes, we will separately discuss CT imaging for these. In theory, CT, like magnetic resonance imaging (MRI), can be clinically effective in patients with acute stroke on five different levels: (1) technical capacity, (2) diagnostic accu-racy, (3) diagnostic impact, (4) therapeutic impact, and (5) patient outcome or prognostic impact.1

We will focus on the use of CT in the acute stroke setting. Whenever applicable, we will compare CT with MRI—the other important acute stroke imaging modality discussed in a separate chapter.

Noncontrast CTFeasibility and Technical Capacity

A potential advantage of CT over MRI is its wide avail-ability and excellent feasibility.2 Even with older genera-tion scanners a plain CT scan can be performed within minutes. Performing a CTA or CTP requires a spiral CT scanner, the application of contrast media, and process-ing afterward. Each examination will usually only require an extra 5 minutes’ scan time. Recently, CT scanners with up to 320 detector rows that cover a tissue volume of 16 cm thickness have become available.3 These scan-ners can examine the whole brain in less than 1 second and can repeatedly image the entire cerebral circulation, allowing time-resolved images of the brain vessels and whole brain CTP.

Detection of Infarct Core

Acute brain ischemia below the cerebral blood flow (CBF) threshold of 20 to 30 mL/100 g/min leads to loss of neurologic function, cell membrane dysfunction with cel-lular edema (so-called cytotoxic edema), and subsequent shrinkage of the extracellular space. This type of edema is potentially reversible and can be visualized by MRI with diffusion-weighted imaging (DWI). Acute severe brain ischemia with CBF values below 10 mL/100 g/min causes

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immediate net water uptake into gray matter.4,5 This so-called ionic edema6 characterizes brain tissue destined for tissue necrosis, even with early reperfusion.7 Only this net uptake of water into brain tissue causes a decrease in x-ray attenuation on CT.4 The decrease in x-ray attenua-tion is linearly and indirectly correlated to the amount of water uptake. A 1% increase in tissue water causes a decrease of approximately 2 Hounsfield units (HU) in x-ray attenuation that can be detected by the human eye.8 CT is thus a very specific method for depicting irrevers-ible brain infarction.9

Early Signs of Infarction on NCT

Early changes visible on head CT during ischemia are often summarized as “early ischemic changes” (EIC). We should, however, distinguish between at least three dif-ferent kinds of EIC with different pathophysiologic and diagnostic relevance: 1. Reduced x-ray attenuation of gray matter is the com-

mon cause of CT signs such as “loss of the insular or cortical ribbon,” “obscuration of the lentiform nucleus,” reduction in gray matter–white matter con-trast, or “hypodensity.” These phenomena are all con-sequences of ionic cerebral edema and thus represent ischemic damage (infarction) on CT (Fig. 45-1B).

2. Isolated brain tissue swelling without reduced x-ray attenuation (Fig. 45-2): this phenomenon has been extensively studied recently and is likely caused by compensatory vasodilation with an increase of cere-bral blood volume (CBV).10-12 It seems to represent tis-sue at risk of infarction that might be salvaged with reperfusion (ischemic penumbra). It can be observed in 10% to 20% of ischemic brain regions.10 The pres-ence of isolated cortical swelling on CT—even if very extensive—should NOT keep stroke neurologists from attempting urgent recanalization but should rather be taken as a challenge. It is therefore a mistake to call brain tissue swelling per se an “early CT sign of infarc-tion” and to lump this phenomenon together with is chemic x-ray hypoattenuation.

3. The hyperdense artery sign is highly specific for the presence of an intraarterial thrombus,13 but its detec-tion depends on the thrombus’ hematocrit value, which

COMPUTED TOMOGRAPHY–BASED EVALUATION OF CEREBROVASCULAR DISEASE 871

A B

C D

Figure 45-1 Acute middle cerebral artery (MCA) infarction in a patient with occlusion of the internal carotid artery (ICA) and MCA. A, Hyperdense MCA sign (arrow) on baseline noncontrast CT (NCT) scan. B, NCT with hypoattenuation of the right lentiform nucleus, head of caudate nucleus, and insula (arrows). C, Intracranial CT angiography (CTA) source image showing right proximal MCA occlusion (arrow). D, Extracranial CTA maximal intensity projection of the right common carotid artery, external carotid artery, and ICA showing proximal ICA occlusion.

determines its x-ray attenuation.14 The term EIC should not be used for this sign because arterial obstruction by an intraluminal thrombus can be fully compensated for by collateral flow. An arterial obstruction is not a “sign” of brain ischemia but may cause brain ischemia (see Fig. 45-1A).

Diagnostic Accuracy

In the first 6 hours after ischemic stroke, two of three stroke patients will develop ionic edema that can be detected by NCT.15 Poor sensitivity of NCT is often blamed for the fact that ischemic (i.e., ionic) edema cannot be diagnosed early in each and every patient with ischemic stroke. However, stroke symptoms occur at CBF reduc-tion to 20 to 30 mL/100 g/min, which is well above the accepted threshold for occurrence of ionic edema. We can thus assume that around one third of ischemic stroke patients have not yet developed relevant ionic edema (i.e., no irreversible damage) and may have an excellent prog-nosis if reperfusion is achieved. X-ray hypoattenuation on early NCT, however, is subtle and hard to detect without training (see Fig. 45-1B). Interrater reliability for ischemic tissue hypoattenuation varies between a kappa value of 0.4 and 0.6.16 The “sensitivity” of NCT for evidence of infarction on follow-up imaging varies between 20% and

87% depending on image quality, experience, and train-ing.15 Using systematic scores like the Alberta Stroke Pro-gram Early CT Score (ASPECTS) facilitates detection of x-ray hypoattenuation and improves reliability and sensi-tivity.17 Once a hypoattenuating area has been detected, it is highly predictive of subsequent infarction.9

Diagnostic Impact

The diagnostic impact of stroke imaging refers to the proportion of patients in whom the specific diagnosis of stroke type relies on imaging. NCT has a huge diag-nostic impact simply by differentiating ischemic from hemorrhagic stroke, enabling a specific therapy like thrombolysis to be administered. In addition, the extent of hypoattenuation on NCT is an important positive pre-dictor of thrombolysis-induced brain hemorrhage, which is the most feared complication of thrombolysis.18-20 MR DWI is highly sensitive for ischemic brain tissue, even above the CBF level of the penumbra and indicates brain tissue at high risk, if not already irreversibly injured, whereas hypoattenuation on NCT depicts irreversible tis-sue damage with high specificity. The detection of areas with high signal intensity on DWI may allow assessment of the pattern of affected brain territories and the cause

DIAGNOSTIC STUDIES872

B CA

ED F

Figure 45-2 A 79-year-old man seen with acute aphasia and right-sided hemiplegia. Baseline noncontrast CT (NCT) shows hemispheric cortical swelling (arrows) without hypoattenuation (A, D). CT angiography demonstrates dilated cortical vessels in these regions (B, E). The patient had marked spontaneous clinical improvement. Follow-up NCT (C, F) 3 days later revealed minor infarcts in the internal borderzone (arrowheads) and regressive cortical swelling.

of stroke early on and signals an increased risk of stroke in patients with transient ischemic attacks (TIAs).21

Therapeutic Impact

In acute ischemic stroke, thrombolysis with intravenous (IV) recombinant tissue plasminogen activator (rt-PA) within 3 hours of stroke onset can increase the propor-tion of nondisabled patients by an absolute 13%.22 The therapeutic time window of 3 hours may be extended in the future because treatment with IV rt-PA has recently shown a beneficial effect, that is, between 3 and 4.5 hours from symptom onset with an absolute effect size for improved functional outcome of 7%.23 The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Study Group was able to prove benefit for throm-bolysis simply by using NCT to identify ischemic stroke patients. The European Cooperative Acute Stroke Study (ECASS) investigators used NCT to additionally exclude patients with extended ischemic edema.24 These stud-ies show that NCT is sufficient to identify a group of

patients in whom IV thrombolytics have a moderate ben-eficial effect within 4.5 hours of symptom onset. Inter-estingly, none of the completed, large, phase III trials of IV thrombolysis selected patients on the basis of a visible arterial occlusion—the target pathology for immediate recanalizing therapies—and did not check for recanali-zation by treatment. Only the Prolyse in Acute Cerebral Thromboembolism (PROACT) studies investigated the therapeutic impact of thrombolysis in patients selected by angiographically proven middle cerebral artery (MCA) occlusion and slight edema on NCT.25,26 Intraarterial infu-sion of prourokinase within 6 hours of symptom onset achieved an absolute effect size of 15%.

Prognostic Impact

The impact of CT on the functional outcome of stroke patients is the most important level of clinical efficacy. As shown above, NCT enables thrombolysis in ischemic stroke patients and thereby reduces long-term disabil-ity. Moreover, the information on the extent of x-ray


hypoattenuation on NCT is prognostically relevant. There is good evidence that patients with extended hypoattenu-ation (infarction) on NCT have a poorer natural history and less chance to benefit from thrombolysis.18,20,27

In summary, brain tissue imaging by NCT ignores the changes above the CBF threshold of irreversible injury, with the exception of brain tissue swelling with-out hypoattenuation due to compensatory vasodilation. NCT has a rather low sensitivity for identifying brain ischemia but a high specificity for identifying irrevers-ible ischemic injury. One may conclude that mainly patients who have small volumes of hypoattenuating brain tissue on NCT but severe symptoms will benefit from reperfusion therapy. In fact, several studies have demonstrated that the response to thrombolytic ther-apy is associated with the extent of hypoattenuation on early CT.20

CTAFeasibility and Technical Capacity

The advent of “helical” or “spiral” acquisition has enabled CT scanners to acquire data very rapidly. With this tech-nique, data acquisition occurs continuously while the gan-try table moves the patient through the gantry, so a volume of interest can be scanned in a relatively short time.

A CTA study of the neck and head requires about 5 minutes’ examination time and the application of contrast media. Usually, an IV bolus of about 100 mL of an iodin-ated, nonionic and isoosmolar or low osmolar contrast agent is given, and image acquisition will be initiated when the contrast reaches the aortic arch or common carotid artery. In our experience, feasibility of CTA is excellent and images are diagnostic in almost every patient. Imme-diately after data acquisition, CTA source images can be viewed, and large vessel occlusions can be diagnosed instantaneously (see Fig. 45-1C). Within a few minutes, 3D reformats can be generated, enabling detection of periph-eral vessel and other abnormalities (see Fig. 45-1D).

The utility of CTA is tremendous, and it has already replaced conventional catheter angiography in many situ-ations. Recent technical development enables CTA with time-resolution (4D-CTA) and digital subtraction of the bone.

Diagnostic Accuracy

Intracranial Disease

The need for rapid decision making makes CTA an ideal technique in the detection of large vessel intracranial arterial stenosis or occlusion (see Fig. 45-1). For intra-cranial atherosclerotic stenosis, noninvasive imaging modalities should identify lesions with high sensitivity and specificity as compared with the gold standard of digital subtraction angiography (DSA). In the prospec-tive Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) Trial, both transcranial Doppler (TCD) ultrasound and magnetic resonance angiography (MRA) noninvasively identified 50% to 99% of intracranial large vessel stenoses with a substantial negative predic-tive value of about 90%.28 However, the positive predic-tive value (PPV) was only 36% for TCD and 59% for MRA. Thus the authors concluded that abnormal findings on TCD or MRA require a confirmatory test such as angiogra-phy to reliably identify stenosis.

Compared with MRA, CTA has increased sensitivity (70% versus 98%, respectively) and PPV (65% versus 93%, respectively) for revealing intracranial arterial stenosis.29 Similar results were found in a recent study, where the sensitivity of CTA to detect 50% or greater intracranial stenosis was 97.1% and the specificity was 99.5%.30 Thus, CTA seems sufficient to detect or rule out significant intracranial atherosclerotic stenosis. We have recently used CTA to detect intracranial nonocclusive thrombi (iNOT; Fig. 45-3) in patients seen with acute ischemic stroke and TIAs.31 These thrombi seem to be rare (2.7% of patients in our study) but indicate stroke patients with increased risk of clinical deterioration during the hospi-tal course.

CTA also has excellent accuracy in detecting intracra-nial arterial occlusion. Lev et al32 studied 44 consecutive patients with acute ischemic stroke who underwent CTA of the circle of Willis within 6 hours of onset of symp-toms. A total of 572 vessels was evaluated, and angio-graphic correlation was available for 224 of these vessels. Sensitivity and specificity of CTA were both 98%, and accuracy was 99%. The mean time for CTA reconstruc-tion was 15 minutes. The results of Lev et al have been confirmed by a study by Nguyen-Huynh et al,30 in which

A B

Figure 45-3 Example of intracranial nonocclusive thrombus (arrows) in the distal right M1 segment (A) and left M1 segment (B).


both the sensitivity and specificity of CTA to detect large artery intracranial occlusion were 100%.

As an additional prognostic factor and for the pur-pose of immediate treatment decisions, the intracranial thrombus extent can be estimated with CTA. Patients’ prognoses and responses to therapy can be judged by a 10-point clot burden score (CBS; Fig. 45-4). CBS is a simple measure of the location and extent of intracranial thrombus.33 Patients with a higher thrombus burden (i.e., lower CBS scores) had higher baseline Institutes of Health Stroke Scale (NIHSS) scores and more extended infarc-tions compared with patients with less thrombus burden. Moreover, CBS was an independent predictor of indepen-dent functional outcomes and death in this study. These results have been confirmed in a recent study by Tan et al.34 Their study also demonstrated a correlation of CBS with the perfusion defects on CTP maps and CTA source images and confirmed the hypothesis that a higher throm-bus burden is associated with lower recanalization rates with IV thrombolysis.34,35

In summary, CTA is an ideal tool for the rapid and accurate detection of intracranial stenosis and occlusion of major intracranial arteries and may help to differenti-ate patients who will benefit from specific recanalization techniques.

Extracranial Carotid Artery Disease

Cerebral angiography has been the diagnostic procedure of choice for the quantification of extracranial carotid artery stenosis. Although generally safe, angiography is still associated with a 0.5% to 5% rate of stroke as a com-plication when used in routine clinical practice.36,37 With the advent of ultrafast helical CT imaging, the complica-tion is avoided, and CTA is being used with increasing

1

1 1

1

2 2

2

Figure 45-4 A 10-point clot burden score (CBS): 1 or 2 points each (as indicated) are subtracted for absent contrast opacification on CT angiography in the infraclinoid internal carotid artery (ICA) (1), supraclinoid ICA (2), proximal M1 segment (2), distal M1 seg-ment (2), M2 branches (1 each) and A1 segment (1). The CBS score applies only to the symptomatic hemisphere.

frequency in the diagnosis of extracranial carotid artery disease. An example of severe right internal carotid ste-nosis is depicted in Fig. 45-5A, on conventional arteriogra-phy, and in Fig. 45-5B, on CTA (axial cuts).

Several studies to date have reported excellent agree-ment between conventional catheter cerebral angiography and CTA. In a comparative study of CTA, conventional angi-ography, and MRA, a strong correlation was found between CTA and angiography (r = 0.987; P < 0.0001) in 128 carotid bifurcations in 64 patients.38 CTA has the additional benefit of providing precise information regarding the surround-ing vascular and bony anatomy, including arterial wall cal-cification that is not depicted by DSA or MRA.

In a prospective study, 40 patients (80 carotid arteries) underwent evaluation by CTA, digital DSA, and Doppler ultrasonography.39 The overall correlation between Dop-pler ultrasonography and DSA was less robust (r = 0.808) than that between CTA and DSA (r = 0.92); CTA provided superb correlation in the detection of mild stenosis (0% to 29%), stenosis greater than 50%, and carotid occlusion and had sensitivities and specificities exceeding 0.90. CTA performed less well in the detection of 70% to 99% steno-sis and had a sensitivity of 0.73 (axial source images) and a PPV of only 0.62 (negative predictive value, 0.95). The relatively poorer degree of discrimination on CTA in this study between moderate (50% to 69%) and severe (70% to 99%) stenosis is an important limiting factor to con-sider in the use of this technology. It is hoped that further prospective data acquisition with simultaneous 320-slice technology will shed additional light on this issue.

Detection of Infarct Core

In addition to providing information on the vessel status, CTA may also predict the fate of ischemic brain paren-chyma; that is, it improves early detection of ischemic infarction.40 Viewing the CTA source images at a low contrast and window level (e.g., 40/40 HU) downstream to a large vessel occlusion, CTA will show an area of diminished tissue contrast enhancement (Figs. 45-6 and 45-7). This area likely represents severely hypoperfused brain tissue that will be irreversibly damaged without reperfusion. In comparison with NCT, the sensitivity and accuracy in prediction of final infarct extension can be improved.41,42 CTA source images closely correlated to MR DWI sequences.43

Diagnostic Impact

The diagnostic impact of CTA is probably still underes-timated. Within minutes, CTA reliably diagnoses arterial occlusions and stenoses from the aortic arch to the distal intracranial arterial segments. Compared with MRI, CTA is sensitive for calcified plaques and can thus elucidate the underlying stroke etiology in many cases. It was already shown that patients with MCA occlusion have a lesser chance to benefit from IV thrombolytics if the ipsilat-eral carotid is obstructed.44 A systematic study of arterial pathology with CTA may enable more specific treatments of arterial occlusions. In addition, CTA can distinguish patients seen with seizures and postictal paresis (Todd’s paralysis) from those with true ischemic hemiparesis and early seizures by demonstrating arterial occlusion.45


A

C

B

D

Figure 45-5 Conventional angiographic depiction (A, B) of right internal carotid artery occlusion in a patient seen with an acute ischemic right middle cerebral artery distribution infarction. CT angiography source images (C, D) confirm right ICA occlusion (arrow).

A B C

Figure 45-6 Noncontrast CT (NCT) (A) and CT angiography (CTA) source images (B) of a patient 1 hour after acute aphasia and right hemiparesis. NCT shows subtle hypoattenuation of left basal ganglia, insula, and anterior cerebral artery (ACA) territory. CTA clearly shows contrast hypoattenuation in the complete middle cerebral artery and ACA territory caused by an internal carotid artery occlusion. Follow- up CT (C) shows the resulting infarction.


NCT CTA CTA-SI

TTP CBF CBV DWI d 1

Figure 45-7 Noncontrast CT (NCT), CT angiography (CTA), and CT perfusion imaging (CTA-SI) of an 82-year-old patient 2 hours after aphasia and mild right hemiparesis. NCT and CTA results are normal without evidence of intracranial arterial occlusion (upper two rows). Time-to-peak (TTP) and cerebral blood flow (CBF) parameter maps reveal hypoperfusion in the left insula and corona radiata without reduc-tion of cerebral blood volume (CBV, lower two rows). After thrombolysis with recombinant tissue plasminogen activator (rt-PA), follow-up MRI-diffusion-weighted imaging (DWI) shows a tiny infarction in the left insula.

Therapeutic Impact

The usefulness of CTA for therapeutic decision making has not yet been prospectively studied. There is evidence from secondary analyses of randomized trials that patients with a small core of infarction on NCT (or possibly CTA source images) and an intracranial large vessel occlusion on CTA might be ideal candidates for recanalization, even beyond the accepted time window.46 This hypothesis is currently being studied in at least two large, randomized controlled trials.47

Many centers use CTA to select acute ischemic stroke patients for intraarterial interventions. The PROACT II study demonstrated that patients with an MCA occlusion

benefit from intraarterial thrombolysis up to 6 hours after onset.25 Another approach for patients with known intra-cranial occlusions is the intravenous–intraarterial bridg-ing concept. The Interventional Management of Stroke III trial currently investigates whether this strategy is supe-rior to standard IV thrombolysis.47 Potentially, patients with proximal arterial occlusion (e.g., carotid T occlu-sion) and/or large thrombus burden may benefit from additional intraarterial therapy, whereas patients with minor thrombus burden (e.g., MCA M2 branch occlusion) may have no additional benefit. Estimation of thrombus burden with a CBS could be a simple and readily avail-able tool to help in deciding whether a patient will benefit from aggressive treatment paradigms.


CTA might also be useful for excluding patients with-out visible arterial occlusion from thrombolysis. Angio-graphic studies have shown that no arterial occlusion can be detected in one third of patients seen within 6 hours of onset.48 A systematic comparison of the effi-cacy of thrombolysis in acute ischemic stroke patients with arterial occlusion versus those without arterial occlusion, however, has not yet been performed.

CT Perfusion ImagingTechnical Capacity and Feasibility

With the development of helical CT scanning technology, it is now possible to track a bolus of IV contrast material as it passes through the brain. The measurement tech-nique for CBF has its theoretical basis in the central vol-ume principle,49 which relates CBF (mL/100g/min), CBV (mL/100 g), and mean transit time (MTT; seconds) by the following equation:

CBF = CBV

MTT

It is assumed that a linear relationship exists between the CT enhancement and the concentration of contrast material within brain tissue and arteries. After IV administration of a bolus of iodinated contrast agent, measurements are made of the arterial enhancement curve, Ca(t), the supplying artery, and the tissue enhancement curve, Q(t), for a region of the central parenchyma. For the calculation of MTT, a mathematical process of deconvolution is applied to the functions Ca(t) and Q(t) to determine an impulse function, R(t), which would be the theoretical tissue enhancement curve obtained from a rapidly injected bolus of contrast material. The MTT is calculated from the following formula:

MTT = area underneath R(t)height of R(t) plateau

CBV is calculated from Q(t) and Ca(t), the two param-eters measured directly during the CTP study:

CBV =area underneath Q(t)area underneath Ca(t)

Although this technique is rapidly evolving, difficul-ties remain and include patient motion artifacts, partial averaging effects, effects of drawing regions of interest (ROIs) directly over arterial vessels, and the proper selec-tion of the arterial input vessel to yield the most accurate results. Another still significant limitation is the incom-plete coverage of the volume of brain tissue scanned dur-ing contrast passage. Depending on the CT manufacturer, only about 2 to 4 cm (craniocaudal extension) of brain tissue can be covered. This volume is usually placed at the level of the basal ganglia so that perfusion of all major supratentorial vascular territories can be captured. New-generation CT scanners with up to 320 detector rows will provide whole-brain perfusion images.

Attempts at quantitative validation of this technology in humans through comparison with other techniques, such as xenon-CT, are ongoing.50,51

Diagnostic Accuracy

CTP parameter maps improve diagnostic accuracy for tis-sue at risk and irreversibly damaged brain tissue.42,50,52,53 For example, Lin et al studied 28 patients with multi-modal CT seen with territorial infarction within 3 hours of symptom onset and assessed 280 ASPECTS regions for a relative CBV reduction. They found a 91% sensitiv-ity and 100% specificity for predicting a DWI lesion on follow-up imaging.52 Parsons et al42 showed that CBV best predicts final infarct extent in patients with major reper-fusion, whereas CBF and MTT were the best predictor of final infarct size in patients without reperfusion. In some patients with MCA branch or other distal intracranial occlusions not recognized on CTA, time-to-peak (TTP) or MTT parameter maps are helpful in identifying the pres-ence and site of occlusion (Fig. 45-7).

Diagnostic Impact

CTP facilitates and improves identification of the infarct core and has the potential to identify tissue at risk. Acute multimodal CT imaging is limited in detecting small ischemic lesions. In patients with normal NCT, CTA, and CTP findings but persistent neurologic deficit, immedi-ate MR DWI will usually show one or multiple small ischemic lesions, for example, in the brainstem or one that is bihemispheric. In patients without a DWI lesion an ischemic cause becomes very unlikely.

Therapeutic and Prognostic Impact

The therapeutic impact of CTP is still unclear. Acute stroke patients presenting within 4 to 5 hours of symp-tom onset should not be excluded from thrombolysis on the grounds of CTP imaging findings. In patients present-ing beyond the accepted time window for thrombolysis, CTP might help to identify the tissue at risk, thereby facil-itating decision making on late recanalization strategies.

Similar to NCT, CTP is prognostically relevant because it identifies the core of infarction. Patients with an exten-sive CBV lesion have reduced chances of achieving an independent functional outcome.42,54

Limitations of a Multimodal CT Protocol

Before initiation of a multimodal CT examination, the fol-lowing contraindications should be kept in mind: known renal insufficiency, contrast media allergy, hyperthyroid-ism, medication with the oral antidiabetic metformin, and pregnancy. Because acute ischemic stroke with the option of thrombolysis is an emergency, waiting for laboratory results such as serum creatinine level should not delay the performance of CT. The risk of developing relevant radiocontrast media nephropathy in acute stroke patients seems to be reasonably low (<0.5%).55,56 In patients taking metformin, the serum creatinine level should be checked at baseline and up to 3 days after the examination so that metformin accumulation with subsequent lactate acidosis is avoided.

Depending on the CT manufacturer, data on the effec-tive radiation dose varies between 5 and 10 mSv. A relevant individual risk of radiation-induced intracranial neoplasm


seems only to exist in children.57 Because of the rapidly increasing frequency of CT examinations, however, there is a cumulative risk that should not be neglected.

Posterior Circulation CT ImagingIschemic Stroke

About 20% of cerebrovascular ischemic events involve the posterior circulation.58 Clinical signs and symptoms are frequently less specific compared with anterior cir-culation stroke. Isolated transient loss-of-consciousness or dizziness can be misattributed to vertebrobasilar isch-emia, whereas many cases of true vertebrobasilar isch-emia remain undiagnosed.59 However, similar to anterior circulation stroke, early diagnosis is crucial for initiating systemic thrombolysis or mechanical revascularization procedures. The relevance of acute brain imaging with CT is to reliably rule out intracranial hemorrhaging and to identify patients with basilar artery occlusion. Latter patients have a devastating prognosis: nearly 80% die or are severely disabled if treated conservatively.60

The sensitivity of DWI for identifying final infarction is better than NCT in posterior circulation ischemia.61 This is relevant in differentiating cerebral ischemic events from other disease entities with similar clinical symptom-atology (e.g., basilar migraine or vestibular neuritis). The reliability of CT to detect hypodensity in the posterior circulation is limited by bony and beam hardening arti-facts in the posterior fossa. Newer-generation CT scan-ners with helical scan techniques seem to diminish this limitation62 but have not been analyzed systematically. The sensitivity for detection of a final infarct in the pos-terior circulation is improved with CTA source images compared with NCT (Fig. 45-8).63 Studies comparing the sensitivity of CTA source images with MR DWI have not been performed.

A hyperdense basilar artery sign64 (see Fig. 45-8) and a hyperdense posterior cerebral artery sign65 specifi-cally indicate occlusion of these arteries. By application of CTA, vertebrobasilar occlusion can be diagnosed with high sensitivity and specificity.32 In the study by Lev et al, the diagnostic accuracy of CTA was 96% for vertebral artery occlusion and 100% for basilar artery occlusion. Thus, in a patient with patency of the basilar artery on CTA, the diagnosis of symptomatic basilar artery occlu-sion can be excluded. In contrast, evidence of basilar artery occlusion on CTA should immediately prompt recanalization strategies. In patients with clinically sus-pected posterior circulation ischemia, both basilar artery occlusion and vertebral artery occlusion on CTA are pre-dictors of increased risk of mortality and poorer func-tional outcome.66

In contrast to anterior circulation stroke, posterior circulation stroke currently has limited imaging-based selection criteria for identifying patients who may ben-efit from thrombolysis. Multimodal CT and MRI have only been analyzed in smaller patient series. Demonstration of small DWI lesions or a diffusion–perfusion mismatch have been proposed for identifying patients with basilar artery occlusion who may potentially benefit from thromboly-sis.24,67 A TTP delay in the posterior cerebral artery ter-ritory on CTP parameter maps indicates vertebrobasilar

occlusion.68 The therapeutic and prognostic implications of these techniques for patients with posterior circulation strokes need to be studied.

Quantification of CTA source image hypoattenuation in the posterior circulation with a systematic score, the posterior circulation Acute Stroke Prognosis Early CT Score, identified patients with basilar artery occlusion who were unlikely to have a favorable functional out-come despite recanalization of the basilar artery.63 In a similar study, CTA source image hypoattenuation in the mesencephalon and pons indicated patients with basilar artery occlusion and poor functional outcomes.69 Both studies demonstrate that CTA source image hypoattenu-ation can identify areas with ischemic changes in the posterior circulation, including the brainstem. Moreover, this information has prognostic relevance in patients with basilar artery occlusion. However, these findings need to be validated prospectively and should not currently influ-ence immediate treatment decision making in patients with posterior circulation strokes, particularly for those with basilar artery occlusion.

NCT and CTA in Acute Hemorrhagic StrokeNCT is the imaging modality of choice in the diagnosis of acute intracerebral hemorrhage. It seems to easily detect the hyperdense (60 to 80 HU) appearance of a fresh blood clot. Studies on the reliability and validity of this find-ing have not, however, been performed. The conditions under which intracerebral blood is not hyperdense on CT are not well studied. Low hematocrit levels and impair-ment of clotting may be possible conditions. CT is as sen-sitive and specific as MRI in detecting acute intracranial hemorrhage. CT is less sensitive in detecting subacute or old intracerebral hematomas.70 The location of intracere-bral hematoma is key in determining etiology. A deep (or basal ganglia) intracerebral hemorrhage is usually hyper-dense, as are thalamic, pontine, or cerebellar locations. Lobar hematomas may be caused by sinus thrombosis, arteriovenous malformations, brain tumors, or coagula-tion disorders, including therapeutic anticoagulation.

The utility of CTA after NCT has shown intracerebral hemorrhage is tremendous and might replace catheter angiography in the future. Cerebral aneurysms can be diagnosed accurately down to a diameter of 2 mm.71 Simi-larly, arteriovenous malformations and venous thrombo-sis can be diagnosed in many cases.

Approximately 30% of acute hemorrhagic stroke patients show evidence of hematoma growth within the first hours after onset.72 This increase in hematoma size is a key factor in predicting a poor prognosis for the disease. When CTA source images are used, it is possible to pre-dict hematoma growth early on. The so-called spot sign characterizes a leak of contrast media that is clearly hyper-dense in relation to the surrounding hematoma. Wada et al73 found the spot sign in 13 of 39 patients (33%) with acute intracerebral hemorrhage within the first 3 hours. The presence of the spot sign was significantly correlated with a poor functional outcome. Several studies are cur-rently testing the predictive value of this sign, and further studies are planned to investigate whether patients with a positive spot sign will respond to factor VIIa therapy.


Figure 45-8 Noncontrast CT (NCT) (upper row) and CT angiography (CTA) source images (middle row) of a patient with acute basilar artery occlusion 3.5 hours and 4.5 hours after symptom onset, respectively. NCT demonstrates hyperdense basilar artery sign (arrow) but does not reveal early ischemic changes. CTA source images demonstrate hypoattenuation in all posterior circulation territories (posterior circulation Acute Stroke Prognosis Early CT Score [pc-ASPECTS] = 0). The patient was treated with systemic thrombolysis with alteplase. Diffusion-weighted MRI (lower row) performed after thrombolysis (6.5 hours after symptom onset) demonstrates lesions in the same territories (pc-ASPECTS = 0). (Images courtesy of the Seaman Family MR Research Centre, University of Calgary, Canada.)

Acknowledgment

We would like to acknowledge Charles A. Jungreis and Steven Goldstein for their work on the previous edition of this chapter.

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Stroke || Computed Tomography–Based Evaluation of Cerebrovascular Disease