Patrik Michel
Practical aspects of acute stroke CT
Plain CT has a long track record of a safe exam that is feasible in most patients. An occasional patient will need sedation or anesthesia for cerebrovascular images after sedation. Two or three injections of contrast are needed to obtain sufficient CT angiog- raphy (CTA) images of head and neck vessels (starting at the aortic arch) and perfusion CT (PCT) from supratentorial structures. Contrast nephrotoxi- city or allergic contrast reactions are a rare occurrence [1], especially if contrast is not administered to patients with a pre-existing history of renal failure and metformin medication. In our institution, con- trast is injected for CTA and PCT before knowledge of the creatinine clearance in hyperacute patients who are potential candidates for revascularization treatment. Several precautions may be applied [2] to help limit nephrotoxicity. Other than a creatinine clearance <30 ml/min/m2 are early pregnancy, thyroid disorders and known contrast allergy.
Non-contrast CT (NCCT)
NCCT can be performed in less than a minute with a helical CT scanner, and is considered sufficient to select patients for intravenous thrombolysis with intravenous recombinant tissue plasminogen activa- tor (RTPA) within 4.5 hours, or endovascular treat- ment within 6 hours. It is a highly accurate method for identifying acute intracerebral hemorrhage (ICH)
and subarachnoid hemorrhage, but quite insensitive for detecting acute ischemia. The approximate sensi- tivity of CT and PCT in different ischemic stroke subtypes is depicted in Figure 3.A.1. The “fogging effect” on NCCT relates to the potential disappear- ance of hypoattenuation from approximately day 7 for up to 2 months after the acute stroke. It may result in false-negative NCCT in the subacute stage of ischemic stroke.
Focal hypoattenuation (hypodensity) is very spe- cific and predictive for irreversible ischemia, whereas early edema without hypoattenuation indicates low perfusion pressure with increased cerebral blood volume (CBV) and therefore represents potentially salvageable tissue [3]. In addition to hypoattenuation, loss of gray–white matter differentiation including in the insular cortex (“insular ribbon sign”) and isodense basal ganglia constitute the four early ischemic changes (EIC) that are mostly irreversible and are used to calculate the Alberta Stroke Program Early CT Score (ASPECTS) [4, 5]. Using this score, detec- tion of EIC is better. It remains uncertain, however, whether the ASPECTS improves the prediction of clinical outcome independently of demographic and clinical variables.
Non-contrast CT (NCCT) is considered sufficient to select patients for intravenous thrombolysis with intravenous RTPA within 4.5 hours, or endovascular treatment within 6 hours.
Regarding treatment response, ASPECTS based on NCCT does not add substantially to prediction of response to intravenous thrombolysis [6, 7], but lower ASPECTS scores are related to a poorer response to endovascular recanalization treatment [6]. EIC on NCCT predict post-thrombolysis symptomatic ICH independently of other factors [8, 9]. On the other Textbook of Stroke Medicine, Second Edition, ed. Michael Brainin and Wolf-Dieter Heiss. Published by Cambridge University
Press. © Michael Brainin and Wolf-Dieter Heiss 2014.
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hand, extent of EIC on very early NCCT has not been shown to predict mass effect after acute ischemic stroke.
Perfusion CT (PCT)
PCT with iodinated contrast may be used in two ways:
as a slow-infusion/whole-brain technique as dynamic PCT with first-pass bolus-tracking
methodology.
The latter is preferable as it is quantitative and allows accurate identification of the ischemic penumbra [10].
In a patient with suspected acute ischemic stroke, a non-contrast baseline cerebral CT is immediately followed by PCT. Then, a CTA of the head and neck, and a contrast-enhanced CT of the brain are per- formed, with a total of about 15 minutes from the start to the end of the examination. If the patient fulfills criteria for intravenous thrombolysis based on the NCCT, treatment may be started in the scan- ner while the patient is undergoing PCT and CTA.
Similarly, image acquisition and processing usually overlap.
PCT examinations usually consist of two 40-second series separated by 5 minutes. For each series, CT scanning is initiated 7 seconds after injec- tion of 50 ml of iso osmolar iodinated contrast mater- ial into an antecubital vein using a power injector.
Multidetector-array technology currently allows the
acquisition of data from four adjacent 5–10 mm sections for each series. The lowest of these eight cerebral CT sections usually cuts through the mid- brain and hippocampi; the other slices cover most of the supratentorial brain.
The PCT data are analyzed according to the central volume principle to create parametric maps of regional cerebral blood volume (rCBV), mean tran- sit time (MTT), and regional cerebral blood flow (rCBF). The rCBV map is calculated from a quantita- tive estimation of the partial size averaging effect, which is completely absent in a reference pixel at the center of the large superior sagittal venous sinus.
The MTT maps result from a deconvolution of the parenchymal time–concentration curves by a refer- ence arterial curve. Finally, the rCBF values can be calculated from the rCBV and MTT values for each pixel using the following equation: rCBF ¼ rCBV/
MTT. The maps can then be displayed graphically (Figure 3.A.2.).
Figure 3.A.1. Approximate likelihood of detecting ischemic stroke on non-contrast CT (NCCT) in territorial (continuous line) and lacunar (dashed line) infarcts. * indicates the fogging effect observed in the subacute phase on NCCT. The dotted line indicates approximate sensitivity of perfusion CT in non-lacunar supratentorial strokes. PCT data are from the ASTRAL registry.
Table 3.A.1. Alterations of MTT, rCBF, and rCBV in case of ischemia (comparison with contralateral homologous region)
MTT rCBF rCBV
Healthy parenchyma ¼ ¼ ¼
Penumbra "" # ¼or"
Infarct """ ## #
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Raw maps of PCT images may be interpreted in a non-quantitative way by comparing the different par- ameters given in Table 3.A.1.
MTT is the most sensitive measure for decreased blood flow but overestimates ischemia. rCBF is more specific in identifying salvageable tissue, and rCBV is the most specific parameter for irreversibly damaged tissue [11, 12], also in white matter [13].
Threshold maps separate reversible from irreversible ischemia [14, 15] and result in high interobserver agreement [15].
The 64-slice CT scanners allowing for eight or more brain slices have increased the detection rate for acute ischemic stroke [16], but diffusion-weighted MRI (DWI) remains more sensitive for small and infratentorial lesions. PCT has an overall sensitivity of about 75% for ischemic stroke, above 85% for non- lacunar supratentorial infarcts (Figure 3.A.1), and a high specificity for ischemia [11, 15].
Several PCT-based threshold models to differen- tiate ischemic, non-viable tissue (“core”), viable tissue (“penumbra”), and non-threatened tissue (“benign oligemia”) have been developed. According to calcu- lations by Wintermark’s group [17], the ischemic area (penumbra and infarct) is defined by pixels with a greater than 145% prolongation of MTT compared with the corresponding region in the contralateral cerebral hemisphere [17]. Within this selected area, 2.0 ml/100 g represents the rCBV threshold: pixels belong to the infarct core if the rCBV value is inferior to the threshold, and to the penumbra if the rCBV value is superior to the threshold. Salvageable
penumbra is displayed in green, and tissue with low likelihood of survival (infarct core) is displayed in red (Figure 3.A.2). According to Parsons’ group, penumbra is present if the relative delay time is>2 seconds [18], and infarct if the mean CBF is <31%
of the contralateral side [19]. Determination of PCT-based thresholds using positron emission tom- ography (PET) is currently ongoing.
PCT also shows brain perfusion alterations in about 25% of patients with transient ischemic attacks, which are sometimes still present after the resolution of the patients’symptoms [20]. Focal hyperperfusion in relationship with epileptic seizures has been described, and focal hypoperfusion is rare [21, 22].
During the migrainous aura, poorly delimited hypo- perfusion contralateral to the aura symptoms is found occasionally [23] and may be mistaken as ischemic stroke.
Overall, in the absence of an abnormality on PCT in a patient with stroke symptoms, one might suspect a posterior fossa stroke, a lacunar stroke, small cor- tical stroke [16], or a stroke-imitating condition (migraine, Todd’s paralysis, venous thrombosis, encephalitis, conversion syndrome). Acute recanaliza- tion treatments might be inappropriate in some of these patients.
Baseline PCT volumes correlate with stroke sever- ity in the acute stage, and do so better in left-sided infarctions [24]. Although several PCT parameters have been associated with clinical outcome, few of them were tested in combination with well- established clinical variables, such as age or initial
Figure 3.A.2. A 77-year-old patient, found on awakening with aphasia and right hemiparesis, NIHSS¼20. Perfusion CT maps depicting (A) regional cerebral blood flow, (B) regional cerebral blood volume, (C) mean transit time, and (D) core infarct maps according to a threshold model [14]. In (D), green: reversible ischemia (penumbra), and red: low likelihood of survival (infarct).
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stroke severity. Initial penumbra volume seems to be an independent predictor depending on recanaliza- tion: if recanalization occurs, large initial penumbra is an indicator of favorable prognosis and vice versa [25, 26].
PCT predictors of treatment response are partially established; it has been shown that thrombolysis saves salvageable tissue as identified by PCT [27], and the presence of large penumbra volumes is associated with better clinical outcome if recanalization is achieved [26]. In patients undergoing endovascular treatment, smaller CBVs were associated with better outcomes [28]. These results points to similar prin- ciples as found in multimodal MRI-based prediction of treatment response.
PCT-based predictors of post-thrombolytic symp- tomatic ICH are only partially known. Severity and volume of hypoperfusion on PCT seems to play a role [29, 30], but independence of such variables from EIC on NCCT, stroke severity, or glucose sugar need to be demonstrated. Similarly, PCT has the potential to predict mass effect after middle cerebral artery (MCA) stroke. No consensus has been found of the
most promising marker, however; volumes of decreases CBF or CBV [31, 32] and blood–brain barrier permeability [33] have been proposed.
Perfusion CT (PCT) has an overall sensitivity of about 75% for ischemic stroke, above 85% for non-lacunar supratentorial infarcts (Figure 3.A.1), and a high specificity for ischemia, but diffusion-weighted MRI (DWI) remains more sensitive for small and infratentorial lesions. Still, in the absence of an abnormality on PCT in a patient with stroke symptoms, acute recanalization treatments might be inappropriate.
CT angiography
Cerebral and cervical CTA is performed using intra- venous administration of 50 ml of iodinated contrast material at a rate of 3 ml per second, and an acquisi- tion delay of about 15 seconds. Data acquisition is performed from the origin of the aortic arch branch vessels to the circle of Willis and reconstructed as maximum-intensity projections (MIP) and three- dimensional reconstructions (Figure 3.A.3).
CTA has been shown to identify the site of arterial occlusion in acute ischemic stroke patients, with
Figure 3.A.3. Same patient as Figure 3.A.2.Upper row:imaging at 12 hours after going to bed: (A) plain CT, (B) CT angiography with occlusion of the middle cerebral artery (white arrow), and (C) perfusion CT with threshold maps. The patient was then given intravenous thrombolysis with rtPA at 13 hours after going to bed and 2.5 hours after awaking (approved study protocol with informed consent from family).Lower row:(D) plain CT at 24 hours with a small left basal ganglion bleed (dotted arrow). (E) CT angiography with repermeabilization, and (F) diffusion-weighted MRI at 5 days, showing a small, partially hemorrhagic lesion.
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similar accuracy as digital subtractive angiography (DSA) and probably better than MR angiography (MRA) [34, 35]. Clot length can be assessed by thin- sliced NCCT [36] and CTA, although the latter may overestimate unless late images with collateral filling are considered [37]. Similar to clot length, a clot burden score can be calculated and correlates with stroke severity [38]. Clot presence, localization, length, and burden seem to predict clinical outcome [38–41], but it is not known whether they do it inde- pendently of known clinical and demographic out- come predictors. Clot length and site do seem to predict recanalization after intravenous thrombolysis, however [36, 42, 43].
Good collateral circulation is associated with smaller early infarct volume and National Institutes of Health Stroke Scale (NIHSS) scores [42, 44, 45].
Correlation with better clinical outcome has been shown [42, 44, 46, 47] but as with clot length, its added value to other predictors needs to be confirmed.
CTA source images (CTA-SI) have been used to estimate infarct core and penumbra in anterior [48, 49] and posterior circulation [50]. The value of this method to predict tissue fate, clinical outcome, and treatment response still requires more work [51].
CT angiography (CTA) has been shown to identify the site of arterial occlusion in acute ischemic stroke patients, with similar accuracy as DSA and probably better than MRA. Clot length can be assessed by thin- sliced NCCT and CTA. Clot presence, localization, length, and burden seem to predict clinical outcome and clot length and site do seem to predict recanalization after intravenous thrombolysis.
CT and intracranial hemorrhage
Hyperintensity in acute intracranial hemorrhage (ICH) is present on NCCT from its onset in virtually all patients. Intraparenchymal calcifications or melanin-containing metastases may sometimes give false-positive results. Adding CTA is debated, but is probably useful in patients with higher risk of vascu- lar malformations underlying the ICH, such as patients with superficial (lobar) ICH, without hyper- tension, and of younger age. One main advantage of adding iodinated contrast in ICH is that contrast extravasation (“leakage”) is an independent predictor of hematoma growth and poorer clinical outcome [52]. It is now a target for immediate hemostatic therapy in randomized trials. Various radiological
methods, including PCT [53], indicate that there is no significant ischemia around the hematoma.