Current guidelines for treatment of acute stroke by intravenous (IV) thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) [
Clinical evaluation and NECT examination are still the most important tools in the workup of acute ischemic stroke. With modern brain CT-imaging, a supplementary overview of cerebral macro- and microcirculation can be obtained in minutes with CT angiography (CTA) and CT perfusion, providing valuable information before or during treatment initiation.
The aim of this study was to illustrate a comprehensive three-step CT imaging protocol for acute stroke consisting of NECT to exclude hemorrhage and other contraindications for IV-thrombolysis, contrast enhanced dynamic CT-perfusion scan (CTP) to evaluate the existence and grade of perfusion deficit, and finally a contrast enhanced CT-angiography (CTA) of the cervical and intracranial arteries to locate and grade possible arterial occlusions. We describe the comprehensive radiological examination and evaluation and discuss the time aspect and present clinical cases emphasizing and discussing the impact of the method on treatment individualization.
Four patients with acute ischemic stroke of different aetiologies or different treatments were chosen for illustration of the comprehensive CT protocol and for demonstrating the impact of the information obtained on treatment decisions.
When the first medical personnel arrived at the scene of a suspected acute stroke they immediately notified the stroke center. In this way the patients entered the stroke fast-track service before physically arriving at the hospital, giving the hospital stroke team, consisting of personnel from the emergency department, a neurologist and the radiology department personnel, time to prepare and coordinate their actions. The neurological deficit was quantified using the National Institutes of Health Stroke Scale (NIHSS) [
Firstly a spiral whole-brain NECT was performed with 16 × 1.0 mm primary slices (120 kV, 355 mAs, CTDI 57 mGy = 2.2 mSv) reconstructed to axial and coronal MPR with 5 and 3 mm slice thickness, respectively, to rule out intracranial hemorrhage and early imaging findings of ischemia, both representing contraindications for intravenous thrombolysis.
If no contraindications for IV thrombolysis were established, dynamic contrast-enhanced CTP was performed with injection of 70 mL Iomeprol 400 mgI/mL (Iomeron, Bracco SA, Milano, Italy) followed by 40 mL saline injected at 5 mL/sec. A total of 34 sequential acquisitions were performed with a scan interval of 1.5 seconds covering a 4 cm-thick section of the brain (80 kV, 170 mAs, CTDI 5.9 mGy/scan × 34 scans = 200 mGy = 1.7 mSv). Each acquisition consisted of eight adjacent 5 mm slices covering 4 cm of brain extending upwards from a level 2 cm above the entrance of the sella. Brain perfusion analysis was performed using the brain perfusion package of the Extended Brilliance Workspace (Philips Medical Systems, Best, The Netherlands). For the arterial input and venous output functions the A2 segment of the anterior cerebral artery and the posterior superior sagittal sinus were used respectively, avoiding occluded arteries or other major abnormalities [
Case 1: 66-year-old male with left-sided stroke symptoms and a normal NECT. Initial comprehensive examination shows reduction of both CBF and CBV in the right hemisphere and an increase in MTT caused by a right-sided M2-segment MCA occlusion (arrow) seen on the CTA. The CTP viability map shows a small area of advanced perfusion defect (red) in the right hemisphere surrounded by a relatively large penumbra (green).
Finally a contrast-enhanced CTA of the cervical and intracranial arteries was performed with 64 × 1.0 mm primary slices (120 kV, 225 mAs, CTDI 943 mGy = 4.6 mSv) in one continuous run after the administration of 100 mL Iomeprol 400 mgI/mL followed by 40 mL saline injected at 5 mL/sec. The CTA scan was started by automated monitoring of the contrast enhancement in the descending aorta. Reconstructions were created with 3 mm-slice thickness in the axial, sagittal and coronal planes in addition to maximum intensity projections (MIP) and three-dimensional images in selected cases.
The effective dose for each examination was estimated from the dose length product (DLP) by the equation E [mSv] = DLP ×
The imaging information was reviewed directly at the workstation during the examination and immediate treatment decisions were made by a joint effort of the neurologist and the neuroradiologist. For intravenous thrombolysis 0.9 mg/kg alteplase (Actilyse) was administered by IV-infusion over 60 minutes (maximum 90 mg). Patients selected for neurointerventional treatment underwent digital subtraction angiography (DSA) followed by intraarterial (IA) thrombolysis and/or mechanical thrombectomy. Time of important events was accurately logged throughout the whole process, from onset of symptoms to treatment initiation (Table
Overview of starting times of relevant events and NIHSS scores for the four different cases.
Event | Case 1 | Case 2 | Case 3 | Case 4 |
---|---|---|---|---|
Onset of symptoms | 0 | 0 | 0 | 0+ |
Arrival at the stroke center | 14 min | 38 min | 38 min | 4 h 0 min |
NIHSS evaluation | ||||
CT-head | 43 min | 56 min | 54 min | 4 h 25 min |
CT-perfusion | 47 min | 63 min | 64 min | 4 h 41 min |
CT-angiography | 51 min | 66 min | 68 min | 4 h 53 min |
IV-thrombolysis | 65 min | 80 min | — | — |
Thrombectomy/IA-thrombolysis | 210 min | — | — | 6 h 30 min |
NIHSS evaluation at discharge |
For followup the patients underwent a magnetic resonance imaging (MRI) examination within 48 hours from symptom onset. The examinations, performed on a Philips Intera (Philips Medical Systems, Best, The Netherlands) or Siemens Allegra (Siemens Medical, Munich, Germany) 3 Tesla scanners, included T1, T2, FLAIR, diffusion weighted imaging (DWI), and in selected cases MR perfusion (MRP) and time-of-flight MR-angiography (MRA).
66-year old male with hypertension and controlled hypercholesterolemia presented with acute onset of left-sided weakness and difficulty speaking. On physical examination he was fully-oriented but had dysarthria, rightward gaze preference, left sided hemiparesis involving the face, and left sensory deficits. The NIHSS score was 14 (Table
Case 1: Repeated NECT and CTP examinations 90 minutes after IV-thrombolysis without clinical improvement. The NECT is still normal and the CTP shows unchanged ischemic core but moderate enlargement of the penumbra. Based on this information the patient underwent intraarterial thrombolysis.
Case 1: DSA images from the right anterior cerebral circulation. The microcatheter is seen in an occluded M2-segment of the right MCA (arrow) during the intervention. The IA-thrombolysis results in complete recanalization of the occluded segment.
Case 1: follow-up MRI with FLAIR, DWI and ADC showing an established infarction in the right basal ganglia region, with minor hemorrhagic transformation, corresponding well to the previously defined CTP ischemic core.
65-year-old male with controlled hypertension and paroxysmal atrial fibrillation who presented with acute onset of left-sided weakness and difficulty speaking the day after electrical defibrillation. On physical examination he was fully oriented but had general left-sided hemiparesis, facial weakness, mild dysarthria and hemi-inattention (neglect) to more than one sensory modality and scored 9 on NIHSS (Table
Case 2: 65-year-old male left-sided stroke symptoms and a normal NECT. The CTP viability map shows multiple perfusion defects (green) and a small area of advanced perfusion deficit (red) in the right hemisphere consistent with fragmented cardiogenic embolism. The CTA showed no major arterial occlusion obviating neurointervention.
Case 2: follow-up MRI with FLAIR, DWI, and ADC showing an established infarction in the right frontal lobe matching the CTP-delineated ischemic core.
49-year-old male with uncontrolled hypertension presented with acute onset of right-sided weakness and difficulty speaking. On physical examination he was fully oriented but had dysarthria and right-sided hemiplegia including facial nerve palsy but no sensory deficits. The NIHSS score was 14 (Table
Case 3: 49-year-old male with right sided stroke symptoms and a normal NECT. The CTP source images show a small perfusion deficit in the left corona radiata with a marked decrease of both CBF and CBF (circle) that was initially missed by both the radiologist and the automated viability map software. CTA was normal.
Case 3: Follow-up MRI with FLAIR, DWI and ADC showing a small lacunar infarction in the right corona radiata that is also seen retrospectively on the CTP maps (Figure
27-year-old woman using oral contraceptives and with prior history of migraine and benign childhood epilepsy woke up with fluctuating left-sided weakness. Prior to admission she experienced 5 episodes of weakness each lasting 5–10 minutes and followed by near-complete recovery. NECT, CTA, and CT venography (CTV) performed at a local hospital were judged normal. In retrospect a dense media sign was seen on the NECT and an occlusion of the right MCA M2-segment on the CTA. The patient was referred to the stroke center and upon arrival she was fully oriented but physical examination revealed left sided hemiplegia and facial nerve palsy. The current symptom episode had persisted for over 1 hour without any recovery, unlike the previous attacks. Her NIHSS score was 11 (Table
Case 4: 27-year-old woman with left-sided stroke symptoms of unknown onset and a normal NECT. The CTP viability map showed no ischemic core but a relatively large penumbra (green) in the right basal ganglia caused by a M2-segment MCA occlusion (arrow) seen on the CTA.
Case 4: acute MRI with FLAIR, DWI and ADC showing an established infarction in the right basal ganglia that was not detected by the CTP examination.
Case 4: DSA images from the right anterior cerebral circulation before recanalization showed an occluded right MCA M2-segment. During IA-thrombolysis partial revascularization was achieved with a remaining clot.
Case 4: follow-up MRI with FLAIR, DWI, ADC showing a relatively small infarction with minor hemorrhage in the right basal ganglia in comparison to the large penumbra seen on the initial CTP examination. The MRA shows complete recanalization of the previously partially revascularized right MCA. NECT shows a small hemorrhagic transformation in the right basal ganglia and parenchymal contrast leakage due to increased permeability secondary to ischemia and neurointervention.
According to current guidelines all patients with suspected acute ischemic stroke receive the same treatment within the given time frame, regardless of imaging findings which potentially might be used to individualize treatment.
A negative comprehensive CT examination does not exclude patients with clinically suspected acute ischemic stroke from receiving IV thrombolysis because symptomatic small vessel occlusions (Case 3) can be difficult to detect both on CTA and CTP. On the contrary a positive comprehensive CT examination can be valuable when choosing the optimal treatment. When a large vessel occlusion is identified on CTA (Cases 1 and 4) an evaluation of the collateral circulation in the affected territory with CTP can be useful to identify patients with perfusion mismatch suggesting tissue at risk that might be salvaged. These patients should be considered for IV-thrombolysis but the treatment can be converted to IA thrombolysis (bridging) for more aggressive approach if needed, potentially increasing the chance of a good outcome as in case 1 [
Moreover the information from the CTP might introduce some flexibility to the currently fixed therapeutic time window and increase safety when the time of onset is unknown (Case 4).
Recently the time frame for treatmtent with IV thrombolysis was extended from 3 hours after symptom onset [
In some instances the CTP can reveal the underlying pathological process as in case 2 where the patient had multiple small ischemic regions in both the anterior and posterior circulation consistent with fragmented cardiac emboli without major vessel occlusion, excluding treatment with thrombectomy or IA thrombolysis.
Still studies on the clinical application of CTP results are lacking so even though the comprehensive CT examination is promising in many ways the impact of the method on the clinical outcome is yet unknown.
DWI/MRP is currently the gold standard for infarct evaluation in acute ischemic stroke because of the superiority of DWI in assessing tissue viability [
Using perfusion data to assess tissue viability as in CTP is inherently inaccurate because the result of disturbed perfusion is both tissue- and time-dependent. The color coded infarct core (red) and surrounding penumbra (green) in CTP-viability maps is therefore merely a rough estimate on the current status of a dynamic process [
Nevertheless, CTP has over the last years gained acceptance as an alternative examination to DWI/MRP in the acute phase of ischemic stroke, mostly because of technical and practical advantages. It offers faster examination time and more effective workflow since it can be done in continuity with the standard NECT examination. It has been estimated that approximately 1.9 million neurons are lost every minute following the occlusion of a major cerebral artery [
Additionally CTP is more robust than MRP because it offers quantitative measurement of perfusion with higher spatial resolution and a linear relationship between contrast concentration and attenuation [
Until recently a major disadvantage of CTP has been the limited coverage of the examination whereas DWI covers the whole brain. Common CTP techniques offer only 4–8 cm coverage, with the risk of small peripheral ischemic lesions being missed. This problem has now been overcome with the availability of 320 slice MDCT with 16 cm coverage [
Interpretation of the DWI images in ischemic stroke is generally simple. Misinterpretation of data in CTP can be an obstacle for the novice reader, particularly when relying overly on the computer generated viability map. The CTP software used in our study automatically generates a viability map by comparing the two hemispheres and searching for asymmetric perfusion. Therefore, the software does not detect bilateral symmetric lesions for example in patients with older lesions in the contralateral hemisphere. Furthermore, to reduce noise, the viability map has a size threshold preventing automatic detection of tiny lesions (case 3). Misinterpretation can be avoided by understanding and thoroughly reviewing the basic perfusion images and comparing them with the anatomical images from the NECT and CTA.
When NECT is used as the only radiological base for treatment decision in clinically suspected acute ischemic stroke, it may in some cases be unclear what pathophysiological process actually is being treated. The comprehensive CT examination aims at guiding stroke management in the acute setting, possibly allowing for patient stratification and individualized treatment strategies with improved clinical outcome.
This extended case review shows the potential of combined NECT, CTP and CTA as a fast and safe diagnostic method allowing more accurate diagnosis and making way for early individualized treatment in acute ischemic stroke. However, the method has not yet been systematically evaluated in studies with high evidence class.