The CT scan is certainly the most widespread method of radiological investigation, and its advantages are primarily attributable to the speedy acquisition of images. In the hyperacute phase of stroke, the CT brain scan without contrast is the prime investigative method for excluding stroke mimics and haemorrhagic lesions, which would obviously lead to a completely different management of the patient. With this objective, the CT brain scan has proven highly sensitive. Furthermore, prompt execution of the CT scan on all patients with suspected stroke has proved to be the strategy with the best cost-effectiveness ratio in the management of these patients. The sensitivity of this investigation increases after the first 24 h from onset of symptoms. However, some previous studies showed a 61 % prevalence of early signs of cerebral ischaemia on CT [4]. The main early signs are shown in Fig. 1.1. The presence of these factors is significantly associated with worse prognosis (odds ratio [OR], 3.11; 95 % confidence interval [CI], 2.77–3.49). In particular, middle cerebral artery (MCA) hyperdense signs, which indicate the presence of a thrombus within the lumen of the arterial vessel, can be observed in approximately 30 % of ischaemic stroke patients in the territory of the same artery [5]. Although, as mentioned above, these early signs are associated with a worse clinical outcome, it is currently not completely clear how these factors should be considered when deciding whether or not to administer intravenous thrombolytic therapy [6]. Experienced radiologists, neuroradiologists and neurologists can recognize these signs, although previous studies showed some difficulties in identifying them [7]. Standardized methods such as the Alberta Stroke Program Early CT Score (ASPECTS) have been developed in order to recognize early ischaemia [8]. ASPECTS has been developed to provide a simple and reproducible method for identifying early ischaemic changes at parenchymal level, which have been identified on CT scan. The value of this scale is derived from the evaluation of two axial cuts on the CT scan: one at the level of the thalamus and basal nuclei, and the other at the level of the rostral basal nuclei. The methodology for calculating the ASPECTS scale score is presented in Table 1.3.

Although the use of the ASPECTS score helps in selecting patients, above all for endovascular treatment in the acute phase, it does not apply to the lacunar score, to ischaemia in the midbrain or to other ischaemic lesions involving arterial territories other than the MCA.

The advent of next-generation or multi-slice CT scans has increased the speed at which images are acquired and also means that intra- and extracranial arteries can be evaluated on a CT angiography. Furthermore, spiral CT scan is a technology that allows integration of conventional image acquisition with functional elements, such as perfusion methods; early assessment of the canalization level of the arteries and of parenchymal perfusion can be checked immediately after a basal CT scan and over a period of 5–10 min [9].

This method is used to observe and verify that the main extra- and intracranial arterial branches are correctly canalized. After rapid intravenous administration of a bolus of contrast medium, the CT scan acquires the images of how the contrast medium is distributed in the cranial vascular district and highlights any filling defects of the artery corresponding to the presence of a thrombus occluding the same vessel. This instrumental method currently is a highly important management element for the potential administration of therapy in the acute phase of an ischaemic stroke and in particular for choosing to carry out mechanical thrombectomy. Study of the cerebral pial collateral circulation can be performed through the use of a multiphase CT angiography that allows the images to be acquired in three different phases after administering the contrast medium: (1) acquisition of images from the aortic arch to the summit during arterial peak, (2) acquisition during the intermediate venous phase and (3) acquisition during the delayed venous phase [10]. Unlike the perfusion CT scan (see below), multiphase CT angiography means the whole brain can be included, reducing any possible background ‘noise’ created by the patient moving and allowing rapid assessment of collateral circulation, and, finally, there is no need for any further contrast medium. In a recent trial, multiphase CT angiography was used in order to positively select the patients to be given mechanical thrombectomy (ESCAPE trial) [11]. In addition to these purposes, this kind of method allows the patency of the extracranial carotid system to be studied while simultaneously looking for any stenosis or obstructions that may justify the acute event observed.

The volume of the entire brain perfusion can be mapped through intravenous administration of a bolus of contrast medium. With this method, scanning is repeated over time in the same portion of the cerebral parenchyma, according to where the bolus of contrast medium passes through the arterial wall [12]. The images displayed need to be analysed and interpreted. Hypodense areas correlate to cerebral ischaemic regions. In addition, quantitative analysis of the kinetics of the contrast medium through the brain allows estimation of the cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) necessary for the blood to pass from the vascular compartment through the cerebral tissue [13]. The limit values of CBF and CBV might be used to predict whether the brain parenchyma will be able to survive or if they will die; however, there are no validated and standardized limit values at the moment. Applying the ASPECTS method to CBF or MTT mapping seems to identify the maximum extension of ischaemia in absence of reperfusion, and the difference between CBV and CBF (or MTT) on the ASPECTS scale seems to identify the area of ischaemic penumbra, that is, the brain tissue that can potentially be saved [10].

The diffusion-weighted imaging technique is based on the capacity of the MRI to detect a signal from the movement of water molecules interposed between two close pulses of radiofrequency. This type of investigation can detect anomalies related to cerebral ischaemia within 3–30 min from onset of symptoms, when a traditional MRI and CT scan would not reveal them [15]. Any restrictions in the distinction between cytotoxic and vasogenic oedema, above all in T2 sequences of DWI, are resolved by using the apparent diffusion coefficient (ADC). ADC can quantify the extent of water diffusion. In this context, a hypointense signal in the ADC mappings corresponds to a cytotoxic oedema, while a hyperintense signal represents a vasogenic oedema. A systematic review of the literature published in 2010 concluded that the DWI method is superior to basal CT scan in the diagnosis of ischaemic stroke in patients presenting within 12 h of symptom onset [16]. The study also provided an indication of the predictive value of the clinical and functional outcomes. Since DWI shows ischaemic damage and not the ischaemia itself, PWI can identify the ischaemic area through fast NMR in order to measure the quantity of contrast that reaches the brain tissue. CBF, CBV and MTT maps are processed through several scan phases of the same area of brain parenchyma. Although the aforementioned American systematic review highlighted the association between the volume of the lesion detected by PWI and clinical severity, no evidence has emerged of the usefulness of this technique in daily use for diagnosing ischaemic stroke. Both methods, however, are of critical importance in detecting ischaemic penumbra. Accurate identification of reversible ischaemic brain damage is the key factor in selecting patients for reperfusion, with the aim of achieving the best results in terms of efficacy and safety. The classical ‘mismatch’ pattern between DWI and PWI highlights the cerebral parenchyma area that can still be saved. In particular, while DWI detects the irreversibly damaged brain parenchyma (ischaemic core), PWI can highlight the hypoperfused area which, subtracted from the previous one, defines the ischaemic penumbra area. Although these findings in the past were highlighted in consensus guidelines, their precise role in the management of acute stroke has not yet been clearly defined [17]. However, these laboratory investigations have some useful aspects, as described below:

Similarly to CT angiography, this technique allows extra- and intracranial vessels to be visualized, highlighting any stenosis or occlusion. The percentages of sensitivity and specificity in detecting arterial steno-occlusive lesions vary widely from 86 to 97 % for CT angiography and from 62 to 91 % for MRI angiography [22]. An acute thrombolytic occlusion is usually displayed as a hypointensive image in the large vessels (middle or carotid cerebral artery).

Intravenous administration of alteplase (recombinant tissue-type plasminogen activator – rtPA) has proven effective in reducing disability at 90 and 180 days after stroke. However, the benefit of the drug tends to decrease significantly as time goes by, and the time window currently applied is 4.5 h. At first, alteplase was administered within 3 h from onset of symptoms because of evidence in previous studies such as NINDS, in which 38 % of the treated patients reached a favourable outcome compared to 21 % of the placebo group, with no significant increase in the risk of mortality [29]. ECASS III assessed the efficacy of the treatment by extending the time window to 4.5 h [30]. The main result of the study was the effectiveness of alteplase compared to placebo (OR, 1.34; 95 % CI, 1.02–1.76; number needed to treat [NNT], 14), with no significant difference between the two groups regarding mortality and symptomatic haemorrhages. Further evidence emerged from the SITS-ISTR observational study that confirmed data already presented in a previous randomized trial [31]. To date, no evidence has emerged from literature concerning the efficacy and safety of rtPA between 4.5 and 6 h. IST-3 is the most important trial that has taken this therapeutic window into consideration and has enrolled more than 3,000 patients [32]. It has shown that there is no temporally positive trend for a favourable outcome, and in particular, the subanalysis of 1,007 patients treated within 4.5 and 6 h has shown a statistically significant difference between the groups of treated and untreated patients (47 % versus 43 %; OR, 1.31; 95 % CI, 0.89–1.93). A previous meta-analysis published in 2012 involved over 7,000 patients treated within 6 h [33]. Globally, the results showed that thrombolytic treatment was superior to placebo (OR, 1.17; 95 % CI, 1.06–1.29), with a net benefit for those who were treated within 3 h. In fact, the patients treated between 3 and 6 h did not benefit significantly from the treatment (OR, 1–07; 95 % CI, 0.96–1.20). In conclusion, a recent meta-analysis has taken into consideration the trials previously published and has analysed the outcomes of almost 7,000 patients [34]. The main observations emerging from this analysis concern the clear benefit of receiving thrombolytic therapy within 3 h (OR, 1.75; 95 % CI, 1.35–2.27). The benefit is maintained between 3 and 4.5 h (OR, 1.26; 95 % CI, 1.05–1.51), whereas it decreases between 4.5 and 6 h (OR, 1.15; 95 % CI, 0.95–1.40). An important finding shows that the observed benefit does not depend on the patient’s age or clinical severity. Taking into consideration the data mentioned above, the most relevant message for a clinician can be summarized in one general concept: early intervention in the therapeutic window is the determining factor for the effectiveness of systemic thrombolytic treatment [35, 36].