Introduction

Stroke or cerebrovascular accident (CVA) is an acute central nervous system (CNS) injury and one of the leading causes of death in the developed world. Estimates are that the incidence of stroke is 795000 each year, which causes 140000 deaths annually. Based on the Center for Disease Control and Prevention (CDC) report, stroke has moved from third place in 2007 to the fifth leading cause of death in 2017 in the United States.[1][2][3] Among the strokes that occur in the U.S., approximately 87% are ischemic, 10% are intracerebral hemorrhagic (ICH) strokes, and 3% are aneurysmal subarachnoid hemorrhages (SAH).[1] In the past, neuroimaging was mainly done to exclude hemorrhagic, neoplastic, and infectious etiologies from the ischemic cause of strokes and there was a limited role for diagnostic and therapeutic efficacy of neuroimaging and interventional neuroradiology in the acute management of strokes. With recent advances, neuroimaging is now a critical part of stroke management. Despite advancements in the field of neuroradiology and interventional neuroradiology in the early management of acute stroke and decline in the mortality and morbidity rate in recent years, disability and long-term complications of stroke remain high and cost more than $34 billion each year in the U.S.[1][2][3][4]

Neuroimaging in stroke patients, especially in acute ischemic stroke patients, plays an essential role. It helps to differentiate other causes of stroke (i.e., stroke mimics such as migraine headache, tumors, seizure, metabolic disturbance, and peripheral or cranial nerve disorders), early detection of hemorrhagic stroke, distinguishing irreversible infarcted tissues from salvageable tissue, identification of vascular malformations, treatment planning for intravenous thrombolysis and intra-arterial thrombectomy, and outcomes prediction.[5][6] This activity presents a review of the different modalities and advances imaging techniques in the diagnosis and management of stroke.

Anatomy

Cerebral arteries distribution

Knowledge of the anatomy of the brain and arterial distribution is essential in the management of acute stroke.

There are three pairs of main arteries in the brain: anterior cerebral artery (ACA), middle cerebral artery (MCA), and posterior cerebral artery (PCA).

The blood supply in the brain subdivides into two main categories: Anterior circulation and posterior circulation. Anastomosis between these two main systems comprises the circle of Willis.

Anterior circulation arteries:

The ACA branches from the internal carotid artery. It supplies the anteromedial surface of the brain, i.e., midline portion of the frontal lobe, superior midline portion of the parietal lobe, and anterior portion of the internal capsule and anterior basal ganglia. Ischemic stroke lesions in this territory cause the motor and sensory deficits of the lower limb and account for contralateral paralysis and sensory loss in the lower limbs, and urinary incontinence.

The MCA also branches from the internal carotid artery. It supplies the lateral surface of the brain, i.e., anterior and lateral portions of the temporal lobes, part of the internal capsule, and basal ganglia. The MCA divides into four segments: M1 (sphenoidal or horizontal segment), M2 (insular segment), M3 (opercular segment), and M4 (cortical segment). Ischemic stroke lesions in this territory cause the motor and sensory cortical lesions of the upper limb and face and account for contralateral paralysis and a sensory deficit of the upper limb and face. The MCA also supplies the temporal lobe (Wernicke area) and frontal lobe (Broca area) and lesions in this dominant lobe (usually left) result in aphasia.

Posterior circulation arteries:

The PCA arises from the basilar artery. It supplies the posterior and inferior surface of the brain, i.e., the posteromedial portion of the temporal lobe and occipital lobe. Damage to the visual cortex located on the occipital lobe, which is responsible for the contralateral field of vision, can result in contralateral hemianopia with macular sparing. The cerebellar hemispheres receive vascular supply from branches of the vertebral-basilar circulation, including posterior inferior cerebellar artery (PICA), superior cerebellar artery (SCA), and anterior inferior cerebellar artery (AICA).

The PICA supplies the lateral medulla, vestibular nuclei, sympathetic fibers, and inferior cerebellar peduncle. Infarction in this area results in lateral medullary (Wallenberg) syndrome.[7] Superior cerebellar artery infarcts involve the superior cerebellar hemispheres, cerebellar vermis, and parts of the midbrain. The AICA supplies lateral pons, vestibular nuclei, sympathetic fibers, and middle and inferior cerebellar peduncles. Infarction in this area results in lateral pontine syndrome. Figure 1 demonstrates the vascular territory of the brain.

Plain Films

Plain films of the skull can determine skull fractures, possible depression, and the presence of foreign bodies or tumors. They can provide images of the skull foramen and sinuses. Also, skull X-rays can rule out foreign metal objects before an MRI.

The plain film radiograph has no role in stroke imaging.

Summary of different available imaging modalities for stroke imaging

CT, CT angiography (CTA), CT perfusion (CTP), CT venography (CTV), MRI, MR angiography (MRA), MR perfusion (MRP), ultrasonography, nuclear medicine, and angiography are the primary different imaging modalities useful for stroke imaging. Each modality has its pros and cons.

Computed Tomography

Different CT modalities that are options in stroke imaging include non-contrasted CT (NCCT), CTA, CTV, and CTP.

Pros: CT scan has fast image attainment, which is not sensitive to motion (except for CTP, which is motion-sensitive). CT scan is widely available in the emergency rooms these days, and it makes high-resolution images of the brain.

Cons: All CT modalities, except for NCCT, require intravenous administration of ionized contrast agents, and is challenging in a patient with renal impairments or allergy to contrast agents.[8]

Non-contrasted computed tomography

NCCT is the first imaging technique done in all patients suspected of stroke mainly to exclude hemorrhagic stroke. Besides, NCCT is sensitive to identifying calcification, which is vital in the detection of any lesion. NCCT should be done immediately as the patient has stabilized in the emergency room. NCCT findings in ischemic stroke depend on the age of infarction: hyperacute (less than 12 hours), acute (12 to 24 hours), subacute (24 hours to 5 days), and old (within weeks after stroke). In the "hyperacute phase," the main role of non-contrast brain CT is to exclude intracranial hematoma. Sometimes an intra-arterial thrombus has high attenuation in NCCT and can be detected. This phenomenon is called "hyperdense vessel sign." In "acute" infarction NCCT can show subtle loss of gray-white matter interface (differentiation) due to the rise of water content result of cytotoxic edema.[9][10][11][12][13][14] In "subacute" infarction, NCCT shows vasogenic edema with mass effect and well-defined margins. The risk of mass effect and herniation is high in this stage. In "old" findings, NCCT shows volume loss of brain parenchyma and hypoattenuation compatible with encephalomalacia.[15]

Non-contrast CT is essential in the management of patients with ischemic stroke. In patients with a large infarction, thrombolysis is not helpful but can increase the risk of post-treatment intracranial hematoma, a severe complication with the risk of brain herniation and death. In this context, different criteria and scoring systems have been developed to exclude the patients with very large infarction from treatment. The most common one is the “Alberta stroke program early CT score (ASPECTS).” In ASPECTS, 10 different areas of MCA territory are evaluated visually on non-contrast CT. For any area with subtle hypodensity, 1 point is subtracted from 10. Patients with an ASPECT score of less than 7 usually demonstrate worse outcomes.[16] (Figure 2) A similar score system has been proposed for posterior circulation (PC-ASPECTS).

Computed tomography angiography

 CTA is performed by administration of intravenous CT contrast through a line in antecubital fossa. In the acute stroke setting, CTA is done to identify any vessel thrombosis or occlusion, vascular malformations, dissection, vasculitis, and aneurysm. Maximum intensity projection (MIP) images and 3D reconstructions are suitable for the rapid detection of distal vascular stenosis and cloth length. CTA is a reliable method to detect any stenosis or occlusion in the large intracranial vessels such as internal carotid artery and middle cerebral artery trunk in the secondary (M2) or tertiary (M3) branch vessels.[17][18]

Computed tomography perfusion

CTP is done with rapid injection of contrast in the peripheral vein (usually antecubital vein) and repeating brain CT many times and observe the brain parenchymal enhancement. The speed of parenchymal enhancement is proportional to the blood perfusion. The CTP is capable of measuring different perfusion parameters in the brain including the cerebral blood volume (CBV), cerebral blood flow (CBF), mean transient time (MTT), time to peak transient time (TTP), and time to maximum (T max). CBV is the total volume of blood in a unit volume of the brain, which includes blood in the arteries, arterioles, capillaries, venules, and veins. CBF is the volume of blood moving through a given unit volume of the brain per unit time. MTT is the average of the transit time of blood through a brain region. MTT is calculated using the CBV and CBF according to MTT = CBV / CBF. The CBV and CBF are used to detect the core infarction. Usually, the decrease of CBF more than 30 percent of normal parenchyma is considered consistent with “core infarction” by many CTP software. On CTP “ischemic penumbra” is considered as areas of preserved CBF and CBV but increased MTT, TTP, or Tmax around the “core infarction.” For detection of ischemia Tmax more than 6 seconds is the most commonly used parameter by many CTP software. CTP is a functional test, rich in functional data but low in anatomic data. There are many challenges and artifacts in CTP which the radiologist must consider for interpretation. (Figure 3)

Magnetic Resonance

Given higher soft-tissue contrast of MRI, MRI is superior to CT in hyperacute and acute phases. MRI of the brain is performed with and without gadolinium IV contrast, and it is used to evaluate acute ischemic stroke, transient ischemic attack (TIA), and hemorrhagic brain lesions. MRI was previously contraindicated in a patient who had pacemakers, metallic foreign bodies, aneurysm clips, implantable devices, and claustrophobia to MRI. But recently many of the medical devices are MR compatible or MR conditional (they are safe by MR scanners using low magnetic fields and under certain conditions). It is also challenging to perform MRI in morbidly obese patients. IV gadolinium contrast requires caution in a patient with renal impairment or contrast allergy.[19]

Conventional MRI sequences

Findings of conventional MRI sequences such as fluid-attenuated inversion recovery (FLAIR), T2-Weighted imaging (T2WI), and T1-Weighted imaging (T1WI) are subtle in acute ischemic stroke in the first few hours. FLAIR images may show abnormal signal earlier than other conventional sequences and demonstrate signal changes within 3 hours after stroke onset.[20] (Figure 4 A and B) High signal intensity on T2WI usually appears about eight hours after the stroke onset. T1WI may take even longer than 8 hours to show low signal intensity.[21][22] Besides, FLAIR is highly sensitive to detect subarachnoid hemorrhage and make a high signal in sulci in patients with subarachnoid bleeding.[23]

Diffusion-weighted imaging

Diffusion-weighted imaging (DWI) is now the best sequence to detect brain infarction earlier than CT or other MR sequences. It is one of the most sensitive (88% to 100%) and specific (95% to 100%) and accurate (95%) imaging modalities to detect ischemic core within minutes after onset (while conventional MRI and CT images are still normal at this stage).[24][25][26][27]

The basic mechanism of DWI is beyond this text, but DWI works by measuring the Brownian motion of water molecules within a voxel of tissue. In the brain, infarction and hypoxia cause impairment of mitochondrial function. Secondary depletion of ATP causes malfunction of Na-K pumps and cellular welling by shifting the extracellular water to the intracellular space where the higher concentration of proteins and cell membrane reduces the Brownian motion of water molecules. The final result will be the diffusion restriction of water molecules in the infarcted tissue, which can be detected by the DW sequence. The diffusion restriction is depicted on DWI as hyper signal intensity.

It merits noting that not every hyper signal intensity on DWI is “true” diffusion restriction. The DWI is basically a T2 sequence and sometimes a T2 hypersignaling lesion (e.g., brain edema) will appear as a hypersignal on DWI a phenomenon called "T2 shine-effect”. To differentiate the “true” diffusion restriction (infarction) versus “T2 shine effect,” another sequence called apparent diffusion coefficient (ADC) is necessary. To generate the ADC map, we repeat the DW sequences with different parameters and directions. The true diffusion restriction has a lower signal on the ADC map than the T2 shine effect (Figure 4 C and D).

Magnetic resonance angiography

Like CTA, MRA can be performed in stroke patients to evaluate large vessel occlusions and atherosclerotic lesions. It is useful in patients with allergy to IV CT iodinated contrast and could not receive these contrasts.[28][15] In comparison to CTA, the MRA is more time consuming and is not available in all hospitals. It is most common in the subacute phase of infarction.

Ultrasonography

Duplex ultrasound is the usual choice for screening of carotid artery stenosis in patients suspected of stroke. Transcranial Doppler ultrasound is commonly used for screening of cerebral artery vasospasm after SAH.

Ultrasonography is cheap and usually available in every emergency room and can be performed at the patient's bedside. It has no radiation, is non-invasive, and is a safe modality compared to other imaging options. However, ultrasonography is a highly operator-dependent modality. It may be challenging to obtain the appropriate acoustic window of visualization on the area of interest.

Nuclear Medicine

Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) can predict the vulnerability of carotid plaque for rupture. F, C, N, and O  commonly use in PET imaging. F-fluorodeoxyglucose (FDG) PET can detect and predict the vulnerability of carotid plaque for the rapture. FDG accumulates in the inflammatory lesions and therefore is a key to determine atherosclerotic plaques. SPECT can evaluate the content of atherosclerotic plaques such as oxidized LDL and apoptotic bodies.[29]

O-PET is the gold standard to visualize the penumbra. In a PET scan, areas with loss of blood flow, ischemic penumbra, and infarction demonstrate abnormal glucose and oxygen metabolism. Perfusion SPECT is also a consideration in the management of acute stroke. The decreased vascular reserve can be evaluated in SPECT using an acetazolamide challenge, which can predict the development of ischemic lesions in patients undergoing endarterectomy.[29]

Although SPECT is also valuable for evaluating cerebral blood flow, PET is widely available and is cost-benefit compared to SPECT, and this modality is more common to use in the acute setting.

Angiography

The vast majority of ischemic stroke patients demonstrate arterial stenosis on angiography, which is usually performed 6 to 8 hours post-stroke admission.[30][31] A catheter-based cerebral angiography or digital subtraction angiography (DSA) is the gold standard imaging for carotid artery stenosis, vasculitis, cerebral aneurysms, and cerebrovascular malformations. DSA is an invasive procedure; therefore, it is not the first choice imaging modality, except for evaluating patients presented with SAH. In addition to diagnostic value, angiography allows the interventionist to treat occluded or stenotic vessel or vascular malformations.

Patient Positioning

Patient positioning in brain CT scan

The patient is a supine position on the CT table, and the tube rotates around the patients. Patients’ head should place in the head holder. To prevent motion artifacts, patients should be as comfortable and immobile as they can. To prevent unnecessary irradiation to the patient’s head and neck, especially to the lens of the eye, head CT performs in an angle parallel to the base of the skull called glabellomeatal. Brain CT starts from this point and moves superiorly. Brain CT is performable with, without, or with and without IV contrast enhancement.

Patient positioning in brain MRI

To perform MRI, initially ask the patient about pacemakers, metallic foreign body, aneurysm clips, implantable devices, etc. Evaluate the patients for any previous allergy to contrast media if gadolinium will be used and explain all the risk and the benefits of possible contrast allergy. Check the patient’s renal function if using gadolinium. Gadolinium is only an option in patients if their GFR is over 30. Request the patient to remove all metal objects, including any jewelry, keys, hearing aid devices, etc. Evaluate the patient for previous claustrophobia and provide a chaperone or sedation for claustrophobic patients. Patients' positioning is supine, the receiver coil placed around the head, and the patient immobilized using cushions. Cushions under the knee are an option for extra patient comfort. Locate the laser beam over the glabella.

Clinical Significance

Imaging in stroke patients is an early and essential evaluation which should be done as soon as possible to confirm the diagnosis and start the appropriate therapy.

Stroke imaging performs in patients for the three main reasons:

• To differentiate the ischemic from hemorrhagic stroke and intracerebral hemorrhages; non-contrast CT is the primary modality for this process.
• To exclude other causes of stroke (i.e., stroke mimics such as tumors, seizure, etc.).
• To estimate the volume and location of the infarcted tissue and tissue at risk for infarction.
• To find the occluded artery in ischemic stroke and to help the treatment planning.

NCCT is the first-line imaging modality in most centers as the patient admitted and stabilized in the emergency room. It is performing to exclude hemorrhagic stroke and intracranial hemorrhage. The next imaging is CTP and CTA. In modern CT scanners, it is possible to perform the CTP and CTA at the same time with a single dose of contrast, but still, in many stroke centers, CTP and CTA are done by two contrast infusion. The non-contrast CT, CTA, and CTP are the backbone of ischemic “code-stroke” imaging in many stroke centers.[32] In most ischemic stroke guidelines, there is a general trend to extend the window of treatment for the tissue at risk (ischemic penumbra) up to 24 hours after the insult. This approach has increased the number of CTPs and CTAs.  Brain MRI with DWI has the most sensitivity and specificity and is the best option to diagnose acute stroke. It is superior to NCCT to early detection of acute ischemic stroke; however, MRI/MRA may not always be available in all centers, and performing this modality is time-consuming. So, it is not a routine part of “code-stroke” imaging in the hyperacute phase, although it is valuable in the subacute phase. DSA angiography is the gold standard to evaluate carotid and vertebral arteries, intracranial vascular narrowing/occlusion, vasculopathy, and vasculitis but given the advancement of non-invasive imaging techniques, its main role is for the treatment rather than solo diagnosis. The Doppler duplex ultrasonography is mainly used to follow the patients with SAH to detect vasospasm as a complication of SAH.