Applied Radiology

Dr. Bradley is Director of MRI at Long Beach Memorial Medical Center in Long Beach, CA, and Professor of Radiology at the University of California, Irvine, in Orange, CA.

A "stroke" is defined as an acute neurologic event. Approximately 85% of strokes are thromboembolic events, ¹ most of which present with normal findings on CT in the first 6 hours. CT is performed in these patients not to confirm the diagnosis of infarction but to exclude hemorrhage when symptoms are still evolving and heparin treatment is planned. Hemorrhage (from a ruptured aneurysm, an AVM, a tumor, or a hemorrhagic infarct) is a contraindication for heparinization.

Following exclusion of hemorrhage, the carotid arteries usually are evaluated with duplex Doppler ultrasonography. Subsequently, MRI of the brain usually is performed, followed by MR angiography (MRA) of the carotids. If a flow-limiting stenosis is not detected in the carotid artery, MR angiography of the circle of Willis usually is performed.

This paper focuses on the MR appearance of acute ischemic infarction, hemorrhage, and MR angiography of the head and neck as it would appear on both a conventional MR imager and on the newer, echo planar imaging (EPI) systems.

Ischemic infarction

The most common cause of ischemic infarction is vascular occlusion due to an embolus or thrombosis. If the collateral blood supply to a region is insufficient, the oxygen supply to that area of the brain decreases. The normal blood supply to the brain is 50 ml/min/100 gm of brain. ² When the blood supply drops to one-third of the normal level (17 ml/min/100 gm), neurons cease to function--i.e., symptoms and EEG abnormalities appear, but no morphologic changes are seen on either CT or MRI. ²

When the blood supply falls to approximately 20% of normal (10 ml/min/100 gm) the ATP levels fall, the sodium-potassium pump fails, and water and sodium begin to enter the
cell, resulting in intracellular swelling (cytotoxic edema). ² Whether or not this initially reversible ischemic injury continues on to irreversible cell death depends on two factors: the degree and the duration of reduced blood supply. Reversible cytotoxic edema can be maintained for several days in the setting of vasculopathy (e.g., lupus) without infarction. On the other hand, complete anoxia for a few minutes will result in irreversible infarction, blood brain barrier breakdown (BBBB), and vasogenic edema.

During the first few hours, CT studies generally appear normal in the setting of ischemic infarction. On conventional MR images, mass effect is minimal during the cytotoxic phase. This is because the water entering the swollen cells has merely been transferred from the local extracellular space (i.e., there is no net increase in water content per unit volume of brain). With increasing time and the development of vasogenic edema due to BBBB from infarction, there will be increased water content in the brain. This leads to decreased signal on T1-weighted MR images and increased signal on T2-weighted MR images, with associated mass effect (figure 1). ¹ When this pattern is seen in a vascular territory, the diagnosis of ischemic infarction can confidently be made. During this period, MR contrast agents (gadolinium chelates) also can confirm the diagnosis of acute vascular occlusion, demonstrating vascular stasis and leptomeningeal collaterals to the infarcted region (figure 2). ^3,4

With the newest generation of EPI-capable MRI units, the diagnosis of ischemic infarction can be made with a great deal of certainty in minutes rather than hours (figure 3). ^5-7 These systems are characterized by strong, fast gradients which allow echo planar images to be acquired in one-tenth of a second per slice. ⁸ (It should be noted that this is 10 times faster than even the newest generation of spiral CT scanners, and is as fast as electron beam CT.)

By modifying the basic EPI pulsing sequence, it can be made to be very sensitive to the diffusion of water. Such "EPI diffusion images" highlight areas of restricted water diffusion, such as those found on the inside of cells swollen with cytotoxic edema due to acute ischemia. ⁷ This restricted motion of water leads to high signal on EPI diffusion images (figure 3C), allowing the rapid diagnosis of acute cerebral ischemia while it may still be reversible. EPI diffusion images remain positive for about three weeks after infarction has occurred, presumably representing a mixed population of infarcted and cytotoxic cells. ⁵

If conventional T2*-weighted EPI images are acquired every second for 40 seconds following an injection of gadolinium, perfusion information can be obtained for the entire brain. ¹⁰ As the bolus of paramagnetic gadolinium passes through the capillary circulation, it causes a temporary drop in signal intensity due to T2*-shortening from magnetic susceptibility effects. (When it is inside a magnetic field, the gadolinium in the capillary gets more magnetized than the adjacent nonparamagnetic tissues, leading to magnetic nonuniformity, T2*-shortening, and signal loss.) If this signal loss is plotted over time, information regarding the blood supply to a particular part of the brain can be determined, including the relative cerebral blood volume (rCBV) and the mean transit time (MTT). ⁸ The calculated rCBV and MTT values for each voxel in the brain can then be presented as maps of brain anatomy illustrating these two characteristics of brain perfusion. ¹⁰

MTT perfusion scans (figure 3D) tend to be positive at milder levels of vascular compromise than diffusion scans. The mismatch between the two abnormalities--the so-called "ischemic penumbra", ⁷ --is an indicator of the brain at risk for extension of the initial infarction (figure 3E). This is the target area for many of the new "neuroprotective" agents being developed. These drugs are designed to protect the brain after the initial insult has occurred and to limit further damage. However, recent studies have indicated that administering thrombolytic agents intra-arterially (IA) within the first three hours of stroke may still lead to hemorrhage if the rCBV is reduced by more than two-thirds of the normal level. ¹¹ On the other hand, IA thrombolysis can be performed as late as 10 hours post-ictus if the rCBV is at greater than half the normal level. ¹¹ Thus, it is quite likely that EPI diffusion and perfusion imaging will be used more and more in the future to guide stroke therapy.

Using EPI techniques, four categories of ischemia can be distinguished: 1) reversible ischemia (cytotoxic edema) not requiring further treatment; 2) completed infarction without immediate risk of extension (no ischemic penumbra); 3) completed infarction with likely extension (ischemic penumbra present); and 4) completed infarction with increased chance of bleeding with thrombolysis (markedly reduced rCBV due to poor collaterals).

MR angiography

Having made the initial diagnosis of a transient ischemic attack (TIA) or early infarct, the diagnostic work-up is then directed towards the cause (i.e., a flow-limiting carotid stenosis, or a source
of emboli). Unlike its catheter-based cousin, conventional MR angiography is noninvasive. In approximately 15 minutes, most of the common and internal carotid artery can be examined (figure 4A). Many centers are now combining two noninvasive techniques, MRA and duplex Doppler ultrasound, to evaluate the carotid arteries in the setting of stroke or TIA symptoms. ¹² If both indicate a 70% or greater stenosis, then an endarterectomy can be performed without the need for a catheter study (catheter studies are now used only when there is a discrepancy between the ultrasound and MR angiographic results).

At our hospital, stroke is still worked up with an initial CT scan (to exclude hemorrhage) and a duplex Doppler ultrasound. Following that, MR angiography of the carotids is performed, as well as MR imaging of the brain with EPI diffusion imaging to confirm the clinical diagnosis of infarction. If a flow-limiting stenosis is not identified in the carotid, intracranial MRA is performed to examine the circle of Willis and its major branches. This takes about 10 minutes with conventional MR technology.

With the recent gradient advances which led to clinical echo planar imaging, faster imaging of the carotid arteries can now be performed. For example, it is now possible to scan both carotid arteries from origin to siphon in 10 seconds (figure 4B). ¹³ These contrast-enhanced first-pass MR angiographic (CE MRA) techniques are not only faster, they also are much more accurate in sizing stenoses than conventional MRA. In addition, the carotid and vertebral origins and the carotid siphons are able to be visualized 90% of the time. The estimated degree of stenosis is always within 10% of that measured by catheter angiography for CE MRA, compared to 50% of the time for conventional MRA. Thus it seems likely that in the future contrast enhanced MRA will be the only imaging test required to evaluate the carotid arteries in the setting of stroke or TIA.

Hemorrhage

Fifteen percent of strokes are due to hemorrhage from ruptured aneurysms, AVMs (figure 5), or tumors. In the imaging of hemorrhage, MRI offers two advantages: 1) it can be detected quickly, and 2) the time between the bleeding episode and scanning can be assessed fairly accurately. While a complete discussion of the MR appearance of hemorrhage is beyond the scope of this article, suffice it to say that five stages of hemorrhage can be distinguished (table 1) based on the MR appearance on T1- and T2-weighted images. ^14,15

Recently it has been shown that both parenchymal hematomas and subarachnoid hemorrhage can be diagnosed immediately by MRI. On T2-weighted MR images, hyperacute hematomas are surrounded by a low intensity border. ¹⁶ This is due to the formation of short T2 paramagnetic deoxyhemoglobin at the interface between the hematoma and the normally metabolizing brain. Hyperacute subarachnoid hemorrhage also
can be diagnosed immediately using FLAIR. ¹⁷ Because the nulling of CSF ¹⁸ is based on its long T1, and because its T1 decreases immediately due to the protein content of the serum, subarachnoid hemorrhage (SAH) can be diagnosed within seconds using this technique. Thus, MRI can be used instead of CT for the detection of hemorrhage in the acute stroke patient.

Conclusion

In patients presenting with acute stroke, it is likely that there will only be time to perform one diagnostic imaging study in order to attempt to reverse ischemic injury. Current protocols for intravenous tissue plasminogen activator (t-PA) require that the patient be treated within three hours of observed onset of symptoms. As CT generally is only used to diagnose hemorrhage, it is quite likely that it will be replaced by MRI, which can accurately diagnose both hemorrhage and ischemia. In addition, MRI diffusion and perfusion sequences are likely to guide not only thrombolytic therapy but also the newer neuroprotective agents as they are introduced over the next few years.

In addition to giving a clear picture of the physiology of acute ischemia in the brain, MRI can noninvasively depict patency of the carotid arteries and intracranial circulation within a few minutes. In fact, the entire MRI stroke protocol takes 20 minutes or less. Clearly, there will be an increasing tendency for newer, EPI-capable MRI units to be sited near emergency departments to assist in the management of stroke. AR