Intraarterial Signal on Fluid-attenuated Inversion Recovery Images: A Measure of Hemodynamic Stress?
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* Ronald L. Wolf

Since its introduction in 1992 (1), fluid-attenuated inversion recovery (FLAIR) sequences have become a routine part of standard imaging protocols. An inversion pulse is used with long TR and TE to create heavy T2 weighting with CSF nulling, providing improved contrast adjacent to CSF and brain interfaces (2). Dependence on longitudinal relaxation provides another source of contrast, which several authors have exploited to study abnormalities in the CSF itself. For example, increased protein content and subarachnoid hemorrhage have been shown to be detectable using FLAIR sequences (3–5).

More recently, investigators have noted increased intensity in cerebral blood vessels in the setting of acute ischemia (6, 7). The presence of hyperintense vessels on FLAIR images is thought to indicate the presence of slow flow or stasis in small arteries, veins, and collateral vessels. The mechanism of increased intravascular signal on FLAIR images is most likely due to a combination of slow flow (with resultant decreased intravoxel phase dispersion and time-of-flight effects), flow-related enhancement (slow, but not static flow), and T1 shortening in some cases (development of methemoglobin).

The hyperintense vessel signal (HVS) in FLAIR imaging is analogous to the finding of intravascular enhancement (IE) in the setting of acute stroke, described by several investigators (8–11). In the case of IE, the bright vessels are also due to a combination of slow flow, flow-related enhancement, and perhaps T1 shortening attributable to methemoglobin; however, the presence of an intraluminal T1 shortening substance (eg, gadolinium chelate) also contributes. Correlation with angiography suggested that IE was associated with angiographic slowing. Mueller et al (10) found that 64% of patients showing IE had significant symptoms, whereas those patients without IE had mild or no symptoms. Associations with cerebrovascular occlusive disease have also been reported in which patients are asymptomatic. Essig et al (11) found that IE was present in 59% of patients with acute (within 48 hours) infarct, correlating positively with extent of infarction; but IE was also present in 65% of patients with high-grade stenosis or occlusion of one or both carotid arteries who were asymptomatic at the time of the study, correlating positively with degree of carotid stenosis in this instance. They also found low vascular reactivity to carbon dioxide stimulation, and concluded that IE in such patients may indicate impaired reserve and increased risk of future infarction.

What then is the significance of IE or HVS in the acute or chronic setting? The mechanisms of IE and HVS are related, and in some ways identical. As for studies describing IE, sufficient pilot data are available to suggest that the presence of HVS on FLAIR images represents altered hemodynamics. The correlation with angiographic slowing and HVS is at least one indicator that this is probably true. In this issue of the *AJNR,* Toyoda et al (page 1021) present a retrospective study of 60 patients with hyperacute cerebral ischemia caused by major intracranial arterial occlusion. They found that HVS on FLAIR sequences was present in 58 (97%) of 60 patients in this selected population, and present in 25 (100%) of 25 patients studied within 3 hours of symptom onset. Cosnard et al (6) reported a prospective study of 53 patients who underwent MR imaging within 6 hours of onset of suspected acute stroke (6). In the 42 patients with confirmed infarct, HVS was seen in 26 (62%). Infarct volumes were larger in stroke cases with HVS on FLAIR images than in those without HVS. Kamran et al (12) found HVS in 30 (45%) of 66 MR studies obtained within 24 hours in acute stroke patients. A recent study at our institution (12) showed HVS on FLAIR images in 27 (84%) of 32 acute cerebrovascular events and in 26 (41%) of 61 studies in patients with chronic cerebrovascular disease. Perfusion was also assessed in this population by using a continuous arterial spin labeling MR perfusion method (13), which demonstrated regional hypoperfusion in 22 (69%) of 32 acute studies and 33 (54%) of 61 chronic studies. Perhaps more importantly, as many as 20% of patients with evidence of regional hypoperfusion did not show HVS in the acute setting.

For potential measures of “hemodynamic stress”, it is important to be aware of exactly what is being measured. Hyperintensity in arteries and collateral vessels may represent slow flow, but its presence might represent an adequate compensatory response to proximal stenosis or occlusion. For example, Pantano et al (14) suggest that marked IE and increased cerebral blood volume might indicate good compensatory hemodynamic response via collaterals in middle cerebral artery occlusion in the setting of acute stroke. There are limited data addressing the question of prognosis in the setting of acute infarct without HVS, although acute stroke patients without HVS tended to have smaller stroke volumes in Cosnard et al's study (6). In Kamran et al's study (7), six patients without HVS demonstrated internal carotid or middle cerebral artery occlusion but good leptomeningeal collaterals and no evidence of slow flow on angiograms. 

In Toyoda's study, perfusion “abnormalities” are reported to correspond to HVS regions. While perfusion parameters like cerebral blood volume, delayed time-to-peak, increased transit time, reduction of peak curve height, and delayed washout may reflect an abnormality, clinical relevance in the acute or chronic setting is not yet clear. For example, a proximal stenosis may cause a delay in peak signal change and a reduction in curve height, but how much of a delay signifies brain tissue at risk? Moreover, calculation of the area of HVS is semiquantitative. A grading system based on extent of HVS in the sylvian fissure and over vascular territories has been proposed (7), but the vessels evaluated are primarily over cortical surfaces, whereas areas of hypoperfusion using perfusion techniques are more directly measurable. Subcortical ischemia may not be well represented by HVS (6).

One might try instead to use a method measuring absolute CBF, determining a CBF value below which brain is at risk and below which tissue damage is not reversible. Xenon CT data suggest that recovery from decreased perfusion does not occur below 12 cc/100 g/min (15), and in some cases as low as 6 cc/100 g/min (16). MR perfusion and positron emission tomography techniques may also be used for quantitation of CBF. On the other hand, perfusion abnormalities are only part of the pathophysiology of ischemia, and assessment of other parts of the pathway such as oxygen extraction fraction may be just as important (17, 18). Metabolic disturbances can also be addressed with proton spectroscopy, where a simple measurement like the ratio of *N*-acetyl aspartate to choline may be an indicator of tissue at risk (19).

In the acute setting, the primary goal of stroke imaging is to guide treatment strategy. With this in mind, the practical significance of a sign like HVS on FLAIR needs to be examined critically. In the broadest sense, the ultimate goal is early detection of a significant mismatch in energy supply and demand, in the hopes that discovery occurs prior to development of irreversible metabolic derangements so that interventions such as thrombolysis will have maximal probability of success. Even with tests addressing different aspects of the ischemic cascade, clinical examination still plays a crucial role in the decision to treat or not to treat. With evidence that HVS or IE or both can be seen in asymptomatic chronic cerebrovascular disease, these signs may be misleading in the acute setting.

Not only is the ischemic cascade complex, but it is also a dynamic process. A combined approach will most likely be necessary, and relative serial measurements may be more practical than absolute measurements (20). Thus, instead of replacing an examination like dynamic contrast-enhanced perfusion MR imaging or predicating its performance on the presence or absence of HVS on FLAIR images, it may be helpful to combine these findings and perhaps others, such as oxygen extraction fraction. The prognostic value of signs like HVS and tests addressing hemodynamic impairment needs to be evaluated with a large prospective study in acute and chronic settings to become clinically useful.

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