MR Perfusion Imaging of Hyperacute Stroke
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* John A. Detre

Hypoperfusion is the proximate cause of all ischemic stroke, and it stands to reason that perfusion imaging should be useful in the evaluation of acute ischemic stroke. Patients presenting with neurologic symptoms on an ischemic basis should manifest regional hypoperfusion, and the distribution of observed hypoperfusion with respect to known vascular distributions should be diagnostically informative. In principle, perfusion imaging should provide the greatest sensitivity for stroke detection because hypoperfusion occurs in advance of metabolic and subsequent structural changes. Unfortunately, imaging of perfusion at high spatial resolution is challenging, and as yet no perfusion imaging method can approach the structural resolution of conventional MR. Nonetheless, over the past several decades, a variety of methods have been used to image cerebral perfusion in acute stroke. They include positron emission tomography, single-photon emission CT, xenon CT, and MR imaging with dynamic susceptibility (exogenous) contrast enhancement or arterial spin labeling (endogenous) diffusible tracer.

Information about regional perfusion obtained using these methods has contributed to our understanding of stroke pathophysiology, often in combination with metabolic information. It remains unclear which method provides the best compromise between image quality, convenience, cost, and time, and the capabilities of each technique are constantly being improved. In the case of MR, diffusion imaging provides a contrast mechanism thought to be sensitive to cytotoxic edema, a relatively early structural abnormality in brain ischemia. Diffusion contrast is simple to obtain from MR imaging, and has already been incorporated into most commercial scanning software. Perfusion MR imaging is somewhat more complicated to perform, minimally requiring dynamic scanning during contrast injection and postprocessing to produce maps reflecting hemodynamic parameters (many of which are not strictly related to classical perfusion, which is expressed in units of milliliters of blood flow per gram of tissue per unit time). For these reasons, diffusion MR has preceded perfusion MR for widespread use in stroke imaging.

Sunshine and colleagues in this issue of AJNR (page 915) find that perfusion MR imaging provides greater accuracy than does diffusion MR imaging for categorizing the vascular distribution of ischemia in patients scanned within 6 hours of ischemic onset. These findings are based on a retrospective analysis of patients presenting with acute stroke symptoms who underwent ultrafast MR scanning assessed by correlation with other clinical and imaging data that were subsequently collected. Patients showing hypoperfusion in a large vessel distribution on perfusion MR images were included. Of 62 such patients, perfusion MR imaging provided the best evidence of large artery distribution ischemia in 16 cases, with many of these patients showing no diffusion abnormality or diffusion changes in small vessel distributions. These findings support the concept that perfusion changes occur in advance of metabolic and structural changes and are also consistent with previous results showing that perfusion MR imaging correlates better with clinical severity than does diffusion MR imaging (1).

Although these findings support the general value of perfusion MR imaging in stroke assessment, the study population in Sunshine et al's article was biased toward perfusion, because patients were selected for inclusion on the basis of the presence of large artery abnormalities on perfusion MR images. Only a prospective study can truly eliminate this type of bias. Furthermore, in many cases large artery involvement was confirmed on the basis of angiographic abnormalities. However, the presence of large artery stenosis does not in and of itself necessarily indicate ischemia throughout that vascular distribution, because perfusion can be maintained by autoregulatory vasodilation and through collateral sources of blood flow. Large artery stenosis can also delay the time-to-peak susceptibility after contrast bolus, the parameter chosen as the surrogate for perfusion in this study, producing apparent hypoperfusion. Accounting for regional variations in arterial transit time and contrast-induced susceptibility effects remains a major challenge for the interpretation and quantification of dynamic susceptibility contrast perfusion MR imaging. A better understanding of pathophysiological effects on the measured parameter of time-to-peak is required for correct interpretation of dynamic susceptibility contrast studies. It is, therefore, likely that experimentally determined thresholds of ischemia made using classical perfusion methods will not translate directly to related hemodynamic measures such as time-to-peak.

Despite some methodological shortcomings, this study clearly shows that a negative diffusion-weighted MR image does not exclude the presence of clinically significant ischemia. In addition, positive findings on diffusion MR images are clearly useful in stroke evaluation (2); eg, lesions in multiple vascular distributions suggesting an embolic etiology. However, the diagnosis of acute ischemic stroke ultimately remains a clinical one. Indeed, there remains great controversy concerning the real value of diffusion imaging in acute stroke management (3), particularly because the pathophysiological basis for diffusion changes remain incompletely characterized and are not entirely specific to ischemia. Several recent reports now also describe diffusion-negative ischemic symptoms. Arguably, the absence of any imaging lesion at all should provide the greatest impetus for urgent stroke evaluation, because the opportunity for prevention is greatest in that situation.

The successful validation of intravenous thrombolytic therapy for patients presenting within several hours of ischemic onset presents more specific challenges for hyperacute stroke imaging. Intravenous thrombolytic therapy is far from universally effective, and six to eight patients must be treated for one to benefit (4). The efficacy of intravenous thrombolytic therapy could be improved through better selection of patients that might benefit and elimination of patients at risk of hemorrhagic complications. The presence of a large perfusion-diffusion mismatch currently represents a reasonable working model for selecting patients for thrombolytic therapy, perhaps even beyond the current 3-hour window. Regions with severe hypoperfusion or a particularly low apparent diffusion coefficient may potentially represent regions of early necrosis and therefore be at high risk for hemorrhage. Finally, patients with normal perfusion might be spared the risk of thrombolytic therapy, because they have presumably reperfused spontaneously and have an excellent prognosis if untreated (5). However, the utility of these imaging criteria must be carefully validated in a prospective trial. In addition, because time to thrombolysis has been shown to be a major determinant of outcome from thrombolytic therapy (6), any delays in therapy due to imaging and image processing must be factored into the equation.

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    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.1159/000016105&link_type=DOI) 
    
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    [Abstract/FREE Full Text](http://www.ajnr.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NToiYnJhaW4iO3M6NToicmVzaWQiO3M6OToiMTE5LzIvNDA5IjtzOjQ6ImF0b20iO3M6MTk6Ii9ham5yLzIyLzUvODA2LmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

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