The Four Ps of Acute Stroke Imaging: Parenchyma, Pipes, Perfusion, and Penumbra
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* Howard A. Rowley

Stroke imaging and intervention are advancing at a dramatic and welcome pace. Triage of acute stroke patients and choice of treatment are increasingly driven by advanced imaging findings. The fresh perspective of new imaging techniques like fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging help us rediscover basic principles of stroke pathophysiology. Getting back to these basics lets us analyze and reorganize the imaging approach so that each critical component in the ischemic process is assessed.

In this issue, Maeda et al (page 632) report that focal intravascular abnormalities are commonly seen on FLAIR sequences in acute stroke patients. Their 11 patients were studied by both FLAIR and diffusion-weighted images within 6 hours of symptom onset. All proved to have acute infarctions: 10 of 11 already had parenchymal changes on diffusion-weighted images at baseline, and the other case manifested similar findings a few days later. The central finding was that eight of 11 cases also showed abnormal intravascular signal on FLAIR images in the arterial territory leading to the infarcted parenchyma shown by diffusion-weighted imaging. In one case, a subtle intravascular abnormality was even seen by use of FLAIR before diffusion-weighted imaging showed positive findings. In the three cases with negative imaging findings, the vessels affected were probably too small to see. This article adds to the growing literature attesting to the value of FLAIR in the evaluation of stroke, already known to be helpful for detection of subarachnoid hemorrhage and for non-acute ischemic lesions adjacent to spinal fluid spaces (1, 2). How often this intravascular sign might be seen as a false-positive finding, such as an artifact or slow flow (but not frank ischemia), is left for future studies.

Maeda et al's undoubtledly useful observations about vascular signal changes in acute stroke should come as no surprise. Although acute imaging has traditionally focused on damage to the end organ, the brain, findings in the brain parenchyma are really the end result of a predictable chain of vascular events. When a vessel becomes occluded, and collaterals are insufficient, this leads to a perfusion defect. If the perfusion defect is of sufficient degree and duration, infarction will occur. This sequence of events leading up to brain infarction can be organized into a few critical steps, and new imaging techniques stand ready to assess each of these critical components.

One practical way to help organize and recall each of the key steps is to remember the four Ps of stroke: parenchyma, pipes, perfusion, and penumbra. Consideration and measurement of each of the four Ps, in their correct order, are necessary to understand the cause and potential treatment options for stroke in a particular patient. Comprehensive neurovascular imaging protocols using CT or MR imaging can now measure each of these 4 Ps within minutes after the patient arrives at the hospital. And each of the Ps has its own imaging story to tell.

## Parenchyma

The first task of imaging is to divide the strokes into ischemic (85%) or hemorrhagic (15%) subtypes. Distinction of hemorrhage versus infarction is the initial critical branch point in acute stroke triage, and directs care toward medical therapy or tailored intervention such as endovascular aneurysm coiling or thrombolysis. Hemorrhage is most efficiently excluded by CT, but can also be reliably assessed using MR imaging, which includes both T2*-weighted and FLAIR sequences. Parenchymal ischemic changes can be detected in most patients within several hours by either CT or routine MR (T2-weighted or FLAIR) sequences. But by far the most sensitive way to detect acute infarction is through diffusion-weighted imaging, which is able to clearly show ischemic changes beginning within minutes to a few hours after symptom onset (3). The novel tissue contrast mechanism of diffusion-weighted imaging and its “light bulb” bright signal of infarction make it a robust and reliable method for anyone on the stroke team. Diffusion-weighted imaging interpretation does not require the detailed scrutiny required of the intravascular FLAIR findings reported by Maeda et al. With increasing stroke awareness, many more patients are being seen in the first minutes to hours after stroke onset. At these time points, a positive diffusion scan usually means infarction has already occurred, but reversibility of diffusion defects has been seen in children and after thrombolysis. In the future, sodium MR imaging may give a firmer prediction of absolutely dead tissue versus likely infarcted brain.

## Pipes

Stroke begins as a vascular event on either a large or small scale, and the “pipes” of this mnemonic refer to the large arteries (or veins) ultimately causing either hemorrhage or infarction. The “pipes” seen by imaging are grossly visible vessels on the order of 0.5 mm or larger—the aortic arch, carotid and vertebral vessels of the neck, the major branches of the circle of Willis, and the proximal cortical branches. Identifying a lesion in the “pipes” has important therapeutic implications for understanding the source of thrombi or emboli, identifying sites for potential thrombolysis, and assessing gross collateral flow patterns. On CT scans, we have some indirect signs to assess disease in the “pipes”, such as the hyperdense artery sign (thrombus), and some direct methods, such as CT angiography (vessel narrowing or occlusion). MR imaging has a richer set of signs related to the “pipes”: loss or alteration of intravascular signal (flow) voids (4), stasis of gadolinium in slow-flowing territories (5), and loss of flow-related enhancement on MR angiography. Maeda et al's finding of intravascular high signal on FLAIR images is a natural extension of these well-known MR concepts—ie, lack of flow voids and presence of either intravascular thrombus or very slow flow, leading to high arterial signal.

## Perfusion

The third P, perfusion, indicates the sum total cerebral blood flow arriving at a particular brain region at a given moment in time, both via normal routes and recruited collaterals. It is not sufficient to know at what level the “pipes” are occluded: it is the individual variation in collaterals, vascular autoregulation, and resulting net perfusion that means brain survival or infarction. An internal carotid or middle cerebral artery occlusion in one patient may be an incidental finding, provided there are good collaterals; but in the next, it may lead to a devastating or fatal infarction. The difference lies in the time course of occlusion and the potential collateral pathways, not the site of vessel occlusion per se. Single-photon emission CT, xenon CT, CT perfusion, and perfusion-weighted MR imaging all offer the opportunity to noninvasively assess this component (6).

## Penumbra

The fourth P, penumbra, is ultimately the most important in ischemic stroke, and is the focus of all the preceding Ps. One working definition of the penumbra is brain tissue that is ischemic but not yet infarcted, and is therefore at risk for further damage unless flow is rapidly restored. Although present treatment methods cannot be expected to reverse infarction that has already occurred, detection of a perfusion-diffusion mismatch gives us a realistic target for potential intervention (7). The key to detection of the penumbra is not based on a single imaging feature, but by integration of all three of the preceding Ps: the site of vessel occlusion (the pipes), the extent and degree of oligemia at that moment (perfusion), and the mismatch between this perfusion defect and the brain already infarcted (parenchyma). New imaging observations such as those shown by Maeda et al help us recognize these sometimes subtle but critical signs in the four-P stroke pathway so that appropriate therapy can be undertaken.

## References

1.  Brant-Zawadzki M, Atkinson D, et al. **Fluid-attenuated inversion recovery (FLAIR) for assessment of cerebral infarction. Initial clinical experience in 50 patients.** Stroke 1996;27:1187-1191
    
    [Abstract/FREE Full Text](http://www.ajnr.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToic3Ryb2tlYWhhIjtzOjU6InJlc2lkIjtzOjk6IjI3LzcvMTE4NyI7czo0OiJhdG9tIjtzOjE5OiIvYWpuci8yMi80LzU5OS5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

2.  Noguchi K, Ogawa T, et al. **Subacute and chronic subarachnoid hemorrhage: diagnosis with fluid-attenuated inversion-recovery MR imaging.** Radiology 1997;203:257-262
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=9122404&link_type=MED&atom=%2Fajnr%2F22%2F4%2F599.atom) 
    
    [Web of Science](http://www.ajnr.org/lookup/external-ref?access_num=A1997WP24100044&link_type=ISI) 

3.  Provenzale JM, Sorensen AG. **Diffusion-weighted MR imaging in acute stroke: theoretic considerations and clinical applications.** AJR Am J Roentgenol 1999;173:1459-1467
    
    [CrossRef](http://www.ajnr.org/lookup/external-ref?access_num=10.2214/ajr.173.6.10584783&link_type=DOI) 
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=10584783&link_type=MED&atom=%2Fajnr%2F22%2F4%2F599.atom) 
    
    [Web of Science](http://www.ajnr.org/lookup/external-ref?access_num=000083818500007&link_type=ISI) 

4.  Brant-Zawadzki M. **Routine MR imaging of the internal carotid artery siphon: angiographic correlation with cervical carotid lesions.** AJR Am J Roentgenol 1990;155:359-363
    
    [PubMed](http://www.ajnr.org/lookup/external-ref?access_num=2115269&link_type=MED&atom=%2Fajnr%2F22%2F4%2F599.atom) 

5.  Yuh WT, Crain MR, et al. **MR imaging of cerebral ischemia: findings in the first 24 hours.** AJNR Am J Neuroradiol 1991;12:621-629
    
    [Abstract/FREE Full Text](http://www.ajnr.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiYWpuciI7czo1OiJyZXNpZCI7czo4OiIxMi80LzYyMSI7czo0OiJhdG9tIjtzOjE5OiIvYWpuci8yMi80LzU5OS5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

6.  Ueda T, Yuh WT, et al. **Current and future imaging of acute cerebral ischemia: assessment of tissue viability by perfusion imaging.** J Comput Assist Tomogr 1999;23: [Suppl 1] S3-S7
    
    

7.  Schlaug G, Benfield A, et al. **The ischemic penumbra: operationally defined by diffusion and perfusion MRI.** Neurology 1999;53:1528-1537
    
    [Abstract/FREE Full Text](http://www.ajnr.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToibmV1cm9sb2d5IjtzOjU6InJlc2lkIjtzOjk6IjUzLzcvMTUyOCI7czo0OiJhdG9tIjtzOjE5OiIvYWpuci8yMi80LzU5OS5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

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