Salvageable penumbra

Despite these potential issnes with absolnte thresholds, they have been applied with good resnlts in some centers - most notably for core CBV assessment [33,188-190]. Receiver operating characteristic cnrve analysis in 130 patients snspected of acnte ischemic stroke suggested that relative MTT with an optimal threshold of 145% was the CTP parameter most accurately characterizing salvageable penumbra, and absolute CBV the parameter most accurately characterizing infarct core at admission, again with an optimal threshold of 2.0 mL/100 g [187]. 

The Best Possible Perfusion Parameter to Define Salvageable Penumbra... 

Schaefer, F.W., et al., First-pass quantitative CT perfusion identifies thresholds for salvageable penumbra in acute stroke patients treated with intra-arterial therapy.jsee comment]. AJNR Am J Neuroradiol, 2006. 27(1) p. 20-5. 

Qualitative analysis of perfusion images is usually based on two assumptions that are derived from the pathophysiologic principles discussed above. First, tissue with visibly decreased CBV is so severely ischemic that it is unlikely to survive and lies within the core of the infarct. Second, tissue with decreased CBF or prolonged MTT may be mildly or severely ischemic and may or may not be salvageable. If this tissue does not appear abnormal in another, more specific type of image (such as CBV or DWI), it represents the ischemic penumbra and may potentially be rescued by immediate therapy. 

Further natural history studies supported the mismatch model of the penumbra by demonstrating that if early reperfusion of the PI lesion occurs, growth of the acute DWI lesion is inhibited. Thus, there is salvage of the mismatch region and these patients may experience substantial clinical improvement (Barber et al. 1998b). 

Of great relevance to the potential use of multimodal MRI in extending the time window for thrombolysis have been the observations that perfusion-diffusion mismatch was present for up to 24 h after symptom onset (Table 3.2). Whilst the presence and volume of mismatch decreases over time, at least 50% of patients still have significant tissue at risk 24 h after stroke onset (Fig. 3.4). This correlates well with positron emission tomography studies that show penumbral tissue persists up to 48 h after symptom onset, and that spontaneous survival of this tissue results in clinical improvement (Markus et al. 2003 Read et al. 2000). There is mounting evidence that the time window for salvage of the penumbra is well beyond 3 h and multimodal MRI can identify such patients. 

The concept of critical flow thresholds provides the rational basis for attempts to salvage the ischemic penumbra. In the clinical environment, the successful application of thrombolysis in stroke patients (NINDS Study Group 1995) could be shown to be related to this issue fair clinical outcome correlated positively with early recanalization (von Kummer et al. 1995) and even small improvements of local CBF in the 10% range predicted the reversibility of ischemic tissue changes (Butcher et al. 2003). 

Is there a penumbra of severely ischemic but potentially salvageable tissue ... 

The results of the 2008 European Cooperative Acute Stroke Study (ECASS 111) expanded the 3-h time window for IV thrombolysis and revealed that although safe and effective up to 4.5 h after stroke onset, treatment benefits roughly one-half as many patients as those treated within 3 h [2, 158, 159]. Hence, the ratio between the hemorrhagic risk of treatment and the potential clinical benefit of treatment becomes a more critical consideration as the time window for therapy is expanded with newer IV and lA techniques. It is the mismatch between the size of the infarct core (proportional to hemorrhagic risk) and the size of the ischemic penumbra (proportional to potentially salvageable tissue), as determined by CTP, that provides an imaging measure of this risk-to-benefit ratio. Evidence suggests that core/penumbra mismatch may persist up to 24 h in some patients [160,161]. 

Soares, B.P., J.D. Chien, M. Wintermark, MR and CT monitoring of recanalization, repeifusion, and penumbra salvage everything that recanalizes does not necessarily reperfuse Stroke, 2009. 40(3 Suppl) p. S24-7. 

To summarize the above discussion, the portion of an acute stroke patient s brain that appears normal in DWI images, but underperfused in PWI maps, is generally presumed to represent the ischemic penumbra, i.e., the tissue that is at risk of infarction but still potentially salvageable by reperfusion. This presumption has several implications that can be tested empirically. First, it implies that patients with a large diffusion-perfusion... 

The concept of the ischemic penumbra has proven to be an extremely valuable construct for both experimental studies of ischemic stroke and for the development of tools for the management of patients with this disorder. Indeed, a major driver in the development of treatments for ischemic stroke is the belief that in many acute stroke patients, there is a region of salvageable brain that is threatened with permanent injury. This region of brain corresponds to the ischemic penumbra originally described in experimental stroke studies. The clinical condition does not strictly meet the criteria as originally defined by experimentalists. Nonetheless, the concept is clinically valuable, and a suitable modification of its definition applicable to the clinical condition is appropriate. 

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