Response to Letters by Lee et al and Lev et al
We appreciate the comments by Lee et al and Lev et al concerning our systematic review on CBF thresholds and ischemic stroke.1
Lee et al rightly raise the issue of CBF thresholds variability attributable to the different measurement techniques used. We addressed this important problem in our review, and the different thresholds are reported in Table 2.1 We identified the “adoption of standardized CBF measurement techniques” as a major field for improvement. Only 3 studies used PET, the “de facto” reference standard. The scarcity of published studies actually precluded a meta-analysis as well as subgroup analyses, such as the type of analysis used for calculating CBF (voxel-based thresholds versus large region-of-interest analysis).
In order to allow comparison between studies, the authors of the original articles converted relative CBF measurements into absolute values by multiplying the relative measurements by a mean CBF value of 50 mL/100 g per minute. We acknowledge that this method is debatable, particularly in older people.
Lev et al cite 2 recently published articles2,3 and an older article (which we analyzed but did not include because it did not report CBF thresholds4) that propose CT perfusion as a promising tool to accurately measure CBF. As noted by the authors, our review is already dated, an inevitable destiny for research aimed at synthesizing the evidence available at a given time. However, systematic reviews can be updated regularly at little cost after the initial effort.
Concerning the potential influence of time to scan, we did not find a statistically significant correlation between time to scan and CBF thresholds, although this might be attributable to the low power of the analysis given the small number of studies. No studies reported data on time to reperfusion/recanalization, which would require repeated evaluation by means of Doppler ultrasound–related techniques, a neglected aspect even in the most recent studies.
As regards the fact that absolute perfusion CBF thresholds may vary depending on the gray-to-white ratio of the regions where they are measured, we agree with Lev and colleagues that this might help explain some of the variability of the CBF thresholds reported in our review.
Finally, we agree with both groups that CBF is not the only parameter which can (and should) be used to define brain ischemia with perfusion-imaging. Nonetheless, CBF thresholds do currently play an important role in discriminating between reversible and irreversible ischemic damage, and thus need to be carefully evaluated. Moreover, most of the methodological issues highlighted by our review would be relevant to the evaluation of thresholds for other related parameters, including cerebral blood volume and mean transit time.
Consideration of the methodological issues highlighted by our review may help not only to critically evaluate the evidence available but also to design good-quality studies which can provide strong evidence on CBF thresholds obtained with CT perfusion as well as any other diagnostic procedures.
Bandera E, Botteri M, Minelli C, Sutton A, Abrams KR, Latronico N. Cerebral blood flow threshold of ischemic penumbra and infarct core in acute ischemic stroke: a systematic review. Stroke. 2006; 37: 1334–1339.
Wintermark M, Flanders AE, Velthuis B, Meuli R, van Leeuwen M, Goldsher D, Pineda C, Serena J, van der Schaaf I, Waaijer A, Anderson J, Nesbit G, Gabriely I, Medina V, Quiles A, Pohlman S, Quist M, Schnyder P, Bogousslavsky J, Dillon WP, Pedraza S. Perfusion-CT assessment of infarct core and penumbra: receiver operating characteristic curve analysis in 130 patients suspected of acute hemispheric stroke. Stroke. 2006; 37: 979–985.
Schaefer PW, Roccatagliata L, Ledezma C, Hoh B, Schwamm LH, Koroshetz W, Gonzalez RG, Lev MH. First-pass quantitative CT perfusion identifies thresholds for salvageable penumbra in acute stroke patients treated with intra-arterial therapy. AJNR Am J Neuroradiol. 2006; 27: 20–25.
Schaefer PW, Hunter GJ, He J, Hamberg LM, Sorensen AG, Schwamm LH, Koroshetz WJ, Gonzalez RG. Predicting cerebral ischemic infarct volume with diffusion and perfusion mr imaging. AJNR Am J Neuroradiol. 2002; 23: 1785–1794.