Comments on an Article by Kamalian et al

Letters to the Editor Letters to the Editor

Published online before print April 19, 2012, doi: 10.3174/ajnr.A3153
AJNR 2012 33: E94

P. Schramma
aDepartment of Neuroradiology
University Medicine Goettingen
Goettingen, Germany

E. Klotzb
bSiemens Healthcare Sector
Forchheim, Germany

We read with great interest the article by Kamalian et al.1 The authors found, in a carefully selected patient group, that CT perfusion mean transit time maps optimally distinguished benign oligemia from true “at-risk” ischemic penumbra. They postprocessed the same dynamic CT data with 2 commercial software packages from the same vendor, containing a standard and a delay-corrected (DC) deconvolution algorithm, respectively.

For each algorithm considered separately, receiver operating characteristic (ROC) analysis yielded a significantly higher area under the curve for absolute and relative MTT than for the other CTP parameters for identification of brain tissue destined to infarct (all P values < .01). The authors also found that thresholds needed to be adapted. They reported that “absolute and relative MTT thresholds for defining penumbra were 12 seconds and 249% for the standard and 13.5 seconds and 150% for the delay-corrected algorithms, respectively.” That thresholds may vary considerably among different approaches and implementations is well known, but their results appear to have an internal discrepancy that requires clarification. Relative MTTs were calculated by normalizing the ischemic MTT to the one for the corresponding anatomy on the contralateral side. Therefore, one can reversely deduce that the average MTT of the normal brain by using the standard algorithm in their data was approximately 4.8 seconds (12/2.49 seconds); the one in the delay-corrected version, however, would have to be approximately 9 seconds (13.5/1.5 seconds). Nine seconds would be in total disagreement with basically all normal MTT values that can be found in the literature (eg, Wintermark et al2), which are more in the range of 4–6 seconds (in agreement with the results of the standard algorithm).

In addition, a DC algorithm would tend to have an even shorter MTT.3 The gross whole-brain transit time can be estimated from the peak time difference of the arterial input function and the venous outflow function. In our experience, this difference is typically between 6 and 8 seconds; tissue MTT must be shorter. Figures 3 and 4 in a recent review article coauthored by 2 of the authors of the present study clearly confirm this.4If there was no accidental misreporting of numbers, this discrepancy definitely requires an explanation and discussion.

Furthermore, the authors argue at length that DC algorithms are superior to standard ones because they are better adapted to the variable arrival times. We fully agree. Their data, however, appear to demonstrate the opposite. All areas under the curve and specificities for the standard algorithm are consistently higher than those for DC. If the next accurate parameter was CBF, as they report, and the difference between 0.76/0.78 (MTT standard) and 0.73/0.74 (CBF standard) was significant at P < .01, then clearly the difference between 0.76/0.78 (MTT standard) and 0.72/0.71 (MTT DC) will have similar or higher significance. If one were to use the authors’ reasoning about optimal performance, one could also draw the conclusion that the CBF of standard deconvolution software (CTP3 “Std,” GE Healthcare) performs better than the MTT of delay-corrected software (CTP5 “DC”; GE Healthcare). We believe this issue requires further explanation and discussion.

References

  1. Kamalian S, Kamalian S, Konstas AA, et al. CT perfusion mean transit time maps optimally distinguish benign oligemia from true “at-risk” ischemic penumbra, but thresholds vary by postprocessing technique. AJNR Am J Neuroradiol 2012; 33: 545–49 » Abstract/FREE Full Text
  2. Wintermark M, Flanders AE, Velthuis B, et al. Perfusion-CT assessment of infarct core and penumbra: receiver operating characteristic curve analysis in 130 patients suspected of acute hemispheric stroke. Stroke 2006; 37: 979–85 » Abstract/FREE Full Text
  3. Abels B, Klotz E, Tomandl BF, et al. Perfusion CT in acute ischemic stroke: a qualitative and quantitative comparison of deconvolution and maximum slope approach. AJNR Am J Neuroradiol 2010; 31: 1690–98 » Abstract/FREE Full Text
  4. Konstas AA, Wintermark M, Lev MH. CT perfusion imaging in acute stroke. Neuroimaging Clin N Am 2011; 21: 215–38, ix » CrossRefMedline

Reply

Published online before print April 19, 2012, doi: 10.3174/ajnr.A3154
AJNR 2012 33: E95

We thank Drs Schramm and Klotz for their interest in our article and this important topic.1 They are indeed correct that based on our reported delay-insensitive CTP5 software package raw data, “one can reversely deduce that the average MTT of the normal brain … would have to be approximately 9 seconds … in total disagreement with basically all normal MTT values that can be found in the literature. …”

In brief, this discrepancy is explained by the fact that the CTP5 delay-insensitive postprocessing software used for our study—as noted in our “Materials and Methods” section—was a research version that required appropriate DICOM scaling of the raw data values if these were to be used for absolute quantitation of the CTP parameters; this scaling was not automatically performed by the Analyze third-party software package (Analyze 8.1; Analyze-Direct, Mayo Clinic, Rochester, Minnesota) used for our analyses. (The CTP5 beta software was intended for research use only and has since been replaced by the now commercially available CTP 4D software [http://www.gehealthcare.com/usen/ct/products/docs/CT_Clarity_062411_pg48-49.pdf], for which this scaling factor is not an issue).

For absolute quantification of the CTP5 MTT maps, the required scaling factor is 2, meaning that the correct “reversely deduced” average MTT value derived from our results is, in fact, approximately 4.5 seconds. This value is not only in agreement with the literature but is also smaller than the 4.8 seconds derived by using the delay-sensitive (CTP3) standard algorithm and is in keeping with the expected results as outlined in Drs Schramm and Klotz’s letter. (Additionally, if we apply this scaling, our absolute quantitative delay-corrected MTT threshold for “true” ischemic penumbra becomes 6.75, rather than 13.5 seconds.)

Hence, the values we reported for MTT penumbral thresholds were specific to our postprocessing/analysis platforms and were not intended for use to “back-calculate” absolute quantitative MTT parameter values in clinically normal brain. Indeed, the most important conclusions of our article underscore this point—that the CTP threshold values reported in the literature are platform-specific, are not standardized, and hence are not necessarily generalizable to acquisition and postprocessing protocols other than those specifically under investigation (in our case, CTP3 and CTP5). Moreover, absolute quantification of CTP parameter values is highly variable and critically dependent on many factors, such as correct placement of a venous scaling region of interest and estimation of hematocrit. For these reasons, we favor the use of relative, rather than absolute, perfusion values for our clinical stroke work.

The aims of our study were the following: 1) to determine which CTP map or maps optimally distinguish benign oligemia from true “at-risk” penumbra, and 2) to confirm earlier reports suggesting that specific threshold values might vary according to the postprocessing platform used. Despite the considerations discussed above, we found—by using both the delay-sensitive and the delay-insensitive software—that both relative and absolute MTTs were the most accurate CTP maps for determining “critical” penumbra. This result was irrespective of the scaling factors required for absolute quantification or other potentially confounding technical differences between the commercial and beta versions of the software, which were outside the scope of our study (eg, the degree of image noise). In this regard, it was not our goal to compare the accuracy of the delay-sensitive-versus-delay-insensitive platforms. Had this been the case, we would have studied a more homogeneous highly selected patient cohort, all with significant proximal large-vessel occlusions (ICA and/or M1) so as to target the marked contrast arrival-time differences between regions with otherwise similar baseline cerebral blood flow.

We appreciate this opportunity to clarify our work, apologize for any confusion in the interpretation of our results, and again thank Drs Schramm and Klotz for helping to highlight these important issues.

Reference

  1. Kamalian S, Kamalian S, Konstas AA, et al. CT perfusion mean transit time maps optimally distinguish benign oligemia from true “at-risk” ischemic penumbra, but thresholds vary by postprocessing technique. AJNR Am J Neuroradiol 2012;33:545–49 » Abstract/FREE Full Text
Comments on an Article by Kamalian et al