Elsevier

Journal of Neuroradiology

Volume 41, Issue 5, December 2014, Pages 307-315
Journal of Neuroradiology

Original article
Defining acute ischemic stroke tissue pathophysiology with whole brain CT perfusion

https://doi.org/10.1016/j.neurad.2013.11.006Get rights and content

Summary

Background

This study aimed to identify and validate whole brain perfusion computed tomography (CTP) thresholds for ischemic core and salvageable penumbra in acute stroke patients and develop a probability based model to increase the accuracy of tissue pathophysiology measurements.

Methods

One hundred and eighty-three patients underwent multimodal stroke CT using a 320-slice scanner within 6 hours of acute stroke onset, followed by 24 hour MRI that included diffusion weighted imaging (DWI) and dynamic susceptibility weighted perfusion imaging (PWI). Coregistered acute CTP and 24 hour DWI was used to identify the optimum single perfusion parameter thresholds to define penumbra (in patients without reperfusion), and ischemic core (in patients with reperfusion), using a pixel based receiver operator curve analysis. Then, these results were used to develop a sigma curve fitted probability based model incorporating multiple perfusion parameter thresholds.

Results

For single perfusion thresholds, a time to peak (TTP) of +5 seconds best defined the penumbra (area under the curve, AUC 0.79 CI 0.74–0.83) while a cerebral blood flow (CBF) of < 50% best defined the acute ischemic core (AUC 0.73, CI 0.69–0.77). The probability model was more accurate at detecting the ischemic core (AUC 0.80 SD 0.75–0.83) and penumbra (0.85 SD 0.83–0.87) and was significantly closer in volume to the corresponding reference DWI (P = 0.031).

Conclusions

Whole brain CTP can accurately identify penumbra and ischemic core using similar thresholds to previously validated 16 or 64 slice CTP. Additionally, a novel probability based model was closer to defining the ischemic core and penumbra than single thresholds.

Introduction

Whilst used routinely in many centres in acute stroke patients, perfusion imaging has not yet been shown to improve patient selection for acute therapy. The only proven current role of imaging in practice is to exclude intra-cerebral haemorrhage [1], [2]. Nonetheless, the goal of acute reperfusion therapy with rtPA or intra-arterial treatments is to salvage at-risk tissue from infarction, so it is seems logical that imaging tissue at risk of infarction (penumbra) [3], as well as established ischaemia (ischemic core) [4] would guide patient treatment.

However, there are some practical issues to be resolved before perfusion imaging can be translated into routine practice [5]. Perfusion imaging with CT has the most promise because of its accessibility, but one issue has been the lack of whole brain coverage. To date, only magnetic resonance imaging (MRI) is capable of whole brain coverage, which is required to visualise the whole lesion and predict outcome based on the entire volume of ischemic core and penumbra [6], [7]. The latest multi-detector CT scanners solve this issue [8]. The other major issue to be resolved is the accuracy of detection of ischemic core and penumbra using perfusion thresholds. Previous studies have only used limited slice coverage CTP to derive core and penumbra thresholds [9].

Moreover, the previous limited slice coverage of conventional CTP studies used a single threshold approach to define core and penumbra, which is a compromise between sensitivity and specificity based on whole group data. The ‘best’ threshold in an individual may actually vary substantially from the group value. In order to address this issue, ‘probability’ models have been proposed [10] by using multiple perfusion measures to determine if a combination of perfusion thresholds may more accurately measure ischemic core and penumbra [11]. This study aimed to validate a multithreshold measure of CTP ischemic core and penumbra.

Section snippets

Patients

Patients presenting to John Hunter hospital between June 2010 and September 2012, within 6 hours of hemispheric ischemia onset were retrospectively studied. The standard protocol for all patients was acute multimodal CT using an Aquilion One 320 slice CT scanner (Toshiba, Tochigi, Japan), and a 24 hour follow-up MRI. Some patients also had an acute MRI following multimodal CT. The National Institutes of Health Stroke Scale was used to assess clinical stroke severity. Patients were treated with

Results

One hundred and eighty ischemic stroke patients were included in this study. All patients underwent whole brain acute CTP within 6 hours of symptom onset and 24 hour MRI. Thirty-three of these patients also had an acute MRI within one hour of CTP. The median age of patients was 72 (range 39–87), with a median acute NIHSS of 12 (range 4–26). The median time from symptom onset to the end of the CTP was 148 minutes. At 24 hours, 67 (%) patients had no reperfusion, 58 (%) patients had partial

Analysis A. Defining the acute perfusion lesion

In the 67 patients with no reperfusion, a TTP of +5 seconds best defined the perfusion lesion (AUC 0.79 CI 0.74-0.83) (Fig. 1). From the volumetric analysis the TTP +5 seconds lesion overestimated the DWI lesion by a mean of 7.3 cm2 (SD 9.4 cm2).

Analysis B. Defining the ischemic core with acute DWI imaging

From the 33 patients with acute concurrent CTP and MRI imaging, the acute ischemic core was best defined by a CBF of < 50% (AUC 0.75, CI, 0.71–0.79). The lesion volume analysis showed that CBF < 50%, over estimated the acute ischemic core by a mean of 4.2 

Perfusion lesion

Using the data from the AUC calculations for the single threshold analysis, the sensitivity and specificity of various measures were recorded. TTP was the single best measure to define the acute perfusion lesion, with no other perfusion measure reaching a higher sensitivity or specificity (P = 0.04). A single threshold of +5 seconds was optimal (sensitivity 0.82, sensitivity 0.67); however a threshold of +4 seconds was more sensitive (sensitivity 0.72, specificity 0.79), while a threshold of +6 was

Discussion

Whole brain CTP can be reliably used to measure the acute ischemic core and penumbra. Moreover, the novel probability model (combining TTP, MTT, and CBF thresholds) was more sensitive and specific, as well as volumetrically more accurate than the best single perfusion thresholds in defining the acute ischemic core and penumbra.

With respect to the most accurate single threshold in defining ischemic core, we found that CBF was the most accurate, consistent with recent studies, although the value

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.

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