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. Author manuscript; available in PMC: 2021 Jul 1.
Published in final edited form as: Clin Neurol Neurosurg. 2020 Mar 19;194:105797. doi: 10.1016/j.clineuro.2020.105797

Mismatch between automated CTP and ASPECTS score in patients with anterior large vessel occlusion

James E Siegler 1, Andrew Olsen 1, Jon Rosenberg 1, Daniel Cristancho 1, Johannes Pulst-Korenberg 1, Lindsay Raab 1, John H Woo 2, Steven R Messé 1
PMCID: PMC7292739  NIHMSID: NIHMS1580756  PMID: 32222652

Abstract

Objectives:

To evaluate the relationship between delay to computed tomography perfusion and estimated core infarct volumes in patients with large vessel occlusion (LVO).

Patients and Methods:

A retrospective registry of consecutive adults >18 years old who underwent CTP in clinical practice for suspected LVO within 24h of LKN at 3 academic hospitals was queried (06/2017 – 12/2017). CT and CTP findings were compared over time as a continuous variable, and dichotomized by ≤6hr or 6–24hr from LKN.

Results:

Of 410 screened patients, 75 had LVO, of whom 60 (14.6%) met inclusion criteria (median age 78y [IQR 64–84], 36 were female [60%]), and 39 (65.0%) underwent thrombectomy. Thirty (50%) presented in the extended window (6–24hr) and had lower ASPECTS scores compared to patients in the early window (median 7 vs. 9, p<0.01). Perfusion core (rCBF <30%) volumes were similar (median 8 vs. 25, p=0.10). After adjustment for age, NIHSS, and thrombolysis, there was a trend for lower ASPECTS for every hour after LKN (proportional OR 0.92, 95%CI 0.84–1.00, p=0.06), but no change in perfusion core (p=0.37) or Tmax>6s volumes (p=0.29), or mismatch ratios (p=0.48) after adjusting for age, NIHSS, ASPECTS, and thrombolysis.

Conclusion:

As time progresses in anterior LVO, the unenhanced CT is more sensitive than CTP for detecting irreversibly damaged tissue. These results underscore the importance of carefully reviewing the unenhanced and perfusion CT when considering a patient for thrombectomy.

Keywords: CT scan, Perfusion imaging, Acute stroke, Penumbra, ASPECTS, Thrombectomy

INTRODUCTION

Perfusion-weighted imaging has been demonstrated to reliably identify ischemic brain tissue in patients experiencing acute clinical stroke symptoms, even when unenhanced head computed tomography (CT) appears normal.[1] CT perfusion (CTP) has now been recommended as a clinical tool for estimating brain regions with high probability of irreversible infarction (ischemic core), and areas at risk of infarction (penumbra). Identifying a significant difference in these two volumes has been proven effective in clinical decision making for acute stroke with large vessel occlusion (LVO). Recently, the DAWN[2] and DEFUSE-3[3] trials showed that automated magnetic resonance imaging (MRI) and CT perfusion (CTP) post-processing algorithms using RAPID software (IschemaVIEW, Redwood, CA) can select patients who are likely to benefit from thrombectomy up to 24 hours after the time they were last known normal.

With the extension of the time window for treatment of acute LVO up to 24 hours, more centers are expected to incorporate perfusion imaging into their clinical practice[4] with a concomitant increase in number of treated patients.[5] However, it remains unclear how inexperienced centers will incorporate this tool in their medical decision making. This is likely of greatest concern for centers that do not themselves perform thrombectomy, but plan to use perfusion imaging to determine who should be transferred to centers that do. While there is proven utility of automated perfusion mapping for patients with LVO in the rigorous confines of a trial environment, data are controversial as to whether automated volumetric measurements accurately capture irreversibly infarcted tissue in patients seen in routine clinical practice.[6–9] Further, while there is robust evidence that time from symptom onset is associated with progression of infarction, it is unclear how this evolution manifests on CTP.

In the present investigation, we sought to determine how the unenhanced head CT and automated CT perfusion mismatch ratios change over time in a consecutive cohort of patients with acute anterior LVO. We hypothesized that as the time from symptom onset progresses, there would be a decline in the ASPECTS score and a growth in the perfusion core volume as at-risk tissue progresses to infarction.

MATERIALS AND METHODS

Patient selection

A retrospective registry of consecutively evaluated patients over 18 years of age who underwent CTP at 3 academic hospitals in urban Philadelphia was queried (06/01/2017 – 12/31/2017). Patient-level data were abstracted from the electronic medical record with support from the Penn Data Analytics Center. The standard imaging protocol for any patient who presents with sudden focal neurologic deficits concerning for stroke within 24 hours of last normal, or if symptom onset was unknown, includes an unenhanced head CT scan, CT angiogram of the head and neck, and CTP using RAPID.

Patients with acute LVO of the anterior circulation (ICA-terminus, A1, M1, or M2) were included in this analysis. Diagnosis of LVO was confirmed by CTA of the head, which was acquired in conjunction with the unenhanced CT and CTP. Patients were excluded if LVO was thought to be chronic (on the basis of known history of prior LVO, or if it was clinically asymptomatic) as determined by the treating physician, if there were multiple intracranial LVOs, if the patient had an unknown time last seen normal, or if time last seen normal was more than 24 hours prior to CTP acquisition. Patients were not excluded from this analysis on the basis of CT ASPECTS score or the decision to treat or not treat with endovascular thrombectomy. This study was approved by the local Institutional Review Board with waiver of informed consent.

Imaging

Imaging protocols were similar across study sites (see Online Only Supplement). At each site, unenhanced head CT scans were performed on a fourth-generation CT scanner with 5-mm thickness for the entire examination. Conventional brain windows were used. Perfusion CT images were acquired following CT angiography of the head and neck. At all sites, per our institutional protocol, iodinated contrast (100mL Isovue-370) is divided into 2 equivalent doses and administered intravenously through a 20-gauge (or larger) right antecubital catheter, separated by 2-minute intervals. CTP studies were postprocessed using RAPID software to generate automated, operator-independent, motion-corrected, deconvolution-based maps of the ischemic core and hypoperfusion, as in recently published clinical trials.[2, 3, 10, 11] Relative cerebral blood flow (rCBF), cerebral blood volume (CBV), and time-to-maximum of the tissue residue function (Tmax) were calculated and compared to the respective regions of the contralateral hemisphere. RAPID automatically segments and calculates volumes of the ischemic core (rCBF<30%) and of hypoperfusion (Tmax>6s), based on consensus recommendations.[12]

Each unenhanced CT was read by a vascular neurology fellow (JS) after having reviewed the patient’s clinical symptoms as documented in the initial patient encounter. The reader had 5 years of experience with the Alberta Stroke Program Early CT Scale (ASPECTS) score,[13] and calculated it based on anticipated location of cerebral infarction. For patients transferred from an outside institution prior to CTP acquisition, the unenhanced CT that was acquired with the CTP was used to determine the ASPECTS. Each patient’s quantitated perfusion core (rCBF <30%) and hypoperfusion (Tmax>6s) volumes were recorded by separate readers (AO, JR, DC, JPK, or LR). Unenhanced brain magnetic resonance imaging (MRI) was interpreted by an experienced neuroradiologist who was informed of the patient’s clinical symptoms and all prior neuroimaging. Presence of infarction was defined by hyperintensity on diffusion-weighted imaging (DWI) brightness with reduction in the apparent diffusion coefficient and absence of T2 shine-through.

Statistical analysis

The primary independent variable was the time between the patient was last known normal (LKN) and CTP acquisition. Time of symptom onset was recorded as the time LKN when symptoms were witnessed, and is reported in subgroup analyses. Descriptive statistics were used to compare patients based on the timing of image acquisition (≤6h from LKN [“early window”] vs. 6–24h after LKN [“extended window”]). Categorical data were presented as proportions, and continuous data were reported as medians with interquartile range. Normality of data was assessed histographically and confirmed using the Shapiro-Wilk test. The primary outcomes of interest were the ASPECTS score and perfusion core volume. The Pearson correlation coefficient was used to determine a relationship between ASPECTS score and rCBF<30% volume. Secondary pre-specified outcome measures included the absolute mismatch ratio (defined as the volume of hypoperfused tissue [Tmax>6s] divided by the volume of ischemic core [rCBF<30%]), a “favorable mismatch” ratio (mismatch ratio >1.8), and hypoperfusion (Tmax>6s) volumes using RAPID software. Between-group comparisons were made using Chi-square or Fisher’s exact test for categorical variables (when contingency table cell counts were <5), or the Wilcoxon Rank-Sum test, where appropriate. Crude and adjusted logistic and linear regression analyses were performed to correlate independent variables with outcomes of interest. Adjustments were made for age, stroke severity, and ASPECTS score, unless otherwise indicated. IV tPA was also included in multivariable models since transferred patients may have received IV tPA prior to CT and CTP acquisition. Ordered logistic regression was used to generate a proportional odds model for the decline in ASPECTS score over time (grouped by scores 1–5, 6, 7, 8, 9, and 10, due to the small number of patients with ASPECTS <6). This was adjusted for age, baseline NIHSS, and thrombolysis. Similar analyses were performed based on location of LVO (ICA, M1, and M2-only 1 patient had an A1 occlusion so this subgroup was not assessed). The proportional odds assumption was met for this model (p=0.93). No adjustments were made for multiple comparisons as all analyses were exploratory. All tests were performed at the two-sided level using STATA 15.0 (College Station, TX), and p-values <0.05 were considered statistically significant.

RESULTS

Of the 410 patients who underwent CTP, 75 (18.3%) had an acute LVO. Of these, 4 were excluded due to multi-focal, non-tandem LVOs, 7 due to CTP acquired beyond 24h of LKN, and 5 due to occlusion of the basilar or vertebral arteries (1 patient met 2 exclusion criteria), leaving 60 (14.6%) patients available for analysis. The median age was 78 years (IQR 64–84), 36 (60.0%) were female, and 25 (41.7%) were White. The median time from LKN to CTP among all patients was 6.2 hours (IQR 3.8 – 12.8 hours). Thirty patients (50%) had witnessed symptom onset, of whom 26 (86.7%) underwent CTP within 6 hours of time LKN. Seventeen patients (28.3%) received IV tPA, and 39 (65.0%) underwent thrombectomy. See Supplementary Table 1 for the clinical rationales provided for patients who did not undergo thrombectomy. Clinical and demographic factors, including the distribution of LVO locations, were similar between patients who presented within 6 hours and those who presented 6–24 hours after LKN besides the findings that IV tPA was given more frequently in the ≤6-hour group (see Table 1).

Table 1.

Demographic characteristics.

Time to CTP ≤6hr (n=30) CTP 6–24hr (n=30) p-value
Age, median (IQR) 78.5 (62–83) 75.5 (67–85) 0.33
Sex, no. female (%) 16 (53.3%) 20 (66.7%) 0.29
Ethnicity, no. (%) 0.55
 Black 12 (40.0%) 7 (23.3%)
 Caucasian 12 (40.0%) 13 (43.3%)
 Asian 1 (3.3%) 1 (3.3%)
 Other/Unknown 5 (16.7%) 9 (30.0%)
Baseline NIHSS, median (IQR) 17 (13–22) 15.5 (8–24) 0.52
LVO location, no. (%) 0.50
 ICA-T 12 (40.0%) 8 (26.7%)
 M1 12 (40.0%) 16 (53.3%)
 M2 8 (26.7%) 7 (23.3%)
 A1 1 (3.3%) 0 (0.0%)
Tandem LVO, no. (%) 2 (6.7%) 1 (3.3%) 1
ASPECTS, median (IQR) 9 (7–9) 7 (5–8) <0.01
MRI brain within 48hrs, no. (%) 8 (26.7%) 9 (30.0%) 1
Treatment with IV tPA, no. (%) 16 (53.3%) 1 (3.3%) <0.01
Endovascular thrombectomy attempted, no. (%) 21 (70.0%) 18 (60.0%) 0.42
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CTP denotes computed tomography perfusion, IQR interquartile range, LKN last known normal, NIHSS National Institutes of Health Stroke Scale, LVO large vessel occlusion, ASPECTS Alberta Stroke Program Early CT Scale score, MRI magnetic resonance imaging, IV tPA intravenous tissue plasminogen activator.

Overall, the median mismatch ratio was 3.7 (IQR 2.2–9.1), and median hypoperfusion volume was 104cc (IQR 53–155). Twenty-one patients (35.0%, 95%CI 23.1–48.4%) had a rCBF<30% volume of 0cc. There was a mild correlation between the ASPECTS score and rCBF<30% (R=−0.331, p=0.01). However, the ASPECTS scores for the 21 patients with a normal rCBF<30% included 17 patients (81.0%) already showing early infarct signs on the unenhanced CT (Supplementary Table 2).

Compared to patients who presented within 6 hours, those who presented in the extended window had significantly worse ASPECTS scores (median score 7 vs. 9, p<0.01). In contrast, the perfusion core volumes were not different (median 8cc vs. 25cc, p=0.10; Table 2). Considering time as a continuous variable, the ASPECTS score worsened for every hour after LKN (proportional OR 0.91, 95%CI 0.85–0.98, p=0.02), while the perfusion core volume did not change significantly (β=−1.27 cc/hour, 95%CI −2.83 – 0.28, p=0.11). After adjustment for patient age, stroke severity, and IV tPA use, there was a trend for the ASPECTS to decline as time from LKN progressed (proportional OR 0.92, 95%CI 0.84–1.00, p=0.06; See Figure 1a for linear regression). This relationship was driven by patients whose symptom onset was witnessed. Among patients with witnessed symptom onset, after adjusting for age, NIHSS, and IV tPA use, the ASPECTS declined as time from LKN progressed (proportional OR 0.77, 95%CI 0.62–0.95, p=0.02) while there was no association among patients whose symptom onset was unwitnessed (proportional OR 1.00, 95%CI 0.88–1.13, p=1.00; Figure 1b).

Table 2.

Primary and secondary outcome measures.

Time to CTP ≤6hr (n=30) CTP 6–24hr (n=30) p-value
ASPECTS, median (IQR) 9 (7–9) 7 (5–8) <0.01
rCBF (<30%) volume, median cc (IQR) 25 (0–57) 8 (0–21) 0.10
Mismatch ratio, median (IQR) 3.50 (2.34–7.7) 4.57 (2.04–9.08) 0.78
 Proportion with favorable mismatch* 27 (90.0%)** 24 (80.0%) 0.47
Abnormal rCBF (<30%), no. (%) 22 (73.3%) 17 (56.7%) 0.18
Abnormal Tmax (>6s) volume, no. (%) 30 (100.0%) 27 (90.0%) 0.24
Tmax (>6s) volume, median cc (IQR) 110 (77–169) 98 (32–129) 0.36
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*

Favorable mismatch ratio defined as mismatch ratio >1.8.

**

Two patients with acute LVO had rCBF <30% & Tmax >6s volumes = 0cc, therefore ratios were not classified as “favorable”.

CTP denotes computed tomography perfusion, Tmax time-to-peak residue function >6s, rCBF regional cerebral blood flow, IQR interquartile range, and cc cubic centimeter.

Figure 1.

Figure 1.

Figure 1.

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Change in ASPECTS score over time. A) Longer delay from last known normal to CTP was associated with a lower ASPECTS score (ß= −2.42, 95%CI −4.54 - −0.39, p=0.021), and this trend persisted after adjustment for age, National Institutes of Health Stroke Scale and thrombolysis (ß= −2.38, 95%CI −4.83 – 0.06, p=0.056*). B) The relationship between ASPECTS and time was driven largely by patients whose symptoms were witnessed (n=30/60; unadjusted ß=−4.54, 95%CI −7.82 - −1.26, p=0.008; adjusted ß=−5.18, 95%CI −9.14 - −1.23, p=0.012*). There was no significant change in ASPECTS over time among patients with unwitnessed symptom onset in adjusted linear regression (p=0.795*).

ASPECTS denotes Alberta Stroke Program Early Computed Tomography Scale, LVO large vessel occlusion, and CTP computed tomography perfusion.

There was no significant change in hypoperfusion (Tmax>6s) volume or mismatch ratio over time from LKN among included patients (β=−0.05, 95%CI −0.12 – 0.01, p=0.09, and β= −0.06/hr, 95%CI −0.39 – 0.27, p=0.72, respectively; Figure 2). These findings remained unchanged after adjustment for age, NIHSS, ASPECTS, and IV tPA (p=0.37 for core volume, and p=0.22 for hypoperfusion volume). Among patients whose symptom onset was witnessed, there also was no significant relationship between time and perfusion core or hypoperfusion volumes (adjusted p=0.85 and 0.29, respectively).

Figure 2.

Figure 2.

Figure 2.

Figure 2.

Figure 2.

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Change in perfusion abnormalities over time. Patients with unwitnessed onset (red circles) are shown alongside those with witnessed onset (navy dots) of symptoms, with fitted lines in red (solid) and navy (dashed), respectively. For each model, there was no association between time from LKN to CTP in univariable or multivariable regression after adjustment for age, baseline NIHSS, ASPECTS score, and thrombolysis. P-values shown refer to adjusted linear regression models. LVO denotes large vessel occlusion, LKN last known normal, CTP computed tomography perfusion, NIHSS National Institutes of Health Stroke Scale, ASPECTS Alberta Stroke Program Early Computed Tomography Score, and IV tPA intravenous tissue plasminogen activator.

In subgroup analyses based on occlusion location, patients with an ICA occlusions who presented in the extended window had significantly lower ASPECTS (median 6.5 vs. 9, p=0.01; proportional OR 0.04, 95%CI 0.003–0.66, p=0.02), whereas patients with M1 or M2 occlusions only showed a trend for a lower ASPECTS in the extended window (median 7.5 vs. 9, p=0.10; and 7 vs. 9, p=0.13, respectively). After adjustment for age, NIHSS, and treatment with IV tPA, presentation in the extended window with an ICA occlusion remained associated with a lower ASPECTS score (proportional OR 0.04, 95%CI 0.003–0.66, p=0.02). A similar shift in ASPECTS was observed in patients with M2 occlusions (adjusted proportional OR 0.05, 95%CI 0.004–0.72, p=0.03), however there was no significant association between ASPECTS and presentation in the extended window among patients with M1 occlusions. The rCBF volumes were not significantly different among patients who presented in the early versus late window regardless of LVO location, and these relationships remained non-significant after multivariable adjustment.

DISCUSSION

In this multi-center retrospective cohort study of consecutively evaluated patients with anterior LVO, there was no significant change in perfusion mismatch profiles among patients who presented later after LKN. The odds of a favorable mismatch ratio, as defined by DEFUSE 3 (>1.8),[3] also did not decline significantly as time progressed from LKN. Although we found no significant difference in the ASPECTS between patients who presented in the early or late window, there was a significant decay in the ASPECTS score for every hour from LKN, which we interpreted as extension of irreversibly infarcting tissue. Similarly, ASPECTS scores decayed significantly when two of the three LVO locations (ICA and M2) were considered independently. (The lack of a significant relationship among M1s and time to CTP may reflect the underpowered nature of the study.) This infarct growth was not detected on the automated rCBF<30% map on CTP, suggesting perfusion core volumes are fairly constant in acute-to-subacute LVO. In fact, the rCBF<30% volumes appeared to lessen among patients who were imaged at a later time-and still the ASPECTS appeared worse with time. We believe these data suggest that estimates of cerebral perfusion, such as rCBF and Tmax, may be relatively static in acute-to-subacute LVO, as they reflect a stable state of hypoperfusion. Over time, subcritical oligemia progresses to ischemia and growth of irreversibly injured tissue, which is better demonstrated in the decay in the ASPECTS.

While it is possible that these data demonstrate that ASPECTS underestimates core infarct early on and is merely “catching up” with perfusion core volumes over time, we identified 81% of patients with perfusion core volumes of 0cc who had readily apparent infarct using ASPECTS. In patients with significant, established infarction on head CT, a normal rCBF volume on RAPID may have been explained by reperfusion following infarction. However, this seems unlikely given that only patients with intracranial LVO at the time of CTP were included. Alternatively, a normal rCBF may have been the consequence of robust collaterals, and perhaps a higher rCBF threshold would have been required to capture “core” infarction. As shown in the single-center cohort by Payabvash et al, regions like the deep grey nuclei, insula and anterior frontal lobe may be more vulnerable to oligemia than some of the remaining cortical surfaces.[14] Therefore, a more liberal threshold for rCBF (above the 30% cutoff used by RAPID) may be more sensitive for detecting infarct than the generalized <30% threshold.

Our results corroborate prior findings from several cohorts. One study of 144 patients who underwent CTP within 6 hours of LKN (“early window”) reported the rCBF <30% volume did not change significantly over time (p=0.7).[15] In another study of 332 patients who underwent thrombectomy for anterior LVO in the extended window (median time to groin puncture 5.8h [IQR 3.9–8.8h]), the investigators reported that ASPECTS correlated with rCBF within 4.5 hours and beyond 4.5 hours, but they did not provide a linear regression over time.[16] This cohort was also distinct from ours as all patients underwent thrombectomy, and this may have inaccurately captured how perfusion abnormalities change over time in patients with LVO. Further, they did not categorize patients by whether symptom onset was witnessed. Our results add to these prior studies by confirming a stable perfusion core volume in the extended window up to 24 hours.

While our data suggest that rCBF<30% may underestimate real-time infarct volume in patients with anterior LVO who present in the extended window, prior investigations have suggested that perfusion core measurements may overestimate final core infarct volume if thrombectomy is achieved.[17, 18] These studies were limited to patients who presented acutely after symptom onset (within 6 hours) and had favorable ASPECTS scores. We do not believe our results are incongruent with these earlier data since our study involved a wider range of ASPECTS scores and a longer window from LKN to CTP. Furthermore, we did not assess final infarct volume using quantitative neuroimaging. Worth noting is that patients with large volumes of rCBF<30% (irrespective of ASPECTS) are at a high risk of rapid progression and low probability of a good functional outcome with thrombectomy, as has been shown in a recently published, multi-center non-randomized observational cohort.[19, 20] While these data from the SELECT trial are non-randomized, and the proportion of patients with large cores is small, they emphasize the utility of this metric when large regions of critical hypoperfusion are identified.

Limitations

While the unenhanced CT ASPECTS score was used to estimate volume of irreversible tissue injury, it is not a precise tool for quantitative measurements. However, hypoattenuation on unenhanced CT-a finding captured in the ASPECTS-strongly correlates with DWI lesion volume on MRI.[21] Therefore, in the acute setting when MRI may not be available, the ASPECTS was chosen in this study as an acceptable surrogate.

It is possible that the present study was underpowered to detect a clinically important increase in core and hypoperfusion volumes over time. That said, the relationship between core and hypoperfusion volumes over time was not significant in our adjusted analyses (p=0.37 and 0.22, respectively), and the point estimates suggest an inverse relationship between these volumes and time (meaning smaller volumes of injury with longer delay from LKN). Furthermore, these findings have been validated in a recent, multi-center, prospective observational cohort of 177 patients with anterior LVO-in which our site participated, and to which we submitted unique data.[22] While neither the rCBF nor the Tmax volumes reached our a priori threshold of statistical significance, both of these volumes trended in the direction of a smaller volume (while infarct volume on ASPECTS grows). Furthermore, it is important to note that we did see a clear relationship with ASPECTS over time-even within small subgroups based on LVO location, although this did not achieve statistical significance. These results are suggestive, although not conclusive-that the unenhanced CT may be more sensitive than an rCBF threshold of <30% for identifying infarcting tissue as time from symptom onset progresses. There is emerging evidence that alternative thresholds for rCBF may be more sensitive for predicting final infarct volume based on timing of presentation and recanalization strategy.[8, 17] However, we did not collect data on these other thresholds in this investigation. Determination of the ASPECTS score may have been biased by the knowledge of the patient’s presenting symptoms and clinical history (especially the delay to image acquisition), possibly leading to poorer ASPECTS scores in the extended window. Our results may also have been influenced by the fact that only 4 patients who presented 6–24 hours after LKN had witnessed symptom onset, and some patients who present in the extended window may have suffered from a more recent occlusion. For these reasons, time was also analyzed as a continuous variable, and patients were categorized into subgroups according to whether symptom onset was witnessed. Among patients with witnessed stroke symptoms, there was a robust and significant worsening in early CT findings over time, but there was no appreciable change in perfusion core volume, hypoperfusion volume, or mismatch profiles whether the stroke onset was witnessed or not.

The imaging studies presented here were also obtained at single points in time, without serial scans to confirm evolution of perfusion parameters or final infarct volume, which may have been better estimated using MRI FLAIR 24 hours or later after symptom onset. Only a third of patients underwent MRI, so volumetric analysis was not performed. Finally, it is important to note that the ASPECTS score does not directly relate to absolute volume of infarcted tissue, in part due to overemphasis of striatocapsular regions.[23, 24] Even so, lower ASPECTS scores correlate with larger volumes of infarcted tissue[25, 26] and serve as an acceptable surrogate for irreversible injury.[27] Our results should be interpreted with caution as we provide no outcome data, but this also warrants further exploration.

CONCLUSIONS

In this cohort, increasing time from LKN in anterior LVO was associated with poorer ASPECTS scores on unenhanced head CT-and presumably greater infarct burden-but not a worsening of perfusion core volume or mismatch profile. Given that recanalization may fail to benefit (or even harm) patients whose core infarction is too great[28] or who have minimal salvageable penumbra,[29] our findings reinforce the practice of reviewing the unenhanced CT in addition to the CTA and CTP for patients being considered for acute stroke interventions. A normal or low rCBF <30% volume alone is insufficient to justify the decision to proceed with thrombectomy in a patient who presents in the extended window. Further, our results should discourage providers from relying solely on automated CTP output in patients who present in the extended treatment window because CTP is complementary to the unenhanced CT and provides unique estimates of infarcted tissue. Ongoing and planned trials such as IN EXTREMIS may answer the question of whether patients with unfavorable ASPECTS (<6) in the extended window derive some benefit from thrombectomy, and which neuroimaging markers (e.g., rCBF volume or ASPECTS) more strongly correlate with long-term functional outcomes.

Supplementary Material

1

ACKNOWLEDGEMENTS

We would like to thank the Penn Data Store for their assistance in assembling the information used in this study.

SOURCES OF FUNDING

JS was supported by a StrokeNet U10 grant (National Institutes of Health NS086474). All authors report no competing financial interests exist.

Footnotes

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