# Flat Panel CT Scanning Is Helpful in Predicting Hemorrhagic Transformation in Acute Ischemic Stroke Patients Undergoing Endovascular Thrombectomy

Authors: Liuwei Chen; Yi Xu; Rui Shen; Jiping Sun; Xiang Zhang; Quanbin Zhang; Feng Wang
Journal: BioMed Research International
 (2021)

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## Abstract

Purpose. Hyperdense lesions are frequently revealed on flat panel CT (FP-CT) immediately after endovascular thrombectomy in patients with acute ischemic stroke. This study is aimed at discriminating hyperdense lesions caused by extravasation plus hemorrhage from those caused by contrast extravasation alone. Methods. We retrospectively analyzed clinical and radiological data of patients who underwent an immediate postprocedure FP-CT scan and a follow-up noncontrast CT 24 hours after thrombectomy. We especially focused on the Maximum Hounsfield Units (HUmax) of each hyperdense lesion. A hyperdense lesion was judged to be hemorrhagic when it persisted on noncontrast CT and/or developed a mass effect. Results. Of 81 patients included in this study, 32 (39.5%) patients presented 41 hyperdense lesions on FP-CT. The chance of hemorrhagic transformation is higher in patients with hyperdense lesions on FP-CT than that in patients without hyperdense lesions (23/32 vs. 1/49, p<0.001). The HUmax of hyperdensity on FP-CT can predict hemorrhagic transformation with an area under the curve of 0.805 (95% CI: 0.67-0.94, p=0.02). The sensitivity, specificity, positive, and negative predictive values of hyperdensity on FP-CT for hemorrhagic transformation were 96%, 84%, 72%, and 98%, respectively. A HUmax of >600 predicted hemorrhagic transformation with a sensitivity of 50% and a specificity of 100%. Conclusions. The presence of hyperdensity on FP-CT can predict hemorrhagic transformation with a high sensitivity and negative predictive value. The measurement of HUmax of hyperdense lesion on FP-CT can be applied to the management of patients undergoing endovascular recanalization.


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## Body

## 1. Introduction

Mechanical thrombectomy has been regarded as a milestone in the rescue of severe acute ischemic stroke (AIS) with high recanalization rates and dramatically improved results [1]. However, this endovascular treatment may result detrimental mainly because of hemorrhagic transformation (HT) [2]. Detection of intracerebral hemorrhage as early as possible is absolutely critical in the management of this intractable condition. Flat panel computed tomography (FP-CT) is a very useful tool for the detection of peri-interventional complications immediately after procedure without transferring patients to the CT unit [3, 4]. However, this imaging modality poses challenges in diagnosing HT in patients undergoing mechanical thrombectomy as the presence of hyperdense lesions could be either contrast extravasation alone or plus hemorrhage. The goal of this study was to evaluate the potential of FP-CT in the detection of intraparenchymal hemorrhage through analyzing Hounsfield Units of hyperdense areas seen on FP-CT immediately after mechanical thrombectomy.


## 2. Methods and Materials

### 2.1. Patients

AIS patients who were treated with mechanical thrombectomy due to large vessel occlusion between January 2016 and March 2018 at our institution were retrospectively reviewed and analyzed. The inclusion criteria for the study were examined with an immediate postprocedure FP-CT and a follow-up noncontrast computed tomography (NC-CT) 24 hours after thrombectomy. Patients were excluded if their image data were incomplete or nondiagnostic due to motion or other artifacts. This study was approved by the ethics committee of our Institution, and the review board waived the need for written informed consent from the participants.


### 2.2. Stroke Management

In accordance with AHA/ASA guideline’s acute ischemic stroke protocol, patients presenting large vessel occlusions within 6 hours from symptom onset received endovascular recanalization. A combination of Solitaire™ FR revascularization device and Navein guide catheter (ev3, Irvine, CA, USA) was employed for mechanical thrombectomy in all selected cases. Balloon or stent-assisted angioplasty as an alternative was performed only when stent retriever thrombectomy failed due to intracranial stenosis. Details on the arterial occlusion sites, median time from onset to puncture (onset-to-puncture time), procedure time, interval between FP-CT and NC-CT, and so on were recorded for each patient. Recanalization was considered to be successful when the thrombolysis in cerebral infarction (TICI) score was 2b or 3. Decompressive craniectomy was reserved for patients whose neurological condition deteriorated due to significant space-occupying effect. The neurologic outcomes were assessed using the modified Rankin scale (mRS) score at a three-month follow-up. Favorable outcomes were defined asscores≤2.


### 2.3. Image Acquisition

FP-CT scans were regularly performed at the end of thrombectomy, while follow-up NC-CT scans were finished about 24 hours after the procedure. FP-CT scans were performed with a biplane angiography system (Dyna CT, Siemens, Germany) using the following parameters: voltage, 84 kV; tube current, 253 mA; acquisition time, 11.6 ms per frame; projection on 48 cm flat panel size; angulation, frame speed, 30 frames per second, 0.4° per frame; total angle, 196°; exposure time, 20 s. NC-CT images were acquired on a 64-slice multidetector CT (GE LightSpeed VCT, GE Healthcare, USA) at 120 kV, 250 mA, and 1.0 s rotation time. Images were reconstructed with 5 mm section thickness, using a standard reconstruction kernel, a field of view of 250 mm, and a 512×512 matrix.


### 2.4. Image Analysis

Two experienced neurologists blinded to clinical data independently reviewed FP-CT images on a dedicated workstation (syngo Multi-Modality Workplace, Siemens, Germany) and NC-CT images on the PACS (Philips iSite PACS, Netherlands) in randomized order. Afterward, a consensus reading was performed to get a reference standard for statistical analyses.Maximum Hounsfield Units (HUmax) of hyperdense lesions in FP-CT were measured based on visually defined regions of interest. HUmax and location of each hyperdense lesion were separately recorded if there were multiple hyperdense lesions in the same patient. Hyperdense lesions that were no longer discernible on the follow-up NC-CT were regarded as contrast extravasation. Hyperdensity was confirmed to be hemorrhagic transformation (HT) when it persisted on NC-CT and/or developed a mass effect [5, 6]. HT was further categorized as symptomatic and nonsymptomatic. We defined symptomatic hemorrhage according to the SITS-MOST definition [7]: when blood clot exceeds 30% of the infarcted volume with significant mass effect or leads to a decline in NIHSS of ≥4 points or causing death within 36 hours.


### 2.5. Statistical Analysis

Continuous variables are expressed as themean±standarddeviation, ordinal variables are expressed as median (interquartile), and categorical variables are expressed as numbers (frequencies). Bivariate comparisons were performed by the Mann–Whitney U test for continuous variables and the χ2 test for categorical variables (or Fisher’s exact test when the expected cell frequency was <5). The sensitivity, specificity, positive predictive value, and negative predictive value of FP-CT for the prediction of HT were calculated. In addition, receiver operating characteristic analysis was performed to indicate the predictive value of the HUmax of hyperdensity for identifying intraparenchymal hemorrhage. All the statistical analyses were performed with SPSS version 21.0 (SPSS, Chicago, IL, USA). A value of p<0.05 was considered to be significant.


## 2.1. Patients

AIS patients who were treated with mechanical thrombectomy due to large vessel occlusion between January 2016 and March 2018 at our institution were retrospectively reviewed and analyzed. The inclusion criteria for the study were examined with an immediate postprocedure FP-CT and a follow-up noncontrast computed tomography (NC-CT) 24 hours after thrombectomy. Patients were excluded if their image data were incomplete or nondiagnostic due to motion or other artifacts. This study was approved by the ethics committee of our Institution, and the review board waived the need for written informed consent from the participants.


## 2.2. Stroke Management

In accordance with AHA/ASA guideline’s acute ischemic stroke protocol, patients presenting large vessel occlusions within 6 hours from symptom onset received endovascular recanalization. A combination of Solitaire™ FR revascularization device and Navein guide catheter (ev3, Irvine, CA, USA) was employed for mechanical thrombectomy in all selected cases. Balloon or stent-assisted angioplasty as an alternative was performed only when stent retriever thrombectomy failed due to intracranial stenosis. Details on the arterial occlusion sites, median time from onset to puncture (onset-to-puncture time), procedure time, interval between FP-CT and NC-CT, and so on were recorded for each patient. Recanalization was considered to be successful when the thrombolysis in cerebral infarction (TICI) score was 2b or 3. Decompressive craniectomy was reserved for patients whose neurological condition deteriorated due to significant space-occupying effect. The neurologic outcomes were assessed using the modified Rankin scale (mRS) score at a three-month follow-up. Favorable outcomes were defined asscores≤2.


## 2.3. Image Acquisition

FP-CT scans were regularly performed at the end of thrombectomy, while follow-up NC-CT scans were finished about 24 hours after the procedure. FP-CT scans were performed with a biplane angiography system (Dyna CT, Siemens, Germany) using the following parameters: voltage, 84 kV; tube current, 253 mA; acquisition time, 11.6 ms per frame; projection on 48 cm flat panel size; angulation, frame speed, 30 frames per second, 0.4° per frame; total angle, 196°; exposure time, 20 s. NC-CT images were acquired on a 64-slice multidetector CT (GE LightSpeed VCT, GE Healthcare, USA) at 120 kV, 250 mA, and 1.0 s rotation time. Images were reconstructed with 5 mm section thickness, using a standard reconstruction kernel, a field of view of 250 mm, and a 512×512 matrix.


## 2.4. Image Analysis

Two experienced neurologists blinded to clinical data independently reviewed FP-CT images on a dedicated workstation (syngo Multi-Modality Workplace, Siemens, Germany) and NC-CT images on the PACS (Philips iSite PACS, Netherlands) in randomized order. Afterward, a consensus reading was performed to get a reference standard for statistical analyses.Maximum Hounsfield Units (HUmax) of hyperdense lesions in FP-CT were measured based on visually defined regions of interest. HUmax and location of each hyperdense lesion were separately recorded if there were multiple hyperdense lesions in the same patient. Hyperdense lesions that were no longer discernible on the follow-up NC-CT were regarded as contrast extravasation. Hyperdensity was confirmed to be hemorrhagic transformation (HT) when it persisted on NC-CT and/or developed a mass effect [5, 6]. HT was further categorized as symptomatic and nonsymptomatic. We defined symptomatic hemorrhage according to the SITS-MOST definition [7]: when blood clot exceeds 30% of the infarcted volume with significant mass effect or leads to a decline in NIHSS of ≥4 points or causing death within 36 hours.


## 2.5. Statistical Analysis

Continuous variables are expressed as themean±standarddeviation, ordinal variables are expressed as median (interquartile), and categorical variables are expressed as numbers (frequencies). Bivariate comparisons were performed by the Mann–Whitney U test for continuous variables and the χ2 test for categorical variables (or Fisher’s exact test when the expected cell frequency was <5). The sensitivity, specificity, positive predictive value, and negative predictive value of FP-CT for the prediction of HT were calculated. In addition, receiver operating characteristic analysis was performed to indicate the predictive value of the HUmax of hyperdensity for identifying intraparenchymal hemorrhage. All the statistical analyses were performed with SPSS version 21.0 (SPSS, Chicago, IL, USA). A value of p<0.05 was considered to be significant.


## 3. Results

### 3.1. The Study Sample and Clinical Outcomes

Between January 2016 and March 2018, 87 patients underwent both FP-CT and follow-up NC-CT scans after mechanical thrombectomy but 6 were excluded due to poor image quality, yielding a cohort of 81 patients (49 males, 32 females). The mean age of this series was67.4±9.5 years (ranging from 49 to 83 years), and patients presented with a median on-admission NIHSS score of 15 (ranging from 6 to 26). The rate of successful recanalization (TICI 2b and 3) was 88.9% (72/81). Hyperdense lesions were found on 32 patients on the FP-CT. However, HT was revealed in 24 patients on the follow-up NC-CT, among them, 7 were symptomatic. At the 3-month follow-up, we obtained a functional independence rate of 45.7% (37/81) and a mortality rate of 11.1% (9/81). 6 patients died of symptomatic intracranial hemorrhage and/or brain infarction edema; the remaining 3 died because of systematic infection.According to the results of FP-CT scans, patients were divided into hyperdense lesion group (32 cases) and nonhyperdense lesion group (49 cases). There was no significant difference between the two groups regarding age, sex, occlusion sites, NIHSS scores, onset-to-puncture time, procedure time, interval between FP-CT and NC-CT, TICI scores, and so on (see Table1); however, the rate of functional independence at 3 months was 53.1% (26/49) in the nonhyperdense lesion group and 34.3% (11/32) in the hyperdense lesion group (p=0.12); meanwhile, the mortality rate is 6.1% (3/49) in the nonhyperdense lesion group, in comparison to 18.8% (6/32) in the hyperdense lesion group (p=0.14), indicating that hyperdense lesion on FP-CT was related to unfavorable outcomes though statistical difference was not significant possibly due to sample size.Table 1
Comparisons of hyperdensity versus no hyperdensity on flat panel CT performed immediately after mechanical thrombectomy.
FP-CT+ (N=32)FP-CT- (N=49)pHT23 (71.9%)1 (2.0%)p<0.01Age in years66.2±10.966.9±8.60.45Male19 (59.4%)30 (61.2%)>0.99Baseline NIHSS score15 (13-18)15 (12-18)0.54Occluded circulation0.85Anterior26 (81.2%)39 (79.6%)Posterior6 (18.8%)10 (20.4%)Occluded arteries0.98MCA isolated18 (56.2%)27 (55.1%)ICA isolated or tandem with MCA8 (25.0%)12 (24.5%)Posterior circulation6 (18.8%)10 (20.4%)Time from symptom onset to puncture210.2±64.8195.7±80.90.15Procedure time103.0±44.191.1±32.20.24Interval between FP-CT and NC-CT25.1±3.923.7±3.50.37Recanalization after treatment,0.25TICI<2b5 (15.6%)3 (6.1%)TICI≥2b27 (84.4%)46 (93.9%)3-month mRS0.12≤211 (34.4%)26 (53.1%)>221 (65.6%)23 (46.9%)Mortality rate6 (18.8%)3 (6.1%)0.14Data aren (%), median (interquartile), or mean±standarddeviation. Note: FP-CT indicates flat panel CT, HT indicates hemorrhagic transformation, NIHSS indicates National Institutes of Health Stroke Scale, MCA indicates middle cerebral artery, ICA indicates internal carotid artery, TICI indicates thrombolysis in cerebral infarction, mRS indicates modified Rankin scale.


### 3.2. Hyperdensity Could Predict HT

The total number of HT was 24, most of them were from the hyperdense lesion group (23/32, 71.9%), and only one case was from the nonhyperdense lesion group (1/49, 2.0%). The difference was statistically significant (p<0.001). The sensitivity and specificity of hyperdensity on FP-CT for detecting hemorrhage transformation were 96% (23/24) and 84% (48/57), respectively, while positive and negative predictive value were 72% (23/32) and 98% (48/49). Among the 24 cases with HT, 7 cases were categorized as symptomatic and all of them were from the hyperdense lesion group. Sample cases are shown in Figure 1.Figure 1
Images of sample patients. A 56-year-old man with acute occlusion of the left middle cerebral artery (a) received successful recanalization (b). Flat panel CT shows hyperdense lesion in the head of the left caudal nucleus (c), which resolved on noncontrast CT 24 hours after thrombectomy (d). A 67-year-old man with acute occlusion of the right internal carotid artery (e) received successful recanalization (f). Flat panel CT shows hyperdense lesion in the right basal ganglia and right middle cerebral artery territory (g), which persisted on noncontrast CT (h).
(a)(b)(c)(d)(e)(f)(g)(h)There was a total of 41 hyperdense lesions in 32 patients, with 9 patients harboring two isolated hyperdense lesions. As 13 hyperdense lesions disappeared on the following NC-CT scans, they were attributed to oozing of contrast agent. The remaining 28 lesions were judged as hemorrhagic. The clinical features of these hyperdense lesions are shown in Table2. We further divided the hyperdense lesions into the hemorrhagic group and the nonhemorrhagic group. The HUmax of each hyperdense lesion was measured, as a result, the HUmax of the hemorrhagic group was much higher than that of the nonhemorrhagic group (867.3±667.1 verse 300.1±127.0 HU, p=0.02). It was very impressive that in one patient who had both hemorrhagic and nonhemorrhagic hyperdense lesions, the HUmax of the hemorrhagic one was much higher than that of the nonhemorrhagic one (Figure 2). The receiver operating characteristic analysis showed that the HUmax of the hyperdensity on FP-CT can predict HT with an area under the curve of 0.805 (95% CI: 0.67-0.94, p=0.02) (Figure 3). The lowest and highest HUmax was 169 and 2766, respectively, in the 41 hyperdense lesions. With the upregulation of the threshold values, the sensitivity of HUmax for detecting HT decreased, but the specificity increased meanwhile. The highest HUmax of hyperdense lesion finally judged to be contrast extravasation was 561 HU, so when we set HUmax 600 by Youden index as a threshold value, it can predict HT with a sensitivity of 50% (14/28) and a specificity of 100%.Table 2
The clinical features of patients with hyperdense lesions on FP-CT.
VariableTotal hyperdense lesions (n=41)Hemorrhagic lesionspYes (n=28)No (n=13)Age68.6±11.267.5±11.470.9±10.80.34Sex (male)25 (61.0%)19 (67.9%)6 (46.2%)0.18Baseline NIHSS score15 (12-18)16 (13-20)14 (11-14)0.08Occluded arteries (n, %)0.05MCA isolated21 (51.2%)11 (39.3%)10 (76.9%)ICA isolated or tandem with MCA14 (34.1%)11 (39.3%)3 (23.1%)Posterior circulation6 (14.6%)6 (21.4%)0 (0.0%)Time from symptom onset to puncture204.8±66.3211.9±65.9189.6±67.40.31Procedure time105.1±42.7109.0±45.896.5±35.00.58Interval between FP-CT and NC-CT25.0±4.124.5±4.126.0±4.10.20Recanalization after treatment0.39TICI<2b6 (14.6%)5 (17.9%)1 (7.7%)TICI≥2b35 (85.4%)23 (82.1%)12 (92.3%)3-month mRS0.55≤212 (29.3%)9 (32.1%)3 (23.1%)>229 (70.7%)19 (67.9%)10 (76.9%)Mortality rate8 (19.5%)8 (28.6%)0 (0.0%)0.03HUmax687.4±613.7867.3±667.1300.1±127.00.02Data aren (%), median (interquartile), or mean±standarddeviation. Note: HUmax indicates maximum Hounsfield units.Figure 2
Images of post-procedure flat-panel CT (a) and non-contrast CT (b) in one patient. Flat panel CT shows hyperdensity in the left basal ganglia and left temporosphenoid lobe. The HUmax of left basal ganglia is 1405 and the HUmax of left temporosphenoid lobe is 474. Noncontrast CT revealed hemorrhage only in the left basal ganglia.
(a)(b)Figure 3
Receiver operating characteristic curve for the predictive value of HUmax for hemorrhagic transformation. The HUmax value was a predictor of hemorrhagic transformation with statistical significance (area under curve of 0.805; 95% CI: 0.67-0.94, p=0.02).


## 3.1. The Study Sample and Clinical Outcomes

Between January 2016 and March 2018, 87 patients underwent both FP-CT and follow-up NC-CT scans after mechanical thrombectomy but 6 were excluded due to poor image quality, yielding a cohort of 81 patients (49 males, 32 females). The mean age of this series was67.4±9.5 years (ranging from 49 to 83 years), and patients presented with a median on-admission NIHSS score of 15 (ranging from 6 to 26). The rate of successful recanalization (TICI 2b and 3) was 88.9% (72/81). Hyperdense lesions were found on 32 patients on the FP-CT. However, HT was revealed in 24 patients on the follow-up NC-CT, among them, 7 were symptomatic. At the 3-month follow-up, we obtained a functional independence rate of 45.7% (37/81) and a mortality rate of 11.1% (9/81). 6 patients died of symptomatic intracranial hemorrhage and/or brain infarction edema; the remaining 3 died because of systematic infection.According to the results of FP-CT scans, patients were divided into hyperdense lesion group (32 cases) and nonhyperdense lesion group (49 cases). There was no significant difference between the two groups regarding age, sex, occlusion sites, NIHSS scores, onset-to-puncture time, procedure time, interval between FP-CT and NC-CT, TICI scores, and so on (see Table1); however, the rate of functional independence at 3 months was 53.1% (26/49) in the nonhyperdense lesion group and 34.3% (11/32) in the hyperdense lesion group (p=0.12); meanwhile, the mortality rate is 6.1% (3/49) in the nonhyperdense lesion group, in comparison to 18.8% (6/32) in the hyperdense lesion group (p=0.14), indicating that hyperdense lesion on FP-CT was related to unfavorable outcomes though statistical difference was not significant possibly due to sample size.Table 1
Comparisons of hyperdensity versus no hyperdensity on flat panel CT performed immediately after mechanical thrombectomy.
FP-CT+ (N=32)FP-CT- (N=49)pHT23 (71.9%)1 (2.0%)p<0.01Age in years66.2±10.966.9±8.60.45Male19 (59.4%)30 (61.2%)>0.99Baseline NIHSS score15 (13-18)15 (12-18)0.54Occluded circulation0.85Anterior26 (81.2%)39 (79.6%)Posterior6 (18.8%)10 (20.4%)Occluded arteries0.98MCA isolated18 (56.2%)27 (55.1%)ICA isolated or tandem with MCA8 (25.0%)12 (24.5%)Posterior circulation6 (18.8%)10 (20.4%)Time from symptom onset to puncture210.2±64.8195.7±80.90.15Procedure time103.0±44.191.1±32.20.24Interval between FP-CT and NC-CT25.1±3.923.7±3.50.37Recanalization after treatment,0.25TICI<2b5 (15.6%)3 (6.1%)TICI≥2b27 (84.4%)46 (93.9%)3-month mRS0.12≤211 (34.4%)26 (53.1%)>221 (65.6%)23 (46.9%)Mortality rate6 (18.8%)3 (6.1%)0.14Data aren (%), median (interquartile), or mean±standarddeviation. Note: FP-CT indicates flat panel CT, HT indicates hemorrhagic transformation, NIHSS indicates National Institutes of Health Stroke Scale, MCA indicates middle cerebral artery, ICA indicates internal carotid artery, TICI indicates thrombolysis in cerebral infarction, mRS indicates modified Rankin scale.


## 3.2. Hyperdensity Could Predict HT

The total number of HT was 24, most of them were from the hyperdense lesion group (23/32, 71.9%), and only one case was from the nonhyperdense lesion group (1/49, 2.0%). The difference was statistically significant (p<0.001). The sensitivity and specificity of hyperdensity on FP-CT for detecting hemorrhage transformation were 96% (23/24) and 84% (48/57), respectively, while positive and negative predictive value were 72% (23/32) and 98% (48/49). Among the 24 cases with HT, 7 cases were categorized as symptomatic and all of them were from the hyperdense lesion group. Sample cases are shown in Figure 1.Figure 1
Images of sample patients. A 56-year-old man with acute occlusion of the left middle cerebral artery (a) received successful recanalization (b). Flat panel CT shows hyperdense lesion in the head of the left caudal nucleus (c), which resolved on noncontrast CT 24 hours after thrombectomy (d). A 67-year-old man with acute occlusion of the right internal carotid artery (e) received successful recanalization (f). Flat panel CT shows hyperdense lesion in the right basal ganglia and right middle cerebral artery territory (g), which persisted on noncontrast CT (h).
(a)(b)(c)(d)(e)(f)(g)(h)There was a total of 41 hyperdense lesions in 32 patients, with 9 patients harboring two isolated hyperdense lesions. As 13 hyperdense lesions disappeared on the following NC-CT scans, they were attributed to oozing of contrast agent. The remaining 28 lesions were judged as hemorrhagic. The clinical features of these hyperdense lesions are shown in Table2. We further divided the hyperdense lesions into the hemorrhagic group and the nonhemorrhagic group. The HUmax of each hyperdense lesion was measured, as a result, the HUmax of the hemorrhagic group was much higher than that of the nonhemorrhagic group (867.3±667.1 verse 300.1±127.0 HU, p=0.02). It was very impressive that in one patient who had both hemorrhagic and nonhemorrhagic hyperdense lesions, the HUmax of the hemorrhagic one was much higher than that of the nonhemorrhagic one (Figure 2). The receiver operating characteristic analysis showed that the HUmax of the hyperdensity on FP-CT can predict HT with an area under the curve of 0.805 (95% CI: 0.67-0.94, p=0.02) (Figure 3). The lowest and highest HUmax was 169 and 2766, respectively, in the 41 hyperdense lesions. With the upregulation of the threshold values, the sensitivity of HUmax for detecting HT decreased, but the specificity increased meanwhile. The highest HUmax of hyperdense lesion finally judged to be contrast extravasation was 561 HU, so when we set HUmax 600 by Youden index as a threshold value, it can predict HT with a sensitivity of 50% (14/28) and a specificity of 100%.Table 2
The clinical features of patients with hyperdense lesions on FP-CT.
VariableTotal hyperdense lesions (n=41)Hemorrhagic lesionspYes (n=28)No (n=13)Age68.6±11.267.5±11.470.9±10.80.34Sex (male)25 (61.0%)19 (67.9%)6 (46.2%)0.18Baseline NIHSS score15 (12-18)16 (13-20)14 (11-14)0.08Occluded arteries (n, %)0.05MCA isolated21 (51.2%)11 (39.3%)10 (76.9%)ICA isolated or tandem with MCA14 (34.1%)11 (39.3%)3 (23.1%)Posterior circulation6 (14.6%)6 (21.4%)0 (0.0%)Time from symptom onset to puncture204.8±66.3211.9±65.9189.6±67.40.31Procedure time105.1±42.7109.0±45.896.5±35.00.58Interval between FP-CT and NC-CT25.0±4.124.5±4.126.0±4.10.20Recanalization after treatment0.39TICI<2b6 (14.6%)5 (17.9%)1 (7.7%)TICI≥2b35 (85.4%)23 (82.1%)12 (92.3%)3-month mRS0.55≤212 (29.3%)9 (32.1%)3 (23.1%)>229 (70.7%)19 (67.9%)10 (76.9%)Mortality rate8 (19.5%)8 (28.6%)0 (0.0%)0.03HUmax687.4±613.7867.3±667.1300.1±127.00.02Data aren (%), median (interquartile), or mean±standarddeviation. Note: HUmax indicates maximum Hounsfield units.Figure 2
Images of post-procedure flat-panel CT (a) and non-contrast CT (b) in one patient. Flat panel CT shows hyperdensity in the left basal ganglia and left temporosphenoid lobe. The HUmax of left basal ganglia is 1405 and the HUmax of left temporosphenoid lobe is 474. Noncontrast CT revealed hemorrhage only in the left basal ganglia.
(a)(b)Figure 3
Receiver operating characteristic curve for the predictive value of HUmax for hemorrhagic transformation. The HUmax value was a predictor of hemorrhagic transformation with statistical significance (area under curve of 0.805; 95% CI: 0.67-0.94, p=0.02).


## 4. Discussion

FP-CT has the advantage of immediately revealing peri-procedural abnormal conditions without transferring patients, which is especially useful in the management of patients undergoing endovascular recanalization.Our study found that 39.5% of patients (32/81) had hyperdense lesions after mechanical thrombectomy, which is in line with previous reports (from 30% to 87% using NC-CT [8–15] and 16% to 60% using FP-CT [16–18]). As HT is critical in the setting of therapy for AIS patients, we attempted to investigate the potential of FP-CT in the prediction of HT. As a result, the hyperdense lesion on FP-CT demonstrated high sensitivity and negative predictive value for the detection of HT. When focusing on the HUmax of hyperdense lesions, we found that, with the increase of the HUmax value, the risk of HT enhanced accordingly. Berger et al. [19] reported that symptomatic intracranial hemorrhage was the only HT that independently caused clinical deterioration and impacted prognosis. As far as symptomatic hemorrhage is concerned, all the symptomatic cases are from the FP-CT (+) group, indicating that FP-CT can reliably predict symptomatic intracranial hemorrhage.As a dynamic interface between the peripheral circulation and the central nervous system, the blood-brain barrier (BBB) controls the influx and efflux of biological substances needed for the brain metabolic processes, as well as for neuronal function. In the case of acute ischemic stroke, the damage to the BBB is initiated immediately after arterial occlusion, and the extent of BBB disruption is associated with the type, severity, and duration of ischemic insults. When the BBB disruption is relatively mild, the contrast agent is allowed to extravasate due to the increased permeability; however, with the progression of the ischemic/reperfusion injuries, the rupture of the blood-brain barrier takes place, leading to a massive extravasation of both contrast agent and blood elements [20]. Therefore, it is not difficult to explain why patients with hyperdense lesions on FP-CT have more chance of HT than those without hyperdense lesions, and the higher the HUmax of the hyperdense lesions, the greater the risk of symptomatic intracranial hemorrhage.The measurement of HUmax of the hyperdense lesions on FP-CT can be applied to the management of patients receiving endovascular recanalization. A large amount of data suggests that intracranial hemorrhage tends to occur within the first 12–24 hours after treatment [21]. It is proper to delay antiplatelet and anticoagulant drugs when a hyperdense lesion is found on FP-CT until a follow-up NC-CT is performed to rule out hemorrhage. Blood pressure management is another urgent consideration in these patients. Target blood pressure is set according to the recanalization level of the occluded circulation. A systolic blood pressure goal of less than 140 mmHg is recommended for those achieving successful recanalization [22]; however, if hyperdense lesions are presented, neurocritical care, including sedation, analgesia, and strict blood pressure control, is recommended to reduce the risk of HT. When HUmax of the hyperdense lesion breaks a threshold value (600 HU in our study), hemorrhage is almost inevitable, preparation for decompressive craniectomy in advance is strongly suggested when extensive hyperdense lesions are found on FP-CT, considering that the final infarction area can be evaluated on the basis of hyperdense lesions [23].Recanalization of the responsible cerebral vessels is the primary target after the onset of AIS; however, the big gap between the high recanalization rate and the relatively low functional independence rate implies the revascularization in a large proportion of patients is actually futile or even detrimental. How to select the best candidates for recanalization is still a hot topic at present. As FP-CT has the advantage of providing real-time information on the integrity of the blood-brain barrier, the final decision to restore or not to restore the blood flow could be made by referring to the FP-CT image, especially in a dilemma moment. Takes it for example, after temporary blood flow restoration with the deployment of a stent retriever, we can perform an FP-CT scan, if extensive hyperdense lesions already exist while stenting and antiplatelet administration are necessary to achieve a successful recanalization. It is sagacious to abandon recanalization, as the risk of symptomatic hemorrhage is very high after reperfusion.


## 5. Limitations

Our study has several limitations. First, our study was performed retrospectively with a small sample size from a single center, which might result in selection bias. In addition, the amount of contrast media and the number of recanalization attempts were reported to be risk factors for HT [24, 25]; in our study, the dose, volume, type of contrast media administered, and number of recanalization attempts were not available in some patients, which made the evaluation limited.


## 6. Conclusions

The presence of hyperdensity on FP-CT can predict HT with a high sensitivity and negative predictive value. The measurement of HUmax of hyperdense lesion on FP-CT can be applied to the management of patients undergoing endovascular recanalization.



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