CT perfusion derived relative cerebral blood volume < 42% is negatively associated with poor functional outcomes at discharge in anterior circulation large vessel occlusion stroke

Abstract

Background and aim:

Recent studies have shown that the CT Perfusion (CTP) parameter of rCBV <42% lesion volume can predict 90-day functional outcomes in stroke patients. However, its correlation with discharge outcomes, including functional dependence, has not been investigated. Our study aims to evaluate the relationship between rCBV <42% and poor functional outcomes at discharge, defined as a modified Rankin score (mRS) of 3 or higher.

Materials and methods:

This retrospective study analyzed patients with confirmed occlusion on CT angiography, who also received CT perfusion between 9/1/2017 and 10/01/2023. Statistical tests (Student’s T, Mann-Whitney U, and Chi-Square) were used to assess differences. Univariable and multivariable logistic regression analyses were performed to evaluate the associations of rCBV <42% with discharge mRS. A p-value ≤ 0.05 was considered significant.

Results:

A total of 268 patients [median age: 68 years (IQR: 59–77), 56.3% female] met the inclusion criteria. Among them, 85 patients (31.7%) received intravenous thrombolysis (IVT), and 221 patients (82.5%) underwent mechanical thrombectomy (MT). After adjusting for various variables, logistic regression analysis indicated that rCBV <42% lesion volume was associated with poor functional outcomes at discharge (aOR=0.97, p<0.05). T

Conclusion:

The rCBV <42% could be a valuable tool in prognosticating AIS-LVO patients.

INTRODUCTION

Cerebral blood volume (CBV) offers an important assessment of the brain’s compensatory response to a large vessel occlusion (LVO) by quantifying collateral blood flow^1–13. CT perfusion imaging is helpful for automated assessment of CBV, however, there is a considerable variability in the published definitions across studies and in different commercially available CTP softwares^1–4,6,14. Despite these differences CBV remains a critical determinant of ischemic core and infarct growth rate^1–4.

Most automated software platforms estimate CBV in the affected region relative to the non-affected hemisphere. For instance, RAPID (IschemaView, Menlo Park, CA) software calculates relative CBV (rCBV) by comparing the average CBV values in the Tmax >6s region of the affected hemisphere to the average CBV values in the unaffected brain parenchyma within the Tmax ≤4s area, thus indirectly quantifying the degree of compensation in the hypoperfused territory^1,5,7,15.

Recent research has highlighted the prognostic value of rCBV in AIS-LVO patients. A study found that an increased lesion volume with rCBV <42% was independently associated with worse functional outcomes at 90 days and demonstrating superiority of rCBF<42% compared to other rCBV parameters¹⁶. However, it did not specifically assess the relationship between rCBV <42% and short-term outcomes such as functional outcomes at discharge. Additional studies have underscored the importance of early and accurate CBV measurement in guiding therapeutic decisions and improving patient outcomes^17–23.

Understanding and improving discharge functional status can significantly impact patient quality of life and long-term recovery for AIS-LVO patients. Studies have shown that better functional outcomes at discharge correlate with reduced long-term disability and lower healthcare costs. Discharge mRS serves as a predictor for discharge destination, the necessity of post-discharge services such as rehabilitation and nursing care, and provides an estimate of subsequent care needs, resource requirements, and healthcare expenses^24,25. Furthermore, discharge mRS and discharge disposition have also been demonstrated to be good individual predictors of 90-day mRS for ischemic stroke patients following treatment²⁶.

Therefore, the aim of our study is to investigate the relationship between rCBV <42% lesion volume and functional outcomes at discharge in patients with anterior circulation AIS-LVO. We hypothesize that larger rCBV <42% volumes are associated with poorer functional outcomes, defined as a discharge modified Rankin Scale (mRS) score of 3 or higher.

METHODS

Study Design

We performed a retrospective analysis of prospectively maintained stroke databases, and we identified consecutive patients from two comprehensive stroke centers from September 01, 2017 to October 01, 2023 who met our inclusion criteria. This study was approved through the blinded for peer-review institutional review board (IRB #blinded for peer-review).

Study Participants

The inclusion criteria for this study were: a) diagnostically adequate multimodal pretreatment CT imaging including noncontrast head CT (NCCT), CT angiography (CTA), and CTP; b) AIS due to a CTA confirmed large vessel occlusion of the distal supraclinoid segment of the internal carotid artery (ICA), M1-segment of middle cerebral artery (MCA), and proximal M2-segment of MCA²⁷(Figure 1).

Figure 1:

Study flowchart

The study was conducted in accordance with the Declaration of Helsinki and the Health Insurance Portability and Accountability Act (HIPAA). Informed consent was waived by the institutional review boards given the retrospective study design. The decisions to administer IV thrombolysis and/or perform MT were made on an individual basis based on consensus stroke team evaluation per institutional protocols.

Data Collection

The demographics and clinical variables relevant to stroke management were collected through the electronic medical records for each patient. This includes discharge mRS and LOS. The imaging markers on NCCT, CTA and CTP including ASPECTS, site of occlusion and different RAPID derived CTP variables were also collected. All these measures were prospectively collected and maintained in our database.

CTP Image Acquisition and Post-processing:

Whole brain pretreatment CTP was performed on the Siemens Somatom Force (Erlangen, Germany) with the following parameters: 70 kVP, 200 Effective mAs, Rotation Time 0.25 s, Average Acquisition Time 60 s, Collimation 48 × 1.2 mm, Pitch Value 0.7, 4D Range 114 mm × 1.5 seconds.

CTP source images were then post-processed using commercial RAPID perfusion software, version 5.2.2 (iSchemaView, Menlo Park, CA) to generate rCBV <42% volume.

Image Analysis

All the CTPs were assessed by board certified neuroradiologists with 9 years of working experience for diagnostic adequacy of the CTPs, where only those deemed diagnostic adequate were included in the study.

Statistical Analysis

Categorical data was described using contingency tables including counts and percentages; continuous variables were summarized with median (interquartile range). A student t-test was used in the data analysis for continuous variables, Mann-Whitney U test was used in the data analysis for ordinal data and Chi Square test was used for categorical data.

Univariable and multivariable logistic regression models were employed to assess the association of rCBV <42% volume (per 10 ml) and the outcome measure, which was dichotomized as discharge mRS 3 or more²⁶. The multivariable regression model considered several variables, including age (per 10 years), sex, race, hypertension, hyperlipidemia, diabetes mellitus, atrial fibrillation, prior transient ischemic attack or stroke, intravenous thrombolysis (IVT), admission NIH stroke scale, Alberta Stroke Program Early CT Score (ASPECTS), and mechanical thrombectomy (MT). The outcomes were reported as unadjusted odds ratio (uOR) and adjusted odds ratio (aOR) with 95% confidence interval (CI).

The receiver operating characteristic curve (ROC) analysis was performed to assess the ability of rCBV<42% volume to predict poor functional outcomes at discharge. Statistically significant analysis was described as p≤0.05, p<0.01 and p<0.001.

RESULTS

A total of 268 consecutive patients met our inclusion criteria with median age of 68 years (IQR: 59–77) and 56.3% being female. Among these patients, 85 (31.7%) received IVT, and 221 (82.5%) underwent MT (Table 1).

Table 1:

Study demographics

	Total (n=268)
	Number / Median (Percentage / Interquartile range)
Segment Occlusion
M1	193 (72.0%)
Proximal M2	53 (19.8%)
Supraclinoid intracranial ICA	22 (8.2%)
Sex
Female	151 (56.3%)
Male	117 (43.7%)
Age	68.0 (59.0 – 77.0)
Race
African American	115 (42.9%)
Caucasian	133 (49.6%)
Asian	10 (3.7%)
Others	10 (3.7%)
Hypertension	209 (78.0%)
Hyperlipidemia	142 (53.0%)
Heart Disease	139 (51.9%)
Atrial Fibrillation	103 (38.4%)
Prior TIA or stroke	54 (20.1%)
Premorbid mRS
0	175 (65.4%)
1	37 (13.8%)
2	21 (8.0%)
3	32 (12.3%)
4	2 (0.8%)
5	1 (0.4%)
ASPECTS
0	4 (1.5%)
1	1 (0.4%)
2	5 (1.9%)
3	2 (0.7%)
4	5 (1.9%)
5	13 (4.9%)
6	20 (7.5%)
7	23 (8.6%)
8	41 (15.3%)
9	40 (14.9%)
10	114 (42.5%)
rCBF < 30% lesion volume >= 50 ml	51 (19.0%)
rCBF < 30% lesion volume < 50 ml	217 (81.0%)
Hemorrhagic transformation	92 (36.8%)
Mechanical Thrombectomy	221 (82.5%)
mTici
0	8 (3.9%)
1	5 (2.4%)
2A	7 (3.4%)
2B	50 (24.4%)
2C	34 (16.6%)
3	101 (49.3%)
Smoking	132 (50.0%)
Alcohol	80 (30.3%)
IVT	85 (31.7%)
Diabetes	70 (26.1%)
Admission NIHSS	15.0 (10.0 – 20.0)
Admission body mass index (kg/m2)	27.3 (22.8 – 33.0)
rCBF <30% lesion volume in ml	6.5 (0.0 – 35.5)
rCBV <42% lesion volume in ml	6.0 (0.0 – 32.0)
Length of hospitaliztion in days	7.0 (4.0 – 14.0)
Discharge NIHSS	5.0 (2.0 – 12.5)
Symptom onset to door time in minutes	67.0 (42.0 – 138.0)
Door to needle time in minutes	59.0 (44.0 – 82.0)
Door to groin puncture time in minutes	157.5 (128.5 – 235.5)
Door to recanalization time in minutes	280.0 (192.0 – 394.0)

Abbreviations:

rCBV: Relative CBV; NIHSS: National Institute of Health Stroke Scale; CTP: CT perfusion; ICA: internal carotid artery; mRS: Modified Rankin Score; MCA: Middle cerebral artery; IVT: intravenous thrombolysis; mTiCI: Modified treatment in cerebral infarction (mTICI) score; ASPECTS: Alberta Stroke Program Early CT Score

Of the 268 patients, 193 (72.0%) had M1 segment occlusion, 53 (19.8%) had proximal M2 segment occlusion and 22 (8.2%) had supraclinoid intracranial ICA occlusion.

Detailed patient demographics, imaging parameters and stroke treatment information are provided in Table 1 and 2.

Table 2:

Logistic regression analysis with dichotomized functional outcomes at discharge (mRS 0–2 versus 3–6).

Variables to predict discharge mRS 0–2	Univariable logistic regression				Multivariable logistic regression
	Unadjusted OR	95% CI of unadjusted OR		p value	Adjusted OR	95% CI of adjusted OR		p value
		Lower	Upper			Lower	Upper
Age (per 10 years)	0.71	0.60	0.85	<0.001	0.63	0.51	0.79	<0.001
Sex	1.42	0.82	2.45	0.21
Race	1.34	0.93	1.94	0.12
Hypertension	0.50	0.27	0.93	<0.05	0.79	0.39	1.63	0.53
Hyperlipidemia	0.99	0.58	1.71	0.98
Diabetes	0.38	0.18	0.80	<0.05	0.34	0.14	0.79	<0.05
Atrial Fibrillation	0.72	0.41	1.28	0.27
Prior Transient Ischemic Attack or Stroke	0.99	0.50	1.95	0.97
Intravenous Thrombolysis	1.95	1.11	3.44	<0.05	1.61	0.83	3.11	0.16
Admission NIHSS	0.88	0.84	0.92	<0.001	0.91	0.87	0.95	<0.001
ASPECTS	1.27	1.08	1.50	<0.01	1.33	1.07	1.65	<0.01
Mechanical Thrombectomy	1.61	0.74	3.53	0.23
rCBV < 42% lesion volume (per 10 ml)	0.73	0.61	0.87	0.001	0.77	0.62	0.96	<0.05

rCBV <42% lesion volume and discharge mRS

Patients with poor functional outcomes had a significantly larger rCBV <42% lesion volume compared to those with good functional outcomes (9 ml, IQR: 0–38 versus 0 ml, IQR: 0–13, p<0.001) (Figure 2).

Figure 2:

Box and whisker plot showing the distribution of rCBV <42% lesion volume in patients with good and poor functional outcomes at discharge (mRS 0–2 and mRS 3–6). The box plot displays median and interquartile range, while the whiskers represent minimum and maximum values.

Logistic regression analysis showed an inverse relationship between rCBV <42% lesion volume and functional outcomes. A higher rCBV <42% lesion volume was associated with increased odds of a poor functional outcome (mRS 3–6), with an unadjusted odds ratio (uOR) of 0.73 (95% CI: 0.61–0.87, p=0.001) and an adjusted odds ratio (aOR) of 0.77 (95% CI: 0.62–0.96, p<0.05) (Table 2).

ROC analysis of rCBV <42% volume in predicting poor functional outcomes at discharge demonstrated an AUC of 0.65 (p<0.001; 95% CI: 0.58–0.71).

Other variables and discharge mRS

Advanced age (aOR: 0.63, p<0.001), higher admission NIH stroke scale (aOR: 0.91, p<0.001), diabetes (aOR: 0.34, p<0.05), and lower ASPECTS (aOR 1.33, p<0.01), were associated with poor functional outcomes at discharge (Table 2).

In univariable analysis, the presence of hypertension and lack of IVT administration were associated with increased odds of poor functional outcomes. However, after adjusting for other confounding variables, these factors were not significantly associated with discharge mRS (Table 2)

DISCUSSION

Our study found that a higher rCBV <42% lesion volume is associated with poor functional outcomes at discharge in patients with anterior circulation AIS-LVO, a relationship that had not been established previously. This finding underscores the value of rCBV <42% as an additional prognostic biomarker for short-term outcomes in this patient population. Furthermore, in keeping with existing literature advanced age, higher admission NIH stroke scale, diabetes, and lower ASPECTS were also associated with poor functional outcomes.

The rCBV thresholds are used to evaluate cerebral blood volume (CBV) in ischemic regions (Tmax >6s) compared to unaffected areas (Tmax ≤4s), providing an estimate of hypoperfused tissue. In response to ischemia, cerebral autoregulation triggers a typical homeostatic reaction characterized by vasodilation and increased oxygen extraction, thereby elevating CBV through collateral circulation pathways routes^{10,11,28–32}. This process helps to maintain adequate blood flow and oxygen delivery to the affected brain tissue.

However, when compensatory vasodilation is insufficient, CBV is reduced, indicating a failure in cerebral autoregulation. This disruption in autoregulation leads to a higher rate of infarct growth compared to patients who exhibit a more robust compensatory response resulting in greater tissue damage and worsened outcomes10,11,28–32.

A few previous studies have assessed rCBV as a promising imaging biomarker for infarct progression¹, collaterals¹, and 90-day mRS¹⁶. However, none of these studies have examined rCBV as a determinant of functional outcomes at discharge. Poor functional outcomes at discharge are linked to increased morbidity, an increased risk of complications during hospitalization, and increased healthcare costs^33,34.

Our findings further corroborate that rCBV effectively quantifies blood volume in hypoperfused regions and captures the degree of compensatory response and collateral status. The ability to generate a sufficient compensatory response, as reflected by lower volumes of tissue with rCBV <42%, appears to be crucial for better functional outcomes at discharge. This insufficiency in collateral circulation and autoregulation likely leads to greater ischemic damage and slower recovery. These findings align with previous studies that have shown the importance of collateral circulation in maintaining cerebral perfusion and mitigating infarct growth^17,35–42.

There are multiple important limitations in our study including the inherent limitations of a retrospective study design. One specific limitation is that we did not account for unrelated in-hospital medical complications that may affect the functional outcomes at discharge. Additionally, while CTP imaging provides valuable insights, it may not be readily available in smaller stroke centers. This limitation can affect the generalizability of our findings to all stroke care settings. Despite these limitations, our study is strengthened by the substantial sample size of 268 patients from two comprehensive stroke centers that serve diverse demographics.

In conclusion, our results highlight the significance of rCBV <42% lesion volume as a prognostic biomarker of short-term outcomes. This parameter may serve as a valuable adjunct tool in prognostication of AIS-LVO patients. Further research is needed to expand our understanding of the adjunct role of rCBV <42% as compared to other pretreatment imaging-based markers in prognostication for AIS-LVO patients. Additionally, combining rCBV with other imaging biomarkers could provide a more comprehensive prognostic model, improving individualized patient care.

Highlights: Association of CT Perfusion-Derived rCBV <42% Volume with Poor Discharge Outcomes in Anterior Circulation Stroke.

• Our study evaluated the relationship between rCBV <42% and discharge outcomes.

• This study analyzed patients with confirmed occlusion on CT angiography.

• Analysis showed that rCBV <42% was associated with poor outcomes at discharge.

• This parameter could be a valuable tool in prognosticating AIS-LVO patients.

ABBREVIATIONS:

AIS-LVO

Acute ischemic stroke secondary to large vessel occlusion

rCBV

Relative CBV

MT

Mechanical thrombectomy

NCCT

Non-contrast CT head

NIHSS

National Institute of Health Stroke Scale

CTA

CT angiography

CTP

CT perfusion

ICA

internal carotid artery

mRS

Modified Rankin Score

MCA

Middle cerebral artery

IVT

intravenous thrombolysis

mTiCI

Modified treatment in cerebral infarction (mTICI) score

ASPECTS

Alberta Stroke Program Early CT Score