Multimodal Nuclear Magnetic Imaging Prediction of Early Neurological Deterioration in Patients with Acute Stroke Using Intravenous Thrombolysis

doi:10.21203/rs.3.rs-4945314/v1

Background: To explore the relationship between Signal intensity ratio (SIR) levels, a cerebral hemodynamic index, and early neurological function deterioration in patients with acute cerebral infarction under the guidance of multimodal nuclear magnetic resonance imaging (NMRI) with intravenous thrombolysis.

Methods: 157 patients with acute cerebral infarction who received intravenous thrombolysis within 4.5 hours of stroke were obtained from Tianjin Huanhu Hospital between January 2022 and February 2024. early neurological deterioration (END) was defined as an increase in National Institutes of Health Stroke Scale (NIHSS) score of ≥4 points from baseline at 24 hours after intravenous thrombolysis or death. The patients were divided into 36 cases in the END group and 121 cases in the non-END group. Baseline, clinical, and imaging data were collected from patients. Patients who received treatment were followed for 3 months. Magnetic resonance angiography (MRA) was used to determine SIR levels before and after thrombolysis and to analyze the correlation between SIR levels and END.

Results: Patients in the END group had higher baseline systolic blood pressure, diastolic blood pressure, post-thrombolysis hemorrhage conversion, baseline NIHSS score, discharge NIHSS score, and modified Rankin Scale (mRS) score than those in the no-END group, whereas pre- and post-thrombolysis SIR levels were lower than those in the no-END group (P<0.05). Multifactorial logistic regression analysis showed that baseline NIHSS score, post-thrombolytic hemorrhagic conversion, and pre-thrombolytic SIR were independent risk factors for the development of END in patients with acute cerebral infarction treated with intravenous thrombolysis. Receiver operating curve (ROC) analysis showed that the area under the curve (AUC) of END detected by the combination of baseline NIHSS score and pre-thrombolysis SIR level was 0.791 (95% CI: 0.712-0.870), with sensitivity and specificity of 60% and 88.9%, respectively, and P<0.001 (Figure 1), which was higher than that of END detected by the two measures alone (baseline NIHSS score: AUC 0.770, 95% CI: 0.691-0.849, p=0.000; pre-thrombolytic SIR: AUC 0.654, 95% CI: 0.556-0.752, p=0.005). Spearman's correlation analysis showed that pre-thrombolysis SIR level was negatively correlated with the level of mRS score and post-thrombolysis hemorrhagic conversion (r=-0.218, p=0.000; r=-0.166, p=0.038), whereas it was positively correlated with post-thrombolysis SIR level (r=0.408, p=0.000).

Conclusions: SIR levels can be used as a simple, non-invasive and highly reproducible method in combination with baseline NIHSS scores to determine the occurrence of END after intravenous thrombolysis, providing a method for early screening of individuals at risk for END.

acute cerebral infarction

hemodynamics

intravenous thrombolysis

multimodal imaging

neurological function

Acute cerebral infarction (ACI) is a neurological disease associated with high morbidity, disability, and mortality worldwide. According to previous studies, the global incidence of stroke has increased by 70%, the prevalence by 75% and the mortality rate by 43%^[1]. Acute cerebrovascular infarction (ACI) is a class of diseases in which ischemia and hypoxia of brain cells occur due to insufficient blood supply to brain tissues, eventually leading to neurological impairment mainly^[2], among which large artery atherosclerotic cerebral infarction (LAA) is more common, accounting for about 25%^[3]. In previous studies, it was reported that in cases of ACI treated with rt-PA intravenous thrombolysis, the risk of death in patients with early neurological deterioration appeared to be 5.28 times higher than that of patients without END, and the prognosis was relatively poor, which is a difficult point of clinical management^[4]. At present, according to the clinical consensus of ACI intravenous thrombolytic therapy, the time window within 4.5 hours by rt-PA intravenous thrombolytic therapy is still the preferred method. However, early neurological deterioration (END) has been reported to occur in approximately one third of patients treated with intravenous thrombolysis for ACI^[5].

There is still a lack of understanding of the pathogenesis of END after intravenous thrombolytic therapy for ACI. Studies have reported that systolic blood pressure, atrial fibrillation, and baseline NIHSS score are risk factors for END in ischemic stroke patients^[6]. Currently, the NIHSS score is used to assess the severity of acute ischemic stroke patients in terms of 15 aspects such as level of consciousness, speech, and visual field defects. And no single factor leads to END after intravenous thrombolytic therapy for ACI, so screening for early predictive markers that can help predict intravenous thrombolytic therapy for ACI will help clinical diagnosis and treatment.

Cerebral hemodynamics is the mechanics of cerebral blood flow through the cerebral arterial system^[7]. Altered cerebral hemodynamics is a pathophysiological factor in LAA type acute cerebral infarction. When the cerebral blood flow fluctuates greatly or when the cerebral arteries are narrowed, hemodynamic changes in the brain are caused. Especially at the branching or turning point of the vasculature, due to the decrease of cerebral perfusion, the deposition of lipids and other substances occurs, leading to the occurrence of vascular atherosclerosis, endothelial cell damage, platelet aggregation, and so on, causing the reduction of blood supply and leading to the occurrence of acute cerebral infarction^[8]. LAA more likely to develop END^[9]. Time-of-flight magnetic resonance angiography (TOF-MRA) on the basis of the ratio of distal to proximal signal intensity at the stenosis of the middle cerebral artery for blood flow signal intensity (signal intensity ratio, SIR) has been reported to evaluate the degree of cerebral blood perfusion, which is noninvasive, simple, reproducible, and independent of contrast media^[10]. One study reported using SIR to predict the risk of recurrent ischaemic stroke and found that the risk of recurrent stroke was 5.2 times higher in the SIR < 0.9 group than in the SIR > 0.9 group.. Furthermore, the degree of stenosis does not reflect the hemodynamic changes, so it is not the only factor used to determine whether or not END occurs ^[11]. It is concluded that SIR levels for hemodynamic evaluation are clinically useful in predicting the effectiveness and prognosis of patients undergoing intravenous thrombolytic therapy for acute stroke.

Previous studies in patients with symptomatic anterior circulation intracranial atherosclerosis found a significant negative linear correlation between SIR levels and stroke infarct volume (P < 0.05) ^[12]. Additionally, SIR levels were found to be significantly lower in the under-perfused group than in the normal-perfused group in a study of the relationship between unilateral MCA stenosis and cerebral perfusion ^[13]. The measurement of SIR levels by MRA as a non-invasive and easy to perform method has been validated in the previous studies mentioned above.

The aim of this study is to investigate the clinical value of monitoring cerebral haemodynamics (SIR level), NHISS and post-thrombolytic haemorrhagic transformation using magnetic resonance imaging (MRI)-based MRA technology, to comprehensively and systematically analyse the clinical value of prognostic assessment of patients with acute cerebral infarction treated with intravenous thrombolysis, and to provide basic scientific support for the therapeutic prognosis of acute cerebral infarction.

1.1 Subjects of the research

A total of 157 patients with acute cerebral infarction who were admitted to the Department of Neurology, Tianjin Huanhu Hospital from January 2022 to February 2024 were enrolled, including 110 men and 47 women, aged 22-87 (62.59±10.69) years. Grouping was based on an increase of ≥4 points in the baseline NIHSS score at 24 hours after intravenous thrombolysis or death defined as END.Patients were divided into 36 cases in the END group and 121 cases in the non-END group. Inclusion criteria:(1) All patients underwent head MRI+MRA before and after thrombolysis and met the ESO guidelines for intravenous thrombolysis in acute ischemic stroke for screening and treatment^[16]; (2) unilateral or bilateral stenosis of the M1 segment of the middle cerebral artery ranging from 50% to 99%, with the severe side predominating in cases where both sides were stenotic; (3) age ≥18 years; (4) received intravenous thrombolysis within 4. 5 hours of onset; (5) have well-established clinical and imaging data; (6) good compliance. Exclusion criteria: (1) Patients with TIA; (2) Patients with stroke mimics; (3) those who received intravenous thrombolysis and then underwent bridging therapy or neurosurgery; (4) stenosis located at the bifurcation of the vessel or at the orifice of the perforating artery; (5) comorbidities with other diseases, such as inflammation, tumors, hepatic and renal insufficiency, and severe neurological deficits, etc. (6) Incomplete data, such as clinical and imaging data; (7) Poor compliance to participate in the study or refusal to participate in this study. The study was approved by the Ethics Committee of Tianjin Huanhu Hospital (Approval number:2022-047; Data:2022.5.10), and patients signed the corresponding informed consent form.

1.2 Methods

1.2.1 Collection of General Information

Baseline clinical data of the enrolled patients were collected and recorded, including age, sex, BMI, smoking, alcohol consumption, and medical history (hypertension, diabetes mellitus, coronary artery disease, atrial fibrillation, previous cerebral infarction). Before thrombolysis, venous blood was collected from the enrolled subjects for blood cytology, coagulation profile and blood glucose; 24 hours after thrombolysis, fasting venous blood was collected in the morning for routine blood count, coagulation profile, blood lipids (LDL, HDL, TC, TG), fasting blood glucose, homocysteine, liver and kidney function and CRP.

1.2.2 Intravenous Thrombolysis Data Collection

ESSEN score before thrombolysis; NIHSS score before thrombolysis, 1 hour, 24 hours and 7 days after thrombolysis; mRS score 3 months after hospital discharge; examination results before and after thrombolysis (including head MRI+MRA, head CT, routine electrocardiogram, etc.).

1.2.3 Methods to Assess Neurological Function and Prognosis

END was defined as an increase of ≥4 points in the total NIHSS score from the admission NIHSS score within 24 hours of intravenous thrombolysis or death [14]. Patients were followed up at 3 months, and an mRS score of 0-2 points at 3 months after treatment was defined as a good long-term prognosis, indicating that patients could already perform daily work and live independently; an mRS score of 3-6 points at 3 months after treatment was defined as a poor long-term prognosis, indicating that patients were still disabled and could not take care of themselves ^[15]. An mRS score of 3-6 at 3 months after treatment was defined as a poor long-term prognosis, indicating that the patient was still disabled and could not take care of themselves ^[15].

1.2.4 Method of evaluating the SIR value of the middle cerebral artery in head MRA

Magnetic resonance imaging (MRI) was performed using a Siemens (AVANTO) 3.0T superconducting MRI system. On the maximum intensity projection (MIP) of the MRA vessels, symmetrical areas of equal area were selected in the lumen distal and proximal to the stenosis of the MI segment of the middle cerebral artery before and after thrombolysis, and the average SI measurement was performed (it was preferred to cover the lumen just enough to avoid the bifurcation of the vessel and the opening of the perforating arteries). At the same time, the background SI of the left and right sides of the area adjacent to the internal carotid artery without vascular signal was calculated, and the average value was taken as the average background SI.

Calculation formula: SIR = (average SI of distal stenosis - background SI) / (average SI of proximal stenosis - background SI)^[12].

1.3 Statistical Methods

IBM SPSS 23.0 software was used for statistical analysis, and the measurement information was expressed as X±S, and the t-test was used for comparison between two groups. The non-normally distributed measurements were expressed as M (Q1, Q3), and the Mann-Whitney U test was used for comparison between groups, and the count data were expressed as percentages, and the χ2 test was used, and multifactorial logistic regression analysis and Spearman's correlation analysis were used, and the difference was considered statistically significant at P<0.05.

2.1 General Clinical Data of Patients with Acute Cerebral Infarction with or without END after Intravenous Thrombolysis

Among the 157 patients who underwent intravenous thrombolysis for acute cerebral infarction, 36 patients developed END and the remaining 121 did not develop END. The clinical data of all study subjects were collected according to the grouping, and the statistical analysis revealed that the differences between the END cases and those who did not develop END were statistically significant (P<0. 05) for the 6 indexes, including systolic blood pressure, diastolic blood pressure, hemorrhagic transformation after thrombolysis, NIHSS before thrombolysis, NIHSS at the time of discharge, and mRS scores. were statistically significant (P<0.05). The collected data suggest that the above six factors may be involved in the early indicators of neurological deterioration in patients undergoing intravenous thrombolysis for acute cerebral infarction (Table 1).

Table 1. Comparison of baseline clinical data between END and non-END patients

Projects	END (n=36)	Non-END (n=121)	Test Value	P-value
Sex (cases)	24/12	86/35	0.257	0.612
Age (years)	63.58±10.62	62.29±10.73	-0.637	0.525
Body Mass Index (kg/m2)	24.62±3.56	25.13±3.73	-0.799	0.426
Hypertension (cases, %)	26 (72.2)	80 (66.1)	0.472	0.492
Coronary artery disease (cases, %)	9 (25.0)	16 (13.2)	2.874	0.090
Diabetes mellitus (cases, %)	12 (33.3)	40 (33.1)	0.001	0.975
Cerebral infarction (cases, %)	6（16.7）	25（20.7）	0.279	0.597
Atrial fibrillation (cases, %)	6（16.7）	10（8.3）	2.140	0.143
Hyperlipidemia (cases, %)	3（8.3）	18（14.9）	1.025	0.311
Family history (case, %)	7（19.4）	28（23.1）	0.219	0.640
Smoking (case, %)	20 (55.6)	72 (59.5)	0.178	0.673
Alcohol consumption (case, %)	20 (25.6)	58 (47.9)	0.645	0.422
Systolic Blood Pressure (x±s,mmHg)	150.39±19.49	144.58±13.57	-2.025	0.045
Diastolic blood pressure (mmHg)	90.72±13.63	86.16±10.99	-2.067	0.040
Fasting blood glucose (mmol/L)	7.59±4.63	7.21±3.02	-0.579	0.563
Random blood glucose (mmol/L)	7.93±3.73	8.22±3.19	0.458	0.648
TC (mmol/L)	5.13±1.18	4.73±1.06	-1.916	0.057
TG (mmol/L)	1.72±1.11	1.63±1.31	-0.338	0.735
LDL-C (mmol/L)	3.27±0.84	3.03±0.72	-1.696	0.092
HDL-C (mmol/L)	1.22±0.25	1.35±0.59	1.275	0.204
Homocysteine (μmol/L)	18.06±12.72	16.19±7.94	-1.070	0.286
Uric acid (μmol/L)	347.17±88.85	334.45±99.37	-0.690	0.491
CRP (mg/L)	5.20±6.45	4.63±5.95	-0.499	0.618
Before thrombolysis
INR	0.93±0.07	0.95±0.18	0.738	0.462
Fibrinogen	2.92±0.67	2.84±0.63	-0.632	0.528
Prothrombin time	17.38±0.97	17.96±2.94	1.182	0.239
Activated Partial Thromboplastin Time	23.51±4.35	24.07±7.92	0.406	0.685
After thrombolysis
INR	1.41±0.55	1.33±0.50	-0.883	0.379
Fibrinogen	2.71±0.51	2.81±0.51	1.026	0.307
Prothrombin Time	18.11±0.88	18.02±1.49	-0.325	0.746
Activated Partial Thromboplastin Time	41.32±15.84	40.08±15.68	-0.417	0.677
<3 hours [number of cases (%)	8（22.2）	15（12.4）	2.142	0.143
3-4.5 hours [Number of cases (%)	28（77.8）	106（87.6）	2.142	0.143
Hemorrhage conversion after thrombolysis	4 (11.1)	1 (0.8)	9.518	0.002
ESSENCE	3.39±1.15	3.27±1.06	-0.567	0.572
NIHSS before thrombolysis	7.61±2.56	5.50±1.41	-6.420	0.000
NIHSS at discharge	4.19±4.00	1.45±1.98	-5.605	0.000
mRS score	2（1,4）	0（0,1）	-6.115	0.000

2.2 Comparison of the relationship between the presence or absence of END and SIR levels after thrombolysis in acute cerebral infarction

In patients with acute cerebral infarction before intravenous thrombolysis and 24 hours after treatment, the SIR values of patients who developed END in the treated cases were significantly lower than the SIR values of patients in the group who did not develop END. The difference was statistically significant (P<0.05). The experimental results suggest that the presence of END before and 24 hours after intravenous thrombolysis has the potential to predict early neurological deterioration in patients (Table 2).

Table 2. Comparison of SIR levels between the END and non-END groups before and after treating acute stroke

Group	SIR before thrombolysis	SIR 24 hours after thrombolysis
END group (n=36)	0.83(0.66,0.97)	0.89(0.70,1.12)
Non-END group (n=121)	0.90(0.79,1.17)	1.01(0.79,1.40)
t value	-2.800	-2.675
P value	0.005	0.007

Note: (SIR: Signal Intensity Ratio of Blood Flow)

2.3 Correlation between pre-thrombolytic SIR and END in patients with acute cerebral infarction receiving IV thrombolysis

The SIR value was calculated based on the signal intensity ratio proposed by Leng in 2013, and the pre-thrombolytic blood flow signal intensity (SIR) was grouped according to quartiles^[12]. The association between the SIR value and the risk of neurological deterioration in the early stage of intravenous thrombolysis for acute cerebral infarction was analyzed. The results showed that the number of patients in the non-END group tended to increase with increasing SIR level. On the contrary, the number of patients in the END group showed a decreasing trend in the rate of END occurrence as the Q value increased, and the difference in SIR between the two groups was statistically significant when comparing the two groups (P<0.05). The experimental results suggest that there is a correlation between blood flow signal intensity before intravenous thrombolysis for cerebral infarction and the risk of neurological deterioration in the early stage of intravenous thrombolysis for acute cerebral infarction (Table 3). Figure 1 shows two cases demonstrating the use of TOF-MRA to calculate the SIR value and END assessment of the M1 segment of the middle cerebral artery.

Table 3. Correlation analysis between SIR values and risk of END with intravenous thrombolysis in acute stroke


Group	SIR Horizontal Quartile Group				Z*	P-value
Group	Q1(≤0.74)	Q2(0.74-)	P-value	Q4(1.12-)	Z*	P-value
END group (n=36)	16	10	6	4	-3.086	0.002
Non-END group (n=121)	23	38	26	34	-3.086	0.002

Note: (SIR: Signal Intensity Ratio of Blood Flow)

2.4 Multifactorial Analysis of SIR Values and END in Patients Undergoing Intravenous Thrombolysis for Acute Cerebral Infarction

Using the grouping of whether or not neurological deterioration occurred in the early stage of acute cerebral infarction patients undergoing intravenous thrombolysis as the dependent variable (non-END group=0, END group=1), the factors that were statistically significant in the above analysis, including systolic blood pressure, diastolic blood pressure, pre-thrombolysis NIHSS, pre-thrombolysis NIHSS, diastolic blood pressure, pre-thrombolysis NIHSS, pre-thrombolysis SIR value, and post-thrombolysis hemorrhage were transformed to be the independent variables (Table 4) and included in a multifactorial logistic regression model for multifactorial factor analysis. The results showed that pre-thrombolysis NIHSS, pre-thrombolysis SIR, and post-thrombolysis hemorrhage transformation were still associated with early occurrence of neurological deterioration in patients who underwent intravenous thrombolysis for acute cerebral infarction after excluding other confounders (P<0.05) (Table 5).

Table 4. Table of influencing factor variable assignments

Variable Name	Assignment Description
Systolic Blood Pressure (mmHg)	Measured Value
Diastolic Blood Pressure (mmHg)	Measured Value
NIHSS before thrombolysis	Measured Value
SIR before thrombolysis	Measured value
Hemorrhage conversion after thrombolysis	0=No, 1=Yes

Note: (SIR: Signal Intensity Ratio of Blood Flow)

Table 5. Multifactorial logistic regression analysis of END in patients receiving intravenous thrombolysis for acute cerebral infarction

Independent variables	β	SE	Wald	P	OR	OR95%CI
Systolic Blood Pressure (mmHg)	0.028	0.018	2.337	0.126	1.028	0.992~1.066
Diastolic Blood Pressure (mmHg)
NIHSS before thrombolysis	0.013	0.022	0.310	0.577	1.013	0.969~1.058
SIR before thrombolysis	0.564	0.139	16.518	0.000	1.758	1.339~2.307
Bleeding conversion after thrombolysis	-1.858	0.912	4.151	0.042	0.156	0.026~0.932
Systolic Blood Pressure (mmHg)	-2.729	1.354	4.555	0.044	0.065	0.005~0.928

Note: (SIR: Signal Intensity Ratio of Blood Flow)

2.5 Comparison of mRS scores between the 2 groups of patients within 3 months of disease onset

157 patients completed the 3-month follow-up by telephone or in person, including 36 in the END group and 121 in the no-END group. The proportion of mRS score ≥3 in the END group was significantly higher than that in the no-END group (36.1% vs. 5. 8%, P < 0.001), and the proportion of mRS score 0-2 was significantly lower than that in the no-END group (63.9% vs. 94.2%, P < 0.001) (Table 6 and Figure 2).

Table 6. Comparison between the 2 patient groups for 3-month mRS scores

Projects	END group (n=36)	Non-END group (n=121)	Test Value	P-value
mRS (0-2Scores)	23(63.9)	114（94.2）	24.954	＜0.001
mRS (≥3Scores)	13（36.1）	7（5.8）	24.954	＜0.001

2.6 Clinical Value of ROC Curve Analysis of SIR in Predicting END of Intravenous Thrombolysis in Acute Cerebral Infarction

ROC curve analysis showed that the AUC of the two indicators, baseline NIHSS score and pre-thrombolysis SIR value, for the combined detection of END was 0.791 (95% CI: 0.712-0.870), with a sensitivity and specificity of 60% and 88.9%, respectively, higher than that of the two indicators individually, with P<0.001 (see Figure 3). The AUC was improved by 0.137 compared to detection based on SIR alone (baseline NIHSS score: AUC of 0.770, 95% CI: 0.691 to 0.849, P < 0.001 (Figure 3); pre-thrombolysis SIR: AUC of 0.654, 95% CI: 0.556 to 0.752, P = 0.005 (Figure 3), suggesting that the combined test was more helpful in assessing patient status (Table 7).

Table 7. Predictive value of SIR and baseline NIHSS score for END in patients with Acute cerebral infarction receiving intravenous thrombolysis

Projects		Cut-off value optimal	AUC	95%CI	sensitivity	specificity	P-value
Baseline NIHSS Score	5.5		0.770	0.691～0.849	57	86.1	0.000
Pre-thrombolytic SIR	0.75		0.654	0.556～0.752	81	47.2	0.005
Combined test	0.16		0.791	0.712～0.870	60	88.9	0.000

2.7 Biased correlation analysis of baseline NIHSS score in patients with acute cerebral infarction with intravenous thrombolysis

The results of the analysis showed that the bias correlation coefficients of baseline NIHSS score with discharge NIHSS score and mRS score were 0.499 and 0.506, which were positively correlated (P < 0.05) under the condition of END as a control variable. This suggests a significant linear correlation between baseline NIHSS score and discharge NIHSS score and 3-month mRS score, and no correlation with post-thrombolytic hemorrhage (P > 0.05), as shown in Table 8.

Table 8. Correlation analysis of biases in baseline NIHSS scores

Projects	r	p
Discharge NIHSS Score	0.499	0.000
Bleeding after thrombolysis	0.045	0.579
mRS score	0.506	0.000

2.8 Correlation Analysis of Pre-Thrombolytic SIR in Acute Stroke with Intravenous Thrombolysis

Further Spearman correlation analysis was performed in patients with acute cerebral infarction who received intravenous thrombolysis with early neurological dysfunction. The results showed that the pre-thrombolysis SIR value was negatively correlated with the level of mRS score and post-thrombolysis hemorrhagic transformation (r=-0.218, p=0.006; r=-0.166, p=0.038), while it was positively correlated with the post-thrombolysis SIR value (r=0.408, p=0.000) (Table 9).

Table 9. Correlation of pre- and post-thrombolysis SIR values, hemorrhagic conversion, and mRS scores

Projects	r-value	P-value
mRS score	-0.218	0.006
Post-Thrombolytic SIR Values	0.408	0.000
Hemorrhage conversion after thrombolysis	-0.166	0.038

Although intravenous thrombolysis is currently the mainstay of treatment for patients with acute stroke, not all patients benefit from this therapy. Approximately one-third of patients develop neurological deterioration early after thrombolysis, leading to a poor prognosis ^[5]. Among the 157 patients with acute cerebral infarction in this study, the rate of neurological deterioration after 24 hours of intravenous thrombolysis was 22.9%, which is similar to the results reported in previous studies ^[3]. It is of clinical significance how to predict early and accurately the occurrence of END after intravenous thrombolysis so that clinical interventions can be made in time.

In this study, 157 patients with acute cerebral infarction were selected and treated according to the ESO guidelines for intravenous thrombolysis in acute ischemic stroke ^[16]. Comparison of the results between the two groups showed that baseline systolic and diastolic blood pressure, pre-thrombolysis NIHSS score, post-thrombolysis hemorrhagic conversion and mRS scores were significantly higher in the END group than in the non-END group. The number of patients with a poor 3-month prognosis was also significantly higher in the END group than in the no-END group. And the END group was still associated with pre-thrombolysis NIHSS score and post-thrombolysis bleeding conversion after excluding other confounders. This also suggests that the baseline NIHSS score can be used not only to assess the severity of the disease, but also as an indicator to identify patients with potentially poor prognosis before intravenous thrombolysis, which has a certain reference value for early assessment of the occurrence of END ^[17]. Previous studies have also shown that higher baseline NIHSS scores tend to indicate more severe neurological deficit symptoms in patients with acute cerebral infarction and are associated with the risk of malignant cerebral edema and hemorrhagic transformation after thrombolysis. This suggests a poor prognosis and is an independent risk factor for the development of END ^[18]. The present study is basically consistent with the above findings, and the results of partial correlation analysis showed that there was a significant linear correlation between the baseline NIHSS scores and the NIHSS scores at the time of discharge and the mRS scores at 3 months after discharge. In addition, this study found that the pre- and post-thrombolysis SIR values in the END group were significantly lower than those in the non-END group. And logistic regression further confirmed that in addition to pre-thrombolysis NIHSS score and post-thrombolysis hemorrhagic transformation and other factors, abnormal SIR value is also an important risk factor for END in patients with acute cerebral infarction IV thrombolysis. Furthermore, by Spearman correlation analysis, it was found that pre-thrombolysis SIR value was negatively correlated with 3-month mRS score and post-thrombolysis hemorrhagic transformation in patients with acute cerebral infarction, and positively correlated with post-thrombolysis SIR value. It indicates that the lower the pre-thrombolysis SIR value, the higher the risk of post-thrombolysis hemorrhagic transformation and poor prognosis, and the worse their hemodynamic recovery. It is also shown that lower SIR values are involved in the development of END 24 hours after intravenous thrombolysis and are associated with poor prognosis. A previous study on the relationship between SIR values and cerebral perfusion in patients with unilateral middle cerebral artery stenosis found that SIR values were significantly lower in patients in the underperfused group compared to the normally perfused group, and that an SIR value < 0.9 was independently associated with inadequate cerebral perfusion distal to the stenosis ^[19]. Furthermore, Lan et al. found that SIR values were significantly and linearly negatively correlated with cerebral blood volume and blood flow velocity on the ipsilateral side of the lesion when they examined the relationship between SIR values and ipsilateral cerebral perfusion [10]. In our study, we grouped the pre-thrombolysis signal intensity of blood flow (SIR) according to quartiles, and the results showed that the number of patients in the END-free group tended to increase with the increase of the SIR level, while the number of patients in the END group tended to decrease, and the number of patients in the END-free group was significantly increased when the SIR was > 0.9. This may be due to the fact that when atherosclerosis in the brain causes stenosis or occlusion of blood vessels, cerebral perfusion at the distal end of the stenosis decreases, resulting in a change in the hemodynamic index of SIR value, which leads to the occurrence of acute cerebral infarction ^[20]. Therefore, SIR value can be measured by MRA before intravenous thrombolysis to monitor hemodynamic information to assess cerebrovascular blood flow to predict the risk of END in patients with acute cerebral infarction. This also suggests that the SIR value can be used as a non-invasive and practical tool to detect changes in cerebral hemodynamics in patients undergoing intravenous thrombolysis for acute cerebral infarction, which is of high value in evaluating efficacy and prognosis.

Compared with hemodynamic clinical assessment methods such as transcranial Doppler ultrasound, CT cerebrovascular perfusion imaging, and DSA, the acquisition of SIR values by TOF-MRA has the advantages of being noninvasive, simple, highly reproducible, and independent of contrast media ^[10]. In addition, in our study, magnetic resonance imaging (MRI) was performed before and after thrombolysis, which can measure SIR values more accurately and intuitively than in previous studies and can monitor changes in SIR values. The exponential SIR value can be considered as a simple and effective marker of hemodynamic significance before and after thrombolysis.

Intravenous thrombolytic therapy with rt-PA achieves the therapeutic effect of recanalization of occluded blood vessels and salvage of ischemic penumbra by reducing blood viscosity, improving blood coagulation, and inhibiting platelet aggregation ^[21]. In this study, it was found that the SIR value increased after intravenous thrombolytic therapy compared with that before thrombolysis in both END and no-END groups. And the results of Spearman correlation analysis between pre-thrombolysis SIR values and post-thrombolysis SIR values showed a strong correlation. This also suggests that intravenous rt-PA thrombolysis can improve stenotic vessel dynamics and increase blood flow in the infarct area, which is consistent with previous studies ^[22].

Based on the above studies, the clinical value of the three indices of pre-thrombolytic SIR, pre-thrombolytic NIHSS, and post-thrombolytic hemorrhagic conversion in predicting whether END will occur after intravenous thrombolytic therapy was analyzed individually and jointly using ROC curves. The AUC of baseline NIHSS and pre-thrombolysis SIR for the combined detection of END was 0.791, and the sensitivity and specificity were 60% and 88.9%, respectively, higher than the AUC of baseline NIHSS and pre-thrombolysis SIR alone. The results suggest that baseline NIHSS score and pre-thrombolysis SIR value may be auxiliary predictors of END after intravenous thrombolysis for acute cerebral infarction and that the simultaneous detection of both may be a useful predictor of END after intravenous thrombolysis. Adjunctive predictors. The results suggest that the baseline NIHSS score and the pre-thrombolysis SIR value may be additional predictors of END after intravenous thrombolysis in acute cerebral infarction. Previous studies have also found that the SIR value measured by MRA may be a strong predictor of recurrent stroke and can be used for risk stratification of stroke risk within a certain range, which supports the results of this experiment ^[11].

Combining the results of the above experiments, the AUC value of early neurological deterioration in patients with acute cerebral infarction predicted based on magnetic resonance imaging information combined with two indicators of cerebral hemodynamics (SIR values) and baseline NIHSS scores reaches 0.791, which provides a method for early screening of END high-risk groups.

Acknowledgements

Not applicable.

Authors’ contributions

XY.L. First author,wrote the main manuscript text. PR.Z. Partial data collection . B.L. Partial data collection . X.Y. Part of the literature was collected. XY.D. Prepared figures 1. XQ.Y. Prepared figures 2. FF.Z. Prepared figures 2. Y.C. Prepared figures 3. Z.D. Prepared figures 3. PL.Z. Corresponding authors,review papers,verifying that all data, figures, materials.

Funding

This work was supported by the Tianjin Municipal Health Bureau Key Project (grant no. TJWJ2022XK030).

Availability of data and materials

The data of this study were collected from two hospitals in the Shenzhen area.

Ethics approval and consent to participate

This study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethical Committee of the Tianjin Huanhu Hospital（Approval number:2022-047; Data:2022.5.10）. Informed consent has been obtained from the participants, their parents and legally authorized representatives in this study.

Consent for publication

Accepted for publication.

Competing interests

All authors in this study declare that they have no competing interests.

Author details

1, Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin 300222, China.

2, Department of Emergency Medicine, The First Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010000, China.

3, The Second Hospital of Tianjin Medical University, Tianjin 300222, China.

4, Department of Neurology, Tianjin Huanhu Hospital, Tianjin 300222, China.

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No competing interests reported.

Multimodal Nuclear Magnetic Imaging Prediction of Early Neurological Deterioration in Patients with Acute Stroke Using Intravenous Thrombolysis

Status:

Version 1

Abstract

Figures

Introduction

Materials and Methods

Results

Discussion

Declarations

References

Additional Declarations

Status:

Version 1