Optimizing the prediction of sepsis-associated encephalopathy with cerebral circulation time utilizing a nomogram: a pilot study in the intensive care unit.

Background: Sepsis-associated encephalopathy (SAE) is prevalent in intensive care unit (ICU) environments but lacks established treatment protocols, necessitating prompt diagnostic methods for early intervention. Traditional symptom-based diagnostics are non-specific and confounded by sedatives, while emerging biomarkers like neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B) have limited specificity. Transcranial Doppler (TCD) indicators, although is particularly relevant for SAE, requires high operator expertise, limiting its clinical utility. Objective: This pilot study aims to utilize cerebral circulation time (CCT) assessed via contrast-enhanced ultrasound (CEUS) as an innovative approach to investigate the accuracy of SAE prediction. Further, these CCT measurements are integrated into a nomogram to optimize the predictive performance. Methods: This study employed a prospective, observational design, enrolling 67 ICU patients diagnosed with sepsis within the initial 24 h. Receiver operating characteristic (ROC) curve analyses were conducted to assess the predictive accuracy of potential markers including NSE, S100B, TCD parameters, and CCT for SAE. A nomogram was constructed via multivariate Logistic Regression to further explore the combined predictive potential of these variables. The model's predictive performance was evaluated through discrimination, calibration, and decision curve analysis (DCA). Results: SAE manifested at a median of 2 days post-admission in 32 of 67 patients (47.8%), with the remaining 35 sepsis patients constituting the non-SAE group. ROC curves revealed substantial predictive utility for CCT, pulsatility index (PI), and S100B, with CCT emerging as the most efficacious predictor, evidenced by an area under the curve (AUC) of 0.846. Multivariate Logistic Regression identified these markers as independent predictors for SAE, leading to the construction of a nomogram with excellent discrimination, substantiated by an AUC of 0.924 through bootstrap resampling. The model exhibited satisfactory concordance between observed and predicted probabilities, and DCA confirmed its clinical utility for the prompt identification of SAE. Conclusion: This study highlighted the enhanced predictive value of CCT in SAE detection within ICU settings. A novel nomogram incorporating CCT, PI, and S100B demonstrated robust discrimination, calibration, and clinical utility, solidifying it as a valuable tool for early SAE intervention.

Cerebral Circulation Time After Thrombectomy: A Potential Predictor of Outcome After Recanalization in Acute Stroke.

Background Despite successful recanalization, up to half of patients with acute ischemic stroke caused by large-vessel occlusion treated with endovascular treatment (EVT) do not recover to functional independence. We aim to evaluate the role of cerebral circulation time (CCT) as outcome predictor after EVT. Methods and Results We retrospectively enrolled consecutive patients with acute ischemic stroke-large-vessel occlusion undergoing EVT. Three categories of CCT based on digital subtraction angiography were studied: CCT of the stroke side, CCT of the healthy side), and change of CCT of the stroke side versus CCT of the healthy side. Dramatic clinical recovery was defined as a 24-hour National Institutes of Health Stroke Scale score ≤2 or ≥8 points drop. A modified Rankin Scale score ≤2 at 3 months was considered a favorable outcome. Logistic regression analysis was performed to evaluate the prediction of CCT on prognosis. One hundred patients were enrolled, of which 38 (38.0%) experienced a dramatic clinical recovery and 43 (43.0%) achieved a favorable outcome. Logistic regression analysis found that shorter change of CCT of the stroke side versus CCT of the healthy side and CCT of the stroke side were independent positive prognostic factors for dramatic clinical recovery (odds ratio [OR], 0.189; P=0.033; OR, 0.581; P=0.035) and favorable outcomes (OR, 0.142; P=0.020; OR, 0.581; P=0.046) after adjustment for potential confounders. A model including the change of CCT of the stroke side versus CCT of the healthy side also had significantly higher area under the curve values compared with the baseline model in patients with dramatic clinical recovery (0.780 versus 0.742) or favorable outcome (0.759 versus 0.713). Conclusions To our knowledge, this is the first report that CCT based on digital subtraction angiography data exhibits an independent predictive performance for clinical outcome in patients with acute ischemic stroke-large-vessel occlusion after EVT. Given that this readily available CCT can provide alternative perfusion information during EVT, a prospective, multicenter trial is warranted.

Cerebral Circulation Time Is a Potential Predictor of Disabling Ischemic Cerebrovascular Events in Patients With Non-disabling Middle Cerebral Artery Stenosis.

Patients with non-disabling middle cerebral artery (MCA) stenosis (ND-MCAS) are at risk for disabling ischemic cerebrovascular events (DICE) despite aggressive medical therapy. In this study, we aimed to verify whether cerebral circulation time (CCT) was a potential predictor of DICE in patients with ND-MCAS. From January 2015 to January 2020, 46 patients with ND-MCAS treated with aggressive medical therapy were enrolled for digital subtraction angiography (DSA) in this convenience sampling study. They were divided into the DICE (-) and DICE (+) groups based on the occurrence of DICE within 3 months after DSA. The CCT was defined as the time from the appearance of the MCA to the peak intensity of the Trolard vein during DSA. The rCCT (relative CCT) was defined as the ratio of the CCT of the stenotic side (sCCT) to the CCT of the healthy side (hCCT). The differences in sCCT, hCCT, and rCCT between the two groups were analyzed with Mann-Whitney U tests. Logistic regression analysis was performed to evaluate the association between the risk factors and DICE. Receiver operating characteristic (ROC) curves were constructed to assess the predictive value of rCCT in identifying DICE in ND-MCAS patients. The results showed that DICE appeared in 5 of the 46 patients within 3 months. rCCT were significantly increased in the DICE (+) group compared with the DICE (-) group [1.08 (1.05, 1.14) vs. 1.30 (1.22, 1.54), p < 0.001]. Logistic regression analysis found that prolonged rCCT was an independent positive prognostic factor for DICE (odds ratio = 1.273, p = 0.019) after adjustment for potential confounders (age, diabetes, antithrombotic use, and stenosis degree). ROC analysis showed that rCCT provided satisfactory accuracy in distinguishing the DICE (+) group from the DICE (-) group among ND-MCAS patients (area under the curve = 0.985, p < 0.001), with an optimal cutoff point of 1.20 (100% sensitivity, 97.6% specificity). In conclusion, prolonged rCCT is independently associated with the occurrence of DICE in ND-MCAS patients and may be used to identify individuals at risk of DICE.

Insights into Endothelin-3 and Multiple Sclerosis.

Endothelins are powerful vasoconstrictor peptides that play numerous other roles. Endothelin-1 (ET1) is the principal isoform produced by the endothelium in the human cardiovascular system. Endothelin-3 (ET3) and its rPptor affinity have been demonstrated to support neuronal repair mechanisms throughout life. In multiple sclerosis (MS), the role of vasoactive peptides are not well defined. Here we focus on ET3, specifically the plasma levels between MS patients and healthy subjects. Furthermore, we evaluated the changes in ET1 and ET3 plasma levels during different disease phases, the correlation between ET3 and cerebral circulation time, and the relationship between ET1 and ET3. In MS patients, the ET3 plasma levels were altered in a time-dependent manner. These results could support a putative role of ET3 in neuroprotection and/or neuroimmune modulation over time.

Cerebral venous circulation changes caused by aneurysmal subarachnoid hemorrhage.

BACKGROUND: The aneurysmal subarachnoid hemorrhage (aSAH) is an acute severe hemorrhagic stroke with high morbidity and mortality with poor prognosis. OBJECTIVE: This study aims to analyze the changes of cerebral venous circulation in patients with aneurysmal subarachnoid hemorrhage by digital subtraction angiography (DSA). MATERIALS AND METHODS: Totally, 57 patients with aSAH, 48 patients with unruptured aneurysms, and 45 patients without aneurysms (control group) were enrolled. The microvascular cerebral circulation time (mCCT), venous cerebral circulation time (vCCT), cerebral arterioles and cortical veins were analyzed by DSA. RESULTS: There were changes of cerebral microvessels and cortical veins in patients with aSAH. The mCCT (6.15±1.37 s) and vCCT (2.79±0.34 s) of aSAH patients significantly increased compared with control patients (3.74±0.50 s; 2.64±0.32 s) (P < 0.05). However, the mCCT increased more compared with vCCT in aSAH patients (P < 0.001), while the vCCT increased more compared with mCCT in severe aSAH cases (P < 0.01). There was no significant difference in mCCT and vCCT between patients with unruptured aneurysms and controls (P = 0.131; P = 0.621). CONCLUSIONS: The mCCT increases in acute aSAH patients within 72 hours and vCCT increases in severe aSAH cases.

Multiparametric 3D Contrast-Enhanced Ultrasound to Assess Internal Carotid Artery Stenosis: A Pilot Study.

BACKGROUND AND PURPOSE: Extracranial internal carotid artery stenoses (ICASs) may greatly differ with respect to morphological and hemodynamical aspects. The aim of this pilot study was to evaluate the use of multiparametric 3-dimensional (3D) contrast-enhanced ultrasound (3D-CEUS) to comprehensively examine ICAS. METHODS: Fifteen patients with moderate to severe ICAS were examined with multiparametric 3D-CEUS, power-mode 3D ultrasound (3DUS), color-coded duplex sonography (CDS), and digital subtraction angiography (DSA) (n = 9). Multiparametric 3D-CEUS comprised the assessment of the morphology and the stenotic degree of ICAS and the measurement of the ipsistenotic cerebral circulation time (CCT). RESULTS: Multiparametric 3D-CEUS reliably visualized even complex aspects of ICAS such as ulcerated or heavily calcified plaques with high spatial resolution. When comparing the different methods to quantify ICAS, the intermethod agreement was good (ranging from poor to excellent) between 3D-CEUS and CDS, moderate (ranging from poor to good) between 3D-CEUS and DSA, and poor (ranging from poor to good) between CDS and DSA. The CCT was significantly longer in patients with ICAS than in healthy subjects (8.2 ± 1.5 seconds vs. 6.5 ± 1.3 seconds, P = .026). CONCLUSION: In this pilot study, bedside multiparametric 3D-CEUS provided reliable estimations of different morphological and hemodynamical aspects of ICAS, thus ideally complementing CDS.

Cerebral circulation time derived from fMRI signals in large blood vessels.

BACKGROUND: The systemic low-frequency oscillation (sLFO) functional (f)MRI signals extracted from the internal carotid artery (ICA) and the superior sagittal sinus (SSS) are found to have valuable physiological information. PURPOSE: 1) To further develop and validate a method utilizing these signals to measure the delay times from the ICAs and the SSS. 2) To establish the delay time as an effective perfusion biomarker that associates with cerebral circulation time (CCT). 3) To explore within subject variations, and the effects of gender and age on the delay times. STUDY TYPE: Prospective. SUBJECTS: In all, 100 healthy adults (Human Connectome Project [HCP], age range 22-36 years, 54 females and 46 males), 56 healthy children (Adolescent Brain Cognitive Development project) were included. FIELD STRENGTH/SEQUENCE: Echo planar imaging (EPI) sequence at 3T. ASSESSMENT: The sLFO fMRI signals from the ICAs and the SSSs were extracted from the resting state fMRI data. The maximum cross-correlation coefficients and their corresponding delay times were calculated. The gender and age differences of delay times were assessed statistically. STATISTICAL TESTS: T-tests were conducted to measure the gender differences. The Kruskal-Wallis test was used to detect age differences. RESULTS: Consistent and robust results were found from 80% of the 400 HCP scans included. Negative correlations (-0.67) between the ICA and the SSS signals were found with the ICA signal leading the SSS signal by ∼5 sec. Within subject variation was 2.23 sec at the 5% significance level. The delay times were not significantly different between genders (P = 0.9846, P = 0.2288 for the left and right ICA, respectively). Significantly shorter delay times (4.3 sec) were found in the children than in the adults (P < 0.01). DATA CONCLUSION: We have shown that meaningful perfusion information (ie, CCT) can be derived from the sLFO fMRI signals of the large blood vessels. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019;50:1504-1513.

Effects of propofol versus sevoflurane on cerebral circulation time in patients undergoing coiling for cerebral artery aneurysm: a prospective randomized crossover study.

Many neuroendovascular treatments are supported by real-time anatomical and visual hemodynamic assessments through digital subtraction angiography (DSA). Here we used DSA in a single-center prospective randomized crossover study to assess the intracranial hemodynamics of patients undergoing coiling for cerebral aneurysm (n = 15) during sevoflurane- and propofol-based anesthesia. Color-coded DSA was used to define time to peak density of contrast medium (TTP) at several intravascular regions of interest (ROIs). Travel time at a particular ROI was defined as the TTP at the selected ROI minus TTP at baseline position on the internal carotid artery (ICA). Travel time at the jugular bulb on the anterior-posterior view was defined as the cerebral circulation time (CCT), which was divided into four segmental circulation times: ICA, middle cerebral artery (MCA), microvessel, and sinus. When bispectral index values were kept between 40 and 60, CCT (median [interquartile range]) was 10.91 (9.65-11.98) s under propofol-based anesthesia compared with 8.78 (8.32-9.45) s under sevoflurane-based anesthesia (P < 0.001). Circulation times for the ICA, MCA, and microvessel segments were longer under propofol-based anesthesia than under sevoflurane-based anesthesia (P < 0.05 for all). Our results suggest that, relative to sevoflurane, propofol decreases overall cerebral perfusion.

Pseudotumor cerebri and lung cancer-associated jugular vein thrombosis: Role of anatomical variations of torcular herophili.

A 71-year-old male appeared at the facility complaining of disturbance of consciousness and bilateral papilledema. The laboratory test revealed anemia and coagulation abnormality. A physical examination and magnetic resonance imaging (MRI) of the brain with and without gadolinium showed no abnormalities. A lumbar puncture showed a high pressure, but a normal cerebrospinal fluid (CSF) cell count. Cerebral angiography showed no morphological abnormalities, but it revealed an asymmetric right dominant type of confluence of the sinuses with the partially-communicating left transverse sinus in the late phase. Furthermore, there was a delay in the cerebral circulation time (CCT). Subsequently, venography and ultrasonography revealed right internal jugular vein thrombosis associated with lung cancer. The patient recovered from the disturbance of consciousness immediately after an emergency ventriculoperitoneal shunt and anticoagulation therapy. This case was diagnosed as secondary pseudotumor cerebri (PTC). In order to facilitate the early detection of secondary PTC, it is important to take note of symptoms of intracranial hypertension with no remarkable intracranial lesions and to consider the possibility of PTC, especially in the patients with high risk factors for coagulopathy including lung cancer.

Evaluating cerebral hemodynamics using quantitative digital subtraction angiography and flat-detector computed tomography perfusion imaging: A comparative study in patients with carotid stenosis.

BACKGROUND: The efficacy of both quantitative digital subtraction angiography (QDSA) and flat-detector computed tomography perfusion (FD-CTP) is equivalent to that of magnetic resonance perfusion (MRP) in assessing perfusion deficits in carotid stenosis. This study evaluated the feasibility of using FD-CTP to monitor cerebral hemodynamics during carotid stenting. METHODS: Thirteen patients with extracranial carotid stenosis (>70%) were included. Both QDSA and two FD-CTP sessions were performed before and after carotid stenting. Cerebral circulation time (CCT) was defined as the difference between the time to peak (TTP) of the parietal vein and the cavernous internal carotid artery. For FD-CTP and MRP, regions of interest (ROIs) were placed in the middle cerebral artery territory at the basal ganglia level of both stenotic and contralateral hemispheres for measurement. The TTP ratio (rTTP) was defined as stenotic TTP divided by contralateral TTP; and ratio of cerebral blood volume (rCBV), ratio of mean transit time (rMTT), and ratio of cerebral blood flow (rCBF) were defined similarly. Both CCT and ratio perfusion parameters were compared during stenting. RESULTS: Before stenting, only rCBF (r = 0.73) and rTTP (r = 0.58) demonstrated correlations between FD-CTP and MRP; CCT correlated with only rMTT in MRP (r = 0.69). After stenting, only rCBF (r = 0.56) indicated a correlation between FD-CTP and MRP. Regarding cerebral flow after stenting, CCT (4.61 ± 1.6 s) was shortened, rMTT (1.12 ± 0.04) and rTTP (r = 1.05 ± 0.03) decreased, and rCBF (0.91 ± 0.16) increased significantly. CONCLUSION: FD-CTP provides a potentially more comprehensive hemodynamic assessment of parenchymal perfusion changes compared with QDSA during carotid stenting, but FC-CTP requires additional 18 min. FD-CTP confirmed that the normalization of cerebral hemodynamics began immediately and continued for 1-3 days.

Finding the optimal deconvolution algorithm for MR perfusion in carotid stenosis: Correlations with angiographic cerebral circulation time.

PURPOSE: The aim of our study is to explore the impacts of different deconvolution algorithms on correlations between CBF, MTT, CBV, TTP, Tmax from MR perfusion (MRP) and angiography cerebral circulation time (CCT). METHODS: Retrospectively, 30 patients with unilateral carotid stenosis, and available pre-stenting MRP and angiography were included for analysis. All MRPs were conducted in a 1.5-T MR scanner. Standard singular value decomposition, block-circulant, and two delay-corrected algorithms were used as the deconvolution methods. All angiographies were obtained in the same bi-plane flat-detector angiographic machine. A contrast bolus of 12mL was administrated via angiocatheter at a rate of 8mL/s. The acquisition protocols were the same for all cases. CCT was defined as the difference between time to peak from the cavernous ICA and the parietal vein in lateral view. Pearson correlations were calculated for CCT and CBF, MTT, CBV, TTP, Tmax. RESULTS: The correlation between CCT and MTT was highest with Tmax (r=0.65), followed by MTT (r=0.60), CBF (r=-0.57), and TTP (r=0.33) when standard singular value decomposition was used. No correlation with CBV was noted. CONCLUSIONS: MRP using a singular value decomposition algorithm confirmed the feasibility of quantifying cerebral blood flow deficit in steno-occlusive disease within the angio-room. This approach might further improve patient safety by providing immediate cerebral hemodynamics without extraradiation and iodine contrast.

A new method of measurement of cerebral circulation time: contrast-enhanced ultrasonography in healthy adults and patients with intracranial shunts.

Alterations in the cerebral circulation time (CCT) are observed in several cerebrovascular diseases. We designed a new method of global CCT measurement using gray-scale contrast-enhanced ultrasound and studied healthy Chinese adults and patients with intracranial shunts. Eighty-one healthy volunteers and eight patients with intracranial shunt disease were enrolled. The contrast agent Sonovue was used. Perfusion in the carotid artery and internal jugular vein bilaterally was recorded. Start and peak filling CCTs were calculated and analyzed. Imaging of carotid vessels was uncomplicated in all patients. The bilateral start CCT was 6.23 ± 1.39 s in healthy patients. There were no significant differences within subgroups and contrast-dosage groups. In the patient group, the mean start CCT was 3.0 ± 0.56 s. There was a significant difference between the control and patient groups (p < 0.001). This new method using gray-scale contrast imaging can measure CCT and cerebral blood volume accurately. It can be used to visualize blood flow differences in real time and is less dependent on the training of the operator.

The relationship between the cerebral circulation time and disease condition and prognosis in patients with subarachnoid hemorrhage / 中国综合临床

Objective To investigate the relationship between the cerebral circulation time and disease condition and prognosis in patients with acute subarachnoid hemorrhage. Methods DSA were performed to determine the cerebral circulation time (CCT) in 60 patients who had subarachnoid hemorrhage (SAH) within 3 days. The patients were divided into different groups according to the severity of the disease condition,patients with CSC score as 13-15 were assigned as group Ⅰ ,whose CCT was (13.45 ± 1. 89) s. Twenty two patients with GSC score as 3-12 were assigned as group Ⅱ ,whose CCT was (16.79 ± 2. 07) s. There were significant difference between the CCT of the two groups (t =3. 76,P = 0. 001). (2)Twenty-nine patients with Hunt-Hess grade as 1-2 were assigned as group 1,whose CCT was (13.06 ± 1. 83) s. Thirty one patients with Hunt-Hess grade as 3-5 were assigned as group 2, whose CCT was (15. 89 ± 2.06) s. There were significant difference between the CCT of the two groups (t = 3. 39, P =0. 003). (3) Seventeen patients with delayed ischemic damage were assigned as group A, whose CCT was (16. 84 ±1.91) s. Forty three patients without delayed ischemic damage were assigned as group B, whose CCT was (12.94 ± 1. 67) s. There were significant difference between the CCT of the two groups (t = 2. 23, P =0.025). (4)Forty-six patients with GOS score as 4-5 were assigned as group a,whose CCT was (13.07 ±1. 89)s. Fourteen patients with GSC score as 1-3 were assigned as group b,whose CCT was (17.11 ± 1. 71)s. There were significant difference between the CCT of the two groups (t = 3. 27, P = 0.008). Conclusion CCT may reflect the severity of the SAH in early onset patients and has prognostic value.

Evaluation of cerebral circulation time by contrast-enhanced ultrasound in healthy adults / 中华超声影像学杂志

Objective To measure cerebral circulation time(CCT) of a group of normal adults by contrast-enhanced ultrasound. Methods Forty-seven cases of healthy volunteers without any cardio-cerebral disease history were enrolled in the study. Internal carotid artery and vertebral artery were observed and the blood flow was measured with high frequency probe. Contrast-enhanced agent SonoVue was injected bolus into median cubital vein. CCT was measured and calculated according to the contrast curve analysis. Contralateral CCT measurement was repeated when the blood flow signal resume to the baseline intensity. Cerebral blood volume was then calculated according to CCT and cerebral blood flow. Results All the imaging of carotid vessels was presented clearly in all objects. Cerebral blood flow was 603 ～ 990 ml/min with an average (778 ± 171)ml/min. Bi-lateral CCT was measured successfully,the value ranged 4. 1 ～ 10.2 s with average (6.22 ± 1.47) s. There were no significant differences both in contrast of left and right side of the carotid vessels and in contrast of three dosage groups ( P ＞0.05). The cerebral blood volume was 54～96ml with average (76 ± 27)ml. Conclusions Contrast-enhanced ultrasound can be useful in measurement and calculation of CCT and cerebral blood volume.