Generalized models for estimating cerebral lateralisation of young children using functional transcranial Doppler ultrasound.

Thompson et al., 2023 (Generalized models for quantifying laterality using functional transcranial Doppler ultrasound. Human Brain Mapping, 44(1), 35-48) introduced generalised model-based analysis methods for determining cerebral lateralisation from functional transcranial Doppler ultrasound (fTCD) data which substantially decreased the uncertainty of individual lateralisation estimates across several large adult samples. We aimed to assess the suitability of these methods for increasing precision in lateralisation estimates for child fTCD data. We applied these methods to adult fTCD data to establish the validity of two child-friendly language and visuospatial tasks. We also applied the methods to fTCD data from 4- to 7-year-old children. For both samples, the laterality estimates from the complex generalised additive model (GAM) approach correlated strongly with the traditional methods while also decreasing individual standard errors compared to the popular period-of-interest averaging method. We recommend future research using fTCD with young children consider using GAMs to reduce the noise in their LI estimates.

To Accelerate the Process of Brain Death Determination in China Through the Strategy and Practice of Establishing Demonstration Hospitals.

BACKGROUND: Our objective was to explore whether a brain death determination (BDD) strategy with demonstration hospitals can accelerate the process of BDD in China. METHODS: We proposed the construction standards for the BDD quality control demonstration hospitals (BDDHs). The quality and quantity of BDD cases were then analyzed. RESULTS: A total of 107 BDDHs were established from 2013 to 2022 covering 29 provinces, autonomous regions, and municipalities under jurisdiction of the central government of the Chinese mainland (except Qinghai and Tibet). A total of 1,948 professional and technical personnel from these 107 BDDHs received training in BDD, 107 quality control personnel were trained in the quality control management of BDD, and 1,293 instruments for electroencephalography, short-latency somatosensory evoked potential recordings, and transcranial Doppler imaging were provided for BDD. A total of 6,735 BDD cases were submitted to the quality control center. Among the nine quality control indicators for BDD in these cases, the implementation rate, completion rate, and coincidence rate of apnea testing increased the most, reaching 99%. CONCLUSIONS: The strategy of constructing BDDHs to promote BDD is feasible and reliable. Ensuring quality and quantity is a fundamental element for the rapid and orderly popularization of BDD in China.

Noninvasive Intracranial Pressure Monitoring: Are We There Yet?

There is an urgent unmet need for a reliable noninvasive tool to detect elevations in intracranial pressure (ICP) above guideline-recommended thresholds for treatment. Gold standard invasive ICP monitoring is unavailable in many settings, including resource-limited environments, and in situations such as liver failure in which coagulopathy increases the risk of invasive monitoring. Although a large number of noninvasive techniques have been evaluated, this article reviews the potential clinical role, if any, of the techniques that have undergone the most extensive evaluation and are already in clinical use. Elevations in ICP transmitted through the subarachnoid space result in distension of the optic nerve sheath. The optic nerve sheath diameter (ONSD) can be measured with ultrasound, and an ONSD threshold can be used to detect elevated ICP. Although many studies suggest this technique accurately detects elevated ICP, there is concern for risk of bias and variations in ONSD thresholds across studies that preclude routine use of this technique in clinical practice. Multiple transcranial Doppler techniques have been used to assess ICP, but the best studied are the pulsatility index and the Czosnyka method to estimate cerebral perfusion pressure and ICP. Although there is inconsistency in the literature, recent prospective studies, including an international multicenter study, suggest the estimated ICP technique has a high negative predictive value (> 95%) but a poor positive predictive value (≤ 30%). Quantitative pupillometry is a sensitive and objective method to assess pupillary size and reactivity. Proprietary indices have been developed to quantify the pupillary light response. Limited data suggest these quantitative measurements may be useful for the early detection of ICP elevation. No current noninvasive technology can replace invasive ICP monitoring. Where ICP monitoring is unavailable, multimodal noninvasive assessment may be useful. Further innovation and research are required to develop a reliable, continuous technique of noninvasive ICP assessment.

Clinical applications of point-of-care ultrasound in brain injury: a narrative review.

The use of point-of-care ultrasound has increased considerably over the last two decades. It has become a readily available, non-invasive bed-side modality for the rapid diagnosis and management of patients in various settings. Point-of-care ultrasound for assessing the heart, lung, abdomen, airway and vascular systems is now well established. Transcranial Doppler ultrasound for assessing cerebral blood flow has been in use for many years. In recent years, brain ultrasonography has been shown to be a powerful tool in the rapid bed-side assessment of cerebral haemodynamics and structural pathology. Brain ultrasound has been shown to be useful in both the emergency department and neurocritical care setting for the non-invasive assessment of raised intracranial pressure, cerebral autoregulation and diagnosis of intracranial haematoma and other space-occupying lesions. Point-of-care ultrasound is an important alternative technique to routine imaging and invasive monitoring techniques, and results are comparable. Competence is easily attainable without formal radiology training. With technological advancement, applications for the use of brain ultrasound continue to grow. This review discusses the clinical use of point-of-care ultrasound in the diagnosis and management of brain injury.

Serial neurosonography in fetuses with congenital heart defects shows mild delays in cortical development.

INTRODUCTION: Neurodevelopmental delay is more common in children born with congenital heart defects (CHD), even with optimal perinatal and peri-operative care. It is hypothesized that fetuses with CHD are prone to neurological impairment in utero due to their cardiac defect, possibly leading to delayed cortical development. METHODS: Cerebral cortical maturation was assessed with advanced neurosonographic examinations every 4 weeks in fetuses with CHD and compared to control fetuses. Five different primary fissures and four areas were scored (ranging 0-5) by blinded examiners using a cortical maturation scheme. RESULTS: Cortical staging was assessed in 574 ultrasound examinations in 85 CHD fetuses and 61 controls. Small differences in grading were seen in Sylvian and cingulate fissures. (Sylvian fissure: -0.12 grade, 95% CI (-0.23; -0.01) p = 0.05, cingulate fissure: -0.24 grade, 95% CI (-0.38; -0.10) p = <0.001. Other cortical areas showed normal maturation as compared to control fetuses. CONCLUSION: Small differences were seen in three of the nine analyzed cortical areas in CHD fetuses, in contrast to previous reports on progressive third-trimester delay. The clinical implications of the small differences however, remain unknown.

Acoustic biomolecules enhance hemodynamic functional ultrasound imaging of neural activity.

Hemodynamic functional ultrasound imaging (fUS) of neural activity provides a unique combination of spatial coverage, spatiotemporal resolution and compatibility with freely moving animals. However, deep and transcranial monitoring of brain activity and the imaging of dynamics in slow-flowing blood vessels remains challenging. To enhance fUS capabilities, we introduce biomolecular hemodynamic enhancers based on gas vesicles (GVs), genetically encodable ultrasound contrast agents derived from buoyant photosynthetic microorganisms. We show that intravenously infused GVs enhance ultrafast Doppler ultrasound contrast and visually-evoked hemodynamic contrast in transcranial fUS of the mouse brain. This hemodynamic contrast enhancement is smoother than that provided by conventional microbubbles, allowing GVs to more reliably amplify neuroimaging signals.

Transtemporal Ultrasound (US) Assessment of Third Ventricle Diameter (TVD): Comparison of US and MRI TVD in Pediatric Patients.

INTRODUCTION: In a retrospective magnetic resonance imaging (MRI)-based study, we showed that changes of the third ventricle diameter (TVD) are a reliable mirror of changes of the entire ventricular system. The third ventricle is easily accessible in more than 90% of children and adults using ultrasound (US) via the transtemporal bone-window; thus it can be assessed quickly and free of radiation. In order to use transtemporal US determination of TVD instead of MRI/CT in clinical practice, it is important to know if there is a correlation and bias between both methods, which is addressed in this study. MATERIALS AND METHOD: This prospective study investigates 122 children (newborn-18 years). Diagnoses encompassed hydrocephalus (50%), tumors (14.8%), and other intracranial pathologies (35.2%). US-based TVD was measured via the transtemporal bone-window using a phased array 1 to 4MHz transducer. Results were compared with TVD measured on simultaneously acquired axial T1-weighted axial MRI or computed tomography (CT) scans. RESULTS: Overall mean values for TVD were 6.56 ± 5.84 and 6.47 ± 5.64 mm for US and MRI, respectively. There was an outstanding correlation between TVD measured by MRI and US (r = 0.991, p < 0.01). Bland-Altman analysis showed a mean bias of 0.096 mm with limits of agreement of -0.99 and 1.18 mm. CONCLUSION: US- and MRI-based TVD measurements correlate excellently and measure almost identical TVD values. US-based TVD is in mean ∼0.096 mm larger than MRI-based TVD due to a more angulated measurement plane. US is equal to the gold-standard MRI, a fact, opening new avenues for US-based TVD as a first-line assessment tool of ventricular width.

Increased substantia nigra echogenicity correlated with visual hallucinations in Parkinson's disease: a Chinese population-based study.

As a noninvasive technique, transcranial sonography (TCS) of substantia nigra (SN) has gradually showed its effectiveness not only in diagnosis but also in understanding clinical features of Parkinson's Disease (PD). This study aimed to further evaluate TCS for clinical diagnosis of PD, and to explore the association between sonographic manifestations and visual hallucinations (VH). A total of 226 subjects including 141 PD patients and 85 controls were recruited. All participants received TCS. A series of rating scales to evaluate motor and non-motor symptoms were performed in PD patients. Results showed that 172 subjects were successfully assessed by TCS. The area of SN was greater in PD patients than that in controls (P < 0.001). As receiver-operating characteristic (ROC) curve analysis showed, the best cutoff value for the larger SN echogenicity size was 23.5 mm2 (sensitivity 70.3%, specificity 77.0%). Patients with VH had larger SN area (P = 0.019), as well as higher Non-Motor Symptoms Scale (NMSS) scores (P = 0.018). Moreover, binary logistic regression analysis indicated that SN hyperechogenicity (odds ratio = 4.227, P = 0.012) and NMSS scores (odds ratio = 0.027, P = 0.042) could be the independent predictors for VH. In conclusion, TCS can be used as an auxiliary diagnostic tool for Parkinson's disease. Increased SN echogenicity is correlated with VH in Parkinson's disease, possibly because the brain stem is involved in the mechanism in the onset of VH. Further studies are needed to confirm these findings.

Comparative Analysis of Simultaneous Transcranial Doppler and Perfusion Computed Tomography for Cerebral Perfusion Evaluation in Patients with Traumatic Brain Injury.

The aim was to investigate the feasibility of simultaneous comparison of cerebral circulation in major vessels and microvasculature in patients suffering traumatic brain injury (TBI) with or without intracranial hematomas (IH). METHODS: 170 patients were divided into two groups: Group 1 - diffuse TBI (75 patients); and Group 2 - TBI with IH (95 patients: 18 epidural, 65 subdural and 12 multiple). Perfusion computed tomography (PCT) for assessment of volumetric cerebral blood flow (CBF) was done 2-15 days after admission to hospital. Simultaneous assessment of cerebral blood flow velocity (CBFV) in both middle cerebral arteries was done by transcranial Doppler. RESULTS: In patients with diffuse TBI, CBF had statistically valid correlations with CBFV (r = 0.28, p = 0.0149 on the left side; r = 0.382, p = 0.00075 on the right side). In patients with TBI and IH, the analysis did not reveal any reliable correlations between the CBFV and CBF velocity in the temporal lobes, either on the side of the removed IH or on the opposite side. CONCLUSION: The greatest linear correlation was noted in patients with diffuse TBI without the development of a coarse shift of the midline structures and dislocation syndrome. This correlation decreases with the increase in injury severity and development of secondary complications in the acute period, which probably reflects impairment of the coupling of oxygen consumption by brain tissue and cerebral microcirculation.

Validation of non-invasive cerebrovascular pressure reactivity and pulse amplitude reactivity indices in traumatic brain injury.

BACKGROUND: Two transcranial Doppler (TCD) estimators of cerebral arterial blood volume (CaBV) coexist: continuous outflow of arterial blood outside the cranium through a low-pulsatile venous system (continuous flow forward, CFF) and pulsatile outflow through regulating arterioles (pulsatile flow forward, PFF). We calculated non-invasive equivalents of the pressure reactivity index (PRx) and the pulse amplitude index PAx with slow waves of mean CaBV and its pulse amplitude. METHODS: About 273 individual TBI patients were retrospectively reviewed. PRx is the correlation coefficient between 30 samples of 10-second averages of ICP and mean ABP. PAx is the correlation coefficient between 30 samples of 10-second averages of the amplitude of ICP (AMP, derived from Fourier analysis of the raw full waveform ICP tracing) and mean ABP. nPRx is calculated with CaBV instead of ICP and nPAx with the pulse amplitude of CaBV instead of AMP (calculated using both the CFF and PFF models). All reactivity indices were additionally compared with Glasgow Outcome Score (GOS) to verify potential outcome-predictive strength. RESULTS: When correlated, slow waves of ICP demonstrated good coherence between slow waves in CaBV (>0.75); slow waves of AMP showed good coherence with slow waves of the pulse amplitude of CaBV (>0.67) in both the CFF and PFF models. nPRx was moderately correlated with PRx (R = 0.42 for CFF and R = 0.38 for PFF; p < 0.0001). nPAx correlated with PAx with slightly better strength (R = 0.56 for CFF and R = 0.41 for PFF; p < 0.0001). nPAx_CFF showed the strongest association with outcomes. CONCLUSIONS: Non-invasive estimators (nPRx and nPAx) are associated with their invasive counterparts and can provide meaningful associations with outcome after TBI. The CFF model is slightly superior to the PFF model.

Brain Ultrasonography Consensus on Skill Recommendations and Competence Levels Within the Critical Care Setting.

BACKGROUND: To report a consensus on the different competency levels for the elaboration of skill recommendations in performing brain ultrasonography within the neurocritical care setting. METHODS: Four brain ultrasound experts, supported by a methodologist, performed a preselection of indicators and skills based on the current literature and clinical expertise. An international panel of experts was recruited and subjected to web-based questionnaires according to a Delphi method presented in three separate rounds. A pre-defined threshold of agreement was established on expert subjective opinions, > 84% of votes was set to support a strong recommendation and > 68% for a weak recommendation. Below these thresholds, no recommendation reached. RESULTS: We defined four different skill levels (basic, basic-plus, pre-advanced, advanced). Twenty-five experts participated to the full process. After four rounds of questions, two items received a strong recommendation in the basic skill category, three in the advanced, twelve in the basic-plus, and seven in the pre-advanced. Two items in the pre-advanced category received a weak recommendation and three could not be collocated and were excluded from the list. CONCLUSIONS: Results from this consensus permitted stratification of the different ultrasound examination skills in four levels with progressively increasing competences. This consensus can be useful as a guide for beginners in brain ultrasonography and for the development of specific training programs within this field.

Latin American Consensus Statement for the Use of Contrast-Enhanced Transcranial Ultrasound as a Diagnostic Test for Detection of Right-to-Left Shunt.

BACKGROUND: The role of patent foramen ovale is a field of debate and current publications have increasing controversies about the patients' management in young undetermined stroke. Work up with echocardiography and transcranial Doppler (TCD) can aid the decision with better anatomical and functional characterization of right-to-left shunt (RLS). Medical and interventional strategy may benefit from this information. SUMMARY: a group of experts from the Latin American participants of the Neurosonology Research Group (NSRG) of World Federation of Neurology created a task force to review literature and describe the better methodology of contrast TCD (c-TCD). All signatories of the present consensus statement have published at least one study on TCD as an author or co-author in an indexed journal. Two meetings were held while the consensus statement was being drafted, during which controversial issues were discussed and voted on by the statement signatories. The statement paper was reviewed and approved by the Executive Committee of the NSRG of the World Federation of Neurology. The main objective of this consensus statement is to establish a standardization of the c-TCD technique and its interpretation, in order to improve the informative quality of the method, resulting in expanding the application of TCD in the clinical setting. These recommendations optimize the comparison of different diagnostic methods and encourage the use of c-TCD for RLS screening and complementary diagnosis in multicenter studies.

Role of magnetic resonance imaging in fetuses with mild or moderate ventriculomegaly in the era of fetal neurosonography: systematic review and meta-analysis.

OBJECTIVES: To report the rate of additional central nervous system (CNS) anomalies detected exclusively on prenatal magnetic resonance imaging (MRI) in fetuses diagnosed with isolated mild or moderate ventriculomegaly (VM) on ultrasound, according to the type of ultrasound protocol adopted (dedicated neurosonography vs standard assessment of the fetal brain), and to explore whether the diagnostic performance of fetal MRI in detecting such anomalies is affected by gestational age at examination and laterality and degree of ventricular dilatation. METHODS: MEDLINE, EMBASE, CINAHL and Clinicaltrials.gov were searched for studies reporting on the prenatal MRI assessment of fetuses diagnosed with isolated mild or moderate VM (ventricular dilatation of 10-15 mm) on ultrasound. Additional anomalies detected only on MRI were classified as callosal, septal, posterior fossa, white matter, intraventricular hemorrhage, cortical, periventricular heterotopia, periventricular cysts or complex malformations. The rate of additional anomalies was compared between fetuses diagnosed on dedicated neurosonography, defined as a detailed assessment of the fetal brain, according to the International Society of Ultrasound in Obstetrics and Gynecology guidelines, and those diagnosed on standard fetal brain assessment. The rate of additional CNS anomalies missed on prenatal MRI and detected only at birth was calculated and compared between fetuses that had early (at or before 24 weeks' gestation) and those that had late (after 24 weeks) MRI. Subanalysis was performed according to the laterality (uni- vs bilateral) and degree (mild vs moderate, defined as ventricular dilatation of 10-12 and 13-15 mm, respectively) of ventricular dilatation. Whether MRI assessment led to a significant change in prenatal management was explored. Random-effects meta-analysis of proportions was used. RESULTS: Sixteen studies (1159 fetuses) were included in the systematic review. Overall, MRI detected an anomaly not identified on ultrasound in 10.0% (95% CI, 6.2-14.5%) of fetuses. However, when stratifying the analysis according to the type of ultrasound assessment, the rate of associated anomalies detected only on MRI was 5.0% (95% CI, 3.0-7.0%) when dedicated neurosonography was performed compared with 16.8% (95% CI, 8.3-27.6%) in cases that underwent a standard assessment of the fetal brain in the axial plane. The overall rate of an additional anomaly detected only at birth and missed on prenatal MRI was 0.9% (95% CI, 0.04-1.5%) (I2 , 0%). There was no difference in the rate of an associated anomaly detected only after birth when fetal MRI was carried out before, compared with after, 24 weeks of gestation (P = 0.265). The risk of detecting an associated CNS abnormality on MRI was higher in fetuses with moderate than in those with mild VM (odds ratio, 8.1 (95% CI, 2.3-29.0); P = 0.001), while there was no difference in those presenting with bilateral, compared with unilateral, dilatation (P = 0.333). Finally, a significant change in perinatal management, mainly termination of pregnancy owing to parental request, following MRI detection of an associated anomaly, was observed in 2.9% (95% CI, 0.01-9.8%) of fetuses undergoing dedicated neurosonography compared with 5.1% (95% CI, 3.2-7.5%) of those having standard assessment. CONCLUSIONS: In fetuses undergoing dedicated neurosonography, the rate of a CNS anomaly detected exclusively on MRI is lower than that reported previously. Early MRI has an excellent diagnostic performance in identifying additional CNS anomalies, although the findings from this review suggest that MRI performed in the third trimester may be associated with a better detection rate for some types of anomaly, such as cortical, white matter and intracranial hemorrhagic anomalies. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Hemispheric language lateralization in presurgical patients with temporal lobe epilepsy: Improving the retest reliability of functional transcranial Doppler sonography.

Since its introduction, functional transcranial Doppler sonography (fTCD) has been extensively applied in research and clinical settings and has now become part of the routine presurgical work-up of patients with epilepsy. Because of its importance in planning neurosurgical interventions and predicting possible cognitive risks, the reproducibility of fTCD in determining hemispheric language lateralization (HLL) has to be ensured. In the present study, fTCD was performed twice in 33 initially lateralized patients with temporal lobe epilepsy (TLE) as part of their presurgical work-up, using a standard word generation paradigm. Initially, the standard analysis, including only the statistical examination of fTCD data, was applied, and a rather poor retest reliability of r = 0.41 was obtained (p = 0.017). Because of doubts concerning appropriate task performance in some patients, subsequently, a two-step data analysis was introduced, including an additional qualitative evaluation of fTCD data regarding (1) instruction-compliant task performance, (2) sufficient quality of the baseline phase, and (3) adequate increase in cerebral blood flow velocity (CBFV) during the activation phase. Attributable to a more valid interpretation of fTCD data after the application of the qualitative step, the reproducibility of HLL significantly improved (p = 0.007) to a high retest reliability of r = 0.84 (p < 0.000). In clinical settings, psychological and situational factors seem to strongly influence the reproducibility of fTCD determining HLL. Accordingly, we highly recommend the complementation of the standard statistical examination of fTCD data by an additional qualitative evaluation (two-step data analysis), as this extra security is particularly desirable because of its direct implications for the further evaluation of neurosurgical interventions. This article is part of the Special Issue "Individualized Epilepsy Management: Medicines, Surgery and Beyond".

Prediction of Delayed Cerebral Ischemia with Cerebral Angiography: A Meta-Analysis.

OBJECT: Cerebral catheter angiography is the gold standard for diagnosing cerebral artery vasospasm (vasospasm) in aneurysmal subarachnoid hemorrhage (SAH). We have previously published a meta-analysis of prediction of delayed cerebral ischemia (DCI) from transcranial Doppler (TCD) evidence of vasospasm. Analogous data relating to prediction of DCI have not been previously collated for cerebral angiography nor reconciled against TCD. METHODS: We searched PUBMED, the Cochrane database, and clinicaltrials.gov for studies that used cerebral angiography for diagnosis of vasospasm and evaluated DCI in patients with SAH. We performed a random-effects meta-analysis of prediction of DCI with cerebral angiography, reconciling its accuracy against that of TCD. We also report quality of evidence for the value of cerebral angiography and TCD in SAH based on pooled data from our meta-analyses. RESULTS: A total of 15 studies (n = 5463) were included in the meta-analysis. Sensitivity (SN), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) of cerebral angiography for prediction of DCI are 57, 68, 32, and 90%. These metrics for TCD, based on our previous meta-analysis, are 90, 71, 57, and 92%. We report that test accuracy estimates are "moderate" for TCD and "low" for angiography based on pooled data from our meta-analyses. CONCLUSION: TCD evidence of vasospasm is a better predictor of DCI than angiographic vasospasm. Future comparative effectiveness studies can better define the value of these diagnostic tools in patients with SAH.

Comparison of Transcranial Doppler and Ultrasound-Tagged Near Infrared Spectroscopy for Measuring Relative Changes in Cerebral Blood Flow in Human Subjects.

BACKGROUND: Currently, no reliable method exists for continuous, noninvasive measurements of absolute cerebral blood flow (CBF). We sought to determine how changes measured by ultrasound-tagged near-infrared spectroscopy (UT-NIRS) compare with changes in CBF as measured by transcranial Doppler (TCD) in healthy volunteers during profound hypocapnia and hypercapnia. METHODS: Ten healthy volunteers were monitored with a combination of TCD, UT-NIRS (c-FLOW, Ornim Medical), as well as heart rate, blood pressure, end-tidal PCO2 (PEtCO2), end-tidal O2, and inspired O2. Inspired CO2 and minute ventilation were controlled to achieve 5 stable plateau goals of EtCO2 at 15-20, 25-30, 35-40, 45-50, and 55-60 mm Hg, for a total of 7 measurements per subject. CBF was assessed at a steady state, with the TCD designated as the reference standard. The primary analysis was a linear mixed-effect model of TCD and UT-NIRS flow with PEtCO2, which accounts for repeated measures. Receiver operating characteristic curves were determined for detection of changes in CBF. RESULTS: Hyperventilation (nadir PEtCO2 17.1 ± 2.4) resulted in significantly decreased mean flow velocity of the middle cerebral artery from baseline (to 79% ± 22%), but not a consistent decrease in UT-NIRS cerebral flow velocity index (n = 10; 101% ± 6% of baseline). Hypercapnia (peak PEtCO2 59.3 ± 3.3) resulted in a significant increase from baseline in both mean flow velocity of the middle cerebral artery (153% ± 25%) and UT-NIRS (119% ± 11%). Comparing slopes versus PEtCO2 as a percent of baseline for the TCD (1.7% [1.5%-2%]) and UT-NIRS (0.4% [0.3%-0.5%]) shows that the UT-NIRS slope is significantly flatter, P < .0001. Area under the receiver operating characteristic curve was significantly higher for the TCD than for UT-NIRS, 0.97 (95% confidence interval, 0.92-0.99) versus 0.75 (95% confidence interval, 0.66-0.82). CONCLUSIONS: Our data indicate that UT-NIRS cerebral flow velocity index detects changes in CBF only during hypercarbia but not hypocarbia in healthy subjects and with much less sensitivity than TCD. Additional refinement and validation are needed before widespread clinical utilization of UT-NIRS.

ICP Versus Laser Doppler Cerebrovascular Reactivity Indices to Assess Brain Autoregulatory Capacity.

BACKGROUND: To explore the relationship between various autoregulatory indices in order to determine which approximate small vessel/microvascular (MV) autoregulatory capacity most accurately. METHODS: Utilizing a retrospective cohort of traumatic brain injury patients (N = 41) with: transcranial Doppler (TCD), intracranial pressure (ICP) and cortical laser Doppler flowmetry (LDF), we calculated various continuous indices of autoregulation and cerebrovascular responsiveness: A. ICP derived [pressure reactivity index (PRx)-correlation between ICP and mean arterial pressure (MAP), PAx-correlation between pulse amplitude of ICP (AMP) and MAP, RAC-correlation between AMP and cerebral perfusion pressure (CPP)], B. TCD derived (Mx-correlation between mean flow velocity (FVm) and CPP, Mx_a-correlation between FVm and MAP, Sx-correlation between systolic flow velocity (FVs) and CPP, Sx_a-correlation between FVs and MAP, Dx-correlation between diastolic flow index (FVd) and CPP, Dx_a-correlation between FVd and MAP], and LDF derived (Lx-correlation between LDF cerebral blood flow [CBF] and CPP, Lx_a-correlation between LDF-CBF and MAP). We assessed the relationship between these indices via Pearson correlation, Friedman test, principal component analysis (PCA), agglomerative hierarchal clustering (AHC), and k-means cluster analysis (KMCA). RESULTS: LDF-based autoregulatory index (Lx) was most associated with TCD-based Mx/Mx_a and Dx/Dx_a across Pearson correlation, PCA, AHC, and KMCA. Lx was only remotely associated with ICP-based indices (PRx, PAx, RAC). TCD-based Sx/Sx_a was more closely associated with ICP-derived PRx, PAx and RAC. This indicates that vascular-derived indices of autoregulatory capacity (i.e., TCD and LDF based) covary, with Sx/Sx_a being the exception, whereas indices of cerebrovascular reactivity derived from pulsatile CBV (i.e., ICP indices) appear to not be closely related to those of vascular origin. CONCLUSIONS: Transcranial Doppler Mx is the most closely associated with LDF-based Lx/Lx_a. Both Sx/Sx-a and the ICP-derived indices appear to be dissociated with LDF-based cerebrovascular reactivity, leaving Mx/Mx-a as a better surrogate for the assessment of cortical small vessel/MV cerebrovascular reactivity. Sx/Sx_a cocluster/covary with ICP-derived indices, as seen in our previous work.

Noninvasive Intracranial Pressure Assessment in Acute Liver Failure.

BACKGROUND: Elevated intracranial pressure (ICP) is an important cause of death following acute liver failure (ALF). While invasive ICP monitoring (IICPM) is most accurate, the presence of coagulopathy increases bleeding risk in ALF. Our objective was to evaluate the accuracy of three noninvasive ultrasound-based measures for the detection of concurrent ICP elevation in ALF-optic nerve sheath diameter (ONSD) using optic nerve ultrasound (ONUS); middle cerebral artery pulsatility index (PI) on transcranial Doppler (TCD); and ICP calculated from TCD flow velocities (ICPtcd) using the estimated cerebral perfusion pressure (CPPe) technique. METHODS: In this retrospective study, consecutive ALF patients admitted over a 6-year period who underwent IICPM as well as measurement of ONSD, TCD-PI or ICPtcd were included. ONSD was measured offline by a blinded investigator from deidentified videos. The ability of highest ONSD, TCD-PI, and ICPtcd to detect concurrent invasive ICP > 20 mmHg was assessed using receiver operating characteristic (ROC) curves. The ROC area under the curve (AUC) was calculated with 95% confidence interval (95% CI) and evaluated against the null hypothesis of AUC = 0.5. Noninvasive measures were also evaluated as predictors of in-hospital death. RESULTS: Forty-one ALF patients were admitted during the study period. In total, 27 (66%) underwent IICPM, of these, 23 underwent ONUS and 21 underwent TCD. Eleven out of 23 (48%) patients died (two from intracranial hypertension). Results of ROC analysis for detection of concurrent ICP > 20 mmHg were as follows: ONSD AUC = 0.59 (95% CI 0.37-0.79, p = 0.54); TCD-PI AUC = 0.55 (95% CI 0.34-0.75, p = 0.70); and ICPtcd AUC = 0.90 (0.72-0.98, p < 0.0001). None of the noninvasive measures were significant predictors of death. CONCLUSIONS: In patients with ALF, neither ONSD nor TCD-PI reliably detected concurrent ICP elevation on invasive monitoring. Estimation of ICP (ICPtcd) using the TCD CPPe technique was associated with concurrent ICP elevation. Additional studies of TCD CPPe in larger numbers of ALF patients may prove worthwhile.

Transcranial Doppler versus transthoracic echocardiography for the detection of patent foramen ovale in patients with cryptogenic cerebral ischemia: A systematic review and diagnostic test accuracy meta-analysis.

OBJECTIVE: Patent foramen ovale (PFO) can be detected in up to 43% of patients with cryptogenic cerebral ischemia undergoing investigation with transesophageal echocardiography (TEE). The diagnostic value of transthoracic echocardiography (TTE) in the detection of PFO in patients with cryptogenic ischemic stroke or transient ischemic attack has not been compared with that of transcranial Doppler (TCD) using a comprehensive meta-analytical approach. METHODS: We performed a systematic literature review to identify all prospective observational studies of patients with cryptogenic cerebral ischemia that provided both sensitivity and specificity measures of TTE, TCD, or both compared to the gold standard of TEE. RESULTS: Our literature search identified 35 eligible studies including 3,067 patients. The pooled sensitivity and specificity for TCD was 96.1% (95% confidence interval [CI] = 93.0-97.8%) and 92.4% (95% CI = 85.5-96.1%), whereas the respective measures for TTE were 45.1% (95% CI = 30.8-60.3%) and 99.6% (95% CI = 96.5-99.9%). TTE was superior in terms of higher positive likelihood ratio values (LR+ = 106.61, 95% CI = 15.09-753.30 for TTE vs LR+ = 12.62, 95% CI = 6.52-24.43 for TCD; p = 0.043), whereas TCD demonstrated lower negative likelihood values (LR- = 0.04, 95% CI = 0.02-0.08) compared to TTE (LR- = 0.55, 95% CI = 0.42-0.72; p < 0.001). Finally, the area under the summary receiver operating curve (AUC) was significantly greater (p < 0.001) in TCD (AUC = 0.98, 95% CI = 0.97-0.99) compared to TTE studies (AUC = 0.86, 95% CI = 0.82-0.89). INTERPRETATION: TCD is more sensitive but less specific compared to TTE for the detection of PFO in patients with cryptogenic cerebral ischemia. The overall diagnostic yield of TCD appears to outweigh that of TTE.

The accuracy of transcranial Doppler in excluding intracranial hypertension following acute brain injury: a multicenter prospective pilot study.

BACKGROUND: Untimely diagnosis of intracranial hypertension may lead to delays in therapy and worsening of outcome. Transcranial Doppler (TCD) detects variations in cerebral blood flow velocity which may correlate with intracranial pressure (ICP). We investigated if intracranial hypertension can be accurately excluded through use of TCD. METHOD: This was a multicenter prospective pilot study in patients with acute brain injury requiring invasive ICP (ICPi) monitoring. ICP estimated with TCD (ICPtcd) was compared with ICPi in three separate time frames: immediately before ICPi placement, immediately after ICPi placement, and 3 hours following ICPi positioning. Sensitivity and specificity, and concordance correlation coefficient between ICPi and ICPtcd were calculated. Receiver operating curve (ROC) and the area under the curve (AUC) analyses were estimated after measurement averaging over time. RESULTS: A total of 38 patients were enrolled, and of these 12 (31.6%) had at least one episode of intracranial hypertension. One hundred fourteen paired measurements of ICPi and ICPtcd were gathered for analysis. With dichotomized ICPi (≤20 mmHg vs >20 mmHg), the sensitivity of ICPtcd was 100%; all measurements with high ICPi (>20 mmHg) also had a high ICPtcd values. Bland-Altman plot showed an overestimation of 6.2 mmHg (95% CI 5.08-7.30 mmHg) for ICPtcd compared to ICPi. AUC was 96.0% (95% CI 89.8-100%) and the estimated best threshold was at ICPi of 24.8 mmHg corresponding to a sensitivity 100% and a specificity of 91.2%. CONCLUSIONS: This study provides preliminary evidence that ICPtcd may accurately exclude intracranial hypertension in patients with acute brain injury. Future studies with adequate power are needed to confirm this result.