Analysis of phase shift between pulse oscillations of macro- and microvascular cerebral blood flow in patients with traumatic brain injury.

PURPOSE: After a traumatic brain injury (TBI), monitoring of both macrovascular and microvascular blood circulation can potentially yield a better understanding of pathophysiology of potential secondary brain lesions. We investigated the changes in phase shift (PS) between cardiac-induced oscillations of cerebral blood flow (CBF) measured at macro (ultrasound Doppler) and microvascular (laser Doppler) level. Further we assessed the impact of intracranial pressure (ICP) on PS in TBI patients. A secondary aim was to compare PS to TCD-derived cerebral arterial time constant (τ), a parameter that reflects the circulatory transit time. METHODS: TCD blood flow velocities (FV) in the middle cerebral artery, laser Doppler blood microcirculation flux (LDF), arterial blood pressure (ABP), and ICP were monitored in 29 consecutive patients with TBI. Eight patients were excluded because of poor-quality signals. For the remaining 21 patients (median age = 23 (Q1: 20-Q3: 33); men:16,) data were retrospectively analysed. PS between the fundamental harmonics of FV and LDF signals was determined using spectral analysis. τ was estimated as a product of cerebrovascular resistance and compliance, based on the mathematical transformation of FV and ABP, ICP pulse waveforms. RESULTS: PS was negative (median: -26 (Q1: -38-Q3: -15) degrees) indicating that pulse LDF at a heart rate frequency lagged behind TCD pulse. With rising mean ICP, PS became more negative (R = -0.51, p < 0.019) indicating that delay of LDF pulse increases. There was a significant correlation between PS and cerebrovascular time constant (R = -0.47, p = 0.03). CONCLUSIONS: Pulse divergence between FV and LDF became greater with elevated ICP, likely reflecting prolonged circulatory travel time.

Brain blood flow pulse analysis may help to recognize individuals who suffer from hydrocephalus.

BACKGROUND: Normal pressure hydrocephalus (NPH) is often associated with altered cerebral blood flow. Recent research with the use of the ultrasonic method suggests specific changes in the shape of cardiac-related cerebral arterial blood volume (CaBV) pulses in NPH patients. Our study aims to provide a quantitative analysis of the shape of CaBV pulses, estimated based on transcranial Doppler ultrasonography (TCD) in NPH patients and healthy individuals. METHODS: The CaBV pulses were estimated using TCD cerebral blood flow velocity signals recorded from probable NPH adults and age-matched healthy individuals at rest. The shape of the CaBV pulses was compared to a triangular shape with 27 similarity parameters calculated for every reliable CaBV pulse and compared between patients and volunteers. The diagnostic accuracy of the most prominent parameter for NPH classification was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: The similarity parameters were calculated for 31 probable NPH patients (age: 59 years (IQR: 47, 67 years), 14 females) and 23 healthy volunteers (age: 54 years (IQR: 43, 61 years), 18 females). Eighteen of 27 parameters were different between healthy individuals and NPH patients (p < 0.05). The most prominent differences were found for the ascending slope of the CaBV pulse with the AUC equal to 0.87 (95% confidence interval: 0.77, 0.97, p < 0.001). CONCLUSIONS: The findings suggest that in NPH, the ascending slope of the CaBV pulse had a slower rise, was more like a straight line, and generally was less convex than in volunteers. Prospective research is required to verify the clinical utility of these findings.

Quantitative analysis of similarity between cerebral arterial blood volume and intracranial pressure pulse waveforms during intracranial pressure plateau waves.

Introduction: Both intracranial pressure (ICP) and cerebral arterial blood volume (CaBV) have a pulsatile character related to the cardiac cycle. The evolution of the shape of ICP pulses under increasing ICP or decreasing intracranial compliance is well documented. Nevertheless, the exact origin of the alterations in the ICP morphology remains unclear. Research question: Does ICP pulse waveform become similar to non-invasively estimated CaBV pulse during ICP plateau waves. Material and methods: A total of 15 plateau waves recorded in 15 traumatic brain injured patients were analyzed. CaBV pulse waveforms were calculated using global cerebral blood flow model from transcranial Doppler cerebral blood flow velocity (CBFV) signals. The difference index (DI) was used to quantify the similarity between ICP and CaBV waveforms. DI was calculated as the sum of absolute sample-by-sample differences between ICP and CaBV waveforms, representing the area between the pulses. Results: ICP increased (19.4 mm Hg [Q1-Q3: 18.2-23.4 mm Hg] vs. 42.7 mm Hg [Q1-Q3: 36.5-45.1 mm Hg], p < 0.001) while CBFV decreased (44.2 cm/s [Q1-Q3: 34.8-69.5 cm/s] vs. 32.9 cm/s [Q1-Q3: 24.7-68.2 cm/s], p = 0.002) during plateau waves. DI was smaller during the plateau waves (20.4 [Q1-Q3: 15.74-23.0]) compared to the baselines (26.3 [Q1-Q3: 24.2-34.7], p < 0.001). Discussion and conclusion: The area between corresponding ICP and CaBV pulse waveforms decreased during the plateau waves which suggests they became similar in shape. CaBV may play a significant role in determining the shape of ICP pulses during the plateau waves and might be a driving force in formulating ICP elevation.

Analysis of intracranial pressure pulse waveform in traumatic brain injury patients: a CENTER-TBI study.

OBJECTIVE: Intracranial pressure (ICP) pulse waveform analysis may provide valuable information about cerebrospinal pressure-volume compensation in patients with traumatic brain injury (TBI). The authors applied spectral methods to analyze ICP waveforms in terms of the pulse amplitude of ICP (AMP), high frequency centroid (HFC), and higher harmonics centroid (HHC) and also used a morphological classification approach to assess changes in the shape of ICP pulse waveforms using the pulse shape index (PSI). METHODS: The authors included 184 patients from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) High-Resolution Sub-Study in the analysis. HFC was calculated as the average power-weighted frequency within the 4- to 15-Hz frequency range of the ICP power density spectrum. HHC was defined as the center of mass of the ICP pulse waveform harmonics from the 2nd to the 10th. PSI was defined as the weighted sum of artificial intelligence-based ICP pulse class numbers from 1 (normal pulse waveform) to 4 (pathological waveform). RESULTS: AMP and PSI increased linearly with mean ICP. HFC increased proportionally to ICP until the upper breakpoint (average ICP of 31 mm Hg), whereas HHC slightly increased with ICP and then decreased significantly when ICP exceeded 25 mm Hg. AMP (p < 0.001), HFC (p = 0.003), and PSI (p < 0.001) were significantly greater in patients who died than in patients who survived. Among those patients with low ICP (< 15 mm Hg), AMP, PSI, and HFC were greater in those with poor outcome than in those with good outcome (all p < 0.001). CONCLUSIONS: Whereas HFC, AMP, and PSI could be used as predictors of mortality, HHC may potentially serve as an early warning sign of intracranial hypertension. Elevated HFC, AMP, and PSI were associated with poor outcome in TBI patients with low ICP.

Peak appearance time in pulse waveforms of intracranial pressure and cerebral blood flow velocity.

The shape of the pulse waveforms of intracranial pressure (ICP) and cerebral blood flow velocity (CBFV) typically contains three characteristic peaks. It was reported that alterations in cerebral hemodynamics may influence the shape of the pulse waveforms by changing peaks' configuration. However, the changes in peak appearance time (PAT) in ICP and CBFV pulses are only described superficially. We analyzed retrospectively ICP and CBFV signals recorded in traumatic brain injury patients during decrease in ICP induced by hypocapnia (n = 11) and rise in ICP during episodes of ICP plateau waves (n = 8). All three peaks were manually annotated in over 48 thousand individual pulses. The changes in PAT were compared between periods of vasoconstriction (expected during hypocapnia) and vasodilation (expected during ICP plateau waves) and their corresponding baselines. Correlation coefficient (rS) analysis between mean ICP and mean PATs was performed in each individual recording. Vasodilation prolonged PAT of the first peaks of ICP and CBFV pulses and the third peak of CBFV pulse. It also accelerated PAT of the third peak of ICP pulse. In contrast, vasoconstriction shortened appearance time of the first peaks of ICP and CBFV pulses and the second peak of ICP pulses. Analysis of individual recordings demonstrated positive association between changes in PAT of all three peaks in the CBFV pulse and mean ICP (rS range: 0.32-0.79 for significant correlations). Further study is needed to test whether PAT of the CBFV pulse may serve as an indicator of changes in ICP-this may open a perspective for non-invasive monitoring of alterations in mean ICP.

Analysis of relative changes in pulse shapes of intracranial pressure and cerebral blood flow velocity.

Objective.Analysis of relative changes in the shapes of pulse waveforms of intracranial pressure (ICP) and transcranial Doppler cerebral blood flow velocity (CBFV) may provide information on intracranial compliance. We tested this hypothesis, introducing an index named the ratio of pulse slopes (RPS) that is based on inclinations of the ascending parts of the ICP and CBFV pulse waveforms. It has hypothetically a simple interpretation: a value of 1 indicates good compliance and a value less than 1, reduced compliance. Here, we investigated the usefulness of RPS for assessment of intracranial compliance.Approach.ICP and CBFV signals recorded simultaneously in 30 normal-pressure hydrocephalus patients during infusion tests were retrospectively analysed. CBFV was measured in the middle cerebral artery. Changes in RPS during the test were compared with changes in the height ratio of the first and second peak of the ICP pulse (P1/P2) and the shape of the ICP pulse was classified from normal (1) to pathological (4). Values are medians (lower, upper quartiles).Main results.There was a significant correlation between baseline RPS and intracranial elasticity (R = -0.55,p = 0.0018). During the infusion tests, both RPS and P1/P2 decreased with rising ICP [RPS, 0.80 (0.56, 0.92) versus 0.63 (0.44, 0.80),p = 0.00015; P1/P2, 0.58 (0.50, 0.91) versus 0.52 (0.36, 0.71),p = 0.00009] while the ICP pulses became more pathological in shape [class: 3 (2, 3) versus 3 (3, 4),p = 0.04]. The magnitude of the decrease in RPS during infusion was inversely correlated with baseline P1/P2 (R = -0.40,p < 0.03).Significance.During infusion, the slopes of the ascending parts of ICP and CBFV pulses become increasingly divergent with a shift in opposite directions. RPS seems to be a promising methodological tool for monitoring intracranial compliance with no additional volumetric manipulation required.

Analysis of the Shape of Intracranial Pressure Pulse Waveform in Traumatic Brain Injury Patients.

Intracranial pressure (ICP) pulse waveform, i.e., the shape of the ICP signal over a single cardiac cycle, is regarded as a potential source of information about intracranial compliance. In this study we aimed to compare the results of automatic classification of ICP pulse shapes on a scale from normal to pathological with other ICP pulse-derived metrics. Additionally, identification of artifacts was performed simultaneously with pulse classification to assess the effect of artifact removal on the results. Data from 35 traumatic brain injury (TBI) patients were analyzed retrospectively in terms of dominant waveform shape, mean ICP, mean amplitude of ICP (AmpICP), mean index of compensatory reserve (RAP index), and their association with the patient's clinical outcome. Our results show that patients with poor outcome exhibit more pathological waveform shape than patients with good outcome. More pathological ICP pulse shape is associated with higher mean ICP, mean AmpICP, and RAP.Clinical relevance- In the clinical setting, ICP pulse waveform analysis could potentially be used to complement the commonly monitored mean ICP and improve the assessment of intracranial compliance in TBI patients. Artifact removal from the ICP signal could reduce the frequency of false positive detection of clinically adverse events.

Mathematical Modelling in Hydrocephalus.

BACKGROUND: Various studies highlight the significance of alterations in cerebrospinal fluid (CSF) and cerebral blood flow (CBF) dynamics in the pathogenesis of hydrocephalus and suggest the role of mathematical modeling in studying these complex interactions. OBJECTIVE: This narrative review discusses mathematical models of CSF and CBF dynamics, including Marmarou's compartmental model of CSF spaces and a model of cardiac changes in cerebral arterial blood volume. The diagnostic utility of CSF compensatory parameters is described along with current information on secondary model-based indices of cerebral hemodynamics in hydrocephalus. CONCLUSIONS: Compensatory parameters derived from the model of CSF circulation have long been used in the diagnosis and management of hydrocephalus patients. However, recent studies using mathematical models of cerebral circulation also show alterations in CBF dynamics, and model-based indices of cerebral hemodynamics, which can be calculated non-invasively using transracranial Doppler ultrasonography, can be used as a complementary source of information about the state of the cerebrospinal space.