Intracranial Pressure Pulse Waveform Research Articles

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

IntroductionBoth 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 questionDoes ICP pulse waveform become similar to non-invasively estimated CaBV pulse during ICP plateau waves. Material and methodsA 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. ResultsICP 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 conclusionThe 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.

Relationship between the shape of intracranial pressure pulse waveform and computed tomography characteristics in patients after traumatic brain injury

BackgroundMidline shift and mass lesions may occur with traumatic brain injury (TBI) and are associated with higher mortality and morbidity. The shape of intracranial pressure (ICP) pulse waveform reflects the state of cerebrospinal pressure–volume compensation which may be disturbed by brain injury. We aimed to investigate the link between ICP pulse shape and pathological computed tomography (CT) features.MethodsICP recordings and CT scans from 130 TBI patients from the CENTER-TBI high-resolution sub-study were analyzed retrospectively. Midline shift, lesion volume, Marshall and Rotterdam scores were assessed in the first CT scan after admission and compared with indices derived from the first 24 h of ICP recording: mean ICP, pulse amplitude of ICP (AmpICP) and pulse shape index (PSI). A neural network model was applied to automatically group ICP pulses into four classes ranging from 1 (normal) to 4 (pathological), with PSI calculated as the weighted sum of class numbers. The relationship between each metric and CT measures was assessed using Mann–Whitney U test (groups with midline shift > 5 mm or lesions > 25 cm3 present/absent) and the Spearman correlation coefficient. Performance of ICP-derived metrics in identifying patients with pathological CT findings was assessed using the area under the receiver operating characteristic curve (AUC).ResultsPSI was significantly higher in patients with mass lesions (with lesions: 2.4 [1.9–3.1] vs. 1.8 [1.1–2.3] in those without; p << 0.001) and those with midline shift (2.5 [1.9–3.4] vs. 1.8 [1.2–2.4]; p < 0.001), whereas mean ICP and AmpICP were comparable. PSI was significantly correlated with the extent of midline shift, total lesion volume and the Marshall and Rotterdam scores. PSI showed AUCs > 0.7 in classification of patients as presenting pathological CT features compared to AUCs ≤ 0.6 for mean ICP and AmpICP.ConclusionsICP pulse shape reflects the reduction in cerebrospinal compensatory reserve related to space-occupying lesions despite comparable mean ICP and AmpICP levels. Future validation of PSI is necessary to explore its association with volume imbalance in the intracranial space and a potential complementary role to the existing monitoring strategies.

Aeromedical Transportation in an Area Intensive Care Unit: Experimental Study of Aircraft Pilots Undergoing Non-Invasive in-Flight Intracranial Pressure Measurement

Introduction: In certain emergency situations, a patient admitted to a hospital with fewer resources needs to be transferred quickly to a unit better prepared to deal with them. This is when the aeromedical transport service is needed. For this, the aircraft must be staffed by specialized health professionals and have a variety of resources to provide the best care for the patient. Objectives: 1) The general objective of this article was to analyze changes in intracranial pressure (ICP) in Brazilian Air Force pilots undergoing a level straight flight. 2) To help collect data for the development of a non-invasive sensor for monitoring ICP in flight. 3). To verify whether the equipment for measuring non-invasive Intracranial Pressure can be used in air ICUs. Materials and Methods: The work evaluated the presence of morphological changes in non-invasive ICP during level straight flight lasting 30 min among 10 (ten) pilots who volunteered for the collection. Results: It was observed that the ICP pulse waveform did not change during straight level flight, when compared to normal resting situations of an individual in a collection in a terrestrial environment, demonstrating the reliability of the equipment and the research. Final considerations: This study has helped to understand not only the need for rapid diagnosis of non-invasive ICP, but also the possible suitability of this equipment in aircraft prepared for rapid diagnosis and tratament.

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

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). 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). 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). 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.

End-to-End Automatic Morphological Classification of Intracranial Pressure Pulse Waveforms Using Deep Learning.

Mean intracranial pressure (ICP) is commonly used in the management of patients with intracranial pathologies. However, the shape of the ICP signal over a single cardiac cycle, called ICP pulse waveform, also contains information on the state of the craniospinal space. In this study we aimed to propose an end-to-end approach to classification of ICP waveforms and assess its potential clinical applicability. ICP pulse waveforms obtained from long-term ICP recordings of 50 neurointensive care unit (NICU) patients were manually classified into four classes ranging from normal to pathological. An additional class was introduced to simultaneously identify artifacts. Several deep learning models and data representations were evaluated. An independent testing dataset was used to assess the performance of final models. Occurrence of different waveform types was compared with the patients' clinical outcome. Residual Neural Network using 1-D ICP signal as input was identified as the best performing model with accuracy of 93% in the validation and 82% in the testing dataset. Patients with unfavorable outcome exhibited significantly lower incidence of normal waveforms compared to the favorable outcome group even at ICP levels below 20 mm Hg (median [first-third quartile]: 9 [1-36]% vs. 63 [52-88] %, p = 0.002). Results of this study confirm the possibility of analyzing ICP pulse waveform morphology in long-term recordings of NICU patients. Proposed approach could potentially be used to provide additional information on the state of patients with intracranial pathologies beyond 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.

Intracranial pulse pressure waveform analysis using the higher harmonics centroid

BackgroundThe pulse waveform of intracranial pressure (ICP) is its distinctive feature almost always present in the clinical recordings. In most cases, it changes proportionally to rising ICP, and observation of these changes may be clinically useful. We introduce the higher harmonics centroid (HHC) which can be defined as the center of mass of harmonics of the ICP pulse waveform from the 2nd to 10th, where mass corresponds to amplitudes of these harmonics. We investigate the changes in HHC during ICP monitoring, including isolated episodes of ICP plateau waves.Material and methodsRecordings from 325 patients treated between 2002 and 2010 were reviewed. Twenty-six patients with ICP plateau waves were identified. In the first step, the correlation between HHC and ICP was examined for the entire monitoring period. In the second step, the above relation was calculated separately for periods of elevated ICP during plateau wave and the baseline.ResultsFor the values averaged over the whole monitoring period, ICP (22.3 ± 6.9 mm Hg) correlates significantly (R = 0.45, p = 0.022) with HHC (3.64 ± 0.46). During the ICP plateau waves (ICP increased from 20.9 ± 6.0 to 53.7 ± 9.7 mm Hg, p < 10−16), we found a significant decrease in HHC (from 3.65 ± 0.48 to 3.21 ± 0.33, p = 10−5).ConclusionsThe good correlation between HHC and ICP supports the clinical application of pressure waveform analysis in addition to the recording of ICP number only. Mean ICP may be distorted by a zero drift, but HHC remains immune to this error. Further research is required to test whether a decline in HHC with elevated ICP can be an early warning sign of intracranial hypertension, whether individual breakpoints of correlation between ICP and its centroid are of clinical importance.

Intracranial Compliance Assessed by Intracranial Pressure Pulse Waveform.

Background: Morphological alterations in intracranial pressure (ICP) pulse waveform (ICPW) secondary to intracranial hypertension (ICP >20 mmHg) and a reduction in intracranial compliance (ICC) are well known indicators of neurological severity. The exclusive exploration of modifications in ICPW after either the loss of skull integrity or surgical procedures for intracranial hypertension resolution is not a common approach studied. The present study aimed to assess the morphological alterations in ICPW among neurocritical care patients with skull defects and decompressive craniectomy (DC) by comparing the variations in ICPW features according to elevations in mean ICP values. Methods: Patients requiring ICP monitoring because of acute brain injury were included. A continuous record of 10 min-length for the beat-by-beat analysis of ICPW was performed, with ICP elevation produced by means of ultrasound-guided manual internal jugular vein compression at the end of the record. ICPW features (peak amplitude ratio (P2/P1), time interval to pulse peak (TTP) and pulse amplitude) were counterweighed between baseline and compression periods. Results were distributed for three groups: intact skull (exclusive burr hole for ICP monitoring), craniotomy/large fractures (group 2) or DC (group 3). Results: 57 patients were analyzed. A total of 21 (36%) presented no skull defects, 21 (36%) belonged to group 2, whereas 15 (26%) had DC. ICP was not significantly different between groups: ±15.11 for intact, 15.33 for group 2 and ±20.81 mmHg for group 3, with ICP-induced elevation also similar between groups (p = 0.56). Significant elevation was observed for the P2/P1 ratio for groups 1 and 2, whereas a reduction was observed in group 3 (elevation of ±0.09 for groups 1 and 2, but a reduction of 0.03 for group 3, p = 0.01), and no significant results were obtained for TTP and pulse amplitudes. Conclusion: In the present study, intracranial pressure pulse waveform analysis indicated that intracranial compliance was significantly more impaired among decompressive craniectomy patients, although ICPW indicated DC to be protective for further influences of ICP elevations over the brain. The analysis of ICPW seems to be an alternative to real-time ICC assessment.

Use of non-invasive intracranial pressure pulse waveform to monitor patients with End-Stage Renal Disease (ESRD).

End-stage renal disease (ESRD) is treated mainly by hemodialysis, however, hemodialysis is associated with frequent complications, some of them involve the increased intracranial pressure. In this context, monitoring the intracranial pressure of these patients may lead to a better understanding of how intracranial pressure morphology varies with hemodialysis. This study aimed to follow-up patients with ESRD by monitoring intracranial pressure before and after hemodialysis sessions using a noninvasive method. We followed-up 42 patients with ESRD in hemodialysis, for six months. Noninvasive intracranial pressure monitoring data were obtained through analysis of intracranial pressure waveform morphology, this information was uploaded to Brain4care® cloud algorithm for analysis. The cloud automatically sends a report containing intracranial pressure parameters. In total, 4881 data points were collected during the six months of follow-up. The intracranial pressure parameters (time to peak and P2/P1 ratio) were significantly higher in predialysis when compared to postdialysis for the three weekly sessions and throughout the follow-up period (p<0.01) data showed general improvement in brain compliance after the hemodialysis session. Furthermore, intracranial pressure parameters were significantly higher in the first weekly hemodialysis session (p<0.05). In conclusion, there were significant differences between pre and postdialysis intracranial pressure in patients with ESRD on hemodialysis. Additionally, the pattern of the intracranial pressure alterations was consistent over time suggesting that hemodialysis can improve time to peak and P2/P1 ratio which may reflect in brain compliance.

Compliance of the cerebrospinal space: comparison of three methods

BackgroundCerebrospinal compliance describes the ability of the cerebrospinal space to buffer changes in volume. Diminished compliance is associated with increased risk of potentially threatening increases in intracranial pressure (ICP) when changes in cerebrospinal volume occur. However, despite various methods of estimation proposed so far, compliance is seldom used in clinical practice. This study aimed to compare three measures of cerebrospinal compliance.MethodsICP recordings from 36 normal-pressure hydrocephalus patients who underwent infusion tests with parallel recording of transcranial Doppler blood flow velocity were retrospectively analysed. Three methods were used to calculate compliance estimates during changes in the mean ICP induced by infusion of fluid into the cerebrospinal fluid space: (a) based on Marmarou’s model of cerebrospinal fluid dynamics (CCSF), (b) based on the evaluation of changes in cerebral arterial blood volume (CCaBV), and (c) based on the amplitudes of peaks P1 and P2 of ICP pulse waveform (CP1/P2).ResultsIncrease in ICP caused a significant decrease in all compliance estimates (p < 0.0001). Time courses of compliance estimators were strongly positively correlated with each other (group-averaged Spearman correlation coefficients: 0.94 [0.88–0.97] for CCSF vs. CCaBV, 0.77 [0.63–0.91] for CCSF vs. CP1/P2, and 0.68 [0.48–0.91] for CCaBV vs. CP1/P2).ConclusionsIndirect methods, CCaBV and CP1/P2, allow for the assessment of relative changes in cerebrospinal compliance and produce results exhibiting good correlation with the direct method of volumetric manipulation. This opens the possibility of monitoring relative changes in compliance continuously.

Natural Resonance Frequency of the Brain Depends on Only Intracranial Pressure: Clinical Research

The need to understand and control intracranial pressure (ICP) is required for treatments in various clinical situations. The ICP value can only be measured by direct intracranial catheter or sensor placement, and a non-invasive ICP prediction method has not yet been established. We focused on the natural resonance frequency (NRF) of the brain to predict the ICP value. The ICP value, pulse waveform of intracranial pressure (PWICP) and cervical carotid pressure waveform (CCPW) were simultaneously collected from patients who had undergone ventricular drainage or ICP sensor placement for medical treatment in our institute. A total of 43 data were obtained from 27 patients, age ranged 14-48 (mean: 54) years, body height 137-187 (mean 163) cm and body weight 32-103 (mean 61) kg. The total measured time was 29,653 seconds and the measured mean ICP value in each data ranged from 3.82 to 69.39 (mean 25.9) hPa. Consecutive data was cut into 10.24 seconds, which was called a column. To decrease respiratory modulation, the largest positive peak of cardiac pulsation of CCPW was picked up in each column, as well as one ICP pulse waveform. The picked-up CCPW and PWICP were averaged by the weighted average method. The transfer characteristics from CCPW to PWICP were calculated by the transfer function method. The first initial negative peak of transfer characteristics was judged as the NRF of the brain. The relationship between the ICP value and the NRF of the brain was presented on the quadratic functions graph (ICP = 0.0329(NRF)2 + 0.0842NRF). These parameters were strongly correlated to each other (R2= 0.9952 coefficient of determination). The individual NRF, which was calculated by the transfer function method, only depends on the measured ICP value and their relationship can be presented in the simple quadratic functions. Funding: This research was funded by Japan Science and Technology Agency (JST) A-STEP feasibility study in 2012, and by Japan's New Energy and Industrial Technology Development Organization (NEDO) in 2013, and by Grants-in-Aid for scientific research in Ministry of Education, Culture, Sports, Science and Technology-Japan from 2015 to 2017 and 2018 to 2020. Receiver: Kenji Furihata. Declaration of Interest: Although the authors (T.G., K.F. and K.H.) have some patents of non-invasive intracranial pressure monitoring apparatus, the claim of the patents belong to affiliated university not to individuals. All of authors had already opened their COI disclosure in Japanese Neurosurgical Society. The authors have no personal financial or institutional interest in any of the drugs, materials, or devices described. Our proposing theory is a quite new concept. We strongly believe that there is nothing to competing interest declaration. Ethical Approval: The simultaneous measurement of intracranial pressure and cervical carotid artery pressure waveform was approved by Ethical Committee of Shinshu University School of Medicine. “Development of non-invasive intracranial pressure monitoring” approved number 2343.

Relative Position of the Third Characteristic Peak of the Intracranial Pressure Pulse Waveform Morphology Differentiates Normal-Pressure Hydrocephalus Shunt Responders and Nonresponders.

The diversion of cerebrospinal fluid (CSF) remains the principal treatment option for patients with normal-pressure hydrocephalus (NPH). External lumbar drain (ELD) and overnight intracranial pressure (ICP) monitoring are popular prognostic tests for differentiating which patients will benefit from shunting. Using the morphological clustering and analysis of continuous intracranial pulse (MOCAIP) algorithm to extract morphological metrics from the overnight ICP signal, we hypothesize that changes in the third peak of the ICP pulse pressure waveform can be used to differentiate ELD responders and nonresponders. Our study involved 66 patients (72.2 ± 9.8 years) undergoing evaluation for possible NPH, which included overnight ICP monitoring and ELD. ELD outcome was based on clinical notes and divided into nonresponders and responders. MOCAIP was used to extract mean ICP, ICP wave amplitude (waveAmp), and a metric derived to study P3 elevation (P3ratio). Of the 66 patients, 7 were classified as nonresponders and 25 as significant responders. The mean ICP and waveAmp did not vary significantly (p = 0.19 and p = 0.41) between the outcome groups; however, the P3ratio did show a significant difference (p = 0.04). Initial results suggest that the P3ratio might be used as a prognostic indicator for ELD outcome.

Characterization of Cerebral Vascular Response to EEG Bursts Using ICP Pulse Waveform Template Matching.

Neurovascular coupling is the relationship between the activity of the brain and the subsequent change in blood flow to the active region. The most common methods of detecting neurovascular coupling are cumbersome and noncontinuous. However, the integration of intracranial pressure (ICP) and electroencephalography (EEG) may serve as an indirect measure of neurovascular coupling.This study used data collected from burst-suppressed patients who received both ICP and depth EEG monitoring. An adaptive thresholding algorithm was used to detect the start and end of each EEG burst. The morphological clustering and analysis of ICP and pulse morphological template-matching algorithms were then applied to derive several metrics describing the shape of the ICP pulse waveform and track how it changed following an EEG burst. These changes were compared using a template obtained from patients undergoing CO2-induced vasodilation.All segments exhibited a significant period of vasodilation within 1-2 s after burst, and 4 of 5 had a significant period of vasoconstriction within 4-11 s of the EEG burst, suggesting that there might be a characteristic response of vasodilation and subsequent vasoconstriction after a spontaneous EEG burst. Furthermore, these findings demonstrate the potential of integrated EEG and ICP as an indirect measure of neurovascular coupling.

Morphological Feature Extraction From a Continuous Intracranial Pressure Pulse via a Peak Clustering Algorithm.

An increase in intracranial pressure (ICP) is frequently observed in patients with severe traumatic brain injury (TBI). The information derived from the observation of temporal changes in the mean ICP is insufficient for assessment of the compensatory reserve of the injured brain. This assessment can be achieved via continuous morphological analysis of the pulse waveform of the ICP. Continuous arterial blood pressure (ABP) and ICP recordings from 292 TBI patients were analyzed. The algorithm extracted morphological landmarks (peaks, troughs, and flats) from the ICP. Among the extracted peaks, P1, P2, and P3 were assigned through peak clustering. The performance of the proposed method was validated through a comparison of the algorithm-defined peaks and those manually identified by experienced observers. The proposed algorithm successfully identified the three distinguishing peaks of the ICP with satisfactory accuracy (95.3%, 87.8%, and 87.5% for P1, P2, and P3, respectively), even from minimally filtered raw signals. The algorithm extracted the morphological features from both ABP and ICP recordings with high accuracy. The ABP and ICP pulse waveforms can be simultaneously analyzed in real time using the proposed algorithm. The morphological features from these signals may aid the continuous care of patients with TBI.

Phase-shift between arterial flow and ICP pulse during infusion test.

The dynamic relationship between pulse waveform of intracranial pressure (ICP) and transcranial Doppler (TCD) cerebral blood flow velocity (CBFV) may contain information about cerebrospinal compliance. This study investigated the possibility by focusing on the phase shift between fundamental harmonics of CBFV and ICP. Thirty-seven normal pressure hydrocephalus patients (20 men, mean age 58) underwent the cerebrospinal fluid (CSF) infusion tests. The infusion was performed via pre-implanted Ommaya reservoir. The TCD FV was recorded in the middle cerebral artery. Resulting continuous ICP and pressure-volume (PV) signals were analyzed by ICM+ software. In initial stage of the CSF infusion, the phase shift was negative (median value = -11°, range = +60 to -117). There was significant inverse association of phase shift with brain elasticity (R = -0.51; p = 0.0009). In all tests, phase shift consistently decreased during gradual elevation of ICP (p = 0.00001). Magnitude of decrease in phase shift was inversely related to the peak-to-peak amplitude of ICP pulse waveform at a baseline (R = -0.51; p = 0.001). Phase shift between fundamental harmonics of ICP and TCD waveforms decreases during elevation of ICP. This is caused by an increase of time delay between systolic peak of flow velocity wave and ICP pulse.

Morphological changes in ICP pulse waveform as potential markers for early determination of external ventricular drain clamping trial outcome

External ventricular drains (EVD) are widely used to measure and manage intracranial pressure (ICP) for aneurysmal subarachnoid hemorrhage (aSAH) patients. After several days of use a decision is made to remove the drain or replace it with an indwelling shunt. This involves a “clamping trial” whereby the EVD is clamped and transduced and pre and post clamping CT imaging is performed to observe any change in ventricular size and clinical status. This practice may lead to prolonged hospital stay, extra radiation exposure, and neurological insult. The present study aims to apply a widely validated morphological clustering analysis of ICP pulse (MOCAIP) algorithm to detect signatures from the pulse waveform to differentiate an intact CSF circulatory system from an abnormal one during EVD clamping. We hypothesize that an intact CSF system should be stable and pulses with a similar mean ICP level should have similar shapes. This is a retrospective study with 43 out of 107 adult patients that satisfied the inclusion criteria of ICD9 code for SAH, admitted to UCSF Medical Center between 03/2013 and 08/2014, and exclusion criteria of absence of reported EVD clamping trial and ICP signal recordings shorter than 2 hours. By reviewing the clinical notes and pre/post brain imaging results, 25 patients were determined with an intact CSF circulatory system (group A) and 18 patients with an impaired one (group B). Blind to the chart review, the MOCAIP algorithm was applied to the ICP signal recordings to form a series of artifact-free dominant pulses. Then, for each pulse, other pulses with similar mean ICP were identified. Finally, the Euclidean and geodesic inter-pulse distances were calculated in a 4 hours moving window. ANOVA analyses showed a significant difference on the standard deviations of the Euclidean (p<0.001, η2=0.29) and geodesic distance (p=0.001, η2=0.22), between groups A and B. Mann-Whitney U tests were used on the (non-normally distributed) mean distances, showing a significant difference on the Euclidean (p=0.007, r=0.41) and the geodesic distance (p=0.02, r=0.36) between the two groups of patients. The area under the ROC curve was 0.79 and 0.78 for the standard deviations of the Euclidean and geodesic distance, and 0.74 and 0.71 for the mean Euclidean and geodesic distance respectively. Patients with an impaired CSF system showed not only a larger mean but also a larger variability of the inter-pulse distances, indicating frequent changes on the morphology of the pulses. The variability of morphological distances was the best predictor of the effect of EVD clamping trial. This technique may provide a method to rapidly determine if a patient will need surgical placement of an indwelling shunt or can simply have the EVD removed following SAH.

Steady-state indicators of the intracranial pressure dynamic system using geodesic distance of the ICP pulse waveform

Normal functioning of the brain depends on the homeostasis (∼ steady state) of its various physiological sub-systems, one of which is the intracranial pressure (ICP) dynamic system. The ICP dynamic system of an injured brain is susceptible to various acute changes that should ideally be detected by ICP monitoring even for comatose patients. However, the status quo of ICP monitoring solely targets mean ICP. We aimed to demonstrate a novel approach to detect acute deviation from steady state of an ICP dynamic system in an absence of significant mean ICP changes. We hypothesized that steady state of ICP dynamic systems is reflected as ICP pulses of similar mean ICP levels resembling each other for a given subject. A general framework was used to derive such a steady-state indicator that can accommodate different metrics of inter-pulse distance and different statistics of the distance histograms. In addition to conventional Euclidean distance and Pearson correlation, geodesic distance between pulses was introduced as a novel metric. These different ways of calculating steady-state indicators under the proposed framework were evaluated on three types of continuous ICP recordings: (1) those between two consecutive brain imaging studies that demonstrated acute ventricular enlargement for slit ventricle syndrome (SVS) patients undergoing a trial of shunt externalization and clamping (SVS+); (2) those between consecutive brain imaging studies from the SVS patients under the same trial but without ventricular enlargement (SVS−); (3) overnight recordings from normal pressure hydrocephalus (NPH) patients. It was observed that only the standard deviation of geodesic distance correctly differentiated between SVS+ and SVS− and between SVS+ and NPH while avoiding discriminating between SVS− and NPH. It was also found that 45% SVS+ cases had a multimodal geodesic distance histogram while none of SVS− and 3.8% of NPH cases had such a multimodal histogram. Pulses with a large number of distant pulses for the five multimodal-histogram SVS+ cases fell in short time windows indicating that acute ventricular changes may have occurred in these confined time windows during which no significant changes of mean ICP were observed. In contrast, the pulses with a large number of distant pulses for the two multimodal-histogram NPH cases did not cluster temporally. In conclusion, the geodesic inter-pulse distance is a promising metric to quantify distance intrinsic to the underneath geometric structure of ICP signals and hence is a more suitable way to derive a steady-state indicator of an ICP dynamic system.

Intracranial pressure pulse waveform correlates with aqueductal cerebrospinal fluid stroke volume

This study identifies a novel relationship between cerebrospinal fluid (CSF) stroke volume through the cerebral aqueduct and the characteristic peaks of the intracranial pulse (ICP) waveform. ICP waveform analysis has become much more advanced in recent years; however, clinical practice remains restricted to mean ICP, mainly due to the lack of physiological understanding of the ICP waveform. Therefore, the present study set out to shed some light on the physiological meaning of ICP morphological metrics derived by the morphological clustering and analysis of continuous intracranial pulse (MOCAIP) algorithm by investigating their relationships with a well defined physiological variable, i.e., the stroke volume of CSF through the cerebral aqueduct. Seven patients received both overnight ICP monitoring along with a phase-contrast MRI (PC-MRI) of the cerebral aqueduct to quantify aqueductal stroke volume (ASV). Waveform morphological analysis of the ICP signal was performed by the MOCAIP algorithm. Following extraction of morphological metrics from the ICP signal, nine temporal ICP metrics and two amplitude-based metrics were compared with the ASV via Spearman's rank correlation. Of the nine temporal metrics correlated with the ASV, only the width of the P2 region (ICP-Wi2) reached significance. Furthermore, both ICP pulse pressure amplitude and mean ICP did not reach significance. In this study, we showed the width of the second peak (ICP-Wi2) of an ICP pulse wave is positively related to the volume of CSF movement through the cerebral aqueduct. This finding is an initial step in bridging the gap between ICP waveform morphology research and clinical practice.

Impact of duration of symptoms on CSF dynamics in idiopathic normal pressure hydrocephalus

Cerebrospinal fluid (CSF) pressure-volume compensation may change over time as part of normal ageing, where the resistance to CSF outflow increases and the formation of CSF decreases with age. Is CSF compensation dependent on duration of symptoms in idiopathic normal pressure hydrocephalus (iNPH)? We investigated 92 patients presenting with iNPH. Mean age was 73 (range 47-86). There were 60 men and 32 women. They all presented with gait disturbance and ventricular dilatation. Memory deficit occurred in 72% and urinary incontinence in 52% of patients. All patients underwent computerized CSF infusion tests. Sixty-four shunted patients were available for follow-up, and their improvement was expressed using the NPH score. Mean intracranial pressure (ICP) was 10.1±5.1 mmHg, and mean resistance to CSF outflow was 17.3±5.2 mmHg/(ml/min). Mean duration of symptoms was 24±19 months (range from 2 weeks to 86 months). Baseline ICP, magnitude of ICP pulse waveform, brain compliance and improvement after shunting (72% of patients improved) did not exhibit any dependency on the duration of symptoms. The resistance to CSF outflow showed a strong tendency to decrease in time with the duration of symptoms beyond 2 years (R= -0.702; P<0.005). This is a preliminary observation, and it suggests that for patients with duration of symptoms longer than 2-3 years, the threshold for normal resistance to CSF outflow should be duration-adjusted.