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Three clinical studies have demonstrated the safety and effectiveness of the B4C System and its intended use.
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Study 1 - Non-invasive ICP Monitoring for HIV-associated Cryptococcal Meningitis
A critically ill adult subject diagnosed with human immunodeficiency virus-associated cryptococcal meningitis received underwent ICP monitoring with using a previous sensor version of the B4C System while undergoing standard treatment over thirty-four (34) days. The subject underwent real-time non-invasive ICP monitoring at four defined during a 34-day standard treatment period. Non-invasive ICP monitoring was conducted in real-time at four specific time points before and after treatment to collect four corresponding ICP waveforms. Waveform morphology of the ICP pulses at these time points was These waveforms were visually assessed with alongside other recorded clinical parameters to determine whether the waveforms were indicative of the clinical status of the patient. The pulsatile waveform from ICP monitoring on Day 12 before lumbar puncture revealed P2>P1, amplitude of tidal wave greater than that of percussion wave, reflecting characteristics of relative peak height consistent with the presence of neurological symptoms. P1>P2 after lumbar punctureevaluate their correlation with the patient’s clinical status.
On Day 12, the ICP waveform measurement, taken just before a lumbar puncture procedure, indicated that P2 > P1, where the amplitude of the tidal wave exceeded that of the percussion wave, correlating with neurological symptoms. After the lumbar puncture, the waveform the waveform’s morphology changed such that P1 > P2, demonstrating improvement towards the characteristic P1>P2>P3 pattern, where with P3 is being the dicrotic wave, as expected with reduction in reduced ICP post-treatment. Morphology of
By Day 34, the waveforms obtained from Day 34 were more closely representing resembled normal brain compliance (P1>P2>P3), which is consistent with a reduction in ICP following the series of treatment and treatment series, leading to the patient’s discharge that same day. Results of this
This early study demonstrated that the B4C System is able to can continuously monitor ICP changes to acquire signals consistent with , providing signals that reflect the patient’s clinical status.
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Study 2 - Analysis of a Non-Invasive ICP Monitoring Method in Patients with Traumatic Brain Injury
Seven adult subjects who were admitted to the neurointensive care unit presenting with severe or moderate traumatic brain injury with and secondary neurological deterioration requiring intubation and mechanical ventilation were enrolled in the study. The objective of the study was to verify compare the waveform similarities between the Codman® Microsensor Basic Kit (iICP) and the Braincare (nICP) sensors’ waveforms. This assessment sought to provide evidence for the use of the sensors, aiming to evaluate the noninvasive sensor as an a potential alternative to invasive ICP assessments in situations , particularly where the waveform data can provide offer supplementary clinical informationinsights. In additionAdditionally, the study compared noninvasive intracranial pressure and (nICP) waveforms with arterial blood pressure (ABP) waveforms were compared to verify assess the possible potential influence of the extracranial peripheral circulation into on the noninvasive intracranial pressure nICP signal, acknowledged recognized as a potential possible limitation of the B4C System.
Each subject underwent continuous ICP monitoring using both an invasive sensor and a previous sensor version of the B4C System concurrently from point of admittance throughout sensor simultaneously from admission and for the duration of their stay in the neurointensive care unit, with acquisition time monitoring durations ranging from 68 -to 282 hours. Simultaneous ABP measurement directly through measurements via the radial artery and partial pressure of Carbon Dioxide carbon dioxide (PaCO2) were also recorded simultaneously during the monitoring these sessions. Approximately A total of approximately 337 total hours of recordings were analyzed.
The primary endpoint was the comparison of ICP waveform morphology obtained with from the nICP and iICP sensors. A The secondary endpoint was the comparison of involved comparing the nICP and ABP waveforms. Waveforms were compared analyzed in a lower-dimensional space constructed based on signals in the frequency domain. Similarity The similarity between the two devices’ signals was inferred from by calculating the Euclidean distance between the non-linear projection in a the lower-dimensional space of the window power spectral densities (PSD) of the respective signals, in which with PSD was calculated using the short-term Fourier transform. Intra-individual statistical comparisons were performed using the non-parametric Mann-Whitney U test for not non-normally distributed data points , with a significance level set at p<0.05. Measurement The measurement of similarities are is presented in the following table.
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The difference between the iICP-nICP and nICP-ABP waveforms was found to be statistically significant for all seven subjects , (p<0.05, ) using the Mann-Whitney U test. Study The study results demonstrated that indicated a greater similarity exists between the waveforms generated from by the signals of the Codman® Microsensor Basic Kit and the B4C System than compared to those between the B4C System sensor and arterial blood pressure (ABP) measurements.
Although the study had a limited sample size, the intra-individual similarities of between the invasive and noninvasive ICP signals as functions of over time suggest comparable effectiveness of ICP monitoring between that the Braincare Sensor and the invasive provides ICP monitoring effectiveness comparable to that of the Codman® Microsensor Basic Kit, which is representative of the a standard of care. Additionally, no adverse events related to the use of the B4C System were reported, supporting the safety of the Braincare sensor for monitoring intracranial pressure.
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Braincare conducted a combined prospective/retrospective, multi-center, observational study to assess compare the comparison of the acquired ICP waveform signal signals and parameters between obtained from the B4C System and with those from standard of care invasive ICP monitoring methods. The study device consisted of utilized the B4C processing and analytical software used in conjunction with the wired sensor (K182073). Although the a wired sensor was used in during the study, the results reflect the performance are representative of the B4C System's overall performance.
Dataset Description
Total number of centers: 4
Total number of subjects: 123 enrolled, 107 after device label check, 85 after data quality check (78 adults, 7 pediatric)
Collected data: ICP Surrogate Waveform (BcSs-PICNI-2000(K182073) or B4C System) ; Invasive Arterial Blood Pressure, Invasive ICP Waveform (EVD or Bolt)
Range of acquisition sessions time: 5 min to 3.5 hours
Total number of monitoring sessions that passed quality check: 159
Total acquisition time that passed quality check: 4800 minutes (98% adult, 2% pediatric)
Analyzed participants
Seventy-eight adults (18 +and over) who met all eligibility criteria and were admitted to the neurointensive care unit and underwent , undergoing both invasive ICP monitoring and invasive arterial blood pressure monitoring, were considered included in the dataset. Due to the reduced quantity limited number of pediatric subjects, the analysis could was only able to demonstrate statistically relevant significant performance for the adult population.
Total number of analyzed subjects: 78 adults
Total acquisition time analyzed: 4695 minutes
Age of analyzed subjects: 52.7±19.4
Gender of analyzed subjects: 47% female ; 53% male
Study Objective
The goal of the analysis was aimed to verify determine whether the Braincare's new medical device developed by Braincare demonstrated a consistent correlation between consistently correlates its recorded waveform ICP waveforms with the those from invasive devices waveform that are currently used in clinical practice. The Specifically, the objective was to evaluate the reliability and accuracy of the correlation between the Braincare device in monitoring ICP waveform in comparison waveforms compared to gold standard invasive ICP monitoring methods, such as the external ventricular drain or intraparenchymal micro transducers that are currently used in clinical practice, and utilized in the target population in drains and intraparenchymal microtransducers. This evaluation was conducted across different centers and medical settings within the target adult population.
Study Procedures
All centers used Braincare’s non-invasive sensors with , adhering to identical operational principles of operations (3 three centers with used the BcSs-PICNI-2000 sensor ([K182073), 1 with ], while one center used the B4C System wireless sensor). The sensors at At each site, the sensors were positioned according to the same standardized protocols, i.e., specifically in the temporal region, avoiding arteries and adjustment to the point that an acceptable waveform appeared, a procedure that represents real case usage. Patients at all sites had invasive, non invasive and ABP waveforms captured, and adjusted until an waveform of acceptable quality was achieved—mirroring real-world usage. Invasive, non-invasive, and ABP waveforms were captured for patients across all sites.
Study Outcomes
The primary objective was to compare the ICP curve morphology obtained with the Braincare and from Braincare's non-invasive sensors with that from invasive ICP sensors, with . The focus was on analyzing the characteristics of peaks the P1, P2, and P3 peaks, their amplitudes and their ratios, among as well as other characteristics aspects of the ICP pulse waveform, including the lags between wave peaks (time to peak) and the absolute curvature of the peaks. This analysis aimed to determine assess relative changes and trends over time in ICP and brain compliance.
The analysis aimed goal was to evaluate the reliability and accuracy of the Braincare device in assessing ICP waveform in comparison monitoring ICP waveforms compared to gold standard invasive ICP monitoring methods, such as the external ventricular drain drains or intraparenchymal micro transducers as well as the ability to monitor microtransducers. Additionally, the study aimed to assess the device's ability to track relative changes in ICP as well as and trends over time. The study hypothesis was that the ICP pulse morphology (waveform) detected by the Braincare noninvasive device presented non-invasive device would show a statistically significant correlation with the ICP pulse morphology (waveform) detected by the gold standard invasive method(s)methods.
Bland-Altman plots and Deming and Deming regression analyses were used to quantify the agreement between the invasive ICP waveform and the Braincare surrogate ICP waveform parameters – parameters—specifically the estimated P2/P1 ratio and normalized time to peak (TTP), by estimating the differences between the their respective minute-by-minute averages per minute. AdditionallyFurthermore, spearman Spearman and normalized mutual information methods were utilized applied to assess the non-linear behavior between the waveforms. Considering
Given the positional differences in positioning of between the invasive sensors (inside the cranium) and the non-invasive sensors (inside the ventricle compared to outside the skull), strong agreement between the signals was not expectedanticipated. NeverthelessHowever, the study observed a relatively large region of agreement and presented a significant correlation between the parameters was observed and demonstrated statistical significance , as confirmed by additional statistical tests.
Correlation analysis:
Spearman correlation and normalized mutual information were used to assess the statistical dependence on the of ICP waveform parameters between the Braincare sensor and the invasive sensor.
For the normalized time to peak, the Spearman correlation was 0.318 [0.291, 0.345], with p<.0001. The statistical dependence between
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parameters, as estimated using normalized mutual information
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, was 0.612 [0.564, 0.643].
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For the estimated P2/P1 ratio, the Spearman correlation was 0.495 [0.471, 0.517], with p<.0001. The statistical dependence between
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parameters, as estimated using normalized mutual information
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, was 0.561 [0.531, 0.606].
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The joint distributions between ICP and B4C parameters showed demonstrated statistical dependence between them, thus confirming the a statistically significant correlation between the ICP pulse morphology (waveform) detected by the gold standard invasive method(s) methods and the B4C technology with regard to , specifically in terms of the P2/P1 ratio and Time to Peak (TTP).
Agreement analysis:
Bland-Altman plots and Deming regression models were used to quantify the agreement between the invasive and Braincare-measured ICP waveform parameters – parameters—specifically the estimated P2/P1 ratio and normalized time to peak, estimating . These analyses estimated the differences between the respective minute-by-minute averages per minute. Considering the differences in positioning of the invasive and Given the differing sensor placements (inside the ventricle for invasive sensors and outside the skull for non-invasive sensors (inside the ventricle compared to outside the skull), a strong agreement between the signals was not expectedanticipated. NeverthelessHowever, a relatively large region of agreement between the parameters was observed and demonstrate , demonstrating statistical significance as confirmed by additional statistical tests. The
Bland-Altman Analysis:
P2/P1 Ratio: The limits of agreement
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ranged from -0.723 to 0.761
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, with a mean difference (bias) of 0.019
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(95% CI: -0.060, 0.101).
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Normalized Time to Peak: The limits of agreement
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ranged from -0.183 to 0.245
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, with a mean difference (bias) of 0.031
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(95% CI: 0.011, 0.050).
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Deming Regression Estimates (95% CI):
P2/P1
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Ratio: Y = -0.67 [-1.85, 0.02] + 1.60 [0.97, 2.69]X
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Time to Peak
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: Y = 0.00 [-0.11, 0.09] + 0.84 [0.38, 1.39]X
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The Bland-Altman results above, our device tends to generate larger observations for Time to Peak than invasive ICP. There are some observed instances where the Time to Peak measured by the device differed from that measured by invasive ICP by >0.2. Additionally, indicate that while the mean difference in P2/P1 between our the Braincare device and invasive ICP is not significantly different from zero, we observed there were instances where the P2/P1 ratio measured by the device differed from that measured by invasive ICP by >0.7.more than 0.7. Similarly, the Braincare device tended to generate larger Time to Peak observations compared to invasive ICP, with some differences exceeding 0.2.
Both classes of analysis, Blandanalysis—Bland-Altman/Deming Regression, which evaluate agreement, and Normalized Mutual Information/Spearman, which evaluate correlation presented correlation—presented statistically meaningful results.
Safety:
No adverse events were reported.
Study Conclusion
Results The results of this study demonstrated a statistically significant correlation in the ICP signal and waveform parameters between the B4C System and the gold standard invasive ICP monitoring device measured devices over time. The study outcomes demonstrate comparable effectiveness between outcomes indicate that the Braincare device and offers comparable effectiveness to commonly used invasive ICP devices for use in monitoring and assessing variations in ICP waveform-associated parameters over time.
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