Catalog of Regulatory Science Tools to Help Assess New Medical Devices
This regulatory science tool presents a lab method for a comprehensive analysis of benefit-risk of neuro-interventional devices and describes methods for data acquisition and analysis.
Technical Description
Brain electrophysiological signals can be acquired with invasive or non-invasive electrodes. This tool includes several quantitative electrophysiological features that would change after occurrence of brain damage. Detection of such changes implies a safety concern, and the degree of change suggests the level of risk.
Intended Purpose
Electrophysiological biomarkers of brain injury are intended to be used in the non-clinical evaluation of safety of neuro-interventional devices. Neuro-interventional devices include implantable devices which directly cause a physical tissue damage and invasive/noninvasive devices that can induce neuron activity change, for example, deep brain stimulation, transcranial current stimulation, transcranial magnetic stimulation, ultrasound neuromodulation, and so forth.
Brain electrophysiological signals reflect brain functions, which can be used to detect changes induced by any intervention, including an unexpected accidental injury and intentional neurotherapy. The FDA research suggest that electrophysiological biomarkers can be more sensitive to brain functional changes than conventional postmortem histology, the current standard method used in the non-clinical safety evaluation. Therefore, it can reveal some injury that cannot be discovered with histology, providing more insurance in the safety of neuro-interventional devices before they are used in human subject or marketing.
Testing
The tool has been characterized through animal studies in brain injuries induced by ultrasound and mechanical impact and has been compared to other methods used in the non-clinical safety evaluation of neuro-interventional devices. Furthermore, results of this work were further validated by analysis of electrophysiological data from human subjects acquired a brain injury.
The following peer-reviewed research includes the detailed characterization and verification methods and results:
- Ye M, Solarana K, Rafi H, Patel S, Nabili M, Liu Y, Huang S, Fisher JAN, Krauthamer V, Myers M, Welle C. Longitudinal Functional Assessment of Brain Injury Induced by High-Intensity Ultrasound Pulse Sequences. Sci Rep. 2019 Oct 29;9(1):15518. PubMed PMID: 31664091; PubMed Central PMCID: PMC6820547.
- Huang S, Fisher JAN, Ye M, Kim YS, Ma R, Nabili M, Krauthamer V, Myers MR, Coleman TP, Welle CG. Epidermal Electrode Technology for Detecting Ultrasonic Perturbation of Sensory Brain Activity. IEEE Trans Biomed Eng. 2018 Jun;65(6):1272-1280. PubMed PMID: 28858781. PMC9472568
- Fisher JA, Huang S, Ye M, Nabili M, Wilent WB, Krauthamer V, Myers MR, Welle CG. Real-Time Detection and Monitoring of Acute Brain Injury Utilizing Evoked Electroencephalographic Potentials. IEEE Trans Neural Syst Rehabil Eng. 2016 Sep;24(9):1003-1012. PubMed PMID: 26955039. PMC9479576
- Jang H, Huang S, Hammer DX, Wang L, Rafi H, Ye M, Welle CG, Fisher JAN. Alterations in Neurovascular Coupling Following Acute Traumatic Brain Injury. Neurophotonics. 2017; 4(4) PMC5741992
- Vivaldi N, Caiola M, Solarana K, Ye M. Evaluating Performance of EEG Data-Driven Machine Learning for Traumatic Brain Injury Classification. IEEE Trans Biomed Eng. 2021; 68(11), 3205-3216. PMID: 33635785 PMC9513823
Limitations
- To acquire brain electrophysiological signals, certain invasive or noninvasive procedures and equipment are required. Please see the Supporting documents for procedures and equipment.
- Baseline is required to identify the change.
Supporting Documentation
Please refer to the Supporting Document for data acquisition and analysis procedures. In addition, more detailed information can be found in the following publications:
These three papers described two minimally invasive methods, namely epidural recording, for the acquisition of the data and two methods of data analysis (median-nerve stimulation induced somatosensory evoked potential and resting state brain waves):
• Ye M, Solarana K, Rafi H, Patel S, Nabili M, Liu Y, Huang S, Fisher JAN, Krauthamer V, Myers M, Welle C. Longitudinal Functional Assessment of Brain Injury Induced by High-Intensity Ultrasound Pulse Sequences. Sci Rep. 2019 Oct 29;9(1):15518. PubMed PMID: 31664091; PubMed Central PMCID: PMC6820547.
• Fisher JA, Huang S, Ye M, Nabili M, Wilent WB, Krauthamer V, Myers MR, Welle CG. Real-Time Detection and Monitoring of Acute Brain Injury Utilizing Evoked Electroencephalographic Potentials. IEEE Trans Neural Syst Rehabil Eng. 2016 Sep;24(9):1003-1012. PubMed PMID: 26955039. PMC9479576
• Jang H, Huang S, Hammer DX, Wang L, Rafi H, Ye M, Welle CG, Fisher JAN. Alterations in Neurovascular Coupling Following Acute Traumatic Brain Injury. Neurophotonics. 2017; 4(4) PMC5741992
This paper described a non-invasive method for the data acquisition.
• Huang S, Fisher JAN, Ye M, Kim YS, Ma R, Nabili M, Krauthamer V, Myers MR, Coleman TP, Welle CG. Epidermal Electrode Technology for Detecting Ultrasonic Perturbation of Sensory Brain Activity. IEEE Trans Biomed Eng. 2018 Jun;65(6):1272-1280. PubMed PMID: 28858781. PMC9472568