Skip to main content

Examples of Technical Innovation for Traumatic Brain Injury Prevention, Diagnosis, and Care / Search Inside This Book
Return to Search Inside This Book results

396 matches found for How People Learn Brain,Mind,Experience,and School Expanded Edition. in 4 Clinical Decision Support from Data to Impact

Select a page to see where your word(s) or phrase(s) are located in the OpenBook. Excerpts from the chapter provide context.


In the middle of page 47...
... There is a knowledge gap among care providers about traumatic brain injury (TBI) diagnosis and treatment. This results in more patients going undiagnosed and untreated, and who are more likely to experience poor outcomes. (Adell)...
In the middle of page 47...
... Web-based calculators to predict TBI patient risk of mortality and 6-month unfavorable outcome are available free of charge, yet many providers are unaware of these tools. (Ferguson)...
In the middle of page 47...
... Improvements in TBI prediction measures and TBI phenotypes can be achieved through tools in artificial intelligence and machine learning. (Ferguson)...
At the bottom of page 47...
... TBI care and outcomes could be improved by embedding prediction models and clinical decision support tools into electronic health records. (Ferguson)...
At the bottom of page 47...
... Advanced imaging approaches (diffusion tensor imaging and diffusion kurtosis imaging) capture abnormalities associated with TBI and with TBI recovery that structural magnetic resonance imaging (MRI) does not detect. (DeMarco)...
At the bottom of page 47...
... 1 This list is the rapporteurs’ summary of points made by the individual speakers identified, and the statements have not been endorsed or verified by the National Academies of Sciences, Engineering, and Medicine. They are not intended to reflect ...
In the middle of page 48...
... and demonstrate greater sensitivity to brain pathology after TBI, creating the potential for identifying new brain injury biomarkers. (DeMarco)...
In the middle of page 48...
... Electrophysiological biomarkers can aid in initial TBI diagnosis, prediction of recovery rate, and quantitative tracking of change over time. (Prichep)...
In the middle of page 48...
... Machine learning and artificial intelligence models in mild TBI patient populations have identified electroencephalography patterns that serve as TBI biomarkers and have ...
In the middle of page 48...
... Eye-tracking technology provides a physiological measure of brain function that allows assessment of brain injury by using ocular motility to identify affected pathways. (Samadani)...
In the middle of page 48...
... Multiple pathophysiologies can underlie TBI and affect a person’s clinical outcome, and this heterogeneity contributes to failure of TBI therapeutics during clinical trials. More precise hierarchical and multimodal classification tools ... needed to distinguish TBI pathophysiologies for clinical research and treatment, foster development of therapeutics, and improve outcomes. (Samadani)...
At the bottom of page 48...
... Patients often express relief, validation, and empowerment when innovative technologies indicate brain abnormalities for the first time after weeks or months of undiagnosed ongoing symptoms. (...
At the bottom of page 48...
... Objective diagnostic measures are a mechanism for fostering equity in health care and connecting patients to needed treatment. (Samadani, Adell)...
At the bottom of page 48...
... Researchers should take steps to ensure that results from machine learning approaches are interpretable and free from bias. (Ferguson, Prichep, Villarreal)...
At the bottom of page 48...
... The fourth session of the workshop included a firsthand account of difficulties patients with traumatic brain injury (TBI) can face in pursuing diagnosis and treatment. The session also provided an ... of a handful of innovative diagnostic technologies, including machine learning approaches, ultrahigh-performance imaging, and electrophysiological and eye-tracking devices. The objectives of the session included (1) examining emerging approaches to using large and complex datasets from electronic ... records, advanced imaging, and other sources to inform clinical care, and (2) exploring trends in multimodal TBI classification to describe clinical phenotypes and inform treatment approaches. Michelle LaPlaca, professor...
In the middle of page 49...
... and director of the Neurotrauma and Translational Bioengineering Laboratory at the Georgia Institute of Technology and professor at Emory University, moderated the session. She described a need for practices that can be implemented in the clinic that better ... a person’s injury given the heterogeneity and complexity of TBI, and the need to use such knowledge to guide care. LaPlaca remarked that consideration will also need to be given to the copious quantities of data ... by clinical decision tools and the potential for confusion that large amounts of data can create....
In the middle of page 49...
... A LIVED EXPERIENCE PERSPECTIVE...
At the bottom of page 49...
... Patricia Adell, TBI survivor and managing partner at Real Estate Solutions Group, gave an account of sustaining a TBI and the barriers she encountered in obtaining an accurate diagnosis and treatment. She described three incidents of head impact. The first time, she was ... off her bike and her head slammed against the ground, but she was wearing a helmet and experienced no repercussions. The second head impact occurred when she was struck by a car and hit the pavement. Despite a lump that remains on her ... this day, Adell had no other repercussions from that injury. Her third accident was far less dramatic than the first two. She slipped while walking and fell onto the pavement. Upon standing, she immediately realized something was wrong and had difficulty walking home. Struggling with balance, light, ... sound, Adell went to the emergency department (ED), where physicians looked into her eyes, performed a computed tomography (CT) scan, and told her that although she likely had a concussion, they lacked a definitive method of diagnosing it....
At the bottom of page 49...
... After being informed that her symptoms were consistent with concussion and that she did not have a brain bleed, she was instructed to go home and lie down. Adell called her physician, who gave her the same guidance. Searching for help, she reached out to a friend who is a sports medicine ... . He made calls on Adell’s behalf that led to finding Christina Master, pediatrician and sports medicine specialist at Children’s Hospital of Philadelphia and professor at the University of Pennsylvania. Adell described connecting with ... as the beginning of her TBI education and recovery....
At the bottom of page 49...
... Adell recounted that over the course of 3–4 months, she began to feel like herself again. She stated that Master helped her throughout her recovery experience, which included a postconcussion brain bleed. She remarked that most of the TBI survivors she meets have not been able to find a recovery pathway ... a proactive provider who recommends interventions. Adell remarked that in her experience, primary care providers (PCP) have little...
In the middle of page 50...
... to no knowledge about TBI treatment and seem unaware of current care options and appropriate referrals to care....
In the middle of page 50...
... with have experienced the barrier of providers who did not recommend specialists or interventions. Given that TBI can lead to poor outcomes and even death, Adell stated her gratitude at finding effective treatment. She commented that in the absence of tools in the ED to diagnose and assess ... severity of TBI, patients are left without knowing what is wrong, whether it can be treated, and what kind of outcome to expect. Adell remarked that she is surprised that science has been slow in this area, and she is heartened to learn that ... tools are currently being developed and implemented....
In the middle of page 50...
... STATISTICAL AND MACHINE LEARNING APPROACHES TO TBI PREDICTION...
In the middle of page 50...
... Adam Ferguson, professor and director of data science in the Brain and Spinal Injury Center at the University of California San Francisco, discussed machine learning approaches to building TBI prediction models and ... health records (EHR).2 He remarked that the care failures Adell experienced are emblematic of the need for better prediction models. TBI is a complex and extremely heterogeneous condition and affects a variety of biological features that evolve over time (Irvine and Clark, 2018). Furthermore, TBI ...
At the bottom of page 50...
... Two major TBI clinical prediction models currently have traction for the acute phase of injury, Ferguson stated. The Corticosteroid Randomization after Significant Head Injury (CRASH) model and the International Mission for Prognosis and Clinical Trials in TBI (IMPACT) model were both ... in 2008 to provide the probability of 6-month mortality and risk of 6-month unfavorable outcome at 6 months after TBI....
At the bottom of page 50...
... The CRASH study was a randomized controlled trial of corticosteroid therapy in Europe involving 10,000 patients with TBI (Perel et al., 2008). The trial was unsuccessful, but ...
At the bottom of page 50...
..., Department of Veterans Affairs, Department of Defense, Defense Advanced Research Projects Agency, Department of Energy, Craig H. Neilsen Foundation, and Wings for Life Foundation. He is involved in data science consulting for Santa Clara Valley Medical Center, Neuronasal Inc., and SpineX Inc., and he ...
In the middle of page 51...
... a clinical prediction model and cross-validated it with 8,500 patients from IMPACT (Steyerberg et al., 2008). Stratified by levels of economic development, CRASH is an international ... that performs differentially in high-income versus low- and middle-income countries. The IMPACT model, on the other hand, was developed from data on 8,500 patients in 11 completed clinical trials that failed from 1984 to 2007. Data from IMPACT trials were curated, ... into a database, and cross-validated on over 6,000 patients from the CRASH trial. The two models used data from each other in developing the prediction tools, and ... also noted that both models are valid for TBI patients having Glasgow Coma Scale (GCS) scores of less than 12 and therefore exclude those with mild TBI....
In the middle of page 51...
... Both CRASH and IMPACT offer web-based calculators to encourage their use, said Ferguson.3 Anyone with an Internet connection has access to these tools, yet many ... are entered into these fields, the calculators provide a prediction of 6-month outcomes. Both calculators include optional fields for CT information, and the IMPACT tool includes optional fields for biofluid biomarker values....
At the bottom of page 51...
... The Transforming Research and Clinical Knowledge in TBI (TRACK)TBI study (McCrea et al., 2021), a large-scale observational study, validated both the IMPACT and CRASH prognostic ... in a recent paper (Yue et al., 2024). This paper assessed the measures on patients enrolled in TRACK-TBI from 2014 to 2018 and found that both models adequately discriminated mortality and unfavorable outcome. However, the models overpredicted mortality in the overall cohort ... patients with severe and moderate TBI when certain data fields were included; CRASH predictions that incorporated CT values and IMPACT predictions that used biomarker values were found to overpredict mortality for this group. The paper stated, “This suggests the presence of ... for by these models, which were developed using data from over 2 decades ago” (Yue et al., 2024). This raises the question of how to identify and navigate the full set of predictors for TBI outcomes beyond these established models, Ferguson said....
In the middle of page 52...
... Multidimensional TBI Outcome Prediction Models Using AI and Machine Learning...
In the middle of page 52...
... Artificial intelligence (AI) and machine learning tools, which are designed to incorporate as much information as possible, are well suited to incorporating a full set of potential ... associated with TBI, Ferguson stated. These tools have been used in drug development (Chakradhar, 2017), and early signs indicate that applying them to TBI holds potential for improving prediction measures. This type of analysis helps identify groupings of ... with similar features (TBI phenotypes) to further inform development of more tailored TBI classification and care approaches....
In the middle of page 52...
... a topological data analysis examining numerous TBI variables, including GCS score, neurocognitive function, functional changes, molecular biomarkers, and tissue imaging (Nielson et al., 2017). Machine learning tools were used to identify linkages across data layers to establish patient groups and ... patient stratification (see Figure 4-1). Topological data analysis projects all input data onto a map that describes the disease space of TBI and clusters patients that AI deems similar. This allows comparison of an individual patient to other TBI patients, Ferguson explained....
In the middle of page 53...
...—each represented as a point within the map—can be colored according to CT scan results. Patients whose CT scan showed brain injury are in red and patients without brain lesions on CT are in blue (Nielson et al., 2017). The map was also color-coded to reflect each patient’s magnetic resonance ... (MRI) results. Comparing the CT and MRI maps indicates that a subset of patients without lesions on CT did have injury findings on MRI. Additionally, color-coding for functional changes ... on Glasgow Outcome Scale Extended measurements taken at 3 months and 6 months revealed a phenotype of mild TBI with a positive MRI finding and degeneration of function. Layering additional variables indicated that this phenotype features enhanced levels of post-traumatic stress....
In the middle of page 53...
... A novel clinical prediction model that makes use of AI uses patient information—such as blood-based biomarker levels and absence of lesion on CT—to predict outcome, said Ferguson. In collaboration with the U.S. Department of Energy, supercomputers were used to analyze ... intake features from the TRACK-TBI pilot study and all TBI outcome features (Tritt et al., 2023). This process identified 20 subgroups of patients within the dataset. After stratifying patients based ... multiple dimensions of intake and outcome, the researchers developed a canonical correlation in which the full set of intake features is correlated with the full set of outcome ... from other legacy datasets, such as a machine learning algorithm based on data from the Protective Effects of Progesterone (ProTECT) III trial, and a mixture model framework (Bark et al., 2024; Kaplan et al., 2022)....
At the bottom of page 53...
... Ferguson stated that an obvious method of implementing prediction models in clinical care is embedding tools into EHRs. Randomized controlled trials have examined the effects of integrating clinical decision support tools into EHR systems. A meta-analysis of such randomized ...
At the bottom of page 53...
... be significant, as evidenced in other areas of neurology. For instance, multiple sclerosis (MS) researchers collaborated with patients, caregivers, and physicians to develop the MS NeuroShare system, which contains a series of MS management dashboards. The dashboards can be included in the EHR via ... MyChart system and have been imple-...
In the middle of page 54...
... mented in the Sutter Care System in California. This enables physicians, patients, and caregivers to view the prediction models in situ and in real time. Research indicates that this type of system allows sophisticated prediction activity (Bove et al., 2021). Furthermore, a study found ...
In the middle of page 54...
... said that there has been incremental progress in implementing a pediatric clinical decision support tool intended to avoid unnecessary CT scans and associated radiation exposure on children’s developing heads. Two studies demonstrated that the implementation of such decision support tools ... al., 2017; Masterson Creber et al., 2018). Furthermore, the studies found no significant change in the rate of return visits to the ED within 7 days, and return visits were not associated with misdiagnosis. He stated that evidence indicates that embedding prediction tools into the EHR changes TBI care ... may improve recovery. Ferguson remarked that implementing TBI machine learning prediction models into EHRs will be key for clinical translation and physician education in guiding decision-making through clinical decision support pathways....
In the middle of page 54...
... J. Kevin DeMarco, neuroradiologist at Walter Reed National Military Medical Center, discussed advanced MRI technologies and their potential role in TBI diagnosis.4 There remain substantial unmet imaging needs, he said, particularly for patients assessed as having mild TBI ... symptoms but do not show abnormal results on current brain imaging. Even a 3 Tesla (3T) MRI—a form of MRI that features a stronger magnet and creates more detailed images than 1.5T MRI technology—does not always identify anatomical changes related to mild TBI in a significantly ...
At the bottom of page 54...
... 4 DeMarco noted that he received government research funding, but that views expressed in his presentation are those of the authors and do not reflect the official policy of the Department of Army/Navy/Air Force, Department of Defense, or the U.S. government....
In the middle of page 55...
... 367 patients with mild TBI, 28 percent had abnormalities on CT scans, and 47 had positive findings on MRI (Palacios et al., 2022). Researchers sought to determine whether diffusion-weighted imaging would indicate ... after TBI, and whether this could be associated with a poorer recovery outcome....
In the middle of page 55...
... imaging exist. Diffusion tensor imaging (DTI) is a simplified model to describe the anisotropic Brownian motion of water molecules in the brain, and it assumes the Gaussian diffusion process (i.e., no restrictions or barriers are present). The study revealed that DTI abnormalities in axonal ... and mean diffusivity were independently associated with a 6-month incomplete recovery after TBI. Other studies have examined several higher-order ... MRI metrics, DeMarco shared. Diffusion kurtosis imaging (DKI) estimates both the Gaussian and non-Gaussian components of diffusion and is sensitive to boundaries and restrictions of white matter in addition to the direction of brain fiber tracts. DeMarco explained that DKI reveals ...
At the bottom of page 55...
...-body MRI technology—a device that can scan the entire body but does not optimally image the brain—to dedicated head-only gradient 3T systems and said that businesses are recognizing the opportunity to develop ultrahigh-performance brain MRI scanners. These dedicated systems optimize diffusion- ... imaging and enable evaluation of intra-axonal water using ultrahigh b-value diffusion-weighted imaging with a high signal-to-noise ratio, making it possible to ...
At the bottom of page 55...
... DeMarco provided an overview of how MRI technology generates an image. A whole-body MRI scanner contains miles of wire, and it operates by chilling this wire to extremely cold temperatures to induce superconducting properties that generate high static magnetic field ... . A radio frequency coil transmits radio waves, which the patient absorbs and releases, creating an image. Specifying that gradient refers to linear change, he explained that gradient coils in the three orthogonal planes ( ... magnetic field that modifies the large static magnetic field, making it possible to localize the point in space where the MR signal is coming from and to generate various types of contrast, such as diffusion. DeMarco noted that MRI technology has evolved significantly in the past 20 years, but this ...
In the middle of page 56...
... mittee for Combat Casualty Care (JPC-6)5 funded a collaboration between Walter Reed National Military Medical Center, Uniformed Services University, and GE HealthCare Technologies and Innovation Center to create a novel MRI gradient coil to accommodate only the head, thereby eliminating the need to ... a large whole-body gradient coil system when assessing head injury and ensuring ultrahigh performance optimized for brain imaging....
In the middle of page 56...
.... MAGNUS can produce high gradient strength (Gmax) with a simultaneously very high slew rate (speed at which the gradient signal can be ramped on and off) without painful peripheral nerve stimulation. A faster slew rate enables the MRI signal to be captured more quickly, resulting in decreased ... loss. This increases the signal-to-noise ratio and reduces distortion, especially near air-containing structures like the skull base. Thus, MAGNUS features all the desirable aspects for brain ... imaging: high Gmax, high gradient field, high b-values (another factor reflecting gradient strength, timing, and durations), and substantial increase in signal to noise while minimizing artifacts....
In the middle of page 56...
... b-values to 25 or 30 ms/mm2 results in images of only the water trapped within the axons, which enables direct measurements of the axon diameter and other advanced axonal measurements. DeMarco stated that the MAGNUS technology makes such measurements possible and noted that three of the largest ...
At the bottom of page 56...
... DeMarco shared preliminary evidence suggesting that high-performance head-only MRI could be used to collect effective axonal radius measurements, and that these could be a specific marker of white matter abnormalities in individuals with chronic symptomatic mild TBI that researchers have previously ...
At the bottom of page 56...
... DeMarco and colleagues compared the results of DTI, DKI, and effective axon radius maps. Using the patient as their own internal control, researchers compared the white matter tract parcels on the right and ...
At the bottom of page 56...
... 5 Joint Program Committees consist of U.S. Department of Defense (DoD) and non-DoD medical and military technical experts who coordinate research and development efforts....
In the middle of page 57...
... parcels was seen in these same chronic mild TBI patients. This individual abnormal white matter parcel lateralization is consistent with the understanding that TBI affects different parts of the brain depending on the mechanism of injury....
In the middle of page 57...
... Exploring Next Steps and Opportunities...
In the middle of page 57...
... DeMarco emphasized opportunities for dedicated ultrahigh-performance neuroimaging MRI scanners to contribute to advances in TBI diagnosis and care. DeMarco and colleagues plan to evaluate the benefit of combining high-performance imaging techniques to identify new imaging biomarkers in ... TBI, which offers the additional advantage of collecting data on the same person over multiple time points, thereby decreasing biological variance and correlating symptomology over time. He underscored that ultrahigh b-value diffusion with effective axonal radius measurements has demonstrated ... to pathology that neither DTI nor DKI have been able to achieve in the same population, and that larger studies are needed to fully characterize axon size distributions in people with mild TBI and healthy cohorts....
In the middle of page 57...
... Leslie S. Prichep, chief scientific officer at BrainScope Company, described how electroencephalography (EEG) can be combined with AI and machine learning approaches to identify brain activity abnormalities, classify TBI patients into more precise pathophysiologic subtypes, and predict ...
At the bottom of page 57...
... Prichep explained that EEG, which measures brain electrical activity, is a test often used as part of diagnosing epilepsy and seizures. Quantita-...
At the bottom of page 57...
... 6 Prichep noted that she is an inventor of intellectual property licensed by BrainScope from NYU School of Medicine and that her presentation reports results of independent prospective FDA validation studies, to which BrainScope Company was blinded. The ...
In the middle of page 58...
... tive EEG (qEEG) processes EEG waveforms to characterize the signal into features that can be used to describe brain activity and how it compares to normal, expected brain activity for different ages. In particular, qEEG allows the characterization of aspects of brain electrical ... not visible to the naked eye via visual inspection. The past decade has seen advances in the EEG landscape, including development of a handheld device that performs EEG, analyzes data, and provides feedback in real time. Advances in signal processing have enriched measures derived from ... EEG and have enabled the creation of thousands of features that characterize the signal. Machine learning and AI can be used to develop algorithms to identify signal patterns indicating abnormalities that then become biomarkers....
In the middle of page 58...
... She explained that EEG is uniquely sensitive to brain changes associated with traumatic structural and functional brain injury owing to the millisecond time base and to features that are particularly important in the algorithms developed in this area. ... features include connectivity, complexity, and frequency distribution. Connectivity reflects disruption of neuronal transmission between brain regions, with measures including coherence, phase ... , phase lag, and asymmetries. Complexity of the signal reflects disorganization of the neural networks via fractal dimension, entropy, scale-free brain activity, and ... indicators. Frequency distribution reflects changes in the neurochemistry, oxygen flow, glucose metabolism, and presence of edema (swelling) in the brain. The use of AI and machine learning approaches with qEEG features as inputs enables the development and ...
At the bottom of page 58...
... Multiple sources of information can be used as part of TBI diagnosis, classification, and treatment, and Prichep described EEG-based algorithms developed by BrainScope and cleared by the U.S. Food and Drug Administration (FDA) to explore the likelihood ... brain bleed in patients who are CT positive for a TBI, CT negative, have a concussion, and do not have a concussion. She outlined the process of moving from EEG recordings to TBI classification, emphasizing the importance of having a high ... signal and addressing artifacts (signal features arising from the equipment itself). Otherwise, the artifacts will skew input to the algorithm, and the machine learning approach may separate patients with high levels of artifacts from those with low levels of artifacts rather than separating ...
At the bottom of page 58...
... For signal quality, BrainScope uses a suite of eight artifact algorithms that run in real time, providing user feedback and stopping data collection in the event an artifact is present, Prichep said. After recording the EEG, the...
In the middle of page 59...
... process involves extracting qEEG features and transforming them to age-expected normal values using z-scores. This establishes the same dimensionality of standard deviation units to enable data ... be combined statistically. The data reduction phase can involve extraction of 10,000 features. Prichep noted that inputting 1,000 patients and 10,000 features into a machine learning algorithm will result in excellent separation that cannot be prospectively validated. Additional modalities—...
At the bottom of page 59...
... are predominantly brain connectivity measures that characterize neuronal transmission regions as well as multimodal inputs, such as vestibular and procedural reaction time. A study of 1,577 sessions of data on 580 athlete patients from 10 clinical sites validated the CI (Bazarian et al., 2021). ... a threshold of concussion, the CI classifies patients with a CI score of less than or equal to 70 as likely concussed and those with CI scores above 70 as likely not concussed (see Figure 4-2). The study examined whether patients were above or below the threshold at ... time points: day 0 (i.e., the first 72 hours of injury), clinical determination of return to play (RTP), and 45 days after RTP. Athletes without concussion served as controls, and they were consistently above the concussion threshold at all time points. The ...
At the bottom of page 59...
... At day 0, a highly significant difference between the control and injured groups was evident. At RTP, 80 percent of injured subjects were within normal limits. Prichep underscored that this finding reveals that 20 ... of subjects who passed all RTP guidelines continued to report symptoms and show abnormal brain electrical activity. At 45 days after RTP, all participants were above the concussion threshold. She added that subjects with a ... of less than 14 days after injury had a higher CI value than those with a prolonged RTP of 14 or more days. Therefore, the CI score reflects severity and the potential to predict rate of recovery, she explained....
At the bottom of page 59...
... indicated that those with rapid RTP have higher CI scores at day 5 than those with prolonged RTP, suggesting that change in CI score tracks recovery and that the slope of recovery is different between those who will have prolonged recovery and those who will have rapid recovery (Jacquin et al., 2021). ...
In the middle of page 60...
... FIGURE 4-2 Concussion index values over time in athletes with and without concussion....
At the bottom of page 60...
... between imaging (using DTI) and CI, a study found a significant relationship between several DTI measures and CI in the same patients with concussion in which more abnormal DTI measures are associated with lower CI scores, said Prichep (Wilde et al., 2019). ... finding suggests that CI reflects changes in white matter integrity. Prichep noted that BrainScope’s device only collects data from the frontal and frontal temporal regions of the brain, and this study indicates that this data collection method does not limit reflection of abnormalities found ...
At the bottom of page 60...
... subtypes according to signal characteristics that provide information about gray matter, white matter, the gray–white interface, and underlying pathophysiology. Measures of power, connectivity, and complexity result in different compositions for each of the five subtypes....
In the middle of page 61...
... Prichep noted that this is the first demonstration of electrophysiological subtypes within the heterogeneous group of patients with concussion and offers potential for advancing understanding of underlying pathophysiology. Given that these subtypes come from data taken within 72 hours of injury, ... ability to personalize diagnosis carries implications for treatment recommendations and associated outcomes. She described how a search of available clinical information did not reveal clear correlates between symptoms after concussion ...
In the middle of page 61...
... signal in each region. She described findings from EEG complexity measures of the dorsolateral prefrontal cortex, a region associated with cognitive and executive function. Higher complexity represents higher functioning. Researchers plotted complexity measures at various time points in relation to ... exposure: preexposure baseline, 6 hours postblast, 24 hours postblast, and 2 weeks postblast....
At the bottom of page 61...
... remains at similar levels across time points. This signifies that a set of measures of EEG signal complexity is highly correlated with blast exposure and normalizes over time, Prichep explained, indicating the possibility of developing an EEG-based biomarker for evaluation of subconcussive blast ...
At the bottom of page 61...
... Outlining conclusions from this EEG research, Prichep emphasized that qEEG is a tool to quantify brain electrical activity and that qEEG features can reflect changes in neuronal transmission, integrity of neural networks, and neurochemistry, such as edema (swelling). ... biomarkers can serve as decision support tools and aid in initial diagnosis, prediction of rate of recovery, and quantitative tracking of change over time....
In the middle of page 62...
... She stated that machine learning and AI models in populations of patients with mild TBI have identified patterns of qEEG features that serve as TBI biomarkers and noted that the CI has ... TBI. Prichep described subtyping as an interesting approach to identifying phenotypes that may lead to faster, more personalized treatment planning and potentially to better outcomes....
In the middle of page 62...
... Uzma Samadani, founder of Oculogica and neurosurgeon at the Minneapolis Veterans Administration Medical Center, outlined use of the EyeBOX eye-tracking test and the benefits of using eye ... injury.7 She noted that eye movements have been considered a test for brain injury for approximately 3,000 years. Prior to the invention of radiology and head CT, brain injury was defined by its symptoms, and one of the most obvious symptoms was dysfunctional ocular motility....
At the bottom of page 62...
... relevant; patients may choose to watch music videos, sports, or any other preferred genre. A video window moves to different locations of the screen, and a small camera measures pupil size and position as the eyes follow the video window. EyeBOX takes measurements at 500 hertz (i.e., 500 times per ... ), and the noninvasive test collects x- and y-coordinates of the pupils and size measurements for 220 seconds. EyeBOX does not require a blood draw or centrifuge, the results are instant, and a preinjury baseline is not ...
At the bottom of page 62...
...; Islamic Medical Association of North America; Medtronic Corp; Minnesota Brain Injury Alliance; Minnesota, Texas, Louisiana, Wisconsin, Wyoming High School Coaches Association; National Football League; National Neurotrauma Society; North American Brain Injury Society; Oculogica Inc; Steven and Alexandra ...
In the middle of page 63...
... outlined the benefits of using eye tracking to assess brain injury via cranial nerve function. The cranial nerves are highly sensitive to injury and have a large catchment area inside the brain. A TBI that damages areas controlling relevant cranial nerves can be monitored and measured through ... such as pupil size, pupil reactivity, and pupil position. In a healthy individual, cranial nerves reflexively cause pupils to constrict in higher light levels and both eyes move together. ...
At the bottom of page 63...
... As people age, ciliary muscles become weaker and pupils are not as effective at constricting, but the ability of eyes to move together without conscious effort remains relatively well preserved ( ... control of eye movements). Different pathways coordinate eye coordination, vertical movement up, vertical movement down, and horizontal movements. These eye movements are coordinated in the brain stem, and when a person has an impairment, it manifests itself in particular ... depending on which pathway is impacted. Examining ocular motility can thus enable identification of the affected pathway, and this was the rationale for developing EyeBOX, Samadani explained....
At the bottom of page 63...
... Samadani and colleagues conducted numerous studies exploring the usefulness of eye tracking, including research demonstrating that issues with the third and sixth ... nerves are detectable through eye tracking (Samadani et al., 2015a). Another study demonstrated sensitivity and specificity of eye-movement tracing in an ED population (Samadani et al., 2016). Research indicated that eye tracking detects disconjugate eye ... associated with structural injury from TBI (Samadani et al., 2015b). Other studies examined elevated intracranial pressure and reversible eye-tracking changes (Kolecki et al., 2018), eye-tracking ramifications on TBI diagnosis and classification (Samadani, 2016), and the ... . Rather, Oculogica issues payment to an institution to compensate for an investigator’s time, but this is not passed on to the investigator and they do not receive compensation beyond their regular salary. She also highlighted the existence of studies conducted by researchers not affiliated ...
In the middle of page 64...
... ducted by nonaffiliates has explored the reliability of objective eye-tracking measures among healthy controls (Howell et al., 2020)....
In the middle of page 64...
... Physiologic Measures of the Brain...
In the middle of page 64...
... system (CNS) function, said Samadani. Research submitted to FDA in support of this clearance indicated an intended use population aged 5–67 years and included testing performed in ED and non-ED settings (Samadani et al., 2022). The study used two subsets of the Sport Concussion Assessment Tool 3, ... Symptom Severity Scale Score, and the Standardized Assessment of Cognition....
At the bottom of page 64...
... Samadani described that for millennia, physical and psychological exams were the only methods of assessing CNS function. In more recent times, imaging, EEG, qEEG, and other tests became available. ... provides information about vascularity and the brain’s appearance. Other developments include methods of assessing the integrity of systems, advanced imaging such as 3T MRI, and the ability ... assess cranial pressure and brain oxygenation. Samadani remarked that uncalibrated or non-spatially calibrated eye-movement tracking is a new type of technology most closely ... , but is intended as an automatable, objective, nonrisky, nonradiation exposing, noninvasive physiologic method that is agnostic to language, culture, and education....
At the bottom of page 64...
... Samadani discussed the value of TBI diagnostics as part of refined classification approaches and their connections to early intervention and therapeutic development. Drawing a comparison between cardiac and TBI care, Samadani highlighted how the advent of the cardiac biomarker troponin ... ED treatment of chest pain. The presence of troponin enables numerous causes of chest pain to be ruled out simultaneously and hastens performance of an electrocardiogram or cardiac catheterization. In contrast, patients with head injury generally receive a physical exam and ... , microhemorrhages, epidural hematoma, or subdural hematoma, she noted. Instead, pathophysiologies are grouped together, both for clinical treatment and for research toward developing therapeutics. She remarked that the Glasgow Outcome Scale (GOS) is limited to placing patients within eight categories,...
In the middle of page 65...
... Samadani argued that a collective TBI community should highlight the need for better hierarchical and multimodal classification tools for brain injury, and that multiple metrics should be used to determine what is wrong with the patient, including eye ... , algorithmic analysis of CT and 3T MRI, blood-based biomarkers, and genetics. Samadani described genetics as an elephant in the room in that it plays a role in outcome after brain injury, yet is not often accounted ... all these components into algorithms that classify the nature of brain injury could improve outcomes, she noted. Recognizing TBI soon after injury and classifying physiology could disrupt the undesirable consequences of undiagnosed brain injury and facilitate the ability of patients to receive early ...
At the bottom of page 65...
... & Medicaid Services (CMS) also approved the device. She underscored the steps involved, which included submitting papers, providing data, and demonstrating effectiveness in the intended population, and remarked that the single greatest barrier to wider incorporation of new assessment ...
At the bottom of page 65...
... test is not validated for someone as complicated as the patient or that the patient’s level of functioning is too high for the test’s capability, and therefore the insurer may prefer use of a CT scan and refuse coverage for the eye tracking test. Although some large payers reimburse for eye ... , such as Blue Cross Blue Shield and UnitedHealthcare, she said, not all insurance companies currently reimburse for this service. Insurance companies want indication that use of a ... fails, it can discourage investors from entering the market. She remarked that this has happened to some extent in the area of dementia diagnostics and could happen in TBI....
In the middle of page 66...
... Samadani described a chicken-and-egg dynamic, in which the inability to precisely and accurately classify TBI impedes the development and availability of new therapeutics. Heterogeneity causes trials for TBI therapeutics to fail, she said, while diagnostics are needed to help identify ... the development of better therapeutics, but making reimbursement for diagnostics contingent on their ability to change management creates a chicken-and-egg barrier, she said. Advocacy efforts are needed to shift insurance policy to expand reimbursement for TBI diagnostics, Samadani maintained....
At the bottom of page 66...
... Leslie Wise, chief executive officer at EvidenceMatters, clarified that a CPT code is the numerical representation of a provided service and is not a reimbursement code. Professional societies generally will not support CPT codes outside of their specialties, she noted. The Medicare, ... , and SCHIP Balanced Budget Refinement Act of 1999 requires that the valuation of a new code be accompanied by retiring an existing code or by having all ... specialty revalued for a lower reimbursement.8 Wise described obtaining a Level 1 CPT code as a strategic process that often requires 5 years and involves five publications and an outcome study at Level 2A or higher. Organizations can assist with this time-intensive process. Wise explained that ... the code sets the amount for which the corresponding service will be sold; CMS does not set the amount. She added that the process can be political, and that an organization’s lack of support for a new code may not be indicative of a lack of enthusiasm for the service, but rather reflective of ...
At the bottom of page 66...
... Specialties such as radiation and MRI-guided CT have previously collaborated to establish a group to consider components of a particular disease state, Wise remarked. This approach ... be used to systematically structure and publish an argument for needed evolution within the TBI space that addresses various pieces of the larger context, including imaging, EEG, and eye ...
At the bottom of page 66...
... 8 Medicare, Medicaid, and SCHIP Balanced Budget Refinement Act of 1999, Public Law 106-113, 106th Cong., 1st sess. (November 29, 1999)....
In the middle of page 67...
... ers develop an understanding of what is needed within a field and has the potential to lead to coverage for new services. She argued that randomized controlled trials alone are insufficient for influencing coverage of extremely expensive technologies such as imaging machines; instead, payers ... to a framework that organizes the research and illustrates trends and possibilities of the future space. Breaking down TBI phenotypes and correlating these with types of injury or other characteristics could be effective in helping payers understand the relationships between injuries ...
At the bottom of page 67...
... Cynthia Grossman, subject-matter expert in the science of patient engagement and real-world evidence, emphasized the heterogeneity in TBI patient populations, the substantial effects TBI can have on people, and the role of ... to engaging patient communities in the innovation journey by communicating directly about TBI innovations to illustrate stories behind the advances and their potential benefits. Corinne Peek-Asa, vice chancellor for research at the University of California San Diego, asked about the most appropriate ... frame for engaging patients and how to drive advances toward addressing the symptoms that patients want treated. She commented that the ability to identify disruptions among brain ... and damage to brain white matter is exciting, for example, but that most patients are likely focused on personal ramifications such as why they have a ...
At the bottom of page 67...
... eye tracking had prior interactions with the health care system for their TBI. For instance, several patients went to the ED after their injuries and were told that they did not need a head CT or that the CT was negative, and they should go home and rest. Days, weeks, or even months later, they ... into tears after having TBI identified via eye tracking, communicating that no one had previously believed them. This experience can be validating and empowering, encouraging patients to again seek treatment. Therapeutics or interventions may be available to help address symptoms, but before a ... increased attention on medical gaslighting (i.e., when a provider invalidates or ignores a patient’s concerns), she described that some genders and races are associated with...
In the middle of page 68...
... Prichep recalled experiences in TBI clinics in which high school students with persistent symptoms from sports injuries—and their parents—expressed relief at being identified with a numerical value indicating ...
In the middle of page 68...
... sharing their lived experience, indicating steps toward greater patient engagement.9 He noted that a unique aspect of clinical prediction models and machine learning is that the expertise for these tools resides outside of the medical field, including in fields such as investment banking. A subset ... professionals in those fields will experience TBI, and thus increased engagement with other fields also offers a useful opportunity to drive research, he said....
At the bottom of page 68...
... Highlighting stroke care as an example of implementing advances in the field, DeMarco described that a decade of research identified how to diagnose and treat acute stroke, and these practices are now widely available in any ED. Furthermore, patients in need of more advanced care are now able to be ... and transferred to comprehensive stroke services. Providers are in need of effective instruction on diagnosing TBI, and the progress made in stroke care offers insights on advancing TBI care. Once TBI can be diagnosed in a reproducible, consistent manner across EDs, ... should be given to methods of identifying TBI patients with more complex needs and to the creation of comprehensive care centers that offer the various modalities discussed at this workshop, said DeMarco. He contended that ... in prognostication and enrolling patients could also lead to more effective therapies....
At the bottom of page 68...
... 9 Video from the Traumatic Brain Injury Classification and Nomenclature Workshop, convened by NINDS in January 2024 is available from https://videocast.nih.gov/watch=54118 (accessed July 9, 2024)....
At the bottom of page 69...
... Adell stated her excitement at learning of new TBI diagnostic methods, and she noted that athletes and military personnel seem to be the focus of much TBI research because the cause of injury is more predictable. She remarked that people like her who ... range of unpredictable causes of injury seem to receive less attention. Highlighting the need for increased education efforts for providers in the ED and in primary care, she observed that when providers have difficulty diagnosing TBI, they tend to dismiss patient concerns as emotional or mental health ... she experienced, she described light sensitivity that prevented her from looking at a computer or watching television, noise sensitivity, and lack of balance. She was certain something was wrong with her, but without the help of a physician friend able to locate a care pathway for her, she ... have had to suffer with her symptoms and assume nothing could be done to improve her outcome. Adell said that the workshop has brought the complexity of insurance and reimbursement issues to ...
At the bottom of page 69...
... previously was on the faculty at New York University, during which time she taught the only course offered on brain injury during the 4-year medical school program of study. Most people educated in brain injury are residents in neurosurgery or physical medicine and rehabilitation, as these fields often ... , neurology, and pediatrics have rotations involving patients with brain injury. However, many medical students proceed through 4 years of medical school without attending a lecture on TBI or seeing a patient with brain injury. Samadani recalled a paper indicating that many physicians receive TBI ...
At the bottom of page 69...
... Introducing technologies in the U.S. Department of Veterans Affairs (VA) is a method of simultaneously gaining traction for innovations and educating providers, suggested Wise. Given that VA does not face the same insurance reimbursement issues that the general health care system contends ... than the broader health care system. Moreover, 70 percent of the nation’s physicians train in the VA system at some point in their careers, and doctors tend to carry their training into practice, she remarked. While VA physicians become familiar with an innovation, a company can continue ... through the process of attaining a CPT code and getting a reimbursement structure in place. When physicians move from the VA system into regular practice, they will continue to purchase the technol-...
In the middle of page 70...
... Maheen Mausoof Adamson, professor at the Stanford School of Medicine and senior scientist for rehabilitation services at the VA Palo Alto Healthcare System, stated that in working at a VA facility for ...
In the middle of page 70...
... Joel Scholten, director of Physical Medicine and Rehabilitation at the Department of Veterans Affairs, noted that the patient population at the VA differs from the private sector in that most ... with TBI experienced the incident event at least a year prior during deployment or active duty. He remarked that the VA welcomes innovation and the integration of new technology but requires evidence that it is of benefit for long-term effects and chronic conditions. Additionally, the VA has ...
At the bottom of page 70...
... Potential Drawbacks in Machine Learning and Artificial Intelligence...
At the bottom of page 70...
... Darío Villarreal, head of science and technology at Toyota Way Forward Fund, highlighted that eye-tracking research explores cause and effect from the physiological perspective to understand why pupils dilate. He asked about the implications of the black box in machine learning, in ... to make predictions. Remarking on the difficulty of determining whether a machine learning result is correct or incorrect in the absence of understanding cause and effect, he emphasized that bias could enter the data and lead to unethical results. Villarreal asked how the results of a black box can ... confirmed and determined to be free from bias against certain populations....
At the bottom of page 70...
... Ferguson replied that the danger of overfit is a classic problem in machine learning. For example, results may fit the 15 patients studied but...
In the middle of page 71...
... not fit any future patients. He noted that researchers often cross-validate machine learning models, as was the case with IMPACT and CRASH. Advances toward interpretable machine learning tools are being made (Tritt et al., 2023), such as modern attention networks and expert- ... is then used as input to the machine learning to improve the system. Ferguson remarked that guardrails for machine learning are being developed, and that caution is warranted when implementing machine learning results....
At the bottom of page 71...
... Prichep echoed that attention to black boxes is needed to protect the community into which tools and algorithms are being introduced. She described herself as extremely cautious about overtraining in machine learning and noted that data reduction, ... cross-validations, and independent validations after algorithm finalization are methods BrainScope uses to avoid incorrect results. In cases where expected accuracy cannot ... new to the algorithm, more work remains before results are implemented. Prichep emphasized that the providers who will be using the results and the patients they treat deserve interpretable outputs that have been carefully considered, and the onus for interpretable results is on model ...
At the bottom of page 71...
... A participant asked about the power of AI tools to extract several different features from the EEG signal and how to differentiate between the most realistic features versus those lacking clear rationale. Prichep stated that some methods of interacting with ... . These include initial steps that could be considered heuristic, such as including features demonstrated in literature to be important in the area and omitting any variables that have not been shown to be replicable within more than one EEG sample within a population. She remarked that if a variable ...
At the bottom of page 71...
... in capturing the variety of ways that individuals may be abnormal. Ultimately, AI tools generate a summation of a weighted set of features, and the same score with the same features can be generated via different weightings. Prichep stated that researchers can build protection against results ...
In the middle of page 72...
... Emergency Medical Services and Machine Learning...
In the middle of page 72...
... data have been incorporated into machine learning approaches. If not, Kinsman asked whether NHTSA could collect any crash or prehospital assessment and care data that would fill gaps in machine learning models, particularly as NHTSA considers clinical decision support tools in TBI classification. ...
At the bottom of page 72...
... Jeffrey Bazarian, professor at the University of Rochester, described the ability to identify and target treatment to pathophysiologic endophenotypes10 as the holy grail in TBI research. He asked to what extent technologies presented today could ... used in identifying those endophenotypes and in understanding the best treatments for specific endophenotypes. Bazarian also queried whether AI has a role in this process. Ferguson replied that the ... pathophysiologies, which in turn suggest various treatment interventions. She remarked that the availability of more robust outcome data would expand the ability to identify subtypes....
At the bottom of page 72...
... BrainScope’s outcome data are related specifically to the length of time until individuals were RTP cleared and 45 days beyond. Their outcome data do not include the evolution of different clinical sequela or responses to various treatments. Ultimately, the ...
At the bottom of page 73...
... Michel Baudry, founder and chief scientific advisor at NeurAegis and professor at the Western University of Health Sciences, asked about the use of different technologies in the identification of TBI subtypes and ... eye tracking, EEG, and high-performance MRI identify similar subtypes of patients, reflecting underlying molecular or physiological mechanisms. Samadani replied that eye- ... group. A small percentage will develop abnormal eye-tracking metrics that are more consistent with accommodative disorders or vergence dysfunction and may have persistent symptoms for a longer period of time. Samadani noted that a publication on characterizing subtypes is in preparation, and that ... is also currently applying to FDA to expand EyeBOX’s current clearance for injury within 2 weeks to an indefinite time period. Other measures (levels of different blood biomarkers or imaging ... did not fully clarify whether patient subtypes currently being characterized by different technologies reflect common underlying mechanisms, and more work remains....
At the bottom of page 73...
... Frederick Korley, professor at the University of Michigan, commented that different diagnostic neuromonitoring technologies all have strengths and highlighted the potential value of combining them in an effort to maximize predictive value. He reflected that one challenge, to his knowledge, is ... containing complete information on the same individuals is required. He also asked if the Forum on Traumatic Brain Injury can encourage awareness and efforts toward collecting such multimodal data to assess how different modalities work together....
In the middle of page 74...
... learning tools are capable of accommodating missingness. For example, a mixture model framework specifically measures the pattern of missingness and then creates new features from the missing data pattern (Kaplan et al., 2022). Such models harness the patchwork of missingness that occurs across a ... on the same individuals. The INVICTA study has numerous touch points on each individual soldier, but it focuses on blast exposure, not on blast TBI, and is a different subtype of the general group. She noted that one of INVICTA’s aims is to take measurements from blood biomarkers, EEG, virtual ... , and eye tracking and input them into one model. Prichep stated that the forum could consider developing a method to share data in one place for one population and proceed ...
At the bottom of page 74...
... LaPlaca asked about current and potential data sharing, noting the challenges that are often involved in data sharing within the private sector. She also noted that reimbursement ... could pose a barrier to multimodal testing and asked how this might be addressed. Samadani remarked that data from any clinical tests could be saved and used in a post hoc analysis, a process that creates a real-world experience user database that is reviewed retrospectively. A prospective study would ... . Adding that participants in research studies are not always representative of the general population, Samadani highlighted the value of TRACK-TBI and its fairly representative patient population. Yet, significant ascertainment bias remains present in TRACK-TBI because its participants had the means ... return for multiple follow-up visits, and significant segments of the population lacking the resources or time for return visits are not included in the study, Samadani pointed out....
At the bottom of page 74...
... described that large movement disorder databases have been assembled from accelerometers—such as wearable devices, including smart-phones that many people currently opt to carry on their person throughout the day—that are then used in algorithms that aid in Parkinson’s disease diagnosis. Ferguson ...
At the bottom of page 75...
... of Research and Development at the VA, stated that a law requires the VA to participate in a mental health process that includes TBI. This involves harmonization of ... large datasets, both of which are ongoing, longitudinal datasets primarily focused on TBI but also containing mental health disorders related and not related to TBI. The goal of this effort is to integrate multimodal biomarkers after they have been harmonized between the two datasets, which ...
At the bottom of page 75...
... LaPlaca remarked that many additional technologies are under development, and those presented today represent advances in innovation and highlight the need for multimodal assessments from the research level to clinical use. She emphasized the value of patient engagement and the early ... of aspects related to FDA clearance and reimbursement processes....

A total of pages of uncorrected, machine-read text were searched in this chapter. Please note that the searchable text may be scanned, uncorrected text, and should be presumed inaccurate. Page images should be used as the authoritative version.