Assessing the clinical needs for point of care technologies in neurologic emergencies.

BACKGROUND: Neurologic emergencies are common, frequently devastating, and benefit from timely diagnosis and treatment. Point of care (POC) technologies have the potential to assist clinicians caring for these patients. In order to prioritize development of new POC testing, a thorough assessment of clinical needs is required. We describe the methods of the clinical needs assessment (CNA) process and provide the initial findings of a CNA for POC technologies in neurologic emergencies performed to support a National Institute of Biomedical Imaging and Bioengineering (NIBIB) initiative. METHODS: CNA is an iterative process. An initial survey instrument was developed through consensus by a multi-disciplinary panel and underwent internal validation through beta-testing and face-validity assessment. This survey was distributed at the national meetings of several academic medical societies and results were used to redesign of the survey tool for broader distribution. Analysis of responses from the revised survey supported the release of a request for proposals (RFP) in 2010. Survey revision continues, and expanded CNA efforts with focus groups are being designed in anticipation of another RFP in 2012. RESULTS: The initial survey identified six areas of clinical need and two domains of interest. The revised version gathered additional responses but no new domains or areas of clinical need were identified. The resultant RFP generated 23 letters of intent from industry and academic institutions, of which three were chosen for funding. CONCLUSIONS: Assessing clinical needs is a necessary first step in developing new technologies. A multi-faceted approach assures that the views of interested stakeholders are represented and can influence success.

Dynamic Time-frequency Feature Extraction for Brain Activity Recognition.

The biomedical signal classification accuracy on motor imagery is not always satisfactory, partially because not all the important features have been effectively extracted. This paper proposes an improved dynamic feature extraction approach based on a time-frequency representation and an optimal sequence similarity measurement. Since the wavelet packet decomposition (WPD) generates more detailed signal variation information and the dynamic time warping (DTW) helps optimally measure the sequence similarity, more important features are kept for classification. We apply the extracted features from our proposed method to Electroencephalogram (EEG) based motor imagery through the OpenBCI device and obtain higher classification accuracy. Compared with traditional feature extraction methods, there is a significant classification accuracy improvement from 83.53% to 90.89%. Our work demonstrates the importance of the advanced feature extraction in time series data analysis, e.g. biomedical signal.

Spectrophotometric quantification of bilirubin in hemorrhagic spinal fluid using an innovative algorithm.

Annually, approximately 30,000 people suffer from aneurysmal subarachnoid hemorrhage (SAH) in the United States. In an estimated 5% of these patients, the hemorrhage is difficult to diagnose using conventional methods. Clinicians must rely upon a combination of clinical history, Computerized Tomography (CT) scan evidence and lumbar puncture results to diagnose and differentiate SAH from a traumatic spinal tap (blood in the spinal fluid due to the procedure). Here we describe an algorithm based development of an analytic methodology using visible spectroscopy to reliably quantify bilirubin in hemorrhagic spinal fluid. The analysis, which may be useful for diagnoses concerning hemorrhagic stroke, is based on the detection of bilirubin, and concomitant blood products produced within the Cerebral Spinal Fluid (CSF) following SAH. The algorithm quantifies bilirubin (0.3 to 10 mg/dL) from the resultant absorption spectrum. A model is developed from standard visible spectroscopic absorption curves of bilirubin and hemoglobin by applying traditional Beer's Law principles. The model is coupled to a modified partial least square analysis and control theory concept where the bilirubin is the "signal" and is masked by hemoglobin "noise." This paper describes the computational methods, sensitivity and utility of a system to quantify bilirubin in CSF like solutions containing hemoglobin and bilirubin over 0.5 g/dL-10 g/dL of hemoglobin concentrations.

A Novel Tool for Evaluation of Mild Traumatic Brain Injury Patients in the Emergency Department: Does Robotic Assessment of Neuromotor Performance Following Injury Predict the Presence of Postconcussion Symptoms at Follow-up?

OBJECTIVES: Postconcussion symptoms (PCS) are a common complication of mild traumatic brain injury (TBI). Currently, there is no validated clinically available method to reliably predict at the time of injury who will subsequently develop PCS. The purpose of this study was to determine if PCS following mild TBI can be predicted during the initial presentation to an emergency department (ED) using a novel robotic-assisted assessment of neurologic function. METHODS: All patients presenting to an urban ED with a chief complaint of head injury within the preceding 24 hours were screened for inclusion from March 2013 to April 2014. The enrollment criteria were as follows: 1) age of 18 years or greater, 2) ability and willingness to provide written informed consent, 3) blunt head trauma and clinical diagnosis of isolated mild TBI by the treating physician, and 4) blood alcohol level of <100 mg/dL. Eligible mild TBI patients were enrolled and their neuromotor function was assessed in the ED using a battery of five tests that cover a range of proprioceptive, visuomotor, visuospatial, and executive function performance metrics. At 3 weeks postinjury, participants were contacted via telephone to complete the Rivermead Post-Concussion Symptoms Questionnaire to assess the presence of significant PCS. RESULTS: A total of 66 mild TBI patients were enrolled in the study with 42 of them completing both the ED assessment and the follow-up; 40 patients were included in the analyses. The area under the receiver operating characteristic curve (AUC) for the entire test battery was 0.72 (95% confidence interval [CI] = 0.54 to 0.90). The AUC for tests that primarily measure visuomotor and proprioceptive performance were 0.80 (95% CI = 0.65 to 0.95) and 0.71 (95% CI = 0.53 to 0.89), respectively. CONCLUSIONS: The robotic-assisted test battery has the ability to discriminate between subjects who developed PCS and those who did not. Additionally, poor visuomotor and proprioceptive performance were most strongly associated with subsequent PCS.

Integration of New Technology for Research in the Emergency Department: Feasibility of Deploying a Robotic Assessment Tool for Mild Traumatic Brain Injury Evaluation.

UNLABELLED: The objective of this paper is to demonstrate the effective deployment of a robotic assessment tool for the evaluation of mild traumatic brain injury (mTBI) patients in a busy, resource-constrained, urban emergency department (ED). METHODS: Functional integration of new robotic technology for research in the ED presented several obstacles that required a multidisciplinary approach, including participation from electrical and computer engineers, emergency medicine clinicians, and clinical operations staff of the hospital. Our team addressed many challenges in deployment of this advanced technology including: 1) adapting the investigational device for the unique clinical environment; 2) acquisition and maintenance of appropriate testing space for point-of-care assessment; and 3) dedicated technical support and upkeep of the device. Upon successful placement of the robotic device in the ED, the clinical study required screening of all patients presenting to the ED with complaints of head injury. Eligible patients were enrolled and tested using a robot-assisted test battery. Three weeks after the injury, patients were contacted to complete follow-up assessments. RESULTS: Adapting the existing technology to meet anticipated physical constraints of the ED was performed by engineering a mobile platform. Due to the large footprint of the device, it was frequently moved before ultimately being fully integrated into the ED. Over 14 months, 1423 patients were screened. Twenty-eight patients could not be enrolled because the device was unavailable due to operations limitations. Technical problems with the device resulted in failure to include 20 patients. A total of 66 mTBI patients were enrolled and 42 of them completed both robot-assisted testing and follow-up assessment. Successful completion of screening and enrollment demonstrated that the challenges associated with integration of investigational devices into the ED can be effectively addressed through a collaborative patient-oriented research model. CONCLUSION: Effective deployment and use of new robotic technology for research in an urban academic ED required significant planning, coordination, and collaboration with key personnel from multiple disciplines. Clinical Impact: A pilot clinical study on mTBI patients using the robotic device provided useful data without disrupting the ED workflow. Integration of this technology into the ED serves as an important step toward pursing active clinical research in an acute care setting.

Alveolar air volatile organic compound extractor for clinical breath sampling.

Alveolar air Volatile Organic Compound (VOC) extractor is a handheld breath-sampling device for clinical breath analysis. The device consists two main components: (1) An alveolar air separator, (2) A VOC extractor. The alveolar air separator splits exhaled air based on total exhaled air volume directing alveolar air towards the VOC extractor and dead space air to into an exhaust channel. The VOC extractor collects the VOCs from alveolar air into a modified Sold Phase Micro Extraction (SPME) filament. Feasibility of using the SPME filament to collect a quantifiable breath sample directly from exhaled breath is experimentally validated. Exhaled breath acetone is quantified using alveolar air VOC extractor and a GC/MS system.

An evaluation of exhaled flow measuring mouthpieces for breath sampling devices.

A study is conducted to determine the dimensions of an exhaled flow measuring mouthpiece for a breath-sampling device that requires breathing for an extended period of time. Fleisch, Pitot and Venturi type differential pressure based flow measuring mouthpieces of various dimensions are evaluated. Inner diameters (IDs) of the cylinder shaped Fleisch, Pitot and Venturi mouthpieces are varied from 5mm to 25mm. Based on the study, we conclude IDs ranging from 8.75mm to 12.5mm for Fleisch type, IDs ranging from 10mm to 12.5mm for Pitot type and ID of 10mm for Venturi type are the most suitable dimensions for a breath sampling device.

Feasibility of energy harvesting techniques for wearable medical devices.

Wearable devices are arguably one of the most rapidly growing technologies in the computing and health care industry. These systems provide improved means of monitoring health status of humans in real-time. In order to cope with continuous sensing and transmission of biological and health status data, it is desirable to move towards energy autonomous systems that can charge batteries using passive, ambient energy. This not only ensures uninterrupted data capturing, but could also eliminate the need to frequently remove, replace, and recharge batteries. To this end, energy harvesting is a promising area that can lead to extremely power-efficient portable medical devices. This paper presents an experimental prototype to study the feasibility of harvesting two energy sources, solar and thermoelectric energy, in the context of wearable devices. Preliminary results show that such devices can be powered by transducing ambient energy that constantly surrounds us.

A programmable point-of-care device for external CSF drainage and monitoring.

This paper presents a prototype of a programmable cerebrospinal fluid (CSF) external drainage system that can accurately measure the dispensed fluid volume. It is based on using a miniature spectrophotometer to collect color data to inform drain rate and pressure monitoring. The prototype was machined with 1 µm dimensional accuracy. The current device can reliably monitor the total accumulated fluid volume, the drain rate, the programmed pressure, and the pressure read from the sensor. Device requirements, fabrication processes, and preliminary results with an experimental set-up are also presented.

Quantitative assessment of post-concussion syndrome following mild traumatic brain injury using robotic technology.

Post-Concussion Syndrome (PCS) is a common sequelae of mild Traumatic Brain Injury (mTBI). Currently, there is no reliable test to determine which patients will develop PCS following an mTBI. As a result, clinicians are challenged to identify patients at high risk for subsequent PCS. Hence, there is a need to develop an objective test that can guide clinical risk stratification and predict the likelihood of PCS at the initial point of care in an Emergency Department (ED). This paper presents the results of robotic-assisted neurologic testing completed on mTBI patients in the ED and its ability to predict PCS at 3 weeks post-injury. Preliminary results show that abnormal proprioception, as measured using robotic testing is associated with higher risk of developing PCS following mTBI. In this pilot study, proprioceptive measures obtained through robotic testing had a 77% specificity (95CI: 46%-94%) and a 64% sensitivity (95CI: 41%-82%).

Development and evaluation of hardware for Point-of-Care assessment of upper-limb motor performance.

This paper presents prototypes of a hardware interface that is directed towards possible integration with a Point-of-Care Testing Environment for Neurological Assessment (POCTENA). While the complete system is intended to assist with diagnosis of mild Traumatic Brain Injury (TBI), the focus of this paper is to present designs of necessary hardware that can be used to assess upper-limb motor performance in a point-of-care setting. The hardware interface is expected to facilitate execution of several visuomotor tasks in an attempt to reliably quantify motor deficits. System usability results are shown to corroborate future directions of the POCTENA system.

Modular, bluetooth enabled, wireless electroencephalograph (EEG) platform.

A design for a modular, compact, and accurate wireless electroencephalograph (EEG) system is proposed. EEG is the only non-invasive measure for neuronal function of the brain. Using a number of digital signal processing (DSP) techniques, this neuronal function can be acquired and processed into meaningful representations of brain activity. The system described here utilizes Bluetooth to wirelessly transmit the digitized brain signal for an end application use. In this way, the system is portable, and modular in terms of the device to which it can interface. Brain Computer Interface (BCI) has become a popular extension of EEG systems in modern research. This design serves as a platform for applications using BCI capability.

Changes in behavior of evoked potentials in the brain as a possible indicator of fatigue in people.

Many professions place significant mental and/or physical strain on their workers. Some professionals (such as firefighters, soldiers, and pilots) have an inherent responsibility for the safety of others. Making sure that workers in these remain fit for duty is an important health/safety concern for the workers and those they serve. This paper explores the viability of using EEG as a non-invasive, cost efficient method for assessing fatigue, sleep deprivation, physical exertion and stress. Specifically, P300 evoked potentials are generated in response to certain stimuli. Variations in the response characteristics (magnitude, shape, and peak shift) are explored in relation to sleep deprivation, caffeine usage, and physical exertion. Preliminary data suggests that there are quantifiable changes to the P300 response that may be attributed to fatigue.

Point-of-Care device for quantification of zinc in serum.

With 42,000 cases reported annually in the United States and an approximate 10% mortality rate, [1] pediatric septic shock is a major health problem that is often difficult to treat effectively. Several studies have shown that children experiencing pediatric septic shock often have critically low levels of serum zinc (Zn), suggesting supplementation of Zn to be an effective therapeutic strategy. However, to protect the safety and well-being of the patient, it is extremely important to monitor blood serum concentration of Zn during supplementation in order to ensure that levels remain at or near the physiological norm and thus minimize the risk of heavy metal toxicity from over supplementation. Current methods for quantifying Zn in serum typically require sending serum samples to external laboratory facilities resulting in turnaround times ranging from hours to a few days. Therefore, timely monitoring of Zn levels in serum is often not possible in the clinical setting which ultimately limits the ability to use Zn supplementation as a therapeutic intervention. This paper reports on the development of a Point-of-Care device for rapid electrochemical measurement of Zn in serum. The device is centered on a three electrode sensor which uses Anodic stripping voltammetry (ASV) for sensing Zn levels. The Cu based sensor is read using a reader that has been developed using commercially available embedded system parts in combination with custom analog circuitry that is able to produce quantification results in approximately 6 minutes.

Development of a point-of-care medical device to measure head impact in contact sports.

This paper presents a prototype of a wireless, point-of-care medical device to measure head impacts in contact or collision sports. The device is currently capable of measuring linear acceleration, time, and the duration of impact. The location of the impact can also be recorded by scaling the prototype design to multiple devices. An experimental apparatus was built to simulate head impacts and to verify the data from the device. Preliminary results show that the biomechanical measures from the device are sufficiently accurate.

Design and usability of a medical computing system for diagnosis of mild traumatic brain injury.

In this paper, we present a prototype design of POCTENA (Point-Of-Care Testing Environment for Neurological Assessment), a medical computing system that will be used to assist with diagnosis of mild traumatic brain injury. The design includes an initial set of neurological tests that are built into the system. Component-based usability testing was conducted to examine the effectiveness of the user interface. Results from usability testing are then used to suggest possible system design revisions.

The Value of Clinical Needs Assessments for Point-of-Care Diagnostics.

Most entrepreneurial ventures fail long before the core technology can be brought to the marketplace because of disconnects in performance and usability measures such as accuracy, cost, complexity, assay stability, and time requirements between technology developers' specifications and needs of the end-users. By going through a clinical needs assessment (CNA) process, developers will gain vital information and a clear focus that will help minimize the risks associated with the development of new technologies available for use within the health care system. This article summarizes best practices of the principal investigators of the National Institute of Biomedical Imaging and Bioengineering point-of-care (POC) centers within the National Institute of Biomedical Imaging and Bioengineering POC Technologies Research Network. Clinical needs assessments are particularly important for product development areas that do not sufficiently benefit from traditional market research, such as grant-funded research and development, new product lines using cutting-edge technologies developed in start-up companies, and products developed through product development partnerships for low-resource settings. The objectives of this article were to (1) highlight the importance of CNAs for development of POC devices, (2) discuss methods applied by POC Technologies Research Network for assessing clinical needs, and (3) provide a road map for future CNAs.

Development of a Point-of-Care device to quantify serum zinc to aid the diagnosis and follow-up of pediatric septic shock.

In the Unites States Pediatric septic shock is a major health problem with about 42,000 cases per y ear and a mortality rate of about 10% [1]. Studies have indicated that children with pediatric septic shock have demonstrated critically low levels of serum z inc (Zn) and supplementation of Zn is being suggested as a therapeutic strategy. However, to protect patient safety, it is vital that Z n levels be monitored during supplementation to insure the Zn concentration levels remain at or near physiologic normal levels. Currently Atomic Absorption Spectroscopy (AAS) is used to quantify Zn levels in serum samples. Unfortunately, AAS frequently involves sending serum samples to external laboratory facilities which yields measurement turnaround time that range from hours to days. Thus, timely monitoring of Zn levels is critical to preventing over supplementation that could result in critical conditions such as heavy metal (Zn) toxicity. This paper reports on the development of a Point-of-Care device for rap id electrochemical measurement of Zn. The prototype device is able to accurately quantify Zn in serum with a turn-around time of about 30 minutes. The devices is based on a three electrode sensor which uses Anodic stripping voltammetry (ASV) for sensing Zn levels. The ASV electrode sensor is read using a reader that has be en developed using commercially available embedded system components and custom analog circuitry.

Improved quantification of CSF bilirubin in the presence of hemoglobin using least squares curve-fitting.

Subarachnoid hemorrhage (SAH) is a dangerous neurological event with a very short time window for early diagnosis. Clinical diagnoses performed in a lab seek to quantify bilirubin in cerebrospinal fluid (CSF) as a biomarker for SAHs; however laboratory assays suffer from lengthy protocols, interference from hemoglobin, and the availability of expertise. Substantial improvements in the determination of bilirubin concentration in the presence of hemoglobin in CSF are demonstrated in this work. Concentration estimates within 15% for bilirubin in the range of 0.2 to 1.6 mg /dl were determined for CSF samples containing fresh hemoglobin concentrations ranging from 0.05 to 0.25 g/dl. To demonstrate extensibility of the system with respect to more complete mock SAH samples, sample sets with one additional species of both hemoglobin and bilirubin, methemoglobin and alpha-bilirubin, respectively, were tested and yielded results within 25% of actual values, as measured by standard chemical assays of preparations prior to mixing.

Device for quantification of bilirubin in cerebral spinal fluid.

In North America, an estimated 30,000 patients annually experience an aneurysmal subarachnoid hemorrhage (SAH). In approximately five percent of these patients, the hemorrhage is not visible on computerized tomography scans due to the inability to image blood at time intervals greater than 12 h post symptom onset. For these patients (many of which have experienced a sentinel hemorrhage that is a precursor to a more significant rupture), a method is needed for accurately analyzing cerebral spinal fluid (CSF) for evidence of SAH. Further, it is necessary to differentiate blood associated with the SAH from blood associated with the spinal tap procedure. This letter presents a point-of-care device that is capable of performing such an analysis. The stand-alone prototype device uses commercially available embedded system components to implement a point-of-care device that is capable of collecting and analyzing optical absorbance spectra. A mathematical model for the hemorrhagic CSF sample is then developed by using a partial-least-squares-regression-based regression methodology that is able to differentiate between SAH and blood associated with the spinal tap. This differentiation is achieved by quantifying bilirubin (associated with the breakdown of old blood) in the CSF. Initial testing on the prototype device suggests that the device is able to quantify bilirubin in the presence of hemoglobin over concentrations ranges that are clinically relevant to the patient population of interest.