Imperial College London

ProfessorMartynBoutelle

Faculty of EngineeringDepartment of Bioengineering

Consul for the Faculty of Engineering and Business School
 
 
 
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Contact

 

+44 (0)20 7594 5138m.boutelle Website CV

 
 
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Location

 

B208Bessemer BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

189 results found

Gifford EK, Robbins EM, Jaquins-Gerstl A, Rerick MT, Nwachuku EL, Weber SG, Boutelle MG, Okonkwo DO, Puccio AM, Michael ACet al., 2021, Validation of Dexamethasone-Enhanced Continuous-Online Microdialysis for Monitoring Glucose for 10 Days after Brain Injury., ACS Chem Neurosci, Vol: 12, Pages: 3588-3597

Traumatic brain injury (TBI) induces a pathophysiologic state that can be worsened by secondary injury. Monitoring brain metabolism with intracranial microdialysis can provide clinical insights to limit secondary injury in the days following TBI. Recent enhancements to microdialysis include the implementation of continuously operating electrochemical biosensors for monitoring the dialysate sample stream in real time and dexamethasone retrodialysis to mitigate the tissue response to probe insertion. Dexamethasone-enhanced continuous-online microdialysis (Dex-enhanced coMD) records long-lasting declines of glucose after controlled cortical impact in rats and TBI in patients. The present study employed retrodialysis and fluorescence microscopy to investigate the mechanism responsible for the decline of dialysate glucose after injury of the rat cortex. Findings confirm the long-term functionality of Dex-enhanced coMD for monitoring brain glucose after injury, demonstrate that intracranial glucose microdialysis is coupled to glucose utilization in the tissues surrounding the probes, and validate the conclusion that aberrant glucose utilization drives the postinjury glucose decline.

Journal article

Tyrrell JE, Petkos K, Drakakis EM, Boutelle MG, Campbell AJet al., 2021, Organic electrochemical transistor common‐source amplifier for electrophysiological measurements, Advanced Functional Materials, Vol: 31, Pages: 1-13, ISSN: 1616-301X

The portability of physiological monitoring has necessitated the biocompatibility of components used in circuitry local to biological environments. A key component in processing circuitry is the linear amplifier. Amplifier circuit topologies utilize transistors, and recent advances in bioelectronics have focused on organic electrochemical transistors (OECTs). OECTs have shown the capability to transduce physiological signals at high signal-to-noise ratios. In this study high-performance interdigitated electrode OECTs are implemented in a common source linear amplifier topology. Under the constraints of OECT operation, stable circuit component parameters are found, and OECT geometries are varied to determine the best amplifier performance. An equation is formulated which approximates transistor behavior in the linear, nonlinear, and saturation regimes. This equation is used to simulate the amplifier response of the circuits with the best performing OECT geometries. The amplifier figures of merit, including distortion characterizations, are then calculated using physical and simulation measurements. Based on the figures of merit, prerecorded electrophysiological signals from spreading depolarizations, electrocorticography, and electromyography fasciculations are inputted into an OECT linear amplifier. Using frequency filtering, the primary features of events in the bioelectric signals are resolved and amplified, demonstrating the capability of OECT amplifiers in bioelectronics.

Journal article

Weddell T, Bashford J, Wickham A, Iniesta R, Chen M, Zhou P, Drakakis E, Boutelle M, Mills K, Shaw Cet al., 2021, First-recruited motor units adopt a faster phenotype in amyotrophic lateral sclerosis, JOURNAL OF PHYSIOLOGY-LONDON, Vol: 599, Pages: 4117-4130, ISSN: 0022-3751

Journal article

Jewell S, Hobson S, Brewer G, Rogers M, Hartings JA, Foreman B, Lavrador J-P, Sole M, Pahl C, Boutelle MG, Strong AJet al., 2021, Development and evaluation of a method for automated detection of spreading depolarizations in the injured human brain, Neurocritical Care, ISSN: 1541-6933

BACKGROUND: Spreading depolarizations (SDs) occur in some 60% of patients receiving intensive care following severe traumatic brain injury and often occur at a higher incidence following serious subarachnoid hemorrhage and malignant hemisphere stroke (MHS); they are independently associated with worse clinical outcome. Detection of SDs to guide clinical management, as is now being advocated, currently requires continuous and skilled monitoring of the electrocorticogram (ECoG), frequently extending over many days. METHODS: We developed and evaluated in two clinical intensive care units (ICU) a software routine capable of detecting SDs both in real time at the bedside and retrospectively and also capable of displaying patterns of their occurrence with time. We tested this prototype software in 91 data files, each of approximately 24 h, from 18 patients, and the results were compared with those of manual assessment ("ground truth") by an experienced assessor blind to the software outputs. RESULTS: The software successfully detected SDs in real time at the bedside, including in patients with clusters of SDs. Counts of SDs by software (dependent variable) were compared with ground truth by the investigator (independent) using linear regression. The slope of the regression was 0.7855 (95% confidence interval 0.7149-0.8561); a slope value of 1.0 lies outside the 95% confidence interval of the slope, representing significant undersensitivity of 79%. R2 was 0.8415. CONCLUSIONS: Despite significant undersensitivity, there was no additional loss of sensitivity at high SD counts, thus ensuring that dense clusters of depolarizations of particular pathogenic potential can be detected by software and depicted to clinicians in real time and also be archived.

Journal article

Booth MA, Gowers SAN, Hersey M, Samper IC, Park S, Anikeeva P, Hashemi P, Stevens MM, Boutelle MGet al., 2021, Fiber-based electrochemical biosensors for monitoring pH and transient neurometabolic lactate., Analytical Chemistry, Vol: 93, Pages: 6646-6655, ISSN: 0003-2700

Developing tools that are able to monitor transient neurochemical dynamics is important to decipher brain chemistry and function. Multifunctional polymer-based fibers have been recently applied to monitor and modulate neural activity. Here, we explore the potential of polymer fibers comprising six graphite-doped electrodes and two microfluidic channels within a flexible polycarbonate body as a platform for sensing pH and neurometabolic lactate. Electrodes were made into potentiometric sensors (responsive to pH) or amperometric sensors (lactate biosensors). The growth of an iridium oxide layer made the fiber electrodes responsive to pH in a physiologically relevant range. Lactate biosensors were fabricated via platinum black growth on the fiber electrode, followed by an enzyme layer, making them responsive to lactate concentration. Lactate fiber biosensors detected transient neurometabolic lactate changes in an in vivo mouse model. Lactate concentration changes were associated with spreading depolarizations, known to be detrimental to the injured brain. Induced waves were identified by a signature lactate concentration change profile and measured as having a speed of ∼2.7 mm/min (n = 4 waves). Our work highlights the potential applications of fiber-based biosensors for direct monitoring of brain metabolites in the context of injury.

Journal article

Olsen MH, Olesen ND, Karlsson M, Holmlov T, Sondergaard L, Boutelle M, Mathiesen T, Moller Ket al., 2021, Randomized blinded trial of automated REBOA during CPR in a porcine model of cardiac arrest, RESUSCITATION, Vol: 160, Pages: 39-48, ISSN: 0300-9572

Journal article

Tyrrell J, Boutelle M, Campbell A, 2021, Measurement of electrophysiological signals in vitro using high-performance organic electrochemical transistors, Advanced Functional Materials, Vol: 31, Pages: 1-12, ISSN: 1616-301X

Biological environments use ions in charge transport for information transmission. The properties of mixed electronic and ionic conductivity in organic materials make them ideal candidates to transduce physiological information into electronically processable signals. A device proven to be highly successful in measuring such information is the organic electrochemical transistor (OECT). Previous electrophysiological measurements performed using OECTs show superior signal‐to‐noise ratios than electrodes at low frequencies. Subsequent development has significantly improved critical performance parameters such as transconductance and response time. Here, interdigitated‐electrode OECTs are fabricated on flexible substrates, with one such state‐of‐the‐art device achieving a peak transconductance of 139 mS with a 138 µs response time. The devices are implemented into an array with interconnects suitable for micro‐electrocorticographic application and eight architecture variations are compared. The two best‐performing arrays are subject to the full electrophysiological spectrum using prerecorded signals. With frequency filtering, kHz‐scale frequencies with 10 µV‐scale voltages are resolved. This is supported by a novel quantification of the noise, which compares the gate voltage input and drain current output. These results demonstrate that high‐performance OECTs can resolve the full electrophysiological spectrum and suggest that superior signal‐to‐noise ratios could be achieved in high frequency measurements of multiunit activity.

Journal article

Wannop K, Bashford J, Wickham A, Iniesta R, Drakakis E, Boutelle M, Mills K, Shaw Cet al., 2020, Fasciculation analysis reveals a novel parameter that correlates with predicted survival in amyotrophic lateral sclerosis, MUSCLE & NERVE, Vol: 63, Pages: 392-396, ISSN: 0148-639X

Journal article

Tageldeen MK, Gowers SAN, Leong CL, Boutelle MG, Drakakis EMet al., 2020, Traumatic brain injury neuroelectrochemical monitoring: behind-the-ear micro-instrument and cloud application, Journal of NeuroEngineering and Rehabilitation, Vol: 17, ISSN: 1743-0003

BACKGROUND: Traumatic Brain Injury (TBI) is a leading cause of fatality and disability worldwide, partly due to the occurrence of secondary injury and late interventions. Correct diagnosis and timely monitoring ensure effective medical intervention aimed at improving clinical outcome. However, due to the limitations in size and cost of current ambulatory bioinstruments, they cannot be used to monitor patients who may still be at risk of secondary injury outside the ICU. METHODS: We propose a complete system consisting of a wearable wireless bioinstrument and a cloud-based application for real-time TBI monitoring. The bioinstrument can simultaneously record up to ten channels including both ECoG biopotential and neurochemicals (e.g. potassium, glucose and lactate), and supports various electrochemical methods including potentiometry, amperometry and cyclic voltammetry. All channels support variable gain programming to automatically tune the input dynamic range and address biosensors' falling sensitivity. The instrument is flexible and can be folded to occupy a small space behind the ear. A Bluetooth Low-Energy (BLE) receiver is used to wirelessly connect the instrument to a cloud application where the recorded data is stored, processed and visualised in real-time. Bench testing has been used to validate device performance. RESULTS: The instrument successfully monitored spreading depolarisations (SDs) - reproduced using a signal generator - with an SNR of 29.07 dB and NF of 0.26 dB. The potentiostat generates a wide voltage range from -1.65V to +1.65V with a resolution of 0.8mV and the sensitivity of the amperometric AFE was verified by recording 5 pA currents. Different potassium, glucose and lactate concentrations prepared in lab were accurately measured and their respective working curves were constructed. Finally,the instrument achieved a maximum sampling rate of 1.25 ksps/channel with a throughput of 105 kbps. All measurements were successfully received at the cl

Journal article

Masson J-F, Hashemi P, Boutelle MG, 2020, Analytical science in neurochemistry, ANALYST, Vol: 145, Pages: 3774-3775, ISSN: 0003-2654

Journal article

Bashford J, Masood U, Wickham A, Iniesta R, Drakakis E, Boutelle M, Mills K, Shaw Cet al., 2020, Fasciculations demonstrate daytime consistency in amyotrophic lateral sclerosis, Muscle and Nerve, Vol: 61, Pages: 745-750, ISSN: 0148-639X

IntroductionFasciculations represent early neuronal hyperexcitability in amyotrophic lateral sclerosis (ALS). To aid calibration as a disease biomarker, we set out to characterize the daytime variability of fasciculation firing.MethodsFasciculation awareness scores were compiled from 19 ALS patients. In addition, 10 ALS patients prospectively underwent high‐density surface electromyographic (HDSEMG) recordings from biceps and gastrocnemius at three time‐points during a single day.ResultsDaytime fasciculation awareness scores were low (mean: 0.28 muscle groups), demonstrating significant variability (coefficient of variation: 303%). Biceps HDSEMG recordings were highly consistent for fasciculation potential frequency (intraclass correlation coefficient [ICC] = 95%, n = 19) and the interquartile range of fasciculation potential amplitude (ICC = 95%, n = 19). These parameters exhibited robustness to observed fluctuations in data quality parameters. Gastrocnemius demonstrated more modest levels of consistency overall (44% to 62%, n = 20).DiscussionThere was remarkable daytime consistency of fasciculation firing in the biceps of ALS patients, despite sparse and intermittent awareness among patients’ accounts.

Journal article

Moser N, Leong CL, Hu Y, Cicatiello C, Gowers SAN, Boutelle MG, Georgiou Pet al., 2020, CMOS potentiometric FET array platform using sensor learning for multi-ion imaging., Analytical Chemistry, Vol: 92, Pages: 5276-5285, ISSN: 0003-2700

This work describes an array of 1024 Ion-Sensitive Field-Effect Transistors (ISFETs) using sensor learning techniques to perform multi-ion imaging for concurrent detection of potassium, sodium, calcium and hydrogen. Analyte specific ionophore membranes are deposited on the surface of the ISFET array chip, yielding pixels with quasi-Nernstian sensitivity to K+, Na+ or Ca2+. Uncoated pixels display pH sensitivity from the standard Si3N4 passivation layer. The platform is then trained by inducing a change in single ion concentration and measuring the responses of all pixels. Sensor learning relies on k-means clustering and DBSCAN to yield membrane mapping and sensitivity of each pixel to target electrolytes. We demonstrate multi-ion imaging with an average error of 3.7 % (K+), 4.6 % (Na+), and 1.8 % (pH) for each ion respectively, while Ca2+ incurs a larger error 24.2 % and hence is included to demonstrate versatility. We validate the platform with a brain dialysate fluid sample and demonstrate reading by comparing with a gold-standard spectrometry technique.

Journal article

Gowers S, Samper I, Murray D-S, Smaith G, Jeyaprakash S, Rogers M, Karlsson M, Olsen M, Moller K, Boutelle Met al., 2020, Real-time neurochemical measurement of dynamic metabolic events during cardiac arrest and resuscitation in a porcine model, The Analyst, Vol: 145, Pages: 1894-1902, ISSN: 0003-2654

This work describes a fully-integrated portable microfluidic analysis system for real-time monitoring of dynamic changes in glucose and lactate occurring in the brain as a result of cardiac arrest and resuscitation. Brain metabolites are sampled using FDA-approved microdialysis probes and coupled to a high temporal resolution 3D printed microfluidic chip housing glucose and lactate biosensors. The microfluidic biosensors are integrated with a wireless 2 channel potentiostat forming a compact analysis system that is ideal for use in a crowded operating theatre. Data are transmitted to a custom-written app running on a tablet for real-time visualisation of metabolic trends. In a proof of-concept porcine model of cardiac arrest, the integrated analysis system proved reliable in a challenging environment resembling a clinical setting; noise levels were found to be comparable with those seen in the lab and were not affected by major clinical interventions such as defibrillation of the heart. Using this system, we were able, for the first time, to measure changes in brain glucose and lactate levels caused by cardiac arrest and resuscitation; the system was sensitive to clinical interventions such as infusion of adrenaline. Trends suggest that cardiopulmonary resuscitation alone does not meet the high energy demands of the brain as metabolite levels only return to their values preceding cardiac arrest upon return of spontaneous circulation.

Journal article

Hurst T, Pahl C, Tolias C, Jewell S, Boutelle M, Strong Aet al., 2020, Response to Stevens et al. (DOI: 10.1089/neu.2018.6175) Glucose Dynamics of Cortical Spreading Depolarization in Acute Brain Injury: A Systematic Review, JOURNAL OF NEUROTRAUMA, Vol: 37, Pages: 1266-1267, ISSN: 0897-7151

Journal article

Bashford JA, Wickham A, Iniesta R, Drakakis EM, Boutelle MG, Mills KR, Shaw CEet al., 2020, Accurate interpretation of fasciculation frequency in amyotrophic lateral sclerosis hinges on both muscle type and stage of disease, BRAIN COMMUNICATIONS, Vol: 2

Journal article

Bashford JA, Wickham A, Iniesta R, Drakakis EM, Boutelle MG, Mills KR, Shaw CEet al., 2020, The rise and fall of fasciculations in amyotrophic lateral sclerosis, BRAIN COMMUNICATIONS, Vol: 2

Journal article

Bashford J, Wickham A, Iniesta R, Drakakis E, Boutelle M, Mills K, Shaw CEet al., 2020, Preprocessing surface EMG data removes voluntary muscle activity and enhances SPiQE fasciculation analysis, Clinical Neurophysiology, Vol: 131, Pages: 265-273, ISSN: 1388-2457

ObjectivesFasciculations are a clinical hallmark of amyotrophic lateral sclerosis (ALS). The Surface Potential Quantification Engine (SPiQE) is a novel analytical tool to identify fasciculation potentials from high-density surface electromyography (HDSEMG). This method was accurate on relaxed recordings amidst fluctuating noise levels. To avoid time-consuming manual exclusion of voluntary muscle activity, we developed a method capable of rapidly excluding voluntary potentials and integrating with the established SPiQE pipeline.MethodsSix ALS patients, one patient with benign fasciculation syndrome and one patient with multifocal motor neuropathy underwent monthly thirty-minute HDSEMG from biceps and gastrocnemius. In MATLAB, we developed and compared the performance of four Active Voluntary IDentification (AVID) strategies, producing a decision aid for optimal selection.ResultsAssessment of 601 one-minute recordings permitted the development of sensitive, specific and screening strategies to exclude voluntary potentials. Exclusion times (0.2–13.1 minutes), processing times (10.7–49.5 seconds) and fasciculation frequencies (27.4–71.1 per minute) for 165 thirty-minute recordings were compared. The overall median fasciculation frequency was 40.5 per minute (10.6–79.4 IQR).ConclusionWe hereby introduce AVID as a flexible, targeted approach to exclude voluntary muscle activity from HDSEMG recordings.SignificanceLongitudinal quantification of fasciculations in ALS could provide unique insight into motor neuron health.

Journal article

Bashford J, Wickham A, Iniesta R, Drakakis E, Boutelle M, Mills K, Shaw Cet al., 2020, SPiQE: An automated analytical tool for detecting and characterising fasciculations in amyotrophic lateral sclerosis (vol 130, pg 1083, 2019), Clinical Neurophysiology, Vol: 131, Pages: 350-350, ISSN: 1388-2457

[Correction to https://doi.org/10.1016/j.clinph.2019.03.032]

Journal article

Tamborska A, Bashford J, Wickham A, Iniesta R, Masood U, Cabassi C, Planinc D, Hodson-Tole E, Drakakis E, Boutelle M, Mills K, Shaw Cet al., 2020, Non-invasive measurement of fasciculation frequency demonstrates diagnostic accuracy in amyotrophic lateral sclerosis, BRAIN COMMUNICATIONS, Vol: 2

Journal article

Hamaoui K, Gowers S, Sandhu B, Cook T, Boutelle M, Casanova-Rituerto D, Papalois Vet al., 2020, Cold ischaemia time: is too long really too bad? studies using a porcine kidney ex-vivo reperfusion model, International Journal of Surgery Open, Vol: 23, Pages: 39-47, ISSN: 2405-8572

IntroductionPost-ischaemic hypothermic machine perfusion (HMP) may be beneficial in recovery of marginal kidney grafts. The full capacity of conventional HMP (with passive oxygenation) to recondition an organ has not been realised. We investigated whether HMP can ameliorate ischemic damage caused by extremely prolonged static cold storage (SCS).MethodsPorcine kidneys underwent 4-h (SCS4,n = 4) or 52-h (SCS52,n = 4) SCS, followed by 10 h of HMP and were then subjected to 2 h of isolated normothermic reperfusion (NRP).ResultsThere was a post-SCS graft weight loss in SCS52 vs SCS4 kidneys. SCS52 kidneys showed viable perfusion dynamics during HMP, with significantly shorter times to reach viable parameters vs SCS4 kidneys (p < 0.027). During NRP SCS52 kidneys demonstrated similar trends in perfusion dynamics, renal function, oxygen consumptions, lactate production, and tubular injury to SCS4 kidneys.ConclusionGraft weight loss after SCS, reducing resistance to perfusion, may facilitate better HMP dynamics and graft reconditioning. Clinicians utilising HMP should be aware of this phenomenon when using HMP in kidneys exposed to extreme periods of SCS. HMP after an extended period of SCS can resuscitate kidneys to a level equitable of viability as those after a short period of SCS. Utilising passive oxygenation however may be limiting such recovery and interventions utilising active oxygenation may provide benefit in such organs.

Journal article

Leong CL, Coleman S, Nightingale AM, Sammer-ul H, Voegeli D, Boutelle MG, Niu Xet al., 2019, Lactate monitoring in droplet microfluidics: a cautionary tale in assay miniaturisation, ANALYTICAL METHODS, Vol: 11, Pages: 6119-6123, ISSN: 1759-9660

Journal article

Samper IC, Gowers SAN, Booth MA, Wang C, Watts T, Phairatana T, Vallant N, Sandhu B, Papalois V, Boutelle MGet al., 2019, Portable Microfluidic Biosensing System for Real-Time Analysis of Microdialysate in Transplant Kidneys, ANALYTICAL CHEMISTRY, Vol: 91, Pages: 14631-14638, ISSN: 0003-2700

Journal article

Charalampidis S, Gowers S, Rogers M, Gopal J, Housby N, Learney R, Boutelle M, Papalois Vet al., 2019, CONTINUOUS ONLINE MICRODIALYSIS AS A NOVEL TOOL FOR CONTINUOUS CREATININE MEASUREMENT AND PARENCHYMA ASSESSMENT DURING NORMOTHERMIC MACHINE PERFUSION IN A TRANSLATIONAL EX VIVO PORCINE KIDNEY MODEL, Publisher: WILEY, Pages: 425-425, ISSN: 0934-0874

Conference paper

Bashford J, Wickham A, Iniesta R, Drakakis E, Boutelle M, Mills K, Shaw Cet al., 2019, THE SURFACE POTENTIAL QUANTIFICATION ENGINE INTEGRATES ACTIVE VOLUNTARY IDENTIFICATION TO ENHANCE FASCICULATION ANALYSIS IN AMYOTROPHIC LATERAL SCLEROSIS, Annual Meeting of the American-Association-of-Neuromuscular-and-Electrodiagnostic-Medicine (AANEM), Publisher: WILEY, Pages: S3-S3, ISSN: 0148-639X

Conference paper

Robbins EM, Jaquins-Gerstl A, Fine DF, Leong CL, Dixon CE, Wagner AK, Boutelle MG, Michael ACet al., 2019, Extended (10-Day) Real-Time Monitoring by Dexamethasone-Enhanced Microdialysis in the Injured Rat Cortex., ACS Chem Neurosci, Vol: 10, Pages: 3521-3531

Intracerebral microdialysis has proven useful for chemical monitoring in patients following traumatic brain injury. Recent studies in animals, however, have documented that insertion of microdialysis probes into brain tissues initiates a foreign-body response. Within a few days after probe insertion, the foreign body response impedes the use of microdialysis to monitor the K+ and glucose transients associated with spreading depolarization, a potential mechanism for secondary brain injury. Herein, we show that perfusing microdialysis probes with dexamethasone, a potent anti-inflammatory glucocorticoid, suppresses the foreign body response and facilitates the monitoring of spontaneous spreading depolarizations for at least 10 days following controlled cortical injury in the rat. In addition to spreading depolarizations, results of this study suggest that a progressive, apparently permanent, decline in pericontusional interstitial glucose may be an additional sequela of brain injury. This study establishes extended dexamethasone-enhanced microdialysis in the injured rodent cortex as a new paradigm for investigating trauma-induced metabolic crisis.

Journal article

Gowers S, Rogers M, Booth M, Leong C, Samper I, Phairatana T, Jewell S, Pahl C, Strong A, Boutelle Met al., 2019, Clinical translation of microfluidic sensor devices: Focus on calibration and analytical robustness, Lab on a Chip, Vol: 19, Pages: 2537-2548, ISSN: 1473-0189

We present approaches to facilitate the use of microfluidics outside of the laboratory, in our case within a clinical setting and monitoring from human subjects, where the complexity of microfluidic devices requires high skill and expertise and would otherwise limit translation. Microfluidic devices show great potential for converting complex laboratory protocols into on-chip processes. We demonstrate a flexible microfluidic platform can be coupled to microfluidic biosensors and used in conjunction with clinical microdialysis. The versatility is demonstrated through a series of examples of increasing complexity including analytical processes relevant to a clinical environment such as automatic calibration, standard addition, and more general processes including system optimisation, reagent addition and homogenous enzyme reactions. The precision and control offered by this set-up enables the use of microfluidics by non-experts in clinical settings, increasing uptake and usage in real-world scenarios. We demonstrate how this type of system is helpful in guiding physicians in real-time clinical decision-making.

Journal article

Shuttleworth CW, Andrew RD, Akbari Y, Ayata C, Balu R, Brennan KC, Boutelle M, Carlson AP, Dreier JP, Fabricius M, Farkas E, Foreman B, Helbok R, Henninger N, Jewell SL, Jones SC, Kirov SA, Lindquist BE, Maciel CB, Okonkwo D, Reinhart KM, Robertson RM, Rosenthal ES, Watanabe T, Hartings JAet al., 2019, Which Spreading Depolarizations Are Deleterious To Brain Tissue?, Neurocrit Care

Spreading depolarizations (SDs) are profound disruptions of cellular homeostasis that slowly propagate through gray matter and present an extraordinary metabolic challenge to brain tissue. Recent work has shown that SDs occur commonly in human patients in the neurointensive care setting and have established a compelling case for their importance in the pathophysiology of acute brain injury. The International Conference on Spreading Depolarizations (iCSD) held in Boca Raton, Florida, in September of 2018 included a discussion session focused on the question of "Which SDs are deleterious to brain tissue?" iCSD is attended by investigators studying various animal species including invertebrates, in vivo and in vitro preparations, diseases of acute brain injury and migraine, computational modeling, and clinical brain injury, among other topics. The discussion included general agreement on many key issues, but also revealed divergent views on some topics that are relevant to the design of clinical interventions targeting SDs. A draft summary of viewpoints offered was then written by a multidisciplinary writing group of iCSD members, based on a transcript of the session. Feedback of all discussants was then formally collated, reviewed and incorporated into the final document. It is hoped that this report will stimulate collection of data that are needed to develop a more nuanced understanding of SD in different pathophysiological states, as the field continues to move toward effective clinical interventions.

Journal article

Helbok R, Hartings JA, Schiefecker A, Balança B, Jewel S, Foreman B, Ercole A, Balu R, Ayata C, Ngwenya L, Rosenthal E, Boutelle MG, Farkas E, Dreier JP, Fabricius M, Shuttleworth CW, Carlson Aet al., 2019, What should a clinician do when spreading depolarizations are observed in a patient?, Neurocritical Care, Vol: 32, Pages: 306-310, ISSN: 1541-6933

The International Conference on Spreading Depolarizations (iCSD) held in Boca Raton, Florida, in the September of 2018 devoted a section to address the question, "What should a clinician do when spreading depolarizations are observed in a patient?" Discussants represented a wide range of expertise, including neurologists, neurointensivists, neuroradiologists, neurosurgeons, and pre-clinical neuroscientists, to provide both clinical and basic pathophysiology perspectives. A draft summary of viewpoints offered was then written by a multidisciplinary writing group of iCSD members, based on a transcript of the session. Feedback of all discussants was formally collated, reviewed, and incorporated into the final document which was subsequently approved by all authors.

Journal article

Kontojannis V, Hostettler I, Brogan RJ, Raza M, Harper-Payne A, Kareem H, Boutelle M, Wilson Met al., 2019, Detection of intracranial hematomas in the emergency department using near infrared spectroscopy., Brain Inj, Vol: 33, Pages: 875-883

Hypothesis: Traumatic brain injury (TBI) is one of the most important causes of morbidity and mortality in our society. The development of near infrared technology for the detection of intracranial hematomas may assist earlier diagnosis of TBI. This in turn may enable earlier targeted treatments minimizing the harm and subsequent social and economic effects of TBI. Methods: A handheld, noninvasive Near Infrared Spectroscopy device, Infrascanner 2000, (Infrascan Inc., Philadelphia, PA, USA) was used in a major trauma center to screen for traumatic intracranial hematomas. The Infrascanner was used successfully in 205 patients on their arrival in the emergency department prior to CT head. Results: In the whole cohort, sensitivity was 75%, specificity was 50.43%, with negative predictive value 72.84%, and positive predictive value 53.23%. In 45 patients, where the volume of blood was >3.5mL, the sensitivity was 89.36%, specificity 48.73% with negative predictive value 93.9% and positive predictive value 34.15%. Conclusions: The Infrascanner has a relatively high specificity and negative predictive value; therefore, it could in association with the Neurological examination, help in the triage of the trauma patient with potential brain injury. Further investigation is necessary to determine the use of Infrascanner 2000 as a diagnostic method in TBI.

Journal article

Bashford J, Wickham A, Iniesta R, Drakakis E, Boutelle M, Mills K, Shaw Cet al., 2019, SPiQE: An automated analytical tool for detecting and characterising fasciculations in amyotrophic lateral sclerosis, Clinical Neurophysiology, Vol: 130, Pages: 1083-1090, ISSN: 1388-2457

OBJECTIVES: Fasciculations are a clinical hallmark of amyotrophic lateral sclerosis (ALS). Compared to concentric needle EMG, high-density surface EMG (HDSEMG) is non-invasive and records fasciculation potentials (FPs) from greater muscle volumes over longer durations. To detect and characterise FPs from vast data sets generated by serial HDSEMG, we developed an automated analytical tool. METHODS: Six ALS patients and two control patients (one with benign fasciculation syndrome and one with multifocal motor neuropathy) underwent 30-minute HDSEMG from biceps and gastrocnemius monthly. In MATLAB we developed a novel, innovative method to identify FPs amidst fluctuating noise levels. One hundred repeats of 5-fold cross validation estimated the model's predictive ability. RESULTS: By applying this method, we identified 5,318 FPs from 80 minutes of recordings with a sensitivity of 83.6% (+/- 0.2 SEM), specificity of 91.6% (+/- 0.1 SEM) and classification accuracy of 87.9% (+/- 0.1 SEM). An amplitude exclusion threshold (100 μV) removed excessively noisy data without compromising sensitivity. The resulting automated FP counts were not significantly different to the manual counts (p = 0.394). CONCLUSION: We have devised and internally validated an automated method to accurately identify FPs from HDSEMG, a technique we have named Surface Potential Quantification Engine (SPiQE). SIGNIFICANCE: Longitudinal quantification of fasciculations in ALS could provide unique insight into motor neuron health.

Journal article

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