In-situ AEP amplification and wireless recording of Auditory Evoked Potentials and Otoacoustic Emissions

1. In-situ AEP amplification and wireless recording of Auditory Evoked Potentials and Otoacoustic Emissions Yuri Sokolov, PhD Vivosonic Inc., Toronto, ON Early Hearing Detection and Intervention ConferenceAtlanta,March 3, 2005

2. Audiology clinicians experience significant frustrations with ABR and ASSR Auditory Brainstem Response (ABR) and Auditory Steady State Response (ASSR) are quite difficult to administer for many clinicians, particularly in post-screening assessment environments: • Noise is FRUSTRATION # 1 reported by 84 % of U.S. clinics • Noise leads to unclear results and long test times – up to 90-120 min, typical 45-60 min per test • Long test time results in low patient throughput • Requirement of ≤ 5 kOhm impedance is challenging to achieve, often by abrading the skin until bleeding • Abrading the skin increases the risk of infection(Ferree et al., 2001. Scalp electrode impedance, infection risk, and EEG data quality. Clin. Neurophysiol., 112, p. 536-544) • The above results in higher risks and operating costs Source: Tannenbaum, S: US infant post-screening market survey (The Hearing Review, Jan 2005).

3. ABR and ASSR have very low amplitudes relatively to noise, but largely coincide with noise frequency AEP signal recording, analysis, and detection is simply “about” three things: • Signal, • Noise, and • Signal-to-Noise Ratio (SNR) The three major sources of noise in AEP are: • Physiological • Electric field, RF, and power-line • Magnetic field S SNR N The same signal can or cannot be detected depending on noise and SNR

4. ABR has diagnostic, screening, andthreshold-finding applications Auditory Brainstem Response (ABR) is a transient response, provides valuable information on hearing thresholds and useful for differential diagnostics: • Objective • Non-invasive • Known generators (on the opposite from ASSR) • Well researched over several recent decades • Responses are looked for in the time domain in the form of characteristic waves • Recommended by many established NHS protocols • Amplitude: 0.1-1 μV (millionth of V) • Frequency range: 50-3,000 Hz Source: Multiple publications by J. Hall III, M. Hyde, C. Berlin, L. Hood, and others.

5. Click-ABR is used mostly for screening and differential diagnostics V III I Diagnostic application • Response is generated by Acoustic Nerve and Brainstem • Has characteristic wave structure • 70-80 dB nHL click typical • Looking for Waves I, III, V, and I-III, III-V, I-V intervals • Diagnostics of Acoustic Neuroma and Auditory Neuropathy • Stacked ABR® may detect smaller Acoustic Neuroma Screening application • 30-50 dB nHL 100 μs click stimulus • Looking for Wave V • Typically automated detection (e.g. AABR®) 0 10 ms I-III III-V I-V V 0 10 ms AABR® is a registered trademark of Natus Medical Inc. Stacked ABR® is a trademark of Bio-logic Systems Corp.

6. Tone-burst ABR is used mostly for finding thresholds • Established and recommended protocol • Tone bursts instead of click stimuli: typically 500 (difficult to record), 1000, 2000, 4000 Hz • Frequency-specific • Levels vary to find the threshold • Looking for Wave V threshold • Technically similar to screening click-ABR, but not automated • Detect thresholds up to 80 dB HL V 0 10 ms

7. ASSR is a promising tool for finding hearing thresholds Auditory Steady State Response (ASSR) has been proven to provide valuable information on hearing thresholds, particularly in infants • Objective • Non-invasive • Frequency-specific, as tone-burst-ABR • Not site-specific (generators are unknown) • Typically faster than tone-burst ABR • Accurate, particularly at higher HL, above 40 dB HL • Effective at severe and profound hearing loss, up to 110 dB HL, while tone-burst ABR is limited to 80 dB HL Source: Multiple publications by T. Picton, S. John, D. Stapells, and others.

8. ASSR is a frequency-specific Evoked Potential Auditory Steady State Response (ASSR) is a tone-like response present as long as stimulus is presented. • Elicited by amplitude (AM) or Frequency (FM) or combined AM+FM modulation of carrier frequencies. • Audiometric carrier frequencies: 500, 1000, 2000, 4000 Hz • Modulation • 40 Hz – sensitive to sleep • 80-110 Hz – insensitive to sleep • Responses are looked for in the frequency domain – at modulation frequencies, not carrier frequencies • Thresholds – for carrier frequencies Multiple-frequency ASSR responses • Amplitudes: 10-50 nV (billionth of V) • Frequencies – AM and/or FM 82 84 86 88 92 96 Hz Source: Multiple publications by T. Picton, S. John, D. Stapells, and others.

9. Noises are introduced by multiple sourcesin most clinical environments Physiological • EEG – increases in sleep • ECG – does not decrease in sleep • EOG, EMG – decrease in sleep Electric and magnetic • Power line noise: 50 or 60 Hz and their harmonics • Electric field noise • Magnetic field noise • Radio-frequency (RF) interferences

10. Multiple sources introduce physiological noises in AEP recording Source: Cutmore, James (1999). Identifying and reducing noise in physiological recordings. Int. J. Physiol., V. 32, No. 2, pp. 129-150.

11. ECG noises may be stronger in infants than in adults The heart is positioned more centrally – aligned with the sagittal plain The heart is much larger relatively to the body The heart is closer to the head The heart-beat rate is twice higher than in adults Temporary post-natal heart conditions may increase ECG noise frequency - up to 100 Hz

12. Noise EP Amp 1 BPF Amp 2 Filtering after the first stage of amplification introduces distortion in conventional AEP amplifiers Saturation Distorted signal Distorted signal High gain in the 1st stage results in saturation by the unfiltered, often EEG noise, i.e. reaching the maximum voltage of the 1st stage’s dynamic range. Saturation distorts the signal: The 1st stage output contains periods of the maximum voltage, and these periods become interruptions in EP signal after band-pass filtering (BPF). Low gain reduces EP amplitude and signal-to-noise ratio (SNR) at the amplifier output. Both saturation and low gain complicate signal detection.

13. Electric field noises are introduced through wires and cables acting like antennas Unshielded lead wires Introduced by: • Electronic equipment • Electric wiring • Improper grounding Typical strength of electric fields in North American clinics:, average 5.5 V/m, range 1-200 V/m (5 Hz – 2 kHz band)* Noise amplitude: up to 10 mV (1 mV = a thousandth of V) Can be reduced by: • Shielding of input-circuit wires • Shielding of wires and circuits • Proper grounding Electric fields Differential AEP amplifier * Source: www.niehs.nih.gov/emfrapid/html/Q&A-Workplace.html - Web site of Environmental Health Science, NIH, U.S. Government.

14. Magnetic field noises are introduced through wires and cables acting like antennas Looped lead wires and cables Introduced by: • Transformers • Electric motors and wiring • Looped wires and cables Typical strength of magnetic fields in North American clinics: average 1.7 mG, range0.1-200 mG (milliGauss) (5 Hz – 2 kHz band)* Noise amplitude: up to 10 mV Can be reduced by: • Reducing wire/cable length • Positioning, NOT moving • Reducing loop area • Twisting wires • Very thick shielding (steel) Magnetic fields Loop area Differential AEP amplifier * Source: www.niehs.nih.gov/emfrapid/html/Q&A-Workplace.html - Web site of Environmental Health Science, NIH, U.S. Government.

15. EP EMI Amp A/D DSP Ground lead “Garbage” IN “Garbage” OUT Other leads Long lead wires and cables introduce large electro-magnetic field noises in a conventional amplifier Amp – amplifier A/D – analog-to-digital conversion DSP – digital signal processing

16. RF noise may strongly interfere with EP recording Radio-frequency (RF) noise comes from various sources: • Cell phones, pagers, Blackberry, wireless intercom • FM-systems, FM-radio • Wireless computer networks used in many hospitals • PDAs (Personal Digital Assistants), Palmtops • Medical equipment (ICUs, operating rooms, general offices) • Office equipment: copiers, fax-machines, computers Introduce mostly electrical noise Interferes at EP (low) frequencies despite RF frequencies are much higher – in MHz and GHz ranges – because of amplifier non-linearity There is no common-mode rejection (CMR) at frequencies ≥ 20 kHz Amplitude: up to 10 mV (thousandth of V) Source: Kitchin et al. (2003). Input filter prevents instrumentation-amp RF-rectification errors. EDN, Nov 13, p. 101-102.

17. Power line noise is not only 60 Hz and comes from both electric field and AC power lines AC outlet Power Line noise comes from • Electric field – picked up by electrode wires & cables • AC power outlets when plugged into the wall – introduced through electronic circuits, power supplies • Through USB computer ports (5 V) – introduced through electronic circuits Interferes with EP at a number of frequencies – mostly 50 / 60 Hz & harmonics: 60 Hz, 120 Hz, 180 Hz, 240 Hz … due to amplifier non-linearity Amplitude: up to 10 mV and higher AMP PC USB Power-line noise in AEP amplifiers 60 120 180 240 300 Hz

18. Low A/D resolution can significantly affect AEP recording due to insufficient dynamic range Integrity™ Typical Low

19. Putting all things together: ABR and especially ASSR are very small signals as compared to noises in AEP recording

20. Clinical ABR/ASSR testing is challenging in practice • Long testing time • Best reported: • 19 minutes (Luts, Wooters, unpublished), 21 minute (Perez-Abalo et al., 2001) • Typical 45-60 minutes (John et al., 2003), up to 90 – 120 min (Tannenbaum, 2004) • Sensitivity to electromagnetic interferences • Electromagnetically shielded booth required • Sensitivity to electrode impedance • Requires rubbing the skin • Need for sedation in many cases • Difficult to administer in electro-magnetically shielded booth

21. In-situ AEP amplification and filtering is a novel method of noise reduction in Auditory Evoked Potentials • Amplifier is mounted in-situ – directly on the ground electrode pad, with no lead • Lead length to non-inverting (+) and inverting (-) electrodes minimized to the distance between electrodes • Filtering prior to amplification • Gains optimized for ASSR and ABR • Impedance mismatch monitored in real time • Risk of wrong electrode connection minimized

22. EMI EP A/D DSP In-situ amplification largely eliminates electro-magnetic field-induced noises In-situ pre-amplifier, the Amplitrode™, is mounted directly on the ground electrode eliminating ground lead. The other leads are very short and shielded. This significantly reduces electric and magnetic field-induced and allows for a clearer EP signal at the amplifier output.

23. Noise EP Filtering prior to amplification allows optimizing gain and reducing physiological and RF noises Higher gain: 150,000 for ASSR 15,000 for ABR Exceptionally low intrinsic noise: < 350 nV in 10-10,000 Hz <10 nV in 0.05 Hz bands in 70-110 Hz EP signals at the Amplitrode™ output have large amplitude, contain little noise, have high SNR, and therefore, can be easier converted from analog to digital form, recorded, and detected.

24. In-situ amplification and wireless communications make AEP testing efficient • Reduced physiological noise • Largely reduced electromagnetic noise • No big “boxes” • Less attention to electrode impedance • Easy mounting on electrode pads • No need to achieve ≤5 kOhm impedance • No hassles with long lead wires and cables • Less risk of electrode lead misconnection

25. Amplitrode™ monitors electrode mismatch in real time • Electrode impedance mismatch (EIMM) is more relevant than electrode impedance*. • Amplitrode™ measures EIMM in real time during testing, not only prior to it. • Operator is notified of EIMM immediately. • Reduces set up time. • Measuring EIMM and very high input impedance of the Amplitrode™ eliminates the need for skin abrasion – no need to achieve impedance below 5 kOhm. Ferree et al. (2001). Scalp electrode impedance, infection risk, and EEG data quality. Clin. Neurophysiol., 112, p. 536-544.

26. Amplitrode™ eliminates the risk of improper mounting Amplifier is mounted on the ground electrode pad. The other two leads have different length. Electrode button release makes easy mounting and dismounting amplifier and clips on electrode pads. It is much easier to use even for less experienced practitioners.

27. In-situ AEP recording speeds up testing ABR 800 clicks 100 clicks 400 clicks 1600 clicks Subject: Normal hearing female, 24 yrs, R ear Place: Vivosonic office, EMI ≥ 0.5 mGauss Phone: ER-3A (correction for 0.9 ms) Stimulus: Click, 30 dB nHL, 21.1/sec, ipsi 3200 clicks

28. In “ideal” electro-magnetically shielded room, the benefit of in-situ amplification and filtering is less pronounced ABR in a shielded room (<1 V/m, 0.1 mG) Subject: T.V., 44, normal hearing Stimulus: 1000 clicks 21.1 clicks per second Artifact Rejection disabled ER-3A Insert Headphones Recording: Montage Fz/A1 10.66 ms window Band-pass filter: 30-1500 Hz for Bio-Logic Navigator Pro 30-1200 Hz for Amplitrode Source: I. Kurtz, T. Venema, 2004 (unpublished).

29. Outside a shielded room, the benefit of in-situ amplification and filtering is very significant ABR in moderate electric (12 V/m) and magnetic ( 5.5 mG) fields Correlation coefficient = 0.81 Correlation coefficient = 0.43 Subject: T.V., 44, normal hearing Stimulus: 1000 clicks 21.1 clicks per second Artifact Rejection disabled ER-3A Insert Headphones Recording: Montage Fz/A1 10.66 ms window Band-pass filter: 30-1500 Hz for Bio-Logic Navigator Pro 30-1200 Hz for Amplitrode Source: I. Kurtz, 2004 (unpublished).

30. Wireless recording of OAE and AEP provides mobility and additional noise reduction Wireless communication with PC • No cable to the PC • No noise coming back into the EP and OAE amplifiers from AC power supply • No cable-related hassles • Mobility • Testing can be controlled form anywhere within the reach of Bluetooth® • The patient or a baby’s mother can move around – without the need to disconnect electrodes, connectors, or transducers • Adult and senior patients can take a relieving break. • In the Operating Room, testing can be done from a distance, without cables getting in the way. • Battery operation • No AC-power-related noise in the amplifier circuits

31. Bluetooth®is a wireless communications protocol • Wireless communications protocol • Digital signal in GHz range • Noise-like, broadband (no fixed carrier frequency – unlike FM-radio) • Low energy – below 0.1 mG • Limited area – 30 feet (10m) • Encoded – secure for medical information • FDA-approved for various medical applications Bluetooth®

32. Amplitrode™ ER-3A ER-3A Vivo Link™ Integrity™ is the world’s first and only wireless OAE, ABR, and ASSR system VivoLink™ interface module • Generates DPOAE, TEOAE, ABR, and ASSR stimuli • Conditions stimuli for • ER-3A Insert Phones • B-71 Bone Conductor • Converts EP signals from the Amplitrode™ into digital form, 16 bit • Processes signals and communicates to the computer software through Bluetooth® Integrity™ computer program controls the OAE, ABR, and ASSR, functions • Protocol setting – modular • Test control – modular • Data management - integrated B-71 Integrity™ Wireless Bluetooth communication

33. Questions? Thank you for your interest!