Mechanistic Bases for Examining Effects of Acoustic and Electromagnetic Energy

Exposures

Carey D. BalabanUniversity of Pittsburgh

3D Digitization for “Prescription” Ear Plugs

Personal Protective Equipment (PPE)

In-Ear Dosimetry

Shipboard PPE

Underwater comms & hearing protection

Hearing loss simulator

Incidence, Susceptibility & Evaluation

Assessment tools

Systems Approach for an Integrated 6.1 / 6.2 / 6.3 Program

Source Noise Reduction

Shipboard noise assessment

Shipboard noise path validation

Laboratory modeling/ scale tests of jet noise reduction

Jet noise Reduction

Medical Prevention & Treatment

Blast Auditory Injuries

Cell regeneration

Pharmacologic interventions and drug delivery

ONR Noise-Induced Hearing Loss PortfolioProgram Officer: Kurt Yankaskas

2NIHL markers

Operational Scenario for Technology

US Embassy in Cuba to reduce staff indefinitely after 'health attacks'

By Laura Koran and Patrick Oppmann, CNN Updated 6:38 PM ET, Fri March 2, 2018

The American flag flies at the U.S. Embassy following a ceremony August 14, 2015, in Havana.

Source of Exposure Unknown

• Potential directed energy sources include– Hypersonic sound (and LRAD)– Pulsed radiofrequency– Pulsed laser source– Ultrasound (e.g., from photoacoustic device)

• Receiver characteristics: Waveguide, resonance and cavitation properties of intracranial contents

Order of Discussion

• Overview of literature from 1960s-1990s on ultrasound and RF effects on the inner ear and brain– Organs of hearing include the saccule and utricle

• COTS devices for ultrasound and pulsed RF emissions

• Objective tests of eye movement and pupil coordination that distinguish control, acute mTBI and individuals affected from Havana

Intracranial Wave Guide, Resonance and Cavitation

Carey BalabanJeffrey Vipperman, George Klinzing,

Brandon Saltsman, Scott Mang

Biological Effects of Directed Energy

• Directed energy can produce peripheral and central neurosensory symptoms and signs

• Examples:– Occupational exposures– Environmental exposures– Military domain

Current ONR Support

• Characterize wave guide, resonance and cavitation features of cranial contents– Blood vessels (surrounded by Virchow-Robin

spaces) as coaxial fluid-filled wave guides and resonance cavities

– Ventricles and cisternal system– Inner ear– Air spaces (sinuses, pharynx, etc.)

Integrated View• Cranial resonances may differentially amplify

incident energy

Model from http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0113264

Integrated View• Cranial resonances may differentially amplify

incident energy

Model from http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0113264

Vestibule and Hook Portion

Classical Cochlear Mechanics

Stria Vascularis Structure

• Parallel network of capillaries, fed and drained at even intervals by arterioles and venules, in the lateral cochlear wall

• Capillaries (12-16 µm diameter, 40-50 µm spacing) – Non-pulsatile flow – Packed tightly with blood cells for most of the length

of the cochlea

Acoustic Cavitation

Edmonds PD (ed) Ultrasonics 1981

Energy Thresholds: Transfer to Cochlear Fluids

• Incident sound energy in the audible range produces considerable pressure differences in endolymph and perilymph compartments of the cochlear partition

• Published transfer functions are suitable for predictive modeling of cavitation

• Cavitation noise profiles can be measured directly

Local Strial Blood Flow Altered During Sound Exposure

Integrated View

• Cavitation of water and blood can occur in the audible frequency range at intensities produced in the cochlear fluids

• Pressures recorded in the cochlea during acoustic stimulation suggest that the threshold for blood cavitation is exceeded by several orders of magnitude at maximum resonance sites along the basilar membrane

• Dissolved gas (nitrogen and oxygen) in body fluids may form bubbles

The Frey Effect

• Humans can ‘hear’ radar (microwave) emissions

Aerospace Medicine Dec 1961

The Frey Effect

The American Journal of Medical Electronics 1963

The Frey Effect

• Tyazhelov et al. (Radio Science, 14 (1979), 259-263): Human minimum detection thresholds for pulsed microwaves in the 10-15 kHz pulse repetition range

The Frey Effect

The Frey Effect

• A thermoelastic response of the inner ear was proposed for audibility of radar pulses

• Acoustic cavitation emissions from blood in the stria vascularis and fluids the inner ear (endolymph and perilymph) are one such plausible mechanism

• Effects on utricle and saccule (proximate to hook portion of cochlea) in inner ear? – Excited by sound (Vestibular Evoked Myogenic

Potential)• Intracranial blood vessels may also be affected?

Vestibule and Hook Portion

COTS Device Examples

http://myskunkworks.net/index.php?route=product/product&path=61&product_id=60

COTS Device Examples

COTS Device Examples

On-line pest control products from a major retailer

COTS Device Examples

https://gopestfree.com/pestfree-our-technologies/

COTS Device Examples

https://www.soundlazer.com/

SoundLazer Large (98 Element) Ultrasonic Speaker Array

SPECIFICATIONS FOR ONE TRANSDUCER• 40kHz Operating Frequency• 120 ± 3 dB SPL• 10 V (rms) sine wave• Standoff distance of 30 cm• Capacitance = 2,550 pF @ 1kHz• Operating Temperature -40°C to

85°CReference: Data Sheet for Murata Part No. MA40S4S Ultrasonic Transducer

BRS 8-10-

Operational Scenario for Technology

US Embassy in Cuba to reduce staff indefinitely after 'health attacks'

By Laura Koran and Patrick Oppmann, CNN Updated 6:38 PM ET, Fri March 2, 2018

The American flag flies at the U.S. Embassy following a ceremony August 14, 2015, in Havana.

Vergence Eye Movements Distinguish ‘Havana

Syndrome’ from mild TBI

Colleagues

• Carey D. Balaban (University of Pittsburgh)• Michael E. Hoffer (University of Miami)• Bonnie Levin (University of Miami)

Hardware and Software• Conducted with the I-PASTM (I-Portal® Portable

Assessment System, NKI Pittsburgh), a portable 3D head mounted display (HMD) system with integrated eye tracking technology.

– Sampling rate 100 Hz– Resolution < 0.1°

• All stimuli are created in a virtual environment.• Neuro Kinetics VEST™ software was used to run the

battery of tests and analyze the data.

Prospects for Operational Monitoring of Eye and Pupil Movements

• Video-oculography permits unobtrusive monitoring of eye and pupil movements.

• Eye is imaged with digital video with infrared diode illumination

• Pupil detected and measured• Rotation of eyeball calculated with algorithms from center of

mass of pupil and iris features

Prospects for Operational Monitoring of Eye and Pupil Movements

• Disconjugate Eye Movements (convergence and divergence)– Near response during convergence: Eyes converge, lens

curvature increases, and pupil constricts (e.g., focus on near or approaching target)

– Near response during divergence: Eyes diverge, lens curvature decreases, and pupil dilates (e.g., focus on far or receding target)

Subjects• Controls: 51 normal subjects from University of Miami, Naval

Medical Center San Diego, and Madigan Army Medical Center

• mTBI patients: 18 subjects from University of Miami, Naval Medical Center San Diego, and Madigan Army Medical Center (17 with complete data)

• Havana Affected Subjects: 19 subjects with complete data

I-PAS Vergence Tasks• Each eye viewed a white square with red center (0.1° visual

angle)– Step Binocular Disparity task : Disparity shifts in the horizontal

plane equivalent to symmetric, approximately ± 1.4° vergence eye movement steps.

– Pursuit Binocular Disparity task: Sinusoidal convergence (toward nose) and divergence (laterally) movement in the horizontal plane equivalent to symmetric, approximately ± 2.5° vergence pursuit at 10 sec/cycle.

Control Subjects: Disparity Fusion Task

0 5 10 15 20 25 30 35 40

Ver

genc

e A

ngle

(deg

)

-3

-2

-1

0

1

2

3Binocular Disparity Responses (Control)

Time (s)

0 5 10 15 20 25 30 35 40

Nor

mal

ized

Pup

il A

rea

(% P

LR)

-40

-20

0

20

40

60

80

MP198

MP168

Control Subjects: Disparity Pursuit Task

0 5 10 15 20 25 30

Ver

genc

e A

ngle

(deg

)

-4

-2

0

2

4Control Disparity Pursuit

Time (s)

0 5 10 15 20 25 30

Nor

mal

ized

Pup

il A

rea

(%P

LR)

-60

-40

-20

0

20

40

Data Analysis • Pupillary light response test used to normalize pupil area

– 0.42 to 65.4 cd/m² homogeneous illumination steps• Vergence angle represented in degrees relative to zero at initial fixation• Nonlinear least squares regression estimated:

– Parameters for the vergence disparity response as a weighted sum of phasic

(𝑲𝑲𝒗𝒗𝒗𝒗𝒔𝒔𝒔𝒔−𝒕𝒕𝒗𝒗𝒔𝒔

𝒔𝒔+𝟏𝟏) and tonic ( 𝑲𝑲𝒗𝒗𝒗𝒗𝒔𝒔

−𝒕𝒕𝒗𝒗𝒔𝒔

𝟎𝟎.𝟐𝟐𝟐𝟐𝒔𝒔+𝟏𝟏) processes, with delay tv and gains Kvh and Kvl,

respectively, for converging and diverging half-cycles.– Based upon Sun et al. (1983), the pupil dynamics were fitted from the

vergence data by a transfer function for pupil motion, 𝑲𝑲𝒑𝒑𝒔𝒔−𝒕𝒕𝒑𝒑𝒔𝒔

𝟎𝟎.𝟐𝟐𝟐𝟐𝒔𝒔+𝟏𝟏, with delay tp

and gain Kp. – Symmetry tested by fitting separate gains for convergence versus divergence

and for pupil constriction versus dilatation.

Analysis: Dynamic Modeling of Vergence and Pupil Responses

Data in Black, Modeled response in Grey

Analysis: Affected Individual

Data in Black, Modeled response in Grey

Time (s)0 5 10 15 20 25 30 35 40

Nor

mal

ized

Pup

il A

rea

(% P

LR)

-50

-40

-30

-20

-10

0

10

20

30

40

50

Time (s)0 5 10 15 20 25 30 35 40

Verg

ence

Ang

le (d

eg)

-4

-3

-2

-1

0

1

2

3

4

Step Binocular Disparity Test

Control Group Acute mTBI Havana Affected Tukey HSD (p<0.05) comparisons

Low Pass Convergence Modulation Depth (Kvl converge direction)

1.43 ± 0.09° 0.63 ± 0.16° 1.75 ± 0.14° C>mTBI; C=HA; HA>mTBI

Low Pass Divergence Modulation Depth (Kvl diverge direction)

1.50 ± 0.09° 0.70 ± 0.15° 1.74 ± 0.13° C>mTBI; C=HA; HA>mTBI

Vergence R-squared 0.84 ± 0.04 0.45 ± 0.07 0.80 ± 0.06 C>mTBI; C=HA; HA>mTBI

Pupil Constriction Gain (re: vergence)

7.0 ± 1.2%/° 6.5 ± 2.0%/° 18.6 ± 1.8%/° C=mTBI; HA>C; HA>mTBI

Pupil (re: Vergence) R-squared 0.39 ± 0.04 0.29 ± 0.05 0.61 ± 0.05 C=mTBI; HA>C; HA>mTBI

Pursuit Binocular Disparity Test

Control Group

Acute mTBI Havana Affected

Tukey HSD (p<0.05) comparisons

Low Pass Convergence Modulation Depth (Kvl converge direction)

2.41 ± 0.10° 1.68 ± 0.19° 1.86± 0.16° C>mTBI; C>HA; HA=mTBI

Low Pass Divergence Modulation Depth (Kvl diverge direction)

2.32 ± 0.10° 1.73 ± 0.17° 1.74 ± 0.15° C>mTBI; C>HA; HA=mTBI

Vergence R-squared 0.91 ± 0.04 0.57 ± 0.05 0.82 ± 0.05 C>mTBI; C=HA; HA>mTBI

Pupil Constriction Gain (re: vergence)

7.7 ± 0.7%/° 5.8 ± 1.3%/° 10.5 ± 1.1%/° C=mTBI; C=HA; HA>mTBI

Pupil (re: Vergence) R-squared 0.54 ± 0.03 0.29 ± 0.05 0.58 ± 0.04 C>mTBI; C=HA; HA=mTBI

Classification: Discriminant Analysis (Vergence Data Only)

Control (Predicted)

mTBI(Predicted)

Havana Affected (Predicted)

Control 50 1 0

mTBI 6 11 0

Havana Affected 0 0 19

• Stepwise discriminant analysis, Wilks-lamba criterion, Vergence test data only

• 92.0% of original grouped cases correctly classified• 89.7% correctly classified in 1-out cross-validation

Conclusion• The Havana Affected, Acute mTBI and Control Subjects

can be distinguished objectively by performance in binocular disparity vergence tasks.

• The Havana Affected subjects show an abnormal convergence and near response behavior that is distinct from acute mTBI.

• Binocular disparity vergence testing with a modified software on a COTS device (NKI I-PAS®) is a fieldable test for Havana-type events