Mechanistic Bases for Examining Effects of Acoustic and Electromagnetic Energy Exposures Carey D. Balaban University of Pittsburgh
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
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COTS Device Examples
COTS Device Examples
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COTS Device Examples
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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