Non-Invasive Health
Monitoring using Eye as a
Window to the Body
Rafat R. Ansari, Ph.D.
NASA Glenn Research Center
Cleveland, Ohio
Aerospace Medicine Grand Rounds
Houston, TX, February 25, 2003
Acknowledgments
• NASA OBPR
• NIH-NASA Interagency agreement
• FDA-NASA Interagency agreement
• John Glenn Biomedical Engineering
Consortium (CCF, CWRU, UH, NCMR, NASA
GRC) Works closely with NASA JSC on
critical path roadmap (CPR) issues.
Laboratory Researchers and Students
Kwang Suh, Ph.D.
Russ Messer
Jim King
Alfred Leung
M. Datiles, MD
NIH/NEI
L. Rovati, PhD
U. of Modena
F. Giblin, PhD
J. Sebag, MD
Doheny Eye Clinic. Oakland University
M. Geiser
IRO Switzerland
J. Clark, PhD
U. of Washington
K. Manuel, OD
NASA JSC
M. Chenault, PhD
FDA
Effects of Space Travel on the Human
Body are Similar to that of Aging
(John Glenn, STS-95, 1998)
Our Objective
Diagnose diseases non-invasively long
before the clinical symptoms appear and
help find non-surgical countermeasures
“Eye is a window to
the soul”
Could it be a “window
to the human body” ?
Non-Invasive Optical Probes &
Early Detection of Diseases
• Dynamic Light Scattering (cataract, diabetes,
uveitis, glaucoma, LASIK outcomes)
• Auto-fluoresence (diabetic retinopathy)
• Laser-Doppler (Age-related macular degeneration)
• Raman Scattering (AMD, cancer)
• Polarimetry (glucose sensing)
• Oximetry (tissue metabolism, functional imaging of
brain, stroke, trauma)
• Cappliroscopy (blood vessel tortuosity)
Thanks to microgravity research program,
these problems are now solved.
New Compact Fiber Optic Probes
Office of Future Technology, 1996
Schematic of a Fiber Optic Probe for the
Early Diagnosis of Eye Diseases
U.S. Patent 5973779 October 26, 1999 Ansari and Suh
Association Between Nuclear Opalescence LOCS II Grades
Obtained Clinically and the Nuclear Densities (odu),
Together With 95% Error Bars
Datiles, M. et. al, Brit J. Ophthalmol. Vol. 79, 527-534, 1995
07
Comparison of Particle Size Distributions
and Scheimpflug Images
Exp. Eye Res., Vol. 74, 93-102, January, 2002
08
New NASA-Developed DLS Eye Diagnostics
Device in Clinical Use at NEI/NIH
Cataract
Post LASIK
Evaluation
Uveitis
Drug
screening
Exp. Eye Res., Vol. 74, 93-102, January, 2002
“Space Radiation and Cataracts in
Astronauts”
Space Station and
and Shuttle have
a low-earth orbit
295 astronaut longitudinal study at NASA JSC
“Relatively low doses of space radiation are
linked to an increased incidence and early
appearance of cataracts”
Cucinotta et al., Radiation Research, Vol.156, No. 5, 460466, Nov. 2001.
IN VITRO (State-of-the-art) BIOCHEMICAL ANALYSIS
Hypothesis
Measured by
crushing the lens
Visible
Environmental Ocular Toxicity: Effects of
X-Ray Irradiation (DLS-Rabbit Study)
Outstanding Paper Award: Radiation Track, STAIF February, 2002
Avoid Surgery
Help Find Medical cure
Prevention of Cataract
• Sorbitol lowering drugs: first to be examined
systematically and progressed to clinical trials but the
results were disappointing.
• Micronutrients showed little promise in animals but came
to clinical trial in patients with cataract without the
publication of any major benefit.
• Clinical trial of Pantethine was inconclusive with respect
to effectiveness
Bottleneck:
• Lack of sensitive and quantitative in-vivo techniques for
protein aggregation and opacification.
Countermeasures
Cataract Treatment in Rats (33 Animals Studied)
SLS/DLS
Probe
Probe translation
actuator and
stage
Anesthesia
tube
Animal Close-up
Measurement Time: 5 Sec
Animal
Thermal
pad
Wave-length: 670 nm
Power: 80 microwatts
Ophthalmic Tech. XIII, SPIE Vol. 4951,
2003, in press
Cataract Treatment in Rats with Pantethine
Normal control
Selenite-treated
Pantethine-treated
Slit-Lamp: Lenses remain transparent
Cataract Treatment in Rats (One Day Post-Injection)
Non-Invasive DLS Screening (Static Mode)
I
N
T
E
N
S
I
T
Y
Distance (mm)
Cataract Treatment in Rats
Protein Crystallin Size Distributions from DLS Exponential Sampling
Control
12 Hrs Se
42 Hrs Se/Pan
60 Hrs Se
150
135
Intensity (arbitrary units)
120
105
90
75
Pantethine treatment seems
to protect lens damage
60
45
30
15
0
0.1
1
10
Diameter (nm)
100
1000
10000
Effects of Diabetes on Lens and Treatment
(FDA-NASA Sand Rat Experiments)
Diabetes Tech. & Therapeutics, Vol. 4, No. 5, 2002
LASIK (Laser-Assisted In Situ Keratomileusis)
has Become Popular to Treat Corneal Refractive Errors
UP TO 5% RESULT IN POORER VISION
(USA TODAY, 10-25-01)
Need for new diagnostic capabilities to
better evaluate current refractive surgery
outcomes.
McLeod, S.D., Editorial “Beyond Snellen Acuity: “The
Assessment of Visual Function After Refractive Surgery,”
Arch Ophthalmol, September 2001.
81714
06
May 2002
Successful early evaluation of
Haze and Healing
Early Detection of Alzheimer’s
through the eye
• At present the only sure way is at autopsy
• Can beta amyloid proteins promote
aggregation of lens crystallines?
• If yes, DLS can detect Alzheimer’s early
and non-invasively and help find treatments
Exp. Eye Res. Vol. 73, 859-866 December 2001
Present: Fluorescene Angiography is the Most
Widely Used Technique
NON-INVASIVE AUTO FLUORESENCE
MEASUREMENTS
Natural Fluorescence as a Function of Age
(Oxidative Stress in Humans)
SPIE, Vol. 4611, 2002
Corneal Auto-Fluorescence and Diabetic
Retinopathy
Metabolically active Epithelial and Endothelial cells
contain fluorophores: pyridine nucleotides (NADPH) and
flavins (FMN and protein-linked flavins)
λ = 500-520 nm
Green fluorescence
Blue excitation beam
460-480 nm
Blue excitation beam
λ = 460-480 nm
Eye ball
NADPH fluoresce in the reduced redox state and flavins in
the oxidized redox state
Rovati et al., JBO, Vol 3, No. 3, 357-363, 1998
Change in Visual Acuity in Orbital Flight
To this date this remain of unknown etiology
Measurement of Choroidal Blood Flow on-board KC-135
SPIE, Vol. 4951, 2003, in press
Possible Mechanisms
•Primarily, could choroidal engorgement
mechanism and secondarily some curvature
shape change mechanism of the cornea or lens
be responsible for this change in VA?
•Since the choroid has no baroreceptors to
autoregulate the choroid during fluid shifts as
does the systemic vascular system, the choroid
possibly remains engorged thereby pushing the
macula forward, causing a hyperopic shift of the
eye.
New Helmet-Mounted Laser Doppler Ocular
Blood Flow Meter for Use on KC-135 Flights
Weight: ~2 Lbs
Laser: 875 nm
Power: 100 µW
Duration: 10 s
Non-mydriatic
Major Karen Heupel, MD
USAF, Brooks AFB
Keith Manuel
Rafat Ansari
Jim King
Bobby
Clark
Arterial BP Measurements
Arterial Blood Pressure (mm Hg)
In Parabolic Flight
180
171
162
153
144
135
126
117
108
99
90
81
72
63
54
45
36
27
18
9
0
Systolic in 2g
Systolic in 0g
Diastolic in 2g
Diastolic in 0g
Elapsed Time 1 hr 15 min
Start Time 0 min
Time in Flight
Choroidal RBC Speed (LDF) and G-Levels (SAMS)
S peed
Hi-G
Gravity
S peed
Lo-G
2.00
3.00
2.50
Gravity
2.00
1.00
1.50
1.00
0.50
0.50
0.00
10:55:00
11:00:00
11:05:00
Time
0.00
11:10:00
RBC Speed (kHz)
1.50
Preliminary Results
Measured
Parameters
Ground (Tilt-Table)
Standing-Supine
Flight
(1-G and 0-G)
RBC Speed
6%
13%
RBC Volume
BP Systolic
BP Diastolic
23%
29%
-25%
-35%
75%
105%
-20%
-55%
Pulse rate
-17%
-1.5%
RBC Flow
Detailed data analysis have to wait until all 20
subjects are flown and studied by spring 2003
Factors Linked to AMD
•Age (confirmed)
•Smoking
DRY
•Hypertension
•Gender
•Race
•Nutrition
WET
Raman Scattering
Detection of Carotenoids in the Retina
• Macula contains high concentrations
of lutein and zeaxanthin
• Dietary intakes may help in lowering
the rate of visual loss from AMD
Gellermann et al, Opt. Lett., Vol.
26, No. 15, 2001
What do some Vegetables and the Eye Have in common?
• Caretonoids are C40H56 compounds
• Alternating C-C and C=C bonds with π-electron
conjugation
4000
Mustard Greens
3000
Spinach
2500
Collard Greens
2000
Green Bean
1500
Celery
1000
500
-500
Wavenumber (1/cm)
378
376
374
372
370
368
366
364
362
360
358
356
354
352
350
348
346
344
342
340
338
336
334
332
0
330
Raman Intensity (photons/sec)
3500
CAROTENOIDS IN THE EYE & SKIN
5000
Retina
Raman Intensity (photon/sec)
4500
4000
3500
3000
2500
2000
1500
Skin
1000
500
0
15
20
25
30
35
Age (years)
40
45
50
55
Oximetry in Muscle Tissue
Oscilloscope
Lasers
Power Supply
Multiplexer
4 Fiber optic Channels
Cuff
Fiber Optic
Cables
Sensor
80.00
Post Exercise
70.00
Oxyhemoglobin (µM)
Pre Exercise
60.00
50.00
40.00
30.00
20.00
10.00
0.00
Detector
Healthy Subject
Post Myocardial Infarction
Diabetic Patient
Aggregates in a Diabetic
Courtesy of Yuri Gurfinkel, MD, Ph.D.
FUTURE
Conjunctiva may be a better site for monitoring blood
flow: easy access, no multiple scattering, temperature
equilibration, and early effects of diabetes.
Monitoring Glucose Through the Eye
(New Non-invasive System)
SPIE Vol. 4965, (2003), in press
Glucose Sensing Results
r e l a t iv e R o ta t io n [m d e g r e e s ]
25
20
15
10
5
0
-5
0
100 200 300 400 500 600 700 800 900 1000
Glucose Concentration [mg/dl]
Normal
Glucose Sensing Experimental setup
F633
PD633
DM2
PD543
motor system D
C
F543
PCL
LP
RLP
L543
DM1
L633
Near Future
Head-Mounted Glucose Meter
(Better Diabetes Management)
Non-Invasive Ophthalmic Tele-Health
•
•
•
•
•
•
•
•
Cataract
Glaucoma
AMD
Diabetic retinopathy
Uveitis
Radiation damage
Diabetes
Alzheimer’s
•
•
•
•
•
•
•
•
Tissue metabolism
Functional brain imaging
Blood flow
Retinal detachment
Corneal abnormalities
Blood vessel tortuosity
Glucose sensing
Cholestrol sensing
NASA JSC Critical Path Roadmap: Clinical Capabilities
and Effective Countermeasures
Remote Health
Monitoring
(for the Benefit
of All Human
Kind)
In Fond Memory of the Crew
of STS-107 Columbia
“Eye is really a “window to the body”; This is so cool. I look
forward to using it on orbit some day” (Dr. Kalpana Chawla,
February 2002)