Assessment of wave propagation in mice cornea and lens using phase stabilized swept

source optical coherence tomographyRavi K. Manapuram, Floredes M. Menodiado, Jiasong Li, Salavat R. Aglyamov, Maleeha Mashiatulla, Shang Wang,

Stanislav Emelianov and Kirill V. Larin

SFM 2012

25th September 2012

Why do we should study biomechanical properties of lens

and cornea

Cornea

DiagnosisKeratoconus: Change of corneal curvature

Induces changes in • strain distribution• stiffness• shear modulus• Bending

Keratecstasia and progressive post LASIK (PPLK)

Outcomes of refractive surgeries such as micro incisions, corneal transplants, etc.,

Accurate measurements of IOP.

Corneal Hysteresis

Lens

DiagnosisPresbyopia: Change of corneal curvature

Induces changes in • stiffness of the lens• strain distribution• Young’s Modulus

CataractAstigmatism GlaucomaAge related effects

Better understanding of lens nucleus and cortex

Study the accommodation process

Lens development

General methods

induce a stimulus and measure the ocular tissue response

1. Mechanical stimulus2. Ultrasound3. Laser pulse4. Air puff

1. DMA2. MRI3. B-mode Ultrasound4. Supersonic shear imaging5. Acoustic radiation force6. Electro optical systems (ORA)7. Optical methods including OCT

require tissue stimulation on the order of mm amplitude

Dynamic Mechanical Analyzer (DMA) : in vivo ?

The Ocular Response Analyzer (ORA) is a commercially available clinical instrument

ORA require a large displacement of the corneal surfaceThe predictability of this system is still under investigation

1. General methods to quantify stiffness 1. Induce a stimulus and measure the response (wave

parameters)

2. Phase resolved method for quantifying wave parameters1. Ex vivo and In vitro results published earlier1,2,3

3. 2D amplitude distribution in mice lens in vitro1,2

4. 2D amplitude distribution in mice lens in vivo5

5. Methods to quantify wave velocity

Outline

1Manapuram et al., Laser Phys Lett., 8(2), 164-168 (2011).2Manapuram et al., Proc. SPIE, 7885,78851V (2011).3Manapuram et al., Proc. SPIE, 8209,82090S (2012).

4Manapuram et al., Laser Phys., accepted (2012).5Manapuram et al., Invest. Ophth. Vis. Sci., in preparation (2012).

Excitation unit

Manapuram et al., Laser Phys (accepted) 2012Manapuram et al., Laser Phys Lett., 8(2), 164-168 (2011).

Manapuram et al., Proc. SPIE, 7885,78851V (2011).

System and experiment setup

Excitation unit and measurement unit

Procedure

3D image of the eye showing the excitation point and the points where

phases are measured

2D image of the eye showing the capability of PhS-SSOCT for whole eye

imaging

Manapuram et al., Proc. SPIE, 8209,82090S (2012).

(a)

Procedure

Optical pathlength modulation amplitude

Amplitude Mapping can be achieved with surface distance.

Manapuram et al., Proc. SPIE, 7885,78851V (2011).

Phase response at the surface of the cornea (a) younger (1 month) mice (b) older (9 month) mice; points are the real data whereas the line plot is the smoothened data(Note that the shift in response has no significance due to the lack of knowledge of time of pulse.

Phase response from mice cornea in situ

2D amplitude map mouse cornea in situ

1 month old (attenuation: 93% per mm) 9 month old (43% per mm)

0.714 /mm

0.35 /mm

0.5 /mm

0.2 /mm

This lateral spatial anisotropy is to be expected based upon the non uniform orientation and distribution of collagen fibrils that has been shown in mice.

Manapuram et al., Proc. SPIE, 8209,82090S (2012).Manapuram et al., JBOL (2012).

Damping of wave amplitude as a function of age (mice cornea in

situ )

(a) Damping of normalized amplitude damping over the distance from the tapping point and (b) Mean attenuation versus mice age.

Delay in wave (mice cornea in situ )

The harmonic oscillations took 0.2 ms to travel from top surface to the bottom surface

Results of similar studies on mice lens in vitro

Experiment setup for studies on mice eye (both cornea and lens)

in vivo

Wave quantifying procedure

2D Amplitude map (Lens in vivo)

Top layer Bottom layer

2D Amplitude map (Cornea in vivo)

Top layer Bottom layer

Wave velocity quantification on gelatin phantoms

Conclusions

• We have extended our previously demonstrated method of quantifying nanometer-level vibrations to measure mechanical wave propagation in the mouse lens and cornea in vivo.

• The method utilizes phase response of the tissue surface to a pulsed excitation and the phase response is detected using M-mode imaging capabilities of PhS-SSOCT.

• We have shown that mechanical wave propagation in the cornea of different aged mice vary significantly, which we attribute to differences in stiffness.

• Therefore, PhS-SSOCT could be an effective tool for measurements of mechanical wave propagation in soft tissues.

Acknowledgments