Mapping age-related elasticity changes in porcine lenses using bubble-based acoustic radiation force

Abstract

Bubble-based acoustic radiation force aims to measure highly localized tissue viscoelastic properties. In the current investigation, acoustic radiation force was applied to laser-induced bubbles to measure age-related changes in the spatial distribution of elastic properties within in vitro porcine lenses. A potential in vivo technique to map lens elasticity is crucial to understanding the onset of presbyopia and develop new treatment options. Bubble-based acoustic radiation force was investigated as a technique to measure the spatial elasticity distribution of the lens in its natural state without disrupting the lens capsule.Laser-induced optical breakdown (LIOB) generated microbubbles in a straight line across the equatorial plane of explanted porcine lenses with 1 mm lateral spacing. Optical breakdown occurs when sufficiently high threshold fluence is attained at the focus of femtosecond pulsed lasers, inducing plasma formation and bubble generation. A two-element confocal ultrasonic transducer applied 6.5 ms acoustic radiation force-chirp bursts with the 1.5 MHz outer element while monitoring bubble position within the lens using pulse-echoes with the 7.44 MHz inner element. A crosscorrelation method was used to measure bubble displacements and determine exponential time constants of the temporal responses. Maximum bubble displacements are inversely proportional to the local Young's modulus, while time constants are indicative of viscoelastic properties.The apparent spatial elasticity distributions in 41 porcine lenses, ranging from 4 months to 5 years in age, were measured using bubble-based acoustic radiation force. Bubble displacements decrease closer to the porcine lens center, suggesting that the nucleus is stiffer than the cortex. Bubble displacements decrease with increasing lens age, suggesting that porcine lenses become stiffer with age. Bubble-based acoustic radiation force may be well-suited as a potential in vivo technique to spatially map elastic properties of the lens and guide therapeutic procedures aimed at restoring accommodation.

Estimation of mechanical properties of a viscoelastic medium using a laser-induced microbubble interrogated by an acoustic radiation force

“…It is reported that the lens has a Young's modulus of several tens of Pa to tens of kP. 10,11,20,21,24,27 However, most of these techniques to measure lens elasticity assume direct mechanical testing and usually can be used only in vitro. Among various techniques to measure mechanical properties of tissues noninvasively, radiation force has investigated greatly during last few decades as a means of a palpation tool for imaging soft tissues where external forces cannot reach.…”

“…8,9 While laser-tissue ablation and associated formation of microbubbles play an increasingly important role in laserbased microsurgery, microbubbles could also be used to obtain information about elastic properties of ocular tissues. 10,11 According to the most widely accepted theory of presbyopia, the age-related loss of accommodation is attributed to gradual loss of lens elasticity. Furthermore, there is evidence that nuclear cataract lenses are generally harder than normal lenses.…”

“…[43][44][45][46][47][48] By combining microbubbles created by laser-induced optical breakdown and acoustic radiation force, microbubblebased acoustic radiation force was introduced as a technique to remotely measure the localized viscoelastic properties of the lens. 10,11,[49][50][51] In that approach, laser-induced microbubbles were displaced using a long acoustic pulse to interrogate the mechanical properties of ex vivo porcine and human lenses. 10,11 Elastic properties were evaluated based on the amplitude of the bubble displacement from an equilibrium position.…”

“…10,11,[49][50][51] In that approach, laser-induced microbubbles were displaced using a long acoustic pulse to interrogate the mechanical properties of ex vivo porcine and human lenses. 10,11 Elastic properties were evaluated based on the amplitude of the bubble displacement from an equilibrium position. Such an approach assumes that the acoustic radiation force on the bubble surface is known or deduced by experiments or analytical calculations.…”

Inverse elastographic method for analyzing the ocular lens compression test

“…6 Previous methods for estimating lens sti®ness include spinning tests, [7][8][9] dynamic mechanical analysis, 10 indentation, 11,12 penetration, 13 Brillouin microscopy, [14][15][16][17][18][19] acoustic methods, 20,21 and compression. [22][23][24][25][26][27] The lens capsule has been mechanically characterized by in°ation testing 28,29 and uniaxial tensile testing.…”