Multimodal quantitative optical elastography of the crystalline lens with optical coherence elastography and Brillouin microscopy

Abstract

Assessing the biomechanical properties of the crystalline lens can provide crucial information for diagnosing disease and guiding precision therapeutic interventions. Existing noninvasive methods have been limited to global measurements. Here, we demonstrate the quantitative assessment of the elasticity of crystalline lens with a multimodal optical elastography technique, which combines dynamic wave-based optical coherence elastography (OCE) and Brillouin microscopy to overcome the drawbacks of individual modalities. OCE can provide direct measurements of tissue elasticity rapidly and quantitatively, but it is a challenge to image transparent samples such as the lens because this technique relies on backscattered light. On the other hand, Brillouin microscopy can map the longitudinal modulus with micro-scale resolution in transparent samples. However, the relationship between Brillouin-deduced modulus and Young's modulus is not straightforward and sample dependent. By combining these two techniques, we can calibrate Brillouin measurements with OCE, based on the same sample, allowing us to completely map the Young's modulus of the crystalline lens. The combined system was first validated with tissue-mimicking gelatin phantoms of varying elasticities (N = 9). The OCE data was used to calibrate the Brillouin shift measurements and subsequently map the Young's modulus of the phantoms. After validation, OCE and Brillouin measurements were performed on ex-vivo porcine lenses (N = 6), and the Young's modulus of the lenses was spatially mapped. The results show a strong correlation between Young's moduli measured by OCE and longitudinal moduli measured by Brillouin microscopy. The correlation coefficient R was 0.98 for the phantoms and 0.94 for the lenses, respectively. The mean Young's modulus of the anterior and posterior lens was 1.98 ± 0.74 kPa and 2.93 ± 1.13 kPa, respectively, and the Young's modulus of the lens nucleus was 11.90 ± 2.94 kPa. The results presented in this manuscript open a new way for truly quantitative biomechanical mapping of optically transparent (or low scattering) tissues in 3D.

Characterization of retinal biomechanical properties using Brillouin microscopy

“…We have previously demonstrated quantitative measurements of crystalline lens elasticity by combining Brillouin microscopy with OCE. 41 Performing such measurements on the retina is the next step of our work for truly quantitative measurements of retinal elasticity as well as co-registered structural and biomechanical maps of the retina.…”

Heartbeat optical coherence elastography: corneal biomechanics in vivo

“…However, spatial mapping of the cornea is limited due to relatively long imaging times, and evaluating the relationship between the Brillouin modulus and Young’s modulus is still under investigation. 15 – 17 OCE of the cornea in vivo has been performed using multiple excitation techniques. 18 – 22 While these methods were effective for assessing the mechanical properties of the cornea, there is increasing interest in measuring the biomechanical properties of tissues without any external excitation.…”

Heartbeat OCE: corneal biomechanical response to simulated heartbeat pulsation measured by optical coherence elastography

“…[4][5][6][7][8] Brillouin microscopy has also been effective in assessing the mechanical properties of the cornea indirectly, 9,10 but spatial assessment of tissue elasticity may require long imaging times (∼50 s for a cross sectional scan 11 ), and quantification of material parameters (e.g., Young's modulus) from the Brillouin frequency shift is still an open question. 12 In contrast, elastography has rapidly been growing since its inception in the 90s as a quantitative technique for measuring tissue biomechanical properties. In elastography, tissue motion is measured using an imaging modality, 13,14 and then material parameters (e.g., Young's modulus) are estimated by appropriate mechanical models.…”