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

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.