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Item type:Publication, Multiple optical elastography techniques reveal the regulation of corneal stiffness by collagen XII(Association for Research in Vision and Ophthalmology Inc., 2022-11-01)PURPOSE. Collagen XII plays a role in regulating the structure and mechanical properties of the cornea. In this work, several optical elastography techniques were used to investigate the effect of collagen XII deficiency on the stiffness of the murine cornea. METHODS. A three-prong optical elastography approach was used to investigate the mechanical properties of the cornea. Brillouin microscopy, air-coupled ultrasonic optical coherence elastography (OCE) and heartbeat OCE were used to assess the mechanical properties of wild type (WT) and collagen XII–deficient (Col12a1–/–) murine corneas. The Brillouin frequency shift, elastic wave speed, and compressive strain were all measured as a function of intraocular pressure (IOP). RESULTS. All three optical elastography modalities measured a significantly decreased stiffness in the Col12a1–/– compared to the WT (P < 0.01 for all three modalities). The optical coherence elastography techniques showed that mean stiffness increased as a function of IOP; however, Brillouin microscopy showed no discernable trend in Brillouin frequency shift as a function of IOP. CONCLUSIONS. Our approach suggests that the absence of collagen XII significantly softens the cornea. Although both optical coherence elastography techniques showed an expected increase in corneal stiffness as a function of IOP, Brillouin microscopy did not show such a relationship, suggesting that the Brillouin longitudinal modulus may not be affected by changes in IOP. Future work will focus on multimodal biomechanical models, evaluating the effects of other collagen types on corneal stiffness, and in vivo measurements. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Optical coherence elastography measures the biomechanical properties of the ex vivo porcine cornea after LASIK(SPIE, 2024-01-01)Significance: The biomechanical impact of refractive surgery has long been an area of investigation. Changes to the cornea structure cause alterations to its mechanical integrity, but few studies have examined its specific mechanical impact. Aim: To quantify how the biomechanical properties of the cornea are altered by laser assisted in situ keratomileusis (LASIK) using optical coherence elastography (OCE) in ex vivo porcine corneas. Approach: Three OCE techniques, wave-based air-coupled ultrasound (ACUS) OCE, heartbeat (Hb) OCE, and compression OCE were used to measure the mechanical properties of paired porcine corneas, where one eye of the pair was left untreated, and the fellow eye underwent LASIK. Changes in stiffness as a function of intraocular pressure (IOP) before and after LASIK were measured using each technique. Results: ACUS-OCE showed that corneal stiffness changed as a function of IOP for both the untreated and the treated groups. The elastic wave speed after LASIK was lower than before LASIK. Hb-OCE and compression OCE showed regional changes in corneal strain after LASIK, where the absolute strain difference between the cornea anterior and posterior increased after LASIK. Conclusions: The results of this study suggest that LASIK may soften the cornea and that these changes are largely localized to the region where the surgery was performed. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Dual optical elastography detects TGF-β-induced alterations in the biomechanical properties of skin scaffolds(SPIE, 2024-09-01)Significance: The skin's mechanical properties are tightly regulated. Various pathologies can affect skin stiffness, and understanding these changes is a focus in tissue engineering. Ex vivo skin scaffolds are a robust platform for evaluating the effects of various genetic and molecular interactions on the skin. Transforming growth factor-beta (TGF-β) is a critical signaling molecule in the skin that can regulate the amount of collagen and elastin in the skin and, consequently, its mechanical properties. Aim: This study investigates the biomechanical properties of bio-engineered skin scaffolds, focusing on the influence of TGF-β, a signaling molecule with diverse cellular functions. Approach: The TGF-β receptor I inhibitor, galunisertib, was employed to assess the mechanical changes resulting from dysregulation of TGF-β. Skin scaffold samples, grouped into three categories (control, TGF-β-treated, and TGF-β + galunisertibtreated), were prepared in two distinct culture media.one with aprotinin (AP) and another without. Two optical elastography techniques, namely wave-based optical coherence elastography (OCE) and Brillouin microscopy, were utilized to quantify the biomechanical properties of the tissues. Results: Results showed significantly higher wave speed (with AP, p < 0.001; without AP, p < 0.001) and Brillouin frequency shift (with AP, p < 0.001; without AP, p . 0.01) in TGF-β-treated group compared with the control group. The difference in wave speed between the control and TGF-β + galunisertib with (p = 0.10) and without AP (p = 0.36) was not significant. Moreover, the TGF-β + galunisertibtreated group exhibited lower wave speed without and with AP and reduced Brillouin frequency shift than the TGF-β-treated group without AP, further strengthening the potential role of TGF-β in regulating the mechanical properties of the samples. Conclusions: These findings offer valuable insights into TGF-β-induced biomechanical alterations in bio-engineered skin scaffolds, highlighting the potential of OCE and Brillouin microscopy in the development of targeted therapies in conditions involving abnormal tissue remodeling and fibrosis. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Revealing regional variations in scleral shear modulus in a rabbit eye model using multi-directional ultrasound optical coherence elastography(Nature Research, 2024-12-01)The mechanical properties of the sclera play a critical role in supporting the ocular structure and maintaining its shape. However, non-invasive measurements to quantify scleral biomechanics remain challenging. Recently introduced multi-directional optical coherence elastography (OCE) combined with an air-coupled ultrasound transducer for excitation of elastic surface waves was used to estimate phase speed and shear modulus in ex vivo rabbit globes (n = 7). The scleral phase speed (12.1 ± 3.2 m/s) was directional-dependent and higher than for corneal tissue (5.9 ± 1.4 m/s). In the tested locations, the sclera proved to be more anisotropic than the cornea by a factor of 11 in the maximum of modified planar anisotropy coefficient. The scleral shear moduli, estimated using a modified Rayleigh-Lamb wave model, showed significantly higher values in the circumferential direction (65.4 ± 31.9 kPa) than in meridional (22.5 ± 7.2 kPa); and in the anterior zone (27.3 ± 9.3 kPa) than in the posterior zone (17.8 ± 7.4 kPa). The multi-directional scanning approach allowed both quantification and radial mapping of estimated parameters within a single measurement. The results indicate that multi-directional OCE provides a valuable non-invasive assessment of scleral tissue properties that may be useful in the development of improved ocular models, the evaluation of potential myopia treatment strategies, and disease characterization and monitoring. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Air-Coupled Ultrasonic Optical Coherence Elastography Reveals Protocol-Dependent Corneal Stiffening in Epi-On and Epi-Off Riboflavin Crosslinking(Association for Research in Vision and Ophthalmology, 2026-07-10)Purpose: To evaluate the biomechanical impact of corneal crosslinking (CXL) when combining three different ultraviolet A (UV-A) riboflavin (RB) photosensitizers and protocols (Dresden protocol [DP] and accelerated protocol [AP]) using air-coupled ultrasonic optical coherence elastography in ex vivo rabbit corneas. Methods: An air-coupled ultrasound excitation optical coherence elastography system was used to excite the corneal apex and generate Lamb wave propagation along 16 corneal cross-sectional meridians. Measurements were conducted on ex vivo rabbit eyes (n = 45) during three treatment phases: Virgin, after 30 minutes of RB soaking, and after UV-A irradiation. The protocols used include the DP (3 mW/cm2, 30 minutes) and two accelerated protocols (AP-1: 9 mW/cm2, 10 minutes; and AP-2: 30 mW/cm2, 3 minutes). Each protocol was tested with three photosensitizers: epithelium-on (TE), and epithelium-off with hyperosmolar (M) and hypo-osmolar solutions (D). Lamb wave speed and average corneal thickness were calculated for each meridian to estimate meridian-dependent corneal shear modulus. Differences were statistically analyzed using linear mixed-effects regression. Results: The DP-D produced the strongest significant corneal stiffness increase (480.5 kPa; P < 0.001) during the UV irradiation phase, and the most pronounced corneal thinning (186 µm; P < 0.001). DP-TE achieved the next strongest stiffening (309.5 kPa) during UV irradiation, with no significant thickness change. All other protocol-photosensitizer combinations did not achieve significant corneal stiffening except for AP-1-D and AP-2-D during the RB soaking phase. Conclusions: Accelerated protocols did not produce significant corneal stiffening for any RB photosensitizer except when using dextran-based D. DP-D and DP-TE produced the greatest balance between shear modulus increase and corneal thickness decrease, suggesting DP-TE as a potential compromise between biomechanical impact, corneal integrity, and faster postoperative recovery. Translational Relevance: This work quantified the impact of clinically used crosslinking photosensitizers and protocols on corneal stiffening using an air-coupled ultrasound excitation optical coherence elastography, which holds promise for clinical assessments in patients.