Dynamic evaluation of corneal cross-linking and osmotic diffusion effects using optical coherence elastography.

Dynamic deformation events induced by osmosis or photochemical stiffening substantially influence geometrical and mechanical assessments in post-mortem corneas, therefore need to be carefully monitored in experimental settings. In this study, we employed optical coherence elastography (OCE) to quantify dynamic deformation processes at high resolution in freshly enucleated porcine corneas. Osmotic effects were studied by immerging n = 9 eyes in preservation media of three different tonicities. Dynamic processes underlying corneal cross-linking (CXL) were studied by subjecting n = 6 eyes to standard Dresden treatment, while three control groups were used. The entire procedures were performed under an OCE setup during up to 80 min, acquiring a volumetric scan every 20 s. Changes in OCE-derived axial deformations were incrementally calculated between consecutive scans. Preservation conditions had a strong influence on the observed strain patterns, which were consistent with the tonicity of the medium (swelling in hypotonic, deswelling in hypertonic environment). In the CXL group, we observed deswelling of the anterior stroma 10 min after starting the UV irradiation, which was not observed in any control group (p = 0.007). The presented results proved OCE to be a valuable technique to quantify subtle dynamic biomechanical alterations in the cornea resulting from CXL and preservation solutions.

Optical coherence tomography quantifies gradient refractive index and mechanical stiffness gradient across the human lens.

BACKGROUND: As a key element of ocular accommodation, the inherent mechanical stiffness gradient and the gradient refractive index (GRIN) of the crystalline lens determine its deformability and optical functionality. Quantifying the GRIN profile and deformation characteristics in the lens has the potential to improve the diagnosis and follow-up of lenticular disorders and guide refractive interventions in the future. METHODS: Here, we present a type of optical coherence elastography able to examine the mechanical characteristics of the human crystalline lens and the GRIN distribution in vivo. The concept is demonstrated in a case series of 12 persons through lens displacement and strain measurements in an age-mixed group of human subjects in response to an external (ambient pressure modulation) and an intrinsic (micro-fluctuations of accommodation) mechanical deformation stimulus. RESULTS: Here we show an excellent agreement between the high-resolution strain map retrieved during steady-state micro-fluctuations and earlier reports on lens stiffness in the cortex and nucleus suggesting a 2.0 to 2.3 times stiffer cortex than the nucleus in young lenses and a 1.0 to 7.0 times stiffer nucleus than the cortex in the old lenses. CONCLUSIONS: Optical coherence tomography is suitable to quantify the internal stiffness and refractive index distribution of the crystalline lens in vivo and thus might contribute to reveal its inner working mechanism. Our methodology provides new routes for ophthalmic pre-surgical examinations and basic research.

The lens of the eye changes in shape to enable objects at different distances from the eye to be seen clearly. Loss of ability to change the eyes' focus occurs during aging. We have developed a new way to image the eye that assesses how different lens regions change their shape. We evaluated our approach on twelve people of different ages and showed that those who were older had a stiffer lens, particularly in the central part of the lens. Further development and testing of our method could enable it to be used to both improve routine eye assessments as well as enable more research into how the eye works.

Optomechanical assessment of photorefractive corneal cross-linking via optical coherence elastography.

Purpose: Corneal cross-linking (CXL) has recently been used with promising results to positively affect corneal refractive power in the treatment of hyperopia and mild myopia. However, understanding and predicting the optomechanical changes induced by this procedure are challenging. Methods: We applied ambient pressure modulation based optical coherence elastography (OCE) to quantify the refractive and mechanical effects of patterned CXL and their relationship to energy delivered during the treatment on porcine corneas. Three different patterned treatments were performed, designed according to Zernike polynomial functions (circle, astigmatism, coma). In addition, three different irradiation protocols were analyzed: standard Dresden CXL (fluence of 5.4 J/cm2), accelerated CXL (fluence of 5.4 J/cm2), and high-fluence CXL (fluence of 16.2 J/cm2). The axial strain distribution in the stroma induced by ocular inflation (Δp = 30 mmHg) was quantified, maps of the anterior sagittal curvature were constructed and cylindrical refraction was assessed. Results: Thirty minutes after CXL, there was a statistically significant increase in axial strain amplitude (p < 0.050) and a reduction in sagittal curvature (p < 0.050) in the regions treated with all irradiation patterns compared to the non-irradiated ones. Thirty-6 hours later, the non-irradiated regions showed compressive strains, while the axial strain in the CXL-treated regions was close to zero, and the reduction in sagittal curvature observed 30 minutes after the treatment was maintained. The Dresden CXL and accelerated CXL produced comparable amounts of stiffening and refractive changes (p = 0.856), while high-fluence CXL produced the strongest response in terms of axial strain (6.9‰ ± 1.9‰) and refractive correction (3.4 ± 0.9 D). Tripling the energy administered during CXL resulted in a 2.4-fold increase in the resulting refractive correction. Conclusion: OCE showed that refractive changes and alterations in corneal biomechanics are directly related. A patient-specific selection of both, the administered UV fluence and the irradiation pattern during CXL is promising to allow customized photorefractive corrections in the future.

Elucidating the mechanisms underlying left ventricular function recovery in patients with ischemic heart failure undergoing surgical remodeling: A 3-dimensional ultrasound analysis.

OBJECTIVE: The study objective was to elucidate the mechanisms of left ventricle functional recovery in terms of endocardial contractility and synchronicity after surgical ventricular reconstruction. METHODS: Real-time 3-dimensional transthoracic echocardiography was performed on 20 patients with anterior left ventricle remodeling and ischemic heart failure before surgical ventricular reconstruction and at 6-month follow-up, and on 15 healthy controls matched by age and body surface area. Real-time 3-dimensional transthoracic echocardiography datasets were analyzed through TomTec software (4D LV-Analysis; TomTec Imaging Systems GmbH, Unterschleissheim, Germany): Left ventricle volumes, ejection fraction, and global longitudinal strain were computed; the time-dependent endocardial surface yielded by 3-dimensional speckle-tracking echocardiography was postprocessed through in-house software to quantify local systolic minimum principal strain as a measure of fiber shortening and mechanical dispersion as a measure of fiber synchronicity. RESULTS: Compared with controls, patients with heart failure before surgical ventricular reconstruction showed lower ejection fraction (P < .0001) and significantly impaired mechanical dispersion (P < .0001) and minimum principal strain (P < .0001); the latter worsened progressively from left ventricle base to apex. After surgical ventricular reconstruction, global longitudinal strain improved from -6.7% to -11.3% (P < .0001); mechanical dispersion decreased in every left ventricle region (P ≤ .017) and mostly in the basal region, where computed mechanical dispersion values were comparable to physiologic values (P ≥ .046); minimum principal strain improved mostly in the basal region, changing from -16.6% to -22.3% (P = .0027). CONCLUSIONS: At 6-month follow-up, surgical ventricular reconstruction was associated with significant recovery in global left ventricle function, improved mechanical dispersion indicating a more synchronous left ventricle contraction, and improved left ventricle fiber shortening mostly in the basal region, suggesting the major role of the remote myocardium in enhancing left ventricle functional recovery.

Morphometric Characterization of an Ex Vivo Porcine Model of Functional Tricuspid Regurgitation.

Emerging treatments for tricuspid valve (TV) regurgitation require realistic TV pathological models for preclinical testing. The aim of this work was to investigate structural features of fresh and defrosted porcine right-heart samples as models of mild and severe functional tricuspid regurgitation (FTR) condition in ex-vivo pulsatile flow platform. Ten fresh hearts were tested ex-vivo under steady and pulsatile flow in typical right-heart loading conditions. Hemodynamics and 3D echocardiographic imaging of TV and right ventricle (RV) were acquired. Hearts were then kept frozen for 14 days, defrosted, and tested again with the same protocol. Morphometric parameters of TV and RV were derived from 3D reconstructions based on echo data. Fresh samples showed a slightly dilated TV morphology, with coaptation gaps among the leaflets. Sample freezing induced worsening of TV insufficiency, with significant (p < 0.05) increases in annulus size (annulus area and perimeter 7.7-3.1% respectively) and dilation of RV (9.5%), which led to an increase in tenting volume (123.7%). These morphologic alterations reflected into a significant increment of regurgitation fraction (27%). Together, such results suggest that fresh porcine heart samples may be a reliable ex-vivo model of mild FTR condition, which can be enhanced through freezing/thawing treatment to model a severe pathological condition.

Prognostic value of left atrial strain quantification from 2D ultrasound imaging in post-ischemic heart failure patients: evidence from the REMODEL-HF study.

BACKGROUND: Left atrial (LA) function can be effectively assessed by measuring longitudinal LA strain (LAS) via two-dimensional speckle tracking echocardiography (2DSTE). Here, we test 2DSTE-based LAS as marker of different left ventricle (LV) remodeling patterns and as prognostic index in ischemic heart failure (HF) candidates to surgical ventricular reconstruction. METHODS: We retrospectively considered ischemic HF patients with anterior (group A, n=130) or posterior (group P, n=48) LV remodeling. Based on 2D ultrasound, LV and LA morpho-functional parameters were quantified including reservoir (LASRes), conduit (LASCond) and booster (LASBoost) LAS. We tested their capability to discriminate between groups A and P, and their group-specific prognostic significance for the composite end-point of death or HF re-hospitalization at follow-up (mean follow-up time=40 months, range 3-101 months). RESULTS: Group A and group P displayed similar end-diastolic (p=0.89) and end-systolic (p=0.33) LV volume index, and LA volume index LAVi (p=0.44) corrected for the degree of mitral regurgitation. As compared to group P, group A revealed a significant reduction in LASBoost (9.2±0.4% vs. 11.1±0.7%, p=0.04) and a non-significant reduction in LASRes (16.9±0.7% vs. 19.3±1.1%, p=0.06). Kaplan-Meier curves showed that the median LASRes and LASBoost values effectively stratified patients based on their prognosis in the overall study population (Log-rank p=0.002 and Log_rank p<0.0001) and in group A, where the association was stronger for LASBoost (Log-rank p<0.001) than for LASRes (Log-rank p=0.013). CONCLUSIONS: 2DSTE-based LAS assessment is affordable, repeatable and non-invasive, and could add clinically-relevant mechanistic insight and prognostic value in the stratification of ischemic HF patients.

Cardiac Imaging for the Assessment of Left Atrial Mechanics Across Heart Failure Stages.

The left atrium (LA) is emerging as a key element in the pathophysiology of several cardiac diseases due to having an active role in contrasting heart failure (HF) progression. Its morphological and functional remodeling occurs progressively according to pressure or volume overload generated by the underlying disease, and its ability of adaptation contributes to avoid pulmonary circulation congestion and to postpone HF symptoms. Moreover, early signs of LA dysfunction can anticipate and predict the clinical course of HF diseases before the symptom onset which, particularly, also applies to patients with increased risk of HF with still normal cardiac structure (stage A HF). The study of LA mechanics (chamber morphology and function) is moving from a research interest to a clinical application thanks to a great clinical, prognostic, and pathophysiological significance. This process is promoted by the technological progress of cardiac imaging which increases the availability of easy-to-use tools for clinicians and HF specialists. Two-dimensional (2D) speckle tracking echocardiography and feature tracking cardiac magnetic resonance are becoming essential for daily practice. In this context, a deep understanding of LA mechanics, its prognostic significance, and the available approaches are essential to improve clinical practice. The present review will focus on LA mechanics, discussing atrial physiology and pathophysiology of main cardiac diseases across the HF stages with specific attention to the prognostic significance. Imaging techniques for LA mechanics assessment will be discussed with an overlook on the dynamic (under stress) evaluation of the chamber.