Toward Development of a Portable System for 3D Fluorescence Lymphography.

Lymphoedema is a debilitating disease that results in chronic swelling of a body region due to a dysfunctional lymphatic system. Since a cure is yet to be identified for this disease, management is currently the best option for preventing disease progression and improving patient outcomes. Fluorescence lymphography is a popular approach for mapping the lymphatic vessels to provide information about the underlying lymphatic dysfunction. However, current clinical fluorescence lymphography tools do not enable the creation of comprehensive 3D maps of lymphatics throughout affected limbs. This work presents the development toward multi-camera 3D reconstruction with fluorescence imaging to overcome the current limitations in clinical tools. Pilot studies have been performed that identify suitable instrumentation for this multi-camera approach and techniques for creating a 3D fluorescence lymphography device are discussed.Clinical Relevance- This paper presents development toward new low-cost and portable clinical tools for lymphoedema diagnosis and to facilitate personalised treatment and self-management of this disease.

Non-contact quantification of aortic stenosis and mitral regurgitation using carotid waveforms from skin displacements.

Objective. Early diagnosis of heart problems is essential for improving patient prognosis.Approach. We created a non-contact imaging system that calculates the vessel-induced deformation of the skin to estimate the carotid artery pressure displacement waveforms. We present a clinical study of the system in patients (n= 27) with no underlying condition, aortic stenosis (AS), or mitral regurgitation (MR).Main results. Displacement waveforms were compared to aortic catheter pressures in the same patients. The morphologies of the pressure and displacement waveforms were found to be similar, and pulse wave analysis metrics, such as our modified reflection indices (RI) and waveform duration proportions, showed no significant differences. Compared with the control group, AS patients displayed a greater proportion of time to peak (p= 0.026 andp= 0.047 for catheter and displacement, respectively), whereas augmentation index (AIx)was greater for the displacement waveform only (p= 0.030). The modified RI for MR (p= 0.047 andp= 0.004 for catheter and displacement, respectively) was lower than in the controls. AS and MR were also significantly different for the proportion of time to peak (p= 0.018 for the catheter measurements), RI (p= 0.045 andp= 0.002 for the catheter and displacement, respectively), and AIx (p= 0.005 for the displacement waveform).Significance. These findings demonstrate the ability of our system to provide insights into cardiac conditions and support further development as a diagnostic/telehealth-based screening tool.

Hydrogen bonding dissipating hydrogels: The influence of network structure design on structure-property relationships.

Hydrogels made with semi-interpenetrating networks of the oligomerized polyphenol tannic acid, and poly(acrylamide), exhibit high stiffness and toughness. However, the structure property relationships that give rise to enhanced mechanical properties is not well understood. Herein, we systematically investigate the hydrogels using small angle X-ray scattering and small and Ultra-small angle neutron scattering within a wide length scale range (1 nm to 20 µm), polarized optical microscopy, and rheology. Small angle X-ray and neutron scattering reveal the presence of micron sized hydrogen bonded clusters in the hydrogels. Breaking of hydrogen bonded clusters above a critical solution temperature was clearly observed in the small angle neutron scattering data. Polarized optical microscopy show enhanced anisotropy for the gels with oligomerized tannic acid incorporated - when compared to gels with monomeric tannic acid. Rheological studies at varying temperatures nicely corroborate the structural changes observed at high temperatures and reveal a self-healing behavior of the gels. The knowledge gained from this study will aid in rational design of hydrogels for biomedical applications.

Visible-Light Stiffness Patterning of GelMA Hydrogels Towards In Vitro Scar Tissue Models.

Variations in mechanical properties of the extracellular matrix occurs in various processes, such as tissue fibrosis. The impact of changes in tissue stiffness on cell behaviour are studied in vitro using various types of biomaterials and methods. Stiffness patterning of hydrogel scaffolds, through the use of stiffness gradients for instance, allows the modelling and studying of cellular responses to fibrotic mechanisms. Gelatine methacryloyl (GelMA) has been used extensively in tissue engineering for its inherent biocompatibility and the ability to precisely tune its mechanical properties. Visible light is now increasingly employed for crosslinking GelMA hydrogels as it enables improved cell survival when performing cell encapsulation. We report here, the photopatterning of mechanical properties of GelMA hydrogels with visible light and eosin Y as the photoinitiator using physical photomasks and projection with a digital micromirror device. Using both methods, binary hydrogels with areas of different stiffnesses and hydrogels with stiffness gradients were fabricated. Their mechanical properties were characterised using force indentation with atomic force microscopy, which showed the efficiency of both methods to spatially pattern the elastic modulus of GelMA according to the photomask or the projected pattern. Crosslinking through projection was also used to build constructs with complex shapes. Overall, this work shows the feasibility of patterning the stiffness of GelMA scaffolds, in the range from healthy to pathological stiffness, with visible light. Consequently, this method could be used to build in vitro models of healthy and fibrotic tissue and study the cellular behaviours involved at the interface between the two.

Quantifying optical anisotropy in soft tissue membranes using Mueller matrix imaging.

SIGNIFICANCE: A non-destructive technique for accurately characterizing the spatial distribution of optical properties of soft tissue membranes may give improved outcomes in many tissue engineering applications. AIM: This study aimed to develop a non-destructive macroscopic imaging technique that is sensitive to optical anisotropy, typical of fibrous components in soft tissue membranes, and can address some of the difficulties caused by the complex turbid nature of these tissues. APPROACH: A near-infrared Mueller matrix imaging polarimeter employing logarithm decomposition was developed and used to conduct transmission measurements of all the polarization properties across the full thickness of bovine pericardium tissue. RESULTS: The full Mueller matrix was measured across a 70 mm × 70 mm sample of calf bovine pericardium and revealed significant retardance (linear and circular) and depolarization in this tissue. Regions with a uniform axis of optical anisotropy were identified. Mueller matrix imaging demonstrated that the exhibited circular retardance was sufficient to lead to possible misinterpretation of apparent fiber orientation when using conventional polarization imaging techniques for such tissues. CONCLUSIONS: Mueller matrix imaging can identify regional distributions of optical anisotropy in calf bovine pericardium. This new capability is a promising development in non-destructive imaging for tissue selection.

Optical coherence tomography imaging of cardiac trabeculae.

An integrated instrument is being developed to study live cardiac trabeculae, which is capable of stimulating the muscle under controlled conditions while measuring the heat production, force, and sarcomere length distribution. To improve the accuracy of estimation of stress, strain, and volumetric heat production, the geometry of the muscle must be known. A spectral domain optical coherence tomography system (SD-OCT) has been constructed and calibrated to image the trabecula mounted inside the instrument. This system was mounted above the muscle chamber and a series of equally-spaced cross-sectional images were obtained. These were processed using a workflow developed to extract cross-sectional area and volume. The initial results have demonstrated the feasibility of using OCT to capture the overall geometry of cardiac trabecula mounted in the instrument. Further work will be directed to improve the image quality for larger samples and apply meshing algorithms to the acquired data.