Session F06: Optics in Soft Matter and Medicine

Novel biomedical applications of lasers: dermatology, gynecology, and stomatology

Water is an important constituent of all soft and hard human tissues. For this reason, the Er:YAG laser is of a particular interest for tissue ablation since its wavelength coincides with the major absorption peak of the water molecule. By controlling the temporal structure of Er:YAG pulses it is possible to control the laser-tissue interaction from “cold” to coagulative ablation, thus optimizing the laser either for skin resurfacing or for precise and painless cutting of teeth. The high absorption of the Er:YAG in irrigation fluids has been utilized also for photo-acoustically induced cleaning and disinfection of dental root canals.
On the other hand, the wavelength of the Nd:YAG laser lies in the skin’s optical window and is thus suitable for transcutaneous delivery of laser energy deep into the adipose tissue. This characteristic has been explored for a novel “fat reduction” procedure offering a less invasive alternative to surgical liposuction.
Recently, it was discovered that the extremely short absorption depth of the Er:YAG laser in soft tissues can be utilized also to create extremely short and intense heat shock pulses within the superficial tissue layer without causing irreversible thermal damage or ablation of the tissue. The discovery has led to the development of novel minimally invasive methods in various medical areas, including for treating vaginal atrophy, urinary incontinence or snoring, thus in many cases replacing much more aggressive and risky standard surgical procedures.
  

Understanding coronary plaque biomechanical properties with intravascular imaging

The biomechanical properties of coronary artery atherosclerosis are vital in understanding acute myocardial infarction and the factors that contribute to plaque instability. Intravascular cross-sectional imaging, with a resolution approaching that of histopathology and with high speed to avoid motion artifacts that arise from the dynamic cardiac cycle, can provide a basis for mechanical modeling and analysis to identify the primary compositional and structural factors in lesion vulnerability. We have recently developed a novel approach for real-time modeling that can be used during procedures in the cardiac catheterization laboratory.   

Optical properties of silicone rubber tissue phantoms for biomedical optics applications

In medical physics, tissue phantoms play important role in characterization, validation, calibration and optimization of medical devices. A useful phantom must be well characterized, namely its physical properties must be accurately measured using standard techniques.

A set of silicon rubber tissue phantoms was prepared for applications in biomedical optics. A black pigment served as an absorber and hollow silica micro-spheres as scatterers. Nine samples with different absorber and scatterer concentrations were prepared. Refractive indices of the samples were measured in the 430 – 660 nm spectral range and did not vary significantly (<0.02 %). Optical properties (absorption and scattering coefficients, and similarity parameter γ) were estimated using spatially resolved reflectance spectroscopy in the subdiffusive regime (400 - 1000 nm). The determined optical properties covered the range characteristic for biological tissues.

Silicon rubber tissue phantoms feature many advantageous properties in comparison to other common phantoms in biomedical optics (e.g., intralipid, agar). They are stable, solid, reproducible, and their optical properties can be adjusted according to the application demands. Therefore, they are promising tools for biomedical optics.   

Laser induced jets in needle free drug delivery

Various actuation mechanisms have been used in the past for needle-free injection systems, predominantly springs and compressed gas. However, recent innovation has seen use of pulsed and continuous wave lasers for precise injection of ultra-low doses. Here, we have investigated the feasibility of laser-induced micro-jets as a needle-free injection technique. Effect of various parameters such as capillary diameter, laser pulse energy and distance of the laser focal point on jet dynamics were studied in the past, however, we also varied the fluid viscosity and orifice stand-off relative to the target. To quantify the penetration dynamics and dispersion of the liquid delivered, both gelatin gel (in-vitro) and porcine tissue (ex-vivo) were used as skin models. Lastly, we also discuss the possibility of using a spark-cavitation system to generate high-speed micro-jets instead of pulsed lasers.   

Fourier Transform Laser Speckle Imaging for art conservation

Laser speckle imaging is a powerful imaging technique that visualizes microscopic motion within turbid materials. At current two methods are widely used to analyze speckle data: one is fast but qualitative, the other quantitative but computationally expensive. We have developed a new processing algorithm based on the fast Fourier transform, which converts raw speckle patterns into maps of microscopic motion and is both fast and quantitative, providing a dynamnic spectrum of the material over a frequency range spanning several decades. In this article we show how to apply this algorithm and how to measure a diffusion coefficient with it. We harness the potential of this new approach by constructing a portable laser speckle imaging setup that performs quantitative data processing in real-time on a tablet. We will show one of many possible applications of this method in the form of monitoring the cleanig process of artistic oil paintings.   

Doppler Functional Imaging of Cancer Drug Sensitivity in Living Tumor Biopsies

Biodynamic imaging is a deep-tissue digital holography imaging technique that captures the response of living tissue to applied therapeutics. Biodynamic metrics can predict patient clinical response with high accuracy. However, evaluating drug responses on a sample basis has high variance because of the underlying sample heterogeneity related to tissue features. We introduce a technique called tissue dynamics spectroscopic imaging (TDSI) to reveal drug response variations within small cubic millimeter biopsy samples. By performing tissue dynamics spectroscopy on a voxel basis and extracting biodynamic biomarkers, functional images are obtained of the heterogeneous spatial response of tumor tissue to anticancer drugs. Spatial maps of biodynamic biomarkers are created using a bivariate colormap to represent the spatial distribution of pairs of signed biomarkers. Time-lapse response maps provide further details into drug mechanisms.   

Probing the interior dynamics of shear thickening colloidal suspensions using confocal line scans

Under high stresses, shear thickening suspensions transition from low viscosity to high viscosity or shear jammed states. While both the bulk rheology and the microscopic driving forces of such transitions are well-studied, the bridge between the microscopic and macroscopic scales is incomplete. Measurements at the boundaries indicate that dynamic high stress regions propagate through shear thickening suspensions of colloidal spheres, but the means of propagation within the suspension interior was inaccessible due to imaging limitations. Here we use line scans on a confocal microscope to visualize particle flows in a sheared suspension, increasing our temporal resolution by two orders of magnitude. These line scans reveal that high stress regions are correlated with significant changes in particle speed, density, and order that extend many particle diameters deep into the suspension.   

Nanoscale Optical Imaging of Soft Matter Under Flow

Far-field fluorescence microscopy provides an enticing platform for spatially resolving equilibrium and nonequilibrium dynamics of soft matter systems, ranging from thin films to polymer solutions. However, several long-standing challenges, including limited spatial resolution and poor image contrast in densely labeled systems, have limited its application to such systems. Here, we develop a novel adaptation of super-resolution microscopy based on stimulated emission depletion (STED) coupled with fluorescence anisotropy detection to image concentration profiles of high molecular weight polyelectrolytes in semi- dilute solutions. We use this technique to study depletion layer formation and dynamics under Poiseuille flow, which remains an outstanding problem in fluid mechanics. While the inherently short length scales associated with depletion layer dynamics have traditionally prohibited direct imaging, STED-anisotropy imaging provides sufficient spatial resolution and contrast to measure small changes in polymer concentration over 10s of nanometers.   

Analyzing the Flow Drying Colloidal Suspensions Using Optical Coherence Tomography

In this work, we present the visualization and analysis of flow in drying colloidal suspensions composed of colloidal polymer particles in water. The flow induced particle transport and deposition can influence the final structure of the polymer film deposited. Employing time-lapse, high-speed imaging, Optical Coherence Tomography was used to monitor the dynamic process of drying colloidal droplets. With the aid of high refractive index tracer particles, fluid flows were captured. The speckle contrast analysis differentiates the dynamics of particles, showing the packing process and particle transporting to the edge of droplet. In low particle concentration suspension, this resembles the coffee ring phenomenon. In high concentrations of particles, a situation in practical coatings or ink-jet applications, the viscosity plays an important role in the material flow and deposition, resulting in different flow pattern and final dry film structures, such as cracks, shear bands, and skin formation.   

Hyperspectral imaging as a technique to evaluate peritonitis in mouse models

Hyperspectral imaging (HSI) is an optical technique that combines imaging and spectroscopy. Images can be processed spectroscopically, extracting information about tissue biochemistry and morphology that can be of importance to physicians.

Peritonitis is an inflammation of the peritoneal cavity that can result in death. In animal model studies of the disease, golden standard is histology, while biomolecular techniques can also be used. These techniques only provide either good spatial resolution or area coverage. A technique with large area coverage and resolution is thus desired.

We present a classification method for determination of the state of peritonitis using HSI. The technique provides both good spatial resolution and coverage of the whole organ. Spectra are acquired in reflection geometry and processed using a custom model of light transport in thin samples. Tissue parameters including oxygenation and scattering properties are extracted from the images and used to assess disease state. Per subject scores are used to successfully separate control from model groups. HSI obtained scores are also compared with existing techniques (histology, PCR and Western blot) showing good concordance, meaning that HSI can be a useful tool for disease evaluation.