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PhASE: PhotoAcoustic Schlieren Elastography II Design Team Taryn Connor*, Sarah Janiszewski*, Emmanuel Llado∞, Stephanie Reimer∞, Tristan Swedish* *ECE Dept. ∞ MIE Dept. Design Advisors Prof. Charles A. DiMarzio, ECE, MIE Prof. Gregory Kowalski, MIE Abstract The ability to measure the mechanical properties of the cornea accurately and noninvasively benefits society by providing clinical practice with the potential to diagnose diseases of the cornea earlier than current technology. The objective of this capstone project continues the work of the PhotoAcoustic Schlieren Elastography, PhASE system, by benchmarking it against phantoms of known mechanical properties. The PhASE system operates by utilizing several biomedical optics techniques. First, a pulse generator is used to control a heating laser directed at the cornea to produce an acoustic wave. This acoustic wave changes the index of refraction in a localized region of the tissue as it propagates. The schlieren imaging system is used to track this pressure wave by stroboscopically imaging the induced gradient in the index of refraction of the tissue. Several steps have been laid out in order to bring PhASE II closer to the clinical setting. By focusing on the problems of the original system, it has been deemed necessary to automate the system, while also utilizing a more realistic cornea phantom that has been completely mechanically characterized. LED Phantom Laser Camera Knife-Edge For more information, please contact [email protected] or [email protected] 140 The Need for Project The PhASE system seeks to Over 35 million Americans are estimated to have corneal diseases, create an in-vivo method of which can lead to vision loss. The current diagnostic methods often measuring the mechanical detect these diseases only after irreversible damage has been done. properties of the cornea for Advances are needed in research, modeling, and instrumentation to diagnosing diseased states. provide earlier detection of corneal tissue damage. PhASE II focuses on research of more effective diagnostic methods and computer modeling of the system’s resulting images. More research is necessary before moving from tissue phantoms to excised corneas and in-vivo corneas. The Design Project Objectives and Requirements The objective is to design a Design Objectives system capable of stimulating The objective of this project is to provide researchers with a and observing a mechanical method of characterizing the mechanical properties of the cornea. The response in a cornea-like PhASE system will allow researchers to study the corneal mechanics in phantom, and use the elastic various disease states. PhASE II seeks to create a system that can property data to benchmark the measure the shear modulus and pressure wave modulus of an acoustic system. pressure wave in a phantom and confirm these moduli values with traditional mechanical analysis. The combination of schlieren imaging and computational algorithms should yield the shear modulus and elastic modulus of the sample by finding the velocity of the pressure wave. Once two of the six elastic moduli are known, the remaining can be calculated to fully characterize the phantom. Since the PhASE I system is conceptually accurate, PhASE II seeks to make improvements on the system—such as better signal processing, a fully designed phantom, and an automated measurement process—that will help make this project more credible as a research tool. Design Requirements As this technology is still fairly new, the PhASE system needs to Elastic moduli relations for PhASE and Traditional Mechanical Analysis be benchmarked against a material of known mechanical properties. Phantoms made of silicone were used to calibrate the system and tested mechanically for shear and elastic moduli. Other requirements that must be met for PhASE II to be considered successful include better signal processing and the implementation of a fully automated measurement process. 141 Design Concepts Considered Several non-contact methods Photoacoustic stimulation of waves was identified as the most of mechanical stimulation were reliable non-invasive method. The creation of a photoacoustic wave investigated while focusing on requires heating a small area of material quicker than the heat can optical setups because they dissipate through conduction. A thermal stress confinement induces the require minimal contact with propagation of pressure and shear waves, whose velocities are related the sample and have high to the P-wave and shear modulus. The pulse width of the laser needs to resolution. be short enough to cause a thermal stress confinement within the medium, while conversely it cannot exceed levels of heating which could damage the corneal tissue. The acoustic wave front will travel at the speed of sound in the tissue (approx. 1500 m/s) across the 1.5 cm diameter of the cornea. The detection system must have temporal resolution of about 100 nanoseconds (ns) and a spatial resolution of at least 100 micrometers (m) to capture data at distinct instances of the wave propagation. Schlieren imaging is capable of detecting the pressure wave without contacting the surface of the eye. Transmissive-mode schlieren imaging is the easiest to implement but requires a light source and a detector on opposite sides of the tissue; a reflective-mode system can remain on one side of the sample, but requires costly components. The general schlieren system needs to achieve temporal resolution on the order of 100 nanoseconds. High-speed cameras are potentially capable of meeting the required sampling rate, but are extremely costly. A strobing method was used in which waves are produced and detected at discrete time steps. Wavefront propagation is captured by changing the offset between the initial laser pulse and the image capture. High frequency triggering of the illumination source is attractive in its simplicity, but also requires a rapid illumination rise time. LEDs are capable of high speed triggering and do not have problems with diffraction. Tissue phantoms would be used to validate the system. Hydrogels, PhASE Proof of Concept similar to the material of contact lenses, are most similar to the cornea, but have the same problems in precise measurement: they require constant hydration and are ill-suited to traditional mechanical analysis (TMA). Silicone phantoms are less optically and mechanically similar to the cornea than hydrogels, but don’t degrade and can be tested intensively with TMA. It is important to use a stable material of known 142 mechanical properties to benchmark the system. Recommended Design Concept The proof of concept design Design Description uses a rapidly pulsed heating The heating laser produces 10 Watts (W) at the 850 nm laser to induce mechanical wavelength and is integrated with a high-speed pulse generator to pulse waves in a silicone phantom. A for 50 ns durations. The abstract figure shows the layout of the PhASE strobed-source, transmissive system. The light source of the schlieren system is a high power, 2000+ schlieren imaging system is lumen LED with a 10 ns rise time. A 100 ns output signal from the used to observe the waves and pulse generator is amplified to 40 W and controls the LED strobing. a post-processing algorithm The output is offset from the heating pulse by 100 ns. This strobed results in quantitative source beam is focused onto a high precision slit, and then collimated measurements of elastic by a lens into a circular beam. A sample is placed in the beam path moduli. between the first and second lens. After the second lens, a knife-edge is placed at the focal point to block any un-modulated light propagation. Light refracted by the wave propagation is focused by a third lens onto a high-resolution detector with an infrared filter that ensures that only visible light from the source is imaged. Phantoms were made with Sylgard 184, a clear two-part silicone. Although it is not a perfect mimic, Sylgard 184 is able to maintain its mechanical properties and is capable of TMA due to its durability. To produce a clearer pressure wave, a near-infrared dye will be added to the phantom to increase the level of laser absorption. It is vital that the phantom absorbs the 850 nm wavelength of the heating laser. The image analysis algorithm produces a curve of the pixel intensity with respect to pixel location across a predefined radial vector on an image. The average velocity of each wave is calculated by finding the distance between the wavefronts of two subsequent images, converting this pixel displacement to physical distance, and dividing this value by the time step between the two images. Experimental Investigations An LED was capable of capturing schlieren data in pulsed operation. An optical enclosure for the system was used to improve the signal-to-noise ratio of the image data. The pulse circuits for strobing were tested using an oscilloscope and confirmed the laser/LED signal pulse widths, timing offsets, voltage levels, and amplification gains. Phantoms were fabricated according to a design of experiments to find the combination of variables that yield the most detectable 143 pressure wave. The three variables of experimentation are: base-tocuring agent ratio, concentration of dye in solvent, and optical pulse rate. The use of a near-infrared dye in the phantom will increase the level of laser absorption in the phantom, creating a clearer acoustic wave. The final designed phantom will be mechanically evaluated through tensile testing and 3-point bending to identify its elastic modulus and shear modulus. Key Advantages of Recommended Concept The main advantages of the PhASE system are that two elastic moduli can be found, which allows for complete mechanical characterization of the tissue. Current technology can only measure one modulus, varies in accuracy, and requires excision of the cornea. Silicone phantoms are stable enough to benchmark the system against something of known mechanical properties. Financial Issues The proof of concept’s total Most of the equipment in the PhASE system was donated by lifetime cost is $850, while a Professor DiMarzio’s Optical Science Laboratory. PhASE I spent second-generation, optimized approximately $550 in additional equipment. PhASE II spent system would cost at least approximately $300 for new phantom materials. The total cost of the $25,000. project in a second-generation model with new and optimized components would cost between $25k and $35k. New components would include a high-speed camera for image collection, a pulsed light source with higher luminous intensity, and an optimized wavelength laser diode for photoacoustic stimulation. Recommended Improvements Before being considered a The PhASE system has several required modifications before it diagnostic tool, PhASE will can be considered a non-invasive diagnostic tool. A phase sensitive need to implement a reflective reflectance mode detection scheme would allow in-vivo use by having schlieren system, a higher the detector and light source on the same side of the eye. The laser wavelength laser, a more diode currently used to generate a pressure wave is not safe for human powerful illumination source, use. Infrared radiation from a 1550 nm laser diode would be mostly and a higher speed camera. absorbed by the cornea, meaning less power would be required for heating and almost no harmful light would reach the retina. A more powerful illumination source would also provide higher contrast imaging. The use of a higher speed and more sensitive detector would allow the measurements to be taken more quickly. 144