terahertz imaging of in vivo corneal tissue...

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Introduction and Background A reflective THz imaging system developed for hydration sensing. Materials and Methods Courtney Shen 1,2 , Shijun Sung 1 , Warren S. Grundfest 1,2,3 1. Department of Electrical Engineering, University of California, Los Angeles (UCLA), 2. Department of Bioengineering, UCLA 3. Center for Advanced Surgical and Interventional Technology (CASIT), Department of Surgery David Geffen School of Medicine, UCLA Results Eyes are the most immune-privileged carefully regulated organ. Hydration levels of the eye is carefully regulated, especially in the cornea which provides most of it’s focusing power and visual acuity. Current methods to measure the hydration levels of the eye include central corneal thickness measurements with ultrasound. However, the level of precision with cornea thickness and hydration is very poor. Clarity and health of the cornea is strongly dependent on its relative hydration levels. Furthermore, disruptions of corneal hydration levels are caused by endothelial pump functions of corneal dystrophies, causing swelling and immune responses of corneal graft rejections, inflammation, and edema. Because THz radiation is only sensitive to water, it can be used to provide hydration images of tissues. Early detection and intervention is possible by inspecting low hydration is the tissue. Several studies have shown evidence of variations in water content in several diseased tissues including basal cell carcinoma and breast cancer tumors. THz imaging was successfully used to observe variations in water concentration throughout different eye phantoms. These images confirm the ability of THz radiation to detect solely water content. Monitoring water content and deviations from normal hydration may have significant advantages for diagnosing and disease monitoring in various corneal pathologies including dystrophies, infection, degeneration, inflammation, and graft rejection. Future works include THz imaging for arthritis in bone joints and Traumatic Brain Injury (TBI) detection from corresponding changes in swelling throughout the body. I would like to thank James Che and Harsha Kittur for all of their advice and support throughout this entire research project. I would also like to thank Mr. William Herrera for giving me this amazing opportunity. I would also like to thank all the graduate and post doctorate scholars for teaching me and allowing me to work in their lab. Discussion The system optics were designed to test a new imaging technique for non-planer surfaces. This technique projects a spherical surface onto a Cartesian plane using off-axis parabolic (OAP) mirrors. Conclusion Acknowledgments A series of calibration and test images were taken to evaluate imaging performance The images shown were obtained over an approximate 3- week period. Our objective was to obtain uniform signal strength throughout the entire imaging field while maximizing the amount of signal strength received (Figures 8.1) . Misalignment of the mirrors and calibration often prevented this uniformity. Figures 8.2-8.4 show images of a spherical brass ball. The “hot spots” towards the center of the image indicate a stronger signal strength. After greater uniformity was obtained, patterns of greater specificity were able to be imaged. In figures 8.5-8.7 are images of the brass spherical balls with foil tape attached in a specific pattern. These stripe-like patterns successfully corresponded with the brighter regions of the images. Figure 8.8 is an image of a spherical brass ball with a contact lens attached. The brighter region in the center indicates a greater hydrated region. Hydration variations are crucial to understanding the health of biological tissues. Medical imaging using terahertz radiation can detect these variations of water content. Currently, THz medical imaging is challenged by low available signal and limited imaging components in the THz band. Therefore, imaging studies had been limited to ex vivo, flattened targets, resulting in distortion of the natural structural and chemical composition of these biological tissues. This study aims to image along the curvature of live human corneal tissues with off-axis parabolic (OAP) mirrors. Uniform strength at a normal incidence was achieved as the THz radiation illuminated on the entire spherical surface of the eye phantoms. The images obtained were successfully used to detect trends in hydration variations of the target. Ultimately, we aim to utilize this imaging modality in a clinical setting in order to deliver fast, accurate pre-surgical images and diagnoses. Abstract Figure 1. (THz) radiation lies on the electromagnetic spectrum range from 300 GHz to 3 THz. [2] Figure 2. THz image of basal cell carcinoma tissue [3] Figure 3. THz image of a breast cancer tumor [4] THz device and imaging engineering are continuing field of research. Rigorous imaging optics alignment, optimized signal acquisition methods, and streamlined optical design will improve image quality and acquisition time. This imaging system will be used to image in-vivo ocular tissue in animals and humans. Clinical studies must follow to test the effectiveness of THz hydration imaging of the cornea. Future Work A THz imaging system for corneal hydration sensing was constructed . Characterization experiments were then performed. The construction of the THz imaging system employs Narrowband solid-state THz source Diode-based THz detectors Mirror-based THz optics Optical system calibration and alignment are aided with visible lasers to visually inspect the beam’s path and optimize imaging performance. Figure 4. A block diagram of a reflective THz imaging system developed for hydration sensing. Working at a frequency of approximately 650 GHz Figure 5. Overall construction of the system and an example of visible laser alignment tool developed. System dimension measures 1ft x 1 ft x 2ft in the prototype stage, and can be further compacted to < 1 ft 3 Illumination strength variations are computed with MATLAB, with percent error of ~10% Illumination Imaging field strength Test images of mock eye targets i.e a polypropylene ball with different foil tape patterns . Also shown is an example of an under sampled image. Figure 8.1 Figure 8.2 Figure 8.3 Figure 8.4 Figure 8.7 Figure 8.5 Figure 8.6 Test images of eye surface using a reflective target, with better optical alignment Materials and Methods (cont.) We obtained images along the curvature of the eye while maximizing the amount of signal strength received. Figure 7 The anatomy of the human eye Terahertz Imaging of in vivo Corneal Tissue Hydration Contact lens seen by THz radiation displaying a region in the middle (where the lens was placed) with high signal) Figure 8.8 Expected signal strength: 1mW output with: mirror reflection loss <2% (x4) Signal modulation loss – 2/π 2 x 100 % Curvature: Cornea ~ 6.5mm Sclera ~ 10.8 mm 1.Tonouchi, Cutting Edge Terahertz Technology, Institute of Laser Engineering, Osaka University, Journal, 2007. 2. Terahertz Technology-Properties of Terahertz Radiation. Digital image.Toptica. N.p., n.d. Web. 3. Wallace, et. alt., Terahertz pulsed imaging of basal cell carcinoma ex vivo and in vivo, British Journal of Dermatology, Journal, 2004. 4. Fitzgerald, et. alt., Terahertz Pulsed Imaging of Human Breast Tumors, RSNA Radiology, Journal, 2006. 5. Researchers Regrow Human Corneas: First Known Tissue Grown from a Human Stem Cell. Digital image. Internet Medicine. N.p., 5 July 2014. Web. References 5 .60 Figure 6. An eye piece designed in SolidWorks to hold the target for imaging. Prototype is fabricated with a 3D printer, and tested in the imaging experiment.

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Page 1: Terahertz Imaging of in vivo Corneal Tissue Hydrationesc.seas.ucla.edu/wp-content/uploads/esc/Courtney_Final_Poster.pdfTHz device and imaging engineering are continuing field of research

Introduction and Background

A reflective THz imaging system developed for hydration sensing.

Materials and Methods

Courtney Shen1,2, Shijun Sung1, Warren S. Grundfest1,2,3

1. Department of Electrical Engineering, University of California, Los Angeles (UCLA), 2. Department of Bioengineering, UCLA3. Center for Advanced Surgical and Interventional Technology (CASIT), Department of Surgery David Geffen School of Medicine, UCLA

Results Eyes are the most immune-privileged carefullyregulated organ. Hydration levels of the eye iscarefully regulated, especially in the cornea whichprovides most of it’s focusing power and visualacuity. Current methods to measure the hydrationlevels of the eye include central corneal thicknessmeasurements with ultrasound. However, the levelof precision with cornea thickness and hydration isvery poor. Clarity and health of the cornea is stronglydependent on its relative hydration levels.Furthermore, disruptions of corneal hydration levelsare caused by endothelial pump functions of cornealdystrophies, causing swelling and immune responsesof corneal graft rejections, inflammation, and edema.

Because THz radiation is only sensitive to water, itcan be used to provide hydration images of tissues.Early detection and intervention is possible byinspecting low hydration is the tissue.

Several studies have shown evidence of variations inwater content in several diseased tissues includingbasal cell carcinoma and breast cancer tumors.

THz imaging was successfully used to observe variations inwater concentration throughout different eye phantoms.These images confirm the ability of THz radiation to detectsolely water content. Monitoring water content and deviationsfrom normal hydration may have significant advantages fordiagnosing and disease monitoring in various cornealpathologies including dystrophies, infection, degeneration,inflammation, and graft rejection. Future works include THzimaging for arthritis in bone joints and Traumatic Brain Injury(TBI) detection from corresponding changes in swellingthroughout the body.

I would like to thank James Che and Harsha Kittur for all of their advice and supportthroughout this entire research project. I would also like to thank Mr. William Herrerafor giving me this amazing opportunity. I would also like to thank all the graduate andpost doctorate scholars for teaching me and allowing me to work in their lab.

Discussion

The system optics were designed to test a new imagingtechnique for non-planer surfaces. This techniqueprojects a spherical surface onto a Cartesian plane usingoff-axis parabolic (OAP) mirrors.

Conclusion

Acknowledgments

• A series of calibration and test images were taken to evaluate imaging performance

The images shown were obtained over an approximate 3-week period. Our objective was to obtain uniform signalstrength throughout the entire imaging field whilemaximizing the amount of signal strength received(Figures 8.1) . Misalignment of the mirrors and calibrationoften prevented this uniformity. Figures 8.2-8.4 showimages of a spherical brass ball. The “hot spots” towardsthe center of the image indicate a stronger signalstrength. After greater uniformity was obtained, patternsof greater specificity were able to be imaged. In figures8.5-8.7 are images of the brass spherical balls with foiltape attached in a specific pattern. These stripe-likepatterns successfully corresponded with the brighterregions of the images. Figure 8.8 is an image of aspherical brass ball with a contact lens attached. Thebrighter region in the center indicates a greater hydratedregion.

Hydration variations are crucial to understanding the health of biologicaltissues. Medical imaging using terahertz radiation can detect thesevariations of water content. Currently, THz medical imaging is challengedby low available signal and limited imaging components in the THz band.Therefore, imaging studies had been limited to ex vivo, flattened targets,resulting in distortion of the natural structural and chemical compositionof these biological tissues. This study aims to image along the curvature oflive human corneal tissues with off-axis parabolic (OAP) mirrors. Uniformstrength at a normal incidence was achieved as the THz radiationilluminated on the entire spherical surface of the eye phantoms. Theimages obtained were successfully used to detect trends in hydrationvariations of the target. Ultimately, we aim to utilize this imaging modalityin a clinical setting in order to deliver fast, accurate pre-surgical imagesand diagnoses.

Abstract

Figure 1. (THz) radiation lies on the electromagneticspectrum range from 300 GHz to 3 THz. [2]

Figure 2. THz image of basalcell carcinoma tissue [3]

Figure 3. THz image of abreast cancer tumor [4]

THz device and imaging engineering are continuing field ofresearch. Rigorous imaging optics alignment, optimized signalacquisition methods, and streamlined optical design willimprove image quality and acquisition time. This imagingsystem will be used to image in-vivo ocular tissue in animalsand humans. Clinical studies must follow to test theeffectiveness of THz hydration imaging of the cornea.

Future Work

A THz imaging system for corneal hydration sensing wasconstructed . Characterization experiments were thenperformed.

The construction of the THz imaging system employs• Narrowband solid-state THz source• Diode-based THz detectors• Mirror-based THz opticsOptical system calibration and alignment are aided withvisible lasers to visually inspect the beam’s path andoptimize imaging performance.

Figure 4. A block diagram of a reflective THz imaging systemdeveloped for hydration sensing. Working at a frequency ofapproximately 650 GHz

Figure 5. Overall constructionof the system and an exampleof visible laser alignment tooldeveloped. System dimensionmeasures 1ft x 1 ft x 2ft in theprototype stage, and can befurther compacted to < 1 ft3

Illumination strength variations are computed with MATLAB, with percent error of ~10%

Illumination Imaging field strength

Test images of mock eye targets i.e a polypropylene ball with different foil tape patterns . Also shown is an example of an under sampled image.

Figure 8.1

Figure 8.2 Figure 8.3 Figure 8.4

Figure 8.7Figure 8.5 Figure 8.6

Test images of eye surface using a reflective target, with better optical alignment

Materials and Methods (cont.)

We obtained images along the curvature of the eye while maximizing the amount of signal strength received.

Figure 7 The anatomy of the human eye

Terahertz Imaging of in vivo Corneal Tissue Hydration

Contact lens seen by THz radiation displaying a region in the middle (where the lens was placed) with high signal)

Figure 8.8

Expected signal strength: 1mW output with: • mirror reflection loss <2% (x4)• Signal modulation loss – 2/π2 x 100 %

Curvature:Cornea ~ 6.5mmSclera ~ 10.8 mm

1.Tonouchi, Cutting Edge Terahertz Technology, Institute of Laser Engineering, Osaka University, Journal, 2007.2. Terahertz Technology-Properties of Terahertz Radiation. Digital image.Toptica. N.p., n.d. Web. 3. Wallace, et. alt., Terahertz pulsed imaging of basal cell carcinoma ex vivo and in vivo, British Journal of Dermatology, Journal, 2004.4. Fitzgerald, et. alt., Terahertz Pulsed Imaging of Human Breast Tumors, RSNA Radiology, Journal, 2006.5. Researchers Regrow Human Corneas: First Known Tissue Grown from a Human Stem Cell. Digital image. Internet Medicine. N.p., 5 July 2014. Web.

References

5.60

Figure 6. An eye piece designed inSolidWorks to hold the target forimaging. Prototype is fabricated with a3D printer, and tested in the imagingexperiment.