Photo-Thermal Coherent Confocal Microscope This work is supported in part by the Center for Subsurface Sensing and Imaging Systems, under the Engineering Research Centers Program of the National Science Foundation (Award Number EEC ). Enter text and box will expand Introduction Confocal microscopy has been shown to be useful in imaging skin slightly below the junction of the dermis and epidermis. However, the depth of imaging is a significant limitation. We present a novel concept designed both to improve the depth of penetration and to increase the information content of images obtained with a reflectance confocal microscope. Using an approach similar to opto- acoustics, we plan to explore the use of laser heating to generate tissue expansion, which will be measured by the microscope. The microscope will incorporate a pulsed heating laser along the same optical path as the imaging laser in order to generate localized heating. This will result in periodic thermal expansion and contraction at the focus. Optical quadrature detection is used to measure the phase of the scattered light, and Doppler techniques will be employed to quantify the thermal expansion. For the purposes of imaging, two lasers of different wavelengths will be needed to resolve phase ambiguities in the expansion measurement. The motion resulting from thermal expansion will provide additional discrimination against multiply scattered light. It will also provide a measurement of a mechanical parameter, the coefficient of thermal expansion, which may aid in the characterization of different types of tissue. Abstract  Confocal Microscopy provides resolutions down to 1μm but has limited depth penetration due to multiple scattering. Beyond 100 μm depth, signal to clutter ratio becomes too small 1.  Optical coherence tomography (OCT) uses coherent detection and has deeper penetration than confocal microscopy, but the resolution is not suitable to view cellular structure 2.  The Photo-Thermal Microscope provides a method to provide deeper penetration while maintaining the spatial resolution of confocal microscopy in applications such as skin imaging. State of the Art Sean Sullivan and Charles DiMarzio Optical Science Laboratory, Northeastern University, Boston, MA [1] J. B. Pawley, ed., “Handbook of Biological Confocal Microscopy”, 3rd ed. (Plenum, New York, 1996). [2] A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, “Optical coherence tomography-principles and applications”, Rep. Prog. Phys. 66 (2003) [3] D. O. Hogenboom, and C. A. DiMarzio, “Quadrature Detection of a Doppler Signal”, Applied Optics, 37(13), page 2569, PI CONTACT INFORMATION Prof. Charles A. DiMarzio, Northeastern University Phone: References  Increase depth of penetration.  Filter out the out of focus scattered light.  Increase information content by quantifying the coefficient of thermal expansion. Goals Condenser Lens Objective Lens Point Source of Light Point Detector Aperture In-focus plane containing illuminated spot Out-of-focus Planes Preliminary Results  The pulsed heating laser directed along the same path as the imaging laser creates thermal expansion at the focus (shown above).  A computer simulation of this process is shown at the upper right, where a pulse excites an expansion to either side of the focus.  Using signal processing and Doppler techniques 3, static scatterers away from the focus are filtered from dynamic scatterrers at the focus. Concept of Photo-Thermal Microscope Temperature (mK) Distance (µm) Heat Source (W/m) Time (µsec) Distance (µm) Temperature Change (mK) Time (µsec) Temperature (mK) Divergence of Position (µm) Time (µsec) Temperature (mK) Radial Distance (µm) Unidirectional Position Change (µm) Time (µsec) Temperature (mK) Distance (µm) The above microscope layout incorporates both heating and imaging lasers. The two combined beams are focused onto the sample, shown in pink. The back-scattered light from the sample returns along the same path until it is separated from the incoming beam at the 50/50 beam splitter, and directed towards the I and Q detectors. Using optical quadrature detection, the phase information can be extracted by mixing the reference beam with the backscattered light. Using Doppler techniques, the thermal expansion at the sample can then be measured using the phase changes for the imaging wavelength. Photo-Thermal Coherent Confocal Microscope Layout Q Detector I Detector PBS QWP 45° Dichroic Heating Laser Laser Controller Imaging Laser M1 M2 M3 50/50 BS POL 45° Objective Lens Oscilloscope Pinhole  A second imaging laser will be added in order to eliminate phase ambiguities.  Scanning instrumentation will be added to produce three-dimensional images.  OQM configuration will be added to eliminate the DC terms of the interference. Future Work Our laboratory collaborates with skin-cancer researchers at Memorial Sloan Kettering Cancer Center, and with a manufacturer of commercial confocal microscopes. Members of these groups meet formally twice a year, and informally several times. The present research has been presented at these meetings and, if it proves successful, portions of it will be selected for development and technology transfer. Technology Transfer Significance to CenSSIS