1. Integrated Fluorescent Probe and Radiofrequency Ablator Rachel Riti and Alex Walsh Advisers: Bart Masters and Anita Mahadevan-Jansen Department of Biomedical Engineering, Vanderbilt Biomedical Optics Lab, Nashville, TN Radiofrequency ablation: high frequency electromagnetic waves heat tissue to detrimental temperaturesRadiofrequency ablation: high frequency electromagnetic waves heat tissue to detrimental temperatures Thermocouples on ends of RFA electrodes estimate temperature of ablated tissueThermocouples on ends of RFA electrodes estimate temperature of ablated tissue -Often inaccurate -Can only provide the temperature at electrode A non-invasive method for determining area of ablated tissue necessary for improved ablation techniquesA non-invasive method for determining area of ablated tissue necessary for improved ablation techniques RFA functionality not compromisedRFA functionality not compromised Optical fibers functional during RFAOptical fibers functional during RFA Probe entry not affectedProbe entry not affected Minimal attenuation of light through optical fibersMinimal attenuation of light through optical fibers Fluorescence measurements accurately indicate ablation areaFluorescence measurements accurately indicate ablation area -Determine margins of ablation within 10% INTRODUCTION DESIGNED PROBE CONCLUSIONS More than 500,000 cases of liver cancer per yearMore than 500,000 cases of liver cancer per year Half of all cancers result in liver metastases 1Half of all cancers result in liver metastases 1 Tumor recurrence rates of 4 to 19% have been reported following RFA procedures 2Tumor recurrence rates of 4 to 19% have been reported following RFA procedures 2 Thermocouples used in RFA probes determine temperature of ablated tissueThermocouples used in RFA probes determine temperature of ablated tissue -Thermal damage assessed by applying the temperature to an Arrhenius integral Heating power and ablation duration times cause varying results between patientsHeating power and ablation duration times cause varying results between patients Thermocouples are limited by accuracy of tissue-specific constants, which are different in individual patients 1Thermocouples are limited by accuracy of tissue-specific constants, which are different in individual patients 1 A feedback control that can accurately monitor thermal damage is neededA feedback control that can accurately monitor thermal damage is needed MOTIVATION ACKNOWLEDGEMENTS REFERENCES DESIGN CRITERIA 1. Lin W, Buttemere C, Mahadevan-Jansen A. “Effect of thermal damage on the in vitro optical and fluorescence characteristics of liver tissues.” IEEE J Sel Top Quant. 2003;9:162-170. 2. Buttemere C, Chari RS, Anderson CD, Washington MK, Mahadevan-Jansen A, Lin W. “In vivo assessment of thermal damage in the liver using optical spectroscopy.” J Biomed Opt. 2004;9:1018-1027. 3. Lakowicz, Joseph R. Principles of fluorescence spectroscopy. 3rd ed. Baltimore: Springer Science+Business Media, LLC, 2006. 4. Walsh A, Masters DB, Jansen ED, Welch AJ, Mahadevan-Jansen A. “The Effect of Temperature on Fluorescence: An Animal Study, Lasers in Surgery and Medicine.” Publishing Pending. 5. Masters DB, Walsh A, Welch AJ, Mahadevan-Jansen A, Jansen D. “Effects of temperature on fluorescence in human tissue.” Publishing Pending. PROPOSED REDESIGN What is Fluorescence? Emission of visible light by a substance that has absorbed light of a different wavelengthEmission of visible light by a substance that has absorbed light of a different wavelength -Absorption of a photon triggers emission of a photon with a longer wavelength 3 Why integrate Fluorescence with RFA? Temperature dependence of fluorescence has been demonstrated in various tissues 4,5Temperature dependence of fluorescence has been demonstrated in various tissues 4,5 Relationship suggests that changes in fluorescence signal of liver tissue can be used to quantify temperature as tissue is heated.Relationship suggests that changes in fluorescence signal of liver tissue can be used to quantify temperature as tissue is heated. By integrating fluorescence fibers with the RFA probe, the fluorescence of tissue can be measured and used to assess area of ablated tissueBy integrating fluorescence fibers with the RFA probe, the fluorescence of tissue can be measured and used to assess area of ablated tissue Fluorescence characteristics of liver change as thermal damage occursFluorescence characteristics of liver change as thermal damage occurs Using fluorescence to monitor ablation of a liver tumor will provide feedback indicative of tissue death and area of ablation 1Using fluorescence to monitor ablation of a liver tumor will provide feedback indicative of tissue death and area of ablation 1 FLUORESCENCE FUTURE DIRECTIONS a b c Figure 4. (a) Three-dimensional model of probe; electrodes (red) are surrounded by paired fibers (blue) at various distances from the probe end; (b) Cross section of probe; (c) Instrumentation diagram. Eight sets of two 100μm core fibers will surround the middle RFA electrode and exit the needle with the electrodes during RFA. The fiber pairs will be at varying lengths to for sampling of tissue death at different distances from the electrodes. Measurements from the fibers of varying lengths would be analyzed in a computer program to estimate the region of ablation. a b c Figure 1. (a) Three-dimensional model of probe; (b) cross section of probe; (c) instrumentation diagram. In this design, a 100μm core fiber is used for excitation with a 337nm pulsed nitrogen diode laser. Another 100μm core fiber is used for collection of the fluorescence signal. The fluorescence light collected is captured by a spectrometer and processed in a LabVIEW program. Figure 2. Fluorescence peak value as temperature increases. *Data collected using alternate probe Figure 3. Fluorescence spectra at selected temperatures. *Data collected using alternate probe Tissue degradation from fluorescence of liver tissue can be quantified in two ways:Tissue degradation from fluorescence of liver tissue can be quantified in two ways: -A percentage increase in fluorescence can potentially be used to determine an increase in temperature -The shift in peak position observed in the fluorescence spectra of temperatures above 54°C (Figure 3) can also be an indication of tissue death The preliminary design has shown that one 100μm core excitation fiber and one 100μm collection fiber are sufficient to measure fluorescenceThe preliminary design has shown that one 100μm core excitation fiber and one 100μm collection fiber are sufficient to measure fluorescence -By uniting this concept with fluorescence spectra found, 8 pairs of fibers at varying lengths will allow for optimization of volumetric determination of ablated tissue during RFA Examine electrical circuitry of electrodes of RFA probe to successfully house fibers within RFA needle without compromising efficiency of ablator and fibersExamine electrical circuitry of electrodes of RFA probe to successfully house fibers within RFA needle without compromising efficiency of ablator and fibers Reinforce fiber strength with additional cladding or jacket if fiber is unable to penetrate liver tissue without breakingReinforce fiber strength with additional cladding or jacket if fiber is unable to penetrate liver tissue without breaking -May require increased diameter of RFA needle Thanks to Dr. Mahadevan-Jansen, Chetan Patil, Bart Masters, Dr. Bob Galloway, and Dr. King for their help, support, and guidance. Thanks to the Vanderbilt Optics lab for all of their support. d = 2.1 mm d = 1.5 mm d = 0.35 mm d = 0.14 mm d = 1.5 mm d =.35 mm d = 2.1 mm