Integrated Fluorescent Probe and Radiofrequency AblatorIntegrated Fluorescent Probe and Radiofrequency AblatorRachel Riti and Alex WalshRachel Riti and Alex Walsh

Advisers: Bart Masters and Anita Mahadevan-JansenAdvisers: Bart Masters and Anita Mahadevan-JansenDepartment of Biomedical Engineering, Vanderbilt Biomedical Optics Lab, Nashville, TNDepartment of Biomedical Engineering, Vanderbilt Biomedical Optics Lab, Nashville, TN

• Radiofrequency ablation: high frequency electromagnetic waves heat Radiofrequency ablation: high frequency electromagnetic waves heat tissue to detrimental temperatures tissue to detrimental temperatures

• Thermocouples on ends of RFA electrodes estimate temperature of Thermocouples on ends of RFA electrodes estimate temperature of ablated tissueablated tissue

- Often inaccurateOften inaccurate- Can only provide the temperature at electrodeCan only provide the temperature at electrode

• A non-invasive method for determining area of ablated tissue A non-invasive method for determining area of ablated tissue necessary for improved ablation techniquesnecessary 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%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 metastasesHalf of all cancers result in liver metastases11 • Tumor recurrence rates of 4 to 19% have been reported following Tumor recurrence rates of 4 to 19% have been reported following

RFA proceduresRFA procedures22

• Thermocouples used in RFA probes determine temperature of Thermocouples used in RFA probes determine temperature of ablated tissueablated tissue- Thermal damage assessed by applying the temperature to an Thermal damage assessed by applying the temperature to an

Arrhenius integralArrhenius integral• Heating power and ablation duration times cause varying results Heating power and ablation duration times cause varying results

between patientsbetween patients• Thermocouples are limited by accuracy of tissue-specific constants, Thermocouples are limited by accuracy of tissue-specific constants,

which are different in individual patientswhich are different in individual patients11

• A feedback control that can accurately monitor thermal damage is A feedback control that can accurately monitor thermal damage is neededneeded

MOTIVATION

ACKNOWLEDGEMENTS

REFERENCES

DESIGN CRITERIA

1. Lin W, Buttemere C, Mahadevan-Jansen A. “Effect of thermal damage on the 1. Lin W, Buttemere C, Mahadevan-Jansen A. “Effect of thermal damage on the in vitroin vitro optical optical and fluorescence characteristics of liver tissues.” and fluorescence characteristics of liver tissues.” IEEE J Sel Top QuantIEEE J Sel Top Quant. 2003;9:162-170.. 2003;9:162-170.

2. Buttemere C, Chari RS, Anderson CD, Washington MK, Mahadevan-Jansen A, Lin W. “2. Buttemere C, Chari RS, Anderson CD, Washington MK, Mahadevan-Jansen A, Lin W. “ In In vivovivo assessment of thermal damage in the liver using optical spectroscopy.” assessment of thermal damage in the liver using optical spectroscopy.” J Biomed OptJ Biomed Opt. . 2004;9:1018-1027.2004;9:1018-1027.

3. Lakowicz, Joseph R. 3. Lakowicz, Joseph R. Principles of fluorescence spectroscopyPrinciples of fluorescence spectroscopy. 3rd ed. Baltimore: Springer . 3rd ed. Baltimore: Springer Science+Business Media, LLC, 2006.Science+Business Media, LLC, 2006.

4. Walsh A, Masters DB, Jansen ED, Welch AJ, Mahadevan-Jansen A. “The Effect of 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.” Temperature on Fluorescence: An Animal Study, Lasers in Surgery and Medicine.” Publishing Pending.Publishing Pending.

5. Masters DB, Walsh A, Welch AJ, Mahadevan-Jansen A, Jansen D. “Effects of temperature 5. Masters DB, Walsh A, Welch AJ, Mahadevan-Jansen A, Jansen D. “Effects of temperature on fluorescence in human tissue.” Publishing Pending.on fluorescence in human tissue.” Publishing Pending.

PROPOSED REDESIGN

What is Fluorescence?What is Fluorescence?• Emission of visible light by a substance that has absorbed light of a Emission of visible light by a substance that has absorbed light of a

different wavelengthdifferent wavelength- Absorption of a photon triggers emission of a photon with a longer Absorption of a photon triggers emission of a photon with a longer

wavelengthwavelength33

Why integrate Fluorescence with RFA?Why integrate Fluorescence with RFA?• Temperature dependence of fluorescence has been demonstrated in Temperature dependence of fluorescence has been demonstrated in

various tissuesvarious tissues4,54,5

• Relationship suggests that changes in fluorescence signal of liver Relationship suggests that changes in fluorescence signal of liver tissue can be used to quantify temperature as tissue is heated.tissue can be used to quantify temperature as tissue is heated.

• By integrating fluorescence fibers with the RFA probe, the By integrating fluorescence fibers with the RFA probe, the fluorescence of tissue can be measured and used to assess area of fluorescence of tissue can be measured and used to assess area of ablated tissueablated tissue

• Fluorescence characteristics of liver change as thermal damage Fluorescence characteristics of liver change as thermal damage occursoccurs

• Using fluorescence to monitor ablation of a liver tumor will provide Using fluorescence to monitor ablation of a liver tumor will provide feedback indicative of tissue death and area of ablationfeedback indicative of tissue death and area of ablation11

FLUORESCENCE FUTURE DIRECTIONS

ab c

Figure 4. (a) Figure 4. (a) Three-dimensional model of probe; electrodes (red) are surrounded by paired fibers (blue) Three-dimensional model of probe; electrodes (red) are surrounded by paired fibers (blue) at various distances from the probe end; at various distances from the probe end; (b) (b) Cross section of probe; Cross section of probe; (c) (c) Instrumentation diagram. Instrumentation diagram.

Eight sets of two 100Eight sets of two 100μμm core fibers will surround the middle RFA electrode and exit the needle with the m 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 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 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.analyzed in a computer program to estimate the region of ablation.

a b c

Figure 1. (a) Figure 1. (a) Three-dimensional model of probe; Three-dimensional model of probe; (b)(b) cross section of probe; cross section of probe; (c) (c) instrumentation instrumentation diagram. In this design, a 100μm core fiber is used for excitation with a 337nm pulsed nitrogen diode 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 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.collected is captured by a spectrometer and processed in a LabVIEW program.

Figure 2. Figure 2. Fluorescence peak value as Fluorescence peak value as temperature increases.temperature increases.*Data collected using alternate probe*Data collected using alternate probe

Figure 3.Figure 3. Fluorescence spectra at selected Fluorescence spectra at selected temperatures.temperatures.*Data collected using alternate probe*Data collected using alternate probe

• Tissue degradation from fluorescence of liver tissue can be quantified in two Tissue degradation from fluorescence of liver tissue can be quantified in two ways:ways:

- A percentage increase in fluorescence can potentially be used to A percentage increase in fluorescence can potentially be used to determine an increase in temperaturedetermine an increase in temperature

- The shift in peak position observed in the fluorescence spectra of The shift in peak position observed in the fluorescence spectra of temperatures above 54temperatures above 54°°C (Figure 3) can also be an indication of tissue C (Figure 3) can also be an indication of tissue deathdeath

• The preliminary design has shown that one 100μm core excitation fiber and The preliminary design has shown that one 100μm core excitation fiber and one 100μm collection fiber are sufficient to measure fluorescenceone 100μm collection fiber are sufficient to measure fluorescence

- By uniting this concept with fluorescence spectra found, 8 pairs of fibers By uniting this concept with fluorescence spectra found, 8 pairs of fibers at varying lengths will allow for optimization of volumetric determination at varying lengths will allow for optimization of volumetric determination of ablated tissue during RFAof ablated tissue during RFA

• Examine electrical circuitry of electrodes of RFA probe to successfully house Examine electrical circuitry of electrodes of RFA probe to successfully house fibers within RFA needle without compromising efficiency of ablator and fibers within RFA needle without compromising efficiency of ablator and fibersfibers

• Reinforce fiber strength with additional cladding or jacket if fiber is unable to Reinforce fiber strength with additional cladding or jacket if fiber is unable to penetrate liver tissue without breakingpenetrate liver tissue without breaking

- May require increased diameter of RFA needleMay require increased diameter of RFA needle

Thanks to Dr. Mahadevan-Jansen, Chetan Patil, Bart Masters, Dr. Bob Thanks to Dr. Mahadevan-Jansen, Chetan Patil, Bart Masters, Dr. Bob Galloway, and Dr. King for their help, support, and guidance.Galloway, and Dr. King for their help, support, and guidance.

Thanks to the Vanderbilt Optics lab for all of their support.Thanks to the Vanderbilt Optics lab for all of their support.

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Fluorescence Spectra of Liver Tissue at Selected Wavelengths

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