An optical spectroscopy approach is demonstrated allowing for critical parameters during RF ablation of cardiac tissue to be evaluated in real time. The method is based on incorporating in a typical ablation catheter transmitting and receiving fibers that terminate at the tip of the catheter. By analyzing the spectral characteristics of the NIR diffusely reflected light, information is obtained on such parameters as, contact of catheter with the tissue, lesion formation, depth of penetration of the lesion, formation of char and coagulum during the ablation.
©2008 Optical Society of America
The most frequent cause of cardiac arrhythmias is an abnormal routing of electrical signals generated in the endocardial tissue near the atrial or ventricular walls. Catheter ablation can be used to treat cases when arrhythmia cannot be controlled with medication, or in patients that cannot tolerate these medications. Using an ablation catheter or similar probe having an energy-emitting element, usually in the form of Radiofrequency (RF) energy [1–3], a sufficient amount of energy in the location of suspected centers of this electrical misfiring is delivered leading to the formation of a lesion. These lesions are intended to stop the irregular beating of the heart by creating non-conductive barriers between regions of abnormal electrical activity . Successful treatment depends on the location of the ablation within the heart as well as the spatial characteristics of the lesion.
Attaining contact of the catheter with the tissue is critical for the formation of the lesion. Various methods have been explored as means to provide confirmation of establishing a proper contact during surgery including monitoring of the electrical impedance between the catheter electrode and the dispersive electrode (which utilizes the difference in resistivity between blood and endocardium) and the temperature at the tip of the catheter [5–7]. However, in current practice these methods do not provide a reliable tool to determine proper contact of the catheter with the tissue. As a result, experience and skill of the electrophysiologist performing the procedure play a major part on the clinical outcome.
The effectiveness of lesion therapy is evaluated by a post ablation monitoring of the electrical signals produced in the heart. If it is determined that signals responsible for arrhythmia are still present (suggesting that the lesion was not adequately formed), additional lesions can be created to form a line of lesions to block passage of abnormal currents. However, there is currently no method to assess in real time how the lesion is formed. The ablation process can also cause undesirable side-effects such as charring of the tissue, localized blood coagulation, and vaporization of tissue water that can lead to steam pocket formation and subsequent implosion (steam pop) that can cause severe complications [8,9].
All these side effects can be mitigated by adjusting the RF power of the catheter if the operator was aware of their development [10,11]. Clearly, limited to post ablation evaluation is undesirable since correction requires additional medical procedures while the surgeon has minimal knowledge regarding the development of undesirable ablation side effects. Thus, there is a need for the development of a guidance tool that could help evaluate the lesion in real time as it is being formed in the tissue.
Thermal coagulation of myocardium leads to significant changes in its optical properties [12–16]. For the case of myocardium coagulation via RF ablation, Swartling et al reported that the changes in the optical properties in the near infrared (NIR) spectral region include an increase of the scattering coefficient (≈ 5% higher), a smaller decrease in the scattering anisotropy factor (≈ 2% lower) and an increase in the absorption coefficient (≈ 20% higher) . We hypothesized that these changes in the optical properties of the RF ablated cardiac tissue can be used to provide in vivo monitoring of lesion formation parameters. Considering that absorption by blood and myocardium in the NIR spectral region is minimal, we postulated that in vivo monitoring may be based on NIR light scattering spectroscopy. Such a method could be employed through the vascular system, preferably as a fiber-optic attachment to the RF ablation catheter.
In this work, we present a pilot study of a method for the evaluation of lesion formation via RF ablation in real-time using near infrared (NIR) light scattering spectroscopy. The ablation catheter was modified to incorporate spatially separated light emitting and receiving fibers that are in contact with the tissue as the lesion is formed at the tip of the catheter. Spectral analysis of the light collected by the receiving fiber allows detection of key parameters such as, contact of the catheter with the tissue, onset of lesion formation, depth of penetration of the lesion and, formation of char or coagulum during the ablation.
2. Experimental method
The experimental arrangement is depicted in Fig. 1. Three fresh bovine hearts obtained from a meat processing facility were used to obtain the experimental results shown in this work (Figs.4–7). From each heart, samples were procured with approximate dimensions of 10 cm × 5 cm × 2 cm. Ablations were performed in the central region of each sample keeping a distance of about 2 cm from the edges of the sample. In addition, the spatial separation between ablations performed on the same sample was about 2 cm. The samples were positioned in a holder at the bottom of a container filled with either saline solution or heparinized bovine blood. A circulation and heating system was used to sustain a flow around the sample and maintain a constant temperature of 36 degrees Celsius. The RF ablation catheter was positioned vertically in the surface of the sample and kept at the fixed location during each ablation via a specially designed holder. This holder also enabled the application of a constant contact force of the catheter on the tissue surface at 10 g chosen to simulate typical conditions during in vivo applications.
A schematic diagram of the catheter tip is also shown in Fig. 1. The catheter was custom made and involved an open irrigation design . However, no irrigation was used during our experiments to allow the development during ablation of a monotonically decreasing tissue temperature with distance from the tip of the catheter (open irrigation causes cooling of the surface and temperatures below the surface can be higher). This catheter contained two fibers, 200 µm in diameter. The fibers were terminating at diametrically opposite sites at the distal end of the catheter with their tips aligned with the catheter’s outer metallic surface. The lateral separation between the fibers was 1.7 mm as depicted in Fig. 1. The first (illumination) fiber was connected to a white light source after passing through a 600 nm long wavelength pass filter. The second (collection) fiber was coupled to a spectrograph to analyze and record the spectrum of the scattered light from the tissue. In this way, a sequence of spectra was acquired at a rate of one spectrum per second. The tissue was ablated for periods of time ranging between 30 sec and 90 seconds. Variable settings in the RF power generator created lesions of various depths and depth formation rates. After the experiment, the tissue was dissected to determine the final depth of the lesion via visual inspection and measurement.
3. Experimental results
Figure 2 shows a sequence of spectra obtained prior to, during and after ablation that resulted in a lesion that was 2 mm in depth. The onset and termination of RF power delivery are denoted with “START” and “STOP”, respectively. These spectra represent raw data and have not been normalized for instrument response. The spectra allow to directly appreciate the changes in intensity and spectral characteristics of the scattered light as collected by the receiving fiber occurring during tissue ablation. With the termination of the ablation, there is no additional change observed in the spectrum indicating that the changes in the spectral profile are permanent.
To better quantify these changes, the as recorded spectra were normalized (divided) to the spectrum recorded just before the RF power was turned on. Thus, at the onset of ablation the normalized intensity is about 1 (within the noise of the measurement) through the entire spectral range. Figure 3 illustrates a typical example of the evolution of the spectral profile after normalization during an ablation that resulted to the formation of a 5 mm deep lesion. For clarity, spectral profiles recorded every 5 seconds from the onset of ablation are shown in Fig. 3 and selected corresponding times from onset of ablation (t=0) are provided on the right hand side. There are two characteristic changes in the evolution of the spectral profile of the detected scattered light during lesion formation: a) The intensity of the signal increases with time duration of RF energy deposition and lesion formation; b) The ralative increase in signal intensity is larger for longer wavelengths leading to a change in the slope of the spectral profile from its original horizontal direction towards 45 degrees.
An increase in signal intensity and slope with increasing ablation time was noted in over 100 ablations we performed in every site tested in tissues obtained from different bovine hearts. The increase of the signal intensity after the RF power was turned on provided a clear indication in real time that a lesion started forming. Since both, the intensity and the slope of the normalized spectral profile change during ablation, we explored if these optical “fingerprint” parameters can be used to develop a method to assess the depth of the lesion in real time. A preliminary analysis of the results suggested that there is a tissue dependant variability in the measured absolute value of the intensity (as discussed in more detail later). In addition, motion of the heart and unstable contact of the catheter with the surface of the tissue could make a measurement of the absolute intensity very challenging in a clinical environment. On the other hand, the slope of the normalized spectral profile is independent of the absolute intensity of the signal and may possibly provide more reliable optical signature of the lesion formation parameters.
To test this concept, we performed a set of measurements with the tissue sample inside a blood bath (21 ablations) and in saline solution (47 ablations). From the normalized spectra, we calculated the ratio of the spectral intensity at 910 nm over that at 710 nm. This quantity is referred to in the rest of this document as “slope”. We then plotted the value of the slope at the end of each ablation as a function of the final lesion depth. The data were obtained from lesions formed using different ablation times and power settings resulting on wide range of lesion depths. The results obtained in blood bath were similar to those obtained in saline solution indicating that the blood does not affect the measured spectral ratio.
Figure 4(a) summarizes our experimental results showing the depth of the ablated tissue and the corresponding slope of the accompanying spectral profile. The results are plotted in increments in depth of 0.5 mm representing the accuracy in the measurement of the lesion’s depth. These results indicate a monotonic relationship between these two parameters for lesion depths up to about 6 mm. Above 6 mm depth, the experimental error increases significantly in part for reasons that will be discussed later. To better analyze the dependence of the slope on lesion depth, the average value of the slope was calculated for lesion depths that contained more than 4 data points (obtained in both, saline or blood). The results are summarized in Fig. 4(b) where the average values of the slope along with the corresponding standard deviation are shown. Best fit of these data was obtained using a second order polynomial shown in Fig. 4(b) as a solid line.
The change of the slope during ablation can provide additional information. Figure 5 shows the slope as a function of time during 5 different ablations that resulted to formation of lesions with depths of about 1 mm, 2 mm, 4 mm, 6 mm and 8 mm. This figure clearly illustrates the dependence of the rate that slope change on the catheter power settings stemming from corresponding changes in the rate of lesion formation. Within each individual time profile of the slope during ablation, the change in the value of the ratio is smooth. This suggests that the larger spread in the results around a mean value for each depth shown in Fig. 4 is due to tissue variability and not to experimental error arising form the instrumentation. From this type of data, one can extract the rate of tissue ablation since the slope is related to the depth of the lesion as shown in Fig. 4. This can be particular important for deeper lesions where direct measurement of the depth using the fibers may be impossible. More specifically, initial results suggest that measurements of the slope enable prediction of the final lesion depth, for lesions up to 6 mm (in the bovine tissue used in this experiment) as demonstrated in Fig. 4. However, by measuring the rate of tissue ablation during the initial 6 mm (as it can be deduced from the rate of the change of the measured “ratio” for values smaller than about 2.2), one can extrapolate the ablation time needed to create lesions of larger depth.
For higher power setting of the RF generator and/or longer ablation times, we frequently observed in the post-ablation examination of the tissue sample the presence of tissue charring or blood coagulum . These undesirable during surgery side effects of the ablation process consistently resulted in a change in the detected light scattering spectral profile. Figure 6 shows typical examples of the normalized spectra in the presence of coagulum and charring formed during ablations that resulted in about 7 mm deep lesions. These spectra were selected from a set of over 30 examples produced during the set of measurements to obtain Fig. 4 and subsequent measurements to reproduce these effects. The spectrum obtained in the presence of coagulum contains two valleys located at about 775 nm and 865 nm. This indicates the presence of two absorption peaks at these spectral locations arising from the optical properties of the coagulum. The spectrum in the presence of charring is similar to that of coagulum but it contains only the first absorption peak at 775 nm. However, it is evident by the lower values of the normalized ratio at the shorter wavelengths in the spectral region covered in Fig. 6 (compared to that suggested by results shown in Fig. 3), there is an underlying broader absorption spectral band for both, tissue charring and coagulum. These characteristic spectral features indicate the feasibility to provide in real time information to the operator to detect the onset of tissue charring or formation of blood coagulum during ablation so that appropriate action can be taken to stop further development.
The results discussed above were obtained using the same catheter depicted in Fig. 1. The repeated use of the catheter to deliver RF energy to the tissue could potentially alter the optical parameters of the system, including the light throughput of the fibers and the spectral response. To address this issue, we further analyzed measurements obtained from a sequence of ablations performed on different samples procured from the same bovine heart. Specifically, we utilized the spectra obtained at the onset of each new ablation and before the RF energy was turned on to examine a) the as recorded intensity of the scattered light and b) the ratio of the signal intensity at the wavelengths used to calculate the slope. Figure 7 summarizes the results obtained from a sequence of 50 measurements performed in saline solution. The results are plotted as a percent difference of the values obtained from each measurement compared to the average value from all 50 measurements. The intensity of the collected signal is represented by the intensity at 710 nm and the corresponding results are shown in Fig. 7 as open diamonds. It can be appreciated that the signal intensity from point to point varies significantly, even between neighboring points. When the ratio of intensities at 910 nm and 710 nm is analyzed in the same manner, a much smaller deviation (on the order of 3%) from the average value is observed as shown in Fig. 7 with solid circles. However, fitting of the latter set of data with a line indicated a small increase over time suggesting that the spectral response of the fibers in the catheter slightly changes with repeated ablations. This issue should not be of concern in a clinical setting because the ablation catheters are designed for single use.
The method used to normalize the spectra (see Fig. 3) by division of each spectrum recorded during ablation to that recorded just before the RF power is turned on introduces a systematic noise in the normalized spectra arising from the noise of the reference spectrum. This can be avoided by averaging over a number of spectra prior to the onset of RF ablation. However, we chose this method in order to highlight that the significant changes in the spectral characteristics are directly observable from raw data, as might be needed if this method is implemented in a clinical setting where data must be displayed in real time. Furthermore, the quantification of the spectral changes performed in this work via the use of the ratio of the intensity at two wavelengths can be more detailed involving the use of fitting parameters to the entire spectral profile. However, the use of the spectral ratio approach was motivated by the significant hardware simplifications in future implementation of this method where the spectrometer and white light source could be replaced by photodiodes and illumination in distinct wavelengths as discussed in more detail later.
The ex-vivo experimental results discussed in this work suggest that NIR light scattering spectroscopy implemented via optical fibers positioned at the tip of the RF ablation catheter can provide in real time information that is directly related to the lesion formation parameters. We will next discuss in greater detail these parameters and how they can address current unmet needs in a clinical setting.
4.1 Establishing contact of catheter with the tissue
The detected signal intensity when the catheter is inside blood but not in contact with tissue increases by approximately a factor of 2 when contact is established. This observation is very repeatable and may be useful as a complementary guidance tool during navigation of the catheter through the heart’s compartments to the target location. Currently, the operator uses rotational movements and pressure to ensure proper contact of the tip of the catheter with the tissue.
4.2 Detection of onset of ablation
The results shown in Figs. 2 through 5 demonstrate that the onset of ablation is accompanied by a sharp rise in the detected signal intensity as well as a change in the slope. In a clinical setting, this can provide direct information that the energy is delivered properly on the target location and the lesion is forming. Currently, feedback to the physician is provided by the shift in impedance and increase in temperature . These parameters are readily available to the operator in current high-end instrumentation but provide indirect information since, for example, the temperature of the tip (or impedance) can increase upon RF energy delivery without proper contact of the catheter with the tissue.
4.3 Assessment of lesion depth
As discussed earlier, there is currently no method to assess the depth of the lesion. The results shown in Figs. 4 demonstrate that using a spectral ratio method such as that adopted in this work (defined here as the “slope” of the spectral profile) leads to a parameter that monotonically changes with the depth of the RF ablation lesion. We postulate that this can be used to develop a calibration method that will enable an estimation of the spatial characteristics of the lesion in real time. The mechanism that leads to the relationship of the spectral characteristics of the detected scattered light to lesion depth may be complex. The change in the optical properties of the ablated tissue as described in references 12–17 is a major part of this mechanism and best explains the increase in the scattering intensity with the formation of the lesion. In addition, the dependence of the scattering coefficient of the normal and ablated tissue on the wavelength of the light can introduce spectral changes that depend on the tissue or lesion depth. These changes can be revealed by a spectral ratio technique as discussed in references 19 and 20. Due to the complexity of this issue, we will limit the discussion in this report to only the presentation of our experimental findings.
4.4 Assessment of rate of lesion formation
If the method to translate the spectral information in to lesion depths is validated, it will enable monitoring in real time the rate by which the lesions depth increases as demonstrated in Fig. 5. This information may be valuable in various ways. For example, as discussed in the previous section, this method is sensitive to ablation lesion depths up to approximately 6 mm for the tissue model used in this work. If a lesion with final depth larger than that is required, monitoring the rate by which the lesion is created at the early stages can help project the time needed to continue the ablation in order to achieve the desired final depth. In addition, a high lesion formation rate may be an early warning signal that energy is delivered at a higher rate than that required to avoid overheating of the tissue that can lead to steam pop formation (an issue that is discussed in more detail later).
4.5 Detection of tissue charring and blood coagulation
Tissue charring and thrombus of blood coagulation are undesirable side-effect during RF ablation procedures. These changes take place in the area adjacent to the catheter and as a result, they can strongly affect the spectral characteristics of the detected signal. The characteristic changes of the normalized spectral profiles shown in Fig. 6 demonstrate that this method offer a way to detect the presence of tissue charring or blood coagulation. Preliminary experiments showed that thrombus can be detected even if small quantities were found during the post-examination of the ablated area. Similarly, the detection of charring was possible even when a very small amount was visible by the naked eye in the location of lesion formation during post-examination. The most profound change in the spectral characteristics due to the formation of charring or blood coagulation is the reduction of the signal intensity at shorter wavelengths. This led to a lower value of the normalized intensity in the 700 nm–800 nm spectral range. During our experiments, this signal decline was clearly observable at later times of ablation with higher RF power settings following a “normal” increase in the signal (such as that shown in Fig. 2) in the early part. The origin of this change in the spectral profile is likely a broad absorption band resulting from coagulation of hemoglobin (and corresponding changes in myoglobin) . The narrower in spectral range absorption bands centered at 775 nm and 865 nm as observed in Fig. 6 may be secondary specific features of this broader absorption band associated with coagulation of hemoglobin (both bands) and myoglobin (the 775 nm only)
The reduction in signal intensity at shorter wavelengths due to this absorption band affects the evaluation of the lesion depth as performed in this work through the utilization of the slope of the normalized spectrum. Therefore, a correction factor must be devised to account for the change in the slope in order to accurately evaluate the lesion depth in the presence of spectral characteristics from charring on coagulation. It must be emphasized that in clinical practice the tissue temperature is typically monitored to avoid coagulation affects. It is therefore expected that this issue will represent only a small fraction of the procedures and when it occurs, this method provides the means to be recognized early and mitigated via changes in the RF generator power settings. In current clinical practice, there is no information available to the operator regarding the development of these important side effects which may remain undetected until there are symptomatic evidence.
The experimental results presented in this work also suggest the potential of this methodology to address two additional currently unmet needs in a clinical setting:
4.6 Finding location of pre-existing lesion
The difference in signal intensity when the catheter is in contact with normal tissue compared to that when the catheter is in contact with an ablation lesion can be as high as a factor of 2 or larger as demonstrated in Fig. 3. Furthermore, the slope of the spectral profile as defined in the previous section changes significantly (see Figs. 4 and 5) providing an additional method to accurately detect contact with a preexisting lesion if a follow up ablation is needed in the same location. It is also possible to use the spectral information to detect contact with abnormal tissue. Specifically, comparison of the as detected spectrum to that of healthy and ablated tissue may yield information to identify locations of tissue alteration (such as calcification) due to pre-existing health conditions. Such conditions may lead to cardiac arrhythmia and thus, detecting the abnormal tissue regions can assist in guiding the catheter to the location that needs to be ablated. Although this novel aspect has not been explored in the current study, the potential of this method to execute such a task is apparent if the pre-existing condition causes alteration of the optical properties in the NIR of the affected tissue region.
4.7 Detection of precursors to steam-pop formation
One of the most dangerous side effects of RF ablation is explosive release of gas resulting from excessive heating of the tissue, also referred to as steam pop formation. It is believed that an early sign of tissue overheating that can lead to an explosive release of gas is formation of “microbubbles” [22–24]. The onset of microbubble formation can be as early as about 1 minute prior to explosive release  thus, the development of this process is slow. Such microbubbles will induce large changes in the index of refraction within the tissue thus affecting the scattering of light traveling from the illumination fiber towards the receiving fiber. In turn, this could yield a change (decrease?) in the signal intensity through the entire spectral range of detection. Due to the slow development of this process and its probabilistic nature , an extensive study is required to validate this hypothesis under relevant conditions which is outside the focus of this report.
Ultrasound and magnetic resonance techniques are currently under investigation for the evaluation in real time of lesion formation parameters during RF ablation [26, 27]. Arguably, the optical spectroscopy method described in this work offers a most attractive approach providing monitoring of multiple parameters of lesion formation. In addition, this method is compatible with existing catheter designs.
To transfer this technology in a clinical setting, various modifications are needed for two main reasons. First, the target location is in a moving organ. Second, the catheter is not always positioned vertically with respect to the surface of the tissue. To address the first issue, signal registration issues need to be addressed via synchronization and phase-locking of signal collection to cardiac movement during the procedure. Consequently, signal acquisition must be performed at time intervals much shorter than the cardiac movement cycle. In such operating conditions, the white light source used in this work may be replaced with laser illumination at distinct wavelengths in order to achieve adequate signal-to-noise ratio. These “characteristic” wavelengths must be determined so that a pre-selected set (if not all) of the lesion formation parameters (as discussed in subsection a-g above) can still be accurately monitored using data from only this limited set of wavelengths. These may include wavelengths to monitor the slope (such as 710 nm and 910 nm) of the spectrum or the presence of char and coagulum (775 nm and 865 nm).
To address the second major issue, one or more fibers may be added on the side of the catheter to address signal collection issues when the catheter is at an angle different than normal to the tissue’s surface. Furthermore, advanced designs of the catheter to provide radially symmetric illumination and signal collection may be valuable. More advanced designs could involve a scheme in which a set of fibers terminating at different locations at the tip of the catheter are used alternately for illumination and collection of scattered light in a specific sequence. This configuration may allow selection of the set of fibers that provides the most accurate information regarding the ablation parameters and the surrounding catheter environment. Overall, transferring this technology to the clinic may be a challenging yet a solvable problem.
This work was performed in part under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. This research is supported by funding from Biosense Webster Inc. and the Center for Biophotonics, an NSF Science and Technology Center, managed by the University of California, Davis, under Cooperative Agreement No. PHY 0120999.
References and links
2. P Jais, D. C. Shah, M. Haissaguerre, A. Takahashi, T. Lavergne, M. Hocini, S. Garrigue, S. S. Barold, P. Le Metayer, and J. Clementy, “Efficacy and safety of septal and left-atrial linear ablation for atrial fibrillation,” Am. J. Cardiol. 84, 139R (1999). [CrossRef] [PubMed]
4. S. Nath, C. Lynch, J. G. Whayne, and D. E. Haines, “Cellular electrophysiological effects of hyperthermia on isolated guinea pig papillary muscle implications for catheter ablation,” Circulation 88, 1826 (1993). [PubMed]
5. B. Schumacher, O. Eick, F. Wittkampf, C. Von Pezold, J. Tebbenjohanns, W. Jung, and B. Luderitz, “Temperature response following nontraumatic low power radiofrequency application,” Pacing Clin. Electrophysiol. 22, 339 (1999). [CrossRef] [PubMed]
6. H. Cao, S. Tungjitkusolmun, Y. B. Choy, J. Z. Tsai, V. R. Vorperian, and J. G. Webster, “Using Electrical Impedance to Predict Catheter-Endocardial Contact During RF Cardiac Ablation,” IEEE Trans. Biomed. Eng. 49, 247 (2002). [CrossRef] [PubMed]
7. A. Thiagalingam, A. D’Avila, C. McPherson, Z. Malchano, J. Ruskin, and V. Y. Reddy, “Impedance and temperature monitoring improve the safety of closed-loop irrigated-tip radiofrequency ablation,” J. Cardiovasc. Electrophysiol . 18, 318 (2007). [CrossRef] [PubMed]
8. L. Zhou, D. Keane, G. Reed, and J. Ruskin, “Thromboembolic complications of cardiac radiofrequency catheter ablation: A review of the reported incidence, pathogenesis and current research directions,” J. Cardiovasc. Electrophysiol. 10, 611 (1999). [CrossRef] [PubMed]
9. M. R. Epstein, L. D. Knapp, M. Martindill, J. A. Lulu, J. K. Triedman, H. Calkins, S. K. S. Huang, E. P. Walsh, and J. P. Saul, “Embolic complications associated with radiofrequency catheter ablation,” Am. J. Cardiol. 77, 655 (1996). [CrossRef] [PubMed]
11. K. Yokoyama, H. Nakagawa, F. H. M. Wittkampf, J. V. Pitha, R. Lazzara, and W. M. Jackman, “Comparison of electrode cooling between internal and open irrigation in radiofrequency ablation lesion depth and incidence of thrombus and steam pop,” Circulation , 113, 11 (2006). [CrossRef]
13. R. Splinter, R. H. Svenson, L. Littmann, J. R. Tuntelder, C. H. Chuang, G. P. Tatsis, and M. Thompson, “Optical-properties of normal, diseased, and laser photocoagulated myocardium at the Nd-YAG wavelength,” Lasers Surg. Med. 11, 117 (1991). [CrossRef] [PubMed]
15. J. W. Pickering, S. Bosman, P. Posthumus, P. Blokland, J. F. Beek, and M. J. C. Vangemert, “Changes in the optical-properties (at 632.8 nm) of slowly heated myocardium,” Appl. Opt. ,32, 367 (1993). [CrossRef] [PubMed]
16. R. Agah, A. H. Gandjbakhche, M. Motamedi, R. Nossal, and R. F. Bonner, “Dynamics of temperature dependent optical properties of tissue: Dependence on thermally induced alteration,” IEEE Trans. Biomed. Eng. 43, 839 (1996). [CrossRef] [PubMed]
17. J. Swartling, S. Palsson, P. Platonov, S. B. Olsson, and S. Andersson-Engels, “Changes in tissue optical properties due to radio-frequency ablation of myocardium,” Med. Biol. Eng. Comput. 41, 403 (2003). [CrossRef] [PubMed]
19. B. Lin, V. Chernomordik, A. Gandjbakhche, D. Matthews, and S. Demos, “Investigation of signal dependence on tissue thickness in near infrared spectral imaging,” Opt. Express 15, 16581 (2007). [CrossRef] [PubMed]
20. B. Lin, D. Matthews, V. Chernomordik, A. Gandjbakhche, S. Lane, and S. G. Demos, “Evaluation of Optical Imaging and Spectroscopy Approaches for Cardiac Tissue Depth Assessment,” Proc. SPIE 6864, 68640N (2008). [CrossRef]
21. J. F. Black, J. K. Barton, G. Frangineas, and H. Pummer, “Cooperative Phenomena in Two-Pulse, Two-Color Laser Photocoagulation of Cutaneous Blood Vessels,” Proc. SPIE 4244, 13 (2001). [CrossRef]
22. T. Varghese, U. Techavipoo, J. A. Zagzebski, and F. T. Lee, “Impact of gas bubbles generated during interstitial ablation on elastographic depiction of in vitro thermal lesions,” J. Ultrasound Med. 23, 535 (2004). [PubMed]
25. S. Oh, F. Kilicaslan, Y. H. Zhang, O. Wazni, T. N. Mazgalev, A. Natale, and N. F. Marrouche, “Avoiding microbubbles formation during radiofrequency left atrial ablation versus continuous microbubbles formation and standard radiofrequency ablation protocols: Comparison of energy profiles and chronic lesion characteristics,” J. Cardiovasc. Electrophysiol. 17, 72 (2006). [CrossRef] [PubMed]
26. R. L. King, G. T. Clement, S. Maruvada, and K. Hynynen, “Preliminary results using ultrasound transmission for Image-guided thermal therapy,” Ultrasound Med. Biol. 29, 293 (2003). [CrossRef] [PubMed]
27. A. C. Lardo, E. R. McVeigh, P. Jumrussirikul, R. D. Berger, H. Calkins, J. Lima, and H. R. Halperin, “Visualization and temporal/spatial characterization of cardiac radiofrequency ablation lesions using magnetic resonance imaging,” Circulation, 102, 698 (2000).