University of Southern California The USC Andrew and Erna Viterbi School of Engineering Microwave Systems, Sensors and Imaging Lab

Targeted Treatment of Disease with Heat

Figure 1. Real-Time Microwave Thermal Imaging of Experimental Phantom

Recently, guided thermal therapies have seen increased use in the treatment of a variety of diseases, particularly in cases of soft tissue cancers [1], [2]. During these therapies, thermal monitoring is essential to ensuring the accuracy of both treatment location and thermal dose, and a variety of monitoring methods hav been employed with varying degrees of success. With the goal of providing fast, portable, affordable, and accurate monitoring and guidance of thermal therapies, we have developed a real-time microwave imaging method for non-invasive temperature monitoring and validated this method using laboratory phantoms in a prototype system.

Targeted Thermal Therapies

Thermal therapies can be classified into two types, hyperthermia and thermal ablation:
Hyperthermia consists of heating tissues to 40 to 47 degrees Celsius for tens of minutes, causes irreversible damage to cancer cells by altering the permeability of plasma membranes and denaturing proteins [3]. Hyperthermia has shown therapeutic benefit as an adjuvant to radiotherapy [4] and chemotherapy [5], as well as inducing both apoptotic and necrotic cell death given a sufficient thermal dose [6], [7].
Thermal ablation employs more extreme temperatures over a shorter period to induce rapid and localized tissue destruction. Ablative methods, which include cryoablation, high intensity focused ultrasound (HIFU) [8], radio frequency ablation (RFA), microwave ablation, and laser ablation [9], offer the potential to treat lesions that are not surgically accessible via traditional means due to the morbidity or mortality associated with surgical excision.

Thermal Monitoring

Several different thermal monitoring methods of varying complexity have been employed:
Clinical studies of a system using an invasive electric-field probe to focus within a compressed breast were reported by Dooley et al. [10] and Vargas et al. [11].
Fiber optic sensors have been used in several systems to monitor thermal dose [12]–[14], but coverage is limited to the sensor tip and is inherently invasive.
For full coverage of the treatment region, Proton Resonance Frequency Shift (PRFS) Magnetic Resonance Thermal Imaging (MRTI) has been used, as in the MR-guided phased arrays demonstrated in Stauffer et al. [15], [16] and Dewhirst et al. [17], but expense and complexity has thus far limited its use.

Real-Time Microwave Thermal Monitoring

In our real-time microwave thermal monitoring system, volumetric images of differential temperature can be formed with a refresh rate as fast as 1 frame per second, and a thermal resolution of approximately 1 degree Celsius has been achieved in phantom tests. Example results from these tests are shown below.

 

Figure 2: Microwave Imaging System for Real-Time Thermal Therapy Monitoring

Empirical Studies of Real-Time Microwave Thermal Monitoring in Tissue Mimicking Phantom

The target used to create a differential change in dielectric properties due to a change in temperature was a 4-cm diameter ping-pong ball that was filled with water and sealed. This was meant to emulate the size and shape of a typical thermal therapy treatment region. The target was heated to approximately 55 °C in a water bath, then placed in the cavity and imaged while it cooled. As a control, we measured the change in temperature with an embedded thermistor as the target cooled to the ambient cavity temperature of about 22.5 °C (as shown in Figure 5). Three cases were considered:

Figure 3. Each of the three experimental phantom cases pictured in order from left to right.

Case 1: We first imaged a 4-cm isolated water-filled ping-pong ball as it cooled from 55 °C to 22.5 °C. This is the case pictured in Figure 3 (left). 

Case 2: The same water-filled ping-pong ball was then heated and imaged as it cooled in the presence of additional objects. These objects consisted of two water filled ping-pong balls and a 1-in diameter acrylic sphere as shown in Figure 3 (center).

Case 3: Last, a simple breast phantom with an embedded heated target is shown in Figure 3 (right). The phantom consisted of two plastic bottles creating inner and outer chambers. The inner chamber was filled with a fluid mixture that mimics the dielectric properties of glandular breast tissue, and the outer chamber was filled with vegetable oil to mimic the lower dielectric properties of fatty breast tissue.
 

 

Figure 4. Microwave thermal images in axial, sagittal, and coronal planes through peak temperature location over time for case 3.
Figure 5. Comparison of calibrated temperature predictions with true temperature curve (black dots) for each of the three cases.

Imaging results of case 3 at four time samples are shown in Figure 4, and temperature comparisons of predicted vs. true temperature for all three cases are shown Figure 5. As can be seen from the figures, the imaging system was able to accurately monitor the small changes in dielectric properties associated with temperature in real-time. For the most challenging case of the multilayered phantom, the calibrated temperature prediction was accurate to within 1 degree Celsius (as shown in Figure 5). Further details of the system and validation experiments can be found in: 

 M. Haynes, J. Stang, and M. Moghaddam, Real-time Microwave Imaging of Differential Temperature for Thermal Therapy Monitoring, IEEE Trans. Biomedical Engineering, IEEE Trans. Biomed. Engineering, vol. 61, no. 6, pp. 1787-1797, June 2014.

J. Stang, G. Chen, M. Haynes, and M. Moghaddam, “Advances in real-time non-contact monitoring of medical thermal treatment through multistatic array microwave imaging,” IEEE Conference on Antenna Measurements and Applications, Chiang Mai, Thailand, December 2015.

References
[1] S. Nahum Goldberg, Clement J. Grassi, et al., “Image-guided Tumor Ablation: Standardization of Terminology and Reporting Criteria,” Journal of Vascular and Interventional Radiology, Volume 20, Issue 7, Supplement, July 2009, Pages S377-S390, ISSN 1051-0443, http://dx.doi.org/10.1016/j.jvir.2009.04.011.

[2] Matthew R. Callstrom, John D. York, et al., “Research Reporting Standards for Image-guided Ablation of Bone and Soft Tissue Tumors,” Journal of Vascular and Interventional Radiology, Volume 20, Issue 12, December 2009, Pages 1527-1540, ISSN 1051-0443, http://dx.doi.org/10.1016/j.jvir.2009.08.009.

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[4] CC Vernon, et al., “Radiotherapy with or without hyperthermia in the treatment of superficial localized breast cancer: results from five randomized controlled trials,” Int. J. Radiat. Oncol. Biol. Phys, 35, pp. 731-744, 1996.

[5] Z Vujaskovic, et al., “A Phase I/II Study of Neoadjuvant Liposomal Doxorubicin, Paclitaxel, and Hyperthermia in Locally Advanced Breast Cancer,” Int. J. Hyperthermia 26(5), pp. 514–521, 2010.

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[7] E Jones, D Thrall, MW Dewhirst, and Z Vujaskovic, “Prospective thermal dosimetry: the key to hyperthermias future,” Int. J. Hyperthermia, 22, pp. 247-253, 2006.

[8] JE Kennedy, “High-intensity focused ultrasound in the treatment of solid tumours,” Nature Reviews Cancer, 5, pp. 321–327, 2005.

[9] Hawasli, Ammar H. et al. Magnetic Resonance Imaging-Guided Focused Laser Interstitial Thermal Therapy for Intracranial Lesions: Single-Institution Series. Neurosurgery 73.6, pp, 10071017, 2013.

[10] WC Dooley, HI Vargas, AJ Fenn, MB Tomaselli, and JK Harness, “Focused microwave thermotherapy for preoperative treatment of invasive breast cancer: a review of clinical studies,” Ann. Surg. Oncol, 17, pp. 1076-1093, 2010.

[11] HI Vargas, WC Dooley, RA Gardner, KD Gonzalez, R Venegas, SH Heywang-Kobrunner, and AJ Fenn, “Focused microwave phased array thermotherapy for ablation of early-stage breast cancer: results of thermal dose escalation,” Ann. Surg. Oncol, 11, pp. 139-146, 2004.

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[14] T. V. Samulski, and P. Fessenden, “Thermometry in therapeutic hyperthermia,” Methods of hyperthermia control. Springer, Berlin, pp. 1-34, 1990.

[15] Z Li, M Vogel, PF Maccarini, V Stakhursky, BJ Soher, S Das, OA Arabe, WT Joines, and PR Stauffer, “Improved Hyperthermia Treatment Control using SAR/Temperature Simulation and PRFS Magnetic Resonance Thermal Imaging,” Int. J. Hyperthermia, 27(1), pp. 86–99, 2011.

[16] PR Stauffer, et al., “Conformal Microwave Array (CMA) Applicators for Hyperthermia of Diffuse Chestwall Recurrence,” Int. J. Hyperthermia, 26(7), pp. 686–698, 2010.

[17] KS Cheng, MW Dewhirst, PR Stauffer, S Das, “Effective learning strategies for real-time image-guided adaptive control of multiple source hyperthermia applicators,” Medical Physics, 37(3), pp. 1285–1297, 2010.