Journal of Biomedical Optics 13͑4͒, 044033 ͑July/August 2008͒ Magnetic resonance imaging guidance for laser photothermal therapy Yichao Chen Abstract. Temperature distribution is a crucial factor in determining University of Central Oklahoma the outcome of laser phototherapy in cancer treatment. Magnetic College of Mathematics and Science resonance imaging ͑MRI͒ is an ideal method for 3-D noninvasive tem- Department of Engineering and Physics 100 North University Drive perature measurement. A 7.1-T MRI was used to determine laser- Edmond, OK 73034 induced high thermal gradient temperature distribution of target tissue with high spatial resolution. Using a proton density phase shift method, thermal mapping is validated for in vivo thermal measure- Surya C. Gnyawali ment with light-absorbing enhancement dye. Tissue-simulating phan- Oklahoma State University tom gels, biological tissues, and tumor-bearing animals were used in Department of Physics the experiments. An laser was used to irradiate the samples, Stillwater, Oklahoma 73019 805-nm with laser power in the range of 1to3W. A clear temperature distri- bution matrix within the target and surrounding tissue was obtained Feng Wu with a specially developed processing algorithm. The temperature Chongqing Medical University mapping showed that the selective laser photothermal effect could Institute of Ultrasonic Engineering in Medicine result in temperature elevation in a range of 10 to 45°C. The tem- and perature resolution of the measurement was about 0.37°C with Clinical Center for Tumor Therapy of 2nd Affiliated Hospital 0.4-mm spatial resolution. The results of this study provide in vivo Medical College Road thermal information and future reference for optimizing laser dosage Chongquing 400016, China and dye concentration in cancer treatment. © 2008 Society of Photo-Optical Instrumentation Engineers. ͓DOI: 10.1117/1.2960020͔ Hong Liu Keywords: laser phototherapy; selective photothermal interaction; magnetic reso- University of Oklahoma nance imaging ͑MRI͒; noninvasive temperature measurement; Indocyanine Green School of Computer Electrical Engineering ͑ICG͒. and Paper 07411RR received Oct. 2, 2007; revised manuscript received Feb. 1, 2008; Center for Bioengineering accepted for publication Mar. 12, 2008; published online Jul. 24, 2008. Norman, Oklahoma 73019 Yasvir A. Tesiram Andrew Abbott Rheal A. Towner Oklahoma Medical Research Foundation 825 N.E. 13th Street Oklahoma City, Oklahoma 73104 Wei R. Chen University of Central Oklahoma College of Mathematics and Science Department of Engineering and Physics 100 North University Drive Edmond, OK 73034 1 Introduction immunotherapy1,7–9 are critical and highly desirable for con- firming the target region as well as determining treatment pa- Photothermal interaction has been widely used in immuno- rameters. Specifically, real-time in vivo thermometry during logical stimulation1 and treatment of tumors,2 thermosensitive 3 4 photothermal treatment can improve the treatment effect by microcarries, and heart arrhythmias. In vivo temperature dis- monitoring and optimizing the heat distribution generated by tribution mapping has clinical significance since the body laser irradiation. temperature is closely related to physiological functions. Thermal distribution induced by laser radiation is deter- Noninvasive temperature monitoring during hyperthermia,5 mined by both laser and tissue parameters.10 Selective photo- nonincision surgery using ultrasound,6 and laser thermal interaction, using in situ dye enhancement, can de- stroy tumor cells directly by raising target tissue temperature Address all correspondence to: Wei R. Chen, Ph.D. Professor, Department of above the damage threshold using laser radiation. It could also Engineering and Physics College of Mathematics and Science, University of Central Oklahoma, 100 N. University Drive Edmond, Oklahoma 73034. Tel: ͑405͒ 974-5198; Fax: ͑405͒ 974-3812; E-mail: [email protected]. 1083-3668/2008/13͑4͒/044033/8/$25.00 © 2008 SPIE Journal of Biomedical Optics 044033-1 July/August 2008 b Vol. 13͑4͒ Downloaded From: http://biomedicaloptics.spiedigitallibrary.org/ on 07/06/2015 Terms of Use: http://spiedl.org/terms Chen et al.: Magnetic resonance imaging guidance for laser photothermal therapy be used as an adjuvant to immunotherapy by exposing tumor 2 Materials and Methods antigens when combined with active immunological stimula- 2.1 Physical Basis tion. Due to unknown differences in thermal conductivity, dif- The PRF method was first investigated by Hindman17 in his fusion, and physiological cooling effects, the hyperthermic study of hydrogen bond formation between water molecules. efficiency is hard to determine. The optimum outcome of the The magnetic field experienced by a proton within tissue, laser photothermal interaction is to kill as many target tumor Blocal, has the following relationship with the main external cells as possible, while preserving tumor proteins for recog- 17,18 magnetic field, B0, which has the same unit of tesla: nition of the host immune system. In order to achieve such ͓ ␴͑ ͔͒ ͑ ͒ effects while avoiding undesirable thermal damage to sur- Blocal = 1+ T B0,, 1 rounding healthly tissue, the rise in temperature in target re- where ␴͑T͒, the chemical shift, is the screening factor and is gions needs to be tightly controlled. The treatment effect has a unitless. close relationship with the thermal distribution inside the tar- When temperature increases, the screening factor de- get tumor and surrounding tissue. creases, causing decrease of B . ͑ ͒ local Magnetic resonance imaging MRI is ideal for noninva- Using the assumption of linear temperature dependence of sive, real-time, 3-D temperature mapping and target visualiza- ␴͑T͒, this can lead to:12 tion. Unlike many other thermal measurement modalities, MRI can determine temperature distribution in tissue without ⌬␴͑T͒ = ␣⌬T, ͑2͒ disturbing treatment procedures. There are several MRI mea- ␣ surement methods for temperature profiling.11 The water pro- where is the temperature-dependent water proton chemical shift in ppm/°C and ⌬T is the temperature change in Celsius. ton resonance frequency shift ͑PRF͒ method is now the most With a certain phase image as a reference, one can acquire promising method for thermology with high spatial resolution 19 the temperature changes between two acquisition intervals: and fast data acquisition.12–14 In the PRF method, temperature dependence comes from weak local magnetic field shielding ⌬␸ ␥⌬ ␥ ␣⌬ ͑ ͒ =TE Blocal =TE B0 T, 3 caused by the moving electron clouds around the proton. ␥ ͑␥ When temperature increases, the screening effect of bounded where is the gyromagnetic ratio of hydrogen ␲ / ͒ electrons increases, resulting in a lower local magnetic field =2 ·42.57 MHz T , and TE is the echo time of the gradient and consequently a negative shift of water PRF. A simple echo pulse sequence with a unit of sec. Within physiological ␣ 12,20 gradient echo sequence can be deployed, and the calibration temperature ranges, can be considered a constant. Therefore, the temperature change is proportional to the phase curve is not needed because each tissue contains water mol- change of the image at each corresponding pixel. ecules. The PRF method has been shown to be the most ac- curate method in the case of low motion state. There are sev- eral reports on PRF using materials such as optical tissue-like 2.2 Experiment Setup phantoms and tissue in vitro.12,15 Optical tissue-simulating All experiments were carried out on a 7.1-T Bruker 730 USR phantom gels such as agarose gels have been used in the 16 30-cm horizontal-bore small animal MR imaging system, thermal MRI measurement. For the live animal model, this controlled by ParaVision 3.0.2 software ͑Bruker BioSpin MRI method has the challenge of decreasing the movement error GmbH, Germany͒. because of phase subtraction. Respiratory gating is needed An 805-nm laser was used in our experiments, and the with anesthetized animals. delivery system is shown in Fig. 1. The laser power was de- In this study, the PRF method was used for the 3-D tem- livered through a 7-m microlens fiber ͑Pioneer Optics, Wind- perature mapping under laser irradiation using a 7-T small sor Locks, Connecticut͒ to the sample. The fiber contains a animal MR scanner. The high magnetic field can lead to high 400-␮m core, with an output spot of 57-mm-diam at sensitivity and fine resolution, which are crucial in point-like 100 mm with a half-angle divergence of 15.9 deg. A series of thermal distribution during laser irradiation. The temperature tests were performed using phantom gel, chicken tissue, and distributions were measured using in vivo and ex vivo tissues, rat tumors. The laser power was chosen in a range of phantom gels, and live animals. A phantom gel with tissue- 1.0 to 3.0 W, according to the treated samples. The phantom / 2 like optical properties has not been previously used for such gel was irradiated with a laser power density of 1.27 W cm ͑beam diameter of and laser power of ͒. The applications. The temperature increase of various samples 1.0 cm 1.0 W chicken breast was irradiated by laser with a power density of were measured by MRI and calibrated by thermocouples and 1.17 W/cm2 ͑beam diameter of 1.8 cm and laser power of fiber temperature sensor systems. The influence of external 3W͒, and tumor-bearing rats were treated with a power den- magnetic field fluctuation and system noise was investigated. sity of 2.55 W/cm2 ͑beam diameter of 1.0 cm and laser The current study could lead to better understanding of the power of 2.0 W͒. The laser irradiation duration was 10 min. relationship between the tissue parameters and laser param- A chemical shift based on water proton density resonance eters in photothermal therapy. It may also provide a funda- frequency was used for temperature mapping. The typical mental framework for understanding the immunological re- MRI parameters used in our experiments were: TE=10 ms sponses induced by phototherapy, since temperature has been and TR=158 ms.