A non-invasive multimodal sono-contrast NIR spectroscopy system for breast cancer diagnosis: Clinical trial

2010 IEEE International Conference on Bioinformatics and Bioengineering

A noninvasive multimodal sono-contrast NIR spectroscopy system for breast cancer diagnosis Kaiguo Yan, Tarun Podder, Ke Huang, Yan Yu

Lydia Liao

Department of Radiation Oncology Jefferson Medical College, Thomas Jefferson University Philadelphia, PA 19107 USA

Department of Radiology Cooper University Voorhees, NJ 08043 USA tissue. Two 1 MHz focused transducers (Channel Industries, Santa Barbara, CA) are aligned orthogonally inside the scanhead to create a focal area at the intersection of the axes. A commercial ultrasound probe (Philips L12-5, Valhalla, NY), which is located in the same plane as the focused transducers, is used for image co-registration with the NIR spectroscopy information, tissue density information and blood flow information. The ultrasound probe and focused transducers have two degrees-of-freedom, so that the focal zone can be scanned in tissue depth-wise and laterally. Three force sensors (Honeywell model 53, Morristown, NJ) are incorporated on the lower concave compression plate of the scanhead to measure the force exerted on the breast.

Abstract—We have developed a multimodal imaging system that combines three modalities, optical spectroscopy, ultrasonography and acoustic radiation force (ARF) for improving diagnosis of breast cancer based on noninvasive interrogation of vasculature. This paper presents a detailed system design. The safety issues regarding the use of laser and ultrasound have also been addressed in this paper. The maximum exposure to skin for laser was controlled within 0.2 W·cm-2 (ANSI Z136.1); exposure from ARF fields were maintained below the FDA diagnostic limit (0.72 W·cm-2). This multimodal system has the potential to improve tumor detection by deploying ARF to produce a measurable difference in the dynamic behavior of the tissue blood supply environment as interrogated by optical spectroscopy, which was demonstrated to be highly diagnostic in a murine tumor model. Pilot clinical study is being carried out.

The optical spectroscopy system consists of 18 customized 15-foot long and 2.5-mm diameter fiber bundles terminating at the concave bottom plate of the scanhead. Out of these 18 fiber bundles, 6 are used as sources and 12 are used as detectors. The 6 sources are illuminated by two laser diodes (LG-Laser Technologies, Germany) through a multichannel optical switch (O/E land Inc., Canada) that has 2 input channels and 6 output channels. Diffuse reflectance signals are collected by the 12 detectors, amplified by 12 avalanche photodiodes (Hamamatsu C5460-01, Bridgewater, NJ), and then transmitted through 1 multi-channel data acquisition card (National Instrument, Austin, TX) to the computer for analysis.

Keywords- multimodal imaging system, optical spectroscopy, ARF, breast cancer

I.

INTRODUCTION

Optical techniques offer spectral information about biological tissues and add functional information to anatomic imaging. Compared to other available clinical modalities, optical imaging is capable of gathering unique spectroscopic information directly related to the physiological status of tissue [1]. There exists an “optical window” in the near infrared (NIR) region at approximately 650-950 nm in the electromagnetic spectrum, where tissue absorption is dominated by oxyhemoglobin and deoxyhemoglobin chromophores. This provides an opportunity to image tumor blood oxygenation and vasculature via noninvasive and nonionizing measurements. Several research groups have developed optical imaging instrument for tissue characterization [2-5]. In this paper, a multimodal imaging system that combines three modalities, i.e. the optical spectroscopy, ultrasonography and ARF has been designed for improving diagnosis of breast cancer based on noninvasive interrogation of vasculature. This present work differs from the other techniques in that the overall goal of sono-contrast spectroscopy (SCS) is to achieve optical functional imaging of the blood vessel network, angiogenesis and hypoxia via the differentiating effects of acoustic radiation force on blood flow. II.

The ultrasound imaging probe is connected to a commercial ultrasound system (Philips iU22, Valhalla, NY) for image co-registration. The focused ultrasound transducers are driven by a function generator (Agilent 33250A, Santa Clara CA) connected to an RF amplifier (Amplifier Research 25A250A, Souderton, PA). During the operation, the forward and reverse power level is monitored via a directional coupler (Amplifier Research DC3010, Souderton, PA) using an oscilloscope (Tektronix TDS 2022, Richardson, TX), for ensuring the electrical safety. A mobile hydraulic cart is used to host the instruments, as shown in Fig. 1(b). III. A.

Laser power calibration for maximum permissible exposure (MPE) According to ANSI Z136.1 (1993) Safe Use of Lasers, for wavelength 0.647-0.905 μ m , the maximum permissible exposure (MPE) to skin is 0.2-0.5 W·cm-2. Here we selected 0.2 W·cm-2 as the threshold. Two continuous wave (CW)

SYSTEM DESIGN

A scanhead (Fig. 1 (a)) has been designed to deliver focused acoustic radiation fields up to about 2.4 cm deep in

978-0-7695-4083-2/10 $26.00 © 2010 IEEE DOI 10.1109/BIBE.2010.55

SYSTEM CALIBRATION

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unless otherwise specified. From the start to the end of the examination, the scanhead should not be moved. Any motion of the tissue or the scanhead is likely to disturb the image correlation.

laser diodes are used in the spectroscopy system: one has a wavelength of 685 nm with the maximum output of 50 mW; the other has a wavelength of 830 nm with the maximum output of 110 mW. The power output for the two laser systems can be adjusted using the knob in the front panel. The threshold laser output W at the source terminals was calculated to be 9.8 mW for the two laser units. A laser power meter system (Coherent LabMax, Santa Clara, CA) was used to calibrate and mark the corresponding threshold positions on the two units.

(a)

IV.

CONCLUSIONS AND FUTURE WORK

In this paper, we present a multimodal imaging system that combines three modalities, optical spectroscopy, ultrasonography and ARF for improving diagnosis of breast cancer based on noninvasive interrogation of vasculature. We also include force sensors in the system to ensure consistent, slight compression. Consistency of the degree of compression would be important for longitudinal studies (comparison studies for the same patient at different time points), co-registration under deformable image fusion techniques, as well as for ensuring adequate blood flow baselines. We have calibrated the lasers and the ARF fields of the multimodal system to meet the safety guidelines. This multimodal system has the potential to improve the tumor detection by deploying ARF as the contrast agent to produce a measurable difference in the dynamic behavior of the tissue blood supply environment as interrogated by optical spectroscopy. This sono-contrast spectroscopy technique was demonstrated to be highly diagnostic in a murine tumor model. Pilot clinical study is being carried.

(b)

Fig. 1. Hardware system. (a) Scanhead installed on the ring gantry; (b) Mobile cart hosting the instruments.

B. ARF calibration and registration Based on the FDA guideline, the derated global maximum acoustic output of the diagnostic ultrasound equipment should not exceed Pre-amendments acoustic output exposure levels, i.e. derated ISPTA ≤0.72 W·cm-2. We calibrated the ARF radiation fields to ensure it is within the limit.

ACKNOWLEDGMENT Work supported by National Cancer Institute (NCI) grant R33-CA107860. REFERENCES [1]. Demos, S.G., Voge A.U., Gandjbakhche A.H.: Advances in optical spectroscopy and imaging of breast lesions, J

The ARF focal spot that has the maximum peak-positive voltage signal on the oscilloscope was found at about 2 cm below the bottom plate, which is the designed intersection of the axes of the two focused transducers. The Spatial Peak Temporal Average Intensity (ISPTA) was calculated, which was determined to be 0.4 W·cm-2, below the FDA therapeutic ultrasound limits (0.72 W·cm-2). The focal spot was then registered in the ultrasonography system for image guidance during treatment. This calibration established the baseline of the dual-transducer focused acoustic radiation field. A quality assurance (QA) protocol has been developed following the same procedure.

[2].

[3].

[4].

C. Clinical procedure The scanhead is mounted on a positioning platform with adjustable height, so as to be gently placed upon the surface of the skin near the breast mass. The force exerted on the tissue can be observed from GUI which displays calibrated force sensor data. At the start, the physician will adjust the tissue under inspection to the ultrasound focal spot using the knobs on the scanhead via image guidance. After that, the data collection procedure can begin, which will take 5.5 min

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