Alexander A. Karabutov

Sensitivity of laser opto-acoustic imaging in detection of small deeply embedded tumors

Current imaging modalities fail to detect small tumors in the breast. Opto-acoustic tomography is a novel technique for early cancer detection with promising diagnostic capability. The experimental limit of sensitivity and maximal depth of the laser opto-acoustic detection for small model tumors located within bulk phantom tissue were studied. Two phantoms with optical properties similar to that of breast tissue in the near infrared spectral range were used in these studies: turbid gelatin slabs with the thickness of 100 mm and chicken breast muscle slabs with the thickness of up to 80 mm. Gelatin spheres with enhanced absorption coefficient relative to the background absorption and liver tissue were used to simulate small tumors. The experiments demonstrated the capability of laser optoacoustic imaging to detect and localize phantom tumors with the diameter of 2 mm at a depth of up to 60 mm within the gelatin phantoms and 3/spl times/2/spl times/0.6-mm piece of liver tissue within 80-mm chicken breast tissue. Theoretical studies on sensitivity of opto-acoustic detection at various diameters, depths of location, and absorption coefficients of small tumors were performed using the experimental data. Our results suggest that the opto-acoustic imaging may occupy a significant niche in early detection of cancer in the breast and other organs.

TIME-RESOLVED LASER OPTOACOUSTIC TOMOGRAPHY OF INHOMOGENEOUS MEDIA

The methods of time-resolved laser optoacoustic tomography of inhomogeneous media and related problems are reviewed. Time-resolved laser optoacoustic tomography allows one to measure the distribution of light absorption in turbid media with depth resolution up to several microns in real time. The theory of laser excitation of acoustic waves by absorbing of light in particles, dispersed in transparent, light-absorbing or scattering media, is developed. The distribution of light absorption can be obtained from the temporal course of acoustic pressure. Two schemes of acoustic wave detection — in the medium under testing (direct detection) and in transparent medium, coupled to the investigated one (indirect detection) — are discussed. In both cases the reconstruction of light absorption can be made by simple calculations. Test experiments with homogeneous and layered media confirm the proposed theoretical models and the possibility of using the proposed experimental schemes. Light absorption in homogeneous, inhomogeneous media and in absorbing particles dispersed in turbid media was investigated. The experimental setup allows one to measure the absorption coefficients over the range 1-500 cm−1 with the depth resolution 10–15 μm over the depth 1–1.5 mm.

Backward mode detection of laser-induced wide-band ultrasonic transients with optoacoustic transducer

Time-resolved piezoelectric detection of wide-band ultrasonic transients induced by laser pulses in absorbing medium was studied. An optoacoustic transducer was developed for measuring the profiles of ultrasonic transients propagating in backward direction out of the laser-irradiated medium. For this purpose, an optical fiber for delivery of laser pulses to the surface of absorbing medium and a wide-band lithium niobate acoustic transducer were incorporated in one compact system, optoacoustic front surface transducer (OAFST). The transducer possesses temporal resolution (rise time) of 3.5 ns, low effective thermal noise pressure (10 Pa), and high sensitivity of piezoelectric detection (10 μV/Pa) over the ultrasonic frequency range from 1 to 100 MHz. Nd:YAG laser pulses at 355 nm were employed to generate distribution of acoustic sources in water solutions of potassium chromate with various concentrations. A temporal course of ultrasonic transients launched into an optically and acoustically transparent me...

Detection of ultrawide-band ultrasound pulses in optoacoustic tomography

A laser optoacoustic imaging system (LOIS) uses time-resolved detection of laser-induced pressure profiles in tissue in order to reconstruct images of the tissue based on distribution of acoustic sources. Laser illumination with short pulses generates distribution of acoustic sources that accurately replicates the distribution of absorbed optical energy. The complex spatial profile of heterogeneous distribution of acoustic sources can be represented in the frequency domain by a wide spectrum of ultrasound ranging from tens of kilohertz to tens of megahertz. Therefore, LOIS requires a unique acoustic detector operating simultaneously within a wide range of ultrasonic frequencies. Physical principles of an array of ultrawide-band ultrasonic transducers used in LOIS designed for imaging tumors in the depth of tissue are described. The performance characteristics of the transducer array were modeled and compared with experiments performed in gel phantoms resembling optical and acoustic properties of human tissue with small tumors. The amplitude and the spectrum of laser-induced ultrasound pulses were measured in order to determine the transducer sensitivity and the level of thermal noises within the entire ultrasonic band of detection. Spatial resolution of optoacoustic images obtained with an array of piezoelectric transducers and its transient directivity pattern within the field of view are described. The detector design considerations essential for obtaining high-quality optoacoustic images are presented.

Laser opto-acoustic imaging of the breast : Detection of cancer angiogenesis

First clinical prototype laser optoacoustic imaging system (LOIS) for breast cancer detection was designed and fabricated using a compact Nd:YAG laser, fiberoptic light delivery system, a linear array of 12 wide-band acoustic transducers, and a data acquisition card operated by computer with original signal processing and image reconstruction code. Initially images of small absorbing spheres were recorded in the milk with optical properties resembling those of the breast at the wavelength of 1064-nm. The system was optimized for contrast, sensitivity and axial (in-depth) resolution. The small number of acoustic transducers (12), which in turn was determined by the system cost and the time of image acquisition limited the lateral resolution of the images. Clinical ex-vivo studies on radical mastectomy specimens were performed and compared with x-ray radiography, MRI and ultrasound imaging. The results of our pilot clinical studies showed pronounced opto-acoustic contrast of ~300% between breast tumors and normal breast tissues. This contrast substantially exceeds any other endogenous tissue contrast currently utilized in clinical ultrasonography, MRI and x-ray mammography. Based on literature data and our gross observations of tumor cross-sections we hypothesize that the opto-acoustic contrast results primarily from increased optical absorption in the dense microvascularity of the tumors. In patients receiving radiotherapy, tumors were found to contain enhances concentration of dense highly scattering fiberotic tissue.

Optoacoustic imaging of absorbing objects in a turbid medium: ultimate sensitivity and application to breast cancer diagnostics

One of the major medical applications of optoacoustic (OA) tomography is in the diagnostics of early-stage breast cancer. A numerical approach was developed to characterize the following parameters of an OA imaging system: resolution, maximum depth at which the tumor can be detected, and image contrast. The parameters of the 64-element focused array transducer were obtained. The results of numerical modeling were compared with known analytical solutions and further validated by phantom experiments. The OA images of a 3 mm piece of bovine liver immersed in diluted milk at various depths were obtained. Based on the results of modeling, a signal filtering algorithm for OA image contrast enhancement has been proposed.

Ultimate sensitivity of time-resolved optoacoustic detection

The major limitation in sensitivity of the optical tomography is associated with strong optical attenuation in human tissues. Opto-acoustic tomography overcomes this limitation utilizing detection of acoustic waves instead of detection of transmitted photons. Exceptional sensitivity of the opto-acoustic tomography allows early detection of small tumors located dep in human tissues, such as breast. This paper demonstrates that an optimally designed opto-acoustic imaging system can detect early 1-mm tumors with minimal blood content of only 7 percent at the depth of up to 7-cm within the breast attenuating laser irradiation 3.3 times per each 1-cm of its depth. A theoretical consideration of the ultimate sensitivity of piezo-detection in a wide ultrasonic frequency band is developed. The detection sensitivity is presented as a function of the ultrasonic frequency, tumor dimensions and optical absorption coefficient. Comparative analysis of piezo and optical interferometric detection of opto-acoustic transients is presented. The theoretical models of piezo detection were developed for the open-circuit and short-circuit schemes of operation. The ultimate sensitivity limited by thermal noise of electric capacitor of the piezo-element was estimated. It was shown that the limit of detection depends on the frequency band, the electric capacity of the transducer and the sped of sound in the piezo-element. Comparative analysis of various piezo-materials was made from the point of view of their utility for sensitive opto-acoustic detection.

Enhancement of optoacoustic tissue contrast with absorbing nanoparticles

Laser induced phase transition in the water surrounding absorbing nanoparticle results in dramatic enhancement of the thermoacoustic efficiency and excitation of high- amplitude pressure waves. Feasibility study was performed in tissue phantoms. Experiments supported with theoretical model demonstrated possibility to increase the efficiency of optoacoustic generation in tissue up to two orders of magnitude by application of absorbing carbon and gold nanoparticles.

Imaging of layered structures in biological tissues with optoacoustic front surface transducer

Optoacoustic tomography is a promising technique for imaging skin layered structures and vascular and pigmented lesions in vivo. The imaging of skin is complicated by necessity to perform laser irradiation and acoustic detection from the same site at the surface. We designed an opto-acoustic transducer incorporating a fiber-optic light delivery system and a LiNbO3 piezoelectric detector in one device. The results of test experiments in phantoms, chicken cockscomb, and human hand yielded the following parameters of the opto-acoustic transducer: (1) sensitivity of 0.98 V/bar, (2) temporal resolution of acoustic detection of 5 ns. This fast response time allows one to achieve an in-depth resolution of 10 - 15 micrometer. A small size of the detector provides lateral resolution of 200 micrometer. Feasibility studies demonstrated that the current design of the optoacoustic transducer permits monitoring of the light absorbing heterogeneities at the dept up to 4 mm. The principle scheme of the opto-acoustic transducer design, theoretical background and experimental testing is presented. Theoretical model of the wide-band ultrasonic detection is developed. The principles of the opto- acoustic image reconstruction under conditions of significant diffraction of acoustic wave are described. A basic algorithm for reconstruction of 3-D images from the laser-induced acoustic waves recorded in backward mode is also presented.

Laser ablation of aqueous solutions with spatially homogeneous and heterogeneous absorption

The ablation efficiency of aqueous solutions with different concentrations and spatially homogeneous (CuCl2 solution) and heterogeneous (ink solution) absorption was studied as a function of the pulse-energy fluence (Nd:YAG laser, λ=1064 nm, τp = 20 ns). The latter was varied over a wide range from 0.15 J/cm2 to 8.00 J/cm2. The ablation threshold of solutions with heterogeneous absorption was found to be much lower (3 to 4 times) than the ablation threshold of solutions with homogeneous absorption and with the same average absorption coefficient. The ablation efficiency of heterogeneous solutions was higher by more than an order of magnitude. It was found that the ablation efficiency increases drastically for both types of solutions as the pulse energy fluence was raised to exceed the ablation threshold by 2 or 3 times. At such energy fluences, along with small droplets, larger droplets (1.5–2 mm cross section) could be ejected. This points to the ablation of solutions being affected by a hydrodynamic shock formed as a result of the pulsed recoil pressure excerted by the ablation products. The differences between the ablation processes for solutions with homogeneous and heterogeneous absorption as well as the hydrodynamic destruction at high energy fluences are discussed.