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Principles Of Optics Electromagnetic Theory Of Propagation Interference And Diffraction Of Light

Photoacoustic (PA) imaging, also called optoacoustic imaging, is a new biomedical imaging modality based on the use of laser-generated ultrasound that has emerged over the last decade. It is a hybrid modality, combining the high-contrast and spectroscopic-based specificity of optical imaging with the high spatial resolution of ultrasound imaging. In essence, a PA image can be regarded as an ultrasound image in which the contrast depends not on the mechanical and elastic properties of the tissue, but its optical properties, specifically optical absorption. As a consequence, it offers greater specificity than conventional ultrasound imaging with the ability to detect haemoglobin, lipids, water and other light-absorbing chomophores, but with greater penetration depth than purely optical imaging modalities that rely on ballistic photons. As well as visualizing anatomical structures such as the microvasculature, it can also provide functional information in the form of blood oxygenation, blood flow and temperature. All of this can be achieved over a wide range of length scales from micrometres to centimetres with scalable spatial resolution. These attributes lend PA imaging to a wide variety of applications in clinical medicine, preclinical research and basic biology for studying cancer, cardiovascular disease, abnormalities of the microcirculation and other conditions. With the emergence of a variety of truly compelling in vivo images obtained by a number of groups around the world in the last 2–3 years, the technique has come of age and the promise of PA imaging is now beginning to be realized. Recent highlights include the demonstration of whole-body small-animal imaging, the first demonstrations of molecular imaging, the introduction of new microscopy modes and the first steps towards clinical breast imaging being taken as well as a myriad of in vivo preclinical imaging studies. In this article, the underlying physical principles of the technique, its practical implementation, and a range of clinical and preclinical applications are reviewed.

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Biomedical photoacoustic imaging

Photoacoustic imaging is a promising method for visualizing biological tissues with optical absorbers. This article provides an overview of the rapidly developing field of photoacoustic imaging. Photoacoustics, the physical basis of photoacoustic imaging, is analyzed briefly. The merits of photoacoustic technology, compared with optical imaging and ultrasonic imaging, are described. Various imaging techniques are also discussed, including scanning tomography, computed tomography and original detection of photoacoustic imaging. Finally, some biomedical applications of photoacoustic imaging are summarized.

Photoacoustic imaging in biomedicine

We describe a novel optical system for bidirectional color Doppler imaging of flow in biological tissues with micrometer-scale resolution and demonstrate its use for in vivo imaging of blood flow in an animal model. Our technique, color Doppler optical coherence tomography (CDOCT), performs spatially localized optical Doppler velocimetry by use of scanning low-coherence interferometry. CDOCT is an extension of optical coherence tomography (OCT), employing coherent signal-acquisition electronics and joint time-frequency analysis algorithms to perform flow imaging simultaneous with conventional OCT imaging. Cross-sectional maps of blood flow velocity with <50-μm spatial resolution and <0.6-mm/s velocity precision were obtained through intact skin in living hamster subdermal tissue. This technology has several potential medical applications.

In vivo bidirectional color Doppler flow imaging of picoliter blood volumes using optical coherence tomography

Optoacoustic imaging, or photoacoustic imaging, is insensitive to photon scattering within biological tissue and, unlike conventional optical imaging methods, makes high-resolution optical visualization deep within tissue possible. Recent advances in laser technology, detection strategies and inversion techniques have led to significant improvements in the capabilities of optoacoustic systems. A key empowering feature is the development of video-rate multispectral imaging in two and three dimensions, which offers fast, spectral differentiation of distinct photoabsorbing moieties. We review recent advances and capabilities in the technology and its corresponding emerging biological and clinical applications.

Advances in real-time multispectral optoacoustic imaging and its applications

We demonstrate carbon nanotube (CNT) composite-based optoacoustic transmitters that generate strong and high frequency ultrasound. The composite consists of CNTs grown on a substrate, which are embedded in elastomeric polymer used as an acoustic transfer medium. Under pulsed laser excitation, the composite generates very strong optoacoustic pressure: 18 times stronger than a Cr film reference and five times stronger than a gold nanoparticle composite with the same polymer. This enhancement persists over a broadband frequency range of up to 120 MHz and is confirmed by calculation. We suggest the CNT-polymer composites as highly efficient optoacoustic transmitters for high resolution ultrasound imaging.

/pdf/carbon-nanotube-composite-optoacoustic-transmitters-for-2c8vqyhl6v.pdf

Carbon nanotube composite optoacoustic transmitters for strong and high frequency ultrasound generation

Smooth sidewall silicon micro-ring molds have been fabricated using resist reflow and thermal oxidation method. High Q factor polymer micro-ring resonators have been fabricated using these molds. Quality factors as high as 105 have been measured at telecommunication wavelength range. By carefully examining the different loss mechanisms in polymer micro-ring, we find that the surface scattering loss can be as low as 0.23 dB/cm, much smaller than the absorption loss of the polystyrene polymer used in our devices. When used as an ultrasound detector such a high Q polymer micro-ring device can achieve an acoustic sensitivity around 36.3 mV/kPa with 240 μW operating power. A noise equivalent pressure (NEP) is around 88 Pa over a bandwidth range of 1–75 MHz. We have improved the NEP by a factor of 3 compared to our previous best result.

https://umji.sjtu.edu.cn/~slchen/publications/2011%20OE-HighQMR.pdf

Fabrication and characterization of High Q polymer micro-ring resonator and its application as a sensitive ultrasonic detector

We demonstrate an ultrasonic detector with unprecedented broad bandwidth and high sensitivity, based on an imprinted polymer optical microring. It has an acoustic response of up to 350 MHz at −3 dB and noise-limited detectable pressure as low as 105 Pa in this frequency range. Application of such a detector in photoacoustic imaging leads to improved axial resolving ability compared with using the conventional ultrasound detector, and sub-3 μm axial resolution is achieved, which is more than a 2-fold improvement with respect to the reported record. The device’s miniaturized cavity height guarantees its broadband response, and at the same time, its high optical quality factor ensures the detection sensitivity. Our work suggests that the polymer-based miniature microring resonator works as a high-performance ultrasound detector and has potential for acquiring volumetric photoacoustic images with cellular/subcellular resolution in three dimensions.

https://umji.sjtu.edu.cn/~slchen/publications/2014%20ACSPho-MRUltraBand.pdf

Ultrabroad Bandwidth and Highly Sensitive Optical Ultrasonic Detector for Photoacoustic Imaging

The concept of pure optical photoacoustic microscopy(POPAM) was proposed based on optical rastering of a focused excitation beam and optically sensing the photoacoustic signal using a microring resonator fabricated by a nanoimprinting technique. After the refinements of the microring’s working wavelength and in the resonator structure and mold fabrication, an ultrahigh Q factor of 3.0×105 was achieved which provided high sensitivity with a noise equivalent detectable pressure(NEDP) value of 29Pa. This NEDP is much lower than the hundreds of Pascals achieved with existing optical resonant structures such as etalons, fiber gratings and dielectric multilayer interference filters available for acoustic measurement. The featured high sensitivity allowed the microring resonator to detect the weak photoacoustic signals from micro- or submicroscale objects. The inherent superbroad bandwidth of the optical microring resonator combined with an optically focused scanning beam provided POPAM with high resolution in the axial as well as both lateral directions while the axial resolution of conventional photoacoustic microscopy (PAM) suffers from the limited bandwidth of PZT detectors. Furthermore, the broadband microring resonator showed similar sensitivity to that of our most sensitive PZT detector. The current POPAM system provides a lateral resolution of 5 μm and an axial resolution of 8 μm, comparable to that achieved by optical microscopy while presenting the unique contrast of optical absorption and functional information complementing other optical modalities. The 3D structure of microvasculature, including capillary networks, and even individual red blood cells have been discerned successfully in the proof-of-concept experiments on mouse bladders ex vivo and mouse ears in vivo. The potential of approximately GHz bandwidth of the microring resonator also might allow much higher resolution than shown here in microscopy of optical absorption and acoustic propagation properties at depths in unfrozen tissue specimens or thicker tissue sections, which is not now imageable with current optical or acoustic microscopes of comparable resolution.

https://umji.sjtu.edu.cn/~slchen/publications/2011%20OE-POPAM.pdf

Pure optical photoacoustic microscopy

Small size ultrahigh Q polymer microrings working at near visible wavelength have been experimentally demonstrated as ultralow noise ultrasound detectors with wide directivity at high frequencies (>20 MHz). By combining a resist reflow and a low bias continuous etching and passivation process in mold fabrication, imprinted polymer microrings with drastically improved sidewall smoothness were obtained. An ultralow noise-equivalent pressure of 21.4 Pa over 1–75 MHz range has been achieved using a fabricated detector of 60 μm diameter. The device’s wide acceptance angle with high sensitivity considerably benefits ultrasound-related imaging.

http://umji.sjtu.edu.cn/~slchen/publications/2011%20APL-SmallMR.pdf

Sung-Liang Chen

Papers

Carbon nanotube composite optoacoustic transmitters for strong and high frequency ultrasound generation

Fabrication and characterization of High Q polymer micro-ring resonator and its application as a sensitive ultrasonic detector

Ultrabroad Bandwidth and Highly Sensitive Optical Ultrasonic Detector for Photoacoustic Imaging

Pure optical photoacoustic microscopy

High-sensitivity and wide-directivity ultrasound detection using high Q polymer microring resonators.