医用超音波における散乱体分布の高解像かつ高感度な画像化に関する研究

Ultrasound imaging as an effective method is widely used in medical diagnosis andNDT (non-destructive testing). In particular, ultrasound imaging plays an important role in medical diagnosis due to its safety, noninvasive, inexpensiveness and real-time compared with other medical imaging techniques. However, in general the ultrasound imaging has more speckles and is low definition than the MRI (magnetic resonance imaging) and X-ray CT (computerized tomography). Therefore, it is important to improve the ultrasound imaging quality. In this study, there are three newproposals. The first is the development of a high sensitivity transducer that utilizes piezoelectric charge directly for FET (field effect transistor) channel control. The second is a proposal of a method for estimating the distribution of small scatterers in living tissue using the empirical Bayes method. The third is a super-resolution imagingmethod of scatterers with strong reflection such as organ boundaries and blood vessel walls. The specific description of each chapter is as follows: Chapter 1: The fundamental characteristics and the main applications of ultrasound are discussed, then the advantages and drawbacks of medical ultrasound are high-lighted. Based on the drawbacks, motivations and objectives of this study are stated. Chapter 2: To overcome disadvantages of medical ultrasound, we advanced our studyin two directions: designing new transducer improves the acquisition modality itself, onthe other hand new signal processing improve the acquired echo data. Therefore, the conventional techniques related to the two directions are reviewed. Chapter 3: For high performance piezoelectric, a structure that enables direct coupling of a PZT (lead zirconate titanate) element to the gate of a MOSFET (metal-oxide semiconductor field-effect transistor) to provide a device called the PZT-FET that acts as an ultrasound receiver was proposed. The experimental analysis of the PZT-FET, in terms of its reception sensitivity, dynamic range and -6 dB reception bandwidth have been investigated. The proposed PZT-FET receiver offers high sensitivity, wide dynamic range performance when compared to the typical ultrasound transducer. Chapter 4: In medical ultrasound imaging, speckle patterns caused by reflection interference from small scatterers in living tissue are often suppressed by various methodologies. However, accurate imaging of small scatterers is important in diagnosis; therefore, we investigated influence of speckle pattern on ultrasound imaging by the empirical Bayesian learning. Since small scatterers are spatially correlated and thereby constitute a microstructure, we assume that scatterers are distributed according to the AR (auto regressive) model with unknown parameters. Under this assumption, the AR parameters are estimated by maximizing the marginal likelihood function, and the scatterers distribution is estimated as a MAP (maximum a posteriori) estimator. The performance of our method is evaluated by simulations and experiments. Through the results, we confirmed that the band limited echo has sufficient information of the AR parameters and the power spectrum of the echoes from the scatterers is properly extrapolated. Chapter 5: The medical ultrasound imaging of strong reflectance scatterers based on the MUSIC algorithm is the main subject of Chapter 5. Previously, we have proposed a super-resolution ultrasound imaging based on multiple TRs (transmissions/receptions) with different carrier frequencies called SCM (super resolution FM-chirp correlation method). In order to reduce the number of required TRs for the SCM, the method has been extended to the SA (synthetic aperture) version called SA-SCM. However, since super-resolution processing is performed for each line data obtained by the RBF (reception beam forming) in the SA-SCM, image discontinuities tend to occur in the lateral direction. Therefore, a new method called SCM-weighted SA is proposed, in this version the SCM is performed on each transducer element, and then the SCM result is used as the weight for RBF. The SCM-weighted SA can generate multiple B-mode images each of which corresponds to each carrier frequency, and the appropriate low frequency images among them have no grating lobes. For a further improvement, instead of simple averaging, the SCM applied to the result of the SCM-weighted SA for all frequencies again, which is called SCM-weighted SA-SCM. We evaluated the effectiveness of all the methods by simulations and experiments. From the results, it can be confirmed that the extension of the SCM framework can help ultrasound imaging reduce grating lobes, perform super-resolution and better SNR(signal-to-noise ratio). Chapter 6: A discussion of the overall content of the thesis as well as suggestions for further development together with the remaining problems are summarized.首都大学東京, 2019-03-25, 博士（工学）首都大学東

Label-free high-throughput photoacoustic tomography of suspected circulating melanoma tumor cells in patients in vivo

Significance: Detection and characterization of circulating tumor cells (CTCs), a key determinant of metastasis, are critical for determining risk of disease progression, understanding metastatic pathways, and facilitating early clinical intervention. Aim: We aim to demonstrate label-free imaging of suspected melanoma CTCs. Approach: We use a linear-array-based photoacoustic tomography system (LA-PAT) to detect melanoma CTCs, quantify their contrast-to-noise ratios (CNRs), and measure their flow velocities in most of the superficial veins in humans. Results: With LA-PAT, we successfully imaged suspected melanoma CTCs in patients in vivo, with a CNR >9. CTCs were detected in 3 of 16 patients with stage III or IV melanoma. Among the three CTC-positive patients, two had disease progression; among the 13 CTC-negative patients, 4 showed disease progression. Conclusions: We suggest that LA-PAT can detect suspected melanoma CTCs in patients in vivo and has potential clinical applications for disease monitoring in melanoma

An ultrasonic system for intravascular measurement and visualisation of anatomical structures and blood flow

Imperial Users onl

MEMS Technology for Biomedical Imaging Applications

Biomedical imaging is the key technique and process to create informative images of the human body or other organic structures for clinical purposes or medical science. Micro-electro-mechanical systems (MEMS) technology has demonstrated enormous potential in biomedical imaging applications due to its outstanding advantages of, for instance, miniaturization, high speed, higher resolution, and convenience of batch fabrication. There are many advancements and breakthroughs developing in the academic community, and there are a few challenges raised accordingly upon the designs, structures, fabrication, integration, and applications of MEMS for all kinds of biomedical imaging. This Special Issue aims to collate and showcase research papers, short commutations, perspectives, and insightful review articles from esteemed colleagues that demonstrate: (1) original works on the topic of MEMS components or devices based on various kinds of mechanisms for biomedical imaging; and (2) new developments and potentials of applying MEMS technology of any kind in biomedical imaging. The objective of this special session is to provide insightful information regarding the technological advancements for the researchers in the community

Photoacoustic brain imaging: from microscopic to macroscopic scales

Human brain mapping has become one of the most exciting contemporary research areas, with major breakthroughs expected in the coming decades. Modern brain imaging techniques have allowed neuroscientists to gather a wealth of anatomic and functional information about the brain. Among these techniques, by virtue of its rich optical absorption contrast, high spatial and temporal resolutions, and deep penetration, photoacoustic tomography (PAT) has attracted more and more attention, and is playing an increasingly important role in brain studies. In particular, PAT complements other brain imaging modalities by providing high-resolution functional and metabolic imaging. More importantly, PAT’s unique scalability enables scrutinizing the brain at both microscopic and macroscopic scales, using the same imaging contrast. In this review, we present the state-of-the-art PAT techniques for brain imaging, summarize representative neuroscience applications, outline the technical challenges in translating PAT to human brain imaging, and envision potential technological deliverables

Photoacoustic microscopy

Photoacoustic microscopy (PAM) is a hybrid in vivo imaging technique that acoustically detects optical contrast via the photoacoustic effect. Unlike pure optical microscopic techniques, PAM takes advantage of the weak acoustic scattering in tissue and thus breaks through the optical diffusion limit (∼1 mm in soft tissue). With its excellent scalability, PAM can provide high-resolution images at desired maximum imaging depths up to a few millimeters. Compared with backscattering-based confocal microscopy and optical coherence tomography, PAM provides absorption contrast instead of scattering contrast. Furthermore, PAM can image more molecules, endogenous or exogenous, at their absorbing wavelengths than fluorescence-based methods, such as wide-field, confocal, and multi-photon microscopy. Most importantly, PAM can simultaneously image anatomical, functional, molecular, flow dynamic and metabolic contrasts in vivo. Focusing on state-of-the-art developments in PAM, this Review discusses the key features of PAM implementations and their applications in biomedical studies

Recent progress in photoacoustic molecular imaging

By acoustically detecting the optical absorption contrast, photoacoustic (PA) tomography (PAT) has broken the penetration limits of traditional high-resolution optical imaging. Through spectroscopic analysis of the target's optical absorption, PAT can identify a wealth of endogenous and exogenous molecules and thus is inherently capable of molecular imaging with high sensitivity. PAT's molecular sensitivity is uniquely accompanied by non-ionizing radiation, high spatial resolution, and deep penetration in biological tissues, which other optical imaging modalities cannot achieve yet. In this concise review, we summarize the most recent technological advancements in PA molecular imaging and highlight the novel molecular probes specifically made for PAT in deep tissues. We conclude with a brief discussion of the opportunities for future advancements

Recent progress in photoacoustic molecular imaging

By acoustically detecting the optical absorption contrast, photoacoustic (PA) tomography (PAT) has broken the penetration limits of traditional high-resolution optical imaging. Through spectroscopic analysis of the target's optical absorption, PAT can identify a wealth of endogenous and exogenous molecules and thus is inherently capable of molecular imaging with high sensitivity. PAT's molecular sensitivity is uniquely accompanied by non-ionizing radiation, high spatial resolution, and deep penetration in biological tissues, which other optical imaging modalities cannot achieve yet. In this concise review, we summarize the most recent technological advancements in PA molecular imaging and highlight the novel molecular probes specifically made for PAT in deep tissues. We conclude with a brief discussion of the opportunities for future advancements

Multiscale Functional and Molecular Photoacoustic Tomography

Photoacoustic tomography (PAT) combines rich optical absorption contrast with the high spatial resolution of ultrasound at depths in tissue. The high scalability of PAT has enabled anatomical imaging of biological structures ranging from organelles to organs. The inherent functional and molecular imaging capabilities of PAT have further allowed it to measure important physiological parameters and track critical cellular activities. Integration of PAT with other imaging technologies provides complementary capabilities and can potentially accelerate the clinical translation of PAT

Photoacoustic tomography and sensing in biomedicine

Photoacoustics has been broadly studied in biomedicine, for both human and small animal tissues. Photoacoustics uniquely combines the absorption contrast of light or radio frequency waves with ultrasound resolution. Moreover, it is non-ionizing and non-invasive, and is the fastest growing new biomedical method, with clinical applications on the way. This review provides a brief recap of recent developments in photoacoustics in biomedicine, from basic principles to applications. The emphasized areas include the new imaging modalities, hybrid detection methods, photoacoustic contrast agents and the photoacoustic Doppler effect, as well as translational research topics