Enhancement of contrast and resolution of B-mode plane wave imaging (PWI) with non-linear filtered delay multiply and sum (FDMAS) beamforming

FDMAS has been successfully used in microwave imaging for breast cancer detection. FDMAS gained its popularity due to its capability to produce results faster than any other adaptive beamforming technique such as minimum variance (MV) which requires higher computational complexity. The average computational time for single point spread function (PSF) at 40 mm depth for FDMAS is 87 times faster than MV. The new beamforming technique has been tested on PSF and cyst phantoms experimentally with the ultrasound array research platform version 2 (UARP II) using a 3-8 MHz 128 element clinical transducer. FDMAS is able to improve both imaging contrast and spatial resolution as compared to DAS. The wire phantom main lobes lateral resolution improved in FDMAS by 40.4% with square pulse excitation signal when compared to DAS. Meanwhile the contrast ratio (CR) obtained for an anechoic cyst located at 15 mm depth for PWI with DAS and FDMAS are -6.2 dB and -14.9 dB respectively. The ability to reduce noise from off axis with auto-correlation operation in FDMAS pave the way to display the B-mode image with high dynamic range. However, the contrast to noise ratio (CNR) measured at same cyst location for FDMAS give less reading compared to DAS. Nevertheless, this drawback can be compensated by applying compound plane wave imaging (CPWI) technique on FDMAS. In overall the new FDMAS beamforming technique outperforms DAS in laboratory experiments by narrowing its main lobes and increases the image contrast without sacrificing its frame rates

Spatial Resolution and Contrast Enhancement in Photoacoustic Imaging with Filter Delay Multiply and Sum Beamforming Technique

Photoacoustic imaging is used to differentiate between tissue types based on light absorption. Different structures, such as vascular density of capillaries in human tissue, can be analysed and provide diagnostic information to detect early stage breast cancer. Delay and sum (DAS) beamforming is the traditional method to reconstruct photoacoustic images. However, for structures located deep in the tissue (>10 mm), signal to noise (SNR) of the photoacoustic signal drops significantly. This study proposes using filter delay multiply and sum (FDMAS) beamforming technique to increase the SNR and enhance the image quality. Experimental results showed that FDMAS beamformer improved the SNR by 6.9 dB and the lateral resolution by 48% compared to the DAS beamformer. Moreover, the effect of aperture size on the proposed method is presented as the sub-group FDMAS, which further increased the improvement in image quality

Elevation resolution enhancement in 3D photoacoustic imaging using FDMAS beamforming

Photoacoustic imaging is a non-invasive and non-ionizing imaging technique that combines the spectral selectivity of laser excitation with the high resolution of ultrasound imaging. It is possible to identity the vascular structure of the cancerous tissue using this imaging modality. However, elevation and lateral resolution of photoacoustic imaging is usually poor for imaging target. In this study, three dimension filter delay multiply and sum beamforming technique (FDMAS(3D)) is used to improve the resolution and enhance the signal to noise ratio (SNR) of the 3D photoacoustic image that is created by using linear array transducer. This beamforming technique showed improvement in the elevation by 36% when its compared with three dimension delay and sum beamforming technique (DAS(3D)). In addition, it enhanced the SNR by 13 dB compared with DAS (3D)

Optimizing the lateral beamforming step for filtered-delay multiply and sum beamforming to improve active contour segmentation using ultrafast ultrasound imaging

As an alternative to delay-and-sum beamforming, a novel beamforming technique called filtered-delay multiply and sum (FDMAS) was introduced recently to improve ultrasound B-mode image quality. Although a considerable amount of work has been performed to evaluate FDMAS performance, no study has yet focused on the beamforming step size, , in the lateral direction. Accordingly, the performance of FDMAS was evaluated in this study by fine-tuning to find its optimal value and improve boundary definition when balloon snake active contour (BSAC) segmentation was applied to a B-mode image in ultrafast imaging. To demonstrate the effect of altering in the lateral direction on FDMAS, measurements were performed on point targets, a tissue-mimicking phantom and in vivo carotid artery, by using the ultrasound array research platform II equipped with one 128-element linear array transducer, which was excited by 2-cycle sinusoidal signals. With 9-angle compounding, results showed that the lateral resolution (LR) of the point target was improved by 67.9% and 81.2%, when measured at −6 dB and −20 dB respectively, when was reduced from to . Meanwhile the image contrast ratio (CR) measured on the CIRS phantom was improved by 10.38 dB at the same reduction and the same number of compounding angles. The enhanced FDMAS results with lower side lobes and less clutter noise in the anechoic regions provides a means to improve boundary definition on a B-mode image when BSAC segmentation is applied

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

Unfocused ultrasound waves for manipulating and imaging microbubbles

With unfocused plane/diverging ultrasound waves, the capability of simultaneous sampling on each element of an array transducer has spawned a branch known as high-frame-rate (HFR) ultrasound imaging, whose frame rate can be two orders of magnitude faster than traditional imaging systems. Microbubbles are micron-sized spheres with a heavy gas core that is stabilized by a shell made of lipids, polymers, proteins, or surfactants. They are excellent ultrasound scatters and have been used as ultrasound contrast agents, and more recently researched as a mechanism for targeted drug delivery. With the Ultrasound Array Research Platform II (UARP II), the objective of this thesis was to develop and advance several techniques for manipulating and imaging microbubbles using unfocused ultrasound waves. These techniques were achieved by combining custom transmit/receiving sequencing and advanced signal processing algorithms, holding promise for enhanced diagnostic and therapeutic applications of microbubbles. A method for locally accumulating microbubbles with fast image guidance was first presented. A linear array transducer performed trapping of microbubble populations interleaved with plane wave imaging, through the use of a composite ultrasound pulse sequence. This technique could enhance image-guided targeted drug delivery using microbubbles. A key component of targeted drug delivery using liposome-loaded microbubbles and ultrasound is the ability to track these drug vehicles to guide payload release locally. As a uniquely identifiable emission from microbubbles, the subharmonic signal is of interest for this purpose. The feasibility of subharmonic plane wave imaging of liposome-loaded microbubbles was then proved. The improved subharmonic sensitivity especially at depth compared to their counterpart of bare (unloaded) microbubbles was confirmed. Following plane wave imaging, the combination of diverging ultrasound waves and microbubbles was investigated. The image formation techniques using coherent summation of diverging waves are susceptible to tissue and microbubble motion artefacts, resulting in poor image quality. A correlation-based 2-D motion estimation algorithm was then proposed to perform motion compensation for HFR contrast-enhanced echocardiography (CEE). A triplex cardiac imaging technique, consisting of B mode, contrast mode and 2-D vector flow imaging with a frame rate of 250 Hz was presented. It was shown that the efficacy of coherent diverging wave imaging of the heart is reliant on carefully designed motion compensation algorithms capable of correcting for incoherence between steered diverging-wave transmissions. Finally, comparisons were made between the correlation-based method and one established image registration method for motion compensation. Results show that the proposed correlation-based method outperformed the image registration model for motion compensation in HFR CEE, with the improved image contrast ratio and visibility of geometrical borders both in vitro and in vivo

Plasmonic Gold Nanoparticles: Combining Photoacoustic Imaging and Photothermal Therapy for New Cancer Treatments

Cancer is a complex disease with significant variability between cases, and as a result, is one of the leading causes of death worldwide. Lung cancer is a particularly difficult form of cancer to diagnose and treat, due largely to the inaccessibility of lung tumours and the limited available treatment options. There is a need for highly targeted, minimally invasive treatment options that facilitate the complete removal of cancer from a patient while minimising damage to non-malignant tissue. The development of plasmonic gold nanoparticles has lead to their potential use in a large range of disciplines, and in particular, they have shown great promise for application in biomedicine. Plasmonic gold nanoparticles possess many desirable characteristics, such as controllable size and shape during synthesis, the biocompatible and inert nature of gold, the potential functionalisation and surface modification prospects, and tunable surface plasmon resonances, that make them excellent candidates for biological use. These beneficial properties facilitate their use as contrast agents to further enhance existing light-based biomedical techniques, such as photoacoustic imaging and photothermal therapy, while possessing the ability to form new combined treatments. In this thesis, gold nanorods - a subset of gold nanoparticles - will be investigated as a means to mediate photoacoustic imaging and photothermal therapy for combined lung cancer theranostics, while demonstrating their ability to improve current clinical practice. Since gold nanorods can be synthesised to be almost any size, and their aspect ratio governs their peak surface plasmon resonance, there may be an optimal sized AuNR for use in biomedical modalities that absorbs light at a particular wavelength. Four different sized gold nanorods (widths of 10, 25, 40, and 50 nm) with similar aspect ratios and therefore similar surface plasmon resonances (815 ± 26 nm) were considered for use in photoacoustic imaging. It was shown that the larger gold nanorods produced the highest photoacoustic amplitude at an equivalent number of nanoparticles, but were the most toxic, while the smallest gold nanorods were optimal at an equivalent total mass. The results indicate the importance for determining the dependence of total mass or number of nanoparticles on cellular targeting and uptake in vivo. Gold nanorods can also be used as photoabsorbers for therapeutic modalities, such as photothermal therapy. Conventionally, continuous wave lasers are used to generate bulk heating in gold nanorods, that are situated in a target region, and the diseased tissue is destroyed via hyperthermia. However, there are potential negative side-effects of heat-induced cell death, such as the risk of damage to healthy tissue due to heat conducting tothe surrounding environment, and the development of heat and drug resistance. Therefore, the use of pulsed lasers for photothermal therapy was investigated and compared with continuous wave lasers. It was shown that, for continuous wave lasers, a larger number of gold nanorods in the absorbing region resulted in increased cell death, whereas with pulsed lasers, the location of the gold nanorods, with respect to the cells, was the most important factor governing laser-induced toxicity. Furthermore, gold nanorods targeted to lung cancer EGFR receptors showed enhanced therapeutic efficacy under pulsed laser illumination. Finally, the potential for gold nanorods to enhance endobronchial ultrasound - an existing clinical procedure for guiding lung cancer needle biopsies - was considered. This routine practice uses conventional B-mode ultrasound and a wide field of view to facilitate the locating of lymph nodes and guide the staging of lung cancer. This technique could be further improved with the use of gold nanorod mediated photoacoustic imaging with potentially minimal adaptation, since the underlying technology required to combine these modalities already exists. It was shown that inclusions of gold nanorods can be observed under pulsed laser illumination using imaging and transducer parameters comparable to that of endobronchial ultrasound. The potential for this promising new multimodality was demonstrated, with the aim of guiding future development. Overall, the work presented in this thesis provided valuable insights into the development of gold nanorods for biomedicine, and has demonstrated the potential for improving new and existing theranostic modalities