Novel Techniques for Tissue Imaging and Characterization Using Biomedical Ultrasound

The use of ultrasound technology in the biomedical field has been widely increased in recent decades. Ultrasound modalities are considered more safe and cost effective than others that use ionizing radiation. Moreover, the use of high-frequency ultrasound provides means of high-resolution and precise tissue assessment. Consequently, ultrasound elastic waves have been widely used to develop non-invasive techniques for tissue assessment. In this work, ultrasound waves have been used to develop non-invasive techniques for tissue imaging and characterization in three different applications.;Currently, there is a lack of imaging modalities to accurately predict minute structures and defects in the jawbone. In particular, the inability of 2D radiographic images to detect bony periodontal defects resulted from infection of the periodontium. They also may carry known risks of cancer generation or may be limited in accurate diagnosis scope. Ultrasonic guided waves are sensitive to changes in microstructural properties, while high-frequency ultrasound has been used to reconstruct high-resolution images for tissue. The use of these ultrasound techniques may provide means for early diagnosis of marrow ischemic disorders via detecting focal osteoporotic marrow defect, chronic nonsuppurative osteomyelitis, and cavitations in the mandible (jawbone). The first part of this work investigates the feasibility of using guided waves and high frequency ultrasound for non-invasive human jawbone assessment. The experimental design and the signal/image processing procedures for each technique are developed, and multiple in vitro studies are carried out using dentate and non-dentate mandibles. Results from both the ultrasonic guided waves analysis and the high frequency 3D echodentographic imaging suggest that these techniques show great potential in providing non-invasive methods to characterize the jawbone and detect periodontal diseases at earlier stages.;The second part of this work describes indirect technique for characterization via reconstructing high-resolution microscopic images. The availability of well-defined genetic strains and the ability to create transgenic and knockout mice makes mouse models extremely significant tools in different kinds of research. For example, noninvasive measurement of cardiovascular function in mouse hearts has become a valuable need when studying the development or treatment of various diseases. This work describes the development and testing of a single-element ultrasound imaging system that can reconstruct high-resolution brightness mode (B-mode) images for mouse hearts and blood vessels that can be used for quantitative measurements in vitro. Signal processing algorithms are applied on the received ultrasound signals including filtering, focusing, and envelope detection prior to image reconstruction. Additionally, image enhancement techniques and speckle reduction are adopted to improve the image resolution and quality. The system performance is evaluated using both phantom and in vitro studies using isolated mouse hearts and blood vessels from APOE-KO and its wild type control. This imaging system shall provide a basis for early and accurate detection of different kinds of diseases such as atherosclerosis in mouse model.;The last part of this work is initialized by the increasing need for a non-invasive method to assess vascular wall mechanics. Endothelial dysfunction is considered a key factor in the development of atherosclerosis. Flow-mediated vasodilatation (FMD) measurement in brachial and other conduit arteries has become a common method to assess the endothelial function in vivo. In spite of the direct relationship that could be between the arterial wall multi-component strains and the FMD response, direct measurement of wall strain tensor due to FMD has not yet been reported in the literature. In this work, a noninvasive direct ultrasound-based strain tensor measuring (STM) technique is presented to assess changes in the mechanical parameters of the vascular wall during post-occlusion reactive hyperemia and/or FMD, including local velocities and displacements, diameter change, local strain tensor and strain rates. The STM technique utilizes sequences of B-mode ultrasound images as its input with no extra hardware requirement. The accuracy of the STM algorithm is assessed using phantom, and in vivo studies using human subjects during pre- and post-occlusion. Good correlations are found between the post-occlusion responses of diameter change and local wall strains. Results indicate the validity and versatility of the STM algorithm, and describe how parameters other than the diameter change are sensitive to reactive hyperemia following occlusion. This work suggests that parameters such as local strains and strain rates within the arterial wall are promising metrics for the assessment of endothelial function, which can then be used for accurate assessment of atherosclerosis

Curved array photoacoustic tomographic system for small animal imaging

We present systematic characterization of a photoacoustic imaging system optimized for rapid, high-resolution tomographic imaging of small animals. The system is based on a 128-element ultrasonic transducer array with a 5-MHz center frequency and 80% bandwidth shaped to a quarter circle of 25mm radius. A 16-channel data-acquisition module and dedicated channel detection electronics enable capture of a 90-deg field-of-view image in less than 1s and a complete 360-deg scan using sample rotation within 15s. Measurements on cylindrical phantom targets demonstrate a resolution of better than 200μm and high-sensitivity detection of 580-μm blood tubing to depths greater than 3cm in a turbid medium with reduced scattering coefficient μ′s =7.8cm^(−1). The system is used to systematically investigate the effects of target size, orientation, and geometry on tomographic imaging. As a demonstration of these effects and the system imaging capabilities, we present tomographic photoacoustic images of the brain vasculature of an ex vivo mouse with varying measurement aperture. For the first time, according to our knowledge, resolution of sub-200-μm vessels with an overlying turbid medium of greater than 2cm depth is demonstrated using only intrinsic biological contrast

3D Super-Resolution Ultrasound with Adaptive Weight-Based Beamforming

Super-resolution ultrasound (SRUS) imaging through localising and tracking sparse microbubbles has been shown to reveal microvascular structure and flow beyond the wave diffraction limit. Most SRUS studies use standard delay and sum (DAS) beamforming, where large main lobe and significant side lobes make separation and localisation of densely distributed bubbles challenging, particularly in 3D due to the typically small aperture of matrix array probes. This study aims to improve 3D SRUS by implementing a low-cost 3D coherence beamformer based on channel signal variance, as well as two other adaptive weight-based coherence beamformers: nonlinear beamforming with p-th root compression and coherence factor. The 3D coherence beamformers, together with DAS, are compared in computer simulation, on a microflow phantom, and in vivo. Simulation results demonstrate that the adaptive weight-based beamformers can significantly narrow the main lobe and suppress the side lobes for modest computational cost. Significantly improved 3D SR images of microflow phantom and a rabbit kidney are obtained through the adaptive weight-based beamformers. The proposed variance-based beamformer performs best in simulations and experiments.Comment: Ultrasound localisation microscopy (ULM), super-resolution, contrast-enhanced ultrasound, 3D beamformin

Development, Optimization and Clinical Evaluation Of Algorithms For Ultrasound Data Analysis Used In Selected Medical Applications.

The assessment of soft and hard tissues is critical when selecting appropriate protocols for restorative and regenerative therapy in the field of dental surgery. The chosen treatment methodology will have significant ramifications on healing time, success rate and overall long-time oral health. Currently used diagnostic methods are limited to visual and invasive assessments; they are often user-dependent, inaccurate and result in misinterpretation. As such, the clinical need has been identified for objective tissue characterization, and the proposed novel ultrasound-based approach was designed to address the identified need. The device prototype consists of a miniaturized probe with a specifically designed ultrasonic transducer, electronics responsible for signal generation and acquisition, as well as an optimized signal processing algorithm required for data analysis. An algorithm where signals are being processed and features extracted in real-time has been implemented and studied. An in-depth algorithm performance study has been presented on synthetic signals. Further, in-vitro laboratory experiments were performed using the developed device with the algorithm implemented in software on animal-based samples. Results validated the capabilities of the new system to reproduce gingival assessment rapidly and effectively. The developed device has met clinical usability requirements for effectiveness and performance

A real-time photoacoustic tomography system for small animals

A real-time 512-element photoacoustic tomography system for small animal imaging using a ring ultrasound array has been developed. The system, based upon a 5 MHz transducer array formed along a 50 mm circular aperture, achieves sub-200 micron lateral resolution over a 2 cm disk-shaped region. Corresponding elevation resolutions of 0.6 to 2.5 mm over the central volume enable depth-resolved 3D tomographic imaging with linear translation. Using 8:1 electronic multiplexing, imaging at up to 8 frame/sec is demonstrated for both dynamic phantoms and in vivo mouse and brain samples. The real-time, full 2D tomographic capability of the system paves the way for functional photoacoustic tomographic imaging studies in small animals with sub-second time frame

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

A fast 512-element ring array photoacoustic imaging system for small animals

A 512-element photoacoustic tomography system for small animal imaging using a ring ultrasound array has been developed. The system features a 5 MHz piezocomposite transducer array formed into a complete circular aperture. Custom receiver electronics consisting of dedicated preamplifiers, 8:1 multiplexed post-amplifiers, and a 64-channel data acquisition module provide full tomographic imaging at up to 8 frames/second. We present details of the system design along with characterization results of the resolution, imaging volume, and sensitivity. Small animal imaging performance is demonstrated through images of mice brain vasculature at different depths and real-time spectroscopic scans. This system enables real-time tomographic imaging for functional photoacoustic studies for the first time

High-intensity focused ultrasound therapy in the uterine fibroid: a clinical case study of poor heating efficacy

A clinical case study of high-intensity focused ultrasound (HIFU) treatment in the uterine fibroid was conducted. During the therapy, poor heating efficacy was observed which could be attributed to several factors such as the local perfusion rate, patient-specific anatomy or changes in acoustic parameters of the ultrasound field. In order to determine the cause of the diminished heating, perfusion analyses and ultrasound simulations were conducted using the magnetic resonance imaging (MRI) data from the treatment. The perfusion analysis showed high local perfusion rate in the myoma (301.0 +- 25.6 mL/100 g/min) compared to the surrounding myometrium (233.8 +- 16.2 mL/100 g/min). The ultrasound simulations did not show large differences in the focal point shape or the acoustic pressure (2.07 +- 0.06 MPa) when tilting the transducer. However, a small shift (-2.2 +- 1.3 mm) in the axial location of the focal point was observed. The main causes for the diminished heating were likely the high local perfusion and ultrasound attenuation due to the deep location of the myoma.Comment: Conference Proceedin

Small-animal whole-body imaging using a photoacoustic full-ring array system

In this report, we present a novel 3D photoacoustic computed tomography (PACT) system for small-animal whole-body imaging. The PACT system, based on a 512-element full-ring transducer array, received photoacoustic signals primarily from a 2-mm-thick slice. The light was generated by a pulse laser, and can either illuminate from the top or be reshaped to illuminate the sample from the side, using a conical lens and an optical condenser. The PACT system was capable of acquiring an in-plane image in 1.6 s; by scanning the sample in the elevational direction, a 3D tomographic image could be constructed. We tested the system by imaging a cylindrical phantom made of human hairs immersed in a scattering medium. The reconstructed image achieved an in-plane resolution of 0.1 mm and an elevational resolution of 1 mm. After deconvolution in the elevational direction, the 3D image was found to match well with the phantom. The system was also used to image a baby mouse in situ; the spinal cord and ribs can be seen easily in the reconstructed image. Our results demonstrate that the PACT system has the potential to be used for fast small-animal whole-body tomographic imaging