Design and Analysis of MEMS Based PVDF Ultrasonic Transducers for Vascular Imaging

Polyvinilidene fluoride (PVDF) single-element transducers for high-frequency (>30 MHz) ultrasound imaging applications have been developed using MEMS (Micro-electro-Mechanical Systems) compatible techniques. Performance of these transducers has been investigated by analyzing the sources and effects of on-chip parasitic capacitances on the insertion-loss of the transducers. Modeling and experimental studies showed that on-chip parasitic capacitances degraded the performance of the transducers and an improved method of fabrication was suggested and new devices were built. New devices developed with minimal parasitic effects were shown to improve the performance significantly. A 1-mm aperture PVDF device developed with minimal parasitic effects has resulted in a reduction of insertion loss of 21 dB compared with devices fabricated using a previous method

Development of a Focused Broadband Ultrasonic Transducer for High Resolution Fundamental and Harmonic Intravascular Imaging

Intravascular ultrasound (IVUS) is increasingly employed for detection and evaluation of coronary artery diseases. Tissue Harmonic Imaging provides different tissue information that could additionally be used to improve diagnostic accuracy. However, current IVUS systems, with their unfocussed transducers, may not be capable of operating in harmonic imaging mode. Thus, there is a need to develop suitable transducers and appropriate techniques to allow imaging in multi modes for complementary diagnostic information. Focused PVDF TrFE transducers were developed using MEMS (Micro-Electro-Mechanical-Systems) compatible protocols. The transducers were characterized using pulse-echo techniques and exhibited broad bandwidth (110 at -6dB) with axial resolutions of Such promising results suggest that focused, broadband PVDF TrFE transducers have opened up the potential to incorporate harmonic imaging modality in IVUS and also improve the image quality. In addition, the transducer\u27s multimodality imaging capability, not possible with the current systems, could enhance the functionality and thereby the clinical use of IVU

Development of a Focused Broadband Ultrasonic Transducer for High Resolution Fundamental and Harmonic Intravascular Imaging

Intravascular ultrasound (IVUS) is increasingly employed for detection and evaluation of coronary artery diseases. Tissue Harmonic Imaging provides different tissue information that could additionally be used to improve diagnostic accuracy. However, current IVUS systems, with their unfocussed transducers, may not be capable of operating in harmonic imaging mode. Thus, there is a need to develop suitable transducers and appropriate techniques to allow imaging in multi modes for complementary diagnostic information. Focused PVDF TrFE transducers were developed using MEMS (Micro-Electro-Mechanical-Systems) compatible protocols. The transducers were characterized using pulse-echo techniques and exhibited broad bandwidth (110 at -6dB) with axial resolutions of Such promising results suggest that focused, broadband PVDF TrFE transducers have opened up the potential to incorporate harmonic imaging modality in IVUS and also improve the image quality. In addition, the transducer\u27s multimodality imaging capability, not possible with the current systems, could enhance the functionality and thereby the clinical use of IVU

Development of a Focused Broadband Ultrasonic Transducer for High Resolution Fundamental and Harmonic Intravascular Imaging

Intravascular ultrasound (IVUS) is increasingly employed for detection and evaluation of coronary artery diseases. Tissue Harmonic Imaging provides different tissue information that could additionally be used to improve diagnostic accuracy. However, current IVUS systems, with their unfocussed transducers, may not be capable of operating in harmonic imaging mode. Thus, there is a need to develop suitable transducers and appropriate techniques to allow imaging in multi modes for complementary diagnostic information. Focused PVDF TrFE transducers were developed using MEMS (Micro-Electro-Mechanical-Systems) compatible protocols. The transducers were characterized using pulse-echo techniques and exhibited broad bandwidth (110 at -6dB) with axial resolutions of Such promising results suggest that focused, broadband PVDF TrFE transducers have opened up the potential to incorporate harmonic imaging modality in IVUS and also improve the image quality. In addition, the transducer\u27s multimodality imaging capability, not possible with the current systems, could enhance the functionality and thereby the clinical use of IVU

Development of High-speed Photoacoustic Imaging technology and Its Applications in Biomedical Research

Photoacoustic (PA) tomography (PAT) is a novel imaging modality that combines the fine lateral resolution from optical imaging and the deep penetration from ultrasonic imaging, and provides rich optical-absorption–based images. PAT has been widely used in extracting structural and functional information from both ex vivo tissue samples to in vivo animals and humans with different length scales by imaging various endogenous and exogenous contrasts at the ultraviolet to infrared spectrum. For example, hemoglobin in red blood cells is of particular interest in PAT since it is one of the dominant absorbers in tissue at the visible wavelength.The main focus of this dissertation is to develop high-speed PA microscopy (PAM) technologies. Novel optical scanning, ultrasonic detection, and laser source techniques are introduced in this dissertation to advance the performance of PAM systems. These upgrades open up new avenues for PAM to be applicable to address important biomedical challenges and enable fundamental physiological studies.First, we investigated the feasibility of applying high-speed PAM to the detection and imaging of circulating tumor cells (CTCs) in melanoma models, which can provide valuable information about a tumor’s metastasis potentials. We probed the melanoma CTCs at the near-infrared wavelength of 1064 nm, where the melanosomes absorb more strongly than hemoglobin. Our high-speed PA flow cytography system successfully imaged melanoma CTCs in travelling trunk vessels. We also developed a concurrent laser therapy device, hardware-triggered by the CTC signal, to photothermally lyse the CTC on the spot in an effort to inhibit metastasis.Next, we addressed the detection sensitivity issue in the previous study. We employed the stimulated Raman scattering (SRS) effect to construct a high-repetition-rate Raman laser at 658 nm, where the contrast between a melanoma CTC and the blood background is near the highest. Our upgraded PA flow cytography successfully captured sequential images of CTCs in mouse melanoma xenograft model, with a significantly improved contrast-to-noise ratio compared to our previous results. This technology is readily translatable to the clinics to extract the information of a tumor’s metastasis risks.We extended the Raman laser technology to the field of brain functional studies. We developed a MEMS (micro-electromechanical systems) scanner for fast optical scanning, and incorporated it to a dual-wavelength functional PAM (fPAM) for high-speed imaging of cerebral hemodynamics in mouse. This fPAM system successfully imaged transient changes in blood oxygenation at cerebral micro-vessels in response to brief somatic stimulations. This fPAM technology is a powerful tool for neurological studies.Finally, we explored some approaches of reducing the size the PAM imaging head in an effort to translate our work to the field of wearable biometric monitors. To miniaturize the ultrasonic detection device, we fabricated a thin-film optically transparent piezoelectric detector for detecting PA waves. This technology could enable longitudinal studies on free-moving animals through a wearable version of PAM

Wave of single-impulse-stimulated fast initial dip in single vessels of mouse brains imaged by high-speed functional photoacoustic microscopy

Significance: The initial dip in hemoglobin-oxygenation response to stimulations is a spatially confined endogenous indicator that is faster than the blood flow response, making it a desired label-free contrast to map the neural activity. A fundamental question is whether a single-impulse stimulus, much shorter than the response delay, could produce an observable initial dip without repeated stimulation. Aim: To answer this question, we report high-speed functional photoacoustic (PA) microscopy to investigate the initial dip in mouse brains. Approach: We developed a Raman-laser-based dual-wavelength functional PA microscope that can image capillary-level blood oxygenation at a 1-MHz one-dimensional imaging rate. This technology was applied to monitor the hemodynamics of mouse cerebral vasculature after applying an impulse stimulus to the forepaw. Results: We observed a transient initial dip in cerebral microvessels starting as early as 0.13 s after the onset of the stimulus. The initial dip and the subsequent overshoot manifested a wave pattern propagating across different microvascular compartments. Conclusions: We quantified both spatially and temporally the single-impulse-stimulated microvascular hemodynamics in mouse brains at single-vessel resolution. Fast label-free imaging of single-impulse response holds promise for real-time brain–computer interfaces

Wave of single-impulse-stimulated fast initial dip in single vessels of mouse brains imaged by high-speed functional photoacoustic microscopy

Significance: The initial dip in hemoglobin-oxygenation response to stimulations is a spatially confined endogenous indicator that is faster than the blood flow response, making it a desired label-free contrast to map the neural activity. A fundamental question is whether a single-impulse stimulus, much shorter than the response delay, could produce an observable initial dip without repeated stimulation. Aim: To answer this question, we report high-speed functional photoacoustic (PA) microscopy to investigate the initial dip in mouse brains. Approach: We developed a Raman-laser-based dual-wavelength functional PA microscope that can image capillary-level blood oxygenation at a 1-MHz one-dimensional imaging rate. This technology was applied to monitor the hemodynamics of mouse cerebral vasculature after applying an impulse stimulus to the forepaw. Results: We observed a transient initial dip in cerebral microvessels starting as early as 0.13 s after the onset of the stimulus. The initial dip and the subsequent overshoot manifested a wave pattern propagating across different microvascular compartments. Conclusions: We quantified both spatially and temporally the single-impulse-stimulated microvascular hemodynamics in mouse brains at single-vessel resolution. Fast label-free imaging of single-impulse response holds promise for real-time brain–computer interfaces

High frequency CMUT for continuous monitoring of red blood cells aggregation

Récemment, de nombreuses recherches ont démontré que le transducteur ultrasonore micro-usiné capacitif CMUT peut être une alternative aux transducteurs piézoélectriques dans différents domaines, y compris l’imagerie par ultrasons médicaux. Des travaux antérieurs ont démontré les avantages de CMUT en termes de production à haute fréquence, de sensibilité, de compatibilité avec la technologie complémentaire métal – oxyde – semi-conducteur et de coût de fabrication peu élevé. Ce travail montrera les travaux préliminaires en vue de la fabrication d'un transducteur à ultrasons utilisant des CMUT pour mesurer en continu l'agrégation des globules rouges. Les cellules CMUT ont été conçues et simulées pour obtenir des fréquences de résonance et des dimensions spécifiques répondant à cet objectif, à l'aide de la modélisation par éléments finis avec COMSOL Multiphysics. Des simulations par ultrasons (logiciel Field II) ont été utilisées pour caractériser les faisceaux ultrasonores émis et reçus afin de concevoir la distribution géométrique des cellules. La fabrication a été réalisée en utilisant une photolithographie multicouche et des dépôts. Huit masques ont été conçus pour chaque couche de dépôt. Les masques ont été conçus pour comporter quatre groupes de CMUT, le premier émettant et recevant à 40 MHz, le second émettant à 30 MHz et recevant à 40 MHz, le troisième émettant à 20 MHz et recevant à 30 MHz, et le dernier émettant à 10 MHz. MHz et réception à 30 MHz. La fréquence change avec le rayon de chaque cellule CMUT, mais les dimensions de l'épaisseur sont les mêmes pour toutes les cellules, les épaisseurs des membranes et des couches isolantes sont de 0,3 µm et l'intervalle de vide est de 0,1 µm. Les matrices CMUT ont été fabriquées à l'aide de la technologie de couche de libération sacrificielle du laboratoire Polytechnique LMF.Research has demonstrated that Capacitive Micro machined Ultrasonic Transducer (CMUT) can be an alternative to piezoelectric transducers in different domains including medical ultrasound imaging. Previous work showed advantages of CMUT in terms of high frequency production, sensitivity, its compatibility with complementary metal–oxide–semiconductor technology and its low cost of fabrication. This work will show preliminary work toward fabricating an ultrasound transducer using CMUTs to continuously measure Red Blood Cells aggregation. CMUTs cells were designed and simulated to obtain specific resonant frequencies and dimension that fulfill that purpose using finite element modeling with COMSOL Multiphysics. Ultrasound simulations (Field II software) were used to characterize the emitted and received US beams to design the cells geometrical distribution. Fabrication was done using multilayered photolithography and depositions. Eight masks were designed for each deposition layer. The masks were designed to have four groups of CMUTs, one emitting and receiving at 40MHz, a second emitting at 30 MHz and receiving at 40 MHz, a third one emitting at 20 MHz and receiving at 30 MHz, and a last one emitting at 10 MHz and receiving at 30 MHz. The frequency changes with the radius of each CMUT cell but the thickness dimensions are the same for all the cells, the membranes and insulation layers thicknesses are 0.3 µm and the vacuum gap is 0.1 µm. The CMUT arrays were fabricated using sacrificial release layer technology in Polytechnic LMF Lab

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