Multidimensional embedded MEMS motion detectors for wearable mechanocardiography and 4D medical imaging

Background: Cardiovascular diseases are the number one cause of death. Of these deaths, almost 80% are due to coronary artery disease (CAD) and cerebrovascular disease. Multidimensional microelectromechanical systems (MEMS) sensors allow measuring the mechanical movement of the heart muscle offering an entirely new and innovative solution to evaluate cardiac rhythm and function. Recent advances in miniaturized motion sensors present an exciting opportunity to study novel device-driven and functional motion detection systems in the areas of both cardiac monitoring and biomedical imaging, for example, in computed tomography (CT) and positron emission tomography (PET). Methods: This Ph.D. work describes a new cardiac motion detection paradigm and measurement technology based on multimodal measuring tools — by tracking the heart’s kinetic activity using micro-sized MEMS sensors — and novel computational approaches — by deploying signal processing and machine learning techniques—for detecting cardiac pathological disorders. In particular, this study focuses on the capability of joint gyrocardiography (GCG) and seismocardiography (SCG) techniques that constitute the mechanocardiography (MCG) concept representing the mechanical characteristics of the cardiac precordial surface vibrations. Results: Experimental analyses showed that integrating multisource sensory data resulted in precise estimation of heart rate with an accuracy of 99% (healthy, n=29), detection of heart arrhythmia (n=435) with an accuracy of 95-97%, ischemic disease indication with approximately 75% accuracy (n=22), as well as significantly improved quality of four-dimensional (4D) cardiac PET images by eliminating motion related inaccuracies using MEMS dual gating approach. Tissue Doppler imaging (TDI) analysis of GCG (healthy, n=9) showed promising results for measuring the cardiac timing intervals and myocardial deformation changes. Conclusion: The findings of this study demonstrate clinical potential of MEMS motion sensors in cardiology that may facilitate in time diagnosis of cardiac abnormalities. Multidimensional MCG can effectively contribute to detecting atrial fibrillation (AFib), myocardial infarction (MI), and CAD. Additionally, MEMS motion sensing improves the reliability and quality of cardiac PET imaging.Moniulotteisten sulautettujen MEMS-liiketunnistimien käyttö sydänkardiografiassa sekä lääketieteellisessä 4D-kuvantamisessa Tausta: Sydän- ja verisuonitaudit ovat yleisin kuolinsyy. Näistä kuolemantapauksista lähes 80% johtuu sepelvaltimotaudista (CAD) ja aivoverenkierron häiriöistä. Moniulotteiset mikroelektromekaaniset järjestelmät (MEMS) mahdollistavat sydänlihaksen mekaanisen liikkeen mittaamisen, mikä puolestaan tarjoaa täysin uudenlaisen ja innovatiivisen ratkaisun sydämen rytmin ja toiminnan arvioimiseksi. Viimeaikaiset teknologiset edistysaskeleet mahdollistavat uusien pienikokoisten liiketunnistusjärjestelmien käyttämisen sydämen toiminnan tutkimuksessa sekä lääketieteellisen kuvantamisen, kuten esimerkiksi tietokonetomografian (CT) ja positroniemissiotomografian (PET), tarkkuuden parantamisessa. Menetelmät: Tämä väitöskirjatyö esittelee uuden sydämen kineettisen toiminnan mittaustekniikan, joka pohjautuu MEMS-anturien käyttöön. Uudet laskennalliset lähestymistavat, jotka perustuvat signaalinkäsittelyyn ja koneoppimiseen, mahdollistavat sydämen patologisten häiriöiden havaitsemisen MEMS-antureista saatavista signaaleista. Tässä tutkimuksessa keskitytään erityisesti mekanokardiografiaan (MCG), joihin kuuluvat gyrokardiografia (GCG) ja seismokardiografia (SCG). Näiden tekniikoiden avulla voidaan mitata kardiorespiratorisen järjestelmän mekaanisia ominaisuuksia. Tulokset: Kokeelliset analyysit osoittivat, että integroimalla usean sensorin dataa voidaan mitata syketiheyttä 99% (terveillä n=29) tarkkuudella, havaita sydämen rytmihäiriöt (n=435) 95-97%, tarkkuudella, sekä havaita iskeeminen sairaus noin 75% tarkkuudella (n=22). Lisäksi MEMS-kaksoistahdistuksen avulla voidaan parantaa sydämen 4D PET-kuvan laatua, kun liikeepätarkkuudet voidaan eliminoida paremmin. Doppler-kuvantamisessa (TDI, Tissue Doppler Imaging) GCG-analyysi (terveillä, n=9) osoitti lupaavia tuloksia sydänsykkeen ajoituksen ja intervallien sekä sydänlihasmuutosten mittaamisessa. Päätelmä: Tämän tutkimuksen tulokset osoittavat, että kardiologisilla MEMS-liikeantureilla on kliinistä potentiaalia sydämen toiminnallisten poikkeavuuksien diagnostisoinnissa. Moniuloitteinen MCG voi edistää eteisvärinän (AFib), sydäninfarktin (MI) ja CAD:n havaitsemista. Lisäksi MEMS-liiketunnistus parantaa sydämen PET-kuvantamisen luotettavuutta ja laatua

Computing in Cardiology 2016

Cardiac, respiratory, and patient body motion artifacts degrade the image quality and quantitative accuracy of the nuclear medicine imaging which may lead to incorrect diagnosis, unnecessary treatment and insufficient therapy. We present a new miniaturized system including joint micro electromechanical (MEMS) accelerometer and gyroscope sensors for simultaneous extraction of cardiac and respiratory signals. We employ two tri-axial joint MEMS sensors for selecting an optimal trigger point in a cardiac and respiratory cycle. The 6-axis motion sensing helps to detect candidate features for cardiac and respiratory gating in Positron emission tomography (PET) imaging. The aim of this study was to validate MEMS-derived signals against traditional Real-time Position Management (RPM) and electrocardiography (ECG) measurement systems in 4 healthy volunteers. High agreement and correlation were found between cardiac and respiratory cycle intervals. These promising first results warrant for further investigations. </p

A Biological Global Positioning System: Considerations for Tracking Stem Cell Behaviors in the Whole Body

Many recent research studies have proposed stem cell therapy as a treatment for cancer, spinal cord injuries, brain damage, cardiovascular disease, and other conditions. Some of these experimental therapies have been tested in small animals and, in rare cases, in humans. Medical researchers anticipate extensive clinical applications of stem cell therapy in the future. The lack of basic knowledge concerning basic stem cell biology-survival, migration, differentiation, integration in a real time manner when transplanted into damaged CNS remains an absolute bottleneck for attempt to design stem cell therapies for CNS diseases. A major challenge to the development of clinical applied stem cell therapy in medical practice remains the lack of efficient stem cell tracking methods. As a result, the fate of the vast majority of stem cells transplanted in the human central nervous system (CNS), particularly in the detrimental effects, remains unknown. The paucity of knowledge concerning basic stem cell biology—survival, migration, differentiation, integration in real-time when transplanted into damaged CNS remains a bottleneck in the attempt to design stem cell therapies for CNS diseases. Even though excellent histological techniques remain as the gold standard, no good in vivo techniques are currently available to assess the transplanted graft for migration, differentiation, or survival. To address these issues, herein we propose strategies to investigate the lineage fate determination of derived human embryonic stem cells (hESC) transplanted in vivo into the CNS. Here, we describe a comprehensive biological Global Positioning System (bGPS) to track transplanted stem cells. But, first, we review, four currently used standard methods for tracking stem cells in vivo: magnetic resonance imaging (MRI), bioluminescence imaging (BLI), positron emission tomography (PET) imaging and fluorescence imaging (FLI) with quantum dots. We summarize these modalities and propose criteria that can be employed to rank the practical usefulness for specific applications. Based on the results of this review, we argue that additional qualities are still needed to advance these modalities toward clinical applications. We then discuss an ideal procedure for labeling and tracking stem cells in vivo, finally, we present a novel imaging system based on our experiments

Review of photoacoustic imaging plus X

Photoacoustic imaging (PAI) is a novel modality in biomedical imaging technology that combines the rich optical contrast with the deep penetration of ultrasound. To date, PAI technology has found applications in various biomedical fields. In this review, we present an overview of the emerging research frontiers on PAI plus other advanced technologies, named as PAI plus X, which includes but not limited to PAI plus treatment, PAI plus new circuits design, PAI plus accurate positioning system, PAI plus fast scanning systems, PAI plus novel ultrasound sensors, PAI plus advanced laser sources, PAI plus deep learning, and PAI plus other imaging modalities. We will discuss each technology's current state, technical advantages, and prospects for application, reported mostly in recent three years. Lastly, we discuss and summarize the challenges and potential future work in PAI plus X area

Microsystems technology: objectives

This contribution focuses on the objectives of microsystems technology (MST). The reason for this is two fold. First of all, it should explain what MST actually is. This question is often posed and a simple answer is lacking, as a consequence of the diversity of subjects that are perceived as MST. The second reason is that a map of the somewhat chaotic field of MST is needed to identify sub-territories, for which standardization in terms of system modules an interconnections is feasible. To define the objectives a pragmatic approach has been followed. From the literature a selection of topics has been chosen and collected that are perceived as belonging to the field of MST by a large community of workers in the field (more than 250 references). In this way an overview has been created with `applications¿ and `generic issues¿ as the main characteristics

Micromachined Scanning Devices for 3D Acoustic Imaging

Acoustic imaging (including ultrasound and photoacoustic imaging) refers to a class of imaging methods that use high-frequency sound (ultrasound) waves to generate contrast images for the interrogated media. It provides 3D spatial distribution of structural, mechanical, and even compositional properties in different materials. To conduct 3D ultrasound imaging, 2D ultrasound transducer arrays followed by multi-channel high-frequency data acquisition (DAQ) systems are frequently used. However, as the quantity and density of the transducer elements and also the DAQ channels increase, the acoustic imaging system becomes complex, bulky, expensive, and also power consuming. This situation is especially true for 3D imaging systems, where a 2D transducer array with hundreds or even thousands of elements could be involved. To address this issue, the objective of this research is to achieve new micromachined scanning devices to enable fast and versatile 2D ultrasound signal acquisition for 3D image reconstruction without involving complex physical transducer arrays and DAQ electronics. The new micromachined scanning devices studied in this research include 1) a water-immersible scanning mirror microsystem, 2) a micromechanical scanning transducer, and 3) a multi-layer linear transducer array. Especially, the water-immersible scanning mirror microsystem is capable of scanning focused ultrasound beam (from a single-element transducer) in two dimensions for 3D high-resolution acoustic microscopy. The micromechanical scanning transducer is capable of sending and receiving ultrasound signal from a single-element transducer to a 2D array of locations for 3D acoustic tomography. The multi-layer linear transducer array allows a unique electronic scanning scheme to simulate the functioning of a much larger 2D transducer array for 3D acoustic tomography. The design, fabrication and testing of the above three devices have been successfully accomplished and their applications in 3D acoustic microscopy and tomography have been demonstrated

Micromachined Scanning Devices for 3D Acoustic Imaging

Acoustic imaging (including ultrasound and photoacoustic imaging) refers to a class of imaging methods that use high-frequency sound (ultrasound) waves to generate contrast images for the interrogated media. It provides 3D spatial distribution of structural, mechanical, and even compositional properties in different materials. To conduct 3D ultrasound imaging, 2D ultrasound transducer arrays followed by multi-channel high-frequency data acquisition (DAQ) systems are frequently used. However, as the quantity and density of the transducer elements and also the DAQ channels increase, the acoustic imaging system becomes complex, bulky, expensive, and also power consuming. This situation is especially true for 3D imaging systems, where a 2D transducer array with hundreds or even thousands of elements could be involved. To address this issue, the objective of this research is to achieve new micromachined scanning devices to enable fast and versatile 2D ultrasound signal acquisition for 3D image reconstruction without involving complex physical transducer arrays and DAQ electronics. The new micromachined scanning devices studied in this research include 1) a water-immersible scanning mirror microsystem, 2) a micromechanical scanning transducer, and 3) a multi-layer linear transducer array. Especially, the water-immersible scanning mirror microsystem is capable of scanning focused ultrasound beam (from a single-element transducer) in two dimensions for 3D high-resolution acoustic microscopy. The micromechanical scanning transducer is capable of sending and receiving ultrasound signal from a single-element transducer to a 2D array of locations for 3D acoustic tomography. The multi-layer linear transducer array allows a unique electronic scanning scheme to simulate the functioning of a much larger 2D transducer array for 3D acoustic tomography. The design, fabrication and testing of the above three devices have been successfully accomplished and their applications in 3D acoustic microscopy and tomography have been demonstrated

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

Gyrocardiography: A New Non-invasive Monitoring Method for the Assessment of Cardiac Mechanics and the Estimation of Hemodynamic Variables

Gyrocardiography (GCG) is a new non-invasive technique for assessing heart motions by using a sensor of angular motion - gyroscope - attached to the skin of the chest. In this study, we conducted simultaneous recordings of electrocardiography (ECG), GCG, and echocardiography in a group of subjects consisting of nine healthy volunteer men. Annotation of underlying fiducial points in GCG is presented and compared to opening and closing points of heart valves measured by a pulse wave Doppler. Comparison between GCG and synchronized tissue Doppler imaging (TDI) data shows that the GCG signal is also capable of providing temporal information on the systolic and early diastolic peak velocities of the myocardium. Furthermore, time intervals from the ECG Q-wave to the maximum of the integrated GCG (angular displacement) signal and maximal myocardial strain curves obtained by 3D speckle tracking are correlated. We see GCG as a promising mechanical cardiac monitoring tool that enables quantification of beat-by-beat dynamics of systolic time intervals (STI) related to hemodynamic variables and myocardial contractility

Basic capillary microfluidic chip and highly sensitive optical detector for point of care application

A cost-effective and highly sensitive portable diagnostic device is needed to enable much more widespread monitoring of health conditions in disease prevention, detection, and control. Miniaturized and easy-to-operate devices can reduce the inherent costs and inefficiencies associated with healthcare testing in central laboratories. Hence, clinicians are beginning to use point of care (POC) testing and flexible clinical chemistry testing devices which are beneficial for the patient. In our work, a low-cost and simple autonomous microfluidic device for biochemical detection was developed. The pumpless capillary system with capillary stop valves and trigger valves is fabricated on a silicon (Si) wafer and then bonded with the modified polydimethylsiloxane (PDMS) cover. The key point of this study is the change of the surface contact angle of the PDMS to achieve the functionalities such as timing features (capillary-driven stop valve) and basic logical functions (trigger valves). The polydimethylsiloxane-ethylene oxide polymer (PDMS-b-PEO) is utilized as a surfactant additive to make the PDMS hydrophilic. The contact angle of the modified PDMS can be adjusted from 80.9° to 21.5° with different mixing ratios. The contact angles of PEO-PDMS accepted in this work are from 80.9° to 58.5° to bring the capillary channel and valve into effect. This autonomous capillary-driven device with good microfluidic flow manipulation can be widely applied to a number of microfluidic devices and pumpless fluidic actuation mechanisms, which is suitable for cost-effective diagnostic tools in the biomedical analysis and POC testing applications. Another obstacle for miniaturization of the bio-detection system is the optical detector. We developed a novel, highly sensitive and miniaturized detector. It integrates a light source--light emitting diode (LED), all necessary optical components, and a photodiode with preamplifier into one package about 2 cm x 2 cm x 2 cm, especially for the applications of lab-on-a-chip (LOC), portable bio-detection system and POC diagnostic system. The size of this detector is smaller than the existing miniaturized detector of the size 5 cm x 5 cm x 5 cm. The fluorescence dye 5-Carboxyfluorescein (5-FAM) dissolved into the solvent DMSO (Dimethyl Sulfoxide) and diluted with DI water was used as the testing solution samples. The prototype has been tested to prove a remarkable sensitivity at pico-scale molar, around 1.08 pM, which is the highest sensitivity by now. It is higher than the current limit of detection at 1.96 nm, which will be presented in detail in the latter section