Um mimetizador de tecido, mais conhecido como phantom, é um objeto que mimetiza tecidos biológicos e são importantes para caracterização e calibração de equipamentos de imagens médicas como ultrassonografia, e no desenvolvimento de novas modalidades de imagens como a fotoacústica. Este trabalho aborda o desenvolvimento de um gel à base de óleo mineral e polímeros para phantom para aplicações em técnicas acústicas e ópticas. Os polímeros utilizados foram o elastômero tribloco tipo estireno-etileno/butileno-estireno (SEBS) e o polietileno de baixa densidade (PEBD). Foram confeccionados três grupos géis poliméricos com porcentagem de SEBS entre 5%-15% de SEBS, 0%-9% de PEBD. Os géis foram caracterizados acusticamente pela velocidade do som e coeficiente de atenuação através de transdutores de imersão com frequências entre 2,25 MHz-10 MHz, e opticamente entre 400-1200 nm pelos coeficientes de absorção, espalhamento e Albedo. Foi observada velocidade do som entre 1458,6 ± 3,1 m/s e 1480,7 ± 1,9 m/s, sendo compatíveis com valores para gordura; coeficiente de atenuação entre 0,6 ± 0,1 dB/cm a 2,25 MHz e 11,3 ± 0,1 dB/cm a 10 MHz, compatíveis para tecidos moles; coeficiente de absorção em 532 nm entre 0,11-2,62 cm-1 e em 1064 nm entre 0,09-1,70 cm-1, e uma banda de absorção em torno de 930 nm com gordura; o coeficiente de espalhamento em 532 nm entre 0,15 -3,96 cm-1 e em 1064 nm entre 0,17- 3,20 cm-1, valores inferiores para tecidos moles. O coeficiente Albedo mostrou que os géis apresentam caráter absorvedor entre 400-1200 nm. Foi desenvolvido um phantom para imagem por fotoacústica com um dos géis estudados (7%SEBS/5%PEBD) e com uma inclusão com pigmento de urucum e foram feitas imagens fotoacústicas em 532 nm e 1024 nm. Foi observado o sinal fotoacústico mais intenso para a imagem em 532 nm. Com este trabalho pode-se obter uma boa caracterização acústica e óptica de géis formados a partir de polímeros do tipo SEBS em conjunto com o PEBD ainda não descritos na literatura. Os materiais desenvolvidos se mostraram bons mimetizadores para tecidos compostos de gordura e com potencial para aplicações em fotoacústica. / Phantoms are structures composed by materials that mimic specific properties of biological tissues and they are commonly used to calibrate and characterize current medical imaging techniques such as ultrasound and optical imaging, and new imaging modalities such as photoacoustics. In this dissertation we developed an oil-based tissue mimicking gel material with mineral oil, triblock copolymer styrene-ethylene/butylene styrene (SEBS) and low-density polyethylene (LDPE). The gel phantoms were prepared mixing SEBS and LDPE in mineral oil at room temperature, varying the SEBS concentration between 5%15%, and low-density polyethylene (LDPE) between 0%-9% and glass microspheres. Acoustic properties such speed of sound and attenuation coefficient were measured using five unfocused ultrasound transducers with frequencies ranging between 2.2510 MHz. Optical properties such albedo, scattering and absorption coefficients ranging from 400-1200 nm were measured. Speed of sound from 1458.6 ± 3.1m/s and 1480.7 ± 1.9 m/s, and attenuation from 0.6 ± 0.1 dB/cm at 2.25 MHz and 11.3 ± 0.1 dB/cm at 10 MHz were observed. Absorption coefficient at 532 nm between 0.11-2.62 cm-1; at 1064 nm between 0.09-1.70 cm-1 were observed. Peak absorption around 930 nm was observed for all gels. Scattering coefficient at 532 nm between 0.15 -3.96 cm-1 and at 1064 nm between 0.17-3.20 cm-1 were found. Albedo coefficient showed that gels are absorptive characteristic for the selected range of wavelength. A phantom made with a 7% SEBS/5% LDPE gel containing an optical-absorber spherical inclusion made with the same material and annatto were developed. Photoacoustic spectroscopic images of the phantom were acquired using a laser operating at 532 nm and 1064 nm. The photoacoustic signal from the inclusion showed the highest intensities at 532 nm with as expected according to the measured absorption spectrum of annatto. With this dissertation we obtained a suitable acoustic and optical characterization of the SEBS/LDPE gels that was not described in the literature. The materials developed seem suitable to mimic fat tissue and have potential for applications in photoacoustics.

L’imagerie préclinique est devenue une ressource incontournable pour l’évaluation de paramètres physiopathologiques, pour le suivi du développement tumoral ainsi que pour le développement de thérapies anticancéreuses. Les évolutions technologiques apparues ces dernières années ont conduit au développement de nouvelles modalités d’imagerie ayant un fort potentiel de translation vers la clinique. Ce manuscrit présente diverses approches par imagerie échographique, photoacoustique et de fluorescence dans le proche infrarouge pour le suivi de la pathologie cancéreuse. Dans un premier temps, nous nous sommes intéressés à la caractérisation de l’hypoxie et son suivi au cours du temps dans différents modèles de cancers humains. Différentes stratégies d’imagerie multimodale ont ensuite été mises en oeuvre pour évaluer l’efficacité d’une nouvelle prodrogue thérapeutique permettant la libération d’une molécule active dans le proche environnement tumoral sur des modèles humains de tumeurs pancréatiques, mammaires, pulmonaires. Enfin, dans un contexte de recherche translationnelle, nous avons exploré le potentiel de l’imagerie photoacoustique et de la fluorescence infrarouge pour la mise en évidence de l’invasion ganglionnaire tumorale en mettant en oeuvre des modèles de ganglions sentinelles minimalement envahis. Au cours de ce travail, nous avons montré l’intérêt du suivi de l’hypoxie tumorale en onco-pharmacologie et mis en évidence le fort potentiel de l’imagerie PA pour les approches translationnelles en oncologie. La principale limitation correspond à la profondeur relativement faible des régions explorables, mais ce point suscite actuellement de nombreux développements technologiques. Les études de faisabilité réalisées ainsi que la validation de protocoles de preuves de concept permettront l’exploitation en routine de ces nouvelles modalités d’imagerie. / Preclinical imaging has become an unavoidable step for pathophysiological parameters assessments, for the follow up of tumor growth and for the anticancer therapies development. Technological improvements have emerged in recent years, allowing the emergence of new imaging modalities with a high potential for translation into clinical practice. This manuscript presents several approaches by ultrasound imaging, photoacoustics and near infrared fluorescence in order to monitor the cancer pathology. Initially, we focused on the characterization of hypoxia and its longitudinal assessment in various preclinical models of human cancers. Various multimodal imaging strategies were implemented to assess the efficacy of a new therapeutic prodrug allowing the release of an active molecule in the tumor microenvironment on human models of pancreatic, breast and lung tumors. Finally, in a context of translational research, we explored the potential of photoacoustic and near infrared fluorescence imaging to highlight the lymph node invasion by cancer cells implementing minimally invaded sentinel lymph node models. In this work, we have shown the interest in monitoring the tumor hypoxia in onco-pharmacology and highlighted the high potential of photoacoustic imaging for oncology translational approaches. The main limitation is the relatively shallow depth of regions that we can explore, but this point is currently subject to many technological developments. Feasibility studies performed and validation of proof of concept protocols will enable routine exploitation of these new imaging modalities.

The fast evolution of medical micro- and nanorobots in the endeavor to perform non-invasive medical operations in living organisms has boosted the use of diverse medical imaging techniques in the last years. Among those techniques, photoacoustic imaging (PAI), considered a functional technique, has shown to be promising for the visualization of micromotors in deep tissue with high spatiotemporal resolution as it possesses the molecular specificity of optical methods and the penetration depth of ultrasound. However, the precise maneuvering and function's control of medical micromotors, in particular in living organisms, require both anatomical and functional imaging feedback. Therefore, herein, the use of high-frequency ultrasound and PAI is reported to obtain anatomical and molecular information, respectively, of magnetically-driven micromotors in vitro and under ex vivo tissues. Furthermore, the steerability of the micromotors is demonstrated by the action of an external magnetic field into the uterus and bladder of living mice in real-time, being able to discriminate the micromotors’ signal from one of the endogenous chromophores by multispectral analysis. Finally, the successful loading and release of a model cargo by the micromotors toward non-invasive in vivo medical interventions is demonstrated.

Micro- and nanorobots (MNRs) are small autonomous devices capable of performing complex tasks and have been demonstrated for a variety of non-invasive biomedical applications, such as tissue engineering, drug delivery or assisted fertilization. However, translating such approaches to an in vivo environment is critical. Current imaging techniques do not allow localization and tracking of single or few micromotors at high spatiotemporal resolution in deep tissue. This thesis addresses some of these limitations, by exploring the use of two optical-based techniques (IR and photoacoustic imaging (PAI)) and a combination of both US and PAI. First, we employ an IR imaging setup to visualize mobile reflective micromotors under scattering phantoms and ex vivo mouse skull tissues, without using any labels. The reflective micromotor reflects more than tenfold the light intensity of a simple particle. However, the achieved penetration depth was ca. 100 μm (when using ex vivo tissues), limiting this technique to superficial biomedical applications. In this regard, PAI plays a role that combines the advantages of US such as penetration depth and real-time imaging with the molecular specificity of optics. For the first time, in this thesis, this method is evaluated for dynamic process monitoring, in particular for tracking single micromotor in real-time below ~1 cm deep phantom and ex vivo tissue. However, the precise function control of MNRs in living organisms, demand the combination of both anatomical and functional imaging methods. Therefore, in the end, we report the use of a hybrid US and PA system for the real-time tracking of magnetically driven micromotors (single and swarms) in phantoms, ex vivo, and in vivo (in mice bladder and uterus), envisioning their application for targeted drug-delivery. This achievement is of great importance and opens the possibilities to employ medical micromotors in a living organism and perform a medical task while being externally controlled and monitored.:ABSTRACT 1 1 INTRODUCTION 5 1.1 Motivation 5 1.2 Background 7 1.2.1 Microrobotics 7 1.2.2 Medical Imaging 9 1.3 Objectives and Structure of Thesis 12 2 FUNDAMENTALS 15 2.1 Optical Imaging 15 2.1.1. Reflection-based Imaging 17 2.1.2. Fluorescence-based Imaging 18 2.1.1 Light-Tissue Interaction 20 2.2 Photoacoustic Imaging 23 2.2.1 Theory 23 2.2.2 Implementation 25 2.3 Ultrasound Imaging 26 2.3.1 Theory 26 2.3.2 Implementation 28 3 MATERIALS AND METHODS 30 3.1 Fabrication of Magnetic Micropropellers 30 3.1.1 3D Laser Lithography of Polymeric Resin 30 3.1.2 Self-assembly of SiO2 Particles 31 3.1.3 Electron Beam Evaporation 32 3.1.4 Surface Functionalization 33 3.2 Fabrication of Phantom Tissue and Microfluidic Channels 34 3.2.1 Fabrication of PDMS-Glycerol Phantom 34 3.2.2 Fabrication of Agarose Phantom 35 3.2.3 Phantom based on Ex vivo Tissues (Chicken Breast and Mice Skull) 36 3.2.4 Microfluidic Channel Platform 37 3.3 Sample Characterization 38 3.3.1 Optical Microscopy 38 3.3.2 Scanning Electron Microscopy 38 3.4 Magnetic Actuation 39 3.4.1 Magnetic Force 39 3.4.2 Magnetic Torque 39 3.5 Ethic Statement for Mice Experiments 41 4 OPTICAL IMAGING OF MICROROBOTS 42 4.1 Concept of Reflective Micromotors 42 4.2 Fabrication of Reflective Micromotors 44 4.3 IR Imaging Actuation Setup 45 4.4 Actuation and Propulsion Performance below Phantom 47 4.5 Actuation and Propulsion Performance below Ex Vivo Skull Tissue 50 4.6 Actuation and Propulsion Performance in Blood 51 5 PHOTOACOUSTIC IMAGING OF MICROROBOTS 55 5.1 Absorbers for Deep Tissue Imaging 55 5.2 Absorber Micromotor Design and Fabrication 56 5.3 Photoacoustic Imaging Setup 58 5.4 Actuation Performance below Phantom Tissue 60 5.5 Actuation Performance below Ex Vivo Tissue 65 6 HYBRID ULTRASOUND AND PHOTOACOUSTIC IMAGING 67 6.1 Hybrid Ultrasound/Photoacoustic System 68 6.2 Fabrication and Characterization of Micromotors 69 6.3 Actuation and Propulsion Performance below Phantom 69 6.4 Actuation and Propulsion Performance below Ex Vivo Tissues 71 6.5 Actuation and Propulsion Performance in Mice 72 6.5.1 Swimming of Micromotors in Bladder 72 6.5.2 Actuation of Micromotors in Uterus 74 6.5.3 3D Multispectral Imaging 76 6.5.4 Towards Targeted Drug Delivery 77 7 SUMMARY AND PERSPECTIVES 80 7.1 Summary 80 7.2 Future Perspectives 83 7.2.1 Contrats Enhancing Labels 84 7.2.2 Novel Imaging Concepts 85 8 REFERENCES 88 9 APPENDIX 105 List of Figures 105 List of Tables 107 Abbreviations 108 List of Publications 109 Acknowledgements 110 Selbstständigkeitserklärung 111 Curriculum Vitae 112

No description available.

Micro-and nanorobots have the potential to perform non-invasive drug delivery, sensing, and surgery in living organisms, with the aid of diverse medical imaging techniques. To perform such actions, microrobots require high spatiotemporal resolution tracking with real-time closed-loop feedback. To that end, photoacoustic imaging has appeared as a promising technique for imaging microrobots in deep tissue with higher molecular specificity and contrast. Here, we present different strategies to track magnetically-driven micromotors with improved contrast and specificity using dedicated contrast agents (Au nanorods and nanostars). Furthermore, we discuss the possibility of improving the light absorption properties of the employed nanomaterials considering possible light scattering and coupling to the underlying metal-oxide layers on the micromotor’s surface. For that, 2D COMSOL simulation and experimental results were correlated, confirming that an increased spacing between the Au-nanostructures and the increase of thickness of the underlying oxide layer lead to enhanced light absorption and preservation of the characteristic absorption peak. These characteristics are important when visualizing the micromotors in a complex in vivo environment, to distinguish them from the light absorption properties of the surrounding natural chromophores.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Neste trabalho, desenvolveu-se um sistema de detecção fotoacústico para medidas simultâneas e independentes dos sinais fotoacústicos dianteiro e traseiro, utilizando dois microfones e um único feixe de excitação. Utiliza-se a diferença de fase entre estes sinais para a determinação da difusividade térmica de materiais, com base na abordagem teórica da técnica da Diferença de Fase dos Dois Feixes (T2F). Na metodologia apresentada não há a necessidade de se alternar o feixe de excitação entre as faces da amostra. Esta característica torna mais rápido o procedimento de medida e simplifica o monitoramento automatizado de processos dinâmicos que afetam a difusividade térmica do material, como a cura de resinas poliméricas. É apresentado o procedimento utilizado para determinar a diferença entre as fases intrínsecas dos microfones e o método empregado para compensar tal diferença e, assim, obter a defasagem entre os sinais fotoacústicos dianteiro e traseiro. O sistema de detecção desenvolvido é avaliado em medidas de difusividade térmica de amostras metálicas (aço inoxidável AISI 304 e aço SAE 1020) e poliméricas (polipropileno e polietileno de baixa densidade). Os resultados obtidos concordam de forma satisfatória com dados disponíveis na literatura. Finalmente, a aplicação do sistema proposto ao monitoramento de cura de amostras de resina epóxi indicou sua potencialidade de acompanhar, em tempo real, este tipo de processo dinâmico. / In this work, a photoacoustic detection system was developed for simultaneous and independent measurements of both front and rear photoacoustic signals, using two microphones and a single beam illumination mode. The phase-lag between these signals is used in the determination of thermal diffusivity of materials, based on the theoretical approach of the Two-Beam Phase-Lag technique. In the experimental setup presented in this work there is no need to alternate the light beam between the sample surfaces. This feature provides faster measurements and simplify the automated monitoring of dynamic processes that affect the material thermal diffusivity, as crosslinking processes. The procedure to determine the difference between the intrinsic phases of the microphones is presented, as well as the method to compensate this difference and to obtain the phase-lag between front and rear photoacoustic signals. The developed detection system is tested in thermal diffusivity measurements of metallic (AISI 304 stainless steel and SAE 1020 steel) and polymeric (polypropylene and low-density polyethylene) samples. The results are in good agreement with the available literature values. Finally, the system here proposed is applied in studies of epoxy resin curing, which shows its potentiality for real-time monitoring of dynamic process.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Neste trabalho, desenvolveu-se um sistema de detecção fotoacústico para medidas simultâneas e independentes dos sinais fotoacústicos dianteiro e traseiro, utilizando dois microfones e um único feixe de excitação. Utiliza-se a diferença de fase entre estes sinais para a determinação da difusividade térmica de materiais, com base na abordagem teórica da técnica da Diferença de Fase dos Dois Feixes (T2F). Na metodologia apresentada não há a necessidade de se alternar o feixe de excitação entre as faces da amostra. Esta característica torna mais rápido o procedimento de medida e simplifica o monitoramento automatizado de processos dinâmicos que afetam a difusividade térmica do material, como a cura de resinas poliméricas. É apresentado o procedimento utilizado para determinar a diferença entre as fases intrínsecas dos microfones e o método empregado para compensar tal diferença e, assim, obter a defasagem entre os sinais fotoacústicos dianteiro e traseiro. O sistema de detecção desenvolvido é avaliado em medidas de difusividade térmica de amostras metálicas (aço inoxidável AISI 304 e aço SAE 1020) e poliméricas (polipropileno e polietileno de baixa densidade). Os resultados obtidos concordam de forma satisfatória com dados disponíveis na literatura. Finalmente, a aplicação do sistema proposto ao monitoramento de cura de amostras de resina epóxi indicou sua potencialidade de acompanhar, em tempo real, este tipo de processo dinâmico. / In this work, a photoacoustic detection system was developed for simultaneous and independent measurements of both front and rear photoacoustic signals, using two microphones and a single beam illumination mode. The phase-lag between these signals is used in the determination of thermal diffusivity of materials, based on the theoretical approach of the Two-Beam Phase-Lag technique. In the experimental setup presented in this work there is no need to alternate the light beam between the sample surfaces. This feature provides faster measurements and simplify the automated monitoring of dynamic processes that affect the material thermal diffusivity, as crosslinking processes. The procedure to determine the difference between the intrinsic phases of the microphones is presented, as well as the method to compensate this difference and to obtain the phase-lag between front and rear photoacoustic signals. The developed detection system is tested in thermal diffusivity measurements of metallic (AISI 304 stainless steel and SAE 1020 steel) and polymeric (polypropylene and low-density polyethylene) samples. The results are in good agreement with the available literature values. Finally, the system here proposed is applied in studies of epoxy resin curing, which shows its potentiality for real-time monitoring of dynamic process.

<p>Главни задатак истраживања приказаног у дисертацији је развој модела,<br />заснованог на алгоритмима машинског учења, који описује сложени<br />утицај мерног система на користан, експериментални сигнал са циљем<br />његове елиминације. Студија случаја је широко распрострањена<br />фотоакустична, трансмисиона мерна метода са ћелијом минималне<br />запремине. Мултидисциплинарност и комплексност проблема одредили<br />су следеће кораке у методологији решења: 1) развој софтвера за<br />генерисање симулираних експерименталних података, 2) развој<br />регресионог модела заснованог на трослојној неуронској мрежи, за<br />прецизну и поуздану карактеризацију детектора која се извршава у<br />реалном времену, 3) развој класификационог модела заснованог на<br />неуронској мрежи једноставне структуре за прецизну и поуздану<br />предикцију типа коришћеног детектора која се извршава у реалном<br />времену, 4) спрезање регресионог и класификационог модела уз развој<br />додатног софтвера за прилагођење модела стварном експерименту. На<br />овај начин заокружен је програмски оквир који извршава сложени задатак<br />издвајања &ldquo;правог&rdquo; сигнала oд изобличеног експерименталног сигнала<br />без ангажовања истраживача, односно извршава аутокорекцију.<br />Тестирање је извршено на више различитих детектора и више<br />различитих материјала у фотоаксустичном експерименту. Применом<br />развијеног програмског оквира конкурентност експерименталне технике<br />је знатно порасла: повећана је тачност и поузданост, проширен је мерни<br />опсег и смањено време обраде резултата мерења.</p> / <p>Glavni zadatak istraživanja prikazanog u disertaciji je razvoj modela,<br />zasnovanog na algoritmima mašinskog učenja, koji opisuje složeni<br />uticaj mernog sistema na koristan, eksperimentalni signal sa ciljem<br />njegove eliminacije. Studija slučaja je široko rasprostranjena<br />fotoakustična, transmisiona merna metoda sa ćelijom minimalne<br />zapremine. Multidisciplinarnost i kompleksnost problema odredili<br />su sledeće korake u metodologiji rešenja: 1) razvoj softvera za<br />generisanje simuliranih eksperimentalnih podataka, 2) razvoj<br />regresionog modela zasnovanog na troslojnoj neuronskoj mreži, za<br />preciznu i pouzdanu karakterizaciju detektora koja se izvršava u<br />realnom vremenu, 3) razvoj klasifikacionog modela zasnovanog na<br />neuronskoj mreži jednostavne strukture za preciznu i pouzdanu<br />predikciju tipa korišćenog detektora koja se izvršava u realnom<br />vremenu, 4) sprezanje regresionog i klasifikacionog modela uz razvoj<br />dodatnog softvera za prilagođenje modela stvarnom eksperimentu. Na<br />ovaj način zaokružen je programski okvir koji izvršava složeni zadatak<br />izdvajanja &ldquo;pravog&rdquo; signala od izobličenog eksperimentalnog signala<br />bez angažovanja istraživača, odnosno izvršava autokorekciju.<br />Testiranje je izvršeno na više različitih detektora i više<br />različitih materijala u fotoaksustičnom eksperimentu. Primenom<br />razvijenog programskog okvira konkurentnost eksperimentalne tehnike<br />je znatno porasla: povećana je tačnost i pouzdanost, proširen je merni<br />opseg i smanjeno vreme obrade rezultata merenja.</p> / <p>The main task of the research presented in this dissertation is the development<br />of the model based on machine learning algorithms, which describes the<br />complex influence of the measuring system on a useful, experimental signal,<br />with the aim of the elimination of this influence. The case study is a widespread<br />photoacoustic, transmission measurement method with minimum volume cell<br />configuration. Multidisciplinarity and complexity of the problem determined the<br />following steps in the solution methodology: 1) development of the software for<br />generating simulated experimental data, 2) development of the regression<br />model based on a three-layer neural network, for precise and reliable<br />characterization of detectors, performed in real time, 3) development of the<br />classification model based on a neural network of simple structure for precise<br />and reliable prediction of the type of detector in use, performed in real time, 4)<br />coupling of the regression and the classification model with the development<br />of additional software for adjustment of the model to a real experiment. In this<br />way, the program framework is completed, which performs the complex task<br />of extracting the &quot;true&quot; signal from the distorted experimental signal without the<br />involvement of researchers, performing, thus, the autocorrection. Testing was<br />performed on several different detectors and several different materials in a<br />photoacoustic experiment. With the application of the developed software<br />framework, the competitiveness of the experimental technique has<br />significantly increased: the accuracy and the reliability have been increased,<br />the measurement range has been expanded and the processing time of<br />measurement results has been reduced.</p>

<p>Cardiovascular disease (CVD) is the leading cause of death worldwide and is expected to increase direct medical costs in the U.S. to $749 billion by the year 2035. Diagnosis of CVD through imaging techniques can improve our understanding of CVD progression and its associated risks through visualization of anatomical features and biological constituents. Non-invasive imaging relies on optimal image quality for visualization of such tissue structures that can be difficult to identify and segment. While various imaging modalities are used to determine tissue characteristics, many lack the spatial resolution that optics-based imaging can provide, which can assess hemodynamic parameters in preclinical models of ischemic disease. Acoustic-based imaging can complement optics-based imaging by providing anatomical and location-specific information of tissues with greater penetration depth. Even with all the advancements in imaging technology, however, limitations still exist in non-invasively, efficiently, and accurately capturing biologically relevant information with adequate spatial and temporal resolution. Furthermore, reproducible feature extraction is difficult due to a lack of standardization in the field, making it difficult to implement when image quality varies. In this work, we implement spatial frequency domain imaging (SFDI), ultrasound, and photoacoustic imaging in preclinical models of 1) peripheral artery disease, 2) traumatic brain injury, and 3) myocardial ischemia to capture imaging biomarkers of vascular and cardiac health in longitudinal studies. We also implement deep learning on preclinical ultrasound and photoacoustic images of the cardiac left ventricle to automatically extract regions of interest to calculate radial strain and oxygen saturation. Eventually findings from this work may help improve clinical cardiovascular disease diagnosis, prognosis, and treatment.</p>