<p></p><p>One-sided ultrasonic non-destructive evaluation (UNDE) is extensively used to characterize structures that need to be inspected and maintained from defects and flaws that could affect the performance of power plants, such as nuclear power plants. Most UNDE systems send acoustic pulses into the structure of interest, measure the received waveform and use an algorithm to reconstruct the quantity of interest. The most widely used algorithm in UNDE systems is the synthetic aperture focusing technique (SAFT) because it produces acceptable results in real time. A few regularized inversion techniques with linear models have been proposed which can improve on SAFT, but they tend to make simplifying assumptions that show artifacts and do not address how to obtain reconstructions from large real data sets. In this thesis, we present two studies. The first study covers the model-based iterative reconstruction (MBIR) technique which is used to resolve some of the issues in SAFT and the current linear regularized inversion techniques, and the second study covers the direct deep learning (DDL) technique which is used to further resolve issues related to non-linear interactions between the ultrasound signal and the specimen.</p> <p>In the first study, we propose a model-based iterative reconstruction (MBIR) algorithm designed for scanning UNDE systems. MBIR reconstructs the image by optimizing a cost function that contains two terms: the forward model that models the measurements and the prior model that models the object. To further reduce some of the artifacts in the results, we enhance the forward model of MBIR to account for the direct arrival artifacts and the isotropic artifacts. The direct arrival signals are the signals received directly from the transmitter without being reflected. These signals contain no useful information about the specimen and produce high amplitude artifacts in regions close to the transducers. We resolve this issue by modeling these direct arrival signals in the forward model to reduce their artifacts while maintaining information from reflections of other objects. Next, the isotropic artifacts appear when the transmitted signal is assumed to propagate in all directions equally. Therefore, we modify our forward model to resolve this issue by modeling the anisotropic propagation. Next, because of the significant attenuation of the transmitted signal as it propagates through deeper regions, the reconstruction of deeper regions tends to be much dimmer than closer regions. Therefore, we combine the forward model with a spatially variant prior model to account for the attenuation by reducing the regularization as the pixel gets deeper. Next, for scanning large structures, multiple scans are required to cover the whole field of view. Typically, these scans are performed in raster order which makes adjacent scans share some useful correlations. Reconstructing each scan individually and performing a conventional stitching method is not an efficient way because this could produce stitching artifacts and ignore extra information from adjacent scans. We present an algorithm to jointly reconstruct measurements from large data sets that reduces the stitching artifacts and exploits useful information from adjacent scans. Next, using simulated and extensive experimental data, we show MBIR results and demonstrate how we can improve over SAFT as well as existing regularized inversion techniques. However, even with this improvement, MBIR still results in some artifacts caused by the inherent non-linearity of the interaction between the ultrasound signal and the specimen.</p> <p>In the second study, we propose DDL, a non-iterative model-based reconstruction method for inverting measurements that are based on non-linear forward models for ultrasound imaging. Our approach involves obtaining an approximate estimate of the reconstruction using a simple linear back-projection and training a deep neural network to refine this to the actual reconstruction. While the technique we are proposing can show significant enhancement compared to the current techniques with simulated data, one issue appears with the performance of this technique when applied to experimental data. The issue is a modeling mismatch between the simulated training data and the real data. We propose an effective solution that can reduce the effect of this modeling mismatch by adding noise to the simulation input of the training set before simulation. This solution trains the neural network on the general features of the system rather than specific features of the simulator and can act as a regularization to the neural network. Another issue appears similar to the issue in MBIR caused by the attenuation of deeper reflections. Therefore, we propose a spatially variant amplification technique applied to the back-projection to amplify deeper regions. Next, to reconstruct from a large field of view that requires multiple scans, we propose a joint deep neural network technique to jointly reconstruct an image from these multiple scans. Finally, we apply DDL to simulated and experimental ultrasound data to demonstrate significant improvements in image quality compared to the delay-and-sum approach and the linear model-based reconstruction approach.</p><br><p></p>

Os equipamentos de imagens por ultrassom com varredura eletrônica usam transdutores que não se moldam à superfície a ser examinada, pois são rígidos. Há transdutores com curvaturas fixas para aplicações específicas. Em aplicações médicas, esse não é um problema na maioria dos casos, pois os tecidos do corpo humano tomam a forma da face do transdutor. Isso não ocorre quando há estruturas ósseas próximas às camadas externas de tecidos moles. Nas aplicações industriais as superfícies são sólidas e, portanto, não se ajustam à superfície do transdutor, sendo necessário uma camada variável de acoplamento acústico. A possibilidade de uso de um transdutor flexível exige que sua curvatura seja conhecida para o direcionamento correto do feixe acústico usado na formação de imagens. Assim sendo, um transdutor multielemento flexível apresentaria a vantagem de poder ser acoplado na superfície curva diretamente, tanto em aplicações médicas quanto industriais. Os transdutores flexíveis relatados na literatura científica não são compactos e dispõe de complicados sistemas de sensoriamento usados na determinação de curvaturas, além de demandar por sofisticados sistemas de aquisição e processamento dos sinais. Este trabalho propõe o desenvolvimento de transdutores multielementos flexíveis compactos para serem acoplados diretamente em superfícies curvas de peças mecânicas ou do corpo humano. Neste trabalho os sensores de curvatura responsáveis pela medição da curvatura foram desenvolvidos segundo os princípios básicos de extensômetria e resistência dos materiais para serem embebidos nas camadas do transdutor flexível de ultrassom. No desenvolvimento, foram fabricadas quatro versões de transdutores, com frequências de 1 e 2,25MHz. Todos os materiais usados na fabricação dos protótipos foram especificados segundo suas propriedades mecânicas e acústicas. Os protótipos fabricados foram caracterizados tendo sido medidas a largura de banda de cada elemento do transdutor, o comprimento e a duração dos pulsos, e uma medida da resolução axial. Para o protótipo de 2,25MHz, uma medida estimada da resolução lateral foi feita pela simulação do campo acústico, considerando o transdutor curvado em uma superfície cilíndrica. Para se testar o desempenho dos protótipos, foram realizados diferentes testes de formação de imagem. A versão de transdutor flexível de 1MHz e sem sensor de curvatura foi curvado sobre um cilindro e imerso em um tanque com água para a realização de testes de formação de imagem usado na detecção de objetos e obstáculos. Para as versões de transdutores médicos com sensor de curvatura, construiu-se duas versões de phantom simulando uma interface óssea cortical densa dentro de um tecido mole humano. O phantom usado para testar o protótipo de 2,25MHz foi concebido por uma amostra de tíbia bovina fraturada embebida dentro de um material com propriedades acústicas muito próximas a da água. Os testes de imagem foram realizados com o transdutor de 2,25MHz curvado sobre a superfície cilíndrica do phantom. As imagens de ultrassom das regiões fraturadas do osso foram detectadas, e uma comparação entre as técnicas de varredura setorial e STA usadas na obtenção das imagens foram feitas. Mostrou-se que é possível fabricar, de uma forma simples, transdutores multielementos flexíveis mais compactos e dotados de sensor de curvatura, e sem a necessidade de se usar tecnologias sofisticadas e caras ou de se valer de sistemas complexos de formação e processamento de sinais. As imagens obtidas pelos protótipos mostraram que os protótipos podem ser usados em diferentes aplicações NDT na indústria. Em especial, o protótipo de 2,25MHz mostrou ainda que tem potencial no uso médico para a obtenção de imagens de fraturas em contornos ósseos mais densos. / Ultrasound image equipment with electronic scanning considers that transducers cannot take the shape of the surface to be examined because they are rigid. There are transducers with fixed curvatures for specific applications. In medical applications, this is not a serious problem in most cases, since the face of the transducer can be coupled to the soft tissues of the body. This does not occur when there are bone structures close to the external layers of soft tissue. In industrial applications, the surfaces are solid and therefore do not fit to the transducer surface, where a variable layer of acoustic coupling is necessary. The possibility of using a flexible transducer requires its curvature to be known in order to the correct the direction of the acoustic beam which will be used in imaging applications. Thus, a flexible array transducer would have the advantage of being directly coupled to the curved surface in medical and in industrial applications. Flexible ultrasound transducers reported in the scientific literature are not compact, having complex sensing systems used to determine curvature; furthermore, they require sophisticated signal acquisition and processing systems. The development of flexible compact ultrasound linear array transducers to be coupled directly onto curved surfaces of mechanical parts as well of the human body is proposed here. The bend sensors responsible for measuring the curvature were developed according to the basic principles of strain gauge in extensometry and strength of materials to be embedded in the layers of the flexible ultrasound transducer. During this development, four versions of transducers were manufactured, with frequencies of 1 and 2.25MHz. All the materials used in the prototypes manufacturing were selected based on their mechanical and acoustic properties. The manufactured prototypes were characterized in terms of measured parameters, such as the bandwidth of each transducer element, the length and duration of the pulses, and a measure of axial resolution. For the 2.25MHz prototype, the value of the lateral resolution was estimated by simulating the acoustic field considering the transducer curved over a cylindrical surface. In order to test the transducer prototypes, different ultrasound imaging tests were conducted. The 1MHz flexible transducer version without curvature sensor was bent over a cylinder and immersed in a water tank for performing image formation tests used to detect objects and obstacles. For the medical transducers version with curvature sensor, two versions of phantoms were constructed simulating a dense cortical bone interface located inside the soft human tissue. The phantom applied to test the 2.25 MHz prototype consists of a fractured sample of bovine tibia which was embedded within a material having acoustic properties very close to that of the water. Ultrasound imaging tests were performed with the 2.25MHz transducer curved over the cylindrical surface of the phantom. The regions of the fractured bone were detected in the ultrasound images, and a comparison between the STA and sector scanning techniques used for obtaining the images was made. The study showed that it is possible to manufacture flexible and more compact array transducers provided with curvature sensor, without the need of using sophisticated and expensive technologies or taking advantage of complex formation and signal processing systems. The images obtained by the prototypes showed that they can be employed in different NDT applications in the industry. Particularly, the 2.25MHz prototype also showed its potential for medical imaging fractures in dense bone contours.

Les arbres urbains jouent un rôle écologique, sanitaire et esthétique majeur dans les villes modernes. L’évaluation des risques associés aux arbres dans les villes est essentiellement visuelle, alors que l'ampleur des dégâts internes et le danger associé ne peuvent pas être évalués avec précision par la seule observation. La tomographie par ultrasons pour la détection de la décomposition du bois dans les arbres vivants a été évaluée dans plusieurs études ; les auteurs ont indiqué que cette technique est appropriée pour l’évaluation de la qualité des arbres sur pied. Cependant, cette technique telle qu’utilisée actuellement présente quelques inconvénients : l'effet de l’anisotropie du bois dans la reconstruction de l’image n’est pas pris en compte (l’image obtenue est biaisée) ; la mesure de la vitesse de propagation est imprécise (nécessité de répéter les essais). Afin d’améliorer la tomographie par ultrasons, il est nécessaire de prendre en compte la complexité du matériau bois et de développer des techniques de traitement du signal et de reconstruction d'image adaptées à cette complexité.Une étude a été réalisée pour déterminer les paramètres du signal ultrasonore d'excitation, tels que la forme, la durée et la réponse en fréquence ; puis pour sélectionner une technique de détermination du TOF. Parmi toutes les configurations, celle qui présentait le moins de variations sur les mesures de TOF était la combinaison d’un signal « chirp » (signal modulé en fréquence autour d’une fréquence porteuse) avec la méthode de corrélation croisée.Un modèle numérique a ensuite été développé, avec l’équation de Christoffel, pour simuler la propagation des ondes dans le bois et déterminer le temps de propagation (TOF) de l’onde. La méthode de « raytracing » a été utilisée pour ce modèle. L'anisotropie dans le plan radial-tangentiel du bois modifie la forme des fronts d'onde par rapport au cas d’un matériau isotrope. Les rayons entre émetteur et récepteur sont courbes. Afin de comparer et de valider les résultats obtenus avec l'approche « raytracing », la méthode des éléments finis (FEM) a été utilisée pour modéliser la propagation des ondes élastiques dans le bois. Le modèle FEM a abouti à des estimations des TOF très proches de celles obtenues avec l'approche « raytracing ». Une validation expérimentale du modèle « raytracing » a été effectuée sur des disques de deux essences. Des défauts dans le tronc ont été créés en perçant des trous. Ces défauts ont été testés dans deux positions (centrée et excentrée). Les expériences réalisées ont permis d’obtenir des profils de temps de propagation similaires à ceux obtenus par le modèle numérique.Une méthode de reconstruction d'image tomographique 2D adaptée au bois a été développée. La méthode proposée prend en compte l'orthotropie locale du matériau avec une géométrie cylindrique ; c’est un processus itératif qui reconstruit à la fois les rayons de propagation et les propriétés intrinsèques locales du matériau. Quatre configurations numériques ont été testées représentant des cas réels généralement rencontrés sur le terrain. Les images reconstruites utilisant la méthode proposée ont été comparées à la méthode de reconstruction classique avec l’hypothèse d’isotropie (FBP, rayons droits). La comparaison des images obtenues a mis en évidence une identification et une quantification plus détaillées de l'état interne du tronc avec la méthode proposée. La méthode d'inversion proposée a ensuite été testée expérimentalement sur des échantillons de bois de deux essences pour trois configurations différentes : un cas sain, avec défaut centré et avec un défaut excentré. Comme pour la validation numérique, la méthode développée a permis d'obtenir une représentation plus précise des défauts par rapport à une reconstruction classique par rayons droits, en particulier dans le cas de défauts centrés. / The tree plays a major ecological role in modern cities. The management of the plants is the subject of requests from urban operators: the diagnosis is essentially visual, even when the extent of internal damage and the associated hazard cannot be precisely evaluated by simple observation. Ultrasonic imaging methods allow answering biological questions related to the adaptation of the tree to exogenous constraints, such as pathogenic attacks, presence, and type of internal damages, the extent of degraded or traumatized areas. The major scientific issues are linked to the image production (reconstruction of the intrinsic parameter from a set of measurements) and to the image interpretation (discrimination for detection of alterations and its positioning). The overall aim of this thesis was to develop an ultrasonic imaging method for the diagnosis of the internal condition of urban trees. The scientific objectives were to develop numerical models to study the factors of influence on the propagation of ultrasonic waves in the cross-section of a tree and to propose an image reconstruction solution, suited for orthotropic materials, allowing the discrimination and positioning of decay.Initially, to set-up the ultrasonic chain of measurement, a comparative experimental study was done to choose the excitation signal parameters, such as shape, temporal duration, and frequency response, and then the choice of a suitable time-of-flight determination technique. Then, we were concerned on evaluating the influence of the orthotropic condition of wood on the propagation of ultrasonic waves, by performing a time-of-flight (TOF) estimation using a raytracing approach, a method used in the field of exploration seismography to simulate wavefronts in elastic media. The anisotropy of wood in the radial-tangential plane influenced the wave velocity depending on the direction of propagation, that led to deformed wavefronts compared to the perfectly circular wavefronts for an isotropic case. The paths from each receiver to the transmitter in the wood presented a curvature, therefore the trajectories differed from the straight-line distance obtained for an isotropic case. A numerical comparison was made using the Finite Elements Method (FEM); the TOF estimates and wavefronts agreed with those of the raytracing approach. A similar experimental validation was performed. Wood sections from two species were tested. Defects in the wood were simulated by drilling holes. The shape of TOF curves computed using the raytracing algorithm and those obtained from the experiments were in good agreement.Then, we were interested in the influence of the wood orthotropic condition on the tomography image reconstruction process (inverse problem) and how it should be adapted to the standing tree constraints. For wood, the ray paths between the ultrasonic transmitter and the receivers are not straight as for isotropic media; therefore, the image reconstruction method should be adapted to deal with curved rays. The proposed method considers the orthotropy property of wood material, performing an iterative process that approximated the curved rays. Initially, four numerical configurations were tested representing real cases usually found in standing tree monitoring. The reconstructed images using the proposed method were compared with a straight-ray reconstruction method, highlighting a more detailed identification and quantification of the inner state of the anisotropic structure of the trunk. Then, the inversion procedure was tested using wood samples from two species for three different configurations: a healthy case, a centered defect case, and an off-centered defect case. As for the numerical study, the proposed method resulted in a more accurate defect representation when compared to a straight-ray reconstruction, especially for the case of centered defects.

Coarticulation occurs in running speech when one speech sound or phoneme overlaps with another. It can be considered a result of the way we sequence and organize our articulators to efficiently produce consecutive consonants and vowels in fluent speech. Previous research has suggested that measures of coarticulation can provide insight into the maturity of the motor speech planning system (Barbier, Perrier, Ménard, Payan, Tiede, & Perkell, 2013; Zharkova & Hewlett, 2009; Zharkova, Hewlett, & Hardcastle, 2011). Speech stability has also been suggested as an indicator of motor speech maturity in previous research using ultrasound imaging of velar-vowel targets (Frisch, Maxfield, & Belmont, 2016). This study extends research by Frisch, Maxfield, & Belmont (2016) to investigate patterns of velar-vowel coarticulation and speech stability in bilingual children who wear cochlear implants. Ultrasound and acoustic data were recorded from one English-Spanish bilingual participant (P1) who wears bilateral cochlear implants, one English-Spanish bilingual control child (P2) with no hearing impairment, and one English-Spanish bilingual adult speaker. Measures of velar-vowel coarticulation and speech stability across three productions of English and Spanish words were recorded and analyzed following procedures of Wodzinski and Frisch (2006). The participants were asked to produce three repetitions of fifteen English and fifteen Spanish target words starting with a /k/+ vowel sequence. Ultrasound imaging was used to record and trace tongue movement at the point of maximum velar closure. Data was compared between English and Spanish words, across participants, and between repetitions of the same word. In comparing English and Spanish words, child participants (P1 and P2) demonstrated increased coarticulation during Spanish productions. All participants showed decreased stability in Spanish productions when compared to English. Adult participant (P3) showed greater overall stability in productions and consistent coarticulation across both languages. Measures of coarticulation and overall stability were relatively equal across P1 and P2, while P3 showed greater and more stable coarticulation across both languages. Preliminary results support findings in previous research suggesting that anticipatory coarticulation and speech stability could be used as an index for assessing speech motor planning in bilingual and clinical populations (Barbier, Perrier, Ménard, Payan, Tiede, & Perkell, 2013; Frisch, Allen, Betancourt, & Maxfield, 2016; Frisch, Maxfield, & Belmont, 2016; Frisch & Wodzinski, 2014; Zharkova & Hewlett, 2009; Zharkova, Hewlett, & Hardcastle, 2011). Results additionally indicate that a young cochlear implant user who receives early intervention and is learning two languages can develop commensurate motor speech planning systems to that of a typical bilingual peer and that patterns of coarticulation and stability may be different in English and Spanish contexts.

This thesis presented a microfluidic preparation of bubbles-templated micro-size materials. In particular, this thesis focused on the microfluidic formation and dissolution of CO2 bubbles. First, this thesis described pH-regulated behaviours of CO2 bubbles in the microfluidic channel. This method opened a new way to generate small (<10 µm in diameter) with a narrow size distribution (CV<5%). Second, the microfluidic dissolution of CO2 bubbles possessed the important feature: the local change of pH on the bubble surface. This allowed us to encapsulate the bubbles with various colloidal particles. The bubbles coated with particles showed a high stability against coalescences and Ostwald ripening. The dimensions and shapes of bubbles with a shell of colloidal particle were manipulated by the hydrodynamic and chemical means, respectively. Third, we proposed a microfluidic method for the generation of small and stable bubbles coated with a lysozyme-alginate shell. The local pH decrease at the periphery of CO2 bubbles led to the electrostatic attraction between lysozyme on the bubble surface and alginate in the continuous phase. This produced the bubbles with a shell of biopolymers, which gave a long-term stability (up to a month, at least) against the dissolution and coalescence. Fourth, we presented a single-step method to functionalize bubbles with a variety of nanoparticles. The bubbles showed the corresponding properties of nanoparticles on their surface. Further, we explored the potential applications of these bubbles as contrast agents in ultrasound and magnetic resonance imaging.

This thesis presented a microfluidic preparation of bubbles-templated micro-size materials. In particular, this thesis focused on the microfluidic formation and dissolution of CO2 bubbles. First, this thesis described pH-regulated behaviours of CO2 bubbles in the microfluidic channel. This method opened a new way to generate small (<10 µm in diameter) with a narrow size distribution (CV<5%). Second, the microfluidic dissolution of CO2 bubbles possessed the important feature: the local change of pH on the bubble surface. This allowed us to encapsulate the bubbles with various colloidal particles. The bubbles coated with particles showed a high stability against coalescences and Ostwald ripening. The dimensions and shapes of bubbles with a shell of colloidal particle were manipulated by the hydrodynamic and chemical means, respectively. Third, we proposed a microfluidic method for the generation of small and stable bubbles coated with a lysozyme-alginate shell. The local pH decrease at the periphery of CO2 bubbles led to the electrostatic attraction between lysozyme on the bubble surface and alginate in the continuous phase. This produced the bubbles with a shell of biopolymers, which gave a long-term stability (up to a month, at least) against the dissolution and coalescence. Fourth, we presented a single-step method to functionalize bubbles with a variety of nanoparticles. The bubbles showed the corresponding properties of nanoparticles on their surface. Further, we explored the potential applications of these bubbles as contrast agents in ultrasound and magnetic resonance imaging.

In this thesis, an ultrasound testbed is designed in order to practice the Synthetic Aperture Radar (SAR) techniques. The thesis work is built on the fundamentals of SAR theory. In this respect, four different methods for the reconstruction of SAR image are considered. The ultrasonic testbed is composed of a mobile vehicle where the ultrasound transmitter and receiver are mounted. An analog circuit is designed in order to condition the transmitted and received signals. The receiving signal is processed in a personal computer using MATLAB routines. A GUI is designed for user friendly operation. Different experiments are done with the designed system. The theoretical and practical results for SAR imaging are compared. It is shown that the designed system functions properly with a good approximation to the theoretical results. The deviations from the theoretical results are caused by the idealistic assumptions as well as the distortions introduced by the practical system. More specifically, some of the distortions are generated by the nonuniform velocity of the moving platform, the phase distortion due to the analog filters and imperfect filtering during down-conversion. While the sources of distortions certainly affect the SAR system response, the implemented system is valuable for the practical analysis of SAR system performance.

The recent increase in survival rates of most cancers is due to early detection greatly aided by medical imaging modalities. Combined ultrasound and photoacoustic imaging provide both morphological and functional/molecular information which can help to detect and diagnose cancer in its earliest stages. However, both modalities can benefit from the use of contrast agents. The objective of this thesis was to design, synthesize, and test a nano-sized, dual contrast agent for combined ultrasound and photoacoustic imaging named Photoacoustic nanoDroplets. This agent consists of liquid perfluorocarbon nanodroplets with encapsulated plasmonic nanoparticles. These dual contrast agents utilize optically triggered vaporization for photoacoustic signal generation, providing significantly higher signal amplitude than that from the traditionally used mechanism, thermal expansion. Upon pulsed laser irradiation, liquid perfluorocarbon undergoes a liquid-to-gas phase transition generating giant photoacoustic transients from these dwarf nanoparticles. Once triggered, the gaseous phase provides ultrasound contrast enhancement. Demonstrated in this work are the design, synthesis, characterization, and testing of Photoacoustic nanoDroplets in phantom and animal studies, and preliminary work into adapting these agents into targeted, drug delivery vehicles for simultaneous detection, diagnosis, and treatment of diseases. / text

Nano-sized particles are widely regarded as a tool to study biological events at cellular and molecular levels. However, there are only a few imaging modalities that can visualize interactions between nanoparticles and living cells. A new technique -- pulsed magneto-motive ultrasound imaging, capable of in-vivo imaging of magnetic nanoparticles at improved depth and in real-time is introduced in this study. In pulsed magneto-motive ultrasound imaging, an external high-strength pulsed magnetic field is applied to induce motion within magnetically labeled tissue and ultrasound is used to detect the induced internal tissue motion. A laboratory prototype of a pulsed magneto- motive ultrasound imaging system was built, tested and optimized through modeling and experimental studies using tissue-mimicking phantoms, ex-vivo tissue samples and in- vivo mouse tumor model. The results demonstrated a sufficient contrast between normal and iron-laden tissue labeled with ultra-small magnetic nanoparticles. Finally, further modifications and research directions are discussed which can eventually lead to development of a clinically applicable pulsed magneto-motive ultrasound imaging system. / text

Accurate detection of the spread of cancer is critical for planning the best treatment strategy for a patient. Currently, an invasive sentinel lymph node biopsy is commonly used to detect metastases after a primary tumor is detected. This procedure results in patient morbidity, requires weeks of waiting, and is prone to sampling error. This dissertation presents new developments in an emerging biomedical imaging modality – photoacoustic imaging – and their application to improving the detection of metastases in the lymphatic system in a metastatic mouse model of squamous cell carcinoma of the oral cavity. Label-free spectroscopic photoacoustic imaging is demonstrated to detect hypoxia that results from the development of sub-millimeter cancer foci in the lymph node. In order to improve the sensitivity to micrometastases, molecularly-activated plasmonic nanosensers which are targeted to the epidermal growth factor receptor are introduced. The nanosensors are demonstrated to detect metastases consisting of only a few tens of cells. Improvements to spectroscopic photoacoustic imaging are then demonstrated by selecting imaging wavelengths based on the spectral properties of the optical absorbers. Finally, a new contrast agent – silica-coated gold nanoplates – are used to map the sentinel lymph node with high contrast. The final result is a set of tools that can be used to noninvasively detect micrometastases and improve molecular photoacoustic imaging. / text