Visual Quality Enhancement in Optoacoustic Tomography using Active Contour Segmentation Priors

Segmentation of biomedical images is essential for studying and characterizing anatomical structures, detection and evaluation of pathological tissues. Segmentation has been further shown to enhance the reconstruction performance in many tomographic imaging modalities by accounting for heterogeneities of the excitation field and tissue properties in the imaged region. This is particularly relevant in optoacoustic tomography, where discontinuities in the optical and acoustic tissue properties, if not properly accounted for, may result in deterioration of the imaging performance. Efficient segmentation of optoacoustic images is often hampered by the relatively low intrinsic contrast of large anatomical structures, which is further impaired by the limited angular coverage of some commonly employed tomographic imaging configurations. Herein, we analyze the performance of active contour models for boundary segmentation in cross-sectional optoacoustic tomography. The segmented mask is employed to construct a two compartment model for the acoustic and optical parameters of the imaged tissues, which is subsequently used to improve accuracy of the image reconstruction routines. The performance of the suggested segmentation and modeling approach are showcased in tissue-mimicking phantoms and small animal imaging experiments.Comment: Accepted for publication in IEEE Transactions on Medical Imagin

High resolution tumor targeting in living mice by means of multispectral optoacoustic tomography

BACKGROUND: Tumor targeting is of high clinical and biological relevance, and major efforts have been made to develop molecular imaging technologies for visualization of the disease markers in tissue. Of particular interest is apoptosis which has a profound role within tumor development and has significant effect on cancer malignancy. METHODS: Herein, we report on targeting of phosphatidylserine-exposing cells within live tumor allograft models using a synthetic near infrared zinc(II)-dipicolylamine probe. Visualization of the probe biodistribution is performed with whole body multispectral optoacoustic tomography (MSOT) system and subsequently compared to results attained by planar and tomographic fluorescence imaging systems. RESULTS: Compared to whole body optical visualization methods, MSOT attains remarkably better imaging capacity by delivering high-resolution scans of both disease morphology and molecular function in real time. Enhanced resolution of MSOT clearly showed that the probe mainly localizes in the vessels surrounding the tumor, suggesting that its tumor selectivity is gained by targeting the phosphatidylserine exposed on the surface of tumor vessels. CONCLUSIONS: The current study demonstrates the high potential of MSOT to broadly impact the fields of tumor diagnostics and preclinical drug development

Single-side access, isotropic resolution and multispectral 3D photoacoustic imaging with rotate-translate scanning of ultrasonic detector array

Photoacoustic imaging can achieve high-resolution three-dimensional visualization of optical absorbers at penetration depths ~ 1 cm in biological tissues by detecting optically-induced high ultrasound frequencies. Tomographic acquisition with ultrasound linear arrays offers an easy implementation of single-side access, parallelized and high-frequency detection, but usually comes with an image quality impaired by the directionality of the detectors. Indeed, a simple translation of the array perpendicularly to its median imaging plane is often used, but results both in a poor resolution in the translation direction and in strong limited view artifacts. To improve the spatial resolution and the visibility of complex structures while keeping a planar detection geometry, we introduce, in this paper, a novel rotate-translate scanning scheme, and investigate the performance of a scanner implemented at 15 MHz center frequency. The developed system achieved a quasi-isotropic uniform 3D resolution of ~170 um over a cubic volume of side length 8.5 mm, i.e. an improvement in the resolution in the translation direction by almost one order of magnitude. Dual wavelength imaging was also demonstrated with ultrafast wavelength shifting. The validity of our approach was shown in vitro. We discuss the ability to enable in vivo imaging for preclinical and clinical studies.Comment: 43 pages, 5 figure

Multimodal Contrast Agents for Optoacoustic Brain Imaging in Small Animals

Optoacoustic (photoacoustic) imaging has demonstrated versatile applications in biomedical research, visualizing the disease pathophysiology and monitoring the treatment effect in an animal model, as well as toward applications in the clinical setting. Given the complex disease mechanism, multimodal imaging provides important etiological insights with different molecular, structural, and functional readouts in vivo. Various multimodal optoacoustic molecular imaging approaches have been applied in preclinical brain imaging studies, including optoacoustic/fluorescence imaging, optoacoustic imaging/magnetic resonance imaging (MRI), optoacoustic imaging/MRI/Raman, optoacoustic imaging/positron emission tomography, and optoacoustic/computed tomography. There is a rapid development in molecular imaging contrast agents employing a multimodal imaging strategy for pathological targets involved in brain diseases. Many chemical dyes for optoacoustic imaging have fluorescence properties and have been applied in hybrid optoacoustic/fluorescence imaging. Nanoparticles are widely used as hybrid contrast agents for their capability to incorporate different imaging components, tunable spectrum, and photostability. In this review, we summarize contrast agents including chemical dyes and nanoparticles applied in multimodal optoacoustic brain imaging integrated with other modalities in small animals, and provide outlook for further research

Monitoring mouse brain perfusion with hybrid magnetic resonance optoacoustic tomography

Progress in brain research critically depends on the development of next-generation multi-modal imaging tools capable of capturing transient functional events and multiplexed contrasts noninvasively and concurrently, thus enabling a holistic view of dynamic events in vivo. Here we report on a hybrid magnetic resonance and optoacoustic tomography (MROT) system for murine brain imaging, which incorporates an MR-compatible spherical matrix array transducer and fiber-based light illumination into a 9.4 T small animal scanner. An optimized radiofrequency coil has further been devised for whole-brain interrogation. System's utility is showcased by acquiring complementary angiographic and soft tissue anatomical contrast along with simultaneous dual-modality visualization of contrast agent dynamics in vivo

Optical Imaging

Optical Coherence Tomography (OCT)We describe the fundamental concept of optical coherence tomography (OCT) and discuss the two main working principles time domain OCT and frequency domain OCT. Then, we review extended functionalities including spectrally and polarization-resolved OCT as well as Doppler-OCT and show concepts for contrast enhancement. Based on these fundamentals, we demonstrate the potential of OCT for small animal imaging on the basis of exemplary studies on retinal imaging and lung imaging.Optoacoustic ImagingThis chapter deals with the fascinating topic of optoacoustic imaging, a recent powerful addition to the arsenal of in vivo functional and molecular small animal imaging. Due to its hybrid nature, involving optical excitation and ultrasonic detection, optoacoustics overcomes the imaging depth limitations of optical microscopy related to light scattering in living tissues while further benefiting from the compelling advantages of optical contrast. To this end, optoacoustic imaging has been shown capable of delivering multiple types of imaging contrast (structural, functional, kinetic, molecular) within a single imaging modality. It can further deliver images with high spatiotemporal resolution that rivals performance of other well-established whole-body imaging modalities. As such, optoacoustics can play a vital role in biomedical research, from early disease detection and monitoring of dynamic phenomena noninvasively to accelerating drug discovery.Optical ProbesThis chapter is devoted to the properties and application of fluorescence dyes as probes for optical imaging. A variety of agents have been described to date, including nontargeting dyes, vascular agents, targeted conjugates, activatable dyes, and sensing probes. The major classes encompass polymethine dyes and xanthenes dyes, both of which are commercially available in broad variations. Addressing the purpose of optical animal imaging, the most relevant parameters to apply such probes are discussed, thereby supporting the reader in choosing reasonable imaging probes and in preparing bioconjugates for his studies

Advances in optical imaging for pharmacological studies

Imaging approaches are an essential tool for following up over time representative parameters of in vivo models, providing useful information in pharmacological studies. Main advantages of optical imaging approaches compared to other imaging methods are their safety, straight-forward use and cost-effectiveness. A main drawback, however, is having to deal with the presence of high scattering and high absorption in living tissues. Depending on how these issues are addressed, three different modalities can be differentiated: planar imaging (including fluorescence and bioluminescence in vivo imaging), optical tomography, and optoacoustic approaches. In this review we describe the latest advances in optical in vivo imaging with pharmacological applications, with special focus on the development of new optical imaging probes in order to overcome the strong absorption introduced by different tissue components, especially hemoglobin, and the development of multimodal imaging systems in order to overcome the resolution limitations imposed by scattering.JR acknowledges support from the EC FP7 CIG grant HIGH-THROUGHPUT TOMO, and MINECO grant FIS 2013-41802-R MESO-IMAGIN

Toolbox for in vivo imaging of host-parasite interactions at multiple scales

Animal models have for long been pivotal for parasitology research. Over the last few years, techniques such as intravital, optoacoustic and magnetic resonance imaging, optical projection tomography, and selective plane illumination microscopy developed promising potential for gaining insights into host-pathogen interactions by allowing different visualization forms in vivo and ex vivo. Advances including increased resolution, penetration depth, and acquisition speed, together with more complex image analysis methods, facilitate tackling biological problems previously impossible to study and/or quantify. Here we discuss advances and challenges in the in vivo imaging toolbox, which hold promising potential for the field of parasitology