Raman sensing and its multimodal combination with optoacoustics and OCT for applications in the life sciences

Currently, many optical modalities are being investigated, applied, and further developed for non-invasive analysis and sensing in the life sciences. To befit the complexity of the study objects and questions in this field, the combination of two or more modalities is attempted. We review our work on multimodal sensing concepts for applications ranging from non-invasive quantification of biomolecules in the living organism to supporting medical diagnosis showing the combined capabilities of Raman spectroscopy, optical coherence tomography, and optoacoustics

Multimodal optical spectroscopy for application in the life sciences

Many optical modalities are being investigated, applied, and further developed for non-invasive analysis and sensing in the life sciences. Often, the combination of two or more modalities is required for in depth analysis because of the complexity of the study objects and questions in this field. The work presents multimodal sensing concepts for applications ranging from non-invasive quantification of biomolecules in the living organism to supporting medical diagnosis showing the combined capabilities of Raman spectroscopy, optical coherence tomography, and optoacoustic

Combined ultrasound and photoacoustic C-mode imaging system for skin lesion assessment

Accurate assessment of the size and depth of infiltration is critical for effectively treating and removing skin cancer, especially melanoma. However, existing methods such as skin biopsy and histologic examination are invasive, time-consuming, and may not provide accurate depth results. We present a novel system for simultaneous and co-localized ultrasound and photoacoustic imaging, with the application for non-invasive skin lesion size and depth measurement. The developed system integrates an acoustical mirror that is placed on an ultrasound transducer, which can be translated within a flexible water tank. This allows for 3D (C-mode) imaging, which is useful for mapping the skin structure and determine the invasion size and depth of lesions including skin cancer. For efficient reconstruction of photoacoustic images, we applied the open-source MUST library. The acquisition time per 2D image is <1 s and the pulse energies are below the legal Maximum Permissible Exposure (MPE) on human skin. We present the depth and resolution capabilities of the setup on several self-designed agar phantoms and demonstrate in vivo imaging on human skin. The setup also features an unobstructed optical window from the top, allowing for simple integration with other optical modalities. The perspective towards clinical application is demonstrated

Photoacoustic Imaging in Gastroenterology: Advances and Needs

Gastroenterologists routinely use optical imaging and ultrasound for the minimally invasive diagnosis and treatment of chronic inflammatory diseases and cancerous tumors in gastrointestinal tract and related organs. Recent advances in gastroenterological photoacoustics represent combination of multispectral and multiscale photoacoustic (PA), ultrasound (US), and near-infrared (NIR) fluorescent imaging. The novel PA endoscopic methods have been evaluated in preclinical models using catheter-based miniature probes either noncontact, all-optical, forward-viewing probe or contact, side-viewing probe combined with ultrasound (esophagus and colon). The deep-tissue PA tomography has been applied to preclinical research on targeted contrast agents (pancreatic cancer) using benchtop experimental setups. The clinical studies engaging human tissue ex vivo have been performed on endoscopic mucosal resection tissue with PA-US tomography system and intraoperative imaging of pancreatic tissue with PA and NIR fluorescence multimodality. These emerging PA methods are very promising for early cancer detection and prospective theranostics. The noninvasive transabdominal examination with PA-US handheld probe has been implemented into clinical trials for the assessment of inflammatory bowel disease. To facilitate translational and clinical research in PA imaging in gastroenterology, we discuss potential clinical impact and limitations of the proposed solutions and future needs

Molecular Imaging of Inflammation - current and emerging technologies for diagnosis and treatment

Inflammation is a key factor in multiple diseases including primary immune-mediated inflammatory diseases e.g. rheumatoid arthritis but also, less obviously, in many other common conditions, e.g. cardiovascular disease and diabetes. Together, chronic inflammatory diseases contribute to the majority of global morbidity and mortality. However, our understanding of the underlying processes by which the immune response is activated and sustained is limited by a lack of cellular and molecular information obtained in situ. Molecular imaging is the visualization, detection and quantification of molecules in the body. The ability to reveal information on inflammatory biomarkers, pathways and cells can improve disease diagnosis, guide and monitor therapeutic intervention and identify new targets for research. The optimum molecular imaging modality will possess high sensitivity and high resolution and be capable of non-invasive quantitative imaging of multiple disease biomarkers while maintaining an acceptable safety profile. The mainstays of current clinical imaging are computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US) and nuclear imaging such as positron emission tomography (PET). However, none of these have yet progressed to routine clinical use in the molecular imaging of inflammation, therefore new approaches are required to meet this goal. This review sets out the respective merits and limitations of both established and emerging imaging modalities as clinically useful molecular imaging tools in addition to potential theranostic applications

Molecular imaging of inflammation - Current and emerging technologies for diagnosis and treatment

Inflammation is a key factor in multiple diseases including primary immune-mediated inflammatory diseases e.g. rheumatoid arthritis but also, less obviously, in many other common conditions, e.g. cardiovascular disease and diabetes. Together, chronic inflammatory diseases contribute to the majority of global morbidity and mortality. However, our understanding of the underlying processes by which the immune response is activated and sustained is limited by a lack of cellular and molecular information obtained in situ. Molecular imaging is the visualization, detection and quantification of molecules in the body. The ability to reveal information on inflammatory biomarkers, pathways and cells can improve disease diagnosis, guide and monitor therapeutic intervention and identify new targets for research. The optimum molecular imaging modality will possess high sensitivity and high resolution and be capable of non-invasive quantitative imaging of multiple disease biomarkers while maintaining an acceptable safety profile. The mainstays of current clinical imaging are computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US) and nuclear imaging such as positron emission tomography (PET). However, none of these have yet progressed to routine clinical use in the molecular imaging of inflammation, therefore new approaches are required to meet this goal. This review sets out the respective merits and limitations of both established and emerging imaging modalities as clinically useful molecular imaging tools in addition to potential theranostic applications

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

Photoacoustic evaluation of surfaces via pulsed evanescent field interaction

"May 2014."Dissertation Supervisor: Dr. John A. Viator.Includes vita.In recent years, major research funding and commercial development has been going toward the production and characterization of increasingly useful nanomaterials. These materials such as quantum dots, nanoparticles, and thin films can increase the efficiency of solar panels, create new treatments for cancer, and vastly improve the detection capabilities for various optical sensors for biosensing. Unfortunately, to date, very few methods of characterizing these types of materials exist such as scanning electron microscopy and ellipsometry. These techniques are prohibitively expensive, cannot be used with all materials, and require rigorous preparation schemes before scanning. Therefore, a new method to characterize thin films and detect the properties of nanomaterials is needed. This study proposes a newly revived method, Total Internal Reflection Photoacoustic Spectroscopy, along with related techniques, to deliver cost effective characterization and detection for nanomaterials and thin films.Includes bibliographical references (pages 122-143)