Fluorescence molecular tomography: Principles and potential for pharmaceutical research

Fluorescence microscopic imaging is widely used in biomedical research to study molecular and cellular processes in cell culture or tissue samples. This is motivated by the high inherent sensitivity of fluorescence techniques, the spatial resolution that compares favorably with cellular dimensions, the stability of the fluorescent labels used and the sophisticated labeling strategies that have been developed for selectively labeling target molecules. More recently, two and three-dimensional optical imaging methods have also been applied to monitor biological processes in intact biological organisms such as animals or even humans. These whole body optical imaging approaches have to cope with the fact that biological tissue is a highly scattering and absorbing medium. As a consequence, light propagation in tissue is well described by a diffusion approximation and accurate reconstruction of spatial information is demanding. While in vivo optical imaging is a highly sensitive method, the signal is strongly surface weighted, i.e., the signal detected from the same light source will become weaker the deeper it is embedded in tissue, and strongly depends on the optical properties of the surrounding tissue. Derivation of quantitative information, therefore, requires tomographic techniques such as fluorescence molecular tomography (FMT), which maps the three-dimensional distribution of a fluorescent probe or protein concentration. The combination of FMT with a structural imaging method such as X-ray computed tomography (CT) or Magnetic Resonance Imaging (MRI) will allow mapping molecular information on a high definition anatomical reference and enable the use of prior information on tissue’s optical properties to enhance both resolution and sensitivity. Today many of the fluorescent assays originally developed for studies in cellular systems have been successfully translated for experimental studies in animals. The opportunity of monitoring molecular processes non-invasively in the intact organism is highly attractive from a diagnostic point of view but even more so for the drug developer, who can use the techniques for proof-of-mechanism and proof-of-efficacy studies. This review shall elucidate the current status and potential of fluorescence tomography including recent advances in multimodality imaging approaches for preclinical and clinical drug development

Photoacoustic Microscopy and Computed Tomography: From Bench to Bedside

Photoacoustic imaging (PAI) of biological tissue has seen immense growth in the past decade, providing unprecedented spatial resolution and functional information at depths in the optical diffusive regime. PAI uniquely combines the advantages of optical excitation and those of acoustic detection. The hybrid imaging modality features high sensitivity to optical absorption and wide scalability of spatial resolution with the desired imaging depth. Here we first summarize the fundamental principles underpinning the technology, then highlight its practical implementation, and finally discuss recent advances toward clinical translation

Listening-Mode-Centered Sonification Design for Data Exploration

Grond F. Listening-Mode-Centered Sonification Design for Data Exploration. Bielefeld: Bielefeld University; 2013.From the Introduction to this thesis: Through the ever growing amount of data and the desire to make them accessible to the user through the sense of listening, sonification, the representation of data by using sound has been subject of active research in the computer sciences and the field of HCI for the last 20 years. During this time, the field of sonification has diversified into different application areas: today, sound in auditory display informs the user about states and actions on the desktop and in mobile devices; sonification has been applied in monitoring applications, where sound can range from being informative to alarming; sonification has been used to give sensory feedback in order to close the action and perception loop; last but not least, sonifications have also been developed for exploratory data analysis, where sound is used to represent data with unknown structures for hypothesis building. Coming from the computer sciences and HCI, the conceptualization of sonification has been mostly driven by application areas. On the other hand, the sonic arts who have always contributed to the community of auditory display have a genuine focus on sound. Despite this close interdisciplinary relation of communities of sound practitioners, a rich and sound- (or listening)-centered concept about sonification is still missing as a point of departure for a more application and task overarching approach towards design guidelines. Complementary to the useful organization along fields of applications, a conceptual framework that is proper to sound needs to abstract from applications and also to some degree from tasks, as both are not directly related to sound. I hence propose in this thesis to conceptualize sonifications along two poles where sound serves either a normative or a descriptive purpose. In the beginning of auditory display research, a continuum between a symbolic and an analogic pole has been proposed by Kramer (1994a, page 21). In this continuum, symbolic stands for sounds that coincide with existing schemas and are more denotative, analogic stands for sounds that are informative through their connotative aspects. (compare Worrall (2009, page 315)). The notions of symbolic and analogic illustrate the struggle to find apt descriptions of how the intention of the listener subjects audible phenomena to a process of meaning making and interpretation. Complementing the analogic-symbolic continuum with descriptive and normative purposes of displays is proposed in the light of the recently increased research interest in listening modes and intentions. Similar to the terms symbolic and analogic, listening modes have been discussed in auditory display since the beginning usually in dichotomic terms which were either identified with the words listening and hearing or understood as musical listening and everyday listening as proposed by Gaver (1993a). More than 25 years earlier, four direct listening modes have been introduced by Schaeffer (1966) together with a 5th synthetic mode of reduced listening which leads to the well-known sound object. Interestingly, Schaeffer’s listening modes remained largely unnoticed by the auditory display community. Particularly the notion of reduced listening goes beyond the connotative and denotative poles of the continuum proposed by Kramer and justifies the new terms descriptive and normative. Recently, a new taxonomy of listening modes has been proposed by Tuuri and Eerola (2012) that is motivated through an embodied cognition approach. The main contribution of their taxonomy is that it convincingly diversifies the connotative and denotative aspects of listening modes. In the recently published sonification handbook, multimodal and interactive aspects in combination with sonification have been discussed as promising options to expand and advance the field by Hunt and Hermann (2011), who point out that there is a big need for a better theoretical foundation in order to systematically integrate these aspects. The main contribution of this thesis is to address this need by providing alternative and complementary design guidelines with respect to existing approaches, all of which have been conceived before the recently increased research interest in listening modes. None of the existing contributions to design frameworks integrates multimodality, and listening modes with a focus on exploratory data analysis, where sonification is conceived to support the understanding of complex data potentially helping to identify new structures therein. In order to structure this field the following questions are addressed in this thesis: • How do natural listening modes and reduced listening relate to the proposed normative and descriptive display purposes? • What is the relationship of multimodality and interaction with listening modes and display purposes? • How can the potential of embodied cognition based listening modes be put to use for exploratory data sonification? • How can listening modes and display purposes be connected to questions of aesthetics in the display? • How do data complexity and Parameter-mapping sonification relate to exploratory data analysis and listening modes

Molecular Imaging of Inflammation in Atherosclerosis

Acute rupture of vulnerable plaques frequently leads to myocardial infarction and stroke. Within the last decades, several cellular and molecular players have been identified that promote atherosclerotic lesion formation, maturation and plaque rupture. It is now widely recognized that inflammation of the vessel wall and distinct leukocyte subsets are involved throughout all phases of atherosclerotic lesion development. The mechanisms that render a stable plaque unstable and prone to rupture, however, remain unknown and the identification of the vulnerable plaque remains a major challenge in cardiovascular medicine. Imaging technologies used in the clinic offer minimal information about the underlying biology and potential risk for rupture. New imaging technologies are therefore being developed, and in the preclinical setting have enabled new and dynamic insights into the vessel wall for a better understanding of this complex disease. Molecular imaging has the potential to track biological processes, such as the activity of cellular and molecular biomarkers in vivo and over time. Similarly, novel imaging technologies specifically detect effects of therapies that aim to stabilize vulnerable plaques and silence vascular inflammation. Here we will review the potential of established and new molecular imaging technologies in the setting of atherosclerosis, and discuss the cumbersome steps required for translating molecular imaging approaches into the clinic

Sounding Composition, Composing Sound: Multimodal Listening, Bodily Pedagogies, and Everyday Experience

My dissertation re-imagines the teaching of listening in rhetoric and composition to account for sonic experiences in the twenty-first century. Technologies such as audio editing and music software allow users to control sound in ways that were not possible for the average listener before personal computers and digital audio devices became widely available. While digital technologies have presented new opportunities for re-thinking how to teach listening in relation to composing, they have also resulted in a selective and limited understanding of how sound works and affects in the world at large. The aim of my dissertation is to offer a listening pedagogy that helps students capitalize on the compositional affordances of sound in digital contexts and retrains them to become more thoughtful, sensitive listener-composers of sound in any setting. Drawing from the listening and composing practices of deaf musician Evelyn Glennie, acoustic designers, and automotive acoustic engineers, I propose an expansive, explicitly embodied approach to the teaching of listening in rhetoric and composition. The listening pedagogy I introduce is based on my concept of multimodal listening, a practice that involves attending to the sensory, material, and contextual aspects that comprise and shape a sonic event. Unlike ear-centric listening practices in which listeners’ main goal is to hear and interpret audible sound (often language), multimodal listening practices move beyond the exclusively audible by emphasizing the ecological relationship between sound, bodies, and environments. I argue that cultivating multimodal listening practices will enable students to become more savvy consumers and producers of sound in the composition classroom and in their everyday lives