Imaging and biological function in health and disease

Since the invention of the microscope, imaging has guided the mainstream of science and medicine by revealing structures not visible to the human eye. Views of single cells, organelles, molecules, and even atoms obtained by modern microscopy are now central to biological investigations. In the case of the whole body, biomedical imaging also reveals structures beneath the surface. This “occlusion problem” has been solved by techniques such as x-ray, computerized tomography (CT), positron emission tomography (PET), and MRI, which provide high-resolution views of organs and tissues within the living body. Thus, structure at the highest levels of biologically relevant detail either in the living body or in vitro is currently available for investigation of biological mechanisms and for the diagnosis and treatment of disease. Although a picture may be worth a thousand words, current standards of clinical investigation aim beyond the view in order to understand mechanisms of action. Thus, beyond this unprecedented level of structural detail, overlays of physiological mechanisms add a necessary dimension to biomedical imaging. For example, the technical and structural challenges of imaging a moving object such as a heart must be linked to functional patterns of blood flow and turbulence in order to address more complicated problems related to treatment of heart failure. In the case of the brain, advances in imaging extend well beyond the domains of structures, regardless of size, motion, or occlusion, to the domain of function by identification of active neural tissue. This new form of functional imaging adds a novel dimension to conventional imaging by isolating the neurobiology of specific mental events. Thus, current frontiers in biomedical investigation encompass not only structures and functions of subcellular, cellular, and organ systems but also structures and neural functions that are linked to perceptions, cognition, and volitional action. In keeping with the broad scope and fast pace of new developments in structural and functional imaging, this Perspective series aims to highlight representative new areas where developments in imaging profoundly advance and redirect our understanding and treatment of human disease. Although many potential topics would serve this objective, those included here have been selected to encompass representative advances. These topics would not conventionally fall under a single organizational scheme. The unifying goal is to illuminate frontiers in biomedical imaging that impact our understanding and treatment of human disease. Thus, complex sociomedical issues, such as the scanning of nonsymptomatic individuals to screen for indications of disease, are linked to subcellular processes that lead to gene therapy as examples of new horizons that encompass both structural and functional advances in biomedical imaging. Six emerging areas of clinical investigation and the imaging technologies that drive them are organized around this unifying theme.