Fluorescence lifetime-based optical molecular imaging.
ABSTRACT Fluorescence lifetime is a powerful contrast mechanism for in vivo molecular imaging. In this chapter, we describe instrumentation and methods to optimally exploit lifetime contrast using a time domain fluorescence tomography system. The key features of the system are the use of point excitation in free-space using ultrashort laser pulses and non-contact detection using a gated, intensified CCD camera. The surface boundaries of the imaging volume are acquired using a photogrammetric camera integrated with the imaging system, and implemented in theoretical models of light propagation in biological tissue. The time domain data are optimally analyzed using a lifetime-based tomography approach, which is based on extracting a tomographic set of lifetimes and decay amplitudes from the long time decay portion of the time domain data. This approach improves the ability to locate in vivo targets with a resolution better than conventional optical methods. The application of time domain lifetime multiplexing and tomography are illustrated using phantoms and tumor bearing mouse model of breast adenocarcinoma. In the latter application, the time domain approach allows an improved detection of fluorescent protein signals from intact nude mice in the presence of background autofluorescence. This feature has potential applications for longitudinal pre-clinical evaluation of drug treatment response as well as to address fundamental questions related to tumor physiology and metastasis.
- SourceAvailable from: Erik F J de Vries[Show abstract] [Hide abstract]
ABSTRACT: Insulin-dependent (type 1) diabetes mellitus is a metabolic disease with a complex multifactorial etiology and a poorly understood pathogenesis. Genetic and environmental factors cause an autoimmune reaction against pancreatic β-cells, called insulitis, confirmed in pancreatic samples obtained at autopsy. The possibility to noninvasively quantify β-cell mass in vivo would provide important biological insights and facilitate aspects of diagnosis and therapy, including follow-up of islet cell transplantation. Moreover, the availability of a noninvasive tool to quantify the extent and severity of pancreatic insulitis could be useful for understanding the natural history of human insulin-dependent (type 1) diabetes mellitus, to early diagnose children at risk to develop overt diabetes, and to select patients to be treated with immunotherapies aimed at blocking the insulitis and monitoring the efficacy of these therapies. In this review, we outline the imaging techniques currently available for in vivo, noninvasive detection of β-cell mass and insulitis. These imaging techniques include magnetic resonance imaging, ultrasound, computed tomography, bioluminescence and fluorescence imaging, and the nuclear medicine techniques positron emission tomography and single-photon emission computed tomography. Several approaches and radiopharmaceuticals for imaging β-cells and lymphocytic insulitis are reviewed in detail.Endocrine reviews 08/2012; 33(6). DOI:10.1210/er.2011-1041 · 19.36 Impact Factor