Current Molecular Imaging (v.3, #2)

Editorial (Thematic Issue: Optical Molecular Imaging) by Yu Chen, Xavier Intes (71-71).

Multimodal Biomedical Optical Imaging Review: Towards Comprehensive Investigation of Biological Tissues by Qi Pian, Chao Wang, Xueli Chen, Jimin Liang, Lingling Zhao, Ge Wang, Xavier Intes (72-87).
Optical imaging techniques ranging from mesoscopic to macroscopic levels provide non-invasive, non-ionized and highly sensitive investigation of thick biological tissues with different spatial resolution, penetration depth and contrast mechanisms. Multimodal optical imaging can be understood as the combination of multiple optical imaging modalities and/or fusion with established conventional medical imaging modalities such as computed tomography (CT), magnetic resonance (MR), ultrasound imaging (US) and positron emission tomography (PET). Multimodal optical imaging allows to capture complementary anatomical, physiological and molecular data sets for enhanced diagnosis, therapy monitoring and to assist drug development. Moreover, multimodal optical imaging platforms provides unique tool to validate new imaging paradigms via data cross-validation. Herein, we summarize the recent technical progresses of multimodal optical imaging for thick tissue applications. More particularly, we focus on the mesoscopic imaging regime (optical coherence tomography) and macroscopic imaging (diffuse optical tomography and bioluminescent tomography) applied to subsurface and deep tissue investigation.

Molecular Imaging in Optical Coherence Tomography by Scott P. Mattison, Wihan Kim, Jesung Park, Brian E. Applegate (88-105).
Optical coherence tomography (OCT) is a medical imaging technique that provides tomographic images at micron scales in three dimensions and high speeds. The addition of molecular contrast to the available morphological image holds great promise for extending OCT's impact in clinical practice and beyond. Fundamental limitations prevent OCT from directly taking advantage of powerful molecular processes such as fluorescence emission and incoherent Raman scattering. A wide range of approaches is being researched to provide molecular contrast to OCT. Here we review those approaches with particular attention to those that derive their molecular contrast directly from modulation of the OCT signal. We also provide a brief overview of the multimodal approaches to gaining molecular contrast coincident with OCT.

Cerenkov Luminescence Imaging at a Glance by Federico Boschi, Antonello E. Spinelli (106-117).
Cerenkov luminescence imaging (CLI) is a new technique that has rapidly gained great interest in the molecular imaging field bridging optical imaging and nuclear medicine. Based on the detection of Cerenkov radiation (CR) in biological tissue, in only five years many different applications of CLI were developed spanning from cancer imaging to Alzheimer's disease and many different approaches were tested in order to increase its potentialities. In particular some efforts were made to transform CLI from a planar imaging technique into a tomographic technique or to shift the CR in a red-infrared radiation more suitable for biological applications. Moreover CLI, developed as a preclinical investigation, has obtained very quickly, interesting results on humans. Here we present a schematic and brief overview of the CLI landscape in order to show the principal results and applications to the biology. More precisely we focused on the potentialities of optical detection of radiotracers excluding the application of Cerenkov radiation obtained with the use of external radiation beam.

In vivo Optical Molecular Imaging of Cardiovascular Diseases: Long Road Ahead by Yingfeng Tu, Lei Jiang, Ruiping Zhang, Baozhong Shen, Zhen Cheng (118-128).
Optical molecular imaging is a powerful imaging method, which can in vivo monitor physiological and pathobiological processes at the cellular and molecular levels, as opposed to the anatomical level, bridging the gap between imaging and biological processes. Because of its relevance in cardiovascular diseases research, the use of this technology for imaging of cardiovascular diseases advances at a rapid pace in the past decade. This review summarizes the optical molecular imaging methods for imaging the specific targets in cardiovascular diseases, which hold promise for in vivo applications in cardiovascular diseases research. Collectively, in vivo optical molecular imaging may be highly suitable for discriminating targets that play key roles in the occurrence and development of the instable atherosclerosis, thrombogenesis, myocardial infarction, myocardial apoptosis, angiogenesis, as well as in cardiac cell transplantation.

The process of device evolution from concept to clinical application has been called “bench to bedside”. This term is used by many to define translational research, but it must be recognized that there is much more to translational research than this. We can use the words device translation to refer to the process of moving a technology methodically along a series of measurable milestones from concept to completion. Translational research, on the other hand, is the process of doing all this while at the same time employing a functional quality management system, regulatory adherence (e.g. safety and efficacy), and methods of standardization. The purpose of these intangible enterprises in the research effort is to lower the barriers at the interface between basic science and clinical medicine. Effective translation of technology across this interface is the goal of translational research, and requires the addition of metrics of quality along with sound scientific and engineering judgment. This article reviews the nature of translational research and looks at its key components of quality management and standardization.

FLIM-FRET for Cancer Applications by Shilpi Rajoria, Lingling Zhao, Xavier Intes, Margarida Barroso (144-161).
Optical imaging assays, especially fluorescence molecular assays, are minimally invasive if not completely noninvasive, and thus an ideal technique to be applied to live specimens. These fluorescence imaging assays are a powerful tool in biomedical sciences as they allow the study of a wide range of molecular and physiological events occurring in biological systems. Furthermore, optical imaging assays bridge the gap between the in vitro cell-based analysis of subcellular processes and in vivo study of disease mechanisms in small animal models. In particular, the application of Förster resonance energy transfer (FRET) and fluorescence lifetime imaging (FLIM), well-known techniques widely used in microscopy, to the optical imaging assay toolbox, will have a significant impact in the molecular study of protein-protein interactions during cancer progression. This review article describes the application of FLIM-FRET to the field of optical imaging and addresses their various applications, both current and potential, to anti-cancer drug delivery and cancer research.

Optical Stimulation of Neurons by Alexander C. Thompson, Paul R. Stoddart, E. Duco Jansen (162-177).
Our capacity to interface with the nervous system remains overwhelmingly reliant on electrical stimulation devices, such as electrode arrays and cuff electrodes that can stimulate both central and peripheral nervous systems. However, electrical stimulation has to deal with multiple challenges, including selectivity, spatial resolution, mechanical stability, implant-induced injury and the subsequent inflammatory response. Optical stimulation techniques may avoid some of these challenges by providing more selective stimulation, higher spatial resolution and reduced invasiveness of the device, while also avoiding the electrical artefacts that complicate recordings of electrically stimulated neuronal activity. This review explores the current status of optical stimulation techniques, including optogenetic methods, photoactive molecule approaches and infrared neural stimulation, together with emerging techniques such as hybrid optical-electrical stimulation, nanoparticle enhanced stimulation and optoelectric methods. Infrared neural stimulation is particularly emphasised, due to the potential for direct activation of neural tissue by infrared light, as opposed to techniques that rely on the introduction of exogenous light responsive materials. However, infrared neural stimulation remains imperfectly understood, and techniques for accurately delivering light are still under development. While the various techniques reviewed here confirm the overall feasibility of optical stimulation, a number of challenges remain to be overcome before they can deliver their full potential.