Molecular imaging using visible light to reveal biological changes in the brain (original) (raw)

Towards Noninvasive Molecular Fluorescence Imaging of the Human Brain

Neurodegenerative Diseases, 2008

of 680-850 nm and is thus termed near-infrared spectroscopy (NIRS). Today several commercial systems are available. Their measurements rely on the absorption properties of oxy-and deoxyhemoglobin to determine their concentration changes caused by variation in the regional cerebral blood flow because of functional activation or targeting changes in oxygenation due to pathological alterations. Specific targeting of disease processes, however, must aim at labeling molecules whose concentration depends on, for example, inflammation at a specific site in the brain. In animal models such fluorescence-based optical techniques [near-infrared fluorescence (NIRF)] have been successfully tested to characterize pathological processes in the brain using molecular probes . The goal to noninvasively detect molecular probes profits from the principal technological similarity between NIRS and fluorescence-based imaging: spectral filters in front of the detector block the excitation light remitted from the tissue to allow to selectively image the weaker, however more specific, signal from the fluorescent probe. Therefore techniques incorporating fluorescence detection into the noninvasive NIRS approach may take advantage of the versatility of NIRS while still reaching the high specificity of NIRF imaging. Such an approach will potentially allow for mo-Abstract Fluorescence molecular brain imaging is a new modality allowing the detection of specific contrast agents down to very low concentration ranges (picomolar) in disease models. Here we demonstrate a first noninvasive application of fluorescence imaging in the human brain, where concentrations down to about 100 n M of a nonspecific dye were detected. We argue that due to its high sensitivity, optical molecular imaging of the brain is feasible, which -together with its bedside applicability -makes it a promising technique for use in patients.

Imaging brain structure and function, infection and gene expression in the body using light

Philosophical Transactions of the Royal Society B: Biological Sciences, 1997

Light can be used to probe the function and structure of human tissues. We have been exploring two distinct methods: (i) externally emitting light into tissue and measuring the transmitted light to characterize a region through which the light has passed, and (ii) internally generating light within tissue and using the radiated light as a quantitative homing beacon. The emitted–light approach falls within the domain of spectroscopy, and has allowed for imaging of intracranial haemorrhage in newborns and of brain function in adults. The generated–light approach is conceptually parallel to positron emission tomography (PET) or nuclear medicine scanning, and has allowed for real–time, non–invasive monitoring and imaging of infection and gene expression in vivo using low–light cameras and ordinary lenses. In this paper, we discuss recent results and speculate on the applications of such techniques.

Optical Monitoring of Living Brain Tissue

Alcoholism: Clinical and Experimental Research, 1998

Optical methods can usefully augment classical techniques such as electrical recording for investigating cellular and network physiology. Here, recent developments in optical methods-including confocal and nonlinear fluorescence imaging, semiconductor array imaging, and improved fluorescent indicators of ion concentration and transmembrane electrical potential -are briefly reviewed, and examples are offered that may suggest potential applications to experimental studies in alcoholism research.

www.mdpi.com/journal/sensors Review In Vivo Bioluminescent Imaging (BLI): Noninvasive Visualization and Interrogation of Biological Processes in Living Animals

In vivo bioluminescent imaging (BLI) is increasingly being utilized as a method for modern biological research. This process, which involves the noninvasive interrogation of living animals using light emitted from luciferase-expressing bioreporter cells, has been applied to study a wide range of biomolecular functions such as gene function, drug discovery and development, cellular trafficking, protein-protein interactions, and especially tumorigenesis, cancer treatment, and disease progression. This article will review the various bioreporter/biosensor integrations of BLI and discuss how BLI is being applied towards a new visual understanding of biological processes within the living organism.

In Vivo Bioluminescent Imaging (BLI): Noninvasive Visualization and Interrogation of Biological Processes in Living Animals

Sensors, 2010

In vivo bioluminescent imaging (BLI) is increasingly being utilized as a method for modern biological research. This process, which involves the noninvasive interrogation of living animals using light emitted from luciferase-expressing bioreporter cells, has been applied to study a wide range of biomolecular functions such as gene function, drug discovery and development, cellular trafficking, protein-protein interactions, and especially tumorigenesis, cancer treatment, and disease progression. This article will review the various bioreporter/biosensor integrations of BLI and discuss how BLI is being applied towards a new visual understanding of biological processes within the living organism.

Frontiers in optical imaging of cerebral blood flow and metabolism

Journal of Cerebral Blood Flow & Metabolism, 2012

In vivo optical imaging of cerebral blood flow (CBF) and metabolism did not exist 50 years ago. While point optical fluorescence and absorption measurements of cellular metabolism and hemoglobin concentrations had already been introduced by then, point blood flow measurements appeared only 40 years ago. The advent of digital cameras has significantly advanced twodimensional optical imaging of neuronal, metabolic, vascular, and hemodynamic signals. More recently, advanced laser sources have enabled a variety of novel three-dimensional high-spatialresolution imaging approaches. Combined, as we discuss here, these methods are permitting a multifaceted investigation of the local regulation of CBF and metabolism with unprecedented spatial and temporal resolution. Through multimodal combination of these optical techniques with genetic methods of encoding optical reporter and actuator proteins, the future is bright for solving the mysteries of neurometabolic and neurovascular coupling and translating them to clinical utility.

Method of bioluminescence imaging for molecular imaging of physiological and pathological processes

Methods, 2009

Molecular imaging has emerged as a powerful tool in basic, pre-clinical and clinical research for monitoring a variety of molecular and cellular processes in living organisms. Optical imaging techniques, mainly bioluminescence imaging, have extensively been used to study biological processes because of their exquisite sensitivity and high signal-to noise ratio. However, current applications have mainly been limited to small animals due to attenuation and scattering of light by tissues but efforts are ongoing to overcome these hurdles. Here, we focus on bioluminescence imaging by giving a brief overview of recent advances in instrumentation, current available reporter gene-reporter probe systems and applications such as cell trafficking, protein-protein interactions and imaging endogenous processes.

A Rapid Approach to High-Resolution Fluorescence Imaging in Semi-Thick Brain Slices

Journal of Visualized Experiments, 2011

A fundamental goal to both basic and clinical neuroscience is to better understand the identities, molecular makeup, and patterns of connectivity that are characteristic to neurons in both normal and diseased brain. Towards this, a great deal of effort has been placed on building high-resolution neuroanatomical maps 1-3 . With the expansion of molecular genetics and advances in light microscopy has come the ability to query not only neuronal morphologies, but also the molecular and cellular makeup of individual neurons and their associated networks 4 . Major advances in the ability to mark and manipulate neurons through transgenic and gene targeting technologies in the rodent now allow investigators to 'program' neuronal subsets at will 5-6 . Arguably, one of the most influential contributions to contemporary neuroscience has been the discovery and cloning of genes encoding fluorescent proteins (FPs) in marine invertebrates 7-8 , alongside their subsequent engineering to yield an ever-expanding toolbox of vital reporters 9 . Exploiting cell type-specific promoter activity to drive targeted FP expression in discrete neuronal populations now affords neuroanatomical investigation with genetic precision.

Advances in light microscopy for neuroscience

Annual review of …, 2009

Since the work of Golgi and Cajal, light microscopy has remained a key tool for neuroscientists to observe cellular properties. Ongoing advances have enabled new experimental capabilities using light to inspect the nervous system across multiple spatial scales, including ultrastructural scales finer than the optical diffraction limit. Other progress permits functional imaging at faster speeds, at greater depths in brain tissue, and over larger tissue volumes than previously possible. Portable, miniaturized fluorescence microscopes now allow brain imaging in freely behaving mice. Complementary progress on animal preparations has enabled imaging in head-restrained behaving animals, as well as time-lapse microscopy studies in the brains of live subjects. Mouse genetic approaches permit mosaic and inducible fluorescence-labeling strategies, whereas intrinsic contrast mechanisms allow in vivo imaging of animals and humans without use of exogenous markers. This review surveys such advances and highlights emerging capabilities of particular interest to neuroscientists.