Towards Noninvasive Molecular Fluorescence Imaging of the Human Brain (original) (raw)

Perspective: Prospects of non-invasive sensing of the human brain with diffuse optical imaging

APL Photonics, 2018

Since the initial demonstration of near-infrared spectroscopy (NIRS) for noninvasive measurements of brain perfusion and metabolism in the 1970s, and its application to functional brain studies (fNIRS) in the 1990s, the field of noninvasive optical studies of the brain has been continuously growing. Technological developments, data analysis advances, and novel areas of application keep advancing the field. In this article, we provide a view of the state of the field of cerebral NIRS, starting with a brief historical introduction and a description of the information content of the NIRS signal. We argue that NIRS and fNIRS studies should always report data of both oxy- and deoxyhemoglobin concentrations in brain tissue, as they complement each other to provide more complete functional and physiological information, and may help identify different types of confounds. One significant challenge is the assessment of absolute tissue properties, be them optical or physiological, so that rel...

Non-invasive optical spectroscopy and imaging of human brain function

Trends in Neurosciences, 1997

Brain activity is associated with changes in optical properties of brain tissue. Optical measurements during brain activation can assess haemoglobin oxygenation, cytochrome-c-oxidase redox state, and two types of changes in light scattering reflecting either membrane potential (fast signal) or cell swelling (slow signal), respectively. In previous studies of exposed brain tissue, optical imaging of brain activity has been achieved at high temporal and microscopical spatial resolution. Now, using near-infrared light that can penetrate biological tissue reasonably well, it has become possible to assess brain activity in human subjects through the intact skull non-invasively. After early studies employing single-site near-infrared spectroscopy, first near-infrared imaging devices are being applied successfully for low-resolution functional brain imaging. Advantages of the optical methods include biochemical specificity, a temporal resolution in the millisecond range, the potential of measuring intracellular and intravascular events simultaneously and the portability of the devices enabling bedside examinations.

Molecular imaging using visible light to reveal biological changes in the brain

Neuroimaging clinics of North America, 2006

Advances in imaging have enabled the study of cellular and molecular processes in the context of the living body that include cell migration patterns, location and extent of gene expression, degree of protein-protein interaction, and levels of enzyme activity. These tools, which operate over a range of scales, resolutions, and sensitivities, have opened up broad new areas of investigation where the influence of organ systems and functional circulation is intact. There are a myriad of imaging modalities available, each with its own advantages and disadvantages, depending on the specific application. Among these modalities, optical imaging techniques, including in vivo bioluminescence imaging and fluorescence imaging, use visible light to interrogate biology in the living body. Optimal imaging with these modalities require that the appropriate marker be used to tag the process of interest to make it uniquely visible using a particular imaging technology. For each optical modality, the...

In vivo Near Infrared Spectroscopy: a novel approach for simultaneously estimating molecules and hemodynamic parameters in the human and rat brain: a review

Medical research archives, 2018

There have been great advances in optical brain imaging over the last 50 years and the technique has grown into a richly diverse field. In vivo recording and imaging using light provides extraordinary sensitivity to functional changes through intrinsic contrast, blood, and can even exploit the growing availability of exogenous optical contrast agents. Light can be used to analyze microscopic structures and function in vivo in the exposed animal brain, while also allowing noninvasive imaging of hemodynamics and metabolism in a clinical setting. This review is an overview of approaches that have been applied in vivo optical brain recording, in both animals and humans. The basic principles of each technique are described, emphasizing the techniques used in our laboratory. Techniques include imaging of exposed cortex, in vivo functional spectroscopy of the living brain using optic fibers, and the broad range of noninvasive topography and tomography approaches to near-infrared imaging of...

Noninvasive Near-infrared Imaging of Fluorochromes within the Brains of Live Mice: An In Vivo Phantom Study

Molecular Imaging, 2006

Near-infrared fluorescence (NIRF) imaging has great potential for studying physiological and pathophysiological processes noninvasively in several locations of the body. In this study, we evaluated the feasibility of NIRF imaging to visualize fluorescent compounds within the brains of live mice commonly used in brain research. To simulate the presence of a molecular NIRF reporter agent at the site of a lesion, we developed a new in vivo phantom model wherein capsules containing different amounts of an NIRF dye (Cy5.5) were stereotactically implanted deep into the left hemispheres of living mice. To precisely locate the implanted capsules, magnetic resonance imaging (MRI) was performed. Fluorescence reflectance imaging (FRI) and transillumination fluorescence imaging (TFI) were conducted to analyze and compare sensitivity and targetto-background ratios of the two methods. The sensitivities of FRI and TFI to background fluorescence from circulating dye was tested by imaging fluorescent capsules in mice intravenously injected with increasing amounts of long-circulating Cy5.5-dextran. The results show that capsules containing dye amounts as low as 10 À12 mol can be detected. TFI yielded significantly higher target-to-background ratios than FRI at 10 À11 mol (p < .05). Comparatively low amounts of fluorescence in the blood vessels can extinguish the signal. We conclude that keeping the signal from circulating NIRF dye low, NIRF imaging offers high sensitivity in detecting fluorochromes noninvasively within brains of mice, especially by using TFI. This encourages the application of NIRF for molecular imaging in the mouse brain using NIRF reporters.

Noninvasive near-infrared imaging of fluorochromes within the brain of live mice: an in vivo phantom study

Molecular Imaging

Near-infrared fluorescence (NIRF) imaging has great potential for studying physiological and pathophysiological processes noninvasively in several locations of the body. In this study, we evaluated the feasibility of NIRF imaging to visualize fluorescent compounds within the brains of live mice commonly used in brain research. To simulate the presence of a molecular NIRF reporter agent at the site of a lesion, we developed a new in vivo phantom model wherein capsules containing different amounts of an NIRF dye (Cy5.5) were stereotactically implanted deep into the left hemispheres of living mice. To precisely locate the implanted capsules, magnetic resonance imaging (MRI) was performed. Fluorescence reflectance imaging (FRI) and transillumination fluorescence imaging (TFI) were conducted to analyze and compare sensitivity and target-to-background ratios of the two methods. The sensitivities of FRI and TFI to background fluorescence from circulating dye was tested by imaging fluoresce...

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.

Near-infrared fluorescence imaging with fluorescently labeled albumin: A novel method for non-invasive optical imaging of blood–brain barrier impairment after focal cerebral ischemia in mice

Journal of Neuroscience Methods, 2009

Impairment of the blood-brain barrier (BBB) after cerebral ischemia leads to extravasation of plasma constituents into the brain parenchyma. We describe a novel method using non-invasive near-infrared fluorescence (NIRF) imaging and bovine serum albumin labeled with a NIRF dye (NIRF-BSA) to detect BBB impairment after middle cerebral artery occlusion (MCAO) in mice. We first explored the time course of BBB impairment after transient MCAO using Evans blue (EB), which binds to plasma albumin in vivo. An initial BBB impairment was observed at 4-8 h and a second impairment at 12-16 h after reperfusion. No EB extravasation was detected at 8-12 h. Non-invasive NIRF imaging with NIRF-BSA confirmed biphasic BBB impairment. Upon co-injection of NIRF-BSA with EB we found a strong correlation between the detected NIRF signal and the amount of extravasated EB (r = 0.857, P = 0.00178). When MCAO mice received NIRF-BSA together with gadolinium-diethylene triamine penta-acetic acid (Gd-DTPA), T1weighted images showed Gd-DTPA enhancement at all times while NIRF imaging showed biphasic BBB impairment. In conclusion, NIRF-BSA is a suitable marker of plasma albumin extravasation in the mouse brain. Non-invasive NIRF imaging with NIRF-BSA is a useful tool to study BBB integrity in preclinical models of central nervous system pathology.