A neurovascular high-frequency optical coherence tomography system enables in situ cerebrovascular volumetric microscopy

Intravascular imaging has emerged as a valuable tool for the treatment of coronary and peripheral artery disease; however, no solution is available for safe and reliable use in the tortuous vascular anatomy of the brain. Endovascular treatment of stroke is delivered under image guidance with insufficient resolution to adequately assess underlying arterial pathology and therapeutic devices. High-resolution imaging, enabling surgeons to visualize cerebral arteries\u27 microstructure and micron-level features of neurovascular devices, would have a profound impact in the research, diagnosis, and treatment of cerebrovascular diseases. Here, we present a neurovascular high-frequency optical coherence tomography (HF-OCT) system, including an imaging console and an endoscopic probe designed to rapidly acquire volumetric microscopy data at a resolution approaching 10 microns in tortuous cerebrovascular anatomies. Using a combination of in vitro, ex vivo, and in vivo models, the feasibility of HF-OCT for cerebrovascular imaging was demonstrated

Reproducibility of parameters of postocclusive reactive hyperemia measured by diffuse optical tomography

The application of near-infrared spectroscopy (NIRS) to assess microvascular function has shown promising results. An important limitation when using a single source-detector pair, however, is the lack of depth sensitivity. Diffuse optical tomography (DOT) overcomes this limitation using an array of sources and detectors that allow the reconstruction of volumetric hemodynamic changes. This study compares the key parameters of postocclusive reactive hyperemia measured in the forearm using standard NIRS and DOT. We show that while the mean parameter values are similar for the two techniques, DOT achieves much better reproducibility, as measured by the intraclass correlation coefficient (ICC). We show that DOT achieves high reproducibility for muscle oxygen consumption (ICC: 0.99), time to maximal HbO2HbO2 (ICC: 0.94), maximal HbO2HbO2 (ICC: 0.99), and time to maximal HbT (ICC: 0.99). Absolute reproducibility as measured by the standard error of measurement is consistently smaller and close to zero (ideal value) across all parameters measured by DOT compared to NIRS. We conclude that DOT provides a more robust characterization of the reactive hyperemic response and show how the availability of volumetric hemodynamic changes allows the identification of areas of temporal consistency, which could help characterize more precisely the microvasculature

High-density speckle contrast optical tomography (SCOT) for three dimensional tomographic imaging of the small animal brain

High-density speckle contrast optical tomography (SCOT) utilizing tens of thousands of source-detector pairs, was developed for in vivo imaging of blood flow in small animals. The reduction in cerebral blood flow (CBF) due to local ischemic stroke in a mouse brain was transcanially imaged and reconstructed in three dimensions. The reconstructed volume was then compared with corresponding magnetic resonance images demonstrating that the volume of reduced CBF agrees with the infarct zone at twenty-four hours.Peer ReviewedPostprint (author's final draft

IEEE Trans Biomed Eng

With the wide use of small animals for biomedical studies, in vivo small-animal whole-body imaging plays an increasingly important role. Photoacoustic tomography (PAT) is an emerging whole-body imaging modality that shows great potential for preclinical research. As a hybrid technique, PAT is based on the acoustic detection of optical absorption from either endogenous tissue chromophores, such as oxyhemoglobin and deoxyhemoglobin, or exogenous contrast agents. Because ultrasound scatters much less than light in tissue, PAT generates high-resolution images in both the optical ballistic and diffusive regimes. Using near-infrared light, which has relatively low blood absorption, PAT can image through the whole body of small animals with acoustically defined spatial resolution. Anatomical and vascular structures are imaged with endogenous hemoglobin contrast, while functional and molecular images are enabled by the wide choice of exogenous optical contrasts. This paper reviews the rapidly growing field of small-animal whole-body PAT and highlights studies done in the past decade.DP1 EB016986/DP/NCCDPHP CDC HHS/United StatesDP1 EB016986/EB/NIBIB NIH HHS/United StatesR01 CA134539/CA/NCI NIH HHS/United StatesR01 CA157277/CA/NCI NIH HHS/United StatesR01 CA159959/CA/NCI NIH HHS/United StatesR01 EB008085/EB/NIBIB NIH HHS/United StatesR01 EB008085/EB/NIBIB NIH HHS/United StatesR01 EB010049/EB/NIBIB NIH HHS/United StatesR01 EB010049/EB/NIBIB NIH HHS/United StatesR01 EB016963/EB/NIBIB NIH HHS/United StatesR01 EB016963/EB/NIBIB NIH HHS/United StatesR01CA134539/CA/NCI NIH HHS/United StatesR01CA157277/CA/NCI NIH HHS/United StatesR01CA159959/CA/NCI NIH HHS/United StatesU54 CA136398/CA/NCI NIH HHS/United StatesU54CA136398/CA/NCI NIH HHS/United States2014-05-01T00:00:00Z24108456PMC396565

Optical Imaging

Optical Coherence Tomography (OCT)We describe the fundamental concept of optical coherence tomography (OCT) and discuss the two main working principles time domain OCT and frequency domain OCT. Then, we review extended functionalities including spectrally and polarization-resolved OCT as well as Doppler-OCT and show concepts for contrast enhancement. Based on these fundamentals, we demonstrate the potential of OCT for small animal imaging on the basis of exemplary studies on retinal imaging and lung imaging.Optoacoustic ImagingThis chapter deals with the fascinating topic of optoacoustic imaging, a recent powerful addition to the arsenal of in vivo functional and molecular small animal imaging. Due to its hybrid nature, involving optical excitation and ultrasonic detection, optoacoustics overcomes the imaging depth limitations of optical microscopy related to light scattering in living tissues while further benefiting from the compelling advantages of optical contrast. To this end, optoacoustic imaging has been shown capable of delivering multiple types of imaging contrast (structural, functional, kinetic, molecular) within a single imaging modality. It can further deliver images with high spatiotemporal resolution that rivals performance of other well-established whole-body imaging modalities. As such, optoacoustics can play a vital role in biomedical research, from early disease detection and monitoring of dynamic phenomena noninvasively to accelerating drug discovery.Optical ProbesThis chapter is devoted to the properties and application of fluorescence dyes as probes for optical imaging. A variety of agents have been described to date, including nontargeting dyes, vascular agents, targeted conjugates, activatable dyes, and sensing probes. The major classes encompass polymethine dyes and xanthenes dyes, both of which are commercially available in broad variations. Addressing the purpose of optical animal imaging, the most relevant parameters to apply such probes are discussed, thereby supporting the reader in choosing reasonable imaging probes and in preparing bioconjugates for his studies

Photoacoustic microscopy

Photoacoustic microscopy (PAM) is a hybrid in vivo imaging technique that acoustically detects optical contrast via the photoacoustic effect. Unlike pure optical microscopic techniques, PAM takes advantage of the weak acoustic scattering in tissue and thus breaks through the optical diffusion limit (∼1 mm in soft tissue). With its excellent scalability, PAM can provide high-resolution images at desired maximum imaging depths up to a few millimeters. Compared with backscattering-based confocal microscopy and optical coherence tomography, PAM provides absorption contrast instead of scattering contrast. Furthermore, PAM can image more molecules, endogenous or exogenous, at their absorbing wavelengths than fluorescence-based methods, such as wide-field, confocal, and multi-photon microscopy. Most importantly, PAM can simultaneously image anatomical, functional, molecular, flow dynamic and metabolic contrasts in vivo. Focusing on state-of-the-art developments in PAM, this Review discusses the key features of PAM implementations and their applications in biomedical studies