Imaging of X-Ray-Excited Emissions from Quantum Dots and Biological Tissue in Whole Mouse

© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Optical imaging in clinical and preclinical settings can provide a wealth of biological information, particularly when coupled with targetted nanoparticles, but optical scattering and absorption limit the depth and resolution in both animal and human subjects. Two new hybrid approaches are presented, using the penetrating power of X-rays to increase the depth of optical imaging. Foremost, we demonstrate the excitation by X-rays of quantum-dots (QD) emitting in the near-infrared (NIR), using a clinical X-ray system to map the distribution of QDs at depth in whole mouse. We elicit a clear, spatially-resolved NIR signal from deep organs (brain, liver and kidney) with short (1 second) exposures and tolerable radiation doses that will permit future in vivo applications. Furthermore, X-ray-excited endogenous emission is also detected from whole mouse. The use of keV X-rays to excite emission from QDs and tissue represent novel biomedical imaging technologies, and exploit emerging QDs as optical probes for spatial-temporal molecular imaging at greater depth than previously possible.Peer reviewe

Comparative study on the detection of early dental caries using thermo-photonic lock-in imaging and optical coherence tomography

Early detection of dental caries is known to be the key to the effectiveness of therapeutic and preventive approaches in dentistry. However, existing clinical detection techniques, such as radiographs, are not sufficiently sensitive to detect and monitor the progression of caries at early stages. As such, in recent years, several optics-based imaging modalities have been proposed for the early detection of caries. The majority of these techniques rely on the enhancement of light scattering in early carious lesions, while a few of them are based on the enhancement of light absorption at early caries sites. In this paper, we report on a systemic comparative study on the detection performances of optical coherence tomography (OCT) and thermophotonic lock-in imaging (TPLI) as representative early caries detection modalities based on light scattering and absorption, respectively. Through controlled demineralization studies on extracted human teeth and µCT validation experiments, several detection performance parameters of the two modalities such as detection threshold, sensitivity and specificity have been qualitatively analyzed and discussed. Our experiment results suggests that both modalities have sufficient sensitivity for the detection of well-developed early caries on occlusal and smooth surfaces; however, TPLI provides better sensitivity and detection threshold for detecting very early stages of caries formation, which is deemed to be critical for the effectiveness of therapeutic and preventive approaches in dentistry. Moreover, due to the more specific nature of the light absorption contrast mechanism over light scattering, TPLI exhibits better detection specificity, which results in less false positive readings and thus allows for the proper differentiation of early caries regions from the surrounding intact areas. The major shortcoming of TPLI is its inherent depth-integrated nature, prohibiting the production of depth-resolved/B-mode like images. The outcomes of this research justify the need for a light-absorption based imaging modality with the ability to produce tomographic and depth-resolved images, combining the key advantages of OCT and TPLI.York University Librarie

Photoacoustic computed tomography guided microrobots for targeted navigation in intestines in vivo

Tremendous progress in synthetic micro/nanomotors has been made for potential biomedical applications. However, existing micro/nanomotor platforms are inefficient for deep tissue imaging and motion control in vivo. Here, we present a photoacoustic computed tomography (PACT) guided investigation of micromotors in intestines in vivo. The micromotors enveloped in microcapsules exhibit efficient propulsion in various biofluids once released. PACT has visualized the migration of micromotor capsules toward the targeted regions in real time in vivo. The integration of the developed microrobotic system and PACT enables deep imaging and precise control of the micromotors in vivo

In vivo tomographic imaging of red-shifted fluorescent proteins

We have developed a spectral inversion method for three-dimensional tomography of far-red and near-infrared fluorescent proteins in animals. The method was developed in particular to address the steep light absorption transition of hemoglobin from the visible to the far-red occurring around 600 nm. Using an orthotopic mouse model of brain tumors expressing the red-shifted fluorescent protein mCherry, we demonstrate significant improvements in imaging accuracy over single-wavelength whole body reconstructions. Furthermore, we show an improvement in sensitivity of at least an order of magnitude over green fluorescent protein (GFP) for whole body imaging. We discuss how additional sensitivity gains are expected with the use of further red-shifted fluorescent proteins and we explain the differences and potential advantages of this approach over two-dimensional planar imaging methods

Three dimensional optical imaging of blood volume and oxygenation in the neonatal brain

Optical methods provide a means of monitoring cerebral oxygenation in newborn infants at risk of brain injury. A 32-channel optical imaging system has been developed with the aim of reconstructing three-dimensional images of regional blood volume and oxygenation. Full image data sets were acquired from 14 out of 24 infants studied; successful images have been reconstructed in 8 of these infants. Regional variations in cerebral blood volume and tissue oxygen saturation are present in healthy preterm infants. In an infant with a large unilateral intraventricular haemorrhage, a corresponding region of low oxygen saturation was detected. These results suggest that optical tomography may provide an appropriate technique for investigating regional cerebral haemodynamics and oxygenation at the cotside. (c) 2006 Elsevier Inc. All rights reserved

Fluorescence molecular tomography: Principles and potential for pharmaceutical research

Fluorescence microscopic imaging is widely used in biomedical research to study molecular and cellular processes in cell culture or tissue samples. This is motivated by the high inherent sensitivity of fluorescence techniques, the spatial resolution that compares favorably with cellular dimensions, the stability of the fluorescent labels used and the sophisticated labeling strategies that have been developed for selectively labeling target molecules. More recently, two and three-dimensional optical imaging methods have also been applied to monitor biological processes in intact biological organisms such as animals or even humans. These whole body optical imaging approaches have to cope with the fact that biological tissue is a highly scattering and absorbing medium. As a consequence, light propagation in tissue is well described by a diffusion approximation and accurate reconstruction of spatial information is demanding. While in vivo optical imaging is a highly sensitive method, the signal is strongly surface weighted, i.e., the signal detected from the same light source will become weaker the deeper it is embedded in tissue, and strongly depends on the optical properties of the surrounding tissue. Derivation of quantitative information, therefore, requires tomographic techniques such as fluorescence molecular tomography (FMT), which maps the three-dimensional distribution of a fluorescent probe or protein concentration. The combination of FMT with a structural imaging method such as X-ray computed tomography (CT) or Magnetic Resonance Imaging (MRI) will allow mapping molecular information on a high definition anatomical reference and enable the use of prior information on tissue’s optical properties to enhance both resolution and sensitivity. Today many of the fluorescent assays originally developed for studies in cellular systems have been successfully translated for experimental studies in animals. The opportunity of monitoring molecular processes non-invasively in the intact organism is highly attractive from a diagnostic point of view but even more so for the drug developer, who can use the techniques for proof-of-mechanism and proof-of-efficacy studies. This review shall elucidate the current status and potential of fluorescence tomography including recent advances in multimodality imaging approaches for preclinical and clinical drug development

Quantitative Whole Body Biodistribution of Fluorescent-Labeled Agents by Non-Invasive Tomographic Imaging

When small molecules or proteins are injected into live animals, their physical and chemical properties will significantly affect pharmacokinetics, tissue penetration, and the ultimate routes of metabolism and clearance. Fluorescence molecular tomography (FMT) offers the ability to non-invasively image and quantify temporal changes in fluorescence throughout the major organ systems of living animals, in a manner analogous to traditional approaches with radiolabeled agents. This approach is best used with biotherapeutics (therapeutic antibodies, or other large proteins) or large-scaffold drug-delivery vectors, that are minimally affected by low-level fluorophore conjugation. Application to small molecule drugs should take into account the significant impact of fluorophore labeling on size and physicochemical properties, however, the presents studies show that this technique is readily applied to small molecule agents developed for far-red (FR) or near infrared (NIR) imaging. Quantification by non-invasive FMT correlated well with both fluorescence from tissue homogenates as well as with planar (2D) fluorescence reflectance imaging of excised intact organs (r2 = 0.996 and 0.969, respectively). Dynamic FMT imaging (multiple times from 0 to 24 h) performed in live mice after the injection of four different FR/NIR-labeled agents, including immunoglobulin, 20–50 nm nanoparticles, a large vascular imaging agent, and a small molecule integrin antagonist, showed clear differences in the percentage of injected dose per gram of tissue (%ID/g) in liver, kidney, and bladder signal. Nanoparticles and IgG1 favored liver over kidney signal, the small molecule integrin-binding agent favored rapid kidney and bladder clearance, and the vascular agent, showed both liver and kidney clearance. Further assessment of the volume of distribution of these agents by fluorescent volume added information regarding their biodistribution and highlighted the relatively poor extravasation into tissue by IgG1. These studies demonstrate the ability of quantitative FMT imaging of FR/NIR agents to non-invasively visualize and quantify the biodistribution of different agents over time

Correspondence of Electroencephalography and Near-Infrared Spectroscopy Sensitivities to the Cerebral Cortex using a High-Density Layout

This study investigates the correspondence of the cortical sensitivity of electroencephalography (EEG) and near-infrared spectroscopy (NIRS). EEG forward model sensitivity to the cerebral cortex was calculated for 329 EEG electrodes following the 10-5 EEG positioning system using a segmented structural magnetic resonance imaging scan of a human subject. NIRS forward model sensitivity was calculated for the same subject using 156 NIRS source-detector pairs selected from 32 source and 32 detector optodes positioned on the scalp using a subset of the 10-5 EEG positioning system. Sensitivity correlations between colocalized NIRS source-detector pair groups and EEG channels yielded R=0.46±0.08 . Groups of NIRS source-detector pairs with maximum correlations to EEG electrode sensitivities are tabulated. The mean correlation between the point spread functions for EEG and NIRS regions of interest (ROI) was R=0.43±0.07 . Spherical ROIs with radii of 26 mm yielded the maximum correlation between EEG and NIRS averaged across all cortical mesh nodes. These sensitivity correlations between EEG and NIRS should be taken into account when designing multimodal studies of neurovascular coupling and when using NIRS as a statistical prior for EEG source localization

Imaging of X-Ray-Excited Emissions from Quantum Dots and Biological Tissue in Whole Mouse

Optical imaging in clinical and preclinical settings can provide a wealth of biological information, particularly when coupled with targetted nanoparticles, but optical scattering and absorption limit the depth and resolution in both animal and human subjects. Two new hybrid approaches are presented, using the penetrating power of X-rays to increase the depth of optical imaging. Foremost, we demonstrate the excitation by X-rays of quantum-dots (QD) emitting in the near-infrared (NIR), using a clinical X-ray system to map the distribution of QDs at depth in whole mouse. We elicit a clear, spatially-resolved NIR signal from deep organs (brain, liver and kidney) with short (1 second) exposures and tolerable radiation doses that will permit future in vivo applications. Furthermore, X-ray-excited endogenous emission is also detected from whole mouse. The use of keV X-rays to excite emission from QDs and tissue represent novel biomedical imaging technologies, and exploit emerging QDs as optical probes for spatial-temporal molecular imaging at greater depth than previously possible