Magnetomotive Molecular Nanoprobes

Tremendous developments in the field of biomedical imaging in the past two decades have resulted in the transformation of anatomical imaging to molecular-specific imaging. The main approaches towards imaging at a molecular level are the development of high resolution imaging modalities with high penetration depths and increased sensitivity, and the development of molecular probes with high specificity. The development of novel molecular contrast agents and their success in molecular optical imaging modalities have lead to the emergence of molecular optical imaging as a more versatile and capable technique for providing morphological, spatial, and functional information at the molecular level with high sensitivity and precision, compared to other imaging modalities. In this review, we discuss a new class of dynamic contrast agents called magnetomotive molecular nanoprobes for molecular-specific imaging. Magnetomotive agents are superparamagnetic nanoparticles, typically iron-oxide, that are physically displaced by the application of a small modulating external magnetic field. Dynamic phase-sensitive position measurements are performed using any high resolution imaging modality, including optical coherence tomography (OCT), ultrasonography, or magnetic resonance imaging (MRI). The dynamics of the magnetomotive agents can be used to extract the biomechanical tissue properties in which the nanoparticles are bound, and the agents can be used to deliver therapy via magnetomotive displacements to modulate or disrupt cell function, or hyperthermia to kill cells. These agents can be targeted via conjugation to antibodies, and in vivo targeted imaging has been shown in a carcinogeninduced rat mammary tumor model. The iron-oxide nanoparticles also exhibit negative T2 contrast in MRI, and modulations can produce ultrasound imaging contrast for multimodal imaging application

Hemoglobin contrast in magneto-motive optical doppler tomography, optical coherence tomography, and ultrasound imaging methods and apparatus

Provided herein are systems, methods, and compositions for the use of optical coherence tomography for detection of cells.Board of Regents, University of Texas Syste

Contrast enhanced spectroscopic optical coherence tomography

A method of forming an image of a sample includes performing SOCT on a sample. The sample may include a contrast agent, which may include an absorbing agent and/or a scattering agent. A method of forming an image of tissue may include selecting a contrast agent, delivering the contrast agent to the tissue, acquiring SOCT data from the tissue, and converting the SOCT data into an image. The contributions to the SOCT data of an absorbing agent and a scattering agent in a sample may be quantified separately

Quantum metrology and its application in biology

Quantum metrology provides a route to overcome practical limits in sensing devices. It holds particular relevance to biology, where sensitivity and resolution constraints restrict applications both in fundamental biophysics and in medicine. Here, we review quantum metrology from this biological context, focusing on optical techniques due to their particular relevance for biological imaging, sensing, and stimulation. Our understanding of quantum mechanics has already enabled important applications in biology, including positron emission tomography (PET) with entangled photons, magnetic resonance imaging (MRI) using nuclear magnetic resonance, and bio-magnetic imaging with superconducting quantum interference devices (SQUIDs). In quantum metrology an even greater range of applications arise from the ability to not just understand, but to engineer, coherence and correlations at the quantum level. In the past few years, quite dramatic progress has been seen in applying these ideas into biological systems. Capabilities that have been demonstrated include enhanced sensitivity and resolution, immunity to imaging artifacts and technical noise, and characterization of the biological response to light at the single-photon level. New quantum measurement techniques offer even greater promise, raising the prospect for improved multi-photon microscopy and magnetic imaging, among many other possible applications. Realization of this potential will require cross-disciplinary input from researchers in both biology and quantum physics. In this review we seek to communicate the developments of quantum metrology in a way that is accessible to biologists and biophysicists, while providing sufficient detail to allow the interested reader to obtain a solid understanding of the field. We further seek to introduce quantum physicists to some of the central challenges of optical measurements in biological science.Comment: Submitted review article, comments and suggestions welcom

Deep imaging inside scattering media through virtual spatiotemporal wavefront shaping

The multiple scattering of light makes materials opaque and obstructs imaging. Optimized wavefronts can overcome scattering to focus but typically require restrictive guidestars and only work within an isoplanatic patch. Focusing by lenses and wavefront shaping by spatial light modulators also limit the imaging volume and update speed. Here, we introduce scattering matrix tomography (SMT): use the measured scattering matrix of the sample to construct its volumetric image by scanning a confocal spatiotemporal focus with input and output wavefront correction for every isoplanatic patch, dispersion compensation, and index-mismatch correction--all performed digitally during post-processing without a physical guidestar. The digital focusing offers a large depth of field without constraint by the focal plane's Rayleigh range, and the digital wavefront correction enables image optimization with fast updates unrestricted by the speed of the hardware. We demonstrate SMT with sub-micron diffraction-limited lateral resolution and one-micron bandwidth-limited axial resolution at one millimeter beneath ex vivo mouse brain tissue and inside a dense colloid, where conventional imaging methods fail due to the overwhelming multiple scattering. SMT translates deep-tissue imaging into a computational reconstruction and optimization problem. It is noninvasive and label-free, with prospective applications in medical diagnosis, biological science, colloidal physics, and device inspection

3D nanometrology of transparent objects by phase calibration of a basic bright-field microscope for multiple illumination apertures

Optical retrieval of the structure of transparent objects at the nanoscale requires adapted techniques capable of probing their interaction with light. Here, we considered a method based on calibration of the defocusing with partially coherent illumination and explored its phase retrieval capability over a wide range of illumination angles. We imaged: (1) commercial dielectric nanospheres to assess the phase calibration when measured along the optical axis, (2) custom-made nano-steps micropatterned in a glass substrate to assess the phase calibration when measured along the transversal axis, and (3) human cancer cells deposited on a glass substrate to assess the results of the calibration on complex transparent 3-dimensional samples. We first verified the model prediction in the spatial frequency domain and subsequently obtained a consistent and linear phase-calibration for illumination numerical apertures ranging from 0.1 to 0.5. Finally, we studied the dependence of the phase retrieval of a complex nanostructured object on the illumination aperture

The Advanced Applications For Optical Coherence Tomography In Skin Imaging

Optical coherence tomography (OCT), based on the principle of interferometry, is a fast and non-invasive imaging modality, which has been approved by FDA for dermatologic applications. OCT has high spatial resolution up to micrometer scale compared to traditional ultrasound imaging. In addition, OCT can provide real-time cross-sectional images with 1 to 2 mm penetration depth, which makes it an ideal imaging technique to assess the skin micro-morphology and pathology without any tissue removal. Many studies have investigated the possibilities of using OCT to evaluate dermatologic conditions, such as skin cancer, dermatitis, psoriasis, and skin damages. Hence, OCT has tremendous potential to provide skin histological and pathological information and assist differential diagnosis of various skin diseases. In this study, we used a swept-source OCT with 1305 nm central wavelength to explore its advanced applications in dermatology. This dissertation consists of four major research projects. First, we explored the feasibility of OCT imaging for assisting real-time visualization in skin biopsy. We showed that OCT could be used to guide and track a needle insertion in mouse skin in real-time. The structure of skin and the movement of needle can be clearly seen on the OCT images without any time delay during the procedures. Next, we tested the concept of performing the punch biopsy using OCT hand-held probe attached to a piercing tip in a phantom. We proved that using the OCT is a reliable technique to delineate the margin of lesion in phantom. And it is possible to perform the punch biopsy with the OCT probe. Second, we tested the performance of contrast-enhanced OCT in melanoma detection in an in vitro study. Melanoma is the most lethal type of skin cancer. Early detection could significantly improve the long-term survival rate of patients. In this initial study, a contrast agent (Gal3-USGNPs) is developed by conjugating melanoma biomarker (Gal3) to ultra-small gold nanoparticles (USGNPs). We showed that the contrast agent can differentiate B16 melanoma cells from normal skin keratinocytes in vitro. To avoid systemic administration of USGNPs, the third project continues to explore the enhanced topical delivery of USGNPs. In this study, we used OCT to monitor the topical delivery of nanoparticles on pig skin over time. And the diffusion and penetration of USGNPs in skin can be improved by applying chemical and physical enhancers such as DMSO and sonophoresis. Finally, in addition to image the cross-sectional structure of skin, we also aim to extract quantitative information from OCT images. The skin optical properties such as attenuation coefficient can be measured from OCT images. We measured and compared the skin attenuation coefficient in the skin of forehead and lateral hip, the skin of three different age groups, and the skin of three different Fitzpatrick types. The statistical analysis showed that epidermis has much higher attenuation coefficient than dermis. And the skin type V & VI have a relatively lower attenuation coefficient than the other skin types. These studies could aid the detection of skin cancer using imaging techniques and provide some new insights into the future applications of OCT in dermatology

Development and application of optical imaging techniques in diagnosing cardiovascular disease

textAtherosclerosis and specifically rupture of vulnerable plaques account for 23% of all deaths worldwide, far surpassing both infectious diseases and cancer. Plaque-based macrophages, often associated with lipid deposits, contribute to atherogenesis from initiation through progression, plaque rupture and ultimately, thrombosis. Therefore, the macrophage is an important early cellular marker related to vulnerability of atherosclerotic plaques. The objective of my research is to assess the ability of multiple optical imaging modalities to detect, and further characterize the distribution of macrophages (having taken up plasmonic gold nanoparticles as a contrast agent) and lipid deposits in atherosclerotic plaques. Tissue phantoms and macrophage cell cultures were used to investigate the capability of nanorose as an imaging contrast agent to target macrophages. Ex vivo aorta segments from a rabbit model of atherosclerosis after intravenous nanorose injection were imaged by optical coherence tomography (OCT), photothermal imaging (PTW) and two-photon luminescence microscopy (TPLM), respectively. OCT images depicted detailed surface structure of atherosclerotic plaques. PTW images identified nanorose-loaded macrophages (confirmed by co-registration of a TPLM image and corresponding RAM-11 stain on a histological section) associated with lipid deposits at multiple depths. TPLM images showed three-dimensional distribution of nanorose-loaded macrophages with a high spatial resolution. Imaging results suggest that superficial nanorose-loaded macrophages are distributed at shoulders on the upstream side of atherosclerotic plaques at the edges of lipid deposits. Combination of OCT with PTW or TPLM can simultaneously reveal plaque structure and composition, permitting assessment of plaque vulnerability during cardiovascular interventions.Biomedical Engineerin

Characterizing the localized surface plasmon resonance behaviors of Au nanorings and tracking their diffusion in bio-tissue with optical coherence tomography

The characterization results of the localized surface plasmon resonance (LSPR) of Au nanorings (NRs) with optical coherence tomography (OCT) are first demonstrated. Then, the diffusion behaviors of Au NRs in mouse liver samples tracked with OCT are shown. For such research, aqueous solutions of Au NRs with two different localized surface plasmon resonance (LSPR) wavelengths are prepared and characterized. Their LSPR-induced extinction cross sections at 1310 nm are estimated with OCT scanning of solution droplets on coverslip to show reasonably consistent results with the data at individual LSPR wavelengths and at 1310 nm obtained from transmission measurements of Au NR solutions and numerical simulations. The resonant and non-resonant Au NRs are delivered into mouse liver samples for tracking Au NR diffusion in the samples through continuous OCT scanning for one hour. With resonant Au NRs, the average A-mode scan profiles of OCT scanning at different delay times clearly demonstrate the extension of strong backscattering depth with time. The calculation of speckle variance among successive OCT scanning images, which is related to the local transport speed of Au NRs, leads to the illustrations of downward propagation and spreading of major Au NR motion spot with time