Single Magnetic Particle Motion in Magnetomotive Ultrasound: An Analytical Model and Experimental Validation

Magnetomotive Ultrasound (MMUS) is an emerging imaging modality, in which magnetic nanoparticles (MNPs) are used as contrast agents. MNPs are driven by a time-varying magnetic force, and the resulting movement of the surrounding tissue is detected with a signal processing algorithm. However, there is currently no analytical model to quantitatively predict this magnetically-induced displacement. Toward the goal of predicting motion due to forces on the distribution of MNPs, in this work, a model originally derived from the Navier-Stokes equation for the motion of a single magnetic particle subject to a magnetic gradient force is presented and validated. Displacement amplitudes for a spatially inhomogeneous and temporally sinusoidal force were measured as a function of force amplitude and Young's modulus, and the predicted linear and inverse relationships were confirmed in gelatin phantoms, respectively, with three out of four data sets exhibiting {R}{{2}} ge {0.88}. The mean absolute uncertainty between the predicted displacement magnitude and experimental results was 14%. These findings provide a means by which the performance of MMUS systems may be predicted to verify that systems are working to theoretical limits and to compare results across laboratories

Elastography of soft materials and tissues by holographic imaging of surface acoustic waves

We use optical interferometry to capture coherent surface acoustic waves for elastographic imaging. An inverse method is employed to convert multi-frequency data into an elastic depth profile. Using this methodwe image elastic properties over a 55 mm range with <5 mm resolution. For relevance to breast cancer detectionwe employ a tissue phantom with a tumor-like inclusion. Holographic elastography is also shown to be well-behaved in ex vivo tissuerevealing the subsurface position of a bone. Because digital holography can assess waves over a wide surface areathis constitutes a flexible new platform for large volume and non-invasive elastography

All-fiber probes for endoscopic optical coherence tomography of the large airways

Endoscopic optical coherence tomography of large airways poses unique challenges. A hybrid lens is described that consists of a section of coreless fiber and graded index fiber (GIF), followed by a ball lens section. This design produces lownumerical aperture beams better suited for large airway imaging. The performance of this lens is compared against conventional GIF and ball lens designs. Forward- and side-viewing probes were modeled, fabricated, and tested. The impact of a sheath on the beam profile was also investigated. Probes with working distances larger than 10 mm and depth-of-focus exceeding 12 mm are demonstrated with the proposed design

OCT particle tracking velocimetry of biofluids in a microparallel plate strain induction chamber

Significance: Imaging biofluid flow under physiologic conditions aids in understanding disease processes and health complications. We present a method employing a microparallel plate strain induction chamber (MPPSIC) amenable to optical coherence tomography to track depth-resolved lateral displacement in fluids in real time while under constant and sinusoidal shear. Aim: Our objective is to track biofluid motion under shearing conditions found in the respiratory epithelium, first validating methods in Newtonian fluids and subsequently assessing the capability of motion-tracking in bronchial mucus. Approach: The motion of polystyrene microspheres in aqueous glycerol is tracked under constant and sinusoidal applied shear rates in the MPPSIC and is compared with theory. Then 1.5 wt. % bronchial mucus samples considered to be in a normal hydrated state are studied under sinusoidal shear rates of amplitudes 0.7 to 3.2 s-1. Results: Newtonian fluids under low Reynolds conditions (Re ∼ 10-4) exhibit velocity decreases directly proportional to the distance from the plate driven at both constant and oscillating velocities, consistent with Navier-Stokes's first and second problems at finite depths. A 1.5 wt. % mucus sample also exhibits a uniform shear strain profile. Conclusions: The MPPSIC provides a new capability for studying biofluids, such as mucus, to assess potentially non-linear or strain-rate-dependent properties in a regime that is relevant to the mucus layer in the lung epithelium

Vibrational wave packets in the B1Πu and D1Σu+ states of Cs2: Determination of improved Cs2+(X) and Cs2(B) spectroscopic constants

Vibrational wave packets in the B 1Πu and D 1Σu+ excited states of Cs2 have been studied on the ∼100 fs time scale by pump-probe laser spectroscopy. The temporal behavior of the wave packets was monitored by photoionizing the electronically excited molecule with a time-delayed probe pulse and recording the time and energy-integrated photoelectron signal as a function of time delay between the pump and probe pulses. For the B 1Σu+ experiments, wave packets were produced by exciting the B 1Σu+ ← X 1Σg+ transition in the ∼740-790 nm region and subsequently detected by photoionizing the molecule at wavelengths between 565 nm and 600 nm. By simulating the experimentally observed transients with the density matrix formalism (and explicitly accounting for laser chirp and |Δv|&gt;1 coherences), improved values for the equilibrium internuclear separation for the Cs2(B 1Πu) state and Te for the Cs2+(X) state were determined to be Re(B 1Πu) = 4.93 ±0.03 Å and Te[Cs2+(X)] = 29 930± 100 cm-1, respectively. Similar experiments were conducted for the D 1Σu+ state. Wave packets composed of vibrational levels (v′ ≈ 40-50). perturbed by the bound 2 3Πou state were produced on the D 1Σu+ potential surface by driving the D 1Σu+ ←X1Σg+ transition in the 575-610 nm spectral interval

Diffusion tensor optical coherence tomography

In situ measurements of diffusive particle transport provide insight into tissue architecture, drug delivery, and cellular function. Analogous to diffusion-tensor magnetic resonance imaging (DT-MRI), where the anisotropic diffusion of water molecules is mapped on the millimeter scale to elucidate the fibrous structure of tissue, here we propose diffusion-tensor optical coherence tomography (DT-OCT) for measuring directional diffusivity and flow of optically scattering particles within tissue. Because DT-OCT is sensitive to the sub-resolution motion of Brownian particles as they are constrained by tissue macromolecules, it has the potential to quantify nanoporous anisotropic tissue structure at micrometer resolution as relevant to extracellular matrices, neurons, and capillaries. Here we derive the principles of DT-OCT, relating the detected optical signal from a minimum of six probe beams with the six unique diffusion tensor and three flow vector components. The optimal geometry of the probe beams is determined given a finite numerical aperture, and a high-speed hardware implementation is proposed. Finally, Monte Carlo simulations are employed to assess the ability of the proposed DT-OCT system to quantify anisotropic diffusion of nanoparticles in a collagen matrix, an extracellular constituent that is known to become highly aligned during tumor development

Phase-resolved magnetomotive OCT for imaging nanomolar concentrations of magnetic nanoparticles in tissues

Magnetic nanoparticles (MNPs) are increasingly important in magnetic resonance and biomedical optical imaging. We describe a method for imaging MNPs by detecting nanoscale displacements using a phaseresolved spectral-domain optical coherence tomography (OCT) system. Biological tissues and phantoms are exposed to ∼800 G magnetic fields modulated at 56 and 100 Hz to mechanically actuate embedded iron oxide MNPs (∼20 nm diameter). Sensitivity to 27 μg/g (∼2 nM) MNPs within tissue phantoms is achieved by filtering paramagnetic from diamagnetic vibrations. We demonstrate biological feasibility by imaging topically applied MNPs during their diffusion into an excised rat tumor over a 2 hour time period

Geometric Validation of Continuous, Finely Sampled 3-D Reconstructions From aOCT and CT in Upper Airway Models

Identification and treatment of obstructive airway disorders (OADs) are greatly aided by imaging of the geometry of the airway lumen. Anatomical optical coherence tomography (aOCT) is a promising high-speed and minimally invasive endoscopic imaging modality for providing micrometer-resolution scans of the upper airway. Resistance to airflow in OADs is directly caused by the reduction in luminal cross-sectional area (CSA). It is hypothesized that aOCT can produce airway CSA measurements as accurate as that from computed tomography (CT). Scans of machine hollowed cylindrical tubes were used to develop methods for segmentation and measurement of airway lumen in CT and aOCT. Simulated scans of virtual cones were used to validate 3-D resampling and reconstruction methods in aOCT. Then, measurements of two segments of a 3-D printed pediatric airway phantom from aOCT and CT independently were compared to ground truth CSA. In continuous unobstructed regions, the mean CSA difference for each phantom segment was 2.2 ± 3.5 and 1.5 ± 5.3 mm2 for aOCT, and -3.4 ± 4.3 and -1.9 ± 1.2 mm2 for CT. Because of the similar magnitude of these differences, these results support the hypotheses and underscore the potential for aOCT as a viable alternative to CT in airway imaging, while offering greater potential to capture respiratory dynamics

Optical probes and techniques for molecular contrast enhancement in coherence imaging

Optics has played a key role in the rapidly developing field, of molecular imaging. The spectroscopic nature and high-resolution imaging capabilities of light provide a means for probing biological morphology and function at the cellular and molecular levels. While the use of bioluminescent and fluorescent probes has become a mainstay in optical molecular imaging, a large number of other optical imaging modalities exist that can be included in this emerging field. In vivo imaging technologies such as optical coherence tomography and reflectance confocal microscopy have had limited use of molecular probes. In the last few years, novel nonfluorescent and nonbioluminescent molecular imaging probes have been developed that will initiate new directions in coherent optical molecular imaging. Classes of probes reviewed in this work include those that alter the local optical scattering or absorption properties of the tissue, those that modulate these local optical properties in a predictable manner, and those that are detected utilizing spectroscopic optical coherence tomography (OCT) principles. In addition to spectroscopic OCT, novel nonlinear interferometric imaging techniques have recently been developed to detect endogenous molecules. Probes and techniques designed for coherent molecular imaging are likely to improve the detection and diagnostic capabilities of OCT

Expression order of alpha-v and beta-3 integrin subunits in the N-methyl-N-nitrosourea-induced rat mammary tumor model

We investigated the developmental time course of molecular expression of αvβ3 subunits in a carcinogen-induced rat mammary tumor model for human ductal carcinoma in situ (DCIS). Tumors during various stages of growth (from 2.0 cm) were analyzed immunohistochemically for the expression of the αvβ3 integrin and its subunits. In general, the expression profiles of these integrin subunits were directly proportional to the size of the tumor. The pattern of immunostaining revealed that anti-αvβ3 monoclonal antibody binds to specific sites of tumor sections, forming isolated stained patches. This isolated patch pattern was found in more developed larger tumors. This could be due to the fact that the integrin molecule might be involved in migration and nesting of tumor cells into specific regions to form DCIS or intraductal carcinoma. Results also showed that the αv subunit expresses earlier than the β3 subunit. These data provide insight into tumor cell biology and developmental characteristics that will guide the future construction and use of targeted contrast and therapeutic agents capable of tracking, imaging, or treating a tumor at the earliest stage of formation