Optical coherence elastography (OCE) is an established paradigm for measuring biomechanical properties of tissues and cells noninvasively, in real time, and with high resolution. We present a different development of a spectral domain OCE technique that enables simultaneous measurements of multiple biomechanical parameters of biological tissues. Our approach extends the capabilities of magnetomotive OCE (MM-OCE), which utilizes iron oxide magnetic nanoparticles (MNPs) distributed and embedded in the specimens as transducers for inducing motion. Step-wise application of an external magnetic field results in displacements in the tissue specimens that are deduced from sensitive phase measurements made with the MM-OCE system. We analyzed freshly excised rabbit lung and muscle tissues. We observe that while they present some similarities, rabbit lung and muscle tissue displacements display characteristic differentiating features. Both tissue types undergo a fast initial displacement followed by a rapidly damped oscillation and the onset of creep. However, the damping is faster in muscle compared to lung tissue, while the creep is steeper in muscle. This approach has the potential to become a novel way of performing real-time measurements of biomechanical properties of tissues and to enable the development of different diagnostic and monitoring tools in biology and medicine.
Magnetomotive microscopy techniques are introduced to investigate cell dynamics and biomechanics. These techniques
are based on magnetomotive transducers present in cells and optical coherence imaging techniques. In this study,
magnetomotive transducers include magnetic nanoparticles (MNPs) and fluorescently labeled magnetic microspheres,
while the optical coherence imaging techniques include integrated optical coherence (OCM)and multiphoton (MPM)
microscopy,and diffraction phase microscopy (DPM). Samples used in this study are murine macrophage cells in culture
that were incubated with magnetomotive transducers. MPMis used to visualize multifunctional microspheres based on
their fluorescence, while magnetomotive OCM detects sinusoidal displacements of the sample induced by a magnetic
field. DPM is used to image single cells at a lower frequency magnetic excitation, and with its Fourier transform light
scattering (FTLS) analysis, oscillation amplitude is obtained, indicating the relative biomechanical properties of
macrophage cells. These magnetomotive microscopy method shave potential to be used to image and measure cell
dynamics and biomechanical properties. The ability to measure and understand biomechanical properties of cells and
their microenvironments, especially for tumor cells, is of great importance and may provide insight for diagnostic and
subsequently therapeutic interventions.
Magnetomotive optical coherence tomography (MMOCT) is a method for imaging the distribution of magnetic
nanoparticles in tissue by applying an external dynamic magnetic field gradient during B-mode scanning. We
present a new method for spectral-domain MMOCT imaging which affords increased sensitivity and frame rates
compared to previous work, with a demonstrated sensitivity to <100 ppm iron oxide nanoparticles and imaging time
of 5 s. Agarose phantoms embedded with iron oxide nanoparticles (~20 nm) also provide negative T2 contrast in
magnetic resonance imaging (MRI) with sensitivity <10 ppm, which is promising for multi-modality applications
where MRI and MMOCT provide whole-body and microscopic imaging, respectively. To demonstrate the
biomedical potential of this technique, rats are injected with the same nanoparticles as those used in MRI, and
uptake into the spleen is detected and imaged post mortem by MMOCT. This illustrates a potentially powerful
multi-modal platform for molecular imaging using targeted magnetic nanoparticles.
Mechanical forces play crucial roles in tissue growth, patterning and development. To understand the role of mechanical
stimuli, biomechanical properties are of great importance, as well as our ability to measure biomechanical properties of
developing and engineered tissues. To enable these measurements, a novel non-invasive, micron-scale and high-speed
Optical Coherence Elastography (OCE) system has been developed utilizing a titanium:sapphire based spectral-domain
Optical Coherence Tomography (OCT) system and a mechanical wave driver. This system provides axial resolution of
3 microns, transverse resolution of 13 microns, and an acquisition rate as high as 25,000 lines per second. External lowfrequency
vibrations are applied to the samples in the system. Step and sinusoidal steady-state responses are obtained to
first characterize the OCE system and then characterize samples. Experimental results of M-mode OCE on silicone
phantoms and human breast tissues are obtained, which correspond to biomechanical models developed for this analysis.
Quantified results from the OCE system correspond directly with results from an indentation method from a commercial.
With micron-scale resolution and a high-speed acquisition rate, our OCE system also has the potential to rapidly
measure dynamic 3-D tissue biomechanical properties.
We advance the magnetomotive-optical coherence tomography (MM-OCT) technique for detecting displacements of magnetic nanoparticles embedded in tissue-like phantoms by using apmplitude and phase-resolved methods with spectral-domain optical coherence tomography (SD-OCT). The magnetomotion is triggered by the external, noninvasive application of a magnetic field. We show that both amplitude and phase data are indicative of the presence and motion of light scatterers, and could potentially be used for studying the dynamics of magnetomotion. The magnetic field modulation is synchronized with data acquisition in a controlled, integrated system that includes a console for monitoring and initiating data acquisition, scanning devices, an electromagnet power supply, and the detection system. Using Fourier analysis, we show that the amplitude and phase modulations in the samples that contain magnetic contrast agents match the frequency of the applied magnetic field, while control samples do not respond to magnetic field activity. We vary the strength of the magnetic field and show that the amplitude and phase steps between regions of zero-magnetic field and regions with non-zero magnetic field change accordingly. The phase is shown to be more sensitive.
An instrument for high-resolution imaging and tomography has been built at the APS beamline 34 ID-C, Argonne
National Laboratory. In-line phase contrast tomography can be performed with micrometer resolution. For imaging
and tomography with resolution better than 100nm a hard X-ray microscope has been integrated to the instrument. It
works with a Kirkpatrick-Baez (KB) mirror as condenser and a Fresnel-Zone plate (FZP) as an objective lens. 50
nm-features have been resolved in a Nickel structure operating the microscope at a photon energy of 9keV. Phase
objects with negligible absorption contrast have been imaged. Tomography scans were performed on photonic