High Resolution Phase-Sensitive Magnetomotive Optical Coherence Microscopy for Tracking Magnetic Microbeads and Cellular Mechanics.

We present a real-time multimodal near-infrared imaging technology that tracks externally induced axial motion of magnetic microbeads in single cells in culture. The integrated multimodal imaging technique consists of phase-sensitive magnetomotive optical coherence microscopy (MM-OCM) and multiphoton microscopy (MPM).MPMis utilized for the visualization of multifunctional fluorescent and magnetic microbeads, while MM-OCM detects, with nanometer-scale sensitivity, periodic displacements of the microbeads induced by the modulation of an external magnetic field. Magnetomotive signals are measured from mouse macrophages, human breast primary ductal carcinoma cells, and human breast epithelial cells in culture, and validated with full-field phase-sensitive microscopy. This methodology demonstrates the capability for imaging controlled cell dynamics and has the potential for measuring cell biomechanical properties, which are important in assessing the health and pathological state of cells.

Magnetomotive optical coherence elastography for microrheology of biological tissues.

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.

DYNAMIC OPTICAL COHERENCE ELASTOGRAPHY: A REVIEW.

With the development of optical coherence tomography, the application optical coherence elastography (OCE) has gained more and more attention in biomechanics for its unique features including micron-scale resolution, real-time processing, and non-invasive imaging. In this review, one group of OCE techniques, namely dynamic OCE, are introduced and discussed including external dynamic OCE mapping and imaging of ex vivo breast tumor, external dynamic OCE measurement of in vivo human skin, and internal dynamic OCE including acoustomotive OCE and magnetomotive OCE. These techniques overcame some of the major drawbacks of traditional static OCE, and broadened the OCE application fields. Driven by scientific needs to engineer new quantitative methods that utilize the high micron-scale resolution achievable with optics, results of biomechanical properties were obtained from biological tissues. The results suggest potential diagnostic and therapeutic clinical applications. Results from these studies also help our understanding of the relationship between biomechanical variations and functional tissue changes in biological systems.

Magnetomotive nanoparticle transducers for optical rheology of viscoelastic materials.

The availability of a real-time non-destructive modality to interrogate the mechanical properties of viscoelastic materials would facilitate many new investigations. We introduce a new optical method for measuring elastic properties of samples which employs magnetite nanoparticles as perturbative agents. Magnetic nanoparticles distributed in silicone-based samples are displaced upon probing with a small external magnetic field gradient and depth-resolved optical coherence phase shifts allow for the tracking of scatterers in the sample with nanometer-scale sensitivity. The scatterers undergo underdamped oscillations when the magnetic field is applied step-wise, allowing for the measurement of the natural frequencies of oscillation of the samples. Validation of the measurements is accomplished using a commercial indentation apparatus to determine the elastic moduli of the samples. This real-time non-destructive technique constitutes a novel way of probing the natural frequencies of viscoelastic materials in which magnetic nanoparticles can be introduced.

Optical micro-scale mapping of dynamic biomechanical tissue properties.

Mechanical forces such as adhesion, shear stress and compression play crucial roles in tissue growth, patterning and development. To understand the role of these mechanical stimuli, it is of great importance to measure biomechanical properties of developing, engineered, and natural tissues. To enable these measurements on the micro-scale, a novel, dynamic, non-invasive, high-speed optical coherence elastography (OCE) system has been developed utilizing spectral-domain optical coherence tomography (OCT) and a mechanical wave driver. Experimental results of OCE on silicone phantoms are in good agreement with those obtained from a standardized indentation method. Using phase-resolved imaging, we demonstrate OCE can map dynamic elastic moduli of normal and neoplastic ex vivo human breast tissue with a sensitivity of 0.08%. Spatial micro-scale mapping of elastic moduli of tissue offers the potential for basic science and clinical investigations into the role biomechanics play in health and disease.

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 phase-resolved spectral-domain optical coherence tomography (OCT) system. Biological tissues and phantoms are exposed to approximately 800 G magnetic fields modulated at 56 and 100 Hz to mechanically actuate embedded iron oxide MNPs (approximately 20 nm diameter). Sensitivity to 27 microg/g (approximately 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.