Magnetomotive optical coherence elastography for biomedical applications

This thesis presents a new non-invasive optical method for assessing biomechanical properties of tissues and cells in real time and with micron scale resolution, magnetomotive optical coherence elastography (MM-OCE). Biomechanical properties are important because they relate to the tissues’ state of health and they can be utilized for monitoring changes due to pathological processes or therapeutic treatments. In optical coherence tomography (OCT), the imaging technique that MM-OCE is based on, near infrared light penetrates a few millimeters into highly scattering biological tissues and the backscattered light is detected in real time with interferometry. Post-processing of the optical signal renders structural images and displacement maps of dynamic processes within the specimens, which contain information about the mechanical signature of the tissues or cells. MM-OCE utilizes magnetic nanoparticles or microspheres that are embedded in the samples of interest, and which induce motion in the samples in the presence of an external magnetic field produced by a custom built solenoid coil. Three studies are presented: the first one introduces the MM-OCE technology and demonstrates its feasibility and versatility on a set of tissue-mimicking silicone phantoms, the second one applies MM-OCE to excised rabbit tissues and reveals their intricate biomechanical behavior, and the third one explores the possibility of extending the technique to the study of cells. Finally, I discuss aspects of this work that can be further advanced by future modeling of the biomechanical properties of different types of soft tissue

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

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

Review of tissue simulating phantoms with controllable optical, mechanical and structural properties for use in optical coherence tomography

We review the development of phantoms for optical coherence tomography (OCT) designed to replicate the optical, mechanical and structural properties of a range of tissues. Such phantoms are a key requirement for the continued development of OCT techniques and applications. We focus on phantoms based on silicone, fibrin and poly(vinyl alcohol) cryogels (PVA-C), as we believe these materials hold the most promise for durable and accurate replication of tissue properties

Optical measurements of mechanical resonances in biological tissues via magnetic nanoparticle interrogation

We present a real-time phase-resolved optical coherence tomography-based technique that interrogates the mechanical properties of tissue phantoms with different elasticities as well as healthy and cancerous rat tissues, via the interaction of high susceptibility iron oxide nanoparticles that reside inside the samples and an external magnetic field. A chirped magnetic field selects the region of natural resonance in the probed samples as evidenced by scatterer displacements measured with nanometer-level sensitivity. This methodology, entitled magnetomotive optical coherence elastography (MM-OCE), which exploits frequency dependent viscoelastic response in biological media, has potential for detecting tissue pathologies

Phase-resolved spectral-domain magnetomotive optical coherence tomography

ABSTRACT 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