Magnetomotive Optical Coherence Tomography Research Articles

Magnetic Field-Modulated Plasmonic Scattering of Hybrid Nanorods for FFT-Weighted OCT Imaging in NIR-II.

We report a method for fast Fourier transform (FFT)-weighted optical coherence tomography (OCT) in the second biological tissue transparency window by actively modulating the plasmonic scattering of Fe3O4@Au hybrid nanorods using magnetic fields. Instead of tracking the nanoparticles' lateral displacement in conventional magnetomotive OCT imaging, we monitor the nanorod rotation and optical signal changes under an alternating magnetic field in real time. The coherent rotation of the nanorods with the field produces periodic OCT signals, and the FFT is then used to convert the periodic OCT signals in the time domain to a single peak in the frequency domain. This allows automatic screening of nanorod signals from the random biological noises and reconstruction of FFT-weighted images using a computer program based on a time-sequence image set. Compared with conventional magnetomotive OCT, the FFT-weighted imaging technique creates enhanced OCT images with dB-scale contrast over an order of magnitude higher than the original images.

Near-infrared active superparamagnetic iron oxide nanoparticles for magnetomotive optical coherence tomography imaging and magnetic hyperthermia therapeutic applications

A green chemistry-based approach to nanoparticle synthesis is an eco-friendly, simple, and cost-effective way to fabricate nanoparticles. This study aims at the biomedical applications of green synthesized near-infrared (NIR) active superparamagnetic iron oxide nanoparticles (SPIONs). The SPIONs obtained by the green synthesis route are non-toxic and their surface is free from any chemical impurity. The MTT [3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide] assay was accomplished on human cervical cancer (HeLa) cells and shows that the SPIONs are biocompatible and thus safe for cells even at higher concentrations up to 500 μg/ml. The synthesized SPIONs display an absorbance in the tissue transparent NIR wavelength region. The SPIONs exhibit a superparamagnetic behavior with high saturation magnetization of 66 emu/g. Owing to their excellent optical and magnetic properties, the potential of these green synthesized SPIONs as an exogenous contrast agent in deep-tissue magnetomotive optical coherence tomography (MM-OCT) imaging was evaluated ex-vivo using chicken breast tissue. A significant enhancement in the contrast and the penetration depth was observed with time. The heating response of green synthesized SPIONs was evaluated under the application of an external magnetic field. The results suggest that these SPIONs could be used as theranostic agents for deep tissue biomedical imaging and therapeutic applications.

Polymerically modified superparamagnetic iron oxide nanoparticles as a multi-model molecular probe for functionalized optical coherence tomography

We demonstrate the synthesis, characterization, and potential application of polymerically modified superparamagnetic nanoparticles over bare SPIONs, as a multi-model molecular probe for functionalized optical coherence tomography (fOCT). The synthesized magnetic nanoparticles (MNPs) also have the ability of photo thermionic excitation under near-infrared irradiation (980 nm). By having dual excitation properties, the SPIONs are used as exogenous contrast agents for magnetomotive optical coherence tomography (MMOCT) as well as photothermal optical coherence tomography (PTOCT). We developed a functionalized OCT system and signal processing algorithms for MMOCT and PTOCT. Further, non-invasive in-vivo imaging was performed on swiss-albino mice to demonstrate the potential application of polymerically modified SPIONs. A diffusion dynamics study and contrast-to-noise ratio (CNR) study of the dispersed synthesized SPIONs inside skin tissue of mice as a function of time and depth is also reported. We found that PEG-SPIONs are excellent candidate for molecular contrast agent of functional OCT.

Investigation of Gd2O3: Er3+/Yb3+ Upconversion Nanoparticles (UCNPs) as a Multi-model Contrast Agent for Functional Optical Coherence Tomography (fOCT).

Currently, upconversion nanoparticles (UCNPs) implanted as a contrast agent for optical coherence tomography (OCT) system due to its biocompatibility, anti-stock emission, narrow emission bandwidth non-photobleaching effects etc., but it was not used as multi model imaging probe. We synthesized multimodal imaging probe having upconversion property along with paramagnetic property and used as dual contrast agents for Photothermal Optical Coherence Tomography (PTOCT) and Magnetomotive Optical Coherence Tomography (MMOCT). The synthesized Gd2O3:Er3+/Yb3+ UCNPs shows the bright yellow upconversion emission, biocompatibility with hydrophilic property. A custom built SSOCT setup modified for PTOCT and MMOCT imaging along with custom MATLAB algorithm for signal extraction. A dynamic study was performed with synthesized UCNPs as an imaging probe and functional OCT system for targeted imaging. This shows the utility of the Gd2O3:Er3+/Yb3+ UCNPs as molecular probe for targeted imaging applications.

Biomechanical sensing of in vivo magnetic nanoparticle hyperthermia-treated melanoma using magnetomotive optical coherence elastography.

Rationale: Magnetic nanoparticle hyperthermia (MH) therapy is capable of thermally damaging tumor cells, yet a biomechanically-sensitive monitoring method for the applied thermal dosage has not been established. Biomechanical changes to tissue are known indicators for tumor diagnosis due to its association with the structural organization and composition of tissues at the cellular and molecular level. Here, by exploiting the theranostic functionality of magnetic nanoparticles (MNPs), we aim to explore the potential of using stiffness-based metrics that reveal the intrinsic biophysical changes of in vivo melanoma tumors after MH therapy.Methods: A total of 14 melanoma-bearing mice were intratumorally injected with dextran-coated MNPs, enabling MH treatment upon the application of an alternating magnetic field (AMF) at 64.7 kHz. The presence of the MNP heating sources was detected by magnetomotive optical coherence tomography (MM-OCT). For the first time, the elasticity alterations of the hyperthermia-treated, MNP-laden, in vivo tumors were also measured with magnetomotive optical coherence elastography (MM-OCE), based on the mechanical resonant frequency detected. To investigate the correlation between stiffness changes and the intrinsic biological changes, histopathology was performed on the excised tumor after the in vivo measurements.Results: Distinct shifts in mechanical resonant frequency were observed only in the MH-treated group, suggesting a heat-induced stiffness change in the melanoma tumor. Moreover, tumor cellularity, protein conformation, and temperature rise all play a role in tumor stiffness changes after MH treatment. With low cellularity, tumor softens after MH even with low temperature elevation. In contrast, with high cellularity, tumor softening occurs only with a low temperature rise, which is potentially due to protein unfolding, whereas tumor stiffening was seen with a higher temperature rise, likely due to protein denaturation.Conclusions: This study exploits the theranostic functionality of MNPs and investigates the MH-induced stiffness change on in vivo melanoma-bearing mice with MM-OCT and MM-OCE for the first time. It was discovered that the elasticity alteration of the melanoma tumor after MH treatment depends on both thermal dosage and the morphological features of the tumor. In summary, changes in tissue-level elasticity can potentially be a physically and physiologically meaningful metric and integrative therapeutic marker for MH treatment, while MM-OCE can be a suitable dosimetry technique.

In-vivo analysis of iron-gold composite nanoparticles as potential exogenous contrast agents for magnetomotive optical coherence tomography (MMOCT)

Magnetomotive optical coherence tomography (MMOCT) is a functional modification of conventional optical coherence tomography (OCT). It utilizes the nano-scale displacement embedded magnetic nanoparticles (MNPs) and subsequent amplitude and phase changes in OCT interferogram scattered from samples. We report a new robust method for ‘phase-lock-in’ detection of MMOCT signals and subsequent imaging. We validated this method utilizing iron-gold (Fe-Au) composite nanoparticles as an exogenous contrast agent for MMOCT. High contrast and specific background-subtracted images was generated for Fe-Au MNPs targeted samples. MMOCT with MNPs imaging systems was corroborated with tissue phantoms and in-vivo swiss albino mice model with modulating external magnetic field (resonant frequency of 30 Hz). A time-dependent dynamics study of diffusion for MNPs inside the tissue of mice as a function of time and depth is also reported.

Common-path-based device for magnetomotive OCT noise reduction.

Magnetomotive optical coherence tomography (MMOCT) is a promising imaging method for noninvasive three-dimensional tracking of magnetic nanoparticle (MNP) motions in target tissues or organs. The external B-field is the driving force that provides MMOCT contrast. However, B-field modulation also introduces modulation noise, thereby decreasing the quality of the MMOCT image. In this paper, a common-path-based device is designed for modulation noise reduction. The device is capable of adjusting interference distance, reference light intensity, and imaging position (X-Y translation). The sensitivity of the MMOCT is increased by ∼20 times with the new device. Using the proposed device, the distribution of MNPs injected in zebrafish was imaged.

Superparamagnetic graphene quantum dot as a dual-modality contrast agent for confocal fluorescence microscopy and magnetomotive optical coherence tomography.

A magnetic graphene quantum dot (MGQD) nanoparticle, synthesized by hydrothermally reducing and cutting graphene oxide-iron oxide sheet, was demonstrated to possess the capabilities of simultaneous confocal fluorescence and magnetomotive optical coherence tomography (MMOCT) imaging. This MGQD shows low toxicity, significant tunable blue fluorescence and superparamagnetism, which can thus be used as a dual-modality contrast agent for confocal fluorescence microscopy (CFM) and MMOCT. The feasibility of applying MGQD as a tracer of cells is shown by imaging and visualizing MGQD labeled cells using CFM and our in-house MMOCT. Since MMOCT and CFM can offer anatomical structure and intracellular details, respectively, the MGQD for cell tracking could provide a more comprehensive diagnosis.

Characterization of Magnetic Nanoparticle-Seeded Microspheres for Magnetomotive and Multimodal Imaging.

Magnetic iron-oxide nanoparticles have been developed as contrast agents in magnetic resonance imaging (MRI) and as therapeutic agents in magnetic hyperthermia. They have also recently been demonstrated as contrast and elastography agents in magnetomotive optical coherence tomography and elastography (MM-OCT and MM-OCE, respectively). Protein-shell microspheres containing suspensions of these magnetic nanoparticles in lipid cores, and with functionalized outer shells for specific targeting, have also been demonstrated as efficient contrast agents for imaging modalities such as MM-OCT and MRI, and can be easily modified for other modalities such as ultrasound, fluorescence, and luminescence imaging. By leveraging the benefits of these various imaging modalities with the use of only a single agent, a magnetic microsphere, it becomes possible to use a widefield imaging method (such as MRI or small animal fluorescence imaging) to initially locate the agent, and then use MM-OCT to obtain dynamic contrast images with cellular level morphological resolution. In addition to multimodal contrast-enhanced imaging, these microspheres could serve as drug carriers for targeted delivery under image guidance. Although the preparation and surface modifications of protein microspheres containing iron oxide nanoparticles has been previously described and feasibility studies conducted, many questions regarding their production and properties remain. Since the use of multifunctional microspheres could have high clinical relevance, here we report a detailed characterization of their properties and behavior in different environments to highlight their versatility. The work presented here is an effort for the development and optimization of nanoparticle-based microspheres as multi-modal contrast agents that can bridge imaging modalities on different size scales, especially for their use in MM-OCT and MRI imaging.

Magnetomotive Optical Coherence Tomography as New Method for Endogenous Magnetite Detection

Magnetomotive Optical Coherence Tomography as New Method for Endogenous Magnetite Detection

Improved Imaging of Magnetically Labeled Cells Using Rotational Magnetomotive Optical Coherence Tomography

In this paper, we present a reliable and robust method for magnetomotive optical coherence tomography (MM-OCT) imaging of single cells labeled with iron oxide particles. This method employs modulated longitudinal and transverse magnetic fields to evoke alignment and rotation of anisotropic magnetic structures in the sample volume. Experimental evidence suggests that magnetic particles assemble themselves in elongated chains when exposed to a permanent magnetic field. Magnetomotion in the intracellular space was detected and visualized by means of 3D OCT as well as laser speckle reflectometry as a 2D reference imaging method. Our experiments on mesenchymal stem cells embedded in agar scaffolds show that the magnetomotive signal in rotational MM-OCT is significantly increased by a factor of ~3 compared to previous pulsed MM-OCT, although the solenoid’s power consumption was 16 times lower. Finally, we use our novel method to image ARPE-19 cells, a human retinal pigment epithelium cell line. Our results permit magnetomotive imaging with higher sensitivity and the use of low power magnetic fields or larger working distances for future three-dimensional cell tracking in target tissues and organs.

Magnetomotive Optical Coherence Elastography for Magnetic Hyperthermia Dosimetry Based on Dynamic Tissue Biomechanics.

Magnetic nanoparticles (MNPs) have been used in many diagnostic and therapeutic biomedical applications over the past few decades to enhance imaging contrast, steer drugs to targets, and treat tumors via hyperthermia. Optical coherence tomography (OCT) is an optical biomedical imaging modality that relies on the detection of backscattered light to generate high-resolution cross-sectional images of biological tissue. MNPs have been utilized as imaging contrast and perturbative mechanical agents in OCT in techniques called magnetomotive OCT (MM-OCT) and magnetomotive elastography (MM-OCE), respectively. MNPs have also been independently used for magnetic hyperthermia treatments, enabling therapeutic functions such as killing tumor cells. It is well known that the localized tissue heating during hyperthermia treatments result in a change in the biomechanical properties of the tissue. Therefore, we propose a novel dosimetric technique for hyperthermia treatment based on the viscoelasticity change detected by MM-OCE, further enabling the theranostic function of MNPs. In this paper, we first review the basic principles and applications of MM-OCT, MM-OCE, and magnetic hyperthermia, and present new preliminary results supporting the concept of MM-OCE-based hyperthermia dosimetry.

Imaging of nanoparticle-labeled stem cells using magnetomotive optical coherence tomography, laser speckle reflectometry, and light microscopy.

Cell transplantation and stem cell therapy are promising approaches for regenerative medicine and are of interest to researchers and clinicians worldwide. However, currently, no imaging technique that allows three-dimensional in vivo inspection of therapeutically administered cells in host tissues is available. Therefore, we investigate magnetomotive optical coherence tomography (MM-OCT) of cells labeled with magnetic particles as a potential noninvasive cell tracking method. We develop magnetomotive imaging of mesenchymal stem cells for future cell therapy monitoring. Cells were labeled with fluorescent iron oxide nanoparticles, embedded in tissue-mimicking agar scaffolds, and imaged using a microscope setup with an integrated MM-OCT probe. Magnetic particle-induced motion in response to a pulsed magnetic field of 0.2 T was successfully detected by OCT speckle variance analysis, and cross-sectional and volumetric OCT scans with highlighted labeled cells were obtained. In parallel, fluorescence microscopy and laser speckle reflectometry were applied as two-dimensional reference modalities to image particle distribution and magnetically induced motion inside the sample, respectively. All three optical imaging modalities were in good agreement with each other. Thus, magnetomotive imaging using iron oxide nanoparticles as cellular contrast agents is a potential technique for enhanced visualization of selected cells in OCT.

Intravascular magnetomotive optical coherence tomography of targeted early-stage atherosclerotic changes in ex vivo hyperlipidemic rabbit aortas.

We report the development of an intravascular magnetomotive optical coherence tomography (IV-MM-OCT) system used with targeted protein microspheres to detect early-stage atherosclerotic fatty streaks/plaques. Magnetic microspheres (MSs) were injected in vivo in rabbits, and after 30 minutes of in vivo circulation, excised ex vivo rabbit aorta samples specimens were then imaged ex vivo with our prototype IV-MM-OCT system. The alternating magnetic field gradient was provided by a unique pair of external custom-built electromagnetic coils that modulated the targeted magnetic MSs. The results showed a statistically significant MM-OCT signal from the aorta samples specimens injected with targeted MSs.

Volumetric full-range magnetomotive optical coherence tomography.

Magnetomotive optical coherence tomography (MM-OCT) can be utilized to spatially localize the presence of magnetic particles within tissues or organs. These magnetic particle-containing regions are detected by using the capability of OCT to measure small-scale displacements induced by the activation of an external electromagnet coil typically driven by a harmonic excitation signal. The constraints imposed by the scanning schemes employed and tissue viscoelastic properties limit the speed at which conventional MM-OCT data can be acquired. Realizing that electromagnet coils can be designed to exert MM force on relatively large tissue volumes (comparable or larger than typical OCT imaging fields of view), we show that an order-of-magnitude improvement in three-dimensional (3-D) MM-OCT imaging speed can be achieved by rapid acquisition of a volumetric scan during the activation of the coil. Furthermore, we show volumetric (3-D) MM-OCT imaging over a large imaging depth range by combining this volumetric scan scheme with full-range OCT. Results with tissue equivalent phantoms and a biological tissue are shown to demonstrate this technique.

Magnetomotive Optical Coherence Tomography for the Assessment of Atherosclerotic Lesions Using αvβ3 Integrin-Targeted Microspheres

We investigated the early-stage fatty streaks/plaques detection using magnetomotive optical coherence tomography (MM-OCT) in conjunction with αvβ3 integrin-targeted magnetic microspheres (MSs). The targeting of functionalized MSs was investigated by perfusing ex vivo aortas from an atherosclerotic rabbit model in a custom-designed flow chamber at physiologically relevant pulsatile flow rates and pressures. Aortas were extracted and placed in a flow chamber. Magnetic MS contrast agents were perfused through the aortas and MM-OCT, fluorescence confocal, and bright field microscopy were performed on the ex vivo aorta specimens for localizing the MSs. The results showed a statistically significant and stronger MM-OCT signal (3.30 ± 1.73dB) from the aorta segment perfused with targeted MSs, compared with the nontargeted MSs (1.18 ± 0.94dB) and control (0.78 ± 0.41dB) aortas. In addition, there was a good co-registration of MM-OCT signals with confocal microscopy. Early-stage fatty streaks/plaques have been successfully detected using MM-OCT in conjunction with αvβ3 integrin-targeted magnetic MSs.

Dual-coil magnetomotive optical coherence tomography for contrast enhancement in liquids

Magnetomotive optical coherence tomography (MM-OCT) is a functional extension of OCT which utilizes magnetically responsive materials that are modulated by an external magnetic field for contrast enhancement and for elastography to assess the structural and viscoelastic properties of the surrounding tissues. Traditionally, magnetomotive contrast relies on the interaction between the displacement of magnetic particles induced by an external magnetic field and the micro-environmental restoring (elastic) force acting on the particles. When the restoring force from a sample containing magnetic particles is weak or non-existent, the MM-OCT signal-to-noise ratio (SNR) can degrade significantly. We have developed a novel solenoid configuration to enable MM-OCT imaging in samples that do not have an elastic restoring force, such as liquids. This coil configuration may potentially enable real-time MM-OCT imaging.

Pulsed magneto-motive optical coherence tomography for remote cellular imaging

We developed pulsed magneto-motive optical coherence tomography (PMM-OCT) to reduce environmental temperature in the measurement volume and to expand the effective magnetic field distance from a pulse source. The proposed PMM-OCT system consisted of a spectral-domain OCT system and a customarily designed electrical pulse generator. The enhanced magnetic field allowed the proposed system to be able to image magnetically labeled cells in a distance as far as 30 mm away from the pulse generator. As an easy and sensitive approach, our PMM-OCT may be beneficially applied to a molecular-level imaging systems.

Imaging and Elastometry of Blood Clots Using Magnetomotive Optical Coherence Tomography and Labeled Platelets

Improved methods for imaging and assessment of vascular defects are needed for directing treatment of cardiovascular pathologies. In this paper, we employ magnetomotive optical coherence tomography (MMOCT) as a platform both to detect and to measure the elasticity of blood clots. Detection is enabled through the use of rehydrated, lyophilized platelets loaded with superparamagnetic iron oxides (SPIO-RL platelets) that are functional infusion agents that adhere to sites of vascular endothelial damage. Evidence suggests that the sensitivity for detection is improved over threefold by magnetic interactions between SPIOs inside RL platelets. Using the same MMOCT system, we show how elastometry of simulated clots, using resonant acoustic spectroscopy, is correlated with the fibrin content of the clot. Both methods are based upon magnetic actuation and phase-sensitive optical monitoring of nanoscale displacements using MMOCT, underscoring its utility as a broad-based platform to detect and measure the molecular structure and composition of blood clots.

Imaging and Elastometry of Blood Clots Using Magnetomotive Optical Coherence Tomography and Labeled Platelets

Imaging and Elastometry of Blood Clots Using Magnetomotive Optical Coherence Tomography and Labeled Platelets