Biophotonics Imaging Laboratory

Magnetomotive optical coherence imaging

In vivo MM-OCT imaging of an MNP-laden Xenopus (African frog) tadpole. The dynamic contrast provided by MNPs (green channel) is superimposed with the structural features imaged with OCT (red channel). Magnetomotive contrast is only observed when MNPs are added (c, d). In contrast, little to no MM-OCT signal is induced without the presence of MNPs (a, b).

Magnetomotive optical coherence tomography (MM-OCT) is a functional extension of OCT that detects the magnetic nanoparticles (MNPs) inside biological tissues. The MNPs (typically iron oxide nanoparticles) are biodegradable and can be further functionalized to target tumors or atherosclerotic lesions. After the delivery of MNPs to the targeted tissues, an external magnetic field can be provided to actuate the MNP-laden tissues. The modulated “magnetomotion” at the targeted tissue site can therefore be detected with OCT.

Magnetomotive optical coherence elastography(MM-OCE) is a dynamic OCE technique, which introduces magnetic nanoparticles (MNPs) in the biological tissues, and by applying a small, controlled, external magnetic field, one gains access to the nano-to micro-level interactions between the MNPs and the surrounding microenvironmental matrix. By quantifying the spatiotemporal characteristics of the mechanically-perturbed tissue sample, one can extract the mechanical properties of the sample.

Other than being utilized in MM-OCE, MNPs can also be independently used for magnetic hyperthermia(MH)treatment, which is a therapeutic technique that uses localized tissue heating to kill tumors. The temperature rise during MHtreatment not only can damage the targeted tissue, but can also induce stiffness change. Therefore, a novel dosimetry technique for MH treatment can be allowed, based on the alteration of mechanical properties detected by MM-OCE.

RECENT PUBLICATIONS:
  • Huang P-C, Iyer RR, Liu Y-Z, Boppart SA. Single-shot two-dimensional spectroscopic magnetomotive optical coherence elastography with graphics processing unit acceleration. Optics Letters, 45:4124-4127, 2020. 
  • Huang P-C, Chaney EJ, Iyer RR, Spillman DR Jr., Odintsov B, Sobh NA, Boppart SA. Interstitial magnetic thermotheray dosimetry based on shear wave magnetomotive optical coherence tomorgraphy. Biomedical Optics Express, 10:539-551. 2019.

Atherosclerotic lesion targeting

MNPs can also be loaded in a magnetic microsphere (MS) before delivery.  Coated with polyethylene glycol (PEG), the in vivo circulation time of MSs in the blood stream can be increased.  Functionalized with Arg-Gly-Asp (RGD) peptide, the magnetic MS can target αvβ3 integrins overexpressed in diseased atherosclerotic aortas.   

PUBLICATIONS:
  • Kim J, Ahmad A, Li J, Marjanovic M, Chaney EJ, Suslick KS, Boppart SA.   Intravascular magnetomotive optical coherence tomography of targeted early-stage atherosclerotic changes in ex vivo hyperlipidemic rabbit aortas.   J Biophotonics, 9:109-116. 2016.

  • Kim J, Ahmad A, Marjanovic M, Chaney EJ, Li J, Rasio J, Hubler Z, Spillman D, Suslick KS, Boppart SA. Magnetomotive optical coherence tomography for the assessment of atherosclerotic lesions using αvβ3 integrin-targeted microspheres. Mol Imaging Biol (2014) 16:36Y43 DOI: 10.1007/s11307-013-0671-6. 2014.

In vivo injection of (A, B) RGD-functionalized magnetic MSs, which allows for (C) targeting of atherosclerotic fatter streaks/plaques in rabbit aorta. Ex vivo MM-OCT images validate successfully administration and targeting. 

Magnetomotive displacements for hearing augmentation

The magnetomotive principle can also be exploited for hearing augmentation.  The MNPs can be passively diffused to a tympanic membrane (ear drum).  Afterward, the external magnetic field can be applied to mechanically actuate the MNP-laden ear drum and manipulate the ear drum motion.  As shown in the figure and video below, magnemotions can be successfully induced on MNP-laden ear drum specimens.  This can potentially allow for enhancement of hearing perception or even induce the perception of sound without the use of sound waves.    

PUBLICATIONS:
  • Huang P-C, Chaney EJ, Shelton RL, Boppart SA. Magnetomotive displacement of the tympanic membrane using magnetic nanoparticles: toward enhancement of sound perception. IEEE Trans. Biomedical Engineering, doi:10.1109/TBME.2018.2819649. 2018.

Stronger magnetomotions are observed as a higher concentration of MNPs are delivered to the tympanic membrane (ear drum). 

MM-OCE enabled magnetic nanoparticle hyperthermia dosimetry 

Theranostic functionality of the MNPs can be exploited. The same MNP agents can be delivered to the targeted site, detected via MM-OCT imaging, act as therapeutic agents (magnetic hyperthermia heating), and the thermal dosage can be evaluated with stiffness change sensed with MM-OCE.

PUBLICATIONS:
  • Huang P-C, Pande P, Ahmad A, Marjanovic M, Spillman DR, Odintsov B, Boppart SA. Magnetomotive optical coherence elastography for magnetic hyperthermia dosimetry based on dynamic tissue biomechanics. IEEE J Selected Topics in Quantum Electronics: NanoBiophotonics, 22:6802816. 2016.

MM-OCE detects heat-induced stiffness changes on MNP-laden chicken breast specimen. (a) Spectroscopic MM-OCE reveals a resonant peak shifted toward a high frequency, (b) transient-response MM-OCE shows an increased natural frequency, both of which suggest tissue stiffening after MH treatment (when MNPs are present, MNP+, and AMF is applied, AMF+).  

Shear-wave MM-OCE enabled interstitial magnetic thermotherapy dosimetry 

Similar dosimetry concept can be employed for interstitial magnetic thermotherapy (iMT), which utilizes a magnetic thermoseed to induce highly localized ablation.  The magnetic thermoseed can also act as a perturbative mechanical source in shear-wave MM-OCE.  After the ablation, heat-induced thermal damage on canine soft tissue sarcoma has stiffened, as suggested by the increase shear-wave propagation velocity.

PUBLICATIONS:
  • Huang P-C, Chaney EJ, Iyer RR, Spillman DR Jr., Odintsov B, Sobh NA, Boppart SA. Interstitial magnetic thermotheray dosimetry based on shear wave magnetomotive optical coherence tomorgraphy. Biomedical Optics Express, 10:539-551. 2019.

Canine soft tissue sarcoma (STS) specimen shows increased elasticity after each iMT treatment. (A) Structural OCT images (B) axial displacement maps captured at ~1.37 ms (full video shown below), and (C) reconstructed Young’s modulus maps. (D) Photographs obtained (left) before and (right) after each treatment; thermal images acquired at the (left) 0th and (right) 4th min of each treatment. White arrows indicate the location of magnetic thermoseed. (E) (Bottom) Post-treatment Masson Trichrome stained histology and (top) a zoomed-in area. Collagens were stained blue. Ablation zone is delineated with the dashed line. 

Spectroscopic MM-OCE

When excited by a broadband waveform (e.g. chirp) from the electromagnet, the MNP-laden tissue sample undergoes a forced vibration across a range of frequencies. The responding oscillation of the tissue reaches the maximum amplitude (termed 'resonance') when the excitation frequency hits the natural frequency of the sample. The resonant frequency can therefore be utilized to infer the elastic properties of the tissue sample.

Spectroscopic MM-OCE obtained with mechanical excitations across a wide range of modulation frequencies.  The reconstructed mechanical spectrum for ex vivo (I) muscle, (II) lung, and (III) tumor margin are provided. (IV) The magnetomotions induced vary with different excitation frequencies.  With higher modulation frequency, the stiffer region (tumor) exhibits a greater displacement.  With lower modulation frequency, the softer region (adipose) exhibits a greater displacement. 

PUBLICATIONS:
  • Ahmad A, Huang P-C, Sobh N, Pande P, Kim J, Boppart SA.   Mechanical contrast in spectroscopic magnetomotive optical coherence elastography. J Phys Med Biol 60:6655-6668. 2015.

An accelerated spectroscopic MM-OCE platform has also been developed to allow for in vivo 2D imaging.  By providing a single chirped mechanical excitation to the MNP-laden tissues and acquiring the data with a rapid BM-mode scheme, the resonant frequency can be extracted at each cross-sectional location.  As a result, spatially-resolved MM-OCE elastogram can be achieved in ≤ 2.9 sec.  In addition, accelerated MM-OCE reconstruction (≤618.8 ms) was enabled with the implementation of graphics processing unit (GPU) assisted computing. 

Accelerated spectroscopic MM-OCE achieves in vivo murine skin imaging.  (I) A single chirped excitation is provided as a BM-mode stack of OCT data is rapidly acquired. (II) Heterogeneous phantoms showing the mechanical constrasts between the stiff and soft side of the sample. (III) In vivo murine skin imaging can be validated with the ex vivo imaging, as well as M-mode measurements. 
 
PUBLICATIONS:
  • Huang P-C, Iyer RR, Liu Y-Z, Boppart SA. Single-shot two-dimensional spectroscopic magnetomotive optical coherence elastography with graphics processing unit acceleration. Optics Letters, 45:4124-4127, 2020.