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Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 5, Iss. 7 — Jul. 1, 2014
  • pp: 2349–2361
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Magnetomotive optical coherence elastography using magnetic particles to induce mechanical waves

Adeel Ahmad, Jongsik Kim, Nahil A. Sobh, Nathan D. Shemonski, and Stephen A. Boppart  »View Author Affiliations


Biomedical Optics Express, Vol. 5, Issue 7, pp. 2349-2361 (2014)
http://dx.doi.org/10.1364/BOE.5.002349


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Abstract

Magnetic particles are versatile imaging agents that have found wide spread applicability in diagnostic, therapeutic, and rheology applications. In this study, we demonstrate that mechanical waves generated by a localized inclusion of magnetic nanoparticles can be used for assessment of the tissue viscoelastic properties using magnetomotive optical coherence elastography. We show these capabilities in tissue mimicking elastic and viscoelastic phantoms and in biological tissues by measuring the shear wave speed under magnetomotive excitation. Furthermore, we demonstrate the extraction of the complex shear modulus by measuring the shear wave speed at different frequencies and fitting to a Kelvin-Voigt model.

© 2014 Optical Society of America

1. Introduction

Elastography is the image-based mapping of tissue mechanical properties, which is important in many areas of medicine and biology. Changes in mechanical properties have been shown to be associated with disease progression in several tissues such as in the liver, breast and thyroid [1

1. K. J. Parker, M. M. Doyley, and D. J. Rubens, “Imaging the elastic properties of tissue: the 20 year perspective,” Phys. Med. Biol. 56(1), R1–R29 (2011). [CrossRef] [PubMed]

]. In elastography, the sample is mechanically perturbed and imaging modalities are used to detect the induced displacements, which can subsequently be used to infer the material mechanical properties under certain simplifying assumptions. Elastography techniques differ in the way the sample is mechanically perturbed, how the induced changes are detected, and how the data is processed to assess the material mechanical properties [2

2. J. F. Greenleaf, M. Fatemi, and M. Insana, “Selected methods for imaging elastic properties of biological tissues,” Annu. Rev. Biomed. Eng. 5(1), 57–78 (2003). [CrossRef] [PubMed]

].

Ultrasound-based elastography (UE) and magnetic resonance elastography (MRE) are well established modalities undergoing varying stages of commercialization and clinical trials. Elastography based on optical methods such as optical coherence elastography (OCE) has attracted widespread attention in recent years as it can offer much higher spatial resolution and mechanical sensitivity compared to UE and MRE, however with the well-known tradeoff of a shallow imaging depth (~1–2 mm) in highly scattering tissues. OCE has been demonstrated in a number of tissue sites such as the skin, cornea, arteries, etc [3

3. B. F. Kennedy, K. M. Kennedy, and D. D. Sampson, “A review of optical coherence elastography: fundamentals, techniques and prospects,” IEEE J. Sel. Top. Quantum Electron. 20(2), 272–288 (2014). [CrossRef]

]. In addition, OCE has been demonstrated using needle based configurations that can access deeper underlying structures [4

4. K. M. Kennedy, B. F. Kennedy, R. A. McLaughlin, and D. D. Sampson, “Needle optical coherence elastography for tissue boundary detection,” Opt. Lett. 37(12), 2310–2312 (2012). [CrossRef] [PubMed]

].

Numerous methods for mechanical stimulation have been employed with each having different spatial (internal or external) and temporal (static or dynamic) characteristics. Methods based on static (or quasi-static) excitation subject the sample to static or low frequency loads, and the resulting displacements or strains are measured. Under the assumption that the sample is at mechanical equilibrium during measurements, and the stress is uniform throughout the sample, the measured displacement/strain rate can be used as a substitute for the elastic modulus providing relative mechanical contrast [5

5. S. J. Kirkpatrick, R. K. Wang, and D. D. Duncan, “OCT-based elastography for large and small deformations,” Opt. Express 14(24), 11585–11597 (2006). [CrossRef] [PubMed]

]. Elastography techniques utilizing some form of dynamic mechanical stimulus have received considerable attention in recent years, which compared to the static excitation methods, are more quantitative and less dependent on the boundary conditions outside the region of interest [6

6. X. Liang, V. Crecea, and S. A. Boppart, “Dynamic optical coherence elastography: a review,” J. Innov. Opt. Health Sci. 3(4), 221–233 (2010). [CrossRef] [PubMed]

]. The applied dynamic excitation can be in the form of a short duration (transient) pulse or can be harmonically oscillating at high frequency. Elastography methods that are based on dynamic excitation can be formulated in terms of wave propagation phenomena. The perturbation of a region within the sample results in deformation of the surrounding medium, which can propagate in the form of elastic waves within the sample and be measured using imaging methods such as ultrasound, optical imaging, or MRE [2

2. J. F. Greenleaf, M. Fatemi, and M. Insana, “Selected methods for imaging elastic properties of biological tissues,” Annu. Rev. Biomed. Eng. 5(1), 57–78 (2003). [CrossRef] [PubMed]

, 7

7. R. Muthupillai, D. J. Lomas, P. J. Rossman, J. F. Greenleaf, A. Manduca, and R. L. Ehman, “Magnetic resonance elastography by direct visualization of propagating acoustic strain waves,” Science 269(5232), 1854–1857 (1995). [CrossRef] [PubMed]

]. As the characteristics of mechanical wave propagation are dependent on the sample mechanical properties, they can be used to assess the viscoelastic properties.

A wide variety of methods have been utilized to generate mechanical waves within a sample. Excitation methods such as rods [8

8. V. Dutt, R. R. Kinnick, R. Muthupillai, T. E. Oliphant, R. L. Ehman, and J. F. Greenleaf, “Acoustic shear-wave imaging using echo ultrasound compared to magnetic resonance elastography,” Ultrasound Med. Biol. 26(3), 397–403 (2000). [CrossRef] [PubMed]

], needles [9

9. Q. C. C. Chan, G. Li, R. L. Ehman, R. C. Grimm, R. Li, and E. S. Yang, “Needle shear wave driver for magnetic resonance elastography,” Magn. Reson. Med. 55(5), 1175–1179 (2006). [CrossRef] [PubMed]

, 10

10. M. Orescanin and M. Insana, “Shear modulus estimation with vibrating needle stimulation,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 57(6), 1358–1367 (2010). [CrossRef] [PubMed]

] attached to mechanical/electromechanical actuators, piezo-vibrators, acoustic drivers, etc., or some form of internal excitation such as acoustic radiation force (ARF) [11

11. K. Nightingale, “Acoustic radiation force impulse (ARFI) imaging: a review,” Curr. Med. Imaging Rev. 7(4), 328–339 (2011). [CrossRef] [PubMed]

], have been used. In OCE, mechanical actuators on the surface of the sample [12

12. X. Liang and S. A. Boppart, “Biomechanical properties of in vivo human skin from dynamic optical coherence elastography,” IEEE Trans. Biomed. Eng. 57(4), 953–959 (2010). [CrossRef] [PubMed]

15

15. S. Song, Z. Huang, and R. K. Wang, “Tracking mechanical wave propagation within tissue using phase-sensitive optical coherence tomography: motion artifact and its compensation,” J. Biomed. Opt. 18(12), 121505 (2013). [CrossRef] [PubMed]

], incident acoustic radiation force [16

16. M. Razani, A. Mariampillai, C. Sun, T. W. H. Luk, V. X. D. Yang, and M. C. Kolios, “Feasibility of optical coherence elastography measurements of shear wave propagation in homogeneous tissue equivalent phantoms,” Biomed. Opt. Express 3(5), 972–980 (2012). [CrossRef] [PubMed]

19

19. M. Razani, T. W. H. Luk, A. Mariampillai, P. Siegler, T.-R. Kiehl, M. C. Kolios, and V. X. D. Yang, “Optical coherence tomography detection of shear wave propagation in inhomogeneous tissue equivalent phantoms and ex-vivo carotid artery samples,” Biomed. Opt. Express 5(3), 895–906 (2014). [CrossRef] [PubMed]

], acoustomotive forces [20

20. X. Liang, M. Orescanin, K. S. Toohey, M. F. Insana, and S. A. Boppart, “Acoustomotive optical coherence elastography for measuring material mechanical properties,” Opt. Lett. 34(19), 2894–2896 (2009). [CrossRef] [PubMed]

], air-puffs [21

21. S. Wang, J. Li, R. K. Manapuram, F. M. Menodiado, D. R. Ingram, M. D. Twa, A. J. Lazar, D. C. Lev, R. E. Pollock, and K. V. Larin, “Noncontact measurement of elasticity for the detection of soft-tissue tumors using phase-sensitive optical coherence tomography combined with a focused air-puff system,” Opt. Lett. 37(24), 5184–5186 (2012). [CrossRef] [PubMed]

], and laser induced surface waves [22

22. C. Li, G. Guan, F. Zhang, G. Nabi, R. K. Wang, and Z. Huang, “Laser induced surface acoustic wave combined with phase sensitive optical coherence tomography for superficial tissue characterization: a solution for practical application,” Biomed. Opt. Express 5(5), 1403–1419 (2014). [CrossRef] [PubMed]

], among others, have been utilized to mechanically and dynamically stimulate the sample.

2. Methods

2.1 Experimental setup

A 1310 nm spectral domain OCT system shown in Fig. 1
Fig. 1 Spectral domain magnetomotive optical coherence elastography setup.
was used for the shear wave measurements. The light source was a superluminescent diode (LS2000B, Thorlabs) with 170 nm bandwidth and the measured axial and transverse resolutions (full width at half max) of the system were 6 μm and 16 μm, respectively. A 1024-pixel InGaAs line-scan camera (SU-LDH2, Goodrich) was used in the spectrometer with an optical imaging depth of 2.6 mm. The phase noise of the system was ~20 milli-radians measured at a line-scan rate of 46 kHz with a static sample (IR card) placed in the sample arm. The jitter in the scanning galvanometers was the main contribution to the phase noise which reduces to ~5 milli-radians when the galvanometer scanners are turned off. The coil for generating the magnetic field was placed underneath the sample while the imaging was performed from the top, allowing the coverage of a large field-of-view. The magnetic field strength generated by the coil was measured to be approximately 150 Gauss at the sample surface (~1 cm away from the coil).

The OCT data is acquired by taking multiple M-mode (A-lines measured as a function of time) measurements at different radial positions away from the MNPs as shown in Fig. 2(a)
Fig. 2 Data acquisition and processing (a) M-mode scans are taken radially away from the magnetic inclusion. (b) The timing diagram for the scanning protocol (c) Structural OCT image (z, r) showing the location of the MNP inclusion (d) Depth-averaged space-time (t, r) map showing the sinusoidal response at different radial distances. (e) The linear change in phase as the distance from the excitation source increases.
. Typically very high frame rates are needed to image the propagating shear waves, however, these waves can be visualized by a stroboscopic acquisition scheme [18

18. T.-M. Nguyen, S. Song, B. Arnal, Z. Huang, M. O’Donnell, and R. K. Wang, “Visualizing ultrasonically induced shear wave propagation using phase-sensitive optical coherence tomography for dynamic elastography,” Opt. Lett. 39(4), 838–841 (2014). [CrossRef] [PubMed]

, 33

33. S. Song, Z. Huang, T.-M. Nguyen, E. Y. Wong, B. Arnal, M. O’Donnell, and R. K. Wang, “Shear modulus imaging by direct visualization of propagating shear waves with phase-sensitive optical coherence tomography,” J. Biomed. Opt. 18(12), 121509 (2013). [CrossRef] [PubMed]

]. A trigger signal is used to synchronize the camera data acquisition with the electromagnetic coil activation and scanning galvanometer (M-B mode scan i.e. M-mode data acquired at different spatial locations) as shown in Fig. 2(b). At the beginning of each M-model data acquisition, the electromagnetic coil is activated to generate a square root sinusoidal waveform of 10-20 cycles at a given frequency f. At each radial position (a single M-mode) 2000 A-lines at a scan rate of ~46 kHz was acquired (unless stated otherwise) and a brief waiting time (~1 sec) was given before subsequent M-mode acquisitions to prevent any heating of the coil. The lateral pixel size was ~8 μm (corresponding to 500 radial locations over a scan range of 4 mm) for shear wave visualization while a lateral pixel size of ~40 μm (100 radial locations) was chosen for the shear wave spectroscopy measurements to minimize the amount of data collected and to reduce the data acquisition time.

2.2 Data processing

Figure 2(c) shows representative data where MNPs, acting as the shear wave generating source, can be seen in the structural OCT image. Our shear wave excitation source comprising of an inclusion of MNPs is approximately cylindrical in shape, and hence can be considered as generating cylindrical waves. The displacement of the cylindrical shear wave produced by harmonic force with angular frequency ω=2πf acting along the z-axis is given by uz(r,t)=i4H0(1)(kr)exp(iωt)where uzis the displacement along the z-axis, H0(1)is the zeroth order Hankel function of the first kind, r is the radial distance and k is the shear wave number given by k=2π/λwith λ being the shear wavelength. If the measurements are made at sufficient distance away from the excitation source (kr>1) then it can be shown that the phase of the cylindrical shear wave varies linearly with the radial distance uz(r,t)i42/(πkr)exp(i(krωt+π/4)) [34

34. T. Deffieux, G. Montaldo, M. Tanter, and M. Fink, “Shear wave spectroscopy for in vivo quantification of human soft tissues visco-elasticity,” IEEE Trans. Med. Imaging 28(3), 313–322 (2009). [CrossRef] [PubMed]

]. This linear change in phase can be used to calculate the shear wave speed [35

35. S. Chen, M. Fatemi, and J. F. Greenleaf, “Quantifying elasticity and viscosity from measurement of shear wave speed dispersion,” J. Acoust. Soc. Am. 115(6), 2781–2785 (2004). [CrossRef] [PubMed]

].

The M-mode OCT data acquired at different radial positions away from the MNPs was processed by using standard phase-resolved OCT processing (i.e. resampling, Fourier transform and phase extraction) and subsequently the phase values (across time) were bandpass-filtered around the excitation frequency to remove any noise from other frequency bands [36

36. A. L. Oldenburg, V. Crecea, S. A. Rinne, and S. A. Boppart, “Phase-resolved magnetomotive OCT for imaging nanomolar concentrations of magnetic nanoparticles in tissues,” Opt. Express 16(15), 11525–11539 (2008). [PubMed]

]. These phase values (can also be converted into displacement values based on the system central wavelength and sample refractive index) can then be displayed in the form of a space-time map for any given depth as shown in Fig. 2(d). As expected, there is a phase lag between the measured displacements at different radial positions as we move away from the MNP excitation source. This phase lag for each radial (lateral) location as shown in Fig. 2(e) was computed using a Kalman filter [37

37. Y. Zheng, S. Chen, W. Tan, R. Kinnick, and J. F. Greenleaf, “Detection of tissue harmonic motion induced by ultrasonic radiation force using pulse-echo ultrasound and Kalman filter,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 54(2), 290–300 (2007). [CrossRef] [PubMed]

], where it can be seen that the phase changes linearly with propagation distance. Although the use of a Kalman filter is not necessary when the shear waves displacement amplitude has sufficiently high signal to noise ratio (SNR), in scenarios where the displacements are small (such as when using high excitation frequencies or in stiffer samples), the use of Kalman filter may provide more robust phase and amplitude estimation as has been shown in the ultrasound literature [37

37. Y. Zheng, S. Chen, W. Tan, R. Kinnick, and J. F. Greenleaf, “Detection of tissue harmonic motion induced by ultrasonic radiation force using pulse-echo ultrasound and Kalman filter,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 54(2), 290–300 (2007). [CrossRef] [PubMed]

]. The phase gradient k=Δϕ/Δr was then estimated by performing a linear fit on the radial phase profile and was used to calculate the shear wave speed cs=ωΔr/Δϕ at a particular excitation frequencyω [35

35. S. Chen, M. Fatemi, and J. F. Greenleaf, “Quantifying elasticity and viscosity from measurement of shear wave speed dispersion,” J. Acoust. Soc. Am. 115(6), 2781–2785 (2004). [CrossRef] [PubMed]

]. The first two excitation cycles in each M-mode were excluded from quantitative analysis as these contained a superimposed transient response possibly coming from the settling time of the galvanometer scanners or due to the switching on of the electromagnetic coil. The propagating shear waves can be visualized in the form of a video by playing the phase values in the cross-sectional planes (z, r) across time. In the videos, we applied a binary mask to remove the random phase values in the regions above and below the sample surface. The binary mask was computed by smoothing and thresholding the structural OCT image where the pixels within the sample region were given values of 1 and those outside were assigned a value of 0.

In a viscoelastic medium, the shear modulus is complex and can be quantified by measuring the dispersion of the shear wave speed. The dispersion curves are obtained by measuring the shear wave speed at several different frequencies and can be fitted to tissue rheological models to estimate the complex modulus of the medium [34

34. T. Deffieux, G. Montaldo, M. Tanter, and M. Fink, “Shear wave spectroscopy for in vivo quantification of human soft tissues visco-elasticity,” IEEE Trans. Med. Imaging 28(3), 313–322 (2009). [CrossRef] [PubMed]

, 35

35. S. Chen, M. Fatemi, and J. F. Greenleaf, “Quantifying elasticity and viscosity from measurement of shear wave speed dispersion,” J. Acoust. Soc. Am. 115(6), 2781–2785 (2004). [CrossRef] [PubMed]

, 38

38. S. Chen, M. W. Urban, C. Pislaru, R. Kinnick, Y. Zheng, A. Yao, and J. F. Greenleaf, “Shearwave dispersion ultrasound vibrometry (SDUV) for measuring tissue elasticity and viscosity,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 56(1), 55–62 (2009). [CrossRef] [PubMed]

]. One widely used tissue model is a Kelvin-Voigt model which consists of a spring and dashpot connected in parallel. The shear wave dispersion for this tissue model is given by the expression
cs(ω)=2(G2+ω2η2)ρ(G+G2+ω2η2)
(1)
where csis the shear wave speed, G is the real part of the complex shear modulus, ρis the mass density, andηis the shear viscosity of the material. If a medium is purely elastic i.e. η0 or if the shear (storage) modulus is dominant in comparison to the viscosity (G>>ωη), the above equation simplifies to G=ρcs2 which relates the shear wave speed to the shear modulus for a linear isotropic elastic material [39

39. Y. Yamakoshi, J. Sato, and T. Sato, “Ultrasonic imaging of internal vibration of soft tissue under forced vibration,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 37(2), 45–53 (1990). [CrossRef] [PubMed]

].

2.3 Tissue mimicking phantom preparation

To demonstrate that a localized inclusion of magnetic particles can generate shear waves, we prepared tissue mimicking phantoms using agar gel. Phantoms with different stiffness were prepared by varying the dry-weight concentration (0.3, 0.5, 0.7 and 1.0%) of agarose gel in distilled water, and the solution was subsequently boiled until it became optically clear. The solution was then allowed to cool at room temperature and titanium dioxide particles (size < 5 μm, 2 mg/ml) were added to increase the optical scattering. Subsequently the solution was poured into cylindrical containers (height 5-10 mm and diameter 35-90 mm) and allowed to congeal at room temperature. A cylindrical mold (~2.5 mm in diameter) was placed in the cylindrical container during the agarose congealing process so that an inclusion containing MNPs (Fe3O4, size 50-100 nm) could be placed at that location. The MNPs inclusions were prepared by mixing MNPs (50 mg/ml) in either the same concentration agarose gel or with PDMS gel. The MNP-gel solution was then poured into the center of the cured cylindrical samples. The samples were subsequently allowed to cure at room temperature for 4-6 hours. Although the inclusions did not seem to bond permanently with the surrounding medium, the mechanical coupling between the MNP inclusion and the surrounding medium was sufficient for the generation of shear waves in the medium.

Agar phantoms are known to have an almost purely elastic response [40

40. M. Benkherourou, C. Rochas, P. Tracqui, L. Tranqui, and P. Y. Guméry, “Standardization of a method for characterizing low-concentration biogels: elastic properties of low-concentration agarose gels,” J. Biomech. Eng. 121(2), 184–187 (1999). [CrossRef] [PubMed]

]. Therefore, to validate our MM-OCE method in viscoelastic samples, we prepared oil-in-gelatin phantoms that have been shown in the literature to exhibit significant viscosity by adding oil in gelatin [41

41. M. M. Nguyen, S. Zhou, J. L. Robert, V. Shamdasani, and H. Xie, “Development of oil-in-gelatin phantoms for viscoelasticity measurement in ultrasound shear wave elastography,” Ultrasound Med. Biol. 40(1), 168–176 (2014). [CrossRef] [PubMed]

]. A sample of 8% Gelatin (Type B: 225 Bloom) was prepared by dissolving it in de-ionized water and heating the solution at 65° C for approximately one hour until the solution became clear. Titanium dioxide scattering particles (size < 5 μm, 1 mg/ml) were added as scattering particles. To increase the viscosity of the sample, Castor oil was added to the gelatin and the solution was vigorously stirred using a blender after the addition of a surfactant to help in the emulsification [42

42. E. L. Madsen, J. A. Zagzebski, and G. R. Frank, “Oil-in-gelatin dispersions for use as ultrasonically tissue-mimicking materials,” Ultrasound Med. Biol. 8(3), 277–287 (1982). [CrossRef] [PubMed]

]. The cylindrical inclusions consisted of MNPs (50 mg/ml) mixed with 8% gelatin. The samples were allowed to cure at room temperature for one hour and then left in the refrigerator for 6 hours before imaging.

3. Results

3.1 Homogeneous tissue phantoms

In Fig. 3
Fig. 3 Shear waves in elastically homogeneous phantoms. The MNP inclusions (not shown) are on the right side of the images (a) Visualization of shear waves with phantoms of different agarose concentrations. A line-scan rate of ~92 kHz and 4000 A-lines per M-mode were collected. A sinusoidal excitation at 500 Hz consisting of 20 cycles was used. An increase in the shear wavelength and speed can be seen as the gel stiffness increases (Media 1). (b) Estimated Young’s moduli at different agarose concentrations. A line-scan rate of ~46 kHz, 2000 A-lines per M-mode and 10 cycles at a excitation frequency of 500 Hz was used for these measurements. The error bars correspond to the standard deviation of the measured values at 3 different spatial locations within the same sample (N = 3). The error bars for 0.3% and 0.5% are too small to see, and the values correspond to 4.14 ± 0.25 kPa and 15 ± 1.47 kPa, respectively.
, we show representative examples of shear wave propagation in homogenous agarose phantoms of different stiffness. An excitation frequency of 500 Hz was used and the elastic modulus was estimated using a linear elastic model as agarose gel is largely non-dispersive (data shown in Fig. 6(a)). The changes in shear wave wavenumber can be clearly seen where the soft sample (0.3% agarose) exhibits a higher wavenumber (hence steeper phase gradient and lower shear modulus) compared to the stiffer samples (0.5% and 0.7% agarose). In the video (Media 1) the differences in the shear wave speed can be clearly visualized.

3.2 Heterogeneous phantoms

Figure 4
Fig. 4 Shear waves in a heterogeneous medium. (a) Structural OCT image. The solid lines delineate the shear wave source boundaries while the dashed line indicates the interface between the stiff and soft regions of the sample. (b) Propagating shear waves (Media 2). (c) Depth-averaged space-time map. (d) Young’s modulus map estimated from the localized measurement of the shear wave speed. The black regions correspond to the MNP source location or where the linear fit R2 values were less than the threshold. A line-scan rate ~92 kHz with an excitation frequency of 500 Hz was used for these measurements.
shows the shear wave propagation in a heterogeneous agarose gel phantom prepared in a side-by-side configuration with the two sides having different stiffness values. The embedded MNP inclusion can be seen near the middle of the OCT structural image in Fig. 4(a). A relatively high concentration of MNPs was used (250 mg/ml), therefore, only the top part of the inclusion appears in the OCT structural image. A large field-of-view was acquired by translating the sample between acquisitions and stitching three overlapping cross-sectional data sets in post-processing. The phantom was prepared in two steps. In the first step 0.7% agarose was prepared with the magnetic inclusion and allowed to congeal at room temperature. Subsequently, the 0.3% agarose (representing the soft part) was poured in and allowed to cure. The yellow dashed line shows the boundary between the two different concentrations. In Fig. 4(b) and in the corresponding shear wave propagation video (Media 2), the two different media can be qualitatively identified. In the softer region we can clearly see the wavelength being shorter and the shear wave propagation speed being slower compared to the stiff portions of the sample.

In Fig. 4(c), a representative space-time map is shown, after averaging along the depth. As expected, in the region containing the MNP inclusion, no significant phase lag is observed as these regions move in phase with the excitation waveform. However, as we move away from the MNP inclusion, the phase lags become apparent, and clear differences in shear wave speeds can be seen between the stiff and the soft regions.

Space-time maps similar to the one shown in Fig. 4(c) were extracted for each depth and were used to estimate the elastic modulus map shown in Fig. 4(d). A Kalman filter was used to estimate the phase lag at each depth (z) and lateral location (r) within the sample. The estimated phase profile was smoothed by low-pass and median filtering to remove any random fluctuations of the phase within the sample due to low OCT signal. The local shear wave speeds were calculated by performing a linear fit on the smoothed phase profile over a lateral distance of ~300 μm on a pixel-by-pixel basis, and the linear fits that were below a certain R2 threshold were discarded. The Young’s moduli were estimated using the relationshipE(r,z)3ρcs2(r,z) wherecs(r,z) is the local speed calculated at each lateral position and depth. In the softer regions of the sample that corresponds to 0.3% agarose gel concentration, the mean value of the estimated Young’s modulus values was ~4.3 kPa, which is in good agreement with the measurements shown in Fig. 3(b). In the stiff regions (0.7% agarose concentration), we note that the mean Young’s modulus in the regions away (> 1 mm) from the location of the MNPs was ~30.2 kPa, which also corresponds well to the previously measured values shown in Fig. 3(b). However, in the regions close to the MNPs, the Young’s modulus values were significantly higher (mean value ~80 kPa) than the values measured in Fig. 3(b). This bias is expected due to the diffraction/near-field effects of the presence of compressional waves, mode coupling, and the breakdown of the assumption of a linear phase gradient [18

18. T.-M. Nguyen, S. Song, B. Arnal, Z. Huang, M. O’Donnell, and R. K. Wang, “Visualizing ultrasonically induced shear wave propagation using phase-sensitive optical coherence tomography for dynamic elastography,” Opt. Lett. 39(4), 838–841 (2014). [CrossRef] [PubMed]

, 43

43. J. Bercoff, M. Tanter, M. Muller, and M. Fink, “The role of viscosity in the impulse diffraction field of elastic waves induced by the acoustic radiation force,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 51(11), 1523–1536 (2004). [CrossRef] [PubMed]

, 44

44. S. Catheline, F. Wu, and M. Fink, “A solution to diffraction biases in sonoelasticity: The acoustic impulse technique,” J. Acoust. Soc. Am. 105(5), 2941–2950 (1999). [CrossRef] [PubMed]

]. Moreover, these results can also be biased due to the reflections from the internal elastic boundaries. Despite these limitations, differences in elastic contrast between the soft and the stiff regions within the sample can be seen.

3.3 Biological tissues

3.4 Dispersion curves

4. Discussion and conclusion

Numerous factors such as boundary effects [46

46. Y. Wang and M. F. Insana, “Viscoelastic properties of rodent mammary tumors using ultrasonic shear-wave imaging,” Ultrason. Imaging 35(2), 126–145 (2013). [CrossRef] [PubMed]

], shear wave patterns [43

43. J. Bercoff, M. Tanter, M. Muller, and M. Fink, “The role of viscosity in the impulse diffraction field of elastic waves induced by the acoustic radiation force,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 51(11), 1523–1536 (2004). [CrossRef] [PubMed]

], diffraction and other near-field effects need to be taken into consideration for accurate estimation of the shear modulus [44

44. S. Catheline, F. Wu, and M. Fink, “A solution to diffraction biases in sonoelasticity: The acoustic impulse technique,” J. Acoust. Soc. Am. 105(5), 2941–2950 (1999). [CrossRef] [PubMed]

]. Measurements need to be performed in the far-field and sufficiently away from the boundaries to minimize the bias caused by the contribution of compression waves and wave coupling at the boundaries. In our experiments with phantoms having large dimensions, the rapid attenuation of the shear waves away from the excitation source resulted in minimal boundary effects. However, this will not be the case in heterogeneous tissues which will have local internal boundaries. To ameliorate this effect, directional filters [47

47. T. Deffieux, J. L. Gennisson, J. Bercoff, and M. Tanter, “On the effects of reflected waves in transient shear wave elastography,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 58(10), 2032–2035 (2011). [CrossRef] [PubMed]

] and transient excitation in the form of short pulses can be used to minimize the impact of the reflected waves from the boundaries [48

48. J. Bercoff, S. Chaffai, M. Tanter, L. Sandrin, S. Catheline, M. Fink, J. L. Gennisson, and M. Meunier, “In vivo breast tumor detection using transient elastography,” Ultrasound Med. Biol. 29(10), 1387–1396 (2003). [CrossRef] [PubMed]

].

In principle, estimating the shear wave attenuation (amplitude decay) can provide additional information and can be utilized to extract the viscoelastic properties. However, estimating the attenuation is often unreliable and challenging as the amplitude of shear waves is more susceptible to noise especially if the sample is inhomogeneous. Moreover, attenuation due to geometric spreading and diffraction effects also needs to be taken into consideration. Considering these difficulties, we only utilized the shear wave speed to estimate the mechanical properties.

We limited the frequency range used in these experiments to 300-750 Hz. At lower excitation frequencies, the shear wavelengths would be large making the measurements more susceptible to near-field and boundary effects [44

44. S. Catheline, F. Wu, and M. Fink, “A solution to diffraction biases in sonoelasticity: The acoustic impulse technique,” J. Acoust. Soc. Am. 105(5), 2941–2950 (1999). [CrossRef] [PubMed]

] while also increasing the imaging time. On the other hand, at higher excitation frequencies the rapid attenuation of the shear waves and relatively low magnetic field strength from our coil would substantially decrease the SNR of the obtained measurements. The dynamic range of the measured Gis dependent on the minimum and maximum values of the phase gradient i.e. k=Δϕ/Δr that can be reliably measured while the spatial resolution depends on the length scale Δr over which the local shear wave speed is estimated. The choice of the length scale Δr will be influenced by a number of factors such as the SNR, the displacement amplitudes, excitation frequency and tissue mechanical properties [35

35. S. Chen, M. Fatemi, and J. F. Greenleaf, “Quantifying elasticity and viscosity from measurement of shear wave speed dispersion,” J. Acoust. Soc. Am. 115(6), 2781–2785 (2004). [CrossRef] [PubMed]

, 49

49. M. W. Urban, S. Chen, and J. F. Greenleaf, “Error in estimates of tissue material properties from shear wave dispersion ultrasound vibrometry,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 56(4), 748–758 (2009). [CrossRef] [PubMed]

]. The accuracy of the phase gradient estimation is fundamentally limited by the SNR of the measurements. The minimum amount of phase shift that can be measured (given sufficient SNR) depends on the number of sampling points per excitation cycle and is given byΔϕmin=2π/(Fs/f)where Fs is the sampling rate (equivalent to the line-scan rate of the camera in our experiments). Hence, the phase shift Δϕ induced (which depends onωand the material properties) by the propagating shear waves over a length scale ∆r should be greater than Δϕminand the sampling rate should satisfyFs>ω/Δϕ.

The shape and characteristics of the propagating wave is influenced by the geometry of the mechanical excitation source [43

43. J. Bercoff, M. Tanter, M. Muller, and M. Fink, “The role of viscosity in the impulse diffraction field of elastic waves induced by the acoustic radiation force,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 51(11), 1523–1536 (2004). [CrossRef] [PubMed]

]. In our experiments, surface (Rayleigh) waves may also be generated as our excitation source (comprising MNPs) extends to the surface of the sample. However, the shear and surface waves are almost identical in speed and hence would not significantly impact our measured values. In these measurements, we have assumed that the propagating shear waves are cylindrical in shape. However, this assumption may not always be valid, especially in tissues where controlling the geometry of the localized MNP inclusions may not be possible. If the sample is uniformly loaded with MNPs, then a focused magnetic field can be used to generate a predictable shear wave shape where the excitation region would be dependent on the magnetic field characteristics of the coil. Another way to have an excitation source (with controlled geometry) that can generate a well-defined wave pattern is by using needle-based magnetic actuation or inserting a metallic rod within the specimen [50

50. A. Grimwood, L. Garcia, J. Bamber, J. Holmes, P. Woolliams, P. Tomlins, and Q. A. Pankhurst, “Elastographic contrast generation in optical coherence tomography from a localized shear stress,” Phys. Med. Biol. 55(18), 5515–5528 (2010). [CrossRef] [PubMed]

]. Due to the high magnetic susceptibility of the metallic (e.g. carbon steel) rod, relatively large localized displacements can be induced in the sample. These large displacements cannot only increase the propagation range of the shear waves, but can also potentially be used to measure the non-linear elastic parameters [51

51. S. Catheline, J. L. Gennisson, and M. Fink, “Measurement of elastic nonlinearity of soft solid with transient elastography,” J. Acoust. Soc. Am. 114(6), 3087–3091 (2003). [CrossRef] [PubMed]

] and the elastic properties in an anisotropic medium by placing the rod at different orientations [52

52. J. L. Gennisson, S. Catheline, S. Chaffaï, and M. Fink, “Transient elastography in anisotropic medium: application to the measurement of slow and fast shear wave speeds in muscles,” J. Acoust. Soc. Am. 114(1), 536–541 (2003). [CrossRef] [PubMed]

].

Another consideration when using magnetic excitation is the magnetic properties of the tissue itself. Tissues are known to exhibit a weakly diamagnetic response characterized by an out-of-phase response with the applied excitation [36

36. A. L. Oldenburg, V. Crecea, S. A. Rinne, and S. A. Boppart, “Phase-resolved magnetomotive OCT for imaging nanomolar concentrations of magnetic nanoparticles in tissues,” Opt. Express 16(15), 11525–11539 (2008). [PubMed]

]. However, tissue diamagnetism will not affect our measurements as this response is very weak and the tissue diamagnetic properties are unlikely to change over the phase gradient measurement range.

The generation of shear waves by magnetic particles can potentially explain some of the artifacts seen in MM-OCT and magnetomotive ultrasound [53

53. M. Evertsson, M. Cinthio, S. Fredriksson, F. Olsson, H. W. Persson, and T. Jansson, “Frequency- and phase-sensitive magnetomotive ultrasound imaging of superparamagnetic iron oxide nanoparticles,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 60(3), 481–491 (2013). [CrossRef] [PubMed]

]. From an imaging perspective, the goal of magnetomotive imaging is to spatially localize magnetic particles within the sample. The propagation of elastic waves induced by the magnetic particles can make this spatial localization challenging. However, due to the relatively low scan rates and small displacement amplitudes used in magnetomotive imaging, shear wave propagation is not directly visualized. These artifacts if present can be minimized by phase gating [53

53. M. Evertsson, M. Cinthio, S. Fredriksson, F. Olsson, H. W. Persson, and T. Jansson, “Frequency- and phase-sensitive magnetomotive ultrasound imaging of superparamagnetic iron oxide nanoparticles,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 60(3), 481–491 (2013). [CrossRef] [PubMed]

] or filtering the signals that are out of phase with the excitation [36

36. A. L. Oldenburg, V. Crecea, S. A. Rinne, and S. A. Boppart, “Phase-resolved magnetomotive OCT for imaging nanomolar concentrations of magnetic nanoparticles in tissues,” Opt. Express 16(15), 11525–11539 (2008). [PubMed]

].

Fundamentally, this proposed method is similar to other internal dynamic excitation elastography methods such as ARF elastography. However, ARF-based techniques usually require appropriate acoustic impedance matching between the ultrasound transducer and the sample, have an excitation region that is typically large, and utilize high intensity ultrasound that can potentially damage the areas within the focal regions, making the amplitude of the generated shear waves limited by the local heating effect. Although the proposed method using MNPs is invasive in the sense that it requires the sample to be loaded with magnetic particles, there are current clinical scenarios where these MNPs are already loaded in tissues to serve the purpose of contrast enhancement in MRI or in magnetic hyperthermia applications [54

54. V. I. Shubayev, T. R. Pisanic 2nd, and S. Jin, “Magnetic nanoparticles for theragnostics,” Adv. Drug Deliv. Rev. 61(6), 467–477 (2009). [CrossRef] [PubMed]

]. Under these scenarios, this requirement may not impose a significant limitation.

An appropriate choice of the rheological model is still an open question and would depend on a number of factors including the frequency range used for excitation and the mechanical properties of the material. Rheological model-free methods have been proposed that estimate the complex shear modulus and wavenumber in a viscoelastic medium without making any assumptions of the underlying mechanical model and could be an interesting area for further exploration [55

55. J. Vappou, C. Maleke, and E. E. Konofagou, “Quantitative viscoelastic parameters measured by harmonic motion imaging,” Phys. Med. Biol. 54(11), 3579–3594 (2009). [CrossRef] [PubMed]

]. Future work will include the investigation of the influence of stiffness, size and geometry of the MNP source on the shear wave measurements and any bias introduced by these factors. Future studies should validate the estimated viscoelastic parameters with standard rheometry measurements. However, the low frequency range used in rheometery measurements (< 250 Hz) [56

56. R. W. Chan and M. L. Rodriguez, “A simple-shear rheometer for linear viscoelastic characterization of vocal fold tissues at phonatory frequencies,” J. Acoust. Soc. Am. 124(2), 1207–1219 (2008). [CrossRef] [PubMed]

] may limit a direct comparison with the current technique. In future applications, the generation of shear waves with a spatially focused magnetic field would be more appropriate, enabling this technique to be used in tissue samples uniformly loaded with MNPs. The possibility of generating shear waves using magnetic particles may also be beneficial for studying cellular mechanics where magnetic beads are already widely used for rheological measurements [24

24. C. Wilhelm and F. Gazeau, “Magnetic nanoparticles: Internal probes and heaters within living cells,” J. Magn. Magn. Mater. 321(7), 671–674 (2009). [CrossRef]

, 25

25. V. Crecea, B. W. Graf, T. Kim, G. Popescu, and S. A. Boppart, “High resolution phase-sensitive magnetomotive optical coherence microscopy for tracking magnetic microbeads and cellular mechanics,” IEEE J. Sel. Top. Quantum Electron. 20(2), 25–31 (2014). [CrossRef]

].

Acknowledgments

References and links

1.

K. J. Parker, M. M. Doyley, and D. J. Rubens, “Imaging the elastic properties of tissue: the 20 year perspective,” Phys. Med. Biol. 56(1), R1–R29 (2011). [CrossRef] [PubMed]

2.

J. F. Greenleaf, M. Fatemi, and M. Insana, “Selected methods for imaging elastic properties of biological tissues,” Annu. Rev. Biomed. Eng. 5(1), 57–78 (2003). [CrossRef] [PubMed]

3.

B. F. Kennedy, K. M. Kennedy, and D. D. Sampson, “A review of optical coherence elastography: fundamentals, techniques and prospects,” IEEE J. Sel. Top. Quantum Electron. 20(2), 272–288 (2014). [CrossRef]

4.

K. M. Kennedy, B. F. Kennedy, R. A. McLaughlin, and D. D. Sampson, “Needle optical coherence elastography for tissue boundary detection,” Opt. Lett. 37(12), 2310–2312 (2012). [CrossRef] [PubMed]

5.

S. J. Kirkpatrick, R. K. Wang, and D. D. Duncan, “OCT-based elastography for large and small deformations,” Opt. Express 14(24), 11585–11597 (2006). [CrossRef] [PubMed]

6.

X. Liang, V. Crecea, and S. A. Boppart, “Dynamic optical coherence elastography: a review,” J. Innov. Opt. Health Sci. 3(4), 221–233 (2010). [CrossRef] [PubMed]

7.

R. Muthupillai, D. J. Lomas, P. J. Rossman, J. F. Greenleaf, A. Manduca, and R. L. Ehman, “Magnetic resonance elastography by direct visualization of propagating acoustic strain waves,” Science 269(5232), 1854–1857 (1995). [CrossRef] [PubMed]

8.

V. Dutt, R. R. Kinnick, R. Muthupillai, T. E. Oliphant, R. L. Ehman, and J. F. Greenleaf, “Acoustic shear-wave imaging using echo ultrasound compared to magnetic resonance elastography,” Ultrasound Med. Biol. 26(3), 397–403 (2000). [CrossRef] [PubMed]

9.

Q. C. C. Chan, G. Li, R. L. Ehman, R. C. Grimm, R. Li, and E. S. Yang, “Needle shear wave driver for magnetic resonance elastography,” Magn. Reson. Med. 55(5), 1175–1179 (2006). [CrossRef] [PubMed]

10.

M. Orescanin and M. Insana, “Shear modulus estimation with vibrating needle stimulation,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 57(6), 1358–1367 (2010). [CrossRef] [PubMed]

11.

K. Nightingale, “Acoustic radiation force impulse (ARFI) imaging: a review,” Curr. Med. Imaging Rev. 7(4), 328–339 (2011). [CrossRef] [PubMed]

12.

X. Liang and S. A. Boppart, “Biomechanical properties of in vivo human skin from dynamic optical coherence elastography,” IEEE Trans. Biomed. Eng. 57(4), 953–959 (2010). [CrossRef] [PubMed]

13.

R. Manapuram, S. Aglyamov, F. M. Menodiado, M. Mashiatulla, S. Wang, S. A. Baranov, J. Li, S. Emelianov, and K. V. Larin, “Estimation of shear wave velocity in gelatin phantoms utilizing PhS-SSOCT,” Laser Phys. 22(9), 1439–1444 (2012). [CrossRef]

14.

C. Li, G. Guan, X. Cheng, Z. Huang, and R. K. Wang, “Quantitative elastography provided by surface acoustic waves measured by phase-sensitive optical coherence tomography,” Opt. Lett. 37(4), 722–724 (2012). [CrossRef] [PubMed]

15.

S. Song, Z. Huang, and R. K. Wang, “Tracking mechanical wave propagation within tissue using phase-sensitive optical coherence tomography: motion artifact and its compensation,” J. Biomed. Opt. 18(12), 121505 (2013). [CrossRef] [PubMed]

16.

M. Razani, A. Mariampillai, C. Sun, T. W. H. Luk, V. X. D. Yang, and M. C. Kolios, “Feasibility of optical coherence elastography measurements of shear wave propagation in homogeneous tissue equivalent phantoms,” Biomed. Opt. Express 3(5), 972–980 (2012). [CrossRef] [PubMed]

17.

W. Qi, R. Chen, L. Chou, G. Liu, J. Zhang, Q. Zhou, and Z. Chen, “Phase-resolved acoustic radiation force optical coherence elastography,” J. Biomed. Opt. 17(11), 110505 (2012). [CrossRef] [PubMed]

18.

T.-M. Nguyen, S. Song, B. Arnal, Z. Huang, M. O’Donnell, and R. K. Wang, “Visualizing ultrasonically induced shear wave propagation using phase-sensitive optical coherence tomography for dynamic elastography,” Opt. Lett. 39(4), 838–841 (2014). [CrossRef] [PubMed]

19.

M. Razani, T. W. H. Luk, A. Mariampillai, P. Siegler, T.-R. Kiehl, M. C. Kolios, and V. X. D. Yang, “Optical coherence tomography detection of shear wave propagation in inhomogeneous tissue equivalent phantoms and ex-vivo carotid artery samples,” Biomed. Opt. Express 5(3), 895–906 (2014). [CrossRef] [PubMed]

20.

X. Liang, M. Orescanin, K. S. Toohey, M. F. Insana, and S. A. Boppart, “Acoustomotive optical coherence elastography for measuring material mechanical properties,” Opt. Lett. 34(19), 2894–2896 (2009). [CrossRef] [PubMed]

21.

S. Wang, J. Li, R. K. Manapuram, F. M. Menodiado, D. R. Ingram, M. D. Twa, A. J. Lazar, D. C. Lev, R. E. Pollock, and K. V. Larin, “Noncontact measurement of elasticity for the detection of soft-tissue tumors using phase-sensitive optical coherence tomography combined with a focused air-puff system,” Opt. Lett. 37(24), 5184–5186 (2012). [CrossRef] [PubMed]

22.

C. Li, G. Guan, F. Zhang, G. Nabi, R. K. Wang, and Z. Huang, “Laser induced surface acoustic wave combined with phase sensitive optical coherence tomography for superficial tissue characterization: a solution for practical application,” Biomed. Opt. Express 5(5), 1403–1419 (2014). [CrossRef] [PubMed]

23.

K. M. Krishnan, “Biomedical nanomagnetics: a spin through possibilities in imaging, diagnostics, and therapy,” IEEE Trans. Magn. 46(7), 2523–2558 (2010). [CrossRef] [PubMed]

24.

C. Wilhelm and F. Gazeau, “Magnetic nanoparticles: Internal probes and heaters within living cells,” J. Magn. Magn. Mater. 321(7), 671–674 (2009). [CrossRef]

25.

V. Crecea, B. W. Graf, T. Kim, G. Popescu, and S. A. Boppart, “High resolution phase-sensitive magnetomotive optical coherence microscopy for tracking magnetic microbeads and cellular mechanics,” IEEE J. Sel. Top. Quantum Electron. 20(2), 25–31 (2014). [CrossRef]

26.

A. L. Oldenburg, F. J.-J. Toublan, K. S. Suslick, A. Wei, and S. A. Boppart, “Magnetomotive contrast for in vivo optical coherence tomography,” Opt. Express 13(17), 6597–6614 (2005). [CrossRef] [PubMed]

27.

R. John, R. Rezaeipoor, S. G. Adie, E. J. Chaney, A. L. Oldenburg, M. Marjanovic, J. P. Haldar, B. P. Sutton, and S. A. Boppart, “In vivo magnetomotive optical molecular imaging using targeted magnetic nanoprobes,” Proc. Natl. Acad. Sci. U.S.A. 107(18), 8085–8090 (2010). [CrossRef] [PubMed]

28.

J. Kim, A. Ahmad, M. Marjanovic, E. J. Chaney, J. Li, J. Rasio, Z. Hubler, D. Spillman, K. S. Suslick, and S. A. Boppart, “Magnetomotive optical coherence tomography for the assessment of atherosclerotic lesions using αvβ3 integrin-targeted microspheres,” Mol. Imaging Biol. 16(1), 36–43 (2014). [CrossRef] [PubMed]

29.

J. Koo, C. Lee, H. W. Kang, Y. W. Lee, J. Kim, and J. Oh, “Pulsed magneto-motive optical coherence tomography for remote cellular imaging,” Opt. Lett. 37(17), 3714–3716 (2012). [CrossRef] [PubMed]

30.

V. Crecea, A. Ahmad, and S. A. Boppart, “Magnetomotive optical coherence elastography for microrheology of biological tissues,” J. Biomed. Opt. 18(12), 121504 (2013). [CrossRef] [PubMed]

31.

V. Crecea, A. L. Oldenburg, X. Liang, T. S. Ralston, and S. A. Boppart, “Magnetomotive nanoparticle transducers for optical rheology of viscoelastic materials,” Opt. Express 17(25), 23114–23122 (2009). [CrossRef] [PubMed]

32.

A. L. Oldenburg and S. A. Boppart, “Resonant acoustic spectroscopy of soft tissues using embedded magnetomotive nanotransducers and optical coherence tomography,” Phys. Med. Biol. 55(4), 1189–1201 (2010). [CrossRef] [PubMed]

33.

S. Song, Z. Huang, T.-M. Nguyen, E. Y. Wong, B. Arnal, M. O’Donnell, and R. K. Wang, “Shear modulus imaging by direct visualization of propagating shear waves with phase-sensitive optical coherence tomography,” J. Biomed. Opt. 18(12), 121509 (2013). [CrossRef] [PubMed]

34.

T. Deffieux, G. Montaldo, M. Tanter, and M. Fink, “Shear wave spectroscopy for in vivo quantification of human soft tissues visco-elasticity,” IEEE Trans. Med. Imaging 28(3), 313–322 (2009). [CrossRef] [PubMed]

35.

S. Chen, M. Fatemi, and J. F. Greenleaf, “Quantifying elasticity and viscosity from measurement of shear wave speed dispersion,” J. Acoust. Soc. Am. 115(6), 2781–2785 (2004). [CrossRef] [PubMed]

36.

A. L. Oldenburg, V. Crecea, S. A. Rinne, and S. A. Boppart, “Phase-resolved magnetomotive OCT for imaging nanomolar concentrations of magnetic nanoparticles in tissues,” Opt. Express 16(15), 11525–11539 (2008). [PubMed]

37.

Y. Zheng, S. Chen, W. Tan, R. Kinnick, and J. F. Greenleaf, “Detection of tissue harmonic motion induced by ultrasonic radiation force using pulse-echo ultrasound and Kalman filter,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 54(2), 290–300 (2007). [CrossRef] [PubMed]

38.

S. Chen, M. W. Urban, C. Pislaru, R. Kinnick, Y. Zheng, A. Yao, and J. F. Greenleaf, “Shearwave dispersion ultrasound vibrometry (SDUV) for measuring tissue elasticity and viscosity,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 56(1), 55–62 (2009). [CrossRef] [PubMed]

39.

Y. Yamakoshi, J. Sato, and T. Sato, “Ultrasonic imaging of internal vibration of soft tissue under forced vibration,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 37(2), 45–53 (1990). [CrossRef] [PubMed]

40.

M. Benkherourou, C. Rochas, P. Tracqui, L. Tranqui, and P. Y. Guméry, “Standardization of a method for characterizing low-concentration biogels: elastic properties of low-concentration agarose gels,” J. Biomech. Eng. 121(2), 184–187 (1999). [CrossRef] [PubMed]

41.

M. M. Nguyen, S. Zhou, J. L. Robert, V. Shamdasani, and H. Xie, “Development of oil-in-gelatin phantoms for viscoelasticity measurement in ultrasound shear wave elastography,” Ultrasound Med. Biol. 40(1), 168–176 (2014). [CrossRef] [PubMed]

42.

E. L. Madsen, J. A. Zagzebski, and G. R. Frank, “Oil-in-gelatin dispersions for use as ultrasonically tissue-mimicking materials,” Ultrasound Med. Biol. 8(3), 277–287 (1982). [CrossRef] [PubMed]

43.

J. Bercoff, M. Tanter, M. Muller, and M. Fink, “The role of viscosity in the impulse diffraction field of elastic waves induced by the acoustic radiation force,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 51(11), 1523–1536 (2004). [CrossRef] [PubMed]

44.

S. Catheline, F. Wu, and M. Fink, “A solution to diffraction biases in sonoelasticity: The acoustic impulse technique,” J. Acoust. Soc. Am. 105(5), 2941–2950 (1999). [CrossRef] [PubMed]

45.

K. Chen, A. Yao, E. E. Zheng, J. Lin, and Y. Zheng, “Shear wave dispersion ultrasound vibrometry based on a different mechanical model for soft tissue characterization,” J. Ultrasound Med. 31(12), 2001–2011 (2012). [PubMed]

46.

Y. Wang and M. F. Insana, “Viscoelastic properties of rodent mammary tumors using ultrasonic shear-wave imaging,” Ultrason. Imaging 35(2), 126–145 (2013). [CrossRef] [PubMed]

47.

T. Deffieux, J. L. Gennisson, J. Bercoff, and M. Tanter, “On the effects of reflected waves in transient shear wave elastography,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 58(10), 2032–2035 (2011). [CrossRef] [PubMed]

48.

J. Bercoff, S. Chaffai, M. Tanter, L. Sandrin, S. Catheline, M. Fink, J. L. Gennisson, and M. Meunier, “In vivo breast tumor detection using transient elastography,” Ultrasound Med. Biol. 29(10), 1387–1396 (2003). [CrossRef] [PubMed]

49.

M. W. Urban, S. Chen, and J. F. Greenleaf, “Error in estimates of tissue material properties from shear wave dispersion ultrasound vibrometry,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 56(4), 748–758 (2009). [CrossRef] [PubMed]

50.

A. Grimwood, L. Garcia, J. Bamber, J. Holmes, P. Woolliams, P. Tomlins, and Q. A. Pankhurst, “Elastographic contrast generation in optical coherence tomography from a localized shear stress,” Phys. Med. Biol. 55(18), 5515–5528 (2010). [CrossRef] [PubMed]

51.

S. Catheline, J. L. Gennisson, and M. Fink, “Measurement of elastic nonlinearity of soft solid with transient elastography,” J. Acoust. Soc. Am. 114(6), 3087–3091 (2003). [CrossRef] [PubMed]

52.

J. L. Gennisson, S. Catheline, S. Chaffaï, and M. Fink, “Transient elastography in anisotropic medium: application to the measurement of slow and fast shear wave speeds in muscles,” J. Acoust. Soc. Am. 114(1), 536–541 (2003). [CrossRef] [PubMed]

53.

M. Evertsson, M. Cinthio, S. Fredriksson, F. Olsson, H. W. Persson, and T. Jansson, “Frequency- and phase-sensitive magnetomotive ultrasound imaging of superparamagnetic iron oxide nanoparticles,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 60(3), 481–491 (2013). [CrossRef] [PubMed]

54.

V. I. Shubayev, T. R. Pisanic 2nd, and S. Jin, “Magnetic nanoparticles for theragnostics,” Adv. Drug Deliv. Rev. 61(6), 467–477 (2009). [CrossRef] [PubMed]

55.

J. Vappou, C. Maleke, and E. E. Konofagou, “Quantitative viscoelastic parameters measured by harmonic motion imaging,” Phys. Med. Biol. 54(11), 3579–3594 (2009). [CrossRef] [PubMed]

56.

R. W. Chan and M. L. Rodriguez, “A simple-shear rheometer for linear viscoelastic characterization of vocal fold tissues at phonatory frequencies,” J. Acoust. Soc. Am. 124(2), 1207–1219 (2008). [CrossRef] [PubMed]

OCIS Codes
(110.4500) Imaging systems : Optical coherence tomography
(260.2110) Physical optics : Electromagnetic optics
(350.0350) Other areas of optics : Other areas of optics
(350.5030) Other areas of optics : Phase
(170.6935) Medical optics and biotechnology : Tissue characterization

ToC Category:
Optical Coherence Tomography

History
Original Manuscript: May 9, 2014
Revised Manuscript: June 9, 2014
Manuscript Accepted: June 11, 2014
Published: June 18, 2014

Citation
Adeel Ahmad, Jongsik Kim, Nahil A. Sobh, Nathan D. Shemonski, and Stephen A. Boppart, "Magnetomotive optical coherence elastography using magnetic particles to induce mechanical waves," Biomed. Opt. Express 5, 2349-2361 (2014)
http://www.opticsinfobase.org/boe/abstract.cfm?URI=boe-5-7-2349


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References

  1. K. J. Parker, M. M. Doyley, and D. J. Rubens, “Imaging the elastic properties of tissue: the 20 year perspective,” Phys. Med. Biol.56(1), R1–R29 (2011). [CrossRef] [PubMed]
  2. J. F. Greenleaf, M. Fatemi, and M. Insana, “Selected methods for imaging elastic properties of biological tissues,” Annu. Rev. Biomed. Eng.5(1), 57–78 (2003). [CrossRef] [PubMed]
  3. B. F. Kennedy, K. M. Kennedy, and D. D. Sampson, “A review of optical coherence elastography: fundamentals, techniques and prospects,” IEEE J. Sel. Top. Quantum Electron.20(2), 272–288 (2014). [CrossRef]
  4. K. M. Kennedy, B. F. Kennedy, R. A. McLaughlin, and D. D. Sampson, “Needle optical coherence elastography for tissue boundary detection,” Opt. Lett.37(12), 2310–2312 (2012). [CrossRef] [PubMed]
  5. S. J. Kirkpatrick, R. K. Wang, and D. D. Duncan, “OCT-based elastography for large and small deformations,” Opt. Express14(24), 11585–11597 (2006). [CrossRef] [PubMed]
  6. X. Liang, V. Crecea, and S. A. Boppart, “Dynamic optical coherence elastography: a review,” J. Innov. Opt. Health Sci.3(4), 221–233 (2010). [CrossRef] [PubMed]
  7. R. Muthupillai, D. J. Lomas, P. J. Rossman, J. F. Greenleaf, A. Manduca, and R. L. Ehman, “Magnetic resonance elastography by direct visualization of propagating acoustic strain waves,” Science269(5232), 1854–1857 (1995). [CrossRef] [PubMed]
  8. V. Dutt, R. R. Kinnick, R. Muthupillai, T. E. Oliphant, R. L. Ehman, and J. F. Greenleaf, “Acoustic shear-wave imaging using echo ultrasound compared to magnetic resonance elastography,” Ultrasound Med. Biol.26(3), 397–403 (2000). [CrossRef] [PubMed]
  9. Q. C. C. Chan, G. Li, R. L. Ehman, R. C. Grimm, R. Li, and E. S. Yang, “Needle shear wave driver for magnetic resonance elastography,” Magn. Reson. Med.55(5), 1175–1179 (2006). [CrossRef] [PubMed]
  10. M. Orescanin and M. Insana, “Shear modulus estimation with vibrating needle stimulation,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control57(6), 1358–1367 (2010). [CrossRef] [PubMed]
  11. K. Nightingale, “Acoustic radiation force impulse (ARFI) imaging: a review,” Curr. Med. Imaging Rev.7(4), 328–339 (2011). [CrossRef] [PubMed]
  12. X. Liang and S. A. Boppart, “Biomechanical properties of in vivo human skin from dynamic optical coherence elastography,” IEEE Trans. Biomed. Eng.57(4), 953–959 (2010). [CrossRef] [PubMed]
  13. R. Manapuram, S. Aglyamov, F. M. Menodiado, M. Mashiatulla, S. Wang, S. A. Baranov, J. Li, S. Emelianov, and K. V. Larin, “Estimation of shear wave velocity in gelatin phantoms utilizing PhS-SSOCT,” Laser Phys.22(9), 1439–1444 (2012). [CrossRef]
  14. C. Li, G. Guan, X. Cheng, Z. Huang, and R. K. Wang, “Quantitative elastography provided by surface acoustic waves measured by phase-sensitive optical coherence tomography,” Opt. Lett.37(4), 722–724 (2012). [CrossRef] [PubMed]
  15. S. Song, Z. Huang, and R. K. Wang, “Tracking mechanical wave propagation within tissue using phase-sensitive optical coherence tomography: motion artifact and its compensation,” J. Biomed. Opt.18(12), 121505 (2013). [CrossRef] [PubMed]
  16. M. Razani, A. Mariampillai, C. Sun, T. W. H. Luk, V. X. D. Yang, and M. C. Kolios, “Feasibility of optical coherence elastography measurements of shear wave propagation in homogeneous tissue equivalent phantoms,” Biomed. Opt. Express3(5), 972–980 (2012). [CrossRef] [PubMed]
  17. W. Qi, R. Chen, L. Chou, G. Liu, J. Zhang, Q. Zhou, and Z. Chen, “Phase-resolved acoustic radiation force optical coherence elastography,” J. Biomed. Opt.17(11), 110505 (2012). [CrossRef] [PubMed]
  18. T.-M. Nguyen, S. Song, B. Arnal, Z. Huang, M. O’Donnell, and R. K. Wang, “Visualizing ultrasonically induced shear wave propagation using phase-sensitive optical coherence tomography for dynamic elastography,” Opt. Lett.39(4), 838–841 (2014). [CrossRef] [PubMed]
  19. M. Razani, T. W. H. Luk, A. Mariampillai, P. Siegler, T.-R. Kiehl, M. C. Kolios, and V. X. D. Yang, “Optical coherence tomography detection of shear wave propagation in inhomogeneous tissue equivalent phantoms and ex-vivo carotid artery samples,” Biomed. Opt. Express5(3), 895–906 (2014). [CrossRef] [PubMed]
  20. X. Liang, M. Orescanin, K. S. Toohey, M. F. Insana, and S. A. Boppart, “Acoustomotive optical coherence elastography for measuring material mechanical properties,” Opt. Lett.34(19), 2894–2896 (2009). [CrossRef] [PubMed]
  21. S. Wang, J. Li, R. K. Manapuram, F. M. Menodiado, D. R. Ingram, M. D. Twa, A. J. Lazar, D. C. Lev, R. E. Pollock, and K. V. Larin, “Noncontact measurement of elasticity for the detection of soft-tissue tumors using phase-sensitive optical coherence tomography combined with a focused air-puff system,” Opt. Lett.37(24), 5184–5186 (2012). [CrossRef] [PubMed]
  22. C. Li, G. Guan, F. Zhang, G. Nabi, R. K. Wang, and Z. Huang, “Laser induced surface acoustic wave combined with phase sensitive optical coherence tomography for superficial tissue characterization: a solution for practical application,” Biomed. Opt. Express5(5), 1403–1419 (2014). [CrossRef] [PubMed]
  23. K. M. Krishnan, “Biomedical nanomagnetics: a spin through possibilities in imaging, diagnostics, and therapy,” IEEE Trans. Magn.46(7), 2523–2558 (2010). [CrossRef] [PubMed]
  24. C. Wilhelm and F. Gazeau, “Magnetic nanoparticles: Internal probes and heaters within living cells,” J. Magn. Magn. Mater.321(7), 671–674 (2009). [CrossRef]
  25. V. Crecea, B. W. Graf, T. Kim, G. Popescu, and S. A. Boppart, “High resolution phase-sensitive magnetomotive optical coherence microscopy for tracking magnetic microbeads and cellular mechanics,” IEEE J. Sel. Top. Quantum Electron.20(2), 25–31 (2014). [CrossRef]
  26. A. L. Oldenburg, F. J.-J. Toublan, K. S. Suslick, A. Wei, and S. A. Boppart, “Magnetomotive contrast for in vivo optical coherence tomography,” Opt. Express13(17), 6597–6614 (2005). [CrossRef] [PubMed]
  27. R. John, R. Rezaeipoor, S. G. Adie, E. J. Chaney, A. L. Oldenburg, M. Marjanovic, J. P. Haldar, B. P. Sutton, and S. A. Boppart, “In vivo magnetomotive optical molecular imaging using targeted magnetic nanoprobes,” Proc. Natl. Acad. Sci. U.S.A.107(18), 8085–8090 (2010). [CrossRef] [PubMed]
  28. J. Kim, A. Ahmad, M. Marjanovic, E. J. Chaney, J. Li, J. Rasio, Z. Hubler, D. Spillman, K. S. Suslick, and S. A. Boppart, “Magnetomotive optical coherence tomography for the assessment of atherosclerotic lesions using αvβ3 integrin-targeted microspheres,” Mol. Imaging Biol.16(1), 36–43 (2014). [CrossRef] [PubMed]
  29. J. Koo, C. Lee, H. W. Kang, Y. W. Lee, J. Kim, and J. Oh, “Pulsed magneto-motive optical coherence tomography for remote cellular imaging,” Opt. Lett.37(17), 3714–3716 (2012). [CrossRef] [PubMed]
  30. V. Crecea, A. Ahmad, and S. A. Boppart, “Magnetomotive optical coherence elastography for microrheology of biological tissues,” J. Biomed. Opt.18(12), 121504 (2013). [CrossRef] [PubMed]
  31. V. Crecea, A. L. Oldenburg, X. Liang, T. S. Ralston, and S. A. Boppart, “Magnetomotive nanoparticle transducers for optical rheology of viscoelastic materials,” Opt. Express17(25), 23114–23122 (2009). [CrossRef] [PubMed]
  32. A. L. Oldenburg and S. A. Boppart, “Resonant acoustic spectroscopy of soft tissues using embedded magnetomotive nanotransducers and optical coherence tomography,” Phys. Med. Biol.55(4), 1189–1201 (2010). [CrossRef] [PubMed]
  33. S. Song, Z. Huang, T.-M. Nguyen, E. Y. Wong, B. Arnal, M. O’Donnell, and R. K. Wang, “Shear modulus imaging by direct visualization of propagating shear waves with phase-sensitive optical coherence tomography,” J. Biomed. Opt.18(12), 121509 (2013). [CrossRef] [PubMed]
  34. T. Deffieux, G. Montaldo, M. Tanter, and M. Fink, “Shear wave spectroscopy for in vivo quantification of human soft tissues visco-elasticity,” IEEE Trans. Med. Imaging28(3), 313–322 (2009). [CrossRef] [PubMed]
  35. S. Chen, M. Fatemi, and J. F. Greenleaf, “Quantifying elasticity and viscosity from measurement of shear wave speed dispersion,” J. Acoust. Soc. Am.115(6), 2781–2785 (2004). [CrossRef] [PubMed]
  36. A. L. Oldenburg, V. Crecea, S. A. Rinne, and S. A. Boppart, “Phase-resolved magnetomotive OCT for imaging nanomolar concentrations of magnetic nanoparticles in tissues,” Opt. Express16(15), 11525–11539 (2008). [PubMed]
  37. Y. Zheng, S. Chen, W. Tan, R. Kinnick, and J. F. Greenleaf, “Detection of tissue harmonic motion induced by ultrasonic radiation force using pulse-echo ultrasound and Kalman filter,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control54(2), 290–300 (2007). [CrossRef] [PubMed]
  38. S. Chen, M. W. Urban, C. Pislaru, R. Kinnick, Y. Zheng, A. Yao, and J. F. Greenleaf, “Shearwave dispersion ultrasound vibrometry (SDUV) for measuring tissue elasticity and viscosity,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control56(1), 55–62 (2009). [CrossRef] [PubMed]
  39. Y. Yamakoshi, J. Sato, and T. Sato, “Ultrasonic imaging of internal vibration of soft tissue under forced vibration,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control37(2), 45–53 (1990). [CrossRef] [PubMed]
  40. M. Benkherourou, C. Rochas, P. Tracqui, L. Tranqui, and P. Y. Guméry, “Standardization of a method for characterizing low-concentration biogels: elastic properties of low-concentration agarose gels,” J. Biomech. Eng.121(2), 184–187 (1999). [CrossRef] [PubMed]
  41. M. M. Nguyen, S. Zhou, J. L. Robert, V. Shamdasani, and H. Xie, “Development of oil-in-gelatin phantoms for viscoelasticity measurement in ultrasound shear wave elastography,” Ultrasound Med. Biol.40(1), 168–176 (2014). [CrossRef] [PubMed]
  42. E. L. Madsen, J. A. Zagzebski, and G. R. Frank, “Oil-in-gelatin dispersions for use as ultrasonically tissue-mimicking materials,” Ultrasound Med. Biol.8(3), 277–287 (1982). [CrossRef] [PubMed]
  43. J. Bercoff, M. Tanter, M. Muller, and M. Fink, “The role of viscosity in the impulse diffraction field of elastic waves induced by the acoustic radiation force,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control51(11), 1523–1536 (2004). [CrossRef] [PubMed]
  44. S. Catheline, F. Wu, and M. Fink, “A solution to diffraction biases in sonoelasticity: The acoustic impulse technique,” J. Acoust. Soc. Am.105(5), 2941–2950 (1999). [CrossRef] [PubMed]
  45. K. Chen, A. Yao, E. E. Zheng, J. Lin, and Y. Zheng, “Shear wave dispersion ultrasound vibrometry based on a different mechanical model for soft tissue characterization,” J. Ultrasound Med.31(12), 2001–2011 (2012). [PubMed]
  46. Y. Wang and M. F. Insana, “Viscoelastic properties of rodent mammary tumors using ultrasonic shear-wave imaging,” Ultrason. Imaging35(2), 126–145 (2013). [CrossRef] [PubMed]
  47. T. Deffieux, J. L. Gennisson, J. Bercoff, and M. Tanter, “On the effects of reflected waves in transient shear wave elastography,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control58(10), 2032–2035 (2011). [CrossRef] [PubMed]
  48. J. Bercoff, S. Chaffai, M. Tanter, L. Sandrin, S. Catheline, M. Fink, J. L. Gennisson, and M. Meunier, “In vivo breast tumor detection using transient elastography,” Ultrasound Med. Biol.29(10), 1387–1396 (2003). [CrossRef] [PubMed]
  49. M. W. Urban, S. Chen, and J. F. Greenleaf, “Error in estimates of tissue material properties from shear wave dispersion ultrasound vibrometry,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control56(4), 748–758 (2009). [CrossRef] [PubMed]
  50. A. Grimwood, L. Garcia, J. Bamber, J. Holmes, P. Woolliams, P. Tomlins, and Q. A. Pankhurst, “Elastographic contrast generation in optical coherence tomography from a localized shear stress,” Phys. Med. Biol.55(18), 5515–5528 (2010). [CrossRef] [PubMed]
  51. S. Catheline, J. L. Gennisson, and M. Fink, “Measurement of elastic nonlinearity of soft solid with transient elastography,” J. Acoust. Soc. Am.114(6), 3087–3091 (2003). [CrossRef] [PubMed]
  52. J. L. Gennisson, S. Catheline, S. Chaffaï, and M. Fink, “Transient elastography in anisotropic medium: application to the measurement of slow and fast shear wave speeds in muscles,” J. Acoust. Soc. Am.114(1), 536–541 (2003). [CrossRef] [PubMed]
  53. M. Evertsson, M. Cinthio, S. Fredriksson, F. Olsson, H. W. Persson, and T. Jansson, “Frequency- and phase-sensitive magnetomotive ultrasound imaging of superparamagnetic iron oxide nanoparticles,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control60(3), 481–491 (2013). [CrossRef] [PubMed]
  54. V. I. Shubayev, T. R. Pisanic, and S. Jin, “Magnetic nanoparticles for theragnostics,” Adv. Drug Deliv. Rev.61(6), 467–477 (2009). [CrossRef] [PubMed]
  55. J. Vappou, C. Maleke, and E. E. Konofagou, “Quantitative viscoelastic parameters measured by harmonic motion imaging,” Phys. Med. Biol.54(11), 3579–3594 (2009). [CrossRef] [PubMed]
  56. R. W. Chan and M. L. Rodriguez, “A simple-shear rheometer for linear viscoelastic characterization of vocal fold tissues at phonatory frequencies,” J. Acoust. Soc. Am.124(2), 1207–1219 (2008). [CrossRef] [PubMed]

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