Abstract

Molecularly-specific contrast can greatly enhance the biomedical utility of optical coherence tomography (OCT). We describe a contrast mechanism, magnetomotive OCT (MMOCT), where a modulated magnetic field induces motion of magnetic nanoparticles. The motion of the nanoparticles modifies the amplitude of the OCT interferogram. High specificity is achieved by subtracting the background fluctuations of the specimen, and sensitivity to 220 μg/g magnetite nanoparticles is demonstrated. Optically and mechanically correct tissue phantoms elucidate the relationships between imaging contrast and nanoparticle concentration, imaging depth, tissue optical scattering, and magnetic field strength. MMOCT is demonstrated in a living Xenopus laevis tadpole where the results were consistent with corresponding histology.

© 2005 Optical Society of America

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Appl. Opt. (1)

Cancer Sci. (1)

S. Hamaguchi, I. Tohnai, A. Ito, K. Mitsudo, T. Shigetomi, M. Ito, H. Honda, T. Kobayashi, and M. Ueda, �??Selective hyperthermia using magnetoliposomes to target cervical lymph node metastasis in a rabbit tongue tumor model,�?? Cancer Sci. 94, 834 (2003).
[CrossRef] [PubMed]

CLEO 2003 (1)

A. L. Oldenburg, J. R. Gunther, F. Jean-Jacques Toublan, D. L. Marks, K. S. Suslick, and S. A. Boppart, "Selective OCT imaging of cells using magnetically-modulated optical contrast agents," in Proceedings of the Conference on Lasers and Electro-Optics, pp. 405-406 (2003).

J. Biomed. Opt. (3)

T. L Troy and S. N. Thennadil, "Optical properties of human skin in the near infrared wavelength range of 1000 to 2200 nm," J. Biomed. Opt. 6, 167 (2001).
[CrossRef] [PubMed]

J. M. Schmitt, "Restoration of optical coherence images of living tissue using the CLEAN algorithm," J. Biomed. Opt. 3, 66 (1998).
[CrossRef]

M. Pircher, E. Gotzinger, R. Leitgeb, A. F. Fercher, and C. K. Hitzenberger, "Speckle reduction in optical coherence tomography by frequency compounding," J. Biomed. Opt. 8, 565 (2003).
[CrossRef] [PubMed]

J. Chromatogr. A (1)

H. Watarai and M. Namba, "Capillary magnetophoresis of human blood cells and their magnetophoretic trapping in a flow system," J. Chromatogr. A 961, 3 (2002).
[CrossRef] [PubMed]

Mol. Imaging (1)

A. S. Arbab, G. T. Yocum, L. B. Wilson, A. Parwana, E. K. Jordan, H. Kalish, and J. A. Frank, "Comparison of transfection agents in forming complexes with ferumoxides, cell labeling efficiency, and cellular viability," Mol. Imaging 3, 24 (2004).
[CrossRef] [PubMed]

N. Engl. J. Med. (1)

M. G. Harisinghani, J. Barentsz, P. F. Hahn, W. M. Deserno, S. Tabatabaei, C. Hulsbergen van de Kaa, J. de la Rosette, and R. Weissleder, "Noninvasive detection of clinically occult lymph-node metastases in prostate cancer," N. Engl. J. Med. 348, 2491 (2003).
[CrossRef] [PubMed]

Opt. Express (3)

Opt. Lett. (10)

C. Yang, M. A. Choma, L. E. Lamb, J. D. Simon, and J. A. Izatt, "Protein-based molecular contrast optical coherence tomography with phytochrome as the contrast agent," Opt. Lett. 29, 1396 (2004).
[CrossRef] [PubMed]

C. Xu, J. Ye, D. L. Marks, and S. A. Boppart, "Near-infrared dyes as contrast-enhancing agents for spectroscopic optical coherence tomography," Opt. Lett. 29, 1647 (2004).
[CrossRef] [PubMed]

C. Yang, L. E. L. McGuckin, J. D. Simon, M. A. Choma, B. E. Applegate, and J. A. Izatt, "Spectral triangulation molecular contrast optical coherence tomography with indocyanine green as the contrast agent," Opt. Lett. 29, 2016 (2004).
[CrossRef] [PubMed]

J. S. Bredfeldt, C. Vinegoni, D. L. Marks, and S. A. Boppart, "Molecularly sensitive optical coherence tomography," Opt. Lett. 30, 495 (2005).
[CrossRef] [PubMed]

A. L. Oldenburg, J. R. Gunther, and S. A. Boppart, "Imaging magnetically labeled cells with magnetomotive optical coherence tomography," Opt. Lett. 30, 747 (2005).
[CrossRef] [PubMed]

U. Morgner, W. Drexler, F. X. Kartner, X. D. Li, C. Pitris, E. P. Ippen, and J. G. Fujimoto, "Spectroscopic optical coherence tomography," Opt. Lett. 25, 111 (2000).
[CrossRef]

Y. Jiang, I. Tornov, Y. Wang, and Z. Chen, "Second-harmonic optical coherence tomography," Opt. Lett. 29, 1090 (2004).
[CrossRef] [PubMed]

K. D. Rao, M. A. Choma, S. Yazdanfar, A. M. Rollins, and J. A. Izatt, "Molecular contrast in optical coherence tomography by use of a pump-probe technique," Opt. Lett. 28, 340 (2003).
[CrossRef] [PubMed]

D. J. Faber, E. G. Mik, M. C. G. Aalders, and T. G. van Leeuwen, "Light absorption of (oxy-)hemoglobin assessed by spectroscopic optical coherence tomography," Opt. Lett. 28, 1436 (2003).
[CrossRef] [PubMed]

T.-M. Lee, A. L. Oldenburg, S. Sitafalwalla, D. L. Marks, W. Luo, F. Jean-Jacques Toublan, K. S. Suslick, and S. A. Boppart, "Engineered microsphere contrast agents for optical coherence tomography," Opt. Lett. 28, 1546 (2003).
[CrossRef] [PubMed]

Phys. Rev. Lett. (1)

D. L. Marks and S. A. Boppart, "Nonlinear interferometric vibrational imaging," Phys. Rev. Lett. 92, 123905 (2004).
[CrossRef] [PubMed]

Science (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178 (1991).
[CrossRef] [PubMed]

Syst. Biol. (1)

D. C. Cannatella and R. O. De Sa, "Xenopus laevis as a model organism," Syst. Biol. 42, 476 (1993).
[CrossRef]

Technol. Cancer Res. Treat (1)

C. Loo, A. Lin, L. Hirsch, M.-H. Lee, J. Barton, N. Halas, J. West, and R. Drezek, "Nanoshell-enabled photonics-based imaging and therapy of cancer," Technol. Cancer Res. Treat. 3, 33 (2004).
[PubMed]

Other (4)

S. Palmacci and L. Josephson, "Synthesis of polysaccharaide covered superparamagnetic oxide colloids," United States Patent #5,262,176 (1993).

J. W. Goodman, Statistical Optics (John Wiley & Sons, 1985).

U. Hafeli, W. Schutt, J. Teller, and M. Zborowski, Scientific and Clinical Applications of Magnetic Carriers (Plenum Press, 1997).

G. Bernardini, M. Prati, E. Boneti, and G. Scari, Atlas of Xenopus Development (Springer, 1999).

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Figures (10)

Fig. 1.
Fig. 1.

Diagram of the MMOCT system. Synchronization of image acquisition in x and z with the modulation of the magnetic field B is illustrated in the timing diagram (lower left inset).

Fig. 2.
Fig. 2.

Mechanics of MMOCT. Upper left: Closeup of MMOCT image (20 × 15 μm) of a tissue phantom (ρ=0.93 mg/g), inset a larger view (110 × 90 μm). Upper right: Histogram of Δaon/off values from phantom image in linear (left) and log (right) scales as indicated by the arrows. Lower panels: Log histograms of lateral (Δx) and axial (Δz) displacements from above image.

Fig 3.
Fig 3.

Magnetic field dependence of Δamm2 in tissue phantoms. Triangles: ρ~1.2 mg/g. Squares: ρ~0.77 mg/g. Circles: ρ=0.45 mg/g. The best fits to the model are plotted as dotted lines.

Fig 4.
Fig 4.

Magnetic nanoparticle concentration dependence of Δamm2 in homogenous tissue phantoms. At each concentration, 4 or more images were acquired in different locations. The mean and standard deviation of the image-averaged Δamm2 is plotted.

Fig. 5.
Fig. 5.

Depth-dependent functions Δamm2 , s, fB , and the fB2s2 prediction of Δamm2 are indicated, as averaged laterally across a tissue phantom MMOCT image (ρ=0.93 mg/g). All functions have been scaled separately for the purposes of comparison.

Fig. 6.
Fig. 6.

Scatter plot of fs2 versus s for image sets acquired in tissue phantoms at four concentrations. Black: ρ=5.4 mg/g, red: ρ=2.6 mg/g, green: ρ=0.93 mg/g, and blue: ρ=0.45 mg/g. The associated best fit lines which were fit to data points above the apparent “knee” are drawn.

Fig. 7.
Fig. 7.

Depth-dependence of Δamm2, Daoff , and Smm for a representative image of a tissue phantom (ρ=0.93 mg/g). Daoff and Δamm2 are plotted on a linear scale and are scaled separately for the purposes of comparison (their relative strengths may be determined by Smm ).

Fig. 8.
Fig. 8.

MMOCT images of magnetic nanoparticle-exposed Xenopus laevis tadpole in a single sagittal plane. Approximate image locations are referenced against a microscopy image of a different tadpole of the same age. Points of interest (a-d) are discussed in the text. Scale bars indicate structural OCT (red) and MMOCT (green) scaling displayed in the images.

Fig. 9.
Fig. 9.

MMOCT images of magnetic nanoparticle-exposed Xenopus laevis tadpole in sagittal planes displaced as shown qualitatively against a microscopy image of a different tadpole of the same age. Points of interest (e-g) are discussed in the text. Color scales are identical to those used in Fig. 9.

Fig. 10.
Fig. 10.

Histological slices of a control tadpole (top row), and the magnetite-exposed tadpole (bottom row) from Figs. 8–9. Left column: 1.6 × 1.1 mm images of the tadpole digestive tract illustrating bordering melanophores (both) and ingested magnetic nanoparticles (bottom). Right column: 110 × 110 μm magnified regions of dark particles illustrating melanin (top) and magnetic nanoparticles (bottom) which are distinguished by a Prussian blue-stained halo.

Tables (1)

Tables Icon

Table 1: Magnetic nanoparticle concentration-dependence ρ of the image-averaged values of Smm (shown as S in table), the t-value, and the number of images necessary to achieve the desired sensitivity.

Equations (13)

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( a off ( t + Δ t ) a off ( t ) ) 2 = D a off ( Δ t ) = 2 ( a off 2 ¯ Γ a off ( Δ t ) )
( a on ( t + 2 Δ t ) a off ( t + Δ t ) ) 2 = ( a off ( t + 2 Δ t ) + a mm a off ( t + Δ t ) ) 2 Δ a mm 2 ¯ + D a off ( Δ t )
S mm = 10 log ( ( a on ( t + 2 Δ t ) a off ( t + Δ t ) ) 2 + δ 2 ( a off ( t + Δ t ) a off ( t ) ) 2 + δ 2 ) 10 log ( Δ a mm 2 D a off ( Δ t ) + 1 )
Δ a mm ( r ) = f { s ( r ) , B ( r ) , ρ ( r ) , m pp ( χ m , M sat , V , H c ) , Med ( E ( r ) , η ( r ) ) , b ( r ) }
f s ( s ( r ) ) · f B ( B ( r ) ) · f ρ ( ρ ( r ) ) · f e ( r )
F P = V ( χ p χ med ) B 2 2 μ 0 , M P M sat
F p = VM sat B , M med M p = M sat
Δ z = d ( F tot d 2 E ) = ρF p d 2 E
Δ a mm ( r p , z p ; r 0 , z d ) 2 a 0 ( ( r p r 0 ) · Δ r p w 0 2 + 4 ln 2 ( z p z d ) Δ z p l c 2 ) e ( r p r 0 w 0 ) 2 4 ln 2 ( z p z d l c ) 2
Δ a max = 2 a 0 Δ r p 2 w 0 2 + 4 ln 2 Δ z p 2 l c 2 = 2 a 0 ξ
Δ a mm = f s · f B · f ρ · f e
s n s B n B ρ n ρ
Δ a mm 2 = ( a on ( t + 2 Δ t ) a off ( t + Δ t ) ) 2 ( a off ( t + Δ t ) a off ( t ) ) 2

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