Abstract

In this work, a system is developed for tracking the skin layer to which a needle-free jet injection of fluid has penetrated by incorporating a laser beam into the jet, and measuring the diffuse light emitted from skin tissue. Monitoring the injection in this way offers the ability to improve the reliability of drug delivery with this transdermal delivery method. A laser beam, axially aligned with a jet of fluid, created a distribution of diffuse light around the injection site that varied as the injection progressed. High-speed videography was used to capture the diffuse light emission from laser-coupled jet injections into samples of porcine skin, fat, and muscle. The injection produced a distribution of diffuse light around the injection site that varied as the injection descended. A classifier, trained to distinguish whether the light source was located in the fat or muscle from surface intensity profile measurements, correctly identified the injected layer in ${97.2}{\%}$ of the cases when cross-examined against estimates using the light distribution emitted from the side of the sample.

© 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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References

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  1. S. Mitragotri, “Current status and future prospects of needle-free liquid jet injectors,” Nat. Rev. Drug Discovery 5(7), 543–548 (2006).
    [Crossref]
  2. J. Schramm-Baxter and S. Mitragotri, “Needle-free jet injections: Dependence of jet penetration and dispersion in the skin on jet power,” J. Controlled Release 97(3), 527–535 (2004).
    [Crossref]
  3. J. C. Thow, A. B. Johnson, G. Fulcher, and P. D. Home, “Different absorption of isophane (NPH) insulin from subcutaneous and intramuscular sites suggests a need to reassess recommended insulin injection technique,” Diabetic Med. 7(7), 600–602 (1990).
    [Crossref]
  4. J. Schramm-Baxter, J. Katrencik, and S. Mitragotri, “Jet injection into polyacrylamide gels: Investigation of jet injection mechanics,” J. Biomech. 37(8), 1181–1188 (2004).
    [Crossref]
  5. J. Baxter and S. Mitragotri, “Needle-free liquid jet injections: mechanisms and applications,” Expert Rev. Med. Devices 3(5), 565–574 (2006).
    [Crossref]
  6. E. L. Giudice and J. D. Campbell, “Needle-free vaccine delivery,” Adv. Drug Delivery Rev. 58(1), 68–89 (2006).
    [Crossref]
  7. T. Farrell, M. S. Patterson, and B. C. Wilson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19(4), 879–888 (1992).
    [Crossref]
  8. J. S. Dam, P. E. Andersen, T. Dalgaard, and P. E. Fabricius, “Determination of tissue optical properties from diffuse reflectance profiles by multivariate calibration,” Appl. Opt. 37(4), 772–778 (1998).
    [Crossref]
  9. A. Kienle, L. Lilge, M. S. Patterson, R. Hibst, R. Steiner, and B. C. Wilson, “Spatially resolved absolute diffuse reflectance measurements for noninvasive determination of the optical scattering and absorption coefficients of biological tissue,” Appl. Opt. 35(13), 2304–2314 (1996).
    [Crossref]
  10. B. W. Rice, M. D. Cable, and M. B. Nelson, “In vivo imaging of light-emitting probes,” J. Biomed. Opt. 6(4), 432 (2001).
    [Crossref]
  11. M. Sharma, R. Hennessy, M. K. Markey, and J. W. Tunnell, “Verification of a two-layer inverse Monte Carlo absorption model using multiple source-detector separation diffuse reflectance spectroscopy,” Biomed. Opt. Express 5(1), 40–53 (2014).
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    [Crossref]
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  14. D. C. Comsa, T. J. Farrell, and M. S. Patterson, “Bioluminescence imaging of point sources implanted in small animals post mortem: Evaluation of a method for estimating source strength and depth,” Phys. Med. Biol. 52(17), 5415–5428 (2007).
    [Crossref]
  15. A. Kim, M. Roy, F. N. Dadani, and B. C. Wilson, “Topographic mapping of subsurface fluorescent structures in tissue using multiwavelength excitation,” J. Biomed. Opt. 15(6), 066026 (2010).
    [Crossref]
  16. K. A. Brennan, D. A. N. Kulasingham, P. M. F. Nielsen, A. J. Taberner, and B. P. Ruddy, “High-speed light source depth estimation using spatially-resolved diffuse imaging,” J. Opt. 21(1), 015604 (2019).
    [Crossref]
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  18. K. A. Brennan, B. P. Ruddy, P. M. F. Nielsen, and A. J. Taberner, “High-speed depth estimation of needle-free jet injection using spatially-resolved diffuse imaging,” Submitt. to J. Biophotonics (2019).
  19. J. Baxter and S. Mitragotri, “Jet-induced skin puncture and its impact on needle-free jet injections: Experimental studies and a predictive model,” J. Controlled Release 106(3), 361–373 (2005).
    [Crossref]
  20. T. P. Sullivan, W. H. Eaglstein, S. C. Davis, and x P. Mertz, “The pig as a model for human wound healing,” Wound Repair Regen. 9(2), 66–76 (2001).
    [Crossref]
  21. J. Schramm and S. Mitragotri, “Transdermal drug delivery by jet injectors: energetics of jet formation and penetration,” Pharm. Res. 19(11), 1673–1679 (2002).
    [Crossref]

2019 (1)

K. A. Brennan, D. A. N. Kulasingham, P. M. F. Nielsen, A. J. Taberner, and B. P. Ruddy, “High-speed light source depth estimation using spatially-resolved diffuse imaging,” J. Opt. 21(1), 015604 (2019).
[Crossref]

2014 (1)

2011 (1)

2010 (1)

A. Kim, M. Roy, F. N. Dadani, and B. C. Wilson, “Topographic mapping of subsurface fluorescent structures in tissue using multiwavelength excitation,” J. Biomed. Opt. 15(6), 066026 (2010).
[Crossref]

2007 (1)

D. C. Comsa, T. J. Farrell, and M. S. Patterson, “Bioluminescence imaging of point sources implanted in small animals post mortem: Evaluation of a method for estimating source strength and depth,” Phys. Med. Biol. 52(17), 5415–5428 (2007).
[Crossref]

2006 (3)

S. Mitragotri, “Current status and future prospects of needle-free liquid jet injectors,” Nat. Rev. Drug Discovery 5(7), 543–548 (2006).
[Crossref]

J. Baxter and S. Mitragotri, “Needle-free liquid jet injections: mechanisms and applications,” Expert Rev. Med. Devices 3(5), 565–574 (2006).
[Crossref]

E. L. Giudice and J. D. Campbell, “Needle-free vaccine delivery,” Adv. Drug Delivery Rev. 58(1), 68–89 (2006).
[Crossref]

2005 (1)

J. Baxter and S. Mitragotri, “Jet-induced skin puncture and its impact on needle-free jet injections: Experimental studies and a predictive model,” J. Controlled Release 106(3), 361–373 (2005).
[Crossref]

2004 (2)

J. Schramm-Baxter, J. Katrencik, and S. Mitragotri, “Jet injection into polyacrylamide gels: Investigation of jet injection mechanics,” J. Biomech. 37(8), 1181–1188 (2004).
[Crossref]

J. Schramm-Baxter and S. Mitragotri, “Needle-free jet injections: Dependence of jet penetration and dispersion in the skin on jet power,” J. Controlled Release 97(3), 527–535 (2004).
[Crossref]

2002 (1)

J. Schramm and S. Mitragotri, “Transdermal drug delivery by jet injectors: energetics of jet formation and penetration,” Pharm. Res. 19(11), 1673–1679 (2002).
[Crossref]

2001 (2)

B. W. Rice, M. D. Cable, and M. B. Nelson, “In vivo imaging of light-emitting probes,” J. Biomed. Opt. 6(4), 432 (2001).
[Crossref]

T. P. Sullivan, W. H. Eaglstein, S. C. Davis, and x P. Mertz, “The pig as a model for human wound healing,” Wound Repair Regen. 9(2), 66–76 (2001).
[Crossref]

1998 (1)

1996 (1)

1992 (1)

T. Farrell, M. S. Patterson, and B. C. Wilson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19(4), 879–888 (1992).
[Crossref]

1990 (1)

J. C. Thow, A. B. Johnson, G. Fulcher, and P. D. Home, “Different absorption of isophane (NPH) insulin from subcutaneous and intramuscular sites suggests a need to reassess recommended insulin injection technique,” Diabetic Med. 7(7), 600–602 (1990).
[Crossref]

Andersen, P. E.

Baxter, J.

J. Baxter and S. Mitragotri, “Needle-free liquid jet injections: mechanisms and applications,” Expert Rev. Med. Devices 3(5), 565–574 (2006).
[Crossref]

J. Baxter and S. Mitragotri, “Jet-induced skin puncture and its impact on needle-free jet injections: Experimental studies and a predictive model,” J. Controlled Release 106(3), 361–373 (2005).
[Crossref]

Brennan, K.

K. Brennan, P. M. F. Nielsen, B. P. Ruddy, and A. J. Taberner, High speed, spatially-resolved diffuse imaging for jet injection depth estimation, in Dynamics and Fluctuations in Biomedical Photonics XV, vol. 10493V. V. Tuchin, K. V. Larin, M. J. Leahy, and R. K. Wang, eds. (SPIE, 2018), p. 66.

Brennan, K. A.

K. A. Brennan, D. A. N. Kulasingham, P. M. F. Nielsen, A. J. Taberner, and B. P. Ruddy, “High-speed light source depth estimation using spatially-resolved diffuse imaging,” J. Opt. 21(1), 015604 (2019).
[Crossref]

K. A. Brennan, B. P. Ruddy, P. M. F. Nielsen, and A. J. Taberner, “High-speed depth estimation of needle-free jet injection using spatially-resolved diffuse imaging,” Submitt. to J. Biophotonics (2019).

Cable, M. D.

B. W. Rice, M. D. Cable, and M. B. Nelson, “In vivo imaging of light-emitting probes,” J. Biomed. Opt. 6(4), 432 (2001).
[Crossref]

Campbell, J. D.

E. L. Giudice and J. D. Campbell, “Needle-free vaccine delivery,” Adv. Drug Delivery Rev. 58(1), 68–89 (2006).
[Crossref]

Chen, C.-Y.

Comsa, D. C.

D. C. Comsa, T. J. Farrell, and M. S. Patterson, “Bioluminescence imaging of point sources implanted in small animals post mortem: Evaluation of a method for estimating source strength and depth,” Phys. Med. Biol. 52(17), 5415–5428 (2007).
[Crossref]

Coquoz, O.

O. Coquoz, T. L. Troy, D. Jekic-McMullen, and B. W. Rice, Determination of depth of in vivo bioluminescent signals using spectral imaging techniques, in Genetically Engineered and Optical Probes for Biomedical Applications (International Society for Optics and Photonics, 2003), pp. 37–45

Dadani, F. N.

A. Kim, M. Roy, F. N. Dadani, and B. C. Wilson, “Topographic mapping of subsurface fluorescent structures in tissue using multiwavelength excitation,” J. Biomed. Opt. 15(6), 066026 (2010).
[Crossref]

Dalgaard, T.

Dam, J. S.

Davis, S. C.

T. P. Sullivan, W. H. Eaglstein, S. C. Davis, and x P. Mertz, “The pig as a model for human wound healing,” Wound Repair Regen. 9(2), 66–76 (2001).
[Crossref]

Eaglstein, W. H.

T. P. Sullivan, W. H. Eaglstein, S. C. Davis, and x P. Mertz, “The pig as a model for human wound healing,” Wound Repair Regen. 9(2), 66–76 (2001).
[Crossref]

Fabricius, P. E.

Farrell, T.

T. Farrell, M. S. Patterson, and B. C. Wilson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19(4), 879–888 (1992).
[Crossref]

Farrell, T. J.

D. C. Comsa, T. J. Farrell, and M. S. Patterson, “Bioluminescence imaging of point sources implanted in small animals post mortem: Evaluation of a method for estimating source strength and depth,” Phys. Med. Biol. 52(17), 5415–5428 (2007).
[Crossref]

Fulcher, G.

J. C. Thow, A. B. Johnson, G. Fulcher, and P. D. Home, “Different absorption of isophane (NPH) insulin from subcutaneous and intramuscular sites suggests a need to reassess recommended insulin injection technique,” Diabetic Med. 7(7), 600–602 (1990).
[Crossref]

Giudice, E. L.

E. L. Giudice and J. D. Campbell, “Needle-free vaccine delivery,” Adv. Drug Delivery Rev. 58(1), 68–89 (2006).
[Crossref]

Hennessy, R.

Hibst, R.

Home, P. D.

J. C. Thow, A. B. Johnson, G. Fulcher, and P. D. Home, “Different absorption of isophane (NPH) insulin from subcutaneous and intramuscular sites suggests a need to reassess recommended insulin injection technique,” Diabetic Med. 7(7), 600–602 (1990).
[Crossref]

Jekic-McMullen, D.

O. Coquoz, T. L. Troy, D. Jekic-McMullen, and B. W. Rice, Determination of depth of in vivo bioluminescent signals using spectral imaging techniques, in Genetically Engineered and Optical Probes for Biomedical Applications (International Society for Optics and Photonics, 2003), pp. 37–45

Johnson, A. B.

J. C. Thow, A. B. Johnson, G. Fulcher, and P. D. Home, “Different absorption of isophane (NPH) insulin from subcutaneous and intramuscular sites suggests a need to reassess recommended insulin injection technique,” Diabetic Med. 7(7), 600–602 (1990).
[Crossref]

Katrencik, J.

J. Schramm-Baxter, J. Katrencik, and S. Mitragotri, “Jet injection into polyacrylamide gels: Investigation of jet injection mechanics,” J. Biomech. 37(8), 1181–1188 (2004).
[Crossref]

Kienle, A.

Kim, A.

A. Kim, M. Roy, F. N. Dadani, and B. C. Wilson, “Topographic mapping of subsurface fluorescent structures in tissue using multiwavelength excitation,” J. Biomed. Opt. 15(6), 066026 (2010).
[Crossref]

Kulasingham, D. A. N.

K. A. Brennan, D. A. N. Kulasingham, P. M. F. Nielsen, A. J. Taberner, and B. P. Ruddy, “High-speed light source depth estimation using spatially-resolved diffuse imaging,” J. Opt. 21(1), 015604 (2019).
[Crossref]

Li, Y.-S.

Lilge, L.

Markey, M. K.

Mertz, P.

T. P. Sullivan, W. H. Eaglstein, S. C. Davis, and x P. Mertz, “The pig as a model for human wound healing,” Wound Repair Regen. 9(2), 66–76 (2001).
[Crossref]

Mitragotri, S.

S. Mitragotri, “Current status and future prospects of needle-free liquid jet injectors,” Nat. Rev. Drug Discovery 5(7), 543–548 (2006).
[Crossref]

J. Baxter and S. Mitragotri, “Needle-free liquid jet injections: mechanisms and applications,” Expert Rev. Med. Devices 3(5), 565–574 (2006).
[Crossref]

J. Baxter and S. Mitragotri, “Jet-induced skin puncture and its impact on needle-free jet injections: Experimental studies and a predictive model,” J. Controlled Release 106(3), 361–373 (2005).
[Crossref]

J. Schramm-Baxter and S. Mitragotri, “Needle-free jet injections: Dependence of jet penetration and dispersion in the skin on jet power,” J. Controlled Release 97(3), 527–535 (2004).
[Crossref]

J. Schramm-Baxter, J. Katrencik, and S. Mitragotri, “Jet injection into polyacrylamide gels: Investigation of jet injection mechanics,” J. Biomech. 37(8), 1181–1188 (2004).
[Crossref]

J. Schramm and S. Mitragotri, “Transdermal drug delivery by jet injectors: energetics of jet formation and penetration,” Pharm. Res. 19(11), 1673–1679 (2002).
[Crossref]

Nelson, M. B.

B. W. Rice, M. D. Cable, and M. B. Nelson, “In vivo imaging of light-emitting probes,” J. Biomed. Opt. 6(4), 432 (2001).
[Crossref]

Nielsen, P. M. F.

K. A. Brennan, D. A. N. Kulasingham, P. M. F. Nielsen, A. J. Taberner, and B. P. Ruddy, “High-speed light source depth estimation using spatially-resolved diffuse imaging,” J. Opt. 21(1), 015604 (2019).
[Crossref]

K. Brennan, P. M. F. Nielsen, B. P. Ruddy, and A. J. Taberner, High speed, spatially-resolved diffuse imaging for jet injection depth estimation, in Dynamics and Fluctuations in Biomedical Photonics XV, vol. 10493V. V. Tuchin, K. V. Larin, M. J. Leahy, and R. K. Wang, eds. (SPIE, 2018), p. 66.

K. A. Brennan, B. P. Ruddy, P. M. F. Nielsen, and A. J. Taberner, “High-speed depth estimation of needle-free jet injection using spatially-resolved diffuse imaging,” Submitt. to J. Biophotonics (2019).

Patterson, M. S.

D. C. Comsa, T. J. Farrell, and M. S. Patterson, “Bioluminescence imaging of point sources implanted in small animals post mortem: Evaluation of a method for estimating source strength and depth,” Phys. Med. Biol. 52(17), 5415–5428 (2007).
[Crossref]

A. Kienle, L. Lilge, M. S. Patterson, R. Hibst, R. Steiner, and B. C. Wilson, “Spatially resolved absolute diffuse reflectance measurements for noninvasive determination of the optical scattering and absorption coefficients of biological tissue,” Appl. Opt. 35(13), 2304–2314 (1996).
[Crossref]

T. Farrell, M. S. Patterson, and B. C. Wilson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19(4), 879–888 (1992).
[Crossref]

Rice, B. W.

B. W. Rice, M. D. Cable, and M. B. Nelson, “In vivo imaging of light-emitting probes,” J. Biomed. Opt. 6(4), 432 (2001).
[Crossref]

O. Coquoz, T. L. Troy, D. Jekic-McMullen, and B. W. Rice, Determination of depth of in vivo bioluminescent signals using spectral imaging techniques, in Genetically Engineered and Optical Probes for Biomedical Applications (International Society for Optics and Photonics, 2003), pp. 37–45

Roy, M.

A. Kim, M. Roy, F. N. Dadani, and B. C. Wilson, “Topographic mapping of subsurface fluorescent structures in tissue using multiwavelength excitation,” J. Biomed. Opt. 15(6), 066026 (2010).
[Crossref]

Ruddy, B. P.

K. A. Brennan, D. A. N. Kulasingham, P. M. F. Nielsen, A. J. Taberner, and B. P. Ruddy, “High-speed light source depth estimation using spatially-resolved diffuse imaging,” J. Opt. 21(1), 015604 (2019).
[Crossref]

K. A. Brennan, B. P. Ruddy, P. M. F. Nielsen, and A. J. Taberner, “High-speed depth estimation of needle-free jet injection using spatially-resolved diffuse imaging,” Submitt. to J. Biophotonics (2019).

K. Brennan, P. M. F. Nielsen, B. P. Ruddy, and A. J. Taberner, High speed, spatially-resolved diffuse imaging for jet injection depth estimation, in Dynamics and Fluctuations in Biomedical Photonics XV, vol. 10493V. V. Tuchin, K. V. Larin, M. J. Leahy, and R. K. Wang, eds. (SPIE, 2018), p. 66.

Schramm, J.

J. Schramm and S. Mitragotri, “Transdermal drug delivery by jet injectors: energetics of jet formation and penetration,” Pharm. Res. 19(11), 1673–1679 (2002).
[Crossref]

Schramm-Baxter, J.

J. Schramm-Baxter and S. Mitragotri, “Needle-free jet injections: Dependence of jet penetration and dispersion in the skin on jet power,” J. Controlled Release 97(3), 527–535 (2004).
[Crossref]

J. Schramm-Baxter, J. Katrencik, and S. Mitragotri, “Jet injection into polyacrylamide gels: Investigation of jet injection mechanics,” J. Biomech. 37(8), 1181–1188 (2004).
[Crossref]

Sharma, M.

Steiner, R.

Sullivan, T. P.

T. P. Sullivan, W. H. Eaglstein, S. C. Davis, and x P. Mertz, “The pig as a model for human wound healing,” Wound Repair Regen. 9(2), 66–76 (2001).
[Crossref]

Sung, K.-B.

Taberner, A. J.

K. A. Brennan, D. A. N. Kulasingham, P. M. F. Nielsen, A. J. Taberner, and B. P. Ruddy, “High-speed light source depth estimation using spatially-resolved diffuse imaging,” J. Opt. 21(1), 015604 (2019).
[Crossref]

K. Brennan, P. M. F. Nielsen, B. P. Ruddy, and A. J. Taberner, High speed, spatially-resolved diffuse imaging for jet injection depth estimation, in Dynamics and Fluctuations in Biomedical Photonics XV, vol. 10493V. V. Tuchin, K. V. Larin, M. J. Leahy, and R. K. Wang, eds. (SPIE, 2018), p. 66.

K. A. Brennan, B. P. Ruddy, P. M. F. Nielsen, and A. J. Taberner, “High-speed depth estimation of needle-free jet injection using spatially-resolved diffuse imaging,” Submitt. to J. Biophotonics (2019).

Thow, J. C.

J. C. Thow, A. B. Johnson, G. Fulcher, and P. D. Home, “Different absorption of isophane (NPH) insulin from subcutaneous and intramuscular sites suggests a need to reassess recommended insulin injection technique,” Diabetic Med. 7(7), 600–602 (1990).
[Crossref]

Troy, T. L.

O. Coquoz, T. L. Troy, D. Jekic-McMullen, and B. W. Rice, Determination of depth of in vivo bioluminescent signals using spectral imaging techniques, in Genetically Engineered and Optical Probes for Biomedical Applications (International Society for Optics and Photonics, 2003), pp. 37–45

Tseng, T.-Y.

Tunnell, J. W.

Wilson, B. C.

A. Kim, M. Roy, F. N. Dadani, and B. C. Wilson, “Topographic mapping of subsurface fluorescent structures in tissue using multiwavelength excitation,” J. Biomed. Opt. 15(6), 066026 (2010).
[Crossref]

A. Kienle, L. Lilge, M. S. Patterson, R. Hibst, R. Steiner, and B. C. Wilson, “Spatially resolved absolute diffuse reflectance measurements for noninvasive determination of the optical scattering and absorption coefficients of biological tissue,” Appl. Opt. 35(13), 2304–2314 (1996).
[Crossref]

T. Farrell, M. S. Patterson, and B. C. Wilson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19(4), 879–888 (1992).
[Crossref]

Adv. Drug Delivery Rev. (1)

E. L. Giudice and J. D. Campbell, “Needle-free vaccine delivery,” Adv. Drug Delivery Rev. 58(1), 68–89 (2006).
[Crossref]

Appl. Opt. (2)

Biomed. Opt. Express (2)

Diabetic Med. (1)

J. C. Thow, A. B. Johnson, G. Fulcher, and P. D. Home, “Different absorption of isophane (NPH) insulin from subcutaneous and intramuscular sites suggests a need to reassess recommended insulin injection technique,” Diabetic Med. 7(7), 600–602 (1990).
[Crossref]

Expert Rev. Med. Devices (1)

J. Baxter and S. Mitragotri, “Needle-free liquid jet injections: mechanisms and applications,” Expert Rev. Med. Devices 3(5), 565–574 (2006).
[Crossref]

J. Biomech. (1)

J. Schramm-Baxter, J. Katrencik, and S. Mitragotri, “Jet injection into polyacrylamide gels: Investigation of jet injection mechanics,” J. Biomech. 37(8), 1181–1188 (2004).
[Crossref]

J. Biomed. Opt. (2)

B. W. Rice, M. D. Cable, and M. B. Nelson, “In vivo imaging of light-emitting probes,” J. Biomed. Opt. 6(4), 432 (2001).
[Crossref]

A. Kim, M. Roy, F. N. Dadani, and B. C. Wilson, “Topographic mapping of subsurface fluorescent structures in tissue using multiwavelength excitation,” J. Biomed. Opt. 15(6), 066026 (2010).
[Crossref]

J. Controlled Release (2)

J. Schramm-Baxter and S. Mitragotri, “Needle-free jet injections: Dependence of jet penetration and dispersion in the skin on jet power,” J. Controlled Release 97(3), 527–535 (2004).
[Crossref]

J. Baxter and S. Mitragotri, “Jet-induced skin puncture and its impact on needle-free jet injections: Experimental studies and a predictive model,” J. Controlled Release 106(3), 361–373 (2005).
[Crossref]

J. Opt. (1)

K. A. Brennan, D. A. N. Kulasingham, P. M. F. Nielsen, A. J. Taberner, and B. P. Ruddy, “High-speed light source depth estimation using spatially-resolved diffuse imaging,” J. Opt. 21(1), 015604 (2019).
[Crossref]

Med. Phys. (1)

T. Farrell, M. S. Patterson, and B. C. Wilson, “A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19(4), 879–888 (1992).
[Crossref]

Nat. Rev. Drug Discovery (1)

S. Mitragotri, “Current status and future prospects of needle-free liquid jet injectors,” Nat. Rev. Drug Discovery 5(7), 543–548 (2006).
[Crossref]

Pharm. Res. (1)

J. Schramm and S. Mitragotri, “Transdermal drug delivery by jet injectors: energetics of jet formation and penetration,” Pharm. Res. 19(11), 1673–1679 (2002).
[Crossref]

Phys. Med. Biol. (1)

D. C. Comsa, T. J. Farrell, and M. S. Patterson, “Bioluminescence imaging of point sources implanted in small animals post mortem: Evaluation of a method for estimating source strength and depth,” Phys. Med. Biol. 52(17), 5415–5428 (2007).
[Crossref]

Wound Repair Regen. (1)

T. P. Sullivan, W. H. Eaglstein, S. C. Davis, and x P. Mertz, “The pig as a model for human wound healing,” Wound Repair Regen. 9(2), 66–76 (2001).
[Crossref]

Other (3)

O. Coquoz, T. L. Troy, D. Jekic-McMullen, and B. W. Rice, Determination of depth of in vivo bioluminescent signals using spectral imaging techniques, in Genetically Engineered and Optical Probes for Biomedical Applications (International Society for Optics and Photonics, 2003), pp. 37–45

K. Brennan, P. M. F. Nielsen, B. P. Ruddy, and A. J. Taberner, High speed, spatially-resolved diffuse imaging for jet injection depth estimation, in Dynamics and Fluctuations in Biomedical Photonics XV, vol. 10493V. V. Tuchin, K. V. Larin, M. J. Leahy, and R. K. Wang, eds. (SPIE, 2018), p. 66.

K. A. Brennan, B. P. Ruddy, P. M. F. Nielsen, and A. J. Taberner, “High-speed depth estimation of needle-free jet injection using spatially-resolved diffuse imaging,” Submitt. to J. Biophotonics (2019).

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Figures (11)

Fig. 1.
Fig. 1. Diagram of the injection system for coupling a laser into a jet of fluid as it is injected into tissue. A ${2} \,{\textrm {mm}}$ needle extends from the orifice to pierce the toughest skin layer.
Fig. 2.
Fig. 2. Diagram of the system for controlling the descent of a fiber optical light source into tissue. A optical fibre is guided into tissue through a hypodermic needle.
Fig. 3.
Fig. 3. a) Photograph of a tissue sample with the fat-muscle boundary indicated, and the corresponding view of the side distribution where the light source is approaching the boundary (false colour). b) Depth of the fat-muscle boundary (${\textrm {mm}}$) below the skin surface for ten trials of each experiment type.
Fig. 4.
Fig. 4. Diagram showing the image processing of the high-speed video frames. The surface intensity profile is measured by averaging the view of surface distribution circumferentially. The side view of the sample exhibits two modes in the light distribution. The location of the light source is tracked using the ratio of the integrated emission between the fat and muscle.
Fig. 5.
Fig. 5. Ratio of light emitted from fat and muscle for controlled-source experiments.
Fig. 6.
Fig. 6. Classification of the source layer by applying a threshold to the side light emission ratio. Successful classification is shown as blue dots, while orange cross represent incorrectly classified points. The dashed lines represents the muscle layer boundary.
Fig. 7.
Fig. 7. Representative normalized surface intensity profiles from controlled-source experiments, labeled according to whether the source was in the fat (blue) or muscle (red). The median profiles are represented as solid lines and the dotted lines represent the 95-percentile profiles.
Fig. 8.
Fig. 8. LOOCV of layer classification from the surface intensity profile of controlled-source experiments, using $k$-nearest neighbor classification. Successful classification is displayed as blue dots while orange crosses represent incorrectly classified points. The dashed line represents the depth of the muscle boundary.
Fig. 9.
Fig. 9. Post-injection X-ray images of skin, fat, and muscle samples. Trials 1 through 10 are arranged left to right, top to bottom.
Fig. 10.
Fig. 10. Muscle-fat light emission ratio, calculated over the time course of ten injections. The injections that were delivered into the muscle are represented as dashed lines. The threshold for distinguishing layer penetration from the side emission ratio is represented as the dashed horizontal line. The dotted trace indicates the nominal jet speed profile for the injections.
Fig. 11.
Fig. 11. LOOCV of distinguishing layer penetration from the surface intensity profile of jet injections, using $k$-nearest neighbor classification. Triangles represent the injections that remained in the fat and circles represent intramuscular injections. Successful classification is depicted with unfilled markers, while the unfilled markers represent incorrectly classified points. The dashed line represents the threshold on the side emission ratio used to label the data in the feature set.

Equations (5)

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I f x , z d m I ( x , z ) d x d z
I m x , d m < z 2 d m I ( x , z ) d x d z .
I m f = I m I f ,
y ¯ i = y i y 1 y i , d 0 ,
w j = | | P j p | |

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