Abstract

Tuberculosis is one of the deadliest infectious diseases worldwide. New tools to study pathogenesis and monitor subjects in pre-clinical studies to develop treatment regimens are critical for progress. We developed an improved optical system for detecting bacteria in lungs of mice using internal illumination. We present a computational optical model of the full mouse torso to characterize the optical system. Simulated theoretical limits for the lowest detectable bacterial load support the experimental improvements with an internal illumination source, and suggest that protocol improvements could further lower the detection threshold.

© 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. World Health Organization, “Global tuberculosis report 2016,” (2016).
  2. G. Sgaragli and M. Frosini, “Human Tuberculosis I. Epidemiology, Diagnosis and Pathogenetic Mechanisms,” Curr. Med. Chem. 23(25), 2836–2873 (2016).
    [Crossref]
  3. B. J. Marais, R. P. Gie, H. S. Schaaf, N. Beyers, P. R. Donald, and J. R. Starke, “Childhood Pulmonary Tuberculosis,” Am. J. Respir. Crit. Care Med. 173(10), 1078–1090 (2006).
    [Crossref]
  4. H.-J. Yang, Y. Kong, Y. Cheng, H. Janagama, H. Hassounah, H. Xie, J. Rao, and J. D. Cirillo, “Real-Time Imaging of Mycobacterium tuberculosis Using a Novel Near-Infrared Fluorescent Substrate,” J. Infect. Dis. 215(3), jiw298 (2016).
    [Crossref]
  5. Y. Kong, S. Subbian, S. L. G. Cirillo, and J. D. Cirillo, “Application of optical imaging to study of extrapulmonary spread by tuberculosis,” Tuberculosis (Oxford, U. K.) 89, S15–S17 (2009).
    [Crossref]
  6. F. Nooshabadi, H.-J. Yang, Y. Cheng, M. S. Durkee, H. Xie, J. Rao, J. D. Cirillo, and K. C. Maitland, “Intravital excitation increases detection sensitivity for pulmonary tuberculosis by whole-body imaging with β-lactamase reporter enzyme fluorescence,” J. Biophotonics 10(6-7), 821–829 (2017).
    [Crossref]
  7. M. Baker, “Whole-animal imaging: The whole picture,” Nature 463(7283), 977–979 (2010).
    [Crossref]
  8. F. Leblond, S. C. Davis, P. A. Valdés, and B. W. Pogue, “Pre-clinical whole-body fluorescence imaging: Review of instruments, methods and applications,” J. Photochem. Photobiol., B 98(1), 77–94 (2010).
    [Crossref]
  9. H. Xie, J. Mire, Y. Kong, M. Chang, H. A. Hassounah, C. N. Thornton, J. C. Sacchettini, J. D. Cirillo, and J. Rao, “Rapid point-of-care detection of the tuberculosis pathogen using a BlaC-specific fluorogenic probe,” Nat. Chem. 4(10), 802–809 (2012).
    [Crossref]
  10. F. Nooshabadi, H.-J. Yang, J. N. Bixler, Y. Kong, J. D. Cirillo, and K. C. Maitland, “Intravital fluorescence excitation in whole-animal optical imaging,” PLoS One 11(2), e0149932 (2016).
    [Crossref]
  11. M. S. Durkee, F. Nooshabadi, J. D. Cirillo, and K. C. Maitland, “Optical model of the murine lung to optimize pulmonary illumination,” J. Biomed. Opt. 23(07), 1–12 (2018).
    [Crossref]
  12. V. Tuchin, Tissue Optics: Light Scattering Methods and Instruments for Medical Diagnostics, 3 ed. (SPIE, Bellingham, Washington, USA, 2015).
  13. “LightTools Biological Materials Library,” (Synopsys, Inc., 2014).
  14. H. Bachofen and S. Schürch, “Alveolar surface forces and lung architecture,” Comp. Biochem. Physiol., Part A: Mol. Integr. Physiol. 129(1), 183–193 (2001).
    [Crossref]
  15. S. Jayaraman, Y. Song, L. Vetrivel, L. Shankar, and A. S. Verkman, “Noninvasive in vivo fluorescence measurement of airway-surface liquid depth, salt concentration, and pH,” J. Clin. Invest. 107(3), 317–324 (2001).
    [Crossref]
  16. M. S. Durkee, G. K. Fletcher, C. Carlson, K. Matheson, S. K. Swift, D. J. Maitland, J. D. Cirillo, and K. C. Maitland, “Light scattering by pulmonary alveoli and airway surface liquid using a concentric sphere model,” Opt. Lett. 43(20), 5001–5004 (2018).
    [Crossref]
  17. M. Zellweger, D. Goujon, R. Conde, M. Forrer, H. van den Bergh, and G. Wagnières, “Absolute autofluorescence spectra of human healthy, metaplastic, and early cancerous bronchial tissue in vivo,” Appl. Opt. 40(22), 3784–3791 (2001).
    [Crossref]
  18. R. N. Day and M. W. Davidson, “The fluorescent protein palette: tools for cellular imaging,” Chem. Soc. Rev. 38(10), 2887–2921 (2009).
    [Crossref]
  19. N. Soundrarajan, H.-s. Cho, B. Ahn, M. Choi, L. M. Thong, H. Choi, S.-Y. Cha, J.-H. Kim, C.-K. Park, K. Seo, and C. Park, “Green fluorescent protein as a scaffold for high efficiency production of functional bacteriotoxic proteins in Escherichia coli,” Sci. Rep. 6(1), 20661 (2016).
    [Crossref]
  20. N. Mufti, Y. Kong, J. D. Cirillo, and K. C. Maitland, “Fiber optic microendoscopy for preclinical study of bacterial infection dynamics,” Biomed. Opt. Express 2(5), 1121–1134 (2011).
    [Crossref]
  21. P. J. Dodd, C. Sismanidis, and J. A. Seddon, “Global burden of drug-resistant tuberculosis in children: a mathematical modelling study,” Lancet Infect. Dis. 16(10), 1193–1201 (2016).
    [Crossref]
  22. D. S. Armstrong, “In Celebration of Expectoration,” Am. J. Respir. Crit. Care Med. 168(12), 1412–1413 (2003).
    [Crossref]

2018 (2)

2017 (1)

F. Nooshabadi, H.-J. Yang, Y. Cheng, M. S. Durkee, H. Xie, J. Rao, J. D. Cirillo, and K. C. Maitland, “Intravital excitation increases detection sensitivity for pulmonary tuberculosis by whole-body imaging with β-lactamase reporter enzyme fluorescence,” J. Biophotonics 10(6-7), 821–829 (2017).
[Crossref]

2016 (5)

F. Nooshabadi, H.-J. Yang, J. N. Bixler, Y. Kong, J. D. Cirillo, and K. C. Maitland, “Intravital fluorescence excitation in whole-animal optical imaging,” PLoS One 11(2), e0149932 (2016).
[Crossref]

G. Sgaragli and M. Frosini, “Human Tuberculosis I. Epidemiology, Diagnosis and Pathogenetic Mechanisms,” Curr. Med. Chem. 23(25), 2836–2873 (2016).
[Crossref]

H.-J. Yang, Y. Kong, Y. Cheng, H. Janagama, H. Hassounah, H. Xie, J. Rao, and J. D. Cirillo, “Real-Time Imaging of Mycobacterium tuberculosis Using a Novel Near-Infrared Fluorescent Substrate,” J. Infect. Dis. 215(3), jiw298 (2016).
[Crossref]

N. Soundrarajan, H.-s. Cho, B. Ahn, M. Choi, L. M. Thong, H. Choi, S.-Y. Cha, J.-H. Kim, C.-K. Park, K. Seo, and C. Park, “Green fluorescent protein as a scaffold for high efficiency production of functional bacteriotoxic proteins in Escherichia coli,” Sci. Rep. 6(1), 20661 (2016).
[Crossref]

P. J. Dodd, C. Sismanidis, and J. A. Seddon, “Global burden of drug-resistant tuberculosis in children: a mathematical modelling study,” Lancet Infect. Dis. 16(10), 1193–1201 (2016).
[Crossref]

2012 (1)

H. Xie, J. Mire, Y. Kong, M. Chang, H. A. Hassounah, C. N. Thornton, J. C. Sacchettini, J. D. Cirillo, and J. Rao, “Rapid point-of-care detection of the tuberculosis pathogen using a BlaC-specific fluorogenic probe,” Nat. Chem. 4(10), 802–809 (2012).
[Crossref]

2011 (1)

2010 (2)

M. Baker, “Whole-animal imaging: The whole picture,” Nature 463(7283), 977–979 (2010).
[Crossref]

F. Leblond, S. C. Davis, P. A. Valdés, and B. W. Pogue, “Pre-clinical whole-body fluorescence imaging: Review of instruments, methods and applications,” J. Photochem. Photobiol., B 98(1), 77–94 (2010).
[Crossref]

2009 (2)

Y. Kong, S. Subbian, S. L. G. Cirillo, and J. D. Cirillo, “Application of optical imaging to study of extrapulmonary spread by tuberculosis,” Tuberculosis (Oxford, U. K.) 89, S15–S17 (2009).
[Crossref]

R. N. Day and M. W. Davidson, “The fluorescent protein palette: tools for cellular imaging,” Chem. Soc. Rev. 38(10), 2887–2921 (2009).
[Crossref]

2006 (1)

B. J. Marais, R. P. Gie, H. S. Schaaf, N. Beyers, P. R. Donald, and J. R. Starke, “Childhood Pulmonary Tuberculosis,” Am. J. Respir. Crit. Care Med. 173(10), 1078–1090 (2006).
[Crossref]

2003 (1)

D. S. Armstrong, “In Celebration of Expectoration,” Am. J. Respir. Crit. Care Med. 168(12), 1412–1413 (2003).
[Crossref]

2001 (3)

M. Zellweger, D. Goujon, R. Conde, M. Forrer, H. van den Bergh, and G. Wagnières, “Absolute autofluorescence spectra of human healthy, metaplastic, and early cancerous bronchial tissue in vivo,” Appl. Opt. 40(22), 3784–3791 (2001).
[Crossref]

H. Bachofen and S. Schürch, “Alveolar surface forces and lung architecture,” Comp. Biochem. Physiol., Part A: Mol. Integr. Physiol. 129(1), 183–193 (2001).
[Crossref]

S. Jayaraman, Y. Song, L. Vetrivel, L. Shankar, and A. S. Verkman, “Noninvasive in vivo fluorescence measurement of airway-surface liquid depth, salt concentration, and pH,” J. Clin. Invest. 107(3), 317–324 (2001).
[Crossref]

Ahn, B.

N. Soundrarajan, H.-s. Cho, B. Ahn, M. Choi, L. M. Thong, H. Choi, S.-Y. Cha, J.-H. Kim, C.-K. Park, K. Seo, and C. Park, “Green fluorescent protein as a scaffold for high efficiency production of functional bacteriotoxic proteins in Escherichia coli,” Sci. Rep. 6(1), 20661 (2016).
[Crossref]

Armstrong, D. S.

D. S. Armstrong, “In Celebration of Expectoration,” Am. J. Respir. Crit. Care Med. 168(12), 1412–1413 (2003).
[Crossref]

Bachofen, H.

H. Bachofen and S. Schürch, “Alveolar surface forces and lung architecture,” Comp. Biochem. Physiol., Part A: Mol. Integr. Physiol. 129(1), 183–193 (2001).
[Crossref]

Baker, M.

M. Baker, “Whole-animal imaging: The whole picture,” Nature 463(7283), 977–979 (2010).
[Crossref]

Beyers, N.

B. J. Marais, R. P. Gie, H. S. Schaaf, N. Beyers, P. R. Donald, and J. R. Starke, “Childhood Pulmonary Tuberculosis,” Am. J. Respir. Crit. Care Med. 173(10), 1078–1090 (2006).
[Crossref]

Bixler, J. N.

F. Nooshabadi, H.-J. Yang, J. N. Bixler, Y. Kong, J. D. Cirillo, and K. C. Maitland, “Intravital fluorescence excitation in whole-animal optical imaging,” PLoS One 11(2), e0149932 (2016).
[Crossref]

Carlson, C.

Cha, S.-Y.

N. Soundrarajan, H.-s. Cho, B. Ahn, M. Choi, L. M. Thong, H. Choi, S.-Y. Cha, J.-H. Kim, C.-K. Park, K. Seo, and C. Park, “Green fluorescent protein as a scaffold for high efficiency production of functional bacteriotoxic proteins in Escherichia coli,” Sci. Rep. 6(1), 20661 (2016).
[Crossref]

Chang, M.

H. Xie, J. Mire, Y. Kong, M. Chang, H. A. Hassounah, C. N. Thornton, J. C. Sacchettini, J. D. Cirillo, and J. Rao, “Rapid point-of-care detection of the tuberculosis pathogen using a BlaC-specific fluorogenic probe,” Nat. Chem. 4(10), 802–809 (2012).
[Crossref]

Cheng, Y.

F. Nooshabadi, H.-J. Yang, Y. Cheng, M. S. Durkee, H. Xie, J. Rao, J. D. Cirillo, and K. C. Maitland, “Intravital excitation increases detection sensitivity for pulmonary tuberculosis by whole-body imaging with β-lactamase reporter enzyme fluorescence,” J. Biophotonics 10(6-7), 821–829 (2017).
[Crossref]

H.-J. Yang, Y. Kong, Y. Cheng, H. Janagama, H. Hassounah, H. Xie, J. Rao, and J. D. Cirillo, “Real-Time Imaging of Mycobacterium tuberculosis Using a Novel Near-Infrared Fluorescent Substrate,” J. Infect. Dis. 215(3), jiw298 (2016).
[Crossref]

Cho, H.-s.

N. Soundrarajan, H.-s. Cho, B. Ahn, M. Choi, L. M. Thong, H. Choi, S.-Y. Cha, J.-H. Kim, C.-K. Park, K. Seo, and C. Park, “Green fluorescent protein as a scaffold for high efficiency production of functional bacteriotoxic proteins in Escherichia coli,” Sci. Rep. 6(1), 20661 (2016).
[Crossref]

Choi, H.

N. Soundrarajan, H.-s. Cho, B. Ahn, M. Choi, L. M. Thong, H. Choi, S.-Y. Cha, J.-H. Kim, C.-K. Park, K. Seo, and C. Park, “Green fluorescent protein as a scaffold for high efficiency production of functional bacteriotoxic proteins in Escherichia coli,” Sci. Rep. 6(1), 20661 (2016).
[Crossref]

Choi, M.

N. Soundrarajan, H.-s. Cho, B. Ahn, M. Choi, L. M. Thong, H. Choi, S.-Y. Cha, J.-H. Kim, C.-K. Park, K. Seo, and C. Park, “Green fluorescent protein as a scaffold for high efficiency production of functional bacteriotoxic proteins in Escherichia coli,” Sci. Rep. 6(1), 20661 (2016).
[Crossref]

Cirillo, J. D.

M. S. Durkee, F. Nooshabadi, J. D. Cirillo, and K. C. Maitland, “Optical model of the murine lung to optimize pulmonary illumination,” J. Biomed. Opt. 23(07), 1–12 (2018).
[Crossref]

M. S. Durkee, G. K. Fletcher, C. Carlson, K. Matheson, S. K. Swift, D. J. Maitland, J. D. Cirillo, and K. C. Maitland, “Light scattering by pulmonary alveoli and airway surface liquid using a concentric sphere model,” Opt. Lett. 43(20), 5001–5004 (2018).
[Crossref]

F. Nooshabadi, H.-J. Yang, Y. Cheng, M. S. Durkee, H. Xie, J. Rao, J. D. Cirillo, and K. C. Maitland, “Intravital excitation increases detection sensitivity for pulmonary tuberculosis by whole-body imaging with β-lactamase reporter enzyme fluorescence,” J. Biophotonics 10(6-7), 821–829 (2017).
[Crossref]

H.-J. Yang, Y. Kong, Y. Cheng, H. Janagama, H. Hassounah, H. Xie, J. Rao, and J. D. Cirillo, “Real-Time Imaging of Mycobacterium tuberculosis Using a Novel Near-Infrared Fluorescent Substrate,” J. Infect. Dis. 215(3), jiw298 (2016).
[Crossref]

F. Nooshabadi, H.-J. Yang, J. N. Bixler, Y. Kong, J. D. Cirillo, and K. C. Maitland, “Intravital fluorescence excitation in whole-animal optical imaging,” PLoS One 11(2), e0149932 (2016).
[Crossref]

H. Xie, J. Mire, Y. Kong, M. Chang, H. A. Hassounah, C. N. Thornton, J. C. Sacchettini, J. D. Cirillo, and J. Rao, “Rapid point-of-care detection of the tuberculosis pathogen using a BlaC-specific fluorogenic probe,” Nat. Chem. 4(10), 802–809 (2012).
[Crossref]

N. Mufti, Y. Kong, J. D. Cirillo, and K. C. Maitland, “Fiber optic microendoscopy for preclinical study of bacterial infection dynamics,” Biomed. Opt. Express 2(5), 1121–1134 (2011).
[Crossref]

Y. Kong, S. Subbian, S. L. G. Cirillo, and J. D. Cirillo, “Application of optical imaging to study of extrapulmonary spread by tuberculosis,” Tuberculosis (Oxford, U. K.) 89, S15–S17 (2009).
[Crossref]

Cirillo, S. L. G.

Y. Kong, S. Subbian, S. L. G. Cirillo, and J. D. Cirillo, “Application of optical imaging to study of extrapulmonary spread by tuberculosis,” Tuberculosis (Oxford, U. K.) 89, S15–S17 (2009).
[Crossref]

Conde, R.

Davidson, M. W.

R. N. Day and M. W. Davidson, “The fluorescent protein palette: tools for cellular imaging,” Chem. Soc. Rev. 38(10), 2887–2921 (2009).
[Crossref]

Davis, S. C.

F. Leblond, S. C. Davis, P. A. Valdés, and B. W. Pogue, “Pre-clinical whole-body fluorescence imaging: Review of instruments, methods and applications,” J. Photochem. Photobiol., B 98(1), 77–94 (2010).
[Crossref]

Day, R. N.

R. N. Day and M. W. Davidson, “The fluorescent protein palette: tools for cellular imaging,” Chem. Soc. Rev. 38(10), 2887–2921 (2009).
[Crossref]

Dodd, P. J.

P. J. Dodd, C. Sismanidis, and J. A. Seddon, “Global burden of drug-resistant tuberculosis in children: a mathematical modelling study,” Lancet Infect. Dis. 16(10), 1193–1201 (2016).
[Crossref]

Donald, P. R.

B. J. Marais, R. P. Gie, H. S. Schaaf, N. Beyers, P. R. Donald, and J. R. Starke, “Childhood Pulmonary Tuberculosis,” Am. J. Respir. Crit. Care Med. 173(10), 1078–1090 (2006).
[Crossref]

Durkee, M. S.

M. S. Durkee, F. Nooshabadi, J. D. Cirillo, and K. C. Maitland, “Optical model of the murine lung to optimize pulmonary illumination,” J. Biomed. Opt. 23(07), 1–12 (2018).
[Crossref]

M. S. Durkee, G. K. Fletcher, C. Carlson, K. Matheson, S. K. Swift, D. J. Maitland, J. D. Cirillo, and K. C. Maitland, “Light scattering by pulmonary alveoli and airway surface liquid using a concentric sphere model,” Opt. Lett. 43(20), 5001–5004 (2018).
[Crossref]

F. Nooshabadi, H.-J. Yang, Y. Cheng, M. S. Durkee, H. Xie, J. Rao, J. D. Cirillo, and K. C. Maitland, “Intravital excitation increases detection sensitivity for pulmonary tuberculosis by whole-body imaging with β-lactamase reporter enzyme fluorescence,” J. Biophotonics 10(6-7), 821–829 (2017).
[Crossref]

Fletcher, G. K.

Forrer, M.

Frosini, M.

G. Sgaragli and M. Frosini, “Human Tuberculosis I. Epidemiology, Diagnosis and Pathogenetic Mechanisms,” Curr. Med. Chem. 23(25), 2836–2873 (2016).
[Crossref]

Gie, R. P.

B. J. Marais, R. P. Gie, H. S. Schaaf, N. Beyers, P. R. Donald, and J. R. Starke, “Childhood Pulmonary Tuberculosis,” Am. J. Respir. Crit. Care Med. 173(10), 1078–1090 (2006).
[Crossref]

Goujon, D.

Hassounah, H.

H.-J. Yang, Y. Kong, Y. Cheng, H. Janagama, H. Hassounah, H. Xie, J. Rao, and J. D. Cirillo, “Real-Time Imaging of Mycobacterium tuberculosis Using a Novel Near-Infrared Fluorescent Substrate,” J. Infect. Dis. 215(3), jiw298 (2016).
[Crossref]

Hassounah, H. A.

H. Xie, J. Mire, Y. Kong, M. Chang, H. A. Hassounah, C. N. Thornton, J. C. Sacchettini, J. D. Cirillo, and J. Rao, “Rapid point-of-care detection of the tuberculosis pathogen using a BlaC-specific fluorogenic probe,” Nat. Chem. 4(10), 802–809 (2012).
[Crossref]

Janagama, H.

H.-J. Yang, Y. Kong, Y. Cheng, H. Janagama, H. Hassounah, H. Xie, J. Rao, and J. D. Cirillo, “Real-Time Imaging of Mycobacterium tuberculosis Using a Novel Near-Infrared Fluorescent Substrate,” J. Infect. Dis. 215(3), jiw298 (2016).
[Crossref]

Jayaraman, S.

S. Jayaraman, Y. Song, L. Vetrivel, L. Shankar, and A. S. Verkman, “Noninvasive in vivo fluorescence measurement of airway-surface liquid depth, salt concentration, and pH,” J. Clin. Invest. 107(3), 317–324 (2001).
[Crossref]

Kim, J.-H.

N. Soundrarajan, H.-s. Cho, B. Ahn, M. Choi, L. M. Thong, H. Choi, S.-Y. Cha, J.-H. Kim, C.-K. Park, K. Seo, and C. Park, “Green fluorescent protein as a scaffold for high efficiency production of functional bacteriotoxic proteins in Escherichia coli,” Sci. Rep. 6(1), 20661 (2016).
[Crossref]

Kong, Y.

F. Nooshabadi, H.-J. Yang, J. N. Bixler, Y. Kong, J. D. Cirillo, and K. C. Maitland, “Intravital fluorescence excitation in whole-animal optical imaging,” PLoS One 11(2), e0149932 (2016).
[Crossref]

H.-J. Yang, Y. Kong, Y. Cheng, H. Janagama, H. Hassounah, H. Xie, J. Rao, and J. D. Cirillo, “Real-Time Imaging of Mycobacterium tuberculosis Using a Novel Near-Infrared Fluorescent Substrate,” J. Infect. Dis. 215(3), jiw298 (2016).
[Crossref]

H. Xie, J. Mire, Y. Kong, M. Chang, H. A. Hassounah, C. N. Thornton, J. C. Sacchettini, J. D. Cirillo, and J. Rao, “Rapid point-of-care detection of the tuberculosis pathogen using a BlaC-specific fluorogenic probe,” Nat. Chem. 4(10), 802–809 (2012).
[Crossref]

N. Mufti, Y. Kong, J. D. Cirillo, and K. C. Maitland, “Fiber optic microendoscopy for preclinical study of bacterial infection dynamics,” Biomed. Opt. Express 2(5), 1121–1134 (2011).
[Crossref]

Y. Kong, S. Subbian, S. L. G. Cirillo, and J. D. Cirillo, “Application of optical imaging to study of extrapulmonary spread by tuberculosis,” Tuberculosis (Oxford, U. K.) 89, S15–S17 (2009).
[Crossref]

Leblond, F.

F. Leblond, S. C. Davis, P. A. Valdés, and B. W. Pogue, “Pre-clinical whole-body fluorescence imaging: Review of instruments, methods and applications,” J. Photochem. Photobiol., B 98(1), 77–94 (2010).
[Crossref]

Maitland, D. J.

Maitland, K. C.

M. S. Durkee, G. K. Fletcher, C. Carlson, K. Matheson, S. K. Swift, D. J. Maitland, J. D. Cirillo, and K. C. Maitland, “Light scattering by pulmonary alveoli and airway surface liquid using a concentric sphere model,” Opt. Lett. 43(20), 5001–5004 (2018).
[Crossref]

M. S. Durkee, F. Nooshabadi, J. D. Cirillo, and K. C. Maitland, “Optical model of the murine lung to optimize pulmonary illumination,” J. Biomed. Opt. 23(07), 1–12 (2018).
[Crossref]

F. Nooshabadi, H.-J. Yang, Y. Cheng, M. S. Durkee, H. Xie, J. Rao, J. D. Cirillo, and K. C. Maitland, “Intravital excitation increases detection sensitivity for pulmonary tuberculosis by whole-body imaging with β-lactamase reporter enzyme fluorescence,” J. Biophotonics 10(6-7), 821–829 (2017).
[Crossref]

F. Nooshabadi, H.-J. Yang, J. N. Bixler, Y. Kong, J. D. Cirillo, and K. C. Maitland, “Intravital fluorescence excitation in whole-animal optical imaging,” PLoS One 11(2), e0149932 (2016).
[Crossref]

N. Mufti, Y. Kong, J. D. Cirillo, and K. C. Maitland, “Fiber optic microendoscopy for preclinical study of bacterial infection dynamics,” Biomed. Opt. Express 2(5), 1121–1134 (2011).
[Crossref]

Marais, B. J.

B. J. Marais, R. P. Gie, H. S. Schaaf, N. Beyers, P. R. Donald, and J. R. Starke, “Childhood Pulmonary Tuberculosis,” Am. J. Respir. Crit. Care Med. 173(10), 1078–1090 (2006).
[Crossref]

Matheson, K.

Mire, J.

H. Xie, J. Mire, Y. Kong, M. Chang, H. A. Hassounah, C. N. Thornton, J. C. Sacchettini, J. D. Cirillo, and J. Rao, “Rapid point-of-care detection of the tuberculosis pathogen using a BlaC-specific fluorogenic probe,” Nat. Chem. 4(10), 802–809 (2012).
[Crossref]

Mufti, N.

Nooshabadi, F.

M. S. Durkee, F. Nooshabadi, J. D. Cirillo, and K. C. Maitland, “Optical model of the murine lung to optimize pulmonary illumination,” J. Biomed. Opt. 23(07), 1–12 (2018).
[Crossref]

F. Nooshabadi, H.-J. Yang, Y. Cheng, M. S. Durkee, H. Xie, J. Rao, J. D. Cirillo, and K. C. Maitland, “Intravital excitation increases detection sensitivity for pulmonary tuberculosis by whole-body imaging with β-lactamase reporter enzyme fluorescence,” J. Biophotonics 10(6-7), 821–829 (2017).
[Crossref]

F. Nooshabadi, H.-J. Yang, J. N. Bixler, Y. Kong, J. D. Cirillo, and K. C. Maitland, “Intravital fluorescence excitation in whole-animal optical imaging,” PLoS One 11(2), e0149932 (2016).
[Crossref]

Park, C.

N. Soundrarajan, H.-s. Cho, B. Ahn, M. Choi, L. M. Thong, H. Choi, S.-Y. Cha, J.-H. Kim, C.-K. Park, K. Seo, and C. Park, “Green fluorescent protein as a scaffold for high efficiency production of functional bacteriotoxic proteins in Escherichia coli,” Sci. Rep. 6(1), 20661 (2016).
[Crossref]

Park, C.-K.

N. Soundrarajan, H.-s. Cho, B. Ahn, M. Choi, L. M. Thong, H. Choi, S.-Y. Cha, J.-H. Kim, C.-K. Park, K. Seo, and C. Park, “Green fluorescent protein as a scaffold for high efficiency production of functional bacteriotoxic proteins in Escherichia coli,” Sci. Rep. 6(1), 20661 (2016).
[Crossref]

Pogue, B. W.

F. Leblond, S. C. Davis, P. A. Valdés, and B. W. Pogue, “Pre-clinical whole-body fluorescence imaging: Review of instruments, methods and applications,” J. Photochem. Photobiol., B 98(1), 77–94 (2010).
[Crossref]

Rao, J.

F. Nooshabadi, H.-J. Yang, Y. Cheng, M. S. Durkee, H. Xie, J. Rao, J. D. Cirillo, and K. C. Maitland, “Intravital excitation increases detection sensitivity for pulmonary tuberculosis by whole-body imaging with β-lactamase reporter enzyme fluorescence,” J. Biophotonics 10(6-7), 821–829 (2017).
[Crossref]

H.-J. Yang, Y. Kong, Y. Cheng, H. Janagama, H. Hassounah, H. Xie, J. Rao, and J. D. Cirillo, “Real-Time Imaging of Mycobacterium tuberculosis Using a Novel Near-Infrared Fluorescent Substrate,” J. Infect. Dis. 215(3), jiw298 (2016).
[Crossref]

H. Xie, J. Mire, Y. Kong, M. Chang, H. A. Hassounah, C. N. Thornton, J. C. Sacchettini, J. D. Cirillo, and J. Rao, “Rapid point-of-care detection of the tuberculosis pathogen using a BlaC-specific fluorogenic probe,” Nat. Chem. 4(10), 802–809 (2012).
[Crossref]

Sacchettini, J. C.

H. Xie, J. Mire, Y. Kong, M. Chang, H. A. Hassounah, C. N. Thornton, J. C. Sacchettini, J. D. Cirillo, and J. Rao, “Rapid point-of-care detection of the tuberculosis pathogen using a BlaC-specific fluorogenic probe,” Nat. Chem. 4(10), 802–809 (2012).
[Crossref]

Schaaf, H. S.

B. J. Marais, R. P. Gie, H. S. Schaaf, N. Beyers, P. R. Donald, and J. R. Starke, “Childhood Pulmonary Tuberculosis,” Am. J. Respir. Crit. Care Med. 173(10), 1078–1090 (2006).
[Crossref]

Schürch, S.

H. Bachofen and S. Schürch, “Alveolar surface forces and lung architecture,” Comp. Biochem. Physiol., Part A: Mol. Integr. Physiol. 129(1), 183–193 (2001).
[Crossref]

Seddon, J. A.

P. J. Dodd, C. Sismanidis, and J. A. Seddon, “Global burden of drug-resistant tuberculosis in children: a mathematical modelling study,” Lancet Infect. Dis. 16(10), 1193–1201 (2016).
[Crossref]

Seo, K.

N. Soundrarajan, H.-s. Cho, B. Ahn, M. Choi, L. M. Thong, H. Choi, S.-Y. Cha, J.-H. Kim, C.-K. Park, K. Seo, and C. Park, “Green fluorescent protein as a scaffold for high efficiency production of functional bacteriotoxic proteins in Escherichia coli,” Sci. Rep. 6(1), 20661 (2016).
[Crossref]

Sgaragli, G.

G. Sgaragli and M. Frosini, “Human Tuberculosis I. Epidemiology, Diagnosis and Pathogenetic Mechanisms,” Curr. Med. Chem. 23(25), 2836–2873 (2016).
[Crossref]

Shankar, L.

S. Jayaraman, Y. Song, L. Vetrivel, L. Shankar, and A. S. Verkman, “Noninvasive in vivo fluorescence measurement of airway-surface liquid depth, salt concentration, and pH,” J. Clin. Invest. 107(3), 317–324 (2001).
[Crossref]

Sismanidis, C.

P. J. Dodd, C. Sismanidis, and J. A. Seddon, “Global burden of drug-resistant tuberculosis in children: a mathematical modelling study,” Lancet Infect. Dis. 16(10), 1193–1201 (2016).
[Crossref]

Song, Y.

S. Jayaraman, Y. Song, L. Vetrivel, L. Shankar, and A. S. Verkman, “Noninvasive in vivo fluorescence measurement of airway-surface liquid depth, salt concentration, and pH,” J. Clin. Invest. 107(3), 317–324 (2001).
[Crossref]

Soundrarajan, N.

N. Soundrarajan, H.-s. Cho, B. Ahn, M. Choi, L. M. Thong, H. Choi, S.-Y. Cha, J.-H. Kim, C.-K. Park, K. Seo, and C. Park, “Green fluorescent protein as a scaffold for high efficiency production of functional bacteriotoxic proteins in Escherichia coli,” Sci. Rep. 6(1), 20661 (2016).
[Crossref]

Starke, J. R.

B. J. Marais, R. P. Gie, H. S. Schaaf, N. Beyers, P. R. Donald, and J. R. Starke, “Childhood Pulmonary Tuberculosis,” Am. J. Respir. Crit. Care Med. 173(10), 1078–1090 (2006).
[Crossref]

Subbian, S.

Y. Kong, S. Subbian, S. L. G. Cirillo, and J. D. Cirillo, “Application of optical imaging to study of extrapulmonary spread by tuberculosis,” Tuberculosis (Oxford, U. K.) 89, S15–S17 (2009).
[Crossref]

Swift, S. K.

Thong, L. M.

N. Soundrarajan, H.-s. Cho, B. Ahn, M. Choi, L. M. Thong, H. Choi, S.-Y. Cha, J.-H. Kim, C.-K. Park, K. Seo, and C. Park, “Green fluorescent protein as a scaffold for high efficiency production of functional bacteriotoxic proteins in Escherichia coli,” Sci. Rep. 6(1), 20661 (2016).
[Crossref]

Thornton, C. N.

H. Xie, J. Mire, Y. Kong, M. Chang, H. A. Hassounah, C. N. Thornton, J. C. Sacchettini, J. D. Cirillo, and J. Rao, “Rapid point-of-care detection of the tuberculosis pathogen using a BlaC-specific fluorogenic probe,” Nat. Chem. 4(10), 802–809 (2012).
[Crossref]

Tuchin, V.

V. Tuchin, Tissue Optics: Light Scattering Methods and Instruments for Medical Diagnostics, 3 ed. (SPIE, Bellingham, Washington, USA, 2015).

Valdés, P. A.

F. Leblond, S. C. Davis, P. A. Valdés, and B. W. Pogue, “Pre-clinical whole-body fluorescence imaging: Review of instruments, methods and applications,” J. Photochem. Photobiol., B 98(1), 77–94 (2010).
[Crossref]

van den Bergh, H.

Verkman, A. S.

S. Jayaraman, Y. Song, L. Vetrivel, L. Shankar, and A. S. Verkman, “Noninvasive in vivo fluorescence measurement of airway-surface liquid depth, salt concentration, and pH,” J. Clin. Invest. 107(3), 317–324 (2001).
[Crossref]

Vetrivel, L.

S. Jayaraman, Y. Song, L. Vetrivel, L. Shankar, and A. S. Verkman, “Noninvasive in vivo fluorescence measurement of airway-surface liquid depth, salt concentration, and pH,” J. Clin. Invest. 107(3), 317–324 (2001).
[Crossref]

Wagnières, G.

Xie, H.

F. Nooshabadi, H.-J. Yang, Y. Cheng, M. S. Durkee, H. Xie, J. Rao, J. D. Cirillo, and K. C. Maitland, “Intravital excitation increases detection sensitivity for pulmonary tuberculosis by whole-body imaging with β-lactamase reporter enzyme fluorescence,” J. Biophotonics 10(6-7), 821–829 (2017).
[Crossref]

H.-J. Yang, Y. Kong, Y. Cheng, H. Janagama, H. Hassounah, H. Xie, J. Rao, and J. D. Cirillo, “Real-Time Imaging of Mycobacterium tuberculosis Using a Novel Near-Infrared Fluorescent Substrate,” J. Infect. Dis. 215(3), jiw298 (2016).
[Crossref]

H. Xie, J. Mire, Y. Kong, M. Chang, H. A. Hassounah, C. N. Thornton, J. C. Sacchettini, J. D. Cirillo, and J. Rao, “Rapid point-of-care detection of the tuberculosis pathogen using a BlaC-specific fluorogenic probe,” Nat. Chem. 4(10), 802–809 (2012).
[Crossref]

Yang, H.-J.

F. Nooshabadi, H.-J. Yang, Y. Cheng, M. S. Durkee, H. Xie, J. Rao, J. D. Cirillo, and K. C. Maitland, “Intravital excitation increases detection sensitivity for pulmonary tuberculosis by whole-body imaging with β-lactamase reporter enzyme fluorescence,” J. Biophotonics 10(6-7), 821–829 (2017).
[Crossref]

H.-J. Yang, Y. Kong, Y. Cheng, H. Janagama, H. Hassounah, H. Xie, J. Rao, and J. D. Cirillo, “Real-Time Imaging of Mycobacterium tuberculosis Using a Novel Near-Infrared Fluorescent Substrate,” J. Infect. Dis. 215(3), jiw298 (2016).
[Crossref]

F. Nooshabadi, H.-J. Yang, J. N. Bixler, Y. Kong, J. D. Cirillo, and K. C. Maitland, “Intravital fluorescence excitation in whole-animal optical imaging,” PLoS One 11(2), e0149932 (2016).
[Crossref]

Zellweger, M.

Am. J. Respir. Crit. Care Med. (2)

B. J. Marais, R. P. Gie, H. S. Schaaf, N. Beyers, P. R. Donald, and J. R. Starke, “Childhood Pulmonary Tuberculosis,” Am. J. Respir. Crit. Care Med. 173(10), 1078–1090 (2006).
[Crossref]

D. S. Armstrong, “In Celebration of Expectoration,” Am. J. Respir. Crit. Care Med. 168(12), 1412–1413 (2003).
[Crossref]

Appl. Opt. (1)

Biomed. Opt. Express (1)

Chem. Soc. Rev. (1)

R. N. Day and M. W. Davidson, “The fluorescent protein palette: tools for cellular imaging,” Chem. Soc. Rev. 38(10), 2887–2921 (2009).
[Crossref]

Comp. Biochem. Physiol., Part A: Mol. Integr. Physiol. (1)

H. Bachofen and S. Schürch, “Alveolar surface forces and lung architecture,” Comp. Biochem. Physiol., Part A: Mol. Integr. Physiol. 129(1), 183–193 (2001).
[Crossref]

Curr. Med. Chem. (1)

G. Sgaragli and M. Frosini, “Human Tuberculosis I. Epidemiology, Diagnosis and Pathogenetic Mechanisms,” Curr. Med. Chem. 23(25), 2836–2873 (2016).
[Crossref]

J. Biomed. Opt. (1)

M. S. Durkee, F. Nooshabadi, J. D. Cirillo, and K. C. Maitland, “Optical model of the murine lung to optimize pulmonary illumination,” J. Biomed. Opt. 23(07), 1–12 (2018).
[Crossref]

J. Biophotonics (1)

F. Nooshabadi, H.-J. Yang, Y. Cheng, M. S. Durkee, H. Xie, J. Rao, J. D. Cirillo, and K. C. Maitland, “Intravital excitation increases detection sensitivity for pulmonary tuberculosis by whole-body imaging with β-lactamase reporter enzyme fluorescence,” J. Biophotonics 10(6-7), 821–829 (2017).
[Crossref]

J. Clin. Invest. (1)

S. Jayaraman, Y. Song, L. Vetrivel, L. Shankar, and A. S. Verkman, “Noninvasive in vivo fluorescence measurement of airway-surface liquid depth, salt concentration, and pH,” J. Clin. Invest. 107(3), 317–324 (2001).
[Crossref]

J. Infect. Dis. (1)

H.-J. Yang, Y. Kong, Y. Cheng, H. Janagama, H. Hassounah, H. Xie, J. Rao, and J. D. Cirillo, “Real-Time Imaging of Mycobacterium tuberculosis Using a Novel Near-Infrared Fluorescent Substrate,” J. Infect. Dis. 215(3), jiw298 (2016).
[Crossref]

J. Photochem. Photobiol., B (1)

F. Leblond, S. C. Davis, P. A. Valdés, and B. W. Pogue, “Pre-clinical whole-body fluorescence imaging: Review of instruments, methods and applications,” J. Photochem. Photobiol., B 98(1), 77–94 (2010).
[Crossref]

Lancet Infect. Dis. (1)

P. J. Dodd, C. Sismanidis, and J. A. Seddon, “Global burden of drug-resistant tuberculosis in children: a mathematical modelling study,” Lancet Infect. Dis. 16(10), 1193–1201 (2016).
[Crossref]

Nat. Chem. (1)

H. Xie, J. Mire, Y. Kong, M. Chang, H. A. Hassounah, C. N. Thornton, J. C. Sacchettini, J. D. Cirillo, and J. Rao, “Rapid point-of-care detection of the tuberculosis pathogen using a BlaC-specific fluorogenic probe,” Nat. Chem. 4(10), 802–809 (2012).
[Crossref]

Nature (1)

M. Baker, “Whole-animal imaging: The whole picture,” Nature 463(7283), 977–979 (2010).
[Crossref]

Opt. Lett. (1)

PLoS One (1)

F. Nooshabadi, H.-J. Yang, J. N. Bixler, Y. Kong, J. D. Cirillo, and K. C. Maitland, “Intravital fluorescence excitation in whole-animal optical imaging,” PLoS One 11(2), e0149932 (2016).
[Crossref]

Sci. Rep. (1)

N. Soundrarajan, H.-s. Cho, B. Ahn, M. Choi, L. M. Thong, H. Choi, S.-Y. Cha, J.-H. Kim, C.-K. Park, K. Seo, and C. Park, “Green fluorescent protein as a scaffold for high efficiency production of functional bacteriotoxic proteins in Escherichia coli,” Sci. Rep. 6(1), 20661 (2016).
[Crossref]

Tuberculosis (Oxford, U. K.) (1)

Y. Kong, S. Subbian, S. L. G. Cirillo, and J. D. Cirillo, “Application of optical imaging to study of extrapulmonary spread by tuberculosis,” Tuberculosis (Oxford, U. K.) 89, S15–S17 (2009).
[Crossref]

Other (3)

World Health Organization, “Global tuberculosis report 2016,” (2016).

V. Tuchin, Tissue Optics: Light Scattering Methods and Instruments for Medical Diagnostics, 3 ed. (SPIE, Bellingham, Washington, USA, 2015).

“LightTools Biological Materials Library,” (Synopsys, Inc., 2014).

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Figures (7)

Fig. 1.
Fig. 1. Mycobacterium tuberculosis can be optically detected using genetic modification to express a fluorescent protein (a), or via a molecular beacon probe that is sensitive to an enzyme found on mycobacteria (b). The fluorescent protein modeled is tdTomato, with an excitation peak at 535 nm and an emission peak at 585 nm (c). The reporter enzyme fluorescent probe contains IRDye 800CW that is excited and emits in the NIR (d).
Fig. 2.
Fig. 2. Methods for in vivo optical detection of Mycobacterium tuberculosis. A whole-body animal imaging system is used for external illumination and fluorescence detection with the animal in both the ventral and dorsal positions (a). Internal illumination is accomplished by incorporating a fluorescence microendoscope (ME) into the whole-body imaging system (b). Using the microendoscope for internal illumination, fluorescence is detected either using the animal imaging system (a) or internally through the fiber microendoscope (b). Separate endoscopes are used for visible and NIR fluorescence excitation. A laser diode (730 nm) or LED (535 nm) light source is passed through a collimating lens (CL) and excitation filter (EX), then reflected off of a dichroic mirror (DM) into an objective lens (OL), which focuses the beam onto the proximal end of the fiber bundle. Fluorescence collected with the fiber bundle is filtered with an emission filter (EM) and imaged with a CCD camera for internal detection.
Fig. 3.
Fig. 3. Layered mouse torso model (a) including the lung, heart, and bulk tissue layer. The optical properties of the lung parenchyma are modeled after a concentric sphere Mie model, given the alveolar and ASL structure (b). Internal illumination of the torso with the modeled ASL (c) shows that the ASL acts as a light guide to help propagate light deeper into the parenchyma compared to just the air-tissue model (d). Both (c) and (d) show the same bisection of the torso, ∼3 mm dorsal from the center of the trachea.
Fig. 4.
Fig. 4. Simulated tissue autofluorescence spectra for 535 nm (a) and 730 nm (b) excitation with spectra for bacteria fluorescence in the respective spectral regions of interest, shown on normalized scale. The relative intensity of the simulated TAF spectra in each spectral region is shown in (c).
Fig. 5.
Fig. 5. Tissue autofluorescence simulations using 535 nm (visible) and 730 nm (NIR) excitation in epi- and trans-illumination (a) and microendoscope illumination with microendoscope detection or external detection (b). External illumination simulations (a) predict a lower tissue autofluorescence signal in NIR compared to visible wavelengths, regardless of animal position or epi-/trans-illumination method. Internal illumination simulations (b) predict a higher tissue autofluorescence signal in NIR compared to visible for both animal positions.
Fig. 6.
Fig. 6. Total simulated fluorescence including TAF and bacterial signal. Dorsal detection (a, c) and ventral detection (b, d) yield different detection thresholds dependent on spectral region and illumination method. Internal detection (only simulated with internal illumination) shows a detection threshold between 102 and 103 CFU for both spectral regions (e). Simulated fluorescence values that are not significantly different from control (CFU = 0) are shaded for external illumination methods (ventral and dorsal illumination). Internal illumination detection thresholds for total simulated photon flux due to fluorescence are denoted by dotted lines.
Fig. 7.
Fig. 7. Bacterial fluorescence signal after spectral unmixing to remove TAF. Shaded regions correspond to values that are not significantly different than simulations of uninfected mice for external illumination simulations. Dotted lines correspond to the detection thresholds for internal illumination methods. For dorsal collection in the tdTomato spectral region (a), dorsal and ventral excitation yield different CFU detection thresholds (103 v. 104, respectively). For dorsal detection in the NIR (b), ventral detection in the tdTomato range (c), and ventral detection in the NIR (d), all illumination methods, including internal, showed spectrally-dependent detection thresholds (104 for tdTomato and 103 for NIR). Unmixed fluorescence for internal detection and illumination (e) also yielded spectrally-dependent results.

Tables (4)

Tables Icon

Table 1. Absorption coefficient (µa), reduced scattering coefficient (µs’), and refractive index (n) for each layer of the mouse torso model within the wavelength regions of interest.

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Table 2. Ratio of TAF signal detected with NIR excitation to TAF signal detected with visible excitation for combinations of ventral, dorsal, and internal illumination and detection.

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Table 3. Level of detection for various illumination/detection configurations.

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Table 4. Linear regressions showing correlation of fluorescence and bacterial load after spectral unmixing of bacterial signal and autofluorescence.