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Detecting small lung tumors in mouse models by refractive-index microradiology

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An Erratum to this article was published on 13 July 2011

Abstract

Refractive-index (phase-contrast) radiology was able to detect lung tumors less than 1 mm in live mice. Significant micromorphology differences were observed in the microradiographs between normal, inflamed, and lung cancer tissues. This was made possible by the high phase contrast and by the fast image taking that reduces the motion blur. The detection of cancer and inflammation areas by phase contrast microradiology and microtomography was validated by bioluminescence and histopathological analysis. The smallest tumor detected is less than 1 mm3 with accuracy better than 1 × 10−3 mm3. This level of performance is currently suitable for animal studies, while further developments are required for clinical application.

Refractive-index microradiology detects small lung cancer tumors (<1 mm) in vivo, with precise size measurements, and yields tomographically reconstructed pictures of tumors on the same scale

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References

  1. Baldwin DR (2011) Imaging in lung cancer: recent advances in PET-CT and screening. Thorax 66:275–277

    Article  Google Scholar 

  2. Van’t Westeinde SC, van Klaveren RJ (2011) Screening and early detection of lung cancer. Cancer J 17:3–10

    Article  Google Scholar 

  3. Henschke CI, Yankelevitz DF, Libby DM, Pasmantier MW, Smith JP, Miettinen OS (2006) Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med 355:1763–1771

    Article  Google Scholar 

  4. Bach PB, Jett JR, Pastorino U, Tockman MS, Swensen SJ, Begg CB (2007) Computed tomography screening and lung cancer outcomes. Jama 297:953–961

    Article  CAS  Google Scholar 

  5. Liang EY, Chan M, Hsiang JH, Walkden SB, Poon WS, Lam WW, Metreweli C (1995) Detection and assessment of intracranial aneurysms: value of CT angiography with shaded-surface display. AJR Am J Roentgenol 165:1497–1502

    CAS  Google Scholar 

  6. Jankowski A, Martinelli T, Timsit JF, Brambilla C, Thony F, Coulomb M, Ferretti G (2007) Pulmonary nodule detection on MDCT images: evaluation of diagnostic performance using thin axial images, maximum intensity projections, and computer-assisted detection. Eur Radiol 17:3148–3156

    Article  CAS  Google Scholar 

  7. Mulshine JL, Sullivan DC (2005) Clinical practice. Lung cancer screening. N Engl J Med 352:2714–2720

    Article  CAS  Google Scholar 

  8. Swensen SJ, Jett JR, Hartman TE, Midthun DE, Mandrekar SJ, Hillman SL, Sykes AM, Aughenbaugh GL, Bungum AO, Allen KL (2005) CT screening for lung cancer: five-year prospective experience. Radiology 235:259–265

    Article  Google Scholar 

  9. Markowitz SB, Miller A, Miller J, Manowitz A, Kieding S, Sider L, Morabia A (2007) Ability of low-dose helical CT to distinguish between benign and malignant noncalcified lung nodules. Chest 131:1028–1034

    Article  Google Scholar 

  10. Haberkorn U, Schoenberg SO (2001) Imaging of lung cancer with CT, MRT and PET. Lung Cancer 34(Suppl 3):S13–S23

    Article  Google Scholar 

  11. Yi CA, Jeon TY, Lee KS, Lee JH, Seo JB, Kim YK, Chung MJ (2007) 3-T MRI: usefulness for evaluating primary lung cancer and small nodules in lobes not containing primary tumors. Am J Roentgenol 189(2):386–392

    Article  Google Scholar 

  12. Ung YC, Maziak DE, Vanderveen JA, Smith CA, Gulenchyn K, Lacchetti C, Evans WK (2007) 18Fluorodeoxyglucose positron emission tomography in the diagnosis and staging of lung cancer: a systematic review. J Natl Cancer Inst 99:1753–1767

    Article  Google Scholar 

  13. Greco C, Rosenzweig K, Cascini GL, Tamburrini O (2007) Current status of PET/CT for tumour volume definition in radiotherapy treatment planning for non-small cell lung cancer (NSCLC). Lung Cancer 57:125–134

    Article  Google Scholar 

  14. Meuli R, Hwu Y, Je JH, Margaritondo G (2004) Synchrotron radiation in radiology: radiology techniques based on synchrotron sources. Eur Radiol 14:1550–1560

    Article  Google Scholar 

  15. Hwu Y, Tsai W-L, Groso A, Margaritondo G, Je JH (2002) Coherence-enhanced synchrotron radiology: simple theory and practical applications. J Phys D Appl Phys 35:R105–R120

    Article  CAS  Google Scholar 

  16. Castelli E, Arfelli F, Dreossi D, Longo R, Rokvic T, Cova MA, Quaia E, Tonutti M, Zanconati F, Abrami A, Chenda V, Menk RH, Quai E, Tromba G, Bregant P, de Guarrini F (2007) Clinical mammography at the SYRMEP beam line. Nucl Instr Meth Phys Res A 572:237–240

    Article  CAS  Google Scholar 

  17. Elleaume H, Fiedler S, Esteve F, Bertrand B, Charvet AM, Berkvens P, Berruyer G, Brochard T, Le Duc G, Nemoz C, Renier M, Suortti P, Thomlinson W, Le Bas JF (2000) First human transvenous coronary angiography at the European Synchrotron Radiation Facility. Phys Med Biol 45:L39–L43

    Article  CAS  Google Scholar 

  18. Dix WR, Kupper W, Dill T, Hamm CW, Job H, Lohmann M, Reime B, Ventura R (2003) Comparison of intravenous coronary angiography using synchrotron radiation with selective coronary angiography. J Synchrotron Radiat 10:219–227

    Article  Google Scholar 

  19. Dreossi D, Abrami A, Arfelli F, Bregant P, Casarin K, Chenda V, Cova MA, Longo R, Menk RH, Quai E, Quaia E, Rigon L, Rokvic T, Sanabor D, Tonutti M, Tromba G, Vascotto A, Zanconati F, Castelli E (2008) The mammography project at the SYRMEP beamline. Eur J Radiol 68:S58–S62

    Article  CAS  Google Scholar 

  20. Fiedler S, Bravin A, Keyrilainen J, Fernandez M, Suortti P, Thomlinson W, Tenhunen M, Virkkunen P, Karjalainen-Lindsberg M (2004) Imaging lobular breast carcinoma: comparison of synchrotron radiation DEI-CT technique with clinical CT, mammography and histology. Phys Med Biol 49:175–188

    Article  CAS  Google Scholar 

  21. Hooper SB, Kitchen MJ, Siew ML, Lewis RA, Fouras A, te Pas AB, Siu KK, Yagi N, Uesugi K, Wallace MJ (2009) Imaging lung aeration and lung liquid clearance at birth using phase contrast X-ray imaging. Clin Exp Pharmacol Physiol 36:117–125

    Article  CAS  Google Scholar 

  22. Zhang L, Li D, Luo S (2011) Non-invasive microstructure and morphology investigation of the mouse lung: qualitative description and quantitative measurement. PLoS ONE 6:e17400

    Article  CAS  Google Scholar 

  23. Liu P, Sun J, Guan Y, Yue W, Xu LX, Li Y, Zhang G, Hwu Y, Je JH, Margaritondo G (2008) Morphological study of early-stage lung cancer using synchrotron radiation. J Synchrotron Radiat 15:36–42

    Article  Google Scholar 

  24. Hwu Y, Tsai WL, Chang HM, Yeh HI, Hsu PC, Yang YC, Su YT, Tsai HL, Chow GM, Ho PC, Li SC, Moser HO, Yang P, Seol SK, Kim CC, Je JH, Stefanekova E, Groso A, Margaritondo G (2004) Imaging cells and tissues with refractive index radiology. Biophys J 87:4180–4187

    Article  CAS  Google Scholar 

  25. Song YF, Chang CH, Liu CY, Chang SH, Jeng US, Lai YH, Liu DG, Chung SC, Tsang KL, Yin GC, Lee JF, Sheu HS, Tang MT, Hwang CS, Hwu YK, Liang KS (2007) X-ray beamlines for structural studies at the NSRRC superconducting wavelength shifter. J Synchrotron Radiat 14:320–325

    Article  CAS  Google Scholar 

  26. Baik S, Kim HS, Jeong MH, Lee CS, Je JH, Hwu Y, Margaritondo G (2004) International consortium on phase contrast imaging and radiology beamline at the Pohang Light Source. Rev Sci Instrum 75:4355–4358

    Article  CAS  Google Scholar 

  27. Margaritondo G, Hwu Y, Je JH (2004) Synchrotron light in medical and materials science radiology. Riv Nuovo Cimento 27:1–40

    Google Scholar 

  28. Hwu Y, Je JH, Margaritondo G (2005) Real-time radiology in the microscale. Nucl Instrum Meth A 551:108–118

    Article  CAS  Google Scholar 

  29. Hamide JP, Qian Z, Xu H, Diethelm L, Skrepnik N, Castaneda-Zuniga WR, Hunt JD (1997) Percutaneous implantation of non-small-cell lung carcinoma: technique and observations. Acad Radiol 4:629–633

    Article  CAS  Google Scholar 

  30. Tong Y, Zhang G, Li Y, Tan M, Wang W, Chen J, Hwu Y, Hsu PC, Je JH, Margaritondo G, Song W, Jiang R, Jiang Z (2006) Synchrotron microradiography study on acute lung injury of mouse caused by PM(2.5) aerosols. Eur J Radiol 58:266–272

    Article  Google Scholar 

  31. Yue W, Zhang G, Liu P, Sun J, Yeukuang H, Je JH, Tan M, Li Y (2007) Aerosol-induced lung injuries observed by synchrotron radiation X-ray phase-contrast imaging technique, vol. 262, no. 2. Elsevier, Amsterdam, PAYS-BAS

    Google Scholar 

  32. Su WY, Jaskot RH, Richards J, Abramson SR, Woessner JF Jr, Yu WH, Dreher KL (2000) Induction of pulmonary matrilysin expression by combustion and ambient air particles. Am J Physiol Lung Cell Mol Physiol 279:L152–L160

    CAS  Google Scholar 

  33. Canny J (1986) A computational approach to edge detection. Pattern analysis and machine intelligence. IEEE Trans PAMI 8:679–698

    Article  Google Scholar 

  34. Xu C, Prince JL (1998) Snakes, shapes, and gradient vector flow. IEEE Trans Image Process 7:359–369

    Article  CAS  Google Scholar 

  35. Kass M, Witkin A, Terzopoulos D (1988) Snakes: active contour models. Int J Comput Vision 1:321–331

    Article  Google Scholar 

  36. Kitchen MJ, Paganin D, Lewis RA, Yagi N, Uesugi K, Mudie ST (2004) On the origin of speckle in x-ray phase contrast images of lung tissue. Phys Med Biol 49:4335–4348

    Article  CAS  Google Scholar 

  37. Tuohimaa T, Otendal M, Hertz HM (2007) Phase-contrast x-ray imaging with a liquid-metal-jet-anode microfocus source. Appl Phys Lett 91:074104

    Article  Google Scholar 

  38. Lazzaro PD, Bollanti S, Conti A, Flora F, Mezi L, Murra D, Zheng CE (2005) Recent results of laser-driven EUV and soft X-rays plasma source at ENEA Frascati. Proc SPIE 5958:595814

    Article  Google Scholar 

  39. Krol A, Ikhlef A, Kieffer JC, Bassano DA, Chamberlain CC, Jiang Z, Pepin H, Prasad SC (1997) Laser-based microfocused x-ray source for mammography: feasibility study. Med Phys 24:725–732

    Article  CAS  Google Scholar 

  40. Yamada H (2003) Novel X-ray source based on a tabletop synchrotron and its unique features. Nucl Instrum Methods Phys Res B 199:509–516

    Article  CAS  Google Scholar 

  41. Zheng D, Frederick WJ, DeStefano C, Vlieks AE, Landahl E, Kwan A, Heritage JP, Norman A, Boone JM, Luhmann NC (2006) The monochromatic Compton X-ray source for cancer diagnostics and therapy. Infrared Millimeter Waves and 14th International Conference on Teraherz Electronics, pp 580–580

  42. Vlieks AE, Akre R, Caryotakis G, Destefano C, Frederick WJ, Heritage JP, Luhmann NC, Martin D, Pellegrini C (2006) Recent measurements and plans for the SLAC Compton X-ray source. AIP Conf Proc 807:481–490

    Article  Google Scholar 

  43. Hwu Y, Tsai WL, Je JH, Seol SK, Kim B, Groso A, Margaritondo G, Lee KH, Seong JK (2004) Synchrotron microangiography with no contrast agent. Phys Med Biol 49:501–508

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Ms. Yi**g Guan for computer processing and Dr. Cyril Petibois for fruitful discussion. This work was supported by NNSF of 11079049 (China) and by CAS of KJCX3,SYW.N3 (China), NPST for Nanoscience and Nanotechnology, Thematic Program of Academia Sinica, the Biomedical NanoImaging Core Facility(Taiwan), Fonds National Suisse, Lausanne Center for Biomedical Imaging (CIBM), and the Creative Research Initiatives (Functional X-ray Imaging) of MOST/KOSEF (Korea).

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Authors and Affiliations

  1. Institute of Physics, Academia Sinica, Nankang, Taipei, 11529, Taiwan

    Chia-Chi Chien, Y. Hwu, Chang Hai Wang, Nanyow Chen, Chien Hung Lu & Ting-Kuo Lee

  2. Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China

    Guilin Zhang, Weisheng Yue, Yan Li & Hongjie Xue

  3. Department of Engineering and System Science, National Tsing Hua University, Hsinchu, 30013, Taiwan

    Chia-Chi Chien & Y. Hwu

  4. Shanghai Jiao Tong University, Shanghai, 200030, China

    ** Liu, Jianqi Sun & Lisa X. Xu

  5. Mackay Memorial Hospital, Taipei City, 104, Taiwan

    Yuh-Cheng Yang & Yen-Ta Lu

  6. Department of Computer Science, National Chiao Tung University, Hsinchu, 300, Taiwan

    Yu-Tai Ching

  7. College of Medicine, National Taiwan University, Taipei, 10617, Taiwan

    T. F. Shih & P. C. Yang

  8. X-ray Imaging Center, Pohang University of Science and Technology Pohang, Pohang CT, Kyungbuk, 790-784, South Korea

    J. H. Je

  9. Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, Switzerland

    G. Margaritondo

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  1. Chia-Chi Chien
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Correspondence to Guilin Zhang.

Additional information

Published in the special issue Imaging Techniques (with Synchrotron Radiation) with Guest Editor Cyril Petibois.

An erratum to this article can be found at http://dx.doi.org/10.1007/s00216-011-5219-5

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Chien, CC., Zhang, G., Hwu, Y. et al. Detecting small lung tumors in mouse models by refractive-index microradiology. Anal Bioanal Chem 401, 827–835 (2011). https://doi.org/10.1007/s00216-011-5117-x

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