Abstract

Crohn’s disease (CD) is a chronic autoimmune disease characterized by obstructing intestinal strictures. Conventional imaging modalities can identify the strictures but cannot characterize whether a stricture is predominantly inflammatory or fibrotic. The purpose of this study is to examine the capability of photoacoustic (PA) imaging to characterize intestinal fibrosis and inflammation in vivo. Intestinal strictures in a rat model of CD were imaged with a PA-ultrasound parallel imaging system. Internal and external illuminations were attempted, both with transcutaneous PA signal reception. The PA signal magnitudes acquired at wavelengths targeting individual molecular components and the derived functional information showed significant differences between the inflammatory and fibrotic strictures, consistent with histological inflammation and fibrosis.

© 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]

2017 (3)

S. Kugathasan, L. A. Denson, T. D. Walters, M.-O. Kim, U. M. Marigorta, M. Schirmer, K. Mondal, C. Liu, A. Griffiths, J. D. Noe, W. V. Crandall, S. Snapper, S. Rabizadeh, J. R. Rosh, J. M. Shapiro, S. Guthery, D. R. Mack, R. Kellermayer, M. D. Kappelman, S. Steiner, D. E. Moulton, D. Keljo, S. Cohen, M. Oliva-Hemker, M. B. Heyman, A. R. Otley, S. S. Baker, J. S. Evans, B. S. Kirschner, A. S. Patel, D. Ziring, B. C. Trapnell, F. A. Sylvester, M. C. Stephens, R. N. Baldassano, J. F. Markowitz, J. Cho, R. J. Xavier, C. Huttenhower, B. J. Aronow, G. Gibson, J. S. Hyams, and M. C. Dubinsky, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” Lancet 389(10080), 1710–1718 (2017).
[Crossref] [PubMed]

F. Knieling, C. Neufert, A. Hartmann, J. Claussen, A. Urich, C. Egger, M. Vetter, S. Fischer, L. Pfeifer, A. Hagel, C. Kielisch, R. S. Görtz, D. Wildner, M. Engel, J. Röther, W. Uter, J. Siebler, R. Atreya, W. Rascher, D. Strobel, M. F. Neurath, and M. J. Waldner, “Multispectral Optoacoustic Tomography for Assessment of Crohn’s Disease Activity,” N. Engl. J. Med. 376(13), 1292–1294 (2017).
[Crossref] [PubMed]

H. Zhang, W. Y. Chao, Q. Cheng, S. Huang, X. Wang, D. Wu, and G. Xu, “Interstitial photoacoustic spectral analysis: instrumentation and validation,” Biomed. Opt. Express 8(3), 1689–1697 (2017).
[Crossref] [PubMed]

2016 (5)

H. Lei, L. A. Johnson, S. Liu, D. S. Moons, T. Ma, Q. Zhou, M. D. Rice, J. Ni, X. Wang, P. D. Higgins, and G. Xu, “Characterizing intestinal inflammation and fibrosis in Crohn’s disease by photoacoustic imaging: feasibility study,” Biomed. Opt. Express 7(7), 2837–2848 (2016).
[Crossref] [PubMed]

G. Xu, Z. X. Meng, J. D. Lin, C. X. Deng, P. L. Carson, J. B. Fowlkes, C. Tao, X. Liu, and X. Wang, “High resolution physio-chemical tissue analysis: towards non-invasive in vivo biopsy,” Sci. Rep. 6(1), 16937 (2016).
[Crossref] [PubMed]

G. Xu, Z. X. Meng, J. D. Lin, C. X. Deng, P. L. Carson, J. B. Fowlkes, C. Tao, X. Liu, and X. Wang, “High resolution Physio-chemical Tissue Analysis: Towards Non-invasive In Vivo Biopsy,” Sci. Rep. 6(1), 16937 (2016).
[Crossref] [PubMed]

C. P. Sabino, A. M. Deana, T. M. Yoshimura, D. F. T. da Silva, C. M. França, M. R. Hamblin, and M. S. Ribeiro, “The optical properties of mouse skin in the visible and near infrared spectral regions,” J. Photochem. Photobiol. B 160, 72–78 (2016).
[Crossref] [PubMed]

R. W. Stidham and P. D. R. Higgins, “Imaging of intestinal fibrosis: current challenges and future methods,” United European Gastroenterol. J. 4(4), 515–522 (2016).
[Crossref] [PubMed]

2015 (1)

J. Rimola, N. Planell, S. Rodríguez, S. Delgado, I. Ordás, A. Ramírez-Morros, C. Ayuso, M. Aceituno, E. Ricart, A. Jauregui-Amezaga, J. Panés, and M. Cuatrecasas, “Characterization of Inflammation and Fibrosis in Crohn’s Disease Lesions by Magnetic Resonance Imaging,” Am. J. Gastroenterol. 110(3), 432–440 (2015).
[Crossref] [PubMed]

2013 (4)

J. R. Dillman, R. W. Stidham, P. D. R. Higgins, D. S. Moons, L. A. Johnson, and J. M. Rubin, “US Elastography-derived Shear Wave Velocity Helps Distinguish Acutely Inflamed from Fibrotic Bowel in a Crohn Disease Animal Model,” Radiology 267(3), 757–766 (2013).
[Crossref] [PubMed]

J. Yuan, G. Xu, Y. Yu, Y. Zhou, P. L. Carson, X. Wang, and X. Liu, “Real-time photoacoustic and ultrasound dual-modality imaging system facilitated with graphics processing unit and code parallel optimization,” J. Biomed. Opt. 18(8), 086001 (2013).
[Crossref] [PubMed]

S. L. Jacques, “Optical properties of biological tissues: a review,” Phys. Med. Biol. 58(11), R37–R61 (2013).
[Crossref] [PubMed]

J. R. Rajian, R. Li, P. Wang, and J.-X. Cheng, “Vibrational Photoacoustic Tomography: Chemical Imaging beyond the Ballistic Regime,” J. Phys. Chem. Lett. 4(19), 3211–3215 (2013).
[Crossref] [PubMed]

2012 (1)

L. V. Wang and S. Hu, “Photoacoustic Tomography: In Vivo Imaging from Organelles to Organs,” Science 335(6075), 1458–1462 (2012).
[Crossref] [PubMed]

2011 (4)

D. A. Fisher, J. T. Maple, T. Ben-Menachem, B. D. Cash, G. A. Decker, D. S. Early, J. A. Evans, R. D. Fanelli, N. Fukami, J. H. Hwang, R. Jain, T. L. Jue, K. M. Khan, P. M. Malpas, R. N. Sharaf, A. K. Shergill, J. A. Dominitz, and ASGE Standards of Practice Committee, “Complications of colonoscopy,” Gastrointest. Endosc. 74(4), 745–752 (2011).
[Crossref] [PubMed]

F. Rieder, I. C. Lawrance, A. Leite, and M. Sans, “Predictors of fibrostenotic Crohn’s disease,” Inflamm. Bowel Dis. 17(9), 2000–2007 (2011).
[Crossref] [PubMed]

R. W. Stidham, J. Xu, L. A. Johnson, K. Kim, D. S. Moons, B. J. McKenna, J. M. Rubin, and P. D. R. Higgins, “Ultrasound Elasticity Imaging for Detecting Intestinal Fibrosis and Inflammation in Rats and Humans with Crohn’s Disease,” Gastroenterology 141(3), 819–826 (2011).
[Crossref] [PubMed]

H.-W. Wang, N. Chai, P. Wang, S. Hu, W. Dou, D. Umulis, L. V. Wang, M. Sturek, R. Lucht, and J.-X. Cheng, “Label-Free Bond-Selective Imaging by Listening to Vibrationally Excited Molecules,” Phys. Rev. Lett. 106(23), 238106 (2011).
[Crossref] [PubMed]

2009 (4)

R. George and L. J. Walsh, “Performance assessment of novel side firing flexible optical fibers for dental applications,” Lasers Surg. Med. 41(3), 214–221 (2009).
[Crossref] [PubMed]

E. Domènech, M. Mañosa, and E. Cabré, “Top-Down Therapy: Is the Evidence Strong Enough?” Dig. Dis. 27(3), 306–311 (2009).
[Crossref] [PubMed]

I. C. Lawrance, C. J. Welman, P. Shipman, and K. Murray, “Correlation of MRI-determined small bowel Crohn’s disease categories with medical response and surgical pathology,” World J. Gastroenterol. 15(27), 3367–3375 (2009).
[Crossref] [PubMed]

P. Paolantonio, R. Ferrari, F. Vecchietti, S. Cucchiara, and A. Laghi, “Current status of MR imaging in the evaluation of IBD in a pediatric population of patients,” Eur. J. Radiol. 69(3), 418–424 (2009).
[Crossref] [PubMed]

2008 (2)

K. Kim, L. A. Johnson, C. Jia, J. C. Joyce, S. Rangwalla, P. D. R. Higgins, and J. M. Rubin, “Noninvasive Ultrasound Elasticity Imaging (UEI) of Crohn’s Disease: Animal Model,” Ultrasound Med. Biol. 34(6), 902–912 (2008).
[Crossref] [PubMed]

D. F. Higgins, K. Kimura, M. Iwano, and V. H. Haase, “Hypoxia-inducible factor signaling in the development of tissue fibrosis,” Cell Cycle 7(9), 1128–1132 (2008).
[Crossref] [PubMed]

2007 (1)

2006 (2)

X. Wang, X. Xie, G. Ku, L. V. Wang, and G. Stoica, “Noninvasive imaging of hemoglobin concentration and oxygenation in the rat brain using high-resolution photoacoustic tomography,” J. Biomed. Opt. 11(2), 024015 (2006).
[Crossref] [PubMed]

G. R. Lichtenstein, A. Olson, S. Travers, R. H. Diamond, D. M. Chen, M. L. Pritchard, B. G. Feagan, R. D. Cohen, B. A. Salzberg, S. B. Hanauer, and W. J. Sandborn, “Factors Associated with the Development of Intestinal Strictures or Obstructions in Patients with Crohn’s Disease,” Am. J. Gastroenterol. 101(5), 1030–1038 (2006).
[Crossref] [PubMed]

2003 (2)

X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, “Noninvasive laser-induced photoacoustic tomography for structural and functional in vivo imaging of the brain,” Nat. Biotechnol. 21(7), 803–806 (2003).
[Crossref] [PubMed]

S. Leungwattanakij, T. J. Bivalacqua, M. F. Usta, D.-Y. Yang, J.-S. Hyun, H. C. Champion, A. B. Abdel-Mageed, and W. J. G. Hellstrom, “Cavernous Neurotomy Causes Hypoxia and Fibrosis in Rat Corpus Cavernosum,” J. Androl. 24(2), 239–245 (2003).
[Crossref] [PubMed]

2002 (1)

E. V. Loftus, P. Schoenfeld, and W. J. Sandborn, “The epidemiology and natural history of Crohn’s disease in population-based patient cohorts from North America: a systematic review,” Aliment. Pharmacol. Ther. 16(1), 51–60 (2002).
[Crossref] [PubMed]

2001 (2)

M. Boudiaf, P. Soyer, C. Terem, J. P. Pelage, E. Maissiat, and R. Rymer, “Ct Evaluation of Small Bowel Obstruction,” Radiographics 21(3), 613–624 (2001).
[Crossref] [PubMed]

J. M. Esteban, L. Maldonado, V. Sanchiz, M. Minguez, and A. Benages, “Activity of Crohn’s disease assessed by colour Doppler ultrasound analysis of the affected loops,” Eur. Radiol. 11(8), 1423–1428 (2001).
[Crossref] [PubMed]

2000 (3)

Z. Tarján, G. Tóth, T. Györke, A. Mester, K. Karlinger, and E. K. Makó, “Ultrasound in Crohn’s disease of the small bowel,” Eur. J. Radiol. 35(3), 176–182 (2000).
[Crossref] [PubMed]

R. D. Cohen, L. R. Larson, J. M. Roth, R. V. Becker, and L. L. Mummert, “The cost of hospitalization in Crohn’s disease,” Am. J. Gastroenterol. 95(2), 524–530 (2000).
[Crossref] [PubMed]

G. Oberhuber, P. C. Stangl, H. Vogelsang, E. Schober, F. Herbst, and C. Gasche, “Significant association of strictures and internal fistula formation in Crohn’s disease,” Virchows Arch. 437(3), 293–297 (2000).
[Crossref] [PubMed]

1990 (1)

W. F. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical properties of biological tissues,” Quantum Electronics, IEEE Journal of 26(12), 2166–2185 (1990).
[Crossref]

1989 (1)

S. M. Dandalides, W. D. Carey, R. Petras, and E. Achkar, “Endoscopic small bowel mucosal biopsy: a controlled trial evaluating forceps size and biopsy location in the diagnosis of normal and abnormal mucosal architecture,” Gastrointest. Endosc. 35(3), 197–200 (1989).
[Crossref] [PubMed]

1963 (1)

Abdel-Mageed, A. B.

S. Leungwattanakij, T. J. Bivalacqua, M. F. Usta, D.-Y. Yang, J.-S. Hyun, H. C. Champion, A. B. Abdel-Mageed, and W. J. G. Hellstrom, “Cavernous Neurotomy Causes Hypoxia and Fibrosis in Rat Corpus Cavernosum,” J. Androl. 24(2), 239–245 (2003).
[Crossref] [PubMed]

Aceituno, M.

J. Rimola, N. Planell, S. Rodríguez, S. Delgado, I. Ordás, A. Ramírez-Morros, C. Ayuso, M. Aceituno, E. Ricart, A. Jauregui-Amezaga, J. Panés, and M. Cuatrecasas, “Characterization of Inflammation and Fibrosis in Crohn’s Disease Lesions by Magnetic Resonance Imaging,” Am. J. Gastroenterol. 110(3), 432–440 (2015).
[Crossref] [PubMed]

Achkar, E.

S. M. Dandalides, W. D. Carey, R. Petras, and E. Achkar, “Endoscopic small bowel mucosal biopsy: a controlled trial evaluating forceps size and biopsy location in the diagnosis of normal and abnormal mucosal architecture,” Gastrointest. Endosc. 35(3), 197–200 (1989).
[Crossref] [PubMed]

Aronow, B. J.

S. Kugathasan, L. A. Denson, T. D. Walters, M.-O. Kim, U. M. Marigorta, M. Schirmer, K. Mondal, C. Liu, A. Griffiths, J. D. Noe, W. V. Crandall, S. Snapper, S. Rabizadeh, J. R. Rosh, J. M. Shapiro, S. Guthery, D. R. Mack, R. Kellermayer, M. D. Kappelman, S. Steiner, D. E. Moulton, D. Keljo, S. Cohen, M. Oliva-Hemker, M. B. Heyman, A. R. Otley, S. S. Baker, J. S. Evans, B. S. Kirschner, A. S. Patel, D. Ziring, B. C. Trapnell, F. A. Sylvester, M. C. Stephens, R. N. Baldassano, J. F. Markowitz, J. Cho, R. J. Xavier, C. Huttenhower, B. J. Aronow, G. Gibson, J. S. Hyams, and M. C. Dubinsky, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” Lancet 389(10080), 1710–1718 (2017).
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Atreya, R.

F. Knieling, C. Neufert, A. Hartmann, J. Claussen, A. Urich, C. Egger, M. Vetter, S. Fischer, L. Pfeifer, A. Hagel, C. Kielisch, R. S. Görtz, D. Wildner, M. Engel, J. Röther, W. Uter, J. Siebler, R. Atreya, W. Rascher, D. Strobel, M. F. Neurath, and M. J. Waldner, “Multispectral Optoacoustic Tomography for Assessment of Crohn’s Disease Activity,” N. Engl. J. Med. 376(13), 1292–1294 (2017).
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Ayuso, C.

J. Rimola, N. Planell, S. Rodríguez, S. Delgado, I. Ordás, A. Ramírez-Morros, C. Ayuso, M. Aceituno, E. Ricart, A. Jauregui-Amezaga, J. Panés, and M. Cuatrecasas, “Characterization of Inflammation and Fibrosis in Crohn’s Disease Lesions by Magnetic Resonance Imaging,” Am. J. Gastroenterol. 110(3), 432–440 (2015).
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Baker, S. S.

S. Kugathasan, L. A. Denson, T. D. Walters, M.-O. Kim, U. M. Marigorta, M. Schirmer, K. Mondal, C. Liu, A. Griffiths, J. D. Noe, W. V. Crandall, S. Snapper, S. Rabizadeh, J. R. Rosh, J. M. Shapiro, S. Guthery, D. R. Mack, R. Kellermayer, M. D. Kappelman, S. Steiner, D. E. Moulton, D. Keljo, S. Cohen, M. Oliva-Hemker, M. B. Heyman, A. R. Otley, S. S. Baker, J. S. Evans, B. S. Kirschner, A. S. Patel, D. Ziring, B. C. Trapnell, F. A. Sylvester, M. C. Stephens, R. N. Baldassano, J. F. Markowitz, J. Cho, R. J. Xavier, C. Huttenhower, B. J. Aronow, G. Gibson, J. S. Hyams, and M. C. Dubinsky, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” Lancet 389(10080), 1710–1718 (2017).
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Baldassano, R. N.

S. Kugathasan, L. A. Denson, T. D. Walters, M.-O. Kim, U. M. Marigorta, M. Schirmer, K. Mondal, C. Liu, A. Griffiths, J. D. Noe, W. V. Crandall, S. Snapper, S. Rabizadeh, J. R. Rosh, J. M. Shapiro, S. Guthery, D. R. Mack, R. Kellermayer, M. D. Kappelman, S. Steiner, D. E. Moulton, D. Keljo, S. Cohen, M. Oliva-Hemker, M. B. Heyman, A. R. Otley, S. S. Baker, J. S. Evans, B. S. Kirschner, A. S. Patel, D. Ziring, B. C. Trapnell, F. A. Sylvester, M. C. Stephens, R. N. Baldassano, J. F. Markowitz, J. Cho, R. J. Xavier, C. Huttenhower, B. J. Aronow, G. Gibson, J. S. Hyams, and M. C. Dubinsky, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” Lancet 389(10080), 1710–1718 (2017).
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R. D. Cohen, L. R. Larson, J. M. Roth, R. V. Becker, and L. L. Mummert, “The cost of hospitalization in Crohn’s disease,” Am. J. Gastroenterol. 95(2), 524–530 (2000).
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Benages, A.

J. M. Esteban, L. Maldonado, V. Sanchiz, M. Minguez, and A. Benages, “Activity of Crohn’s disease assessed by colour Doppler ultrasound analysis of the affected loops,” Eur. Radiol. 11(8), 1423–1428 (2001).
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Ben-Menachem, T.

D. A. Fisher, J. T. Maple, T. Ben-Menachem, B. D. Cash, G. A. Decker, D. S. Early, J. A. Evans, R. D. Fanelli, N. Fukami, J. H. Hwang, R. Jain, T. L. Jue, K. M. Khan, P. M. Malpas, R. N. Sharaf, A. K. Shergill, J. A. Dominitz, and ASGE Standards of Practice Committee, “Complications of colonoscopy,” Gastrointest. Endosc. 74(4), 745–752 (2011).
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M. Boudiaf, P. Soyer, C. Terem, J. P. Pelage, E. Maissiat, and R. Rymer, “Ct Evaluation of Small Bowel Obstruction,” Radiographics 21(3), 613–624 (2001).
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E. Domènech, M. Mañosa, and E. Cabré, “Top-Down Therapy: Is the Evidence Strong Enough?” Dig. Dis. 27(3), 306–311 (2009).
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S. M. Dandalides, W. D. Carey, R. Petras, and E. Achkar, “Endoscopic small bowel mucosal biopsy: a controlled trial evaluating forceps size and biopsy location in the diagnosis of normal and abnormal mucosal architecture,” Gastrointest. Endosc. 35(3), 197–200 (1989).
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G. Xu, Z. X. Meng, J. D. Lin, C. X. Deng, P. L. Carson, J. B. Fowlkes, C. Tao, X. Liu, and X. Wang, “High resolution physio-chemical tissue analysis: towards non-invasive in vivo biopsy,” Sci. Rep. 6(1), 16937 (2016).
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G. Xu, Z. X. Meng, J. D. Lin, C. X. Deng, P. L. Carson, J. B. Fowlkes, C. Tao, X. Liu, and X. Wang, “High resolution Physio-chemical Tissue Analysis: Towards Non-invasive In Vivo Biopsy,” Sci. Rep. 6(1), 16937 (2016).
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J. Yuan, G. Xu, Y. Yu, Y. Zhou, P. L. Carson, X. Wang, and X. Liu, “Real-time photoacoustic and ultrasound dual-modality imaging system facilitated with graphics processing unit and code parallel optimization,” J. Biomed. Opt. 18(8), 086001 (2013).
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D. A. Fisher, J. T. Maple, T. Ben-Menachem, B. D. Cash, G. A. Decker, D. S. Early, J. A. Evans, R. D. Fanelli, N. Fukami, J. H. Hwang, R. Jain, T. L. Jue, K. M. Khan, P. M. Malpas, R. N. Sharaf, A. K. Shergill, J. A. Dominitz, and ASGE Standards of Practice Committee, “Complications of colonoscopy,” Gastrointest. Endosc. 74(4), 745–752 (2011).
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H.-W. Wang, N. Chai, P. Wang, S. Hu, W. Dou, D. Umulis, L. V. Wang, M. Sturek, R. Lucht, and J.-X. Cheng, “Label-Free Bond-Selective Imaging by Listening to Vibrationally Excited Molecules,” Phys. Rev. Lett. 106(23), 238106 (2011).
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S. Leungwattanakij, T. J. Bivalacqua, M. F. Usta, D.-Y. Yang, J.-S. Hyun, H. C. Champion, A. B. Abdel-Mageed, and W. J. G. Hellstrom, “Cavernous Neurotomy Causes Hypoxia and Fibrosis in Rat Corpus Cavernosum,” J. Androl. 24(2), 239–245 (2003).
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Chao, W. Y.

Chen, D. M.

G. R. Lichtenstein, A. Olson, S. Travers, R. H. Diamond, D. M. Chen, M. L. Pritchard, B. G. Feagan, R. D. Cohen, B. A. Salzberg, S. B. Hanauer, and W. J. Sandborn, “Factors Associated with the Development of Intestinal Strictures or Obstructions in Patients with Crohn’s Disease,” Am. J. Gastroenterol. 101(5), 1030–1038 (2006).
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J. R. Rajian, R. Li, P. Wang, and J.-X. Cheng, “Vibrational Photoacoustic Tomography: Chemical Imaging beyond the Ballistic Regime,” J. Phys. Chem. Lett. 4(19), 3211–3215 (2013).
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W. F. Cheong, S. A. Prahl, and A. J. Welch, “A review of the optical properties of biological tissues,” Quantum Electronics, IEEE Journal of 26(12), 2166–2185 (1990).
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S. Kugathasan, L. A. Denson, T. D. Walters, M.-O. Kim, U. M. Marigorta, M. Schirmer, K. Mondal, C. Liu, A. Griffiths, J. D. Noe, W. V. Crandall, S. Snapper, S. Rabizadeh, J. R. Rosh, J. M. Shapiro, S. Guthery, D. R. Mack, R. Kellermayer, M. D. Kappelman, S. Steiner, D. E. Moulton, D. Keljo, S. Cohen, M. Oliva-Hemker, M. B. Heyman, A. R. Otley, S. S. Baker, J. S. Evans, B. S. Kirschner, A. S. Patel, D. Ziring, B. C. Trapnell, F. A. Sylvester, M. C. Stephens, R. N. Baldassano, J. F. Markowitz, J. Cho, R. J. Xavier, C. Huttenhower, B. J. Aronow, G. Gibson, J. S. Hyams, and M. C. Dubinsky, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” Lancet 389(10080), 1710–1718 (2017).
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F. Knieling, C. Neufert, A. Hartmann, J. Claussen, A. Urich, C. Egger, M. Vetter, S. Fischer, L. Pfeifer, A. Hagel, C. Kielisch, R. S. Görtz, D. Wildner, M. Engel, J. Röther, W. Uter, J. Siebler, R. Atreya, W. Rascher, D. Strobel, M. F. Neurath, and M. J. Waldner, “Multispectral Optoacoustic Tomography for Assessment of Crohn’s Disease Activity,” N. Engl. J. Med. 376(13), 1292–1294 (2017).
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G. R. Lichtenstein, A. Olson, S. Travers, R. H. Diamond, D. M. Chen, M. L. Pritchard, B. G. Feagan, R. D. Cohen, B. A. Salzberg, S. B. Hanauer, and W. J. Sandborn, “Factors Associated with the Development of Intestinal Strictures or Obstructions in Patients with Crohn’s Disease,” Am. J. Gastroenterol. 101(5), 1030–1038 (2006).
[Crossref] [PubMed]

R. D. Cohen, L. R. Larson, J. M. Roth, R. V. Becker, and L. L. Mummert, “The cost of hospitalization in Crohn’s disease,” Am. J. Gastroenterol. 95(2), 524–530 (2000).
[Crossref] [PubMed]

Cohen, S.

S. Kugathasan, L. A. Denson, T. D. Walters, M.-O. Kim, U. M. Marigorta, M. Schirmer, K. Mondal, C. Liu, A. Griffiths, J. D. Noe, W. V. Crandall, S. Snapper, S. Rabizadeh, J. R. Rosh, J. M. Shapiro, S. Guthery, D. R. Mack, R. Kellermayer, M. D. Kappelman, S. Steiner, D. E. Moulton, D. Keljo, S. Cohen, M. Oliva-Hemker, M. B. Heyman, A. R. Otley, S. S. Baker, J. S. Evans, B. S. Kirschner, A. S. Patel, D. Ziring, B. C. Trapnell, F. A. Sylvester, M. C. Stephens, R. N. Baldassano, J. F. Markowitz, J. Cho, R. J. Xavier, C. Huttenhower, B. J. Aronow, G. Gibson, J. S. Hyams, and M. C. Dubinsky, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” Lancet 389(10080), 1710–1718 (2017).
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Crandall, W. V.

S. Kugathasan, L. A. Denson, T. D. Walters, M.-O. Kim, U. M. Marigorta, M. Schirmer, K. Mondal, C. Liu, A. Griffiths, J. D. Noe, W. V. Crandall, S. Snapper, S. Rabizadeh, J. R. Rosh, J. M. Shapiro, S. Guthery, D. R. Mack, R. Kellermayer, M. D. Kappelman, S. Steiner, D. E. Moulton, D. Keljo, S. Cohen, M. Oliva-Hemker, M. B. Heyman, A. R. Otley, S. S. Baker, J. S. Evans, B. S. Kirschner, A. S. Patel, D. Ziring, B. C. Trapnell, F. A. Sylvester, M. C. Stephens, R. N. Baldassano, J. F. Markowitz, J. Cho, R. J. Xavier, C. Huttenhower, B. J. Aronow, G. Gibson, J. S. Hyams, and M. C. Dubinsky, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” Lancet 389(10080), 1710–1718 (2017).
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Cuatrecasas, M.

J. Rimola, N. Planell, S. Rodríguez, S. Delgado, I. Ordás, A. Ramírez-Morros, C. Ayuso, M. Aceituno, E. Ricart, A. Jauregui-Amezaga, J. Panés, and M. Cuatrecasas, “Characterization of Inflammation and Fibrosis in Crohn’s Disease Lesions by Magnetic Resonance Imaging,” Am. J. Gastroenterol. 110(3), 432–440 (2015).
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P. Paolantonio, R. Ferrari, F. Vecchietti, S. Cucchiara, and A. Laghi, “Current status of MR imaging in the evaluation of IBD in a pediatric population of patients,” Eur. J. Radiol. 69(3), 418–424 (2009).
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C. P. Sabino, A. M. Deana, T. M. Yoshimura, D. F. T. da Silva, C. M. França, M. R. Hamblin, and M. S. Ribeiro, “The optical properties of mouse skin in the visible and near infrared spectral regions,” J. Photochem. Photobiol. B 160, 72–78 (2016).
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Dandalides, S. M.

S. M. Dandalides, W. D. Carey, R. Petras, and E. Achkar, “Endoscopic small bowel mucosal biopsy: a controlled trial evaluating forceps size and biopsy location in the diagnosis of normal and abnormal mucosal architecture,” Gastrointest. Endosc. 35(3), 197–200 (1989).
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Deana, A. M.

C. P. Sabino, A. M. Deana, T. M. Yoshimura, D. F. T. da Silva, C. M. França, M. R. Hamblin, and M. S. Ribeiro, “The optical properties of mouse skin in the visible and near infrared spectral regions,” J. Photochem. Photobiol. B 160, 72–78 (2016).
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Decker, G. A.

D. A. Fisher, J. T. Maple, T. Ben-Menachem, B. D. Cash, G. A. Decker, D. S. Early, J. A. Evans, R. D. Fanelli, N. Fukami, J. H. Hwang, R. Jain, T. L. Jue, K. M. Khan, P. M. Malpas, R. N. Sharaf, A. K. Shergill, J. A. Dominitz, and ASGE Standards of Practice Committee, “Complications of colonoscopy,” Gastrointest. Endosc. 74(4), 745–752 (2011).
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Delgado, S.

J. Rimola, N. Planell, S. Rodríguez, S. Delgado, I. Ordás, A. Ramírez-Morros, C. Ayuso, M. Aceituno, E. Ricart, A. Jauregui-Amezaga, J. Panés, and M. Cuatrecasas, “Characterization of Inflammation and Fibrosis in Crohn’s Disease Lesions by Magnetic Resonance Imaging,” Am. J. Gastroenterol. 110(3), 432–440 (2015).
[Crossref] [PubMed]

Deng, C. X.

G. Xu, Z. X. Meng, J. D. Lin, C. X. Deng, P. L. Carson, J. B. Fowlkes, C. Tao, X. Liu, and X. Wang, “High resolution physio-chemical tissue analysis: towards non-invasive in vivo biopsy,” Sci. Rep. 6(1), 16937 (2016).
[Crossref] [PubMed]

G. Xu, Z. X. Meng, J. D. Lin, C. X. Deng, P. L. Carson, J. B. Fowlkes, C. Tao, X. Liu, and X. Wang, “High resolution Physio-chemical Tissue Analysis: Towards Non-invasive In Vivo Biopsy,” Sci. Rep. 6(1), 16937 (2016).
[Crossref] [PubMed]

Denson, L. A.

S. Kugathasan, L. A. Denson, T. D. Walters, M.-O. Kim, U. M. Marigorta, M. Schirmer, K. Mondal, C. Liu, A. Griffiths, J. D. Noe, W. V. Crandall, S. Snapper, S. Rabizadeh, J. R. Rosh, J. M. Shapiro, S. Guthery, D. R. Mack, R. Kellermayer, M. D. Kappelman, S. Steiner, D. E. Moulton, D. Keljo, S. Cohen, M. Oliva-Hemker, M. B. Heyman, A. R. Otley, S. S. Baker, J. S. Evans, B. S. Kirschner, A. S. Patel, D. Ziring, B. C. Trapnell, F. A. Sylvester, M. C. Stephens, R. N. Baldassano, J. F. Markowitz, J. Cho, R. J. Xavier, C. Huttenhower, B. J. Aronow, G. Gibson, J. S. Hyams, and M. C. Dubinsky, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” Lancet 389(10080), 1710–1718 (2017).
[Crossref] [PubMed]

Diamond, R. H.

G. R. Lichtenstein, A. Olson, S. Travers, R. H. Diamond, D. M. Chen, M. L. Pritchard, B. G. Feagan, R. D. Cohen, B. A. Salzberg, S. B. Hanauer, and W. J. Sandborn, “Factors Associated with the Development of Intestinal Strictures or Obstructions in Patients with Crohn’s Disease,” Am. J. Gastroenterol. 101(5), 1030–1038 (2006).
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J. R. Dillman, R. W. Stidham, P. D. R. Higgins, D. S. Moons, L. A. Johnson, and J. M. Rubin, “US Elastography-derived Shear Wave Velocity Helps Distinguish Acutely Inflamed from Fibrotic Bowel in a Crohn Disease Animal Model,” Radiology 267(3), 757–766 (2013).
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Domènech, E.

E. Domènech, M. Mañosa, and E. Cabré, “Top-Down Therapy: Is the Evidence Strong Enough?” Dig. Dis. 27(3), 306–311 (2009).
[Crossref] [PubMed]

Dominitz, J. A.

D. A. Fisher, J. T. Maple, T. Ben-Menachem, B. D. Cash, G. A. Decker, D. S. Early, J. A. Evans, R. D. Fanelli, N. Fukami, J. H. Hwang, R. Jain, T. L. Jue, K. M. Khan, P. M. Malpas, R. N. Sharaf, A. K. Shergill, J. A. Dominitz, and ASGE Standards of Practice Committee, “Complications of colonoscopy,” Gastrointest. Endosc. 74(4), 745–752 (2011).
[Crossref] [PubMed]

Dou, W.

H.-W. Wang, N. Chai, P. Wang, S. Hu, W. Dou, D. Umulis, L. V. Wang, M. Sturek, R. Lucht, and J.-X. Cheng, “Label-Free Bond-Selective Imaging by Listening to Vibrationally Excited Molecules,” Phys. Rev. Lett. 106(23), 238106 (2011).
[Crossref] [PubMed]

Dubinsky, M. C.

S. Kugathasan, L. A. Denson, T. D. Walters, M.-O. Kim, U. M. Marigorta, M. Schirmer, K. Mondal, C. Liu, A. Griffiths, J. D. Noe, W. V. Crandall, S. Snapper, S. Rabizadeh, J. R. Rosh, J. M. Shapiro, S. Guthery, D. R. Mack, R. Kellermayer, M. D. Kappelman, S. Steiner, D. E. Moulton, D. Keljo, S. Cohen, M. Oliva-Hemker, M. B. Heyman, A. R. Otley, S. S. Baker, J. S. Evans, B. S. Kirschner, A. S. Patel, D. Ziring, B. C. Trapnell, F. A. Sylvester, M. C. Stephens, R. N. Baldassano, J. F. Markowitz, J. Cho, R. J. Xavier, C. Huttenhower, B. J. Aronow, G. Gibson, J. S. Hyams, and M. C. Dubinsky, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” Lancet 389(10080), 1710–1718 (2017).
[Crossref] [PubMed]

Early, D. S.

D. A. Fisher, J. T. Maple, T. Ben-Menachem, B. D. Cash, G. A. Decker, D. S. Early, J. A. Evans, R. D. Fanelli, N. Fukami, J. H. Hwang, R. Jain, T. L. Jue, K. M. Khan, P. M. Malpas, R. N. Sharaf, A. K. Shergill, J. A. Dominitz, and ASGE Standards of Practice Committee, “Complications of colonoscopy,” Gastrointest. Endosc. 74(4), 745–752 (2011).
[Crossref] [PubMed]

Egger, C.

F. Knieling, C. Neufert, A. Hartmann, J. Claussen, A. Urich, C. Egger, M. Vetter, S. Fischer, L. Pfeifer, A. Hagel, C. Kielisch, R. S. Görtz, D. Wildner, M. Engel, J. Röther, W. Uter, J. Siebler, R. Atreya, W. Rascher, D. Strobel, M. F. Neurath, and M. J. Waldner, “Multispectral Optoacoustic Tomography for Assessment of Crohn’s Disease Activity,” N. Engl. J. Med. 376(13), 1292–1294 (2017).
[Crossref] [PubMed]

Engel, M.

F. Knieling, C. Neufert, A. Hartmann, J. Claussen, A. Urich, C. Egger, M. Vetter, S. Fischer, L. Pfeifer, A. Hagel, C. Kielisch, R. S. Görtz, D. Wildner, M. Engel, J. Röther, W. Uter, J. Siebler, R. Atreya, W. Rascher, D. Strobel, M. F. Neurath, and M. J. Waldner, “Multispectral Optoacoustic Tomography for Assessment of Crohn’s Disease Activity,” N. Engl. J. Med. 376(13), 1292–1294 (2017).
[Crossref] [PubMed]

Esteban, J. M.

J. M. Esteban, L. Maldonado, V. Sanchiz, M. Minguez, and A. Benages, “Activity of Crohn’s disease assessed by colour Doppler ultrasound analysis of the affected loops,” Eur. Radiol. 11(8), 1423–1428 (2001).
[Crossref] [PubMed]

Evans, J. A.

D. A. Fisher, J. T. Maple, T. Ben-Menachem, B. D. Cash, G. A. Decker, D. S. Early, J. A. Evans, R. D. Fanelli, N. Fukami, J. H. Hwang, R. Jain, T. L. Jue, K. M. Khan, P. M. Malpas, R. N. Sharaf, A. K. Shergill, J. A. Dominitz, and ASGE Standards of Practice Committee, “Complications of colonoscopy,” Gastrointest. Endosc. 74(4), 745–752 (2011).
[Crossref] [PubMed]

Evans, J. S.

S. Kugathasan, L. A. Denson, T. D. Walters, M.-O. Kim, U. M. Marigorta, M. Schirmer, K. Mondal, C. Liu, A. Griffiths, J. D. Noe, W. V. Crandall, S. Snapper, S. Rabizadeh, J. R. Rosh, J. M. Shapiro, S. Guthery, D. R. Mack, R. Kellermayer, M. D. Kappelman, S. Steiner, D. E. Moulton, D. Keljo, S. Cohen, M. Oliva-Hemker, M. B. Heyman, A. R. Otley, S. S. Baker, J. S. Evans, B. S. Kirschner, A. S. Patel, D. Ziring, B. C. Trapnell, F. A. Sylvester, M. C. Stephens, R. N. Baldassano, J. F. Markowitz, J. Cho, R. J. Xavier, C. Huttenhower, B. J. Aronow, G. Gibson, J. S. Hyams, and M. C. Dubinsky, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” Lancet 389(10080), 1710–1718 (2017).
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Fanelli, R. D.

D. A. Fisher, J. T. Maple, T. Ben-Menachem, B. D. Cash, G. A. Decker, D. S. Early, J. A. Evans, R. D. Fanelli, N. Fukami, J. H. Hwang, R. Jain, T. L. Jue, K. M. Khan, P. M. Malpas, R. N. Sharaf, A. K. Shergill, J. A. Dominitz, and ASGE Standards of Practice Committee, “Complications of colonoscopy,” Gastrointest. Endosc. 74(4), 745–752 (2011).
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Feagan, B. G.

G. R. Lichtenstein, A. Olson, S. Travers, R. H. Diamond, D. M. Chen, M. L. Pritchard, B. G. Feagan, R. D. Cohen, B. A. Salzberg, S. B. Hanauer, and W. J. Sandborn, “Factors Associated with the Development of Intestinal Strictures or Obstructions in Patients with Crohn’s Disease,” Am. J. Gastroenterol. 101(5), 1030–1038 (2006).
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Ferrari, R.

P. Paolantonio, R. Ferrari, F. Vecchietti, S. Cucchiara, and A. Laghi, “Current status of MR imaging in the evaluation of IBD in a pediatric population of patients,” Eur. J. Radiol. 69(3), 418–424 (2009).
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Fischer, S.

F. Knieling, C. Neufert, A. Hartmann, J. Claussen, A. Urich, C. Egger, M. Vetter, S. Fischer, L. Pfeifer, A. Hagel, C. Kielisch, R. S. Görtz, D. Wildner, M. Engel, J. Röther, W. Uter, J. Siebler, R. Atreya, W. Rascher, D. Strobel, M. F. Neurath, and M. J. Waldner, “Multispectral Optoacoustic Tomography for Assessment of Crohn’s Disease Activity,” N. Engl. J. Med. 376(13), 1292–1294 (2017).
[Crossref] [PubMed]

Fisher, D. A.

D. A. Fisher, J. T. Maple, T. Ben-Menachem, B. D. Cash, G. A. Decker, D. S. Early, J. A. Evans, R. D. Fanelli, N. Fukami, J. H. Hwang, R. Jain, T. L. Jue, K. M. Khan, P. M. Malpas, R. N. Sharaf, A. K. Shergill, J. A. Dominitz, and ASGE Standards of Practice Committee, “Complications of colonoscopy,” Gastrointest. Endosc. 74(4), 745–752 (2011).
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Fowlkes, J. B.

G. Xu, Z. X. Meng, J. D. Lin, C. X. Deng, P. L. Carson, J. B. Fowlkes, C. Tao, X. Liu, and X. Wang, “High resolution Physio-chemical Tissue Analysis: Towards Non-invasive In Vivo Biopsy,” Sci. Rep. 6(1), 16937 (2016).
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G. Xu, Z. X. Meng, J. D. Lin, C. X. Deng, P. L. Carson, J. B. Fowlkes, C. Tao, X. Liu, and X. Wang, “High resolution physio-chemical tissue analysis: towards non-invasive in vivo biopsy,” Sci. Rep. 6(1), 16937 (2016).
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França, C. M.

C. P. Sabino, A. M. Deana, T. M. Yoshimura, D. F. T. da Silva, C. M. França, M. R. Hamblin, and M. S. Ribeiro, “The optical properties of mouse skin in the visible and near infrared spectral regions,” J. Photochem. Photobiol. B 160, 72–78 (2016).
[Crossref] [PubMed]

Fukami, N.

D. A. Fisher, J. T. Maple, T. Ben-Menachem, B. D. Cash, G. A. Decker, D. S. Early, J. A. Evans, R. D. Fanelli, N. Fukami, J. H. Hwang, R. Jain, T. L. Jue, K. M. Khan, P. M. Malpas, R. N. Sharaf, A. K. Shergill, J. A. Dominitz, and ASGE Standards of Practice Committee, “Complications of colonoscopy,” Gastrointest. Endosc. 74(4), 745–752 (2011).
[Crossref] [PubMed]

Gasche, C.

G. Oberhuber, P. C. Stangl, H. Vogelsang, E. Schober, F. Herbst, and C. Gasche, “Significant association of strictures and internal fistula formation in Crohn’s disease,” Virchows Arch. 437(3), 293–297 (2000).
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R. George and L. J. Walsh, “Performance assessment of novel side firing flexible optical fibers for dental applications,” Lasers Surg. Med. 41(3), 214–221 (2009).
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Gibson, G.

S. Kugathasan, L. A. Denson, T. D. Walters, M.-O. Kim, U. M. Marigorta, M. Schirmer, K. Mondal, C. Liu, A. Griffiths, J. D. Noe, W. V. Crandall, S. Snapper, S. Rabizadeh, J. R. Rosh, J. M. Shapiro, S. Guthery, D. R. Mack, R. Kellermayer, M. D. Kappelman, S. Steiner, D. E. Moulton, D. Keljo, S. Cohen, M. Oliva-Hemker, M. B. Heyman, A. R. Otley, S. S. Baker, J. S. Evans, B. S. Kirschner, A. S. Patel, D. Ziring, B. C. Trapnell, F. A. Sylvester, M. C. Stephens, R. N. Baldassano, J. F. Markowitz, J. Cho, R. J. Xavier, C. Huttenhower, B. J. Aronow, G. Gibson, J. S. Hyams, and M. C. Dubinsky, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” Lancet 389(10080), 1710–1718 (2017).
[Crossref] [PubMed]

Görtz, R. S.

F. Knieling, C. Neufert, A. Hartmann, J. Claussen, A. Urich, C. Egger, M. Vetter, S. Fischer, L. Pfeifer, A. Hagel, C. Kielisch, R. S. Görtz, D. Wildner, M. Engel, J. Röther, W. Uter, J. Siebler, R. Atreya, W. Rascher, D. Strobel, M. F. Neurath, and M. J. Waldner, “Multispectral Optoacoustic Tomography for Assessment of Crohn’s Disease Activity,” N. Engl. J. Med. 376(13), 1292–1294 (2017).
[Crossref] [PubMed]

Griffiths, A.

S. Kugathasan, L. A. Denson, T. D. Walters, M.-O. Kim, U. M. Marigorta, M. Schirmer, K. Mondal, C. Liu, A. Griffiths, J. D. Noe, W. V. Crandall, S. Snapper, S. Rabizadeh, J. R. Rosh, J. M. Shapiro, S. Guthery, D. R. Mack, R. Kellermayer, M. D. Kappelman, S. Steiner, D. E. Moulton, D. Keljo, S. Cohen, M. Oliva-Hemker, M. B. Heyman, A. R. Otley, S. S. Baker, J. S. Evans, B. S. Kirschner, A. S. Patel, D. Ziring, B. C. Trapnell, F. A. Sylvester, M. C. Stephens, R. N. Baldassano, J. F. Markowitz, J. Cho, R. J. Xavier, C. Huttenhower, B. J. Aronow, G. Gibson, J. S. Hyams, and M. C. Dubinsky, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” Lancet 389(10080), 1710–1718 (2017).
[Crossref] [PubMed]

Guthery, S.

S. Kugathasan, L. A. Denson, T. D. Walters, M.-O. Kim, U. M. Marigorta, M. Schirmer, K. Mondal, C. Liu, A. Griffiths, J. D. Noe, W. V. Crandall, S. Snapper, S. Rabizadeh, J. R. Rosh, J. M. Shapiro, S. Guthery, D. R. Mack, R. Kellermayer, M. D. Kappelman, S. Steiner, D. E. Moulton, D. Keljo, S. Cohen, M. Oliva-Hemker, M. B. Heyman, A. R. Otley, S. S. Baker, J. S. Evans, B. S. Kirschner, A. S. Patel, D. Ziring, B. C. Trapnell, F. A. Sylvester, M. C. Stephens, R. N. Baldassano, J. F. Markowitz, J. Cho, R. J. Xavier, C. Huttenhower, B. J. Aronow, G. Gibson, J. S. Hyams, and M. C. Dubinsky, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” Lancet 389(10080), 1710–1718 (2017).
[Crossref] [PubMed]

Györke, T.

Z. Tarján, G. Tóth, T. Györke, A. Mester, K. Karlinger, and E. K. Makó, “Ultrasound in Crohn’s disease of the small bowel,” Eur. J. Radiol. 35(3), 176–182 (2000).
[Crossref] [PubMed]

Haase, V. H.

D. F. Higgins, K. Kimura, M. Iwano, and V. H. Haase, “Hypoxia-inducible factor signaling in the development of tissue fibrosis,” Cell Cycle 7(9), 1128–1132 (2008).
[Crossref] [PubMed]

Hagel, A.

F. Knieling, C. Neufert, A. Hartmann, J. Claussen, A. Urich, C. Egger, M. Vetter, S. Fischer, L. Pfeifer, A. Hagel, C. Kielisch, R. S. Görtz, D. Wildner, M. Engel, J. Röther, W. Uter, J. Siebler, R. Atreya, W. Rascher, D. Strobel, M. F. Neurath, and M. J. Waldner, “Multispectral Optoacoustic Tomography for Assessment of Crohn’s Disease Activity,” N. Engl. J. Med. 376(13), 1292–1294 (2017).
[Crossref] [PubMed]

Hamblin, M. R.

C. P. Sabino, A. M. Deana, T. M. Yoshimura, D. F. T. da Silva, C. M. França, M. R. Hamblin, and M. S. Ribeiro, “The optical properties of mouse skin in the visible and near infrared spectral regions,” J. Photochem. Photobiol. B 160, 72–78 (2016).
[Crossref] [PubMed]

Hanauer, S. B.

G. R. Lichtenstein, A. Olson, S. Travers, R. H. Diamond, D. M. Chen, M. L. Pritchard, B. G. Feagan, R. D. Cohen, B. A. Salzberg, S. B. Hanauer, and W. J. Sandborn, “Factors Associated with the Development of Intestinal Strictures or Obstructions in Patients with Crohn’s Disease,” Am. J. Gastroenterol. 101(5), 1030–1038 (2006).
[Crossref] [PubMed]

Hartmann, A.

F. Knieling, C. Neufert, A. Hartmann, J. Claussen, A. Urich, C. Egger, M. Vetter, S. Fischer, L. Pfeifer, A. Hagel, C. Kielisch, R. S. Görtz, D. Wildner, M. Engel, J. Röther, W. Uter, J. Siebler, R. Atreya, W. Rascher, D. Strobel, M. F. Neurath, and M. J. Waldner, “Multispectral Optoacoustic Tomography for Assessment of Crohn’s Disease Activity,” N. Engl. J. Med. 376(13), 1292–1294 (2017).
[Crossref] [PubMed]

Hellstrom, W. J. G.

S. Leungwattanakij, T. J. Bivalacqua, M. F. Usta, D.-Y. Yang, J.-S. Hyun, H. C. Champion, A. B. Abdel-Mageed, and W. J. G. Hellstrom, “Cavernous Neurotomy Causes Hypoxia and Fibrosis in Rat Corpus Cavernosum,” J. Androl. 24(2), 239–245 (2003).
[Crossref] [PubMed]

Herbst, F.

G. Oberhuber, P. C. Stangl, H. Vogelsang, E. Schober, F. Herbst, and C. Gasche, “Significant association of strictures and internal fistula formation in Crohn’s disease,” Virchows Arch. 437(3), 293–297 (2000).
[Crossref] [PubMed]

Heyman, M. B.

S. Kugathasan, L. A. Denson, T. D. Walters, M.-O. Kim, U. M. Marigorta, M. Schirmer, K. Mondal, C. Liu, A. Griffiths, J. D. Noe, W. V. Crandall, S. Snapper, S. Rabizadeh, J. R. Rosh, J. M. Shapiro, S. Guthery, D. R. Mack, R. Kellermayer, M. D. Kappelman, S. Steiner, D. E. Moulton, D. Keljo, S. Cohen, M. Oliva-Hemker, M. B. Heyman, A. R. Otley, S. S. Baker, J. S. Evans, B. S. Kirschner, A. S. Patel, D. Ziring, B. C. Trapnell, F. A. Sylvester, M. C. Stephens, R. N. Baldassano, J. F. Markowitz, J. Cho, R. J. Xavier, C. Huttenhower, B. J. Aronow, G. Gibson, J. S. Hyams, and M. C. Dubinsky, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” Lancet 389(10080), 1710–1718 (2017).
[Crossref] [PubMed]

Higgins, D. F.

D. F. Higgins, K. Kimura, M. Iwano, and V. H. Haase, “Hypoxia-inducible factor signaling in the development of tissue fibrosis,” Cell Cycle 7(9), 1128–1132 (2008).
[Crossref] [PubMed]

Higgins, P. D.

Higgins, P. D. R.

R. W. Stidham and P. D. R. Higgins, “Imaging of intestinal fibrosis: current challenges and future methods,” United European Gastroenterol. J. 4(4), 515–522 (2016).
[Crossref] [PubMed]

J. R. Dillman, R. W. Stidham, P. D. R. Higgins, D. S. Moons, L. A. Johnson, and J. M. Rubin, “US Elastography-derived Shear Wave Velocity Helps Distinguish Acutely Inflamed from Fibrotic Bowel in a Crohn Disease Animal Model,” Radiology 267(3), 757–766 (2013).
[Crossref] [PubMed]

R. W. Stidham, J. Xu, L. A. Johnson, K. Kim, D. S. Moons, B. J. McKenna, J. M. Rubin, and P. D. R. Higgins, “Ultrasound Elasticity Imaging for Detecting Intestinal Fibrosis and Inflammation in Rats and Humans with Crohn’s Disease,” Gastroenterology 141(3), 819–826 (2011).
[Crossref] [PubMed]

K. Kim, L. A. Johnson, C. Jia, J. C. Joyce, S. Rangwalla, P. D. R. Higgins, and J. M. Rubin, “Noninvasive Ultrasound Elasticity Imaging (UEI) of Crohn’s Disease: Animal Model,” Ultrasound Med. Biol. 34(6), 902–912 (2008).
[Crossref] [PubMed]

Hu, S.

L. V. Wang and S. Hu, “Photoacoustic Tomography: In Vivo Imaging from Organelles to Organs,” Science 335(6075), 1458–1462 (2012).
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H.-W. Wang, N. Chai, P. Wang, S. Hu, W. Dou, D. Umulis, L. V. Wang, M. Sturek, R. Lucht, and J.-X. Cheng, “Label-Free Bond-Selective Imaging by Listening to Vibrationally Excited Molecules,” Phys. Rev. Lett. 106(23), 238106 (2011).
[Crossref] [PubMed]

Huang, S.

Hughes, H. K.

Huttenhower, C.

S. Kugathasan, L. A. Denson, T. D. Walters, M.-O. Kim, U. M. Marigorta, M. Schirmer, K. Mondal, C. Liu, A. Griffiths, J. D. Noe, W. V. Crandall, S. Snapper, S. Rabizadeh, J. R. Rosh, J. M. Shapiro, S. Guthery, D. R. Mack, R. Kellermayer, M. D. Kappelman, S. Steiner, D. E. Moulton, D. Keljo, S. Cohen, M. Oliva-Hemker, M. B. Heyman, A. R. Otley, S. S. Baker, J. S. Evans, B. S. Kirschner, A. S. Patel, D. Ziring, B. C. Trapnell, F. A. Sylvester, M. C. Stephens, R. N. Baldassano, J. F. Markowitz, J. Cho, R. J. Xavier, C. Huttenhower, B. J. Aronow, G. Gibson, J. S. Hyams, and M. C. Dubinsky, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” Lancet 389(10080), 1710–1718 (2017).
[Crossref] [PubMed]

Hwang, J. H.

D. A. Fisher, J. T. Maple, T. Ben-Menachem, B. D. Cash, G. A. Decker, D. S. Early, J. A. Evans, R. D. Fanelli, N. Fukami, J. H. Hwang, R. Jain, T. L. Jue, K. M. Khan, P. M. Malpas, R. N. Sharaf, A. K. Shergill, J. A. Dominitz, and ASGE Standards of Practice Committee, “Complications of colonoscopy,” Gastrointest. Endosc. 74(4), 745–752 (2011).
[Crossref] [PubMed]

Hyams, J. S.

S. Kugathasan, L. A. Denson, T. D. Walters, M.-O. Kim, U. M. Marigorta, M. Schirmer, K. Mondal, C. Liu, A. Griffiths, J. D. Noe, W. V. Crandall, S. Snapper, S. Rabizadeh, J. R. Rosh, J. M. Shapiro, S. Guthery, D. R. Mack, R. Kellermayer, M. D. Kappelman, S. Steiner, D. E. Moulton, D. Keljo, S. Cohen, M. Oliva-Hemker, M. B. Heyman, A. R. Otley, S. S. Baker, J. S. Evans, B. S. Kirschner, A. S. Patel, D. Ziring, B. C. Trapnell, F. A. Sylvester, M. C. Stephens, R. N. Baldassano, J. F. Markowitz, J. Cho, R. J. Xavier, C. Huttenhower, B. J. Aronow, G. Gibson, J. S. Hyams, and M. C. Dubinsky, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” Lancet 389(10080), 1710–1718 (2017).
[Crossref] [PubMed]

Hyun, J.-S.

S. Leungwattanakij, T. J. Bivalacqua, M. F. Usta, D.-Y. Yang, J.-S. Hyun, H. C. Champion, A. B. Abdel-Mageed, and W. J. G. Hellstrom, “Cavernous Neurotomy Causes Hypoxia and Fibrosis in Rat Corpus Cavernosum,” J. Androl. 24(2), 239–245 (2003).
[Crossref] [PubMed]

Iwano, M.

D. F. Higgins, K. Kimura, M. Iwano, and V. H. Haase, “Hypoxia-inducible factor signaling in the development of tissue fibrosis,” Cell Cycle 7(9), 1128–1132 (2008).
[Crossref] [PubMed]

Jacques, S. L.

S. L. Jacques, “Optical properties of biological tissues: a review,” Phys. Med. Biol. 58(11), R37–R61 (2013).
[Crossref] [PubMed]

Jain, R.

D. A. Fisher, J. T. Maple, T. Ben-Menachem, B. D. Cash, G. A. Decker, D. S. Early, J. A. Evans, R. D. Fanelli, N. Fukami, J. H. Hwang, R. Jain, T. L. Jue, K. M. Khan, P. M. Malpas, R. N. Sharaf, A. K. Shergill, J. A. Dominitz, and ASGE Standards of Practice Committee, “Complications of colonoscopy,” Gastrointest. Endosc. 74(4), 745–752 (2011).
[Crossref] [PubMed]

Jauregui-Amezaga, A.

J. Rimola, N. Planell, S. Rodríguez, S. Delgado, I. Ordás, A. Ramírez-Morros, C. Ayuso, M. Aceituno, E. Ricart, A. Jauregui-Amezaga, J. Panés, and M. Cuatrecasas, “Characterization of Inflammation and Fibrosis in Crohn’s Disease Lesions by Magnetic Resonance Imaging,” Am. J. Gastroenterol. 110(3), 432–440 (2015).
[Crossref] [PubMed]

Jia, C.

K. Kim, L. A. Johnson, C. Jia, J. C. Joyce, S. Rangwalla, P. D. R. Higgins, and J. M. Rubin, “Noninvasive Ultrasound Elasticity Imaging (UEI) of Crohn’s Disease: Animal Model,” Ultrasound Med. Biol. 34(6), 902–912 (2008).
[Crossref] [PubMed]

Jiang, H.

Johnson, L. A.

H. Lei, L. A. Johnson, S. Liu, D. S. Moons, T. Ma, Q. Zhou, M. D. Rice, J. Ni, X. Wang, P. D. Higgins, and G. Xu, “Characterizing intestinal inflammation and fibrosis in Crohn’s disease by photoacoustic imaging: feasibility study,” Biomed. Opt. Express 7(7), 2837–2848 (2016).
[Crossref] [PubMed]

J. R. Dillman, R. W. Stidham, P. D. R. Higgins, D. S. Moons, L. A. Johnson, and J. M. Rubin, “US Elastography-derived Shear Wave Velocity Helps Distinguish Acutely Inflamed from Fibrotic Bowel in a Crohn Disease Animal Model,” Radiology 267(3), 757–766 (2013).
[Crossref] [PubMed]

R. W. Stidham, J. Xu, L. A. Johnson, K. Kim, D. S. Moons, B. J. McKenna, J. M. Rubin, and P. D. R. Higgins, “Ultrasound Elasticity Imaging for Detecting Intestinal Fibrosis and Inflammation in Rats and Humans with Crohn’s Disease,” Gastroenterology 141(3), 819–826 (2011).
[Crossref] [PubMed]

K. Kim, L. A. Johnson, C. Jia, J. C. Joyce, S. Rangwalla, P. D. R. Higgins, and J. M. Rubin, “Noninvasive Ultrasound Elasticity Imaging (UEI) of Crohn’s Disease: Animal Model,” Ultrasound Med. Biol. 34(6), 902–912 (2008).
[Crossref] [PubMed]

Joyce, J. C.

K. Kim, L. A. Johnson, C. Jia, J. C. Joyce, S. Rangwalla, P. D. R. Higgins, and J. M. Rubin, “Noninvasive Ultrasound Elasticity Imaging (UEI) of Crohn’s Disease: Animal Model,” Ultrasound Med. Biol. 34(6), 902–912 (2008).
[Crossref] [PubMed]

Jue, T. L.

D. A. Fisher, J. T. Maple, T. Ben-Menachem, B. D. Cash, G. A. Decker, D. S. Early, J. A. Evans, R. D. Fanelli, N. Fukami, J. H. Hwang, R. Jain, T. L. Jue, K. M. Khan, P. M. Malpas, R. N. Sharaf, A. K. Shergill, J. A. Dominitz, and ASGE Standards of Practice Committee, “Complications of colonoscopy,” Gastrointest. Endosc. 74(4), 745–752 (2011).
[Crossref] [PubMed]

Kappelman, M. D.

S. Kugathasan, L. A. Denson, T. D. Walters, M.-O. Kim, U. M. Marigorta, M. Schirmer, K. Mondal, C. Liu, A. Griffiths, J. D. Noe, W. V. Crandall, S. Snapper, S. Rabizadeh, J. R. Rosh, J. M. Shapiro, S. Guthery, D. R. Mack, R. Kellermayer, M. D. Kappelman, S. Steiner, D. E. Moulton, D. Keljo, S. Cohen, M. Oliva-Hemker, M. B. Heyman, A. R. Otley, S. S. Baker, J. S. Evans, B. S. Kirschner, A. S. Patel, D. Ziring, B. C. Trapnell, F. A. Sylvester, M. C. Stephens, R. N. Baldassano, J. F. Markowitz, J. Cho, R. J. Xavier, C. Huttenhower, B. J. Aronow, G. Gibson, J. S. Hyams, and M. C. Dubinsky, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” Lancet 389(10080), 1710–1718 (2017).
[Crossref] [PubMed]

Karlinger, K.

Z. Tarján, G. Tóth, T. Györke, A. Mester, K. Karlinger, and E. K. Makó, “Ultrasound in Crohn’s disease of the small bowel,” Eur. J. Radiol. 35(3), 176–182 (2000).
[Crossref] [PubMed]

Keljo, D.

S. Kugathasan, L. A. Denson, T. D. Walters, M.-O. Kim, U. M. Marigorta, M. Schirmer, K. Mondal, C. Liu, A. Griffiths, J. D. Noe, W. V. Crandall, S. Snapper, S. Rabizadeh, J. R. Rosh, J. M. Shapiro, S. Guthery, D. R. Mack, R. Kellermayer, M. D. Kappelman, S. Steiner, D. E. Moulton, D. Keljo, S. Cohen, M. Oliva-Hemker, M. B. Heyman, A. R. Otley, S. S. Baker, J. S. Evans, B. S. Kirschner, A. S. Patel, D. Ziring, B. C. Trapnell, F. A. Sylvester, M. C. Stephens, R. N. Baldassano, J. F. Markowitz, J. Cho, R. J. Xavier, C. Huttenhower, B. J. Aronow, G. Gibson, J. S. Hyams, and M. C. Dubinsky, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” Lancet 389(10080), 1710–1718 (2017).
[Crossref] [PubMed]

Kellermayer, R.

S. Kugathasan, L. A. Denson, T. D. Walters, M.-O. Kim, U. M. Marigorta, M. Schirmer, K. Mondal, C. Liu, A. Griffiths, J. D. Noe, W. V. Crandall, S. Snapper, S. Rabizadeh, J. R. Rosh, J. M. Shapiro, S. Guthery, D. R. Mack, R. Kellermayer, M. D. Kappelman, S. Steiner, D. E. Moulton, D. Keljo, S. Cohen, M. Oliva-Hemker, M. B. Heyman, A. R. Otley, S. S. Baker, J. S. Evans, B. S. Kirschner, A. S. Patel, D. Ziring, B. C. Trapnell, F. A. Sylvester, M. C. Stephens, R. N. Baldassano, J. F. Markowitz, J. Cho, R. J. Xavier, C. Huttenhower, B. J. Aronow, G. Gibson, J. S. Hyams, and M. C. Dubinsky, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” Lancet 389(10080), 1710–1718 (2017).
[Crossref] [PubMed]

Khan, K. M.

D. A. Fisher, J. T. Maple, T. Ben-Menachem, B. D. Cash, G. A. Decker, D. S. Early, J. A. Evans, R. D. Fanelli, N. Fukami, J. H. Hwang, R. Jain, T. L. Jue, K. M. Khan, P. M. Malpas, R. N. Sharaf, A. K. Shergill, J. A. Dominitz, and ASGE Standards of Practice Committee, “Complications of colonoscopy,” Gastrointest. Endosc. 74(4), 745–752 (2011).
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Kielisch, C.

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Liu, X.

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S. Kugathasan, L. A. Denson, T. D. Walters, M.-O. Kim, U. M. Marigorta, M. Schirmer, K. Mondal, C. Liu, A. Griffiths, J. D. Noe, W. V. Crandall, S. Snapper, S. Rabizadeh, J. R. Rosh, J. M. Shapiro, S. Guthery, D. R. Mack, R. Kellermayer, M. D. Kappelman, S. Steiner, D. E. Moulton, D. Keljo, S. Cohen, M. Oliva-Hemker, M. B. Heyman, A. R. Otley, S. S. Baker, J. S. Evans, B. S. Kirschner, A. S. Patel, D. Ziring, B. C. Trapnell, F. A. Sylvester, M. C. Stephens, R. N. Baldassano, J. F. Markowitz, J. Cho, R. J. Xavier, C. Huttenhower, B. J. Aronow, G. Gibson, J. S. Hyams, and M. C. Dubinsky, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” Lancet 389(10080), 1710–1718 (2017).
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S. Kugathasan, L. A. Denson, T. D. Walters, M.-O. Kim, U. M. Marigorta, M. Schirmer, K. Mondal, C. Liu, A. Griffiths, J. D. Noe, W. V. Crandall, S. Snapper, S. Rabizadeh, J. R. Rosh, J. M. Shapiro, S. Guthery, D. R. Mack, R. Kellermayer, M. D. Kappelman, S. Steiner, D. E. Moulton, D. Keljo, S. Cohen, M. Oliva-Hemker, M. B. Heyman, A. R. Otley, S. S. Baker, J. S. Evans, B. S. Kirschner, A. S. Patel, D. Ziring, B. C. Trapnell, F. A. Sylvester, M. C. Stephens, R. N. Baldassano, J. F. Markowitz, J. Cho, R. J. Xavier, C. Huttenhower, B. J. Aronow, G. Gibson, J. S. Hyams, and M. C. Dubinsky, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” Lancet 389(10080), 1710–1718 (2017).
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G. Xu, Z. X. Meng, J. D. Lin, C. X. Deng, P. L. Carson, J. B. Fowlkes, C. Tao, X. Liu, and X. Wang, “High resolution Physio-chemical Tissue Analysis: Towards Non-invasive In Vivo Biopsy,” Sci. Rep. 6(1), 16937 (2016).
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G. Xu, Z. X. Meng, J. D. Lin, C. X. Deng, P. L. Carson, J. B. Fowlkes, C. Tao, X. Liu, and X. Wang, “High resolution physio-chemical tissue analysis: towards non-invasive in vivo biopsy,” Sci. Rep. 6(1), 16937 (2016).
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Mester, A.

Z. Tarján, G. Tóth, T. Györke, A. Mester, K. Karlinger, and E. K. Makó, “Ultrasound in Crohn’s disease of the small bowel,” Eur. J. Radiol. 35(3), 176–182 (2000).
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Minguez, M.

J. M. Esteban, L. Maldonado, V. Sanchiz, M. Minguez, and A. Benages, “Activity of Crohn’s disease assessed by colour Doppler ultrasound analysis of the affected loops,” Eur. Radiol. 11(8), 1423–1428 (2001).
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Mondal, K.

S. Kugathasan, L. A. Denson, T. D. Walters, M.-O. Kim, U. M. Marigorta, M. Schirmer, K. Mondal, C. Liu, A. Griffiths, J. D. Noe, W. V. Crandall, S. Snapper, S. Rabizadeh, J. R. Rosh, J. M. Shapiro, S. Guthery, D. R. Mack, R. Kellermayer, M. D. Kappelman, S. Steiner, D. E. Moulton, D. Keljo, S. Cohen, M. Oliva-Hemker, M. B. Heyman, A. R. Otley, S. S. Baker, J. S. Evans, B. S. Kirschner, A. S. Patel, D. Ziring, B. C. Trapnell, F. A. Sylvester, M. C. Stephens, R. N. Baldassano, J. F. Markowitz, J. Cho, R. J. Xavier, C. Huttenhower, B. J. Aronow, G. Gibson, J. S. Hyams, and M. C. Dubinsky, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” Lancet 389(10080), 1710–1718 (2017).
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Moulton, D. E.

S. Kugathasan, L. A. Denson, T. D. Walters, M.-O. Kim, U. M. Marigorta, M. Schirmer, K. Mondal, C. Liu, A. Griffiths, J. D. Noe, W. V. Crandall, S. Snapper, S. Rabizadeh, J. R. Rosh, J. M. Shapiro, S. Guthery, D. R. Mack, R. Kellermayer, M. D. Kappelman, S. Steiner, D. E. Moulton, D. Keljo, S. Cohen, M. Oliva-Hemker, M. B. Heyman, A. R. Otley, S. S. Baker, J. S. Evans, B. S. Kirschner, A. S. Patel, D. Ziring, B. C. Trapnell, F. A. Sylvester, M. C. Stephens, R. N. Baldassano, J. F. Markowitz, J. Cho, R. J. Xavier, C. Huttenhower, B. J. Aronow, G. Gibson, J. S. Hyams, and M. C. Dubinsky, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” Lancet 389(10080), 1710–1718 (2017).
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Mummert, L. L.

R. D. Cohen, L. R. Larson, J. M. Roth, R. V. Becker, and L. L. Mummert, “The cost of hospitalization in Crohn’s disease,” Am. J. Gastroenterol. 95(2), 524–530 (2000).
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Murray, K.

I. C. Lawrance, C. J. Welman, P. Shipman, and K. Murray, “Correlation of MRI-determined small bowel Crohn’s disease categories with medical response and surgical pathology,” World J. Gastroenterol. 15(27), 3367–3375 (2009).
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Neurath, M. F.

F. Knieling, C. Neufert, A. Hartmann, J. Claussen, A. Urich, C. Egger, M. Vetter, S. Fischer, L. Pfeifer, A. Hagel, C. Kielisch, R. S. Görtz, D. Wildner, M. Engel, J. Röther, W. Uter, J. Siebler, R. Atreya, W. Rascher, D. Strobel, M. F. Neurath, and M. J. Waldner, “Multispectral Optoacoustic Tomography for Assessment of Crohn’s Disease Activity,” N. Engl. J. Med. 376(13), 1292–1294 (2017).
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Ni, J.

Noe, J. D.

S. Kugathasan, L. A. Denson, T. D. Walters, M.-O. Kim, U. M. Marigorta, M. Schirmer, K. Mondal, C. Liu, A. Griffiths, J. D. Noe, W. V. Crandall, S. Snapper, S. Rabizadeh, J. R. Rosh, J. M. Shapiro, S. Guthery, D. R. Mack, R. Kellermayer, M. D. Kappelman, S. Steiner, D. E. Moulton, D. Keljo, S. Cohen, M. Oliva-Hemker, M. B. Heyman, A. R. Otley, S. S. Baker, J. S. Evans, B. S. Kirschner, A. S. Patel, D. Ziring, B. C. Trapnell, F. A. Sylvester, M. C. Stephens, R. N. Baldassano, J. F. Markowitz, J. Cho, R. J. Xavier, C. Huttenhower, B. J. Aronow, G. Gibson, J. S. Hyams, and M. C. Dubinsky, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” Lancet 389(10080), 1710–1718 (2017).
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Oliva-Hemker, M.

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Stoica, G.

X. Wang, X. Xie, G. Ku, L. V. Wang, and G. Stoica, “Noninvasive imaging of hemoglobin concentration and oxygenation in the rat brain using high-resolution photoacoustic tomography,” J. Biomed. Opt. 11(2), 024015 (2006).
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F. Knieling, C. Neufert, A. Hartmann, J. Claussen, A. Urich, C. Egger, M. Vetter, S. Fischer, L. Pfeifer, A. Hagel, C. Kielisch, R. S. Görtz, D. Wildner, M. Engel, J. Röther, W. Uter, J. Siebler, R. Atreya, W. Rascher, D. Strobel, M. F. Neurath, and M. J. Waldner, “Multispectral Optoacoustic Tomography for Assessment of Crohn’s Disease Activity,” N. Engl. J. Med. 376(13), 1292–1294 (2017).
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S. Kugathasan, L. A. Denson, T. D. Walters, M.-O. Kim, U. M. Marigorta, M. Schirmer, K. Mondal, C. Liu, A. Griffiths, J. D. Noe, W. V. Crandall, S. Snapper, S. Rabizadeh, J. R. Rosh, J. M. Shapiro, S. Guthery, D. R. Mack, R. Kellermayer, M. D. Kappelman, S. Steiner, D. E. Moulton, D. Keljo, S. Cohen, M. Oliva-Hemker, M. B. Heyman, A. R. Otley, S. S. Baker, J. S. Evans, B. S. Kirschner, A. S. Patel, D. Ziring, B. C. Trapnell, F. A. Sylvester, M. C. Stephens, R. N. Baldassano, J. F. Markowitz, J. Cho, R. J. Xavier, C. Huttenhower, B. J. Aronow, G. Gibson, J. S. Hyams, and M. C. Dubinsky, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” Lancet 389(10080), 1710–1718 (2017).
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P. Paolantonio, R. Ferrari, F. Vecchietti, S. Cucchiara, and A. Laghi, “Current status of MR imaging in the evaluation of IBD in a pediatric population of patients,” Eur. J. Radiol. 69(3), 418–424 (2009).
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X. Wang, X. Xie, G. Ku, L. V. Wang, and G. Stoica, “Noninvasive imaging of hemoglobin concentration and oxygenation in the rat brain using high-resolution photoacoustic tomography,” J. Biomed. Opt. 11(2), 024015 (2006).
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S. Kugathasan, L. A. Denson, T. D. Walters, M.-O. Kim, U. M. Marigorta, M. Schirmer, K. Mondal, C. Liu, A. Griffiths, J. D. Noe, W. V. Crandall, S. Snapper, S. Rabizadeh, J. R. Rosh, J. M. Shapiro, S. Guthery, D. R. Mack, R. Kellermayer, M. D. Kappelman, S. Steiner, D. E. Moulton, D. Keljo, S. Cohen, M. Oliva-Hemker, M. B. Heyman, A. R. Otley, S. S. Baker, J. S. Evans, B. S. Kirschner, A. S. Patel, D. Ziring, B. C. Trapnell, F. A. Sylvester, M. C. Stephens, R. N. Baldassano, J. F. Markowitz, J. Cho, R. J. Xavier, C. Huttenhower, B. J. Aronow, G. Gibson, J. S. Hyams, and M. C. Dubinsky, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” Lancet 389(10080), 1710–1718 (2017).
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J. Yuan, G. Xu, Y. Yu, Y. Zhou, P. L. Carson, X. Wang, and X. Liu, “Real-time photoacoustic and ultrasound dual-modality imaging system facilitated with graphics processing unit and code parallel optimization,” J. Biomed. Opt. 18(8), 086001 (2013).
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J. Yuan, G. Xu, Y. Yu, Y. Zhou, P. L. Carson, X. Wang, and X. Liu, “Real-time photoacoustic and ultrasound dual-modality imaging system facilitated with graphics processing unit and code parallel optimization,” J. Biomed. Opt. 18(8), 086001 (2013).
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Figures (7)

Fig. 1
Fig. 1 Optical absorption spectra of relevant molecular components in this study. The shaded areas are the wavelengths ranges that are targeting the hemoglobin and collagen contents, respectively. Hb: Hemoglobin.
Fig. 2
Fig. 2 The experiment setups. (a) The internal illumination delivery was achieved using a fiber optic diffuser. (b) The external illumination was delivered by integrating fiber optics to the US probe with a fiber holder. The details of the fiber holder are shown in Fig. 3.
Fig. 3
Fig. 3 PA-US parallel imaging probe (a) Side view; (b) Bottom view; (c) Front view.
Fig. 4
Fig. 4 Gross pathology of the cecum and colon from acute vs. chronic TNBS rats. Ce = cecum, PC = proximal colon (unaffected), DC = affected distal colon. Upper panel inset illustrates the gross luminal differences between the acute and chronic models with hemorrhagic and necrotic regions in the acute model and the thickened, contracted features characteristic of the chronic fibrosis. Histological features of the acute model (A-D). H&E staining (A) identifies increased inflammatory cells (dark blue nuclei, detailed in inset C), and large regions of extravascular red blood cells (B, arrowheads) in the acute model with red blood cell extravasation from blood vessels (asterisks, detailed in inset D). Trichrome staining (B,D) reveled structural collagen only. Large collagen deposition was not observed. In contrast, histological features of the chronic fibrosis model (E-I) demonstrated massive transmural collagen deposition without red blood cell extravasation. H & E staining revealed a healed ulcer (E, arrow) with few inflammatory cells present (inset, G). Trichrome staining (F) illustrates massive disorganized collagen deposition (blue staining, detailed in H) and architectural disruption by collagen extending into the deeper muscle layers (inset I).
Fig. 5
Fig. 5 PA-US parallel imaging with internal illumination. (a) shows the example images of the PA-US parallel images acquired in a chronic TNBS animal. The skin and muscle layers in the US images are shaded in green and purple. (b) shows the statistics with the quantitative values from each animal.
Fig. 6
Fig. 6 The representative US and PA images within the ROIs. The top and bottom rows are acquired in acute and chronic animals, respectively. Column 1 present the US images. The green and purple shaded areas in the first column are skin and muscle layers, respectively. Columns 2-4 are PA images acquired in parallel with the US imaging at 1310, 750 and 850 respectively. Columns 5-6 are the US images with coregistered relative oxygenation and collagen/Hb ratio within the ROIs. M: Membrane supporting the acoustic stand-off. AW: Abdominal wall. BW: Back wall. ROI: Region-of-interest. ISC: Intestinal stricture cross-section. PB: Pelvic bone. Hb: Hemoglobin.
Fig. 7
Fig. 7 Statistical results of the averaged factors derived from all the animals.

Tables (1)

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Table 1 optical properties used for spectral unmixing and optical attenuation along the penetration depth [31–33]. Hb: Hemoglobin.

Equations (3)

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P comp ( d skin , d muscle )= P meas ÷exp{[ μ a_skin (λ)+μ ' s_skin (λ)]× d skin [ μ a_muscle (λ)+μ ' s_muscle (λ)]× d muscle }
[ c HbO c Hb c Collagen ]= [ μ HbO@750nm μ Hb@750nm μ collagen@750nm μ HbO@850nm μ Hb@850nm μ collagen@850nm μ HbO@1310nm μ Hb@1310nm μ collagen@1310nm ] 1 ×[ P 750nm P 850nm P 1310nm ]
Sp O 2 = c HbO c HbO + c Hb , Collagen/Hb= c collagen c HbO + c Hb

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