Molecular Imaging of Pulmonary Tuberculosis in an Ex-Vivo Mouse Model Using Spectral Photon-Counting Computed Tomography and Micro-CT

Chiara Lowe; Ana Ortega-Gil; Mahdieh Moghiseh; Nigel G. Anderson; Arrate Munoz-Barrutia; Juan Jose Vaquero; Aamir Y. Raja; Aysouda Matanaghi; Alexander I. Chernoglazov; Theodorus Dapamede; Sikiru A. Adebileje; Steven Alexander; Maya R. Amma; Marzieh Anjomrouz; Fatemeh Asghariomabad; Ali Atharifard; James Atlas; Kenzie Baer; Stephen T. Bell; Srinidhi Bheesette; Philip H. Butler; Pierre Carbonez; Claire Chambers; Krishna M. Chapagain; Jennifer A. Clark; Frances Colgan; Jonathan S. Crighton; Shishir Dahal; Jerome Damet; Niels J.A. De Ruiter; Robert M.N. Doesburg; Neryda Duncan; Nooshin Ghodsian; Steven P. Gieseg; Brian P. Goulter; Sam Gurney; Joseph L. Healy; Praveen Kumar Kanithi; Tracy Kirkbride; Stuart P. Lansley; V. B.H. Mandalika; Emmanuel Marfo; David Palmer; Raj K. Panta; Hannah M. Prebble; Peter Renaud; Yann Sayous; Nanette Schleich; Emily Searle; Jereena S. Sheeja; Lieza Vanden Broeke; V. S. Vivek; E. Peter Walker; Michael F. Walsh; Manoj Wijesooriya; W. Ross Younger; Anthony P.H. Butler

doi:10.1109/ACCESS.2021.3076432

Molecular Imaging of Pulmonary Tuberculosis in an Ex-Vivo Mouse Model Using Spectral Photon-Counting Computed Tomography and Micro-CT

Chiara Lowe, Ana Ortega-Gil, Mahdieh Moghiseh, Nigel G. Anderson, Arrate Munoz-Barrutia, Juan Jose Vaquero, Aamir Y. Raja, Aysouda Matanaghi, Alexander I. Chernoglazov, Theodorus Dapamede, Sikiru A. Adebileje, Steven Alexander, Maya R. Amma, Marzieh Anjomrouz, Fatemeh Asghariomabad, Ali Atharifard, James Atlas, Kenzie Baer, Stephen T. Bell, Srinidhi BheesettePhilip H. Butler, Pierre Carbonez, Claire Chambers, Krishna M. Chapagain, Jennifer A. Clark, Frances Colgan, Jonathan S. Crighton, Shishir Dahal, Jerome Damet, Niels J.A. De Ruiter, Robert M.N. Doesburg, Neryda Duncan, Nooshin Ghodsian, Steven P. Gieseg, Brian P. Goulter, Sam Gurney, Joseph L. Healy, Praveen Kumar Kanithi, Tracy Kirkbride, Stuart P. Lansley, V. B.H. Mandalika, Emmanuel Marfo, David Palmer, Raj K. Panta, Hannah M. Prebble, Peter Renaud, Yann Sayous, Nanette Schleich, Emily Searle, Jereena S. Sheeja, Lieza Vanden Broeke, V. S. Vivek, E. Peter Walker, Michael F. Walsh, Manoj Wijesooriya, W. Ross Younger, Anthony P.H. Butler

Physics

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

Assessment of disease burden and drug efficacy is achieved preclinically using high resolution micro computed tomography (CT). However, micro-CT is not applicable to clinical human imaging due to operating at high dose. In addition, the technology differences between micro-CT and standard clinical CT prevent direct translation of preclinical applications. The current proof-of-concept study presents spectral photon-counting CT as a clinically translatable, molecular imaging tool by assessing contrast uptake in an ex-vivo mouse model of pulmonary tuberculosis (TB). Iodine, a common contrast used in clinical CT imaging, was introduced into a murine model of TB. The excised mouse lungs were imaged using a standard micro-CT subsystem (SuperArgus) and the contrast enhanced TB lesions quantified. The same lungs were imaged using a spectral photoncounting CT system (MARS small-bore scanner). Iodine and soft tissues (water and lipid) were materially separated, and iodine uptake quantified. The volume of the TB infection quantified by spectral CT and micro-CT was found to be 2.96 mm3 and 2.83 mm3, respectively. This proof-of-concept study showed that spectral photon-counting CT could be used as a predictive preclinical imaging tool for the purpose of facilitating drug discovery and development. Also, as this imaging modality is available for human trials, all applications are translatable to human imaging. In conclusion, spectral photon-counting CT could accelerate a deeper understanding of infectious lung diseases using targeted pharmaceuticals and intrinsic markers, and ultimately improve the efficacy of therapies by measuring drug delivery and response to treatment in animal models and later in humans.

Original language	British English
Article number	9419038
Pages (from-to)	67201-67208
Number of pages	8
Journal	IEEE Access
Volume	9
DOIs	https://doi.org/10.1109/ACCESS.2021.3076432
State	Published - 2021

Keywords

High resolution
micro-CT
photon-counting spectral CT
pulmonary tuberculosis
translatable molecular imaging

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1109/ACCESS.2021.3076432

Cite this

Lowe, C., Ortega-Gil, A., Moghiseh, M., Anderson, N. G., Munoz-Barrutia, A., Vaquero, J. J., Raja, A. Y., Matanaghi, A., Chernoglazov, A. I., Dapamede, T., Adebileje, S. A., Alexander, S., Amma, M. R., Anjomrouz, M., Asghariomabad, F., Atharifard, A., Atlas, J., Baer, K., Bell, S. T., ... Butler, A. P. H. (2021). Molecular Imaging of Pulmonary Tuberculosis in an Ex-Vivo Mouse Model Using Spectral Photon-Counting Computed Tomography and Micro-CT. IEEE Access, 9, 67201-67208. Article 9419038. https://doi.org/10.1109/ACCESS.2021.3076432

@article{6733acd41b424dc79f1be43a55056b08,

title = "Molecular Imaging of Pulmonary Tuberculosis in an Ex-Vivo Mouse Model Using Spectral Photon-Counting Computed Tomography and Micro-CT",

abstract = "Assessment of disease burden and drug efficacy is achieved preclinically using high resolution micro computed tomography (CT). However, micro-CT is not applicable to clinical human imaging due to operating at high dose. In addition, the technology differences between micro-CT and standard clinical CT prevent direct translation of preclinical applications. The current proof-of-concept study presents spectral photon-counting CT as a clinically translatable, molecular imaging tool by assessing contrast uptake in an ex-vivo mouse model of pulmonary tuberculosis (TB). Iodine, a common contrast used in clinical CT imaging, was introduced into a murine model of TB. The excised mouse lungs were imaged using a standard micro-CT subsystem (SuperArgus) and the contrast enhanced TB lesions quantified. The same lungs were imaged using a spectral photoncounting CT system (MARS small-bore scanner). Iodine and soft tissues (water and lipid) were materially separated, and iodine uptake quantified. The volume of the TB infection quantified by spectral CT and micro-CT was found to be 2.96 mm3 and 2.83 mm3, respectively. This proof-of-concept study showed that spectral photon-counting CT could be used as a predictive preclinical imaging tool for the purpose of facilitating drug discovery and development. Also, as this imaging modality is available for human trials, all applications are translatable to human imaging. In conclusion, spectral photon-counting CT could accelerate a deeper understanding of infectious lung diseases using targeted pharmaceuticals and intrinsic markers, and ultimately improve the efficacy of therapies by measuring drug delivery and response to treatment in animal models and later in humans.",

keywords = "High resolution, micro-CT, photon-counting spectral CT, pulmonary tuberculosis, translatable molecular imaging",

author = "Chiara Lowe and Ana Ortega-Gil and Mahdieh Moghiseh and Anderson, {Nigel G.} and Arrate Munoz-Barrutia and Vaquero, {Juan Jose} and Raja, {Aamir Y.} and Aysouda Matanaghi and Chernoglazov, {Alexander I.} and Theodorus Dapamede and Adebileje, {Sikiru A.} and Steven Alexander and Amma, {Maya R.} and Marzieh Anjomrouz and Fatemeh Asghariomabad and Ali Atharifard and James Atlas and Kenzie Baer and Bell, {Stephen T.} and Srinidhi Bheesette and Butler, {Philip H.} and Pierre Carbonez and Claire Chambers and Chapagain, {Krishna M.} and Clark, {Jennifer A.} and Frances Colgan and Crighton, {Jonathan S.} and Shishir Dahal and Jerome Damet and {De Ruiter}, {Niels J.A.} and Doesburg, {Robert M.N.} and Neryda Duncan and Nooshin Ghodsian and Gieseg, {Steven P.} and Goulter, {Brian P.} and Sam Gurney and Healy, {Joseph L.} and Kanithi, {Praveen Kumar} and Tracy Kirkbride and Lansley, {Stuart P.} and Mandalika, {V. B.H.} and Emmanuel Marfo and David Palmer and Panta, {Raj K.} and Prebble, {Hannah M.} and Peter Renaud and Yann Sayous and Nanette Schleich and Emily Searle and Sheeja, {Jereena S.} and Broeke, {Lieza Vanden} and Vivek, {V. S.} and Walker, {E. Peter} and Walsh, {Michael F.} and Manoj Wijesooriya and Younger, {W. Ross} and Butler, {Anthony P.H.}",

note = "Funding Information: This work was supported in part by the Ministry of Business, Innovation and Employment (MBIE), New Zealand, under Contract UOCX1404, in part by MARS Bioimaging Ltd., in part by the Ministry of Education through the MedTech CoRE, in part by the University of Otago, in part by the Instituto de Salud Carlos III (Plan Estatal de I+D+i 2013–2016), in part by the European Social Fund (ESF) (ESF investing in your future), in part by the Innovative Medicines Initiative Joint Undertaking through the European Union Seventh Framework Program (FP7/2007–2013) under Grant 115337 and Grant 853989, in part by the European Federation of Pharmaceutical Industries and Associations (EFPIA) Companies, in part by the Spanish Ministry of Economy under Project TEC2016-78052-R, and in part by the Spanish Ministry of Science and Innovation under Grant PID2019-109820RB-I00. Publisher Copyright: {\textcopyright} 2013 IEEE.",

year = "2021",

doi = "10.1109/ACCESS.2021.3076432",

language = "British English",

volume = "9",

pages = "67201--67208",

journal = "IEEE Access",

issn = "2169-3536",

publisher = "Institute of Electrical and Electronics Engineers Inc.",

}

Lowe, C, Ortega-Gil, A, Moghiseh, M, Anderson, NG, Munoz-Barrutia, A, Vaquero, JJ, Raja, AY, Matanaghi, A, Chernoglazov, AI, Dapamede, T, Adebileje, SA, Alexander, S, Amma, MR, Anjomrouz, M, Asghariomabad, F, Atharifard, A, Atlas, J, Baer, K, Bell, ST, Bheesette, S, Butler, PH, Carbonez, P, Chambers, C, Chapagain, KM, Clark, JA, Colgan, F, Crighton, JS, Dahal, S, Damet, J, De Ruiter, NJA, Doesburg, RMN, Duncan, N, Ghodsian, N, Gieseg, SP, Goulter, BP, Gurney, S, Healy, JL, Kanithi, PK, Kirkbride, T, Lansley, SP, Mandalika, VBH, Marfo, E, Palmer, D, Panta, RK, Prebble, HM, Renaud, P, Sayous, Y, Schleich, N, Searle, E, Sheeja, JS, Broeke, LV, Vivek, VS, Walker, EP, Walsh, MF, Wijesooriya, M, Younger, WR & Butler, APH 2021, 'Molecular Imaging of Pulmonary Tuberculosis in an Ex-Vivo Mouse Model Using Spectral Photon-Counting Computed Tomography and Micro-CT', IEEE Access, vol. 9, 9419038, pp. 67201-67208. https://doi.org/10.1109/ACCESS.2021.3076432

TY - JOUR

T1 - Molecular Imaging of Pulmonary Tuberculosis in an Ex-Vivo Mouse Model Using Spectral Photon-Counting Computed Tomography and Micro-CT

AU - Lowe, Chiara

AU - Ortega-Gil, Ana

AU - Moghiseh, Mahdieh

AU - Anderson, Nigel G.

AU - Munoz-Barrutia, Arrate

AU - Vaquero, Juan Jose

AU - Raja, Aamir Y.

AU - Matanaghi, Aysouda

AU - Chernoglazov, Alexander I.

AU - Dapamede, Theodorus

AU - Adebileje, Sikiru A.

AU - Alexander, Steven

AU - Amma, Maya R.

AU - Anjomrouz, Marzieh

AU - Asghariomabad, Fatemeh

AU - Atharifard, Ali

AU - Atlas, James

AU - Baer, Kenzie

AU - Bell, Stephen T.

AU - Bheesette, Srinidhi

AU - Butler, Philip H.

AU - Carbonez, Pierre

AU - Chambers, Claire

AU - Chapagain, Krishna M.

AU - Clark, Jennifer A.

AU - Colgan, Frances

AU - Crighton, Jonathan S.

AU - Dahal, Shishir

AU - Damet, Jerome

AU - De Ruiter, Niels J.A.

AU - Doesburg, Robert M.N.

AU - Duncan, Neryda

AU - Ghodsian, Nooshin

AU - Gieseg, Steven P.

AU - Goulter, Brian P.

AU - Gurney, Sam

AU - Healy, Joseph L.

AU - Kanithi, Praveen Kumar

AU - Kirkbride, Tracy

AU - Lansley, Stuart P.

AU - Mandalika, V. B.H.

AU - Marfo, Emmanuel

AU - Palmer, David

AU - Panta, Raj K.

AU - Prebble, Hannah M.

AU - Renaud, Peter

AU - Sayous, Yann

AU - Schleich, Nanette

AU - Searle, Emily

AU - Sheeja, Jereena S.

AU - Broeke, Lieza Vanden

AU - Vivek, V. S.

AU - Walker, E. Peter

AU - Walsh, Michael F.

AU - Wijesooriya, Manoj

AU - Younger, W. Ross

AU - Butler, Anthony P.H.

N1 - Funding Information: This work was supported in part by the Ministry of Business, Innovation and Employment (MBIE), New Zealand, under Contract UOCX1404, in part by MARS Bioimaging Ltd., in part by the Ministry of Education through the MedTech CoRE, in part by the University of Otago, in part by the Instituto de Salud Carlos III (Plan Estatal de I+D+i 2013–2016), in part by the European Social Fund (ESF) (ESF investing in your future), in part by the Innovative Medicines Initiative Joint Undertaking through the European Union Seventh Framework Program (FP7/2007–2013) under Grant 115337 and Grant 853989, in part by the European Federation of Pharmaceutical Industries and Associations (EFPIA) Companies, in part by the Spanish Ministry of Economy under Project TEC2016-78052-R, and in part by the Spanish Ministry of Science and Innovation under Grant PID2019-109820RB-I00. Publisher Copyright: © 2013 IEEE.

PY - 2021

Y1 - 2021

N2 - Assessment of disease burden and drug efficacy is achieved preclinically using high resolution micro computed tomography (CT). However, micro-CT is not applicable to clinical human imaging due to operating at high dose. In addition, the technology differences between micro-CT and standard clinical CT prevent direct translation of preclinical applications. The current proof-of-concept study presents spectral photon-counting CT as a clinically translatable, molecular imaging tool by assessing contrast uptake in an ex-vivo mouse model of pulmonary tuberculosis (TB). Iodine, a common contrast used in clinical CT imaging, was introduced into a murine model of TB. The excised mouse lungs were imaged using a standard micro-CT subsystem (SuperArgus) and the contrast enhanced TB lesions quantified. The same lungs were imaged using a spectral photoncounting CT system (MARS small-bore scanner). Iodine and soft tissues (water and lipid) were materially separated, and iodine uptake quantified. The volume of the TB infection quantified by spectral CT and micro-CT was found to be 2.96 mm3 and 2.83 mm3, respectively. This proof-of-concept study showed that spectral photon-counting CT could be used as a predictive preclinical imaging tool for the purpose of facilitating drug discovery and development. Also, as this imaging modality is available for human trials, all applications are translatable to human imaging. In conclusion, spectral photon-counting CT could accelerate a deeper understanding of infectious lung diseases using targeted pharmaceuticals and intrinsic markers, and ultimately improve the efficacy of therapies by measuring drug delivery and response to treatment in animal models and later in humans.

AB - Assessment of disease burden and drug efficacy is achieved preclinically using high resolution micro computed tomography (CT). However, micro-CT is not applicable to clinical human imaging due to operating at high dose. In addition, the technology differences between micro-CT and standard clinical CT prevent direct translation of preclinical applications. The current proof-of-concept study presents spectral photon-counting CT as a clinically translatable, molecular imaging tool by assessing contrast uptake in an ex-vivo mouse model of pulmonary tuberculosis (TB). Iodine, a common contrast used in clinical CT imaging, was introduced into a murine model of TB. The excised mouse lungs were imaged using a standard micro-CT subsystem (SuperArgus) and the contrast enhanced TB lesions quantified. The same lungs were imaged using a spectral photoncounting CT system (MARS small-bore scanner). Iodine and soft tissues (water and lipid) were materially separated, and iodine uptake quantified. The volume of the TB infection quantified by spectral CT and micro-CT was found to be 2.96 mm3 and 2.83 mm3, respectively. This proof-of-concept study showed that spectral photon-counting CT could be used as a predictive preclinical imaging tool for the purpose of facilitating drug discovery and development. Also, as this imaging modality is available for human trials, all applications are translatable to human imaging. In conclusion, spectral photon-counting CT could accelerate a deeper understanding of infectious lung diseases using targeted pharmaceuticals and intrinsic markers, and ultimately improve the efficacy of therapies by measuring drug delivery and response to treatment in animal models and later in humans.

KW - High resolution

KW - micro-CT

KW - photon-counting spectral CT

KW - pulmonary tuberculosis

KW - translatable molecular imaging

UR - http://www.scopus.com/inward/record.url?scp=85105113980&partnerID=8YFLogxK

U2 - 10.1109/ACCESS.2021.3076432

DO - 10.1109/ACCESS.2021.3076432

M3 - Article

AN - SCOPUS:85105113980

SN - 2169-3536

VL - 9

SP - 67201

EP - 67208

JO - IEEE Access

JF - IEEE Access

M1 - 9419038

ER -

Molecular Imaging of Pulmonary Tuberculosis in an Ex-Vivo Mouse Model Using Spectral Photon-Counting Computed Tomography and Micro-CT

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this