Standardization of preclinical PET/CT imaging to improve quantitative accuracy, precision and reproducibility: a multi-center study

Wendy McDougald (Corresponding Author), Christian Vanhove, Adrienne Lehnert, Barbara Lewellen, John Wright, Marco Mingarelli, Carlos Alcaide Corral, Jürgen Schneider, Sven Plein, David Newby, Andy Welch, Robert Miyaoka, Stefaan Vandenberghe, Adriana Alexandre S. Tavares

Research output: Contribution to journalArticle

Abstract

Preclinical Positron Emission Tomography/Computed Tomography (PET/CT) is a well-established non-invasive imaging tool for studying disease development/progression and the development of novel radiotracers and pharmaceuticals for clinical applications. Despite this pivotal role, standardization of preclinical PET/CT protocols, including CT absorbed dose guidelines, is essentially non-existent. This study: (1) quantitatively assesses the variability of current preclinical PET/CT acquisition and reconstruction protocols routinely used across multiple centers and scanners; and (2) proposes acquisition and reconstruction PET/CT protocols for standardization of multi-center data, optimized for routine scanning in preclinical PET/CT laboratory. Methods: Five different commercial preclinical PET/CT scanners in Europe and USA were enrolled. Seven different PET/CT phantoms were used for evaluating biases on default/general scanner protocols; followed by developing standardized protocols. PET, CT and absorbed dose biases were assessed. Results: Site default CT protocols: Greatest extracted Hounsfield Units (HU) for water was 133HU and -967HU for air, significant differences in all tissue equivalent material (TEM) groups were measured. Average CT absorbed dose for mouse and rat was 72mGy and 40mGy, respectively. Standardized CT protocol: Greatest extracted HU for water was -77HU and -990HU for air, TEM precision improved with a reduction in variability for each tissue group. Average CT absorbed dose for mouse and rat was reduced to 37mGy and 24mGy, respectively. Site default PET protocols: Uniformity was substandard in one scanner, Recovery Coefficients (RCs) were either over or under estimated (maximum of 43%), standard uptake values (SUVs) were biased by a maximum of 44%. Standardized PET protocol: Scanner with substandard uniformity improved by 36%, RC variability was reduced by 13% points and SUV accuracy improved to 10%. Conclusion: Data revealed important quantitative bias in preclinical PET/CT and absorbed doses with default protocols. Standardized protocols showed improvements in measured PET/CT accuracy and precision with reduced CT absorbed dose across sites. Adhering to standardized protocols generates reproducible and consistent preclinical imaging datasets, thus augmenting translation of research findings to the clinic.
Original languageEnglish
JournalJournal of Nuclear Medicine
Early online date27 Sep 2019
DOIs
Publication statusE-pub ahead of print - 27 Sep 2019

Fingerprint

Air
X-Ray Computed Tomography Scanners
Positron Emission Tomography Computed Tomography
Water
Disease Progression
Guidelines
Research
Pharmaceutical Preparations
CT protocol
PET protocol
Datasets

Keywords

  • Preclinical PET/CT
  • Standardization
  • Hounsfield Units
  • Absorbed dose
  • Recovery coefficient

Cite this

Standardization of preclinical PET/CT imaging to improve quantitative accuracy, precision and reproducibility : a multi-center study. / McDougald, Wendy (Corresponding Author); Vanhove, Christian; Lehnert, Adrienne; Lewellen, Barbara; Wright, John; Mingarelli, Marco; Corral, Carlos Alcaide; Schneider, Jürgen; Plein, Sven; Newby, David; Welch, Andy; Miyaoka, Robert; Vandenberghe, Stefaan; Tavares, Adriana Alexandre S.

In: Journal of Nuclear Medicine, 27.09.2019.

Research output: Contribution to journalArticle

McDougald, W, Vanhove, C, Lehnert, A, Lewellen, B, Wright, J, Mingarelli, M, Corral, CA, Schneider, J, Plein, S, Newby, D, Welch, A, Miyaoka, R, Vandenberghe, S & Tavares, AAS 2019, 'Standardization of preclinical PET/CT imaging to improve quantitative accuracy, precision and reproducibility: a multi-center study', Journal of Nuclear Medicine. https://doi.org/10.2967/jnumed.119.231308
McDougald, Wendy ; Vanhove, Christian ; Lehnert, Adrienne ; Lewellen, Barbara ; Wright, John ; Mingarelli, Marco ; Corral, Carlos Alcaide ; Schneider, Jürgen ; Plein, Sven ; Newby, David ; Welch, Andy ; Miyaoka, Robert ; Vandenberghe, Stefaan ; Tavares, Adriana Alexandre S. / Standardization of preclinical PET/CT imaging to improve quantitative accuracy, precision and reproducibility : a multi-center study. In: Journal of Nuclear Medicine. 2019.
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abstract = "Preclinical Positron Emission Tomography/Computed Tomography (PET/CT) is a well-established non-invasive imaging tool for studying disease development/progression and the development of novel radiotracers and pharmaceuticals for clinical applications. Despite this pivotal role, standardization of preclinical PET/CT protocols, including CT absorbed dose guidelines, is essentially non-existent. This study: (1) quantitatively assesses the variability of current preclinical PET/CT acquisition and reconstruction protocols routinely used across multiple centers and scanners; and (2) proposes acquisition and reconstruction PET/CT protocols for standardization of multi-center data, optimized for routine scanning in preclinical PET/CT laboratory. Methods: Five different commercial preclinical PET/CT scanners in Europe and USA were enrolled. Seven different PET/CT phantoms were used for evaluating biases on default/general scanner protocols; followed by developing standardized protocols. PET, CT and absorbed dose biases were assessed. Results: Site default CT protocols: Greatest extracted Hounsfield Units (HU) for water was 133HU and -967HU for air, significant differences in all tissue equivalent material (TEM) groups were measured. Average CT absorbed dose for mouse and rat was 72mGy and 40mGy, respectively. Standardized CT protocol: Greatest extracted HU for water was -77HU and -990HU for air, TEM precision improved with a reduction in variability for each tissue group. Average CT absorbed dose for mouse and rat was reduced to 37mGy and 24mGy, respectively. Site default PET protocols: Uniformity was substandard in one scanner, Recovery Coefficients (RCs) were either over or under estimated (maximum of 43{\%}), standard uptake values (SUVs) were biased by a maximum of 44{\%}. Standardized PET protocol: Scanner with substandard uniformity improved by 36{\%}, RC variability was reduced by 13{\%} points and SUV accuracy improved to 10{\%}. Conclusion: Data revealed important quantitative bias in preclinical PET/CT and absorbed doses with default protocols. Standardized protocols showed improvements in measured PET/CT accuracy and precision with reduced CT absorbed dose across sites. Adhering to standardized protocols generates reproducible and consistent preclinical imaging datasets, thus augmenting translation of research findings to the clinic.",
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author = "Wendy McDougald and Christian Vanhove and Adrienne Lehnert and Barbara Lewellen and John Wright and Marco Mingarelli and Corral, {Carlos Alcaide} and J{\"u}rgen Schneider and Sven Plein and David Newby and Andy Welch and Robert Miyaoka and Stefaan Vandenberghe and Tavares, {Adriana Alexandre S.}",
note = "We thank the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) for funding this work (Studentship grant NC/P00170X/1) to WM. AT is funded by the British Heart Foundation (RG/16/10/32375). The British Heart Foundation is greatly acknowledge for providing funding towards establishment of the Edinburgh Preclinical PET/CT laboratory (RE/13/3/30183). The authors would like to thank the radiochemistry teams at Edinburgh Imaging, Queen's Medical Research Institute (QMRI), the University of Aberdeen and Ghent University for their support in supplying the radiotracers used during the site visits.",
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T1 - Standardization of preclinical PET/CT imaging to improve quantitative accuracy, precision and reproducibility

T2 - a multi-center study

AU - McDougald, Wendy

AU - Vanhove, Christian

AU - Lehnert, Adrienne

AU - Lewellen, Barbara

AU - Wright, John

AU - Mingarelli, Marco

AU - Corral, Carlos Alcaide

AU - Schneider, Jürgen

AU - Plein, Sven

AU - Newby, David

AU - Welch, Andy

AU - Miyaoka, Robert

AU - Vandenberghe, Stefaan

AU - Tavares, Adriana Alexandre S.

N1 - We thank the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) for funding this work (Studentship grant NC/P00170X/1) to WM. AT is funded by the British Heart Foundation (RG/16/10/32375). The British Heart Foundation is greatly acknowledge for providing funding towards establishment of the Edinburgh Preclinical PET/CT laboratory (RE/13/3/30183). The authors would like to thank the radiochemistry teams at Edinburgh Imaging, Queen's Medical Research Institute (QMRI), the University of Aberdeen and Ghent University for their support in supplying the radiotracers used during the site visits.

PY - 2019/9/27

Y1 - 2019/9/27

N2 - Preclinical Positron Emission Tomography/Computed Tomography (PET/CT) is a well-established non-invasive imaging tool for studying disease development/progression and the development of novel radiotracers and pharmaceuticals for clinical applications. Despite this pivotal role, standardization of preclinical PET/CT protocols, including CT absorbed dose guidelines, is essentially non-existent. This study: (1) quantitatively assesses the variability of current preclinical PET/CT acquisition and reconstruction protocols routinely used across multiple centers and scanners; and (2) proposes acquisition and reconstruction PET/CT protocols for standardization of multi-center data, optimized for routine scanning in preclinical PET/CT laboratory. Methods: Five different commercial preclinical PET/CT scanners in Europe and USA were enrolled. Seven different PET/CT phantoms were used for evaluating biases on default/general scanner protocols; followed by developing standardized protocols. PET, CT and absorbed dose biases were assessed. Results: Site default CT protocols: Greatest extracted Hounsfield Units (HU) for water was 133HU and -967HU for air, significant differences in all tissue equivalent material (TEM) groups were measured. Average CT absorbed dose for mouse and rat was 72mGy and 40mGy, respectively. Standardized CT protocol: Greatest extracted HU for water was -77HU and -990HU for air, TEM precision improved with a reduction in variability for each tissue group. Average CT absorbed dose for mouse and rat was reduced to 37mGy and 24mGy, respectively. Site default PET protocols: Uniformity was substandard in one scanner, Recovery Coefficients (RCs) were either over or under estimated (maximum of 43%), standard uptake values (SUVs) were biased by a maximum of 44%. Standardized PET protocol: Scanner with substandard uniformity improved by 36%, RC variability was reduced by 13% points and SUV accuracy improved to 10%. Conclusion: Data revealed important quantitative bias in preclinical PET/CT and absorbed doses with default protocols. Standardized protocols showed improvements in measured PET/CT accuracy and precision with reduced CT absorbed dose across sites. Adhering to standardized protocols generates reproducible and consistent preclinical imaging datasets, thus augmenting translation of research findings to the clinic.

AB - Preclinical Positron Emission Tomography/Computed Tomography (PET/CT) is a well-established non-invasive imaging tool for studying disease development/progression and the development of novel radiotracers and pharmaceuticals for clinical applications. Despite this pivotal role, standardization of preclinical PET/CT protocols, including CT absorbed dose guidelines, is essentially non-existent. This study: (1) quantitatively assesses the variability of current preclinical PET/CT acquisition and reconstruction protocols routinely used across multiple centers and scanners; and (2) proposes acquisition and reconstruction PET/CT protocols for standardization of multi-center data, optimized for routine scanning in preclinical PET/CT laboratory. Methods: Five different commercial preclinical PET/CT scanners in Europe and USA were enrolled. Seven different PET/CT phantoms were used for evaluating biases on default/general scanner protocols; followed by developing standardized protocols. PET, CT and absorbed dose biases were assessed. Results: Site default CT protocols: Greatest extracted Hounsfield Units (HU) for water was 133HU and -967HU for air, significant differences in all tissue equivalent material (TEM) groups were measured. Average CT absorbed dose for mouse and rat was 72mGy and 40mGy, respectively. Standardized CT protocol: Greatest extracted HU for water was -77HU and -990HU for air, TEM precision improved with a reduction in variability for each tissue group. Average CT absorbed dose for mouse and rat was reduced to 37mGy and 24mGy, respectively. Site default PET protocols: Uniformity was substandard in one scanner, Recovery Coefficients (RCs) were either over or under estimated (maximum of 43%), standard uptake values (SUVs) were biased by a maximum of 44%. Standardized PET protocol: Scanner with substandard uniformity improved by 36%, RC variability was reduced by 13% points and SUV accuracy improved to 10%. Conclusion: Data revealed important quantitative bias in preclinical PET/CT and absorbed doses with default protocols. Standardized protocols showed improvements in measured PET/CT accuracy and precision with reduced CT absorbed dose across sites. Adhering to standardized protocols generates reproducible and consistent preclinical imaging datasets, thus augmenting translation of research findings to the clinic.

KW - Preclinical PET/CT

KW - Standardization

KW - Hounsfield Units

KW - Absorbed dose

KW - Recovery coefficient

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JO - Journal of Nuclear Medicine

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