An innovative non-invasive technique for subcutaneous tumour measurements


Autoři: Juan Delgado-SanMartin aff001;  Beate Ehrhardt aff002;  Marcin Paczkowski aff001;  Sean Hackett aff001;  Andrew Smith aff001;  Wajahat Waraich aff001;  James Klatzow aff001;  Adeala Zabair aff001;  Anna Chabokdast aff001;  Leonardo Rubio-Navarro aff001;  Amar Rahi aff003;  Zena Wilson aff003
Působiště autorů: Fuel3D, Oxford Science Park, Oxford, England, United Kingdom aff001;  AstraZeneca IMED Biotech Unit, Discovery Sciences, Cambridge Science Park, Cambridge, England, United Kingdom aff002;  AstraZeneca IMED Biotech Unit, Oncology, Alderley Park, Macclesfield, England, United Kingdom aff003
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0216690

Souhrn

Introduction

In oncological drug development, animal studies continue to play a central role in which the volume of subcutaneous tumours is monitored to assess the efficacy of new drugs. The tumour volume is estimated by taking the volume to be that of a regular spheroid with the same dimensions. However, this method is subjective, insufficiently traceable, and is subject to error in the accuracy of volume estimates as tumours are frequently irregular.

Methods & results

This paper reviews the standard technique for tumour volume assessment, calliper measurements, by conducting a statistical review of a large dataset consisting of 2,500 tumour volume measurements from 1,600 mice by multiple operators across 6 mouse strains and 20 tumour models. Additionally, we explore the impact of six different tumour morphologies on volume estimation and the detection of treatment effects using a computational tumour growth model. Finally, we propose an alternative method to callipers for estimating volume–BioVolumeTM, a 3D scanning technique. BioVolume simultaneously captures both stereo RGB (Red, Green and Blue) images from different light sources and infrared thermal images of the tumour in under a second. It then detects the tumour region automatically and estimates the tumour volume in under a minute. Furthermore, images can be processed in parallel within the cloud and so the time required to process multiple images is similar to that required for a single image. We present data of a pre-production unit test consisting of 297 scans from over 120 mice collected by four different operators.

Conclusion

This work demonstrates that it is possible to record tumour measurements in a rapid minimally invasive, morphology-independent way, and with less human-bias compared to callipers, whilst also improving data traceability. Furthermore, the images collected by BioVolume may be useful, for example, as a source of biomarkers for animal welfare and secondary drug toxicity / efficacy.

Klíčová slova:

Animal performance – Animal welfare – Cancer treatment – Computed axial tomography – Magnetic resonance imaging – Mouse models – Oncology – Statistical data


Zdroje

1. Tomayko MM, Reynolds CP. Determination of subcutaneous tumor size in athymic (nude) mice. Cancer Chemother Pharmacol. 1989;

2. Euhus DM, Hudd C, Laregina MC, Johnson FE. Tumor measurement in the nude mouse. J Surg Oncol. 1986;

3. Ishimori T, Tatsumi M, Wahl RL. Tumor response assessment is more robust with sequential CT scanning than external caliper measurements. Acad Radiol. 2005;

4. Ayers GD, McKinley ET, Zhao P, Fritz JM, Metry RE, Deal BC, et al. Volume of preclinical xenograft tumors is more accurately assessed by ultrasound imaging than manual caliper measurements. J Ultrasound Med. 2010;

5. Jensen MM, Jørgensen JT, Binderup T, Kjær A. Tumor volume in subcutaneous mouse xenografts measured by microCT is more accurate and reproducible than determined by 18F-FDG-microPET or external caliper. BMC Med Imaging. 2008;

6. Kersemans V, Cornelissen B, Allen PD, Beech JS, Smart SC. Subcutaneous tumor volume measurement in the awake, manually restrained mouse using MRI. J Magn Reson Imaging. 2013;

7. Song C, Appleyard V, Murray K, Frank T, Sibbett W, Cuschieri A, et al. Thermographic assessment of tumor growth in mouse xenografts. Int J Cancer. 2007;121(5):1055–8. doi: 10.1002/ijc.22808 17487841

8. Delgado San Martin JA, Worthington P, Yates JWT. Non-invasive 3D time-of-flight imaging technique for tumour volume assessment in subcutaneous models. Lab Anim. 2015;

9. Hussain N, Connah D, Ugail H, Cooper PA, Falconer RA, Patterson LH, et al. The use of thermographic imaging to evaluate therapeutic response in human tumour xenograft models. Sci Rep. 2016;

10. Bocci G, Buffa F, Canu B, Concu R, Fioravanti A, Orlandi P, et al. A new biometric tool for three-dimensional subcutaneous tumor scanning in mice. In Vivo (Brooklyn). 2014;28(1):75–80.

11. Girit IC, Jure-Kunkel M, McIntyre KW. A structured light-based system for scanning subcutaneous tumors in laboratory animals. Comp Med. 2008;58(3):264–70. 18589868

12. Delgado-Sanmartin JA, Hare JI, Davies EJ, Yates JWT. Multiscalar cellular automaton simulates in-vivo tumour-stroma patterns calibrated from in-vitro assay data. BMC Med Inform Decis Mak. 2017;17(1):1–12. doi: 10.1186/s12911-016-0389-x

13. Ralli J, Díaz J, Ros E. Spatial and temporal constraints in variational correspondence methods. Mach Vis Appl. 2013;24(2):275–87.

14. Ralli J, Díaz J, Kalkan S, Krüger N, Ros E. Disparity disambiguation by fusion of signal-and symbolic-level information. Mach Vis Appl. 2012;23(1):65–77.

15. Reed GF, Lynn F, Meade BD. Use of coefficient of variation in assessing variability of quantitative assays. Clin Diagn Lab Immunol. 2002;9(6):1235–9. doi: 10.1128/CDLI.9.6.1235-1239.2002 12414755

16. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B. 1995;289–300.

17. Milo R, Jorgensen P, Moran U, Weber G, Springer M. BioNumbers—the database of key numbers in molecular and cell biology. Nucleic Acids Res. 2009;38(suppl_1):D750–3.

18. ATCC - 4T-1 [Internet]. [cited 2019 Jan 22]. Available from: https://www.lgcstandards-atcc.org/products/all/CRL-2539.aspx?geo_country=gb

19. ATCC—A20 [Internet]. [cited 2019 Jan 22]. Available from: https://www.lgcstandards-atcc.org/products/all/TIB-208.aspx?geo_country=gb#generalinformation


Článek vyšel v časopise

PLOS One


2019 Číslo 10