Comparison of Multimodality Image-Based Volumes in Preclinical Tumor Models Using In-Air Micro-CT Image Volume as Reference Tumor Volume

Yongsook C. Lee^1*, Gary D. Fullerton², Beth A. Goins²

¹Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, Kansas, USA.
²Department of Radiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.

DOI: 10.4236/ojmi.2015.53016                

Abstract

Purpose: Changes in tumor volume are used for therapy response monitoring in preclinical studies. Unlike prior studies, this article introduces in-air micro-computed tomography (micro-CT) image volume as reference tumor volume in rodent tumor models. Tumor volumes determined using imaging modalities such as magnetic resonance imaging (MRI), micro-CT and ultrasound (US), and with an external caliper are compared with the reference tumor volume. Materials and Methods: In vivo MR, US and micro-CT imaging was performed 4, 6, 9, 11 and 13 days after tumor cell inoculation into nude rats. On the day of the imaging study, in vivo caliper measurements were also made. After in vivo imaging, tumors were excised followed by in-air micro-CT imaging and ex vivo caliper measurements of excised tumors. The in-air micro-CT image volume of excised tumors was determined as reference tumor volume. Then tumor volumes were calculated using formula V = (π/6) × a × b × c, where a, b and c are maximum diameters in three perpendicular dimensions determined by the three image modalities and caliper, and compared with reference tumor volume by linear regression analysis as well as Bland-Altman plots. Results: The correlation coefficients (R²) of the regression lines for in vivo tumor volumes measured by the three imaging modalities were 0.9939, 0.9669 and 0.9806 for MRI, US and micro-CT respectively. For caliper measurements, the coefficients were 0.9274 and 0.9819 for caliper_{in vivo} and caliperex vivo respectively. In Bland-Altman plots, the average of tumor volume difference from reference tumor volume (bias) was significant for caliper and micro-CT, but not for MRI and US. Conclusion: Using the in-air micro-CT image volume as reference tumor volume, tumor volume measured by MRI was the most accurate among the three imaging modalities. In vivo caliper volume measurements showed unreliability while ex vivo caliper measurements reduced errors.

Keywords

In-Air Micro-CT, Magnetic Resonance Imaging, Ultrasound, Caliper, Tumor Volume Measurements

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Euhus, D.M., Hudd, C., LaRegina, M.C. and Johnson, F.E. (1986) Tumor Measurement in the Nude Mouse. Journal of Surgical Oncology, 31, 229-234. http://dx.doi.org/10.1002/jso.2930310402
[2]	Lee, Y.C., Goins, B.A. and Fullerton, G.D. (2010) QA Procedures for Multimodality Preclinical Tumor Drug Response Testing. Medical Physics, 37, 4806-4816. http://dx.doi.org/10.1118/1.3464491
[3]	Lee, Y.C., Fullerton, G.D., Baiu, C., Lescrenier, M.G. and Goins, B.A. (2011) Preclinical Multimodality Phantom Design for Quality Assurance of Tumor Size Measurement. BMC Medical Physics, 11, 1. http://dx.doi.org/10.1186/1756-6649-11-1
[4]	Sohaib, S.A., Turner, B., Hanson, J.A., Farquharson, M., Oliver, R.T.D. and Reznek, R.H. (2000) CT Assessment of Tumor Response to Treatment: Comparison of Linear, Cross-Sectional and Volumetric Measures of Tumor Size. British Journal of Radiology, 73, 1178-1184. http://dx.doi.org/10.1259/bjr.73.875.11144795
[5]	Tomayko, M.M. and Reynolds, C.P. (1989) Determination of Subcutaneous Tumor Size in Athymic (Nude) Mice. Cancer Chemotherapy and Pharmacology, 24, 148-154. http://dx.doi.org/10.1007/BF00300234
[6]	Prasad, S.R., Jhaveri, K.S., Saini, S., Hahn, P.F., Halpern, E.F. and Sumner, J.E. (2002) CT Tumor Measurement for Therapeutic Response Assessment: Comparison of Unidimensional, Bidimensional, and Volumetric Techniques-Initial Observations. Radiology, 225, 416-419. http://dx.doi.org/10.1148/radiol.2252011604
[7]	Jensen, M.M., Joergensen, J.T., Binderup, T. and Kjaer, A. (2008) Tumor Volume in Subcutaneous Mouse Xenografts Measured by microCT Is More Accurate and Reproducible than Determined by 18F-FDG-microPET or External Caliper. BMC Medical Imaging, 8, 16. http://dx.doi.org/10.1186/1471-2342-8-16
[8]	Folio, L., Derderian, V., Steinberg, S.M., Turkbey, E. and Apolo, A.B. (2014) Assessing Tumor Response Using CT Density-Volume Trajectory in Metastatic Bladder Cancer. Proceedings of ASCO Annual Meeting, Journal of Clinical Oncology, 32, Article ID: 4539.
[9]	Girit, I.C., Jure-Kunke, M. and McIntyre, K.W. (2008) A Structured Light-Based System for Scanning Subcutaneous Tumors in Laboratory Animals. Comparative Medicine, 58, 264-270.
[10]	Ayers, G.D., McKinley, E.T., Zhao, P., Fritz, J.M., Metry, R.E., Deal, B.C., Adlerz, K.M., Coffey, R.J. and Manning, H.C. (2010) Volume of Preclinical Xenograft Tumors Is More Accurately Assessed by Ultrasound Imaging than Manual Caliper Measurements. Journal of Ultrasound Medicine, 29, 891-901.
[11]	Fornage, B.D., Toubas, O. and Morel, M. (1987) Clinical, Mammographic, and Sonographic Determination of Preoperative Breast Cancer Size. Cancer, 60, 765-771. http://dx.doi.org/10.1002/1097-0142(19870815)60:4<765::AID-CNCR2820600410>3.0.CO;2-5
[12]	Ishimori, T., Tatsumi, M. and Wahl, R. (2005) Tumor Response Assessment Is More Robust with Sequential CT Scanning than External Caliper Measurements. Academic Radiology, 12, 776-781. http://dx.doi.org/10.1016/j.acra.2005.03.062
[13]	Shoma, A., Moutamed, A., Ameen, M. and Abdelwahab, A. (2006) Ultrasound for Accurate Measurement of Invasive Breast Cancer Tumor Size. Breast Journal, 12, 252-256. http://dx.doi.org/10.1111/j.1075-122X.2006.00249.x
[14]	Fullerton, G.D., Amurao, M., Rahal, A. and Cameron, I.L. (2011) Micro-CT Dilatometry Measures of Molecular Collagen Hydration Using Bovine Extensor Tendon. Medical Physics, 38, 363-376. http://dx.doi.org/10.1118/1.3514123
[15]	Clark, D.P. and Badea, C.T. (2014) Micro-CT of Rodents: State-of-the-Art and Future Perspectives. Physica Medica, 30, 619-634. http://dx.doi.org/10.1016/j.ejmp.2014.05.011
[16]	Prajapati, S.I., Kilcoyne, A., Samano A.K., Green, D.P., McCarthy, S.D., Blackman, B.A., Brady, M.M., Zarzabal, L.A., Tatiparthy, A.K., Sledz, T.J., Duong, T., Ohshima-Hosoyama, S., Giles, F.J., Michalek, J.E., Rubin, B.P. and Keller, C. (2011) MicroCT-Based Virtual Histology Evaluation of Preclinical Medulloblastoma. Molecular Imaging and Biology, 13, 493-499. http://dx.doi.org/10.1007/s11307-010-0372-3
[17]	Foster, W.K. and Ford, N.L. (2011) Investigating the Effect of Longitudinal Micro-CT Imaging on Tumour Growth in Mice. Physics in Medicine and Biology, 56, 315-326. http://dx.doi.org/10.1088/0031-9155/56/2/002
[18]	Graham, K.C., Ford, N.L., MacKenzie L.T., Postenka, C.O., Groom, A.C., MacDonald, I.C., Holdsworth, D.W., Drangova, M. and Chambers, A.F. (2008) Noninvasive Quantification of Tumor Volume in Preclinical Liver Metastasis Models Using Contrast-Enhanced X-Ray Computed Tomography. Investigative Radiology, 43, 92-99. http://dx.doi.org/10.1097/RLI.0b013e31815603d7
[19]	Boonstra, H., Oosterhuis, J.W., Oosterhuis, A.M. and Fleuren, G.J. (1983) Cervical Tissue Shrinkage by Formaldehyde Fixation, Paraffin Wax Embedding, Section Cutting and Mounting. Virchows Archiv A, 402, 195-201. http://dx.doi.org/10.1007/BF00695061
[20]	Carthew, P., Maronpot, R.R., Foley, J.F., Edwards, R.E. and Nolan, B.M. (1996) Method for Determining Whether the Number of Hepatocytes in Rat Liver Is Increased after Treatment with the Peroxisome Proliferator Gemfibrozil. Journal of Applied Toxicology, 17, 47-51. http://dx.doi.org/10.1002/(SICI)1099-1263(199701)17:1<47::AID-JAT389>3.0.CO;2-4
[21]	Graham, K.C., Wirtzfeld, L.A., MacKenzie, L.T., Postenka, C.O., Groom, A.C., MacDonald, I.C., Fenster, A., Lacefield, J.C. and Chambers, A.F. (2015) Three-Dimensional High-Frequency Ultrasound for Longitudinal Evaluation of Liver Metastases in Preclinical Models. Cancer Research, 65, 5231-5237. http://dx.doi.org/10.1158/0008-5472.CAN-05-0440
[22]	Martiniova, L., Kotys, M.S., Thomasson, D., Schimel, D., Lai, E.W., Bernardo, M., Merino, M.J., Powers, J.F., Ruzicka, J., Kvetnansky, R., Choyke, P.L. and Pacak, K. (2009) Non-Invasive Monitoring of a Murine Model of Metastatic Pheochromocytoma: A Comparison of Contrast Enhanced MicroCT and Non-Enhanced MRI. Journal of Magnetic Resonance Imaging, 29, 685-691. http://dx.doi.org/10.1002/jmri.21654
[23]	Bretschi, M., Franzle, A., Merz, M., Hillengass, J., Semmler, W., Bendl, R. and Bauerle, T. (2014) Assessing Treatment Response of Osteolytic Lesions by Manual Volumetry, Automatic Segmentiation, and RECIST in Experimental Bone Metastases. Academic Radiology, 21, 1177-1184. http://dx.doi.org/10.1016/j.acra.2014.04.011
[24]	Hajitou, A., Lev, D.C., Hannay, J.A., Korchin, B., Staquicini, F.I., Soqhomonyan, S., Alauddin, M.M., Benjamin, R.S., Pollock, R.E., Gelovani, J.G., Pasqualini, R. and Arap, W. (2008) A Preclinical Model for Predicting Drug Response in Soft-Tissue Sarcoma with Targeted AAVP Molecular Imaging. Proceedings of the National Academic Sciences of the United States of America, 105, 4471-4476. http://dx.doi.org/10.1073/pnas.0712184105
[25]	Bao, A., Phillips, W.T., Goins, B., McGuff, H.S., Zheng, X., Woolley, F.R., Natarajan, M., Santoyo, C., Miller, F.R. and Otto, R.A. (2006) Setup and Characterization of a Human Head and Neck Squamous Cell Carcinoma Xenograft Model in Nude Rats. Otolaryngology Head and Neck Surgery, 135, 853-857. http://dx.doi.org/10.1016/j.otohns.2006.06.1257
[26]	Bland, J.M. and Altman, D.G. (1986) Statistical Methods for Assessing Agreement between Two Methods of Clinical Measurement. Lancet, 327, 307-310. http://dx.doi.org/10.1016/S0140-6736(86)90837-8
[27]	Kersemans, V., Cornelissen, B., Allen, P.D., Beech, J.S. and Smart, S.C. (2013) Subcutaneous Tumor Volume Measurement in the Awake, Manually Restrained Mouse Using MRI. Journal of Magnetic Resonance Imaging, 37, 1499- 1504. http://dx.doi.org/10.1002/jmri.23829
[28]	Sharma, R. (2009) Microimaging of Hairless Rat Skin by Magnetic Resonance at 900 MHz. Magnetic Resonance Imaging, 27, 240-255. http://dx.doi.org/10.1016/j.mri.2008.06.013
[29]	Kawano, K., Hattori, Y., Iwakura, H., Akanizu, T. and Maitani. Y. (2012) Adrenal Tumor Volume in a Genetically Engineered Mouse Model of Neuroblastoma Determined by Magnetic Resonance Imaging. Experimental and Therapeutic Medicine, 4, 61-64. http://dx.doi.org/10.3892/etm.2012.564
[30]	Abou-Elkacem, L., Gremse, F., Barth, S., Hoffman, R.M., Kiessling, F. and Lederle, W. (2011) Comparison of μCT, MRI and Optical Reflectance Imaging for Accessing the Growth of GFP/RFP-Expressing Tumors. Anticancer Research, 31, 2907-2913.
[31]	Faustino-Rocha, A., Oliveira, P.A., Pinho-Oliveira, J., Teixeira-Guedes, C., Soares-Maia, R., da Costa, R.G., Colaco, B., Pires, M.J., Colaco, J., Ferreira, R. and Ginja, M. (2013) Estimation of Rat Mammary Tumor Volume Using Caliper and Ultrasonography Measurements. Laboratory Animal, 42, 217-224. http://dx.doi.org/10.1038/laban.254
[32]	Hastie, L.A., Graham, K.C., Groom, A.C., MacDonald, I.C., Chambers, A.F., Fenster, A. and Lacefield, J.C. (2004) Variability of Three-Dimensional High-Frequency Ultrasound Measurements of Small Tumor Volumes. Proceedings of IEEE International Ultrasonic Symposium, Vol. 3, Montréal, 23-27 August 2004, 2185-2188. http://dx.doi.org/10.1109/ultsym.2004.1418272
[33]	Weber, S.W., Peterson, K.A., Durkee, B., Qi, C., Longino, M., Warner, M., Lee, F.T. and Weichert, J.P. (2004) Imaging of Murine Liver Tumor Using MicroCT with a Hepatocyto-Selective Contrast Agent: Accuracy Is Dependent on Adequate Contrast Enhancement. Journal of Surgical Research, 119, 41-45. http://dx.doi.org/10.1016/S0022-4804(03)00357-3
[34]	Ohta, S., Lai, E.W., Morris, J.C., Bakan, D.A., Klaunberg, B., Cleary, S., Powers, J.F., Tischler, A.S., Abu-Asab, M., Schimel, S. and Pacak, K. (2006) MicroCT for High-Resolution Imaging of Ectopic Pheochromocytoma Tumors in the Liver of Nude Mice. International Journal of Cancer, 119, 2236-2241. http://dx.doi.org/10.1002/ijc.22127
[35]	Boone, J.M., Velazquez, O. and Cherry, S.R. (2004) Small-Animal X-Ray Dose from Micro-CT. Molecular Imaging, 3, 149-158. http://dx.doi.org/10.1162/1535350042380326
[36]	Cheung, A.M., Brown, A.S., Hastie, L.A., Cucevic, V., Roy, M., Lacefield, J.C., Fenster, A. and Foster, F.S. (2005) Three-Dimensional Ultrasound Biomicroscopy for Xenograft Growth Analysis. Ultrasound in Medicine and Biology, 31, 856-870. http://dx.doi.org/10.1016/j.ultrasmedbio.2005.03.003