On Day 14, when the tumor volume reached ~500 mm 3, the mice were . PMID: 11208850. This can happen if the mouse is pressed into the mask or if the body is stretched when held. Kim HB, Zeng CH, Kim Y, Jeong S, Kim SH, Kang JM, Park Y, Won DS, Kim JW, Ryu DS, Lim B, Park JH. Mammary tumors similar to those observed in women can be induced in rats by intraperitoneal administration of N-methyl-N-nitrosourea. The caliper mean-percent-error is 10.6%, nearly twice that of the scanners mean-percent-error of 4.6%. A caliper only digitizes the length and width of the tumor. Objectives: Volume measurement of subcutaneous xenograft tumors in nude mice models is an important metric to assess tumor growth or response to therapy. Cancer 60, 765771 (1987). 15, 115121 (2009). In Phase IV, control group members received no bevacizumab. & Pisani, P. Global cancer statistics, 2002. Faustino-Rocha AI, Gama A, Oliveira PA, Vanderperren K, Saunders JH, Pires MJ, Ferreira R, Ginja M. Life Sci. However, if the treatment is lengthy, the problem of side-effects also has to be considered. This process slightly stretches the body and deforms the tumor. Effects of different applied voltages of irreversible electroporation on prostate cancer in a mouse model. No, Is the Subject Area "Mouse models" applicable to this article? Measurement by Caliper In order to estimate tumor volume by external caliper, the greatest longitudinal diameter (length) and the Due to the collaboration between medical doctors and biomedical engineers, model-based treatment protocols can be created. A direct 3D volume capture instrument, such as the TM900, will make a stereographic image of the tumor and reconstruct the tumor topography and shape. The manipulation of the handheld tool is at least as easy as holding a measurement caliper. Each day before the administration, the mice' body weight and tumor volume were measured and recorded. 2023 Jan 20;42(1):25. doi: 10.1186/s13046-022-02578-w. Zhao R, Chen P, Qu C, Liang J, Cheng Y, Sun Z, Tian H. Cell Death Discov. The volume above the red area is not occupied by the tumor, as seen in Figure 8. tumor height has to be approximated. Mammary tumors similar to those observed in women can be induced in rats by intraperitoneal administration of N-methyl-N-nitrosourea. <> stream The data reveals that the mean volume of PTV is 60.8 53.9 cc where these targets exhibit no significant difference between each modality. In both cases, three groups were compared in the experiments. They found that caliper and ultrasonography measurements were significantly correlated but that tumor volumes calculated using different formulas varied substantially. Combining Mechanisms of Growth Arrest in Solid Tumours: A Mathematical Investigation, Dramatic increase in volume versus length of invasive ductal carcinoma mimicking intramammary lymph node in a small nodular lesion, Alteration in Inflammasome Cytokine Profile and Functional Plasticity of Macrophage Phenotype in Arsenic(0) Nanoparticle Treated Murine Fibrosarcoma, Tumoral CD105 promotes immunosuppression, metastasis, and angiogenesis in renal cell carcinoma, Cancel The tumor shown has a dip in its form, which means that its volume will be less than that of a tumor without a dip. A caliper measurement would only take into account the components for length and width and therefore ignore this dip measured by the values for height, which would, in turn, inaccurately measure the tumors volume. It means that a mouse of the case group received 1.11 g bevacizumab (with 45 l 0.9% NaCl solution) every day from the 3rd day for 20 days. 2009, 18 (2009). Please enable it to take advantage of the complete set of features! Figure 7. mum tumor volume of 0.6 mL was reached. In addition, studies using CT scans concluded that CT yielded tumor volume values 11 to 12% less (an underestimate) than those which were measured by calipers, and that CT-based measurements yielded more accurate and consistent values than caliper-based measurements[6, 7]. (2), Whilst studies have shown that tumors can be better estimated with ellipsoid shape than using Eq 1, calculating the volume of an ellipsoid requires the knowledge of the third parameter. Sport. Tumor area was determined with flood fill algorithm [31] from the slides; by knowing the volume of a voxel, tumor volume was calculated from these two values. 35, 18341840 (2003). (8) When using calipers there is dependency in the measured data of the positioning by the operator of the tool on the xenograft. Radiology 254, 110118 (2010). Notice that the caliper-based measurements have a larger standard deviation. Average of tumor volumes for every measurement days of the experiment can be seen in Fig 8. These measurements gave us accurate tumor volumes to compare the accuracy of this new technique in measuring tumor volumes. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Significance of rat mammary tumors for human risk assessment. Since 2004, the target therapy of bevacizumab (Avastin) is widely used to treat colorectal [9], kidney [10], cervical [34], ovarian [35], non-small cell lung cancers [5], melanoma [14] and certain brain tumors (e.g. Determining tumor volume is a useful and quantitative way to monitor tumor progression. Effects of holding an animal on tumor volume while scanning. This formula was the starting point of our examination to find an appropriate mathematical model. Tumours of the rat. Figure 8. . Yes Pritt, B., Ashikaga, T., Oppenheimer, R.G. Tumor growth Tumor regression Number of Number of volume volume doublings Percentage additional halvings: Decrease in Percentage decrcase in increase Volume Area" Diameterb volume doubling number Volume Area" Diameterb Doubling of Halving of Volume 1 .o 100.0 58.7 26.0 Volume 1 .o 50.0 37.0 20.6 & Robinson, S.P. This problem can be explained by our observation, namely tumors which were grown without therapy have more symmetric and solid closed shape, in contrast to tumors which were grown under antiangiogenic therapy. (3), Another relatively new but not widely used approach to estimate tumor volume is to assume hemi-ellipsoid shape [24]. PubMed During the MRI measurements, life parameters of the mice were monitored. 19, 6170 (1989). The 1st Department of Pathology and Experimental Cancer Research of the Semmelweis University (Budapest, Hungary) and the Physiological Controls Group of the Obuda University (Budapest, Hungary) began collaborating on antiangiogenic therapy research in 2012including the current experimental investigations. https://doi.org/10.1371/journal.pone.0142190.g007. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in 54, 401414 (1975). Coauthors PK and DG are employed by Gedeon Richter Ltd. Gedeon Richter Ltd. provided support in the form of salaries for authors PK and DG, and in the form of using the resources of Preclinical Imaging Center of Gedeon Richter Ltd., but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Disclaimer. Usually, 3.0 x 10 6 cells are needed per injection. The obtained data include height and topography changes. The tumor number, from one to ten, is shown against the percent error. VC refers to tumor volume values calculated through the formula VT = 0.5 L W2, and VCH refers to those through the formula VT = 0.5 L W H. VS refers to measurements taken by the scanner, and % Inc. refers to the percent increase between VS and VCH. M}{Gt{zj|&cXx[k?CZ ~AjTxMr0 '~ix$mj/)9?$ t-o6MkVXs's}^E6-^_Yrv#w&r7w@WsQs]#G g$Cn. ), the more correlated a given group (scanner or caliper estimations) is to the black line (r2 = 1), the more accurate the tumor volume measurements are. An average penny has a diameter of 19 mm and a height of 1.27 mm, yielding a volume of 360.1 mm3. 22, 921929 (2003). Predicting tumor volume in radical prostatectomy specimens from patients with prostate cancer. All surgery and sacrifice were performed under sodium pentobarbital anaesthesia (Nembutal, 70 mg/kg), and all efforts were made to minimize suffering. Before Am. A tumor image, its 3D shape and all geometrical data are automatically calculated and stored. constant low-dose therapy because in the case of controller-based administration, the control signal (administration dose) can vary from zero to the maximum tolerable dose according to the perceived tumor volume. Med. The tumor dimensions are L, W, and H. The volume of an ellipsoid VE, using the variables as shown in Figure 1., is. Keller M, Rohlf K, Glotzbach A, Leonhardt G, Lke S, Derksen K, Demirci , Gener D, AlWahsh M, Lambert J, Lindskog C, Schmidt M, Brenner W, Baumann M, Zent E, Zischinsky ML, Hellwig B, Madjar K, Rahnenfhrer J, Overbeck N, Reinders J, Cadenas C, Hengstler JG, Edlund K, Marchan R. J Exp Clin Cancer Res. We have investigated different methods to find the best tumor volume estimation since it creates the possibility for precise and effective drug administration with a much lower dose than in the protocol. Finding the mathematical relationship between MRI-measured tumor volume and tumor mass creates the possibility to estimate tumor volume from caliper-measured data. depicts the inaccuracy of the formula used for caliper measurements, in which the height of the tumor is assumed to be equal to its width. Tumor Volume Measurement et al. Cancer Res. Measured data is the MRI-measured tumor volumetumor mass pairs on the 23rd day of Phase III/3 (case and control group). Under these conditions, the formula for the volume of a tumor becomes. Pursuant to one-sample Kolmogorov-Smirnov test, each sample has normal distribution (ppIV_control = 0.981, ppIV_case1 = 0.998, ppIV_case2 = 0.854). (5) in The Laboratory Mouse (eds. In both cases, the height of the tumor will be much smaller than its length or width (Figure 2.). The other eight tumors exhibit forms that cannot be compared to a perfect ellipsoid. Fornage, B.D., Toubas, O. Mice were humanely sacrificed using cervical dislocation. The results presented here were provided by them. We compared tumor volumes estimated in vivo by BLI and FLI, to those calculated by caliper measurements and found a good correlation between these two techniques (Figure 4). These images also provide extra morphological information about the tumor growth and the effect of the compounds on tumor behavior. Conceived and designed the experiments: ZS JS. In Phase III/3, control group members received 200 g bevacizumab (with 455 l 0.9% NaCl solution) in one dose intraperitoneally on the 3rd day and on the 21st day. One can see experimental settings in Table 1, while MRI image of a control group mouse (C4) that was measured at the end of the experiment can be found in Fig 3. https://doi.org/10.1371/journal.pone.0142190.t001, https://doi.org/10.1371/journal.pone.0142190.g003. 2 0 obj Google Scholar. The protocol was approved by the Hungarian Animal Experimental Research Ethics Council (llatksrleti Tudomnyos Etikai Tancs, ATET), Permit Number: 22.1/1159/3/2010. Tumor cells form and expand subcutaneously in the cavity they are injected, into between the layers of the skin. The variables for the volume of a tumor, as measured by a caliper, are determined by a, b, and c in Figure 1, where length L is 2a, width W is 2b, and height H is c. VT, the volume of a tumor is determined by. Tumor volume determined by microCT, 18 F-FDG-PET and external caliper Tumor volume measured by microCT, PET and caliper all correlated (P < 0.001) with reference volume (figure 1).MicroCT versus reference volume (n = 20) had the best fit of line y = 1.01 0.04x - 6.1 6.3 (R 2 = 0.97; p < 0.001). 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