Tumor Volume Measurement Westerlind, K.C. Tumor volume in subcutaneous mouse xenografts measured by microCT is more accurate and reproducible than determined by 18 F-FDG-microPET or external caliper. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). A tumor image, its 3D shape and all geometrical data are automatically calculated and stored. To compare more than two samples, ANOVA test was applied. One common measure of efficacy is the T/C ratio, the ratio of tumor volume in control versus treated mice at a specified Open Access Our study of the incised tumors in many mouse tumor models showed that this is mostly seen for very large tumors (Volume > ~1.5 cm3) where the tumors start bulging inward toward the flesh. Mammary tumors similar to those observed in women can be induced in rats by intraperitoneal administration of N-methyl-N-nitrosourea. This creates the possibility of further efficient therapeutic agent use (if any) or assists the more effective direct antitumoral effect of bevacizumab. ANOVA test showed significant difference between these means (p = 0.041, using 0.05 level of significance). Accuracy of Optical Imaging for Measuring Tumor Burden In Vivo . This device measures the volume displacement of the water due to any object dipped into a measuring cylinder. The problems with tumor volume measurements by calipers 3.1 Tumor growth: Height is not equal to the width of the tumor . by Mammog raphy (c.c) . 2009, 18 (2009). Provided by the Springer Nature SharedIt content-sharing initiative, Bulletin of the National Research Centre (2022), Lab Animal (Lab Anim) Using an extremely low dosage (as in our study), there is a high probability that these adverse effects can be minimized. CAS Tumor diameters are measured with digital calipers, and the tumor volume in mm 3 is calculated by the formula: Volume = (width) 2 x length/2; Reference Jacob et al, Gene Ther Mol Biol . M}{Gt{zj|&cXx[k?CZ ~AjTxMr0 '~ix$mj/)9?$ t-o6MkVXs's}^E6-^_Yrv#w&r7w@WsQs]#G g$Cn. When the tumor has a symmetrical, solid closed shape (typically without treatment), volume can be evaluated accurately from caliper-measured data with the applied two-dimensional mathematical model. 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. Mammary tumors similar to those observed in women can be induced in rats by intraperitoneal administration of N-methyl-N-nitrosourea. The results of the three investigated cases using C38 mouse colon adenocarcinoma (Phase I, Phase III/3 control group, and Phase III/3 case group) were compared using tumor volume values from MRI measurements (Phase III/3 control and case groups, 23rd day) and evaluated data (Phase I MRI tumor volume calculated from linear curve fit, 24th day). 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. One can see that the two-dimensional mathematical model fits to the MRI-measured values, while the protocol-based values present totally different curve. Result of Phase III/2 was that the effectiveness of the small amount of quasi-continuous dosage is comparable with the effectiveness of one large dose [23], however this result is only based on caliper-measured data. Further geometrical or visual data are not stored simultaneously. In the first four measurement times 30 slices were done from each mouse; in the last two measurement times 40 slices were done from each mouse due to the larger tumor volume. Yes In a 2001 study utilizing MRI, it was concluded that 85% of tumors needed a measurement other than length and the width to yield an accurate volume[5]; caliper-based values do not provide this other measurement. Pathol. In other fields, such as treatment of diabetes mellitus this closed-loop control is already solved; known as artificial pancreas (continuous glucose sensor for measurements, insulin pump for infusion and control algorithm) [47], [48]. Several studies have investigated the effectiveness of bevacizumab therapy according to different types of cancer [3]: lung cancer [4, 5], breast cancer [68], colon cancer [9], renal cell carcinoma [10], gastric cancer [11], pancreatic cancer [12], prostate cancer [13] and melanoma [14]. Similar to the results from the experiments in Figure 18., this error makes the drug seem less effective than it actually is. Scientific Reports Using the above mentioned iterative method, the resulted equation is Linear regression analysis to identify an equation that can be used to calculate tumor depth from tumor length as measured by caliper. All mice were implanted with HT-29 human colorectal adenocarcinoma. Sci Rep. 2022 Dec 26;12(1):22336. doi: 10.1038/s41598-022-25258-3. Lee, J., Koh, D. & Ong, C.N. . Traditionally their volume growth has been monitored by using a mechanical caliper. Davis, P.L. In Phase IV, case2 group members received 1.11 g bevacizumab (with 45 l 0.9% NaCl solution) every day form the 8th day for 15 days. Treat. Tumor growth inhibition rate (%); can be calculated using the following formula: = (Vc 1 -Vt 1 )/ (Vc 0 -Vt 0) X 100. where, Vc 1 is the mean tumor volume in the control group at the time of tumor . In Phase I, 12 mice were implanted with C38 colon adenocarcinoma. Tumor volumes measured with a Plethysmometer (VPleth) independent of caliper and scanner measurements (VC, VS) vs. VC and VS. Table 1. The third subphase (Phase III/3) was designed with the same bevacizumab administration as in Phase III/1 and Phase III/2; nevertheless, tumor volume was measured not only by caliper but by small animal MRI as well. Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. 20, the red dots that represent scanner-based measurements are closer to the black dotted (objective) line than the blue squares that represent caliper-based measurements. Since the real geometric object assumed to represent the tumor is a parallelepiped (rather than an ellipsoid), the flat bottom surface of it will leave a larger section of the tumor below than the interpolated surface following the body contour of the animal as seen in Figure 10, below. A standard deviation of 0% is almost impossible in real life, but a smaller standard deviation is generally favorable. A tumor expands in width rather than height as it grows. Clarke, R. Animal models of breast cancer: their diversity and role in biomedical research. HHS Vulnerability Disclosure, Help Imaging 16, 816 (2008). to calculate several estimates of tumor volume using the equations for the volume of a sphere ([4 /3]r3), Here r is average of a, b and c the volume of an Frozen samples were used to create 15 m frozen cuts. Finally, it finds the volume between these two surfaces and sets this to be the volume of the tumor (shaded red region in Figure 11, red region in Figure 14 below). 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). In Figure 4., the value given by caliper measurements (VC, red squares) does not change when up to 15 pennies are stacked. MeSH A structured light-based system for scanning subcutaneous tumors in laboratory animals. e0142190. Calipers are invasive; they create undue stress on the animal through the awkward handling of the mouse by one hand during the measuring process. Objectives: Volume measurement of subcutaneous xenograft tumors in nude mice models is an important metric to assess tumor growth or response to therapy. During the MRI measurements, life parameters of the mice were monitored. In the case1 group, one mouse died on the 17th day. obtained using vernier calipers (c.c) Vol. Stretching of the skin around the tumor of the mouse will cause an under-estimate of the tumor volume since the tumor is pressed into the body (see Figure 13. below). In the concept of model-based treatment, a continuous and precise tumor volume monitoring is needed concerning which, may be possible in the near future by nanotechnology [38]. In Phase III, we have investigated C38 colon adenocarcinoma growth with bevacizumab therapy. https://doi.org/10.1371/journal.pone.0142190, Editor: Francesco Bertolini, This means that the daily treatment with one-twelfth total dose resulted in significantly smaller tumors than the protocol-based treatment. When tumor cells become able to produce proangiogenic factors (the process is called as angiogenic switch), it will result in abnormal and inefficient vascular network (with high vascular permeability and poor perfusion) due to the hurried process of vessel formation. Mrio Ginja. Measurement by Caliper In order to estimate tumor volume by external caliper, the greatest longitudinal diameter (length) and the Tumor volume measurement cannot happen right after tumor implantation. While the scanner only overestimates by about 2%, the caliper overestimates by 32%, as shown by the slope of the line being 1.32. Front Chem. Yes The explanation of the effectiveness of low dose VEGF therapy is the following ([3944]). A possible solution for height approximation [23] is: <> stream Intrinsic susceptibility MR imaging of chemically induced rat mammary tumors: relationship to histologic assessment of hypoxia and fibrosis. The TM900 also stores an optical image in the measurement data base. To validate our results which come from the experiments where mouse tumor vascularization was inhibited with humanized VEGF, we evaluated the results of Phase IV, where immunocompromized (SCID) mice were used with human colorectal adenocarcinoma (HT-29) xenografts. Tumor volume was measured with digital caliper. 17, 905910 (2004). Lab Anim 42, 217224 (2013). One can find datasets in Table 3. The tumor burden is evaluated by volume calculation using caliper measurement. Federal government websites often end in .gov or .mil. where f is a constant which belongs to a certain tumor type. These measurements gave us accurate tumor volumes to compare the accuracy of this new technique in measuring tumor volumes. Pollok, K.E. This means that mice which were treated with the recommended bevacizumab protocol (one 200 g bevacizumab dose for an 18-day therapy) did not have significantly smaller tumor volume than mice which did not receive therapy at all. Similarly, we may have the possibility to a) measure the tumor volume using nanotechnology, b) create a pump for drug administration and c) design control algorithms for specific tumor types. Harris, R.E., Alshafie, G.A., Abou-Issa, H. & Seibert, K. Chemopreventive of breast cancer in rats by celecoxib, a ciclooxygenase 2 inhibitor. Evaluation of prostate volume by transabdominal ultrasonography with modified ellipsoid formula at different stages of benign prostatic hyperplasia. A caliper only digitizes the length and width of the tumor. 58, 264270 (2008). These images were applied to calculate vascularization area by using ImageJ (NIH, USA) [33] software (Fig 4). . Mice were euthanized by CO2 inhalation if tumors contributed to a gain of >20% in body weight compared to controls at the same time point. By using a caliper, one will measure width and length of the tumor and then calculate the volume using a standard formula, such as /6 x W x W x L or 1/2 x W x W x L thus assuming a standard and constant shape of the tumor. If one measures the volume of a penny using calipers and uses the widely accepted formula, repeating the measurement each time another penny is added to the stack, the stack will yield the same volume each time, regardless of how many pennies are stacked. To overcome all of these difficulties (continuity of the administration and side-effects), model identification should be determined and then a control algorithm (controller) can be designed for the created mathematical model. Tumor volume was calculated by the modified ellipsoidal formula: V = (Length Width 2) . 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 post hoc test resulted in the following. Normality was investigated with one-sample Kolmogorov-Smirnov test, and homogeneity of variance (homoscedasticity) was examined with Levenes test. Homogeneity of variance was examined with Levenes test; the sample variances are equal (p = 0.052). The figure shows the results of a mouse (C4) from control group (first row), and a mouse (E9) from case group (second row). Consequently, when tumor mass data is unavailable (during the experiment), tumor volume value can be validated with MRI; in that way outlier data points (which were calculated using the two-dimensional mathematical model) can be filtered out. 22, 921929 (2003). Open Access Figure 13. A smaller standard deviation in a set of measurements suggests a lesser possibility of error. [45] have found that the combination of low-dose cyclophosphamide and ginsenoside Rg3 therapy can be more effective than the normal administration. On the other hand, values given by a scanner (VS, red triangles) more closely follow the true volume of the pennies (VT, blue diamonds). 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]. Faustino-Rocha AI, Gama A, Oliveira PA, Vanderperren K, Saunders JH, Pires MJ, Ferreira R, Ginja M. Life Sci. To compare the effectiveness of the different investigated treatment methods, statistical analysis was used. 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