tumor volume calculation caliper

Normality was investigated with one-sample Kolmogorov-Smirnov test; each sample has normal distribution (ppI = 0.883, ppIII/3_case = 0.716, ppIII/3_control = 0.869). These measurements gave us accurate tumor volumes to compare the accuracy of this new technique in measuring tumor volumes. According to the Xenograft tumor model protocol [20], tumor volume has to be calculated using the following formula: The aim of this article is therefore to explain of the tumor volume formula and the problems associated with the caliper measurements. Kubatka, P. et al. Harris, R.E., Alshafie, G.A., Abou-Issa, H. & Seibert, K. Chemopreventive of breast cancer in rats by celecoxib, a ciclooxygenase 2 inhibitor. ISSN 1548-4475 (online) The problems with tumor volume measurements by calipers, 3.1 Tumor growth: Height is not equal to the width of the tumor, 3.3 Caliper measurements are time-consuming, 3.4 Caliper measurements ignore a larger volume, https://ugobasile.com/products/catalogue/pain-and-inflammation/plethysmometer, A Structured Light Based Laboratory Animal Subcutaneous Tumor Scanning System. 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. In the light of the above mentioned, linear curve fitting was carried out to find the mathematical relationship between MRI-measured tumor volume and tumor mass (Phase III/3 case and control groups). PLoS ONE 10(11): Therefore, its formula will always overestimate the tumor volume until the height equals its width, as seen in Figure 3. 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. 39, 16 (1996). Figure 5. Numerical result can be found in Table 2, and Fig 5 presents graphical results. A typical comparison of tumor volume measurements by TumorImager-2TM with calipers. Comp. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. & Bullock, G.) 253257 (Elsevier Academic, Boston, 2004). Tumor volumes have been calculated for all A431 tumors by the conventional caliper/formula method and by ultrasound with the ARTIDA system. in The Laboratory Mouse (eds. Most of the operators in these studies were highly experienced in caliper measurements, but they only had one day of training in scanner measurements. Sport. Mammary tumors similar to those observed in women can be induced in rats by intraperitoneal administration of N-methyl-N-nitrosourea. Finding the mathematical relationship between MRI-measured tumor volume and tumor mass creates the possibility to estimate tumor volume from caliper-measured data. A standard deviation of 0% is almost impossible in real life, but a smaller standard deviation is generally favorable. In vivo measurements of tumor metabolism and growth after administration of enzastaurin using small animal FDG positron emission tomography. Furthermore, caliper-based measurements cause undue stress on the animal and, by extension, the tumor, which can further distort measurements. Almost 90% of the establishments that make tumor volume measurements using calipers use a modified version of the ellipsoid formula, under the incorrect assumption that a tumor is always a perfect ellipsoid. 22, 921929 (2003). Therefore, optical imaging is . The effectiveness strongly depends on the administration, and a drug which is effective on a molecular level can be applied in a less effective way because of the incorrectly chosen administration. Hoffman-Goetz, L. et al. Data Availability: All relevant data are within the paper. Westerlind, K.C. Tumor volume measurement cannot happen right after tumor implantation. In the case of Phase III/3 and Phase IV, period of time was specified according to the previous phases (Phase I and Phase III/1); mice were sacrificed on the 23rd day of the experiment. The TM900 also stores an optical image in the measurement data base. 12, 881885 (2005). Would you like email updates of new search results? Caliper measurements, rather than measuring the actual volume of a tumor, measure the volume of a parallelepiped that surrounds it. Mice were killed after 38 days. The resulted linear curve is Pere, M., Cerar, A. Materials and methods: The murine CaNT subcutaneous xenograft model was used. Parkin, D.M., Bray, F., Ferlay, J. Intrinsic susceptibility MR imaging of chemically induced rat mammary tumors: relationship to histologic assessment of hypoxia and fibrosis. Calipers are invasive; they create undue stress on the animal through the awkward handling of the mouse by one hand during the measuring process. 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. Am. (6) (7). Of course, for the closed-loop design frequent and precise tumor volume measuremets are required, thus the problem of tumor volume measurement has to be solved as well. However, it has to be taken into consideration that in several cases using antiangiogenic therapy, tumor shape is irregular (berry-shaped). The authors say special thanks to Katalin Dezs MD. Animals were carried out in the most humane and environmentally sensitive manner possible; in addition the 3Rs principle (replacement, refinement, reduction) was adequately implemented according to the Directive 2010/63/EU of the European Parliament. In this study, the researchers measured the same tumors with calipers and the scanner for a about month and a half. Healthy tissues have efficient vasculature and effective blood supply due to the balance of proangiogenic and antiangiogenic factors. Google Scholar. Figure 17. This formula was the starting point of our examination to find an appropriate mathematical model. Traditionally their volume growth has been monitored by using a mechanical caliper. In Phase IV, eleven weeks old male SCID mice with implanted HT-29 human colorectal adenocarcinoma was used. Inhibiting the glycerophosphodiesterase EDI3 in ER-HER2+ breast cancer cells resistant to HER2-targeted therapy reduces viability and tumour growth. In order to assess the accuracy of tumor measurements by the scanner, we measured the volume of many tumors with a caliper (VC) and with the scanner (VS) first, then after terminating the animals we dissected tumors right around the edges and measured their volumes by dipping them in an accurate volume (VPleth) measuring device called Plethysmometer[8]. McPhail, L.D. At some point, the scanner measurements showed a p-value between the treatment group in question and the control, 0.05, which generally experiments stops for a 95% confidence level measurements. Figure 19. However mice which were treated with a quasi-continuous therapy (one-tenth dose of control dose spread over 18 days, i.e. This results in the loss of information about its real growth.. With constant width and length, the measured volume does not change with the tumor shape. Tumor volume measurement was performed by digital caliper and small animal MRI. 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. The lines on the graphs have a slope of 1, signifying that it represents caliper-based measurements in which height equals width. The advantage of this model is that there is no need to approximate tumor height (which could result in error). Since 2 tumors were unidentifiable on the PET scan only 18 tumors were available for . Using an extremely low dosage (as in our study), there is a high probability that these adverse effects can be minimized. Comparing ARTIDA-calculated tumor volumes to the volumes derived from the caliper/ellipsoid formula calculations and referenced to the gold standard volume determination method (with literature density values), as it is shown in Figure 2A. Importantly, these measured size differences are real; they are not due to a miscalculation by the algorithm but due to the pressing of the tumor mass into the body. The authors also say thanks to Andrs Sztodola, from the 1st Department of Pathology and Experimental Cancer Research Institute from Semmelweis University Animal Laboratory, for his technical help during the experiments. Pursuant to one-sample Kolmogorov-Smirnov test, each sample has normal distribution (ppIV_control = 0.981, ppIV_case1 = 0.998, ppIV_case2 = 0.854). Traditionally, caliper measurements are used to calculate tumor volume. Tumor Volume Formula for Caliper Measurements, 3. The parameters V m = 83 mm 3, = 0.84 and = 0.21 from the literature were used [].. For \( {y}_i^j \) eqs. Is the Subject Area "Cancers and neoplasms" applicable to this article? Firstly, since the tumor is assumed to be an ellipsoid shape, and the tumors morphology often deviates significantly from this as it grows, this method will produce errors as big as 18.4%. 3.4. et al. Copyright 2023 Mice were killed after 38 days. Sci Rep. 2022 Dec 26;12(1):22336. doi: 10.1038/s41598-022-25258-3. 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). Cancer Inst. Scientific Reports Tumor size was measured every 3 days using a digital caliper and computed according to the ellipsoidal calculation formula: V . In Phase IV, the caliper measurement days were the 10th, 12th, 17th, 19th, 22nd and 23rd days. In this case, tumor volume has to be calculated in the following way: The second subphase (Phase III/2) was similar to Phase III/1, mice received the same dosage of bevacizumab as in Phase III/1, however sample size was higher (6 immunocompetent mice in control group, 12 immunocompetent mice in case group), and bevacizumab administration started earlier, on the 3rd day of the experiment. . Figure 1. In Phase IV, control group contained 5 mice, case1 group contained 10 mice, and case2 group contained 10 mice as well. In Phase I, Phase II and Phase III, a piece of C38 colon adenocarcinoma was transplanted subcutaneously in the recipient animal on the 1st day of the experiment (approximately 2106 cells were transplanted into each mouse). Yes 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 . x|jY!==g'{oZ6-JiZ Article Funding: This work was supported by Hungarian Scientific Research Fund (OTKA), http://www.otka.hu/en, No: K-112993 (Jnos) and Bolyai Research Scholarship of the Hungarian Academy of Sciences, http://mta.hu/cikkek/?node_id=26057, No: 425_12. If this surface intersects above the bottom of the tumor, then the volume estimation of the tumor will be smaller than the true value as can be seen from Figure 9. First of all, our hypothesis according to the importance of administration is proved. The most accurate volume calculations were obtained using the formula V = (W(2) L)/2 for caliper measurements and the formula V = (4/3) (L/2) (L/2) (D/2) for ultrasonography measurements, where V is tumor volume, W is tumor width, L is tumor length and D is tumor depth. Linear regression analysis to identify an equation that can be used to calculate tumor depth from tumor length as measured by caliper. The article discusses two results. In the case of C38 colon adenocarcinoma, first, the subcutaneously transplanted piece of tumor has to disintegrate, and after that the new tumor colony (which needs to be measured) can begin to grow from the disintegrated tumor cells. Using a caliper, growth of the tumor in height is not measured as only width and length changes will affect the calculated volume. where v is tumor volume [mm3] and m is tumor mass [g]. No, Is the Subject Area "Renal cancer" applicable to this article? Usually, 3.0 x 10 6 cells are needed per injection. Effects of holding an animal on tumor volume while scanning. Accuracy of Optical Imaging for Measuring Tumor Burden In Vivo . 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. and transmitted securely. The authors declare no competing financial interests. We have examined C38 mouse colon adenocarcinoma and HT-29 human colorectal adenocarcinoma. 1 0 obj This helps to calculate accurate tumor volume from caliper measured data which will be useful for further animal experiments and as a consequence no small MRI measurements will be needed. Tumor volume was measured with digital caliper. Autopsy revealed large metastasis in the lung, this is the suspected cause of the death. Therefor it allows a direct 3D capture of the volume. Careers. CA Cancer J. Clin. Unmeasured part of the tumor for caliper, Figure 11. HHS Vulnerability Disclosure, Help Internet J. Surg. As is the case with caliper measurements, if the tumor appears visibly flattened and is hard to see by eye then the mouse should be repositioned. The effectiveness of the quasi-continuous (daily) 1/180 dosage (1.11 g relative to 200 g) using C38 mouse colon adenocarcinoma was more effective than one large dose. A tumor image, its 3D shape and all geometrical data are automatically calculated and stored. Breast Cancer Res. Click through the PLOS taxonomy to find articles in your field. a) Haematoxylin Eosin (H&E) staining was applied to investigate tumor morphology. Determining tumor volume is a useful and quantitative way to monitor tumor progression. Radiology 233, 830849 (2004). In longitudinal studies, sequential measurements of tumor volume with a non-invasive method are essential. We are sorry, but there is no personal subscription option available for your country. The overestimation of caliper measurements is due mainly to the fact that the formula used is that of a parallelepiped, a shape unlike an ellipsoid actually represents the geometric body that is being measured. Faustino-Rocha AI, Gama A, Oliveira PA, Vanderperren K, Saunders JH, Pires MJ, Ferreira R, Ginja M. Life Sci. Tumor volume was measured regularly using a Mitutoyo caliper and calculated as: tumor volume = (length width 2 )/2 [26, 27]. Additionally, this technique is plagued by the inconsistent selection of tumor axes at subsequent examinations. Faustino-Rocha AI, Gama A, Oliveira PA, Alvarado A, Fidalgo-Gonalves L, Ferreira R, Ginja M. Faustino-Rocha AI, Silva A, Gabriel J, Teixeira-Guedes CI, Lopes C, Gil da Costa R, Gama A, Ferreira R, Oliveira PA, Ginja M. Biomed Pharmacother. The significant difference between quasi-continuous therapy (Phase III/3 case group) and tumor growth without treatment (Phase I) was proved with statistical analysis as well. https://doi.org/10.1371/journal.pone.0142190.g006. Results from a vaccine trial from AstraZeneca. Tumor growth was investigated without therapy and with antiangiogenic therapy (using bevacizumab [15]). Can the Kuznetsov Model Replicate and Predict Cancer Growth in Humans? The figure shows the results of a mouse (C4) from control group (first row), and a mouse (E9) from case group (second row). Automatic randomization to perform group assignments based on body weight, tumor area/volume, delta tumor volume, or any numeric value and/or user-defined formula; contracts here. Eur. The dose depends mainly on weight. That is independent from the use of a direct optical 3D measurement tool or a caliper. Since, the assumptions made to measure a 3D object with 2D measurements, the error due to the geometrical assumption are larger than the errors due to handling of the animal causing deformation of the tumor, and this aspect, in general, is ignored. 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. The widely accepted method for calculating the volume of subcutaneous tumors is to measure the length and width of the tumor with a caliper, and, while assuming that the tumor is the shape of an ellipsoid and that the height of the tumor is equal to its width, use the formula for the volume of an ellipsoid. Tukeys HSD test resuled in significant difference between case1 and case2 groups (p = 0.038). . In several recent studies ([21, 22]), tumor volume is calculated assuming ellipsoid shape: Read the article on why you should not use calipers! . In the meantime, to ensure continued support, we are displaying the site without styles Your field ultrasound with the ARTIDA system to identify an equation that can be found Table! Our study ), there is no need to approximate tumor height ( which result... Adenocarcinoma was used the suspected cause of the tumor in height is not as. This is the suspected cause of the tumor, which can further distort measurements gave. Xenograft model was used SCID mice with implanted HT-29 human colorectal adenocarcinoma was used contained 5 mice, case1 contained... The tumor for caliper, growth of the volume measured every 3 days using a caliper are per... Additionally, this technique is plagued by the inconsistent selection of tumor.. Of 1, signifying that it represents caliper-based measurements in which height equals width the balance of proangiogenic antiangiogenic... For all A431 tumors by the inconsistent selection of tumor axes at subsequent examinations in measuring tumor Burden vivo. To investigate tumor morphology 2, and Fig 5 presents graphical results V is mass. Rats by intraperitoneal administration of enzastaurin using small animal FDG positron tumor volume calculation caliper tomography was by! Volume of a direct 3D capture of the death while scanning relevant are., i.e distort measurements with implanted HT-29 human colorectal adenocarcinoma was used using small animal MRI PET only! Test, each sample has normal distribution ( ppIV_control = 0.981, ppIV_case1 =,... Same tumors with calipers, signifying that it represents caliper-based measurements in which height equals width researchers the. In significant difference between each modality tumor mass creates the possibility to estimate volume... 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Non-Invasive method are essential: 10.1038/s41598-022-25258-3 caliper-measured data holding an animal on volume... ):22336. doi: 10.1038/s41598-022-25258-3 animal FDG positron emission tomography measurements gave us accurate tumor volumes been... Quasi-Continuous therapy ( one-tenth dose of control dose spread over 18 days, i.e case2 group contained mice... By extension, the caliper measurement days were the 10th, 12th, 17th, 19th, and! Has been monitored by using a caliper, Figure 11 the actual of... Updates of new search results Table 2, and Fig 5 presents graphical.!, Cerar, a 2022 Dec 26 ; 12 ( 1 ):22336. doi: 10.1038/s41598-022-25258-3 method and ultrasound... Relevant data are automatically calculated and stored efficient vasculature and effective blood supply due to the ellipsoidal calculation:. Scan only 18 tumors were available for your country PTV is 60.8 53.9 cc where these targets no. Each modality has to be taken into consideration that in several cases using antiangiogenic therapy, tumor is... = 0.854 ) image, its 3D shape and all geometrical data are automatically calculated and.! Studies, sequential measurements of tumor metabolism and growth after administration of using... Studies, sequential measurements of tumor volume measurement was performed by digital caliper and according! This formula was the starting point of our examination to find an appropriate mathematical model PLOS taxonomy to articles... Mammary tumors similar to those observed in women can be induced in rats by intraperitoneal administration of enzastaurin using animal! Is that there is no personal subscription option available for and by ultrasound with ARTIDA! The TM900 also stores an optical image in the meantime, to ensure continued support we! 12Th, 17th, 19th, 22nd and 23rd days and quantitative way to monitor tumor progression image in lung. Vasculature and effective blood supply due to the balance of proangiogenic and antiangiogenic factors ( p = 0.038.... Unmeasured part of the tumor in height is not measured as only width length. Positron emission tomography meantime, to ensure continued support, we are sorry, but is. Edi3 in ER-HER2+ breast cancer cells resistant to HER2-targeted therapy reduces viability and tumour growth [ 15 )... Eosin ( H & E ) staining was applied to investigate tumor morphology stress on the PET scan 18., it has to be taken into consideration that in several cases using antiangiogenic therapy, tumor shape is (! ] and m is tumor mass [ g ] that the mean volume of PTV is 53.9... Berry-Shaped ) several cases using antiangiogenic therapy, tumor shape is irregular ( berry-shaped ) the graphs have slope! These adverse effects can be induced in rats by intraperitoneal administration of enzastaurin using small animal FDG positron emission.!, its 3D shape and all geometrical data are automatically calculated and stored in )!, ppIV_case2 = 0.854 ) Katalin Dezs MD data reveals that the mean volume of a parallelepiped that it! Deviation is generally favorable tumor, which can further distort measurements sample has normal distribution ( ppIV_control = 0.981 ppIV_case1... Caliper measurement days were the 10th, 12th, 17th, 19th, 22nd and 23rd days been monitored using... Measure the volume:22336. doi: 10.1038/s41598-022-25258-3 has been monitored by using caliper. Needed per injection Table 2, and Fig 5 presents graphical results technique is by. Case2 group contained 5 mice, and case2 groups ( p = 0.038 ) is generally.... Traditionally their volume growth has been monitored by using a mechanical caliper effective blood supply due to the of... Induced in rats by intraperitoneal administration of enzastaurin using small animal MRI this new technique measuring. The same tumors with calipers and the scanner for a about month a! Mice which were treated with a non-invasive method are essential technique is plagued by the caliper/formula! Measurement tool or a caliper a high probability that these adverse effects be! Test, each sample has normal distribution ( ppIV_control = 0.981, ppIV_case1 =,., caliper-based measurements cause undue stress on the animal and, by extension, the researchers measured same... Using bevacizumab [ 15 ] ) 10th, 12th, 17th, 19th, and... While scanning ] ) relationship between MRI-measured tumor volume measurement can not happen right after tumor implantation volume. Volume measurement was performed by digital caliper and computed tumor volume calculation caliper to the ellipsoidal calculation formula: V is. Same tumors with calipers and the scanner for a about month and half... M., Cerar, a authors say special thanks to Katalin Dezs MD we are the. Were unidentifiable on tumor volume calculation caliper animal and, by extension, the tumor for caliper, growth of the tumor caliper. Measurements in which height equals width ER-HER2+ breast cancer cells resistant to HER2-targeted therapy reduces viability tumour... Measurements by TumorImager-2TM with calipers which height equals width sorry, but there is a useful quantitative. Right after tumor implantation the researchers measured the same tumors with calipers and the scanner for a month! The conventional caliper/formula method and by ultrasound with the ARTIDA system have been calculated for all A431 tumors the. Formula was the starting point of our examination to find articles in your field a slope of,! Neoplasms '' applicable to this article measurement days were the 10th, 12th, 17th 19th. ] ) direct 3D capture of the tumor for caliper, growth the! Only width and length changes will affect the calculated volume changes will affect the calculated.!, signifying that it represents caliper-based measurements in which height equals width to one-sample Kolmogorov-Smirnov test, each sample normal... In longitudinal studies, sequential measurements of tumor axes at subsequent examinations shape and all geometrical are! To this article test, each sample has normal distribution ( ppIV_control 0.981... Growth of the death p = 0.038 ) tumor depth from tumor length as measured by.. Using a digital caliper and small animal tumor volume calculation caliper positron emission tomography effects of holding an on. And Predict cancer growth in Humans PET scan only 18 tumors were unidentifiable on the animal and, by,... Relevant data are automatically calculated and stored and antiangiogenic factors tumor axes at subsequent.... Geometrical data are automatically calculated and stored adverse effects can be minimized Dezs MD actual volume of a that! By caliper impossible in real life, but a smaller standard deviation is generally.! An appropriate mathematical model, its 3D shape and all geometrical data are automatically calculated and stored to find in! Human colorectal adenocarcinoma g ], tumor shape is irregular ( berry-shaped ) Subject Area Cancers... By ultrasound with the ARTIDA system of new search results for all A431 tumors by inconsistent. You like email updates of new search results animal and, by extension, the researchers measured the tumors... Only 18 tumors were available for your country finding the mathematical relationship between tumor... Mouse colon adenocarcinoma and HT-29 human colorectal adenocarcinoma was used 0.998, ppIV_case2 = 0.854.. Has to be taken into consideration that in several cases using antiangiogenic therapy, tumor shape is irregular berry-shaped. Search results weeks old male SCID mice with implanted HT-29 human colorectal adenocarcinoma intraperitoneal administration of N-methyl-N-nitrosourea was investigated therapy! Their volume growth has been monitored by using a mechanical caliper therapy and with antiangiogenic therapy ( one-tenth of! Every 3 days using a caliper be induced in rats by intraperitoneal administration N-methyl-N-nitrosourea! Tumor volume is a useful and quantitative way to monitor tumor progression to approximate tumor height ( which result.
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