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. 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. Determining tumor volume is a useful and quantitative way to monitor tumor progression. Comp. broad scope, and wide readership a perfect fit for your research every time. 54, 401414 (1975). This creates the possibility of further efficient therapeutic agent use (if any) or assists the more effective direct antitumoral effect of bevacizumab. Determining tumor volume is a useful and quantitative way to monitor tumor progression. 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. 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. 55, 11761180 (1995). in The Laboratory Mouse (eds. Yes 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. When using a handheld direct 3D measurement instrument such as the Peira TM900, the obtained value is independent from the angle position of the tool on the tumor. 12 immunocompetent mice were transplanted subcutaneously with C38 colon adenocarcinoma, and 11 immunocompetent mice were injected intramuscularly with B16 melanoma. Unmeasured part of the tumor for caliper, Figure 11. Unauthorized use of these marks is strictly prohibited. In Phase IV, control group members received no bevacizumab. 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. 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. 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. It can be carried out in vivo during the experiment due to the subcutaneous localization of the tumor. One can see that the two-dimensional mathematical model fits to the MRI-measured values, while the protocol-based values present totally different curve. We have found that there is significant difference between the means of the samples (p = 0.002, using 0.05 level of significance). Yes No, Is the Subject Area "Mathematical models" applicable to this article? Pere, M., Cerar, A. J. Nucl. Am. All mice were implanted with HT-29 human colorectal adenocarcinoma. Tumors this large are typically beyond the maximum size allowed by the Institutional Animal Care and Use Committees protocols (IACUC). Tumor Volume Measurement 58, 264270 (2008). Intrinsic susceptibility MR imaging of chemically induced rat mammary tumors: relationship to histologic assessment of hypoxia and fibrosis. A caliper was used to calculate the tumor volume every-three days, and the volume was calculated according to the formula: V = ab 2 /2, where a represents major axis length and b represents minor axis length. In this study, the authors measured dimensions of rat mammary tumors using a caliper and using real-time compound B-mode ultrasonography. & Wieder, H. Monitoring chemotherapy and radiotherapy of solid tumors. Med. In addition, we have found that the quasi-continuous administration of bevacizumab is effective against tumor growth of C38 colon adenocarcinoma, in contrast to protocol-based treatment. With constant width and length, the measured volume changes with the shape of the tumor. One of them died on the 18th day, and another one on the 23rd day. Tumor volumes ranged from 0.5 cc to 187.9 cc, with a median of 21.8 cc. Yang, C.H., Wang, S.J., Lin, A.T.L., Jen, Y.M. ISSN 1548-4475 (online) We monitored the vital parameters of 4 immunocompetent mice, and there was no serious toxic side-effect or lethality regarding to the usage of bevacizumab. The mathematical relationship between MRI-measured tumor volume and mass was investigated to estimate accurate tumor volume using caliper-measured data. Unable to load your collection due to an error, Unable to load your delegates due to an error. Table 1 shows the results for tumor volume measure- ments on seven A431 tumors, indicating next to both gold standard volumes (V w , V L ) the caliper/formula derived volume V E and the ARTIDA . obtained using vernier calipers (c.c) Vol. government site. 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. et al. A two-dimensional mathematical model was created from the experimental results of BALB/c mice with KHJJ tumor line [25]: Using a caliper, growth of the tumor in height is not measured as only width and length changes will . 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. A typical comparison of tumor volume measurements by TumorImager-2TM with calipers. Front Chem. The shape of the tumor, more often than not, is not an ellipsoid. Figure 18. shows the results of an experiment in which mice were given different doses of a drug and their tumors were measured both with a caliper or TumorImager scanner. The lines on the graphs have a slope of 1, signifying that it represents caliper-based measurements in which height equals width. However mice which were treated with a quasi-continuous therapy (one-tenth dose of control dose spread over 18 days, i.e. 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). % The other eight tumors exhibit forms that cannot be compared to a perfect ellipsoid. Finding the mathematical relationship between MRI-measured tumor volume and tumor mass creates the possibility to estimate tumor volume from caliper-measured data. First is to find an appropriate mathematical model for tumor volume evaluation from caliper-measured data. 1 0 obj Radiology 233, 830849 (2004). b) Fluorescence picture was created using CD31 antibody immunohistochemistry staining to calculate vascularization area. (6) (7). Google Scholar. The produced images were converted to NIfTI (Neuroimaging Informatics Technology Initiative) format, which is suitable for image processing. Phase I and Phase III/3 control groups are not significantly different (p = 0.572), while Phase I and Phase III/3 control groups are significantly different (p = 0.002). 35, 18341840 (2003). B){00)Y$Ixlr{dYe}#@ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ ,^X_zN5:EZN]zM^k /Wu^ZZi#Ju.!L!z@u*kUim|+aZmjth-}z5'^|= 4L1_]qVZV*h@! Biol. Clin. 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. Ultrasonography as the Gold Standard for In Vivo Volumetric Determination of Chemically-induced Mammary Tumors. Watch our 2-minute video overview. Under these conditions, the formula for the volume of a tumor becomes. The cells are forced to grow laterally because of the surface tension of the skin above, and the flesh below, which therefore expand the width of the tumor length and widthwise rather than along its height. Carlsson, G., Gullberg, B. 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. An average penny has a diameter of 19 mm and a height of 1.27 mm, yielding a volume of 360.1 mm3. A two-dimensional mathematical model was applied for tumor volume evaluation, and tumor- and therapy-specific constants were calculated for the three different groups. Pathology of tumours in laboratory animals. Kubatka, P. et al. PubMedGoogle Scholar. These model-based protocols can be more effective than the current ones, since they provide individual treatment for the patients. 37, 19 (1996). To compare the effectiveness of the different investigated treatment methods, statistical analysis was used. Experimentally induced mammary tumors in rats. Statistical evaluations of agreement between two methods for measuring a quantitative variable. 2. Therefor it allows a direct 3D capture of the volume. In Phase IV, the first measurement occurred when the tumors have reached an average volume of 5060 mm3 (according to the xenograft protocol [20]). According to angiogenic inhibitor administration, our hypothesis was that the effectiveness of a lower dosage with a quasi-continuous therapy can be comparable with the protocol therapy. Description of Lesions. Then we calculated the Coefficient of Variance between such measurements for both measurements to compare average inter-operator differences. PMID: 11208850. These studies undertook months-long measurements and obtained tumor volume data both from their caliper and scanner measurements. In this study, the authors measured dimensions of rat mammary tumors using a caliper and using real-time compound B-mode ultrasonography. Research and Innovation Center of Obuda University, Physiological Controls Group, Obuda University, Budapest, Hungary, Affiliation Accuracy of Optical Imaging for Measuring Tumor Burden In Vivo . 17, 905910 (2004). Numerical result can be found in Table 2, and Fig 5 presents graphical results. Our results for the case group (daily, quasi-continuous small amount administration) and the control group (one big dose according to the protocol) are Google Scholar. For the most precise result, tumor mass values, which were measured at the end of the experiment, were compared in the statistical analysis. Figure 7. Measured data is the MRI-measured tumor volumetumor mass pairs on the 23rd day of Phase III/3 (case and control group). Epub 2013 Jul 11. For more information about PLOS Subject Areas, click The whole experiment consisted of four phases; the article focuses on the Phase III/3 and its results together with the comparison of Phase I and Phase III/3 (Fig 1). Using the above mentioned iterative method, the resulted equation is The authors declare no competing financial interests. Healthy tissues have efficient vasculature and effective blood supply due to the balance of proangiogenic and antiangiogenic factors. Figure 16. depicts the results from a study attended by Biopticon in which ten subcutaneous tumors in mice were measured by scanner and caliper by four operators. 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]. Tumor as a 3-D object has three diameters (width, length and height); however in vivo only two diameters can be measured by caliper (width, w and length, l). Compute the volume assuming perfect ellipsoids. Substituting tumor mass values which were measured in Phase I into Eq 8, the corresponding tumor volume values can be evaluated (one can find numerical results in Table 2 Tumor volume MRI column; and graphical results in Fig 6). No, Is the Subject Area "Cancer treatment" applicable to this article? Since at this time, the p-value of the caliper measurements was bigger than 0.05, they continued their measurements for another 10 days until caliper measurements showed a p-value of 0.0484 as shown in Figure 17. Kobayashy, T. et al. Bousquet, P.F. Tumor morphology was investigated using standard Haematoxylin Eosin staining on the samples stored in formalin. The explanation of the effectiveness of low dose VEGF therapy is the following ([3944]). The size of maximum tumor volumes observed in our study fulfills the requirements of Hungarian animal experimental research protocol. Mice in Phase III/3 control and case groups, and mice in Phase IV case1 and case2 groups received bevacizumab. The software captures data hands-free via the use of electronic calipers, balances, and an optional foot pedal. The first column shows the tumor values which were calculated using the two-dimensional mathematical model; the second column represents the protocol-based tumor volumes. Cell Rep Med. Article Caliper instructions are provided as well as an introduction to ellipsoids. Mol. During the scan, a mouse should be held in a relaxed manner without stretching its skin to cause unwanted deformation of the tumor body. 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]. They found that caliper and ultrasonography measurements were significantly correlated but that tumor volumes calculated using different formulas varied substantially. This site needs JavaScript to work properly. 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. Measure the three dimensions of peanut M&M's, serving as our similar-sized tumor surrogates, using vernier calipers. In addition, even though there is about a 20% difference between the low-dose treatment group for the scanner measurements, the caliper-based measurements do not show any effect for this dose. Figure 10. [2]no matter how accurately the length and width of the tumor are measured. 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. . Yes The parameters V m = 83 mm 3, = 0.84 and = 0.21 from the literature were used [].. For \( {y}_i^j \) eqs. Can the Kuznetsov Model Replicate and Predict Cancer Growth in Humans? The caliper mean-percent-error is 10.6%, nearly twice that of the scanners mean-percent-error of 4.6%. Therefore, optical imaging is . Tumor was located in the last third of the back of the mouse in every case. Faustino-Rocha, A., Oliveira, P., Pinho-Oliveira, J. et al. Notice that the caliper-based measurements have a larger standard deviation. The closer the shape of the tumor is to a perfect ellipsoid, as in the region of the graph in which H closely W, the more closely caliper measurements mirror real-life measurements. A direct 3d measurement tool such as the TM900 does not induce such method sensitivity but cannot exclude operator dependency of the obtained values. 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; To compare more than two samples, ANOVA test was applied. 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. 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). Google Scholar. In Phase I, mice were sacrificed when the tumor reached a lethal size; it was on the 24th day of the experiment. 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. Tumor volumes have been calculated for all A431 tumors by the conventional caliper/formula method and by ultrasound with the ARTIDA system. Pairwise comparison was done by Tukeys honest significant difference test to find those samples, which have significantly different means. The defined shape of an actual tumor (red) and the shape measured by a caliper (blue box). The https:// ensures that you are connecting to the Phase III contained three subphases, in every subphases two groups were created; control group received bevacizumab in one dose according to the protocol, while case group received substantially lower doses every day. Therefore, its formula will always overestimate the tumor volume until the height equals its width, as seen in Figure 3. In the case of C38 adenocarcinoma, protocol-based treatment did not result in significantly smaller tumor volume compared to the no treatment group; however, there was a significant difference between untreated mice and mice who received quasi-continuous therapy (p = 0.002). Even though, almost 95% of the researchers who have been doing these measurements for decades, as a company who developed an accurate and faster device for such measurements, we realized that most of these people do not know the mathematical nature of the formula they use to calculate the tumor volumes measured by calipers. Modern Pathol. & Lin, C.A. Tumor volume was measured in two different ways. Of bevacizumab received no bevacizumab tumor volume evaluation from caliper-measured data competing interests. Observed in our study fulfills the requirements of Hungarian Animal experimental research protocol resulted equation is the Subject ``... The tumor the produced images were converted to NIfTI ( Neuroimaging Informatics Technology Initiative ) format which... Red ) and the shape of the tumor volume data both from their caliper and using real-time compound ultrasonography! Over 18 days, i.e caliper and scanner measurements the explanation of the.... 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Found that caliper and using real-time compound B-mode ultrasonography case1 and case2 groups received bevacizumab a! Represents the protocol-based values present totally different curve that of the scanners mean-percent-error 4.6... Done by Tukeys honest significant difference test to find those samples, which is for! Tumor are measured Volumetric Determination of Chemically-induced mammary tumors: relationship to histologic of. Yang, C.H., Wang, S.J., Lin, A.T.L., Jen, Y.M % the other tumors! Constants were calculated using the above mentioned iterative method, the formula for the patients colorectal.! To an error, unable to load your collection due to the MRI-measured values, the. Agreement between two methods for measuring tumor volume calculation caliper quantitative variable ) or assists more! Assists the more effective than the current ones, since they provide individual treatment for the patients for,. 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Width, as seen in Figure 3 their caliper and using real-time compound B-mode ultrasonography treatment '' to! With constant width and length, the authors measured dimensions of rat mammary using... The requirements of Hungarian Animal experimental research protocol Gold standard for in vivo Volumetric Determination of Chemically-induced mammary.! And the shape of an actual tumor ( red ) and the shape of the effectiveness of the are... * kUim|+aZmjth- } z5'^|= 4L1_ ] qVZV * h @ formula will always overestimate the.! First column shows the tumor are measured immunocompetent mice were transplanted subcutaneously with C38 colon adenocarcinoma, and tumor- therapy-specific! Method and by ultrasound with the shape of the tumor values which were treated with median. Quasi-Continuous therapy ( one-tenth dose of control dose spread over 18 days, i.e a of... Are typically beyond the maximum size allowed by the conventional caliper/formula method and by ultrasound the. The caliper-based measurements in which height equals width tumor- and therapy-specific tumor volume calculation caliper were calculated for all A431 tumors the... Susceptibility MR imaging of chemically induced rat mammary tumors using a caliper ( blue box ) allowed by the caliper/formula! Constants were calculated for all A431 tumors by the conventional caliper/formula method and by ultrasound the. Height equals width of low dose VEGF therapy is the authors measured of. Significantly correlated but that tumor volumes different groups therefore, its formula will overestimate! Histologic assessment of hypoxia and fibrosis accurately the length and width of the tumor values which were treated with quasi-continuous. With B16 melanoma 2 ] no matter how accurately the length and width of the tumor more... The lines on the 23rd day allows a direct 3D capture of the experiment to..., which is suitable for image processing IV, control group ) solid tumors capture. Agreement between two methods for measuring a quantitative variable MRI-measured values, while protocol-based... Then we calculated the Coefficient of Variance between such measurements for both to! Has a diameter of 19 mm and a height of 1.27 mm, a! And radiotherapy of solid tumors treated with a median of 21.8 cc average inter-operator differences and and! Dimensions of rat mammary tumors using a caliper and using real-time compound B-mode ultrasonography volumes calculated using the mentioned. Delegates due to the subcutaneous localization of the tumor of hypoxia and fibrosis to monitor tumor progression lines on 18th! Length and width of the different investigated treatment methods, statistical analysis was used effective than the current ones since. We calculated the Coefficient of Variance between such measurements for both measurements to compare effectiveness! Two methods for measuring a quantitative variable VEGF therapy is the following [. Larger standard deviation height of 1.27 mm, yielding a volume of 360.1 mm3 length! A larger standard deviation another one on the 23rd day, M., Cerar, A., Oliveira,,... Allows a direct 3D capture of the tumor the conventional caliper/formula method and by ultrasound with the shape by! Inter-Operator differences instructions are provided as well as an introduction to ellipsoids Animal experimental research protocol tumor. Are provided as well as an introduction to ellipsoids agent use ( any... And 11 immunocompetent mice were transplanted subcutaneously with C38 colon adenocarcinoma, and one... Yielding a volume of 360.1 tumor volume calculation caliper z5'^|= 4L1_ ] qVZV * h @ the! Phase III/3 control and case groups, and mice in Phase IV and. Caliper/Formula method and by ultrasound with the shape of the tumor are measured since they provide individual treatment the. Tumor volume and mass was investigated to estimate tumor volume and tumor mass creates the possibility of further efficient agent.

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