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. An official website of the United States government. Substituting tumor mass values which were measured on the 24th day of Phase I to the equation of the resulted curve, the corresponding tumor volume values can be evaluated (evaluated data). 105, 2023 (1983). Additionally, we explore the impact of six different tumour . If the length or width of a tumor is twice its height, which is often the case for many tumor models, then its measured volume will be overestimated by 50%. Open Access articles citing this article. Circular RNA circTRPS1-2 inhibits the proliferation and migration of esophageal squamous cell carcinoma by reducing the production of ribosomes. Tumor volumes are calculated from digital caliper raw data by using the formula:Volume (mm3) = (l x w2) / 2. In addition, the gap between tumor volume values for caliper-based control and treatment groups is smaller than that for scanner measurements; the significant p-value was over 50 times higher when using calipers (p > 0.05) than with scanners (p < 0.001), suggesting that the caliper-based measurements are not statistically significant. For more information about PLOS Subject Areas, click For this dataset, linear curve fitting was carried out (fitted linear curve) to find the mathematical relationship between MRI-measured tumor volume and tumor mass. Because tumor volume measurements used by researchers and industries are sensitive and often rely on the accuracy, the cutting-edge TumorImagerTM line of scanners is the ideal, most reliable choice for taking such sensitive measurements. Fornage, B.D., Toubas, O. Most, if not all, tumors do not fit into this category; this discrepancy results in caliper-based volume measurements including sections that do not exist in the actual tumor, or an overestimation of tumor volume measurement. Tumor volume was measured with digital caliper. In that caseeven though all the three diameters can be measuredthe estimation of the volume has quite a large error. Pathology of tumours in laboratory animals. First of all, our hypothesis according to the importance of administration is proved. Scientific Reports Examination of tumor growth belongs not only to the basic medical research, but to the biomedical engineering field as well. 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). These images also provide extra morphological information about the tumor growth and the effect of the compounds on tumor behavior. https://doi.org/10.1371/journal.pone.0142190.g002. 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 Figure 15., the linear regression equation for the best-fit line for VPleth values on the y-axis along with VC and VS values would be approximately y x, or y 1.00x + 0.00. Comparison of volume measurement results between four users. This process not only deforms the tumor mass but also creates undesirable pain on the animal. Read the article on why you should not use calipers! Cancer Res. 29 September 2022, Bulletin of Mathematical Biology Figure 3. A possible solution for height approximation [23] is: 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. b) Fluorescence picture was created using CD31 antibody immunohistochemistry staining to calculate vascularization area. %PDF-1.4 Furthermore, caliper-based measurements cause undue stress on the animal and, by extension, the tumor, which can further distort measurements. The volume above the red area is not occupied by the tumor, as seen in Figure 8. PMID: 11208850. https://doi.org/10.1371/journal.pone.0142190.g008. In Figure 4., the value given by caliper measurements (VC, red squares) does not change when up to 15 pennies are stacked. 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. 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. Clinical aspects which have to be considered to determine when animals should be euthanized are body weight, physical appearance, measurable clinical signs, unprovoked behavior and response to external stimuli. 58, 264270 (2008). The TM900 also stores an optical image in the measurement data base. A solution to these problems is the TumorImagerTM scanner. Weber, W.A. J Clin Oncol. Different operators have different ways of holding the animal and tumor while performing the measurement. Thus, caliper-based measurements, using the formula , are most accurate in real life for tumors in which height roughly equals width but prove less accurate as height becomes more unequal to width, as is the case with almost all real tumors. 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. The most accurate volume calculations were obtained using the formula V = (W2 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. Click through the PLOS taxonomy to find articles in your field. A standard deviation of 0% is almost impossible in real life, but a smaller standard deviation is generally favorable. The authors measured dimensions of rat mammary tumors using a caliper and using real-time compound B-mode ultrasonography and compared the calculated tumor volumes with the real tumor volume to identify the formulas that gave the most accurate volume calculations. To evaluate tumor volume, first the shape of the tumor has to be assumed, and if it is necessary for volume calculation, the third diameter (height, h) has to be approximated. Mrio Ginja. Finally, measurements made with the TumorImager scanner showed a significant difference 10 days earlier between the treatment and control group as opposed to caliper-based measurements. The R2 value for the scanner is 0.99, as opposed to that for the caliper being 0.90, which signifies that the scanner is more precise in its measurements than the caliper. 37, 19 (1996). A patented algorithm running in the TumorManagerTM program calculates the tumor volume by creating a 3D surface map of the tumor (red-colored surface in Figure 12.). Comparison of clinical assessment, mammography and ultrasound in pre-operative estimation of primary breast-cancer size: a practical approach. J. Nucl. Contrast agents improve the visibility, but it is an extra strain to the organism, which can be lethal to animals which are in the final stage of cancer. (Fig 2). In the meantime, to ensure continued support, we are displaying the site without styles Unable to load your collection due to an error, Unable to load your delegates due to an error. Mammary tumors seemed to take on an oblate spheroid geometry. To reduce the time of analysis one could e.g. In this phase, 5 immunocompetent mice in control group, and 9 immunocompetent mice in case group were used. 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. Yes Pairwise comparison was done by Tukeys honest significant difference test to find those samples, which have significantly different means. Careers. Tumor volume was calculated by the modified ellipsoidal formula: V = (Length Width 2) . In each case the reference value is the MRI-measured tumor volume. Faustino-Rocha AI, Gama A, Oliveira PA, Vanderperren K, Saunders JH, Pires MJ, Ferreira R, Ginja M. Life Sci. All mice were implanted with HT-29 human colorectal adenocarcinoma. 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. An average penny has a diameter of 19 mm and a height of 1.27 mm, yielding a volume of 360.1 mm3. In addition, we have found that the quasi-continuous administration of bevacizumab is effective against tumor growth of C38 colon adenocarcinoma, in contrast . 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). We have found that mice which have received therapy had tumor with irregular, and in several cases berry-shaped structure, especially when reaching large volume. Mice in Phase III/3 control and case groups, and mice in Phase IV case1 and case2 groups received bevacizumab. Figure 14. Unmeasured part of the tumor for caliper, Figure 11. The caliper, unlike the scanner, does not consider that the height of the stack changes while the length and width remain the same. Similarly, Zhang et al. In this study, the authors measured dimensions of rat mammary tumors using a caliper and using real-time . 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. The problems with tumor volume measurements by calipers 3.1 Tumor growth: Height is not equal to the width 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. The width of a fully formed tumor will be much larger than its height. Make sure you get accurate measurements for length, width and height. This is a preview of subscription content, access via your institution. The results presented here were provided by them. Role of real-time sonography in assessment of breast diseases: a review of 200 cases (Abstr). In this phase, three groups were created. 54, 401414 (1975). 37, 331337 (2011). Forbes, D., Blom, H., Kostomitsopoulos, N., Moore, G. & Perretta, G. Euroguide: On the Accommodation and Care of Animals Used for Experimental and Other Scientific Purposes (Federation of European Laboratory Animal Science Associations, London, 2007). Federal government websites often end in .gov or .mil. The tumor can be more and sometimes less visible or popped up from under the skin. (Inbred C57Bl/6 mice from our institute were used throughout the studies.) where V m is the measurement threshold that represents the smallest measurable tumor volume using a caliper. Nevertheless the result of our study shows that the effectiveness is even better. sharing sensitive information, make sure youre on a federal A typical comparison of tumor volume measurements by TumorImager-2TM with calipers. https://doi.org/10.1371/journal.pone.0142190.g005, https://doi.org/10.1371/journal.pone.0142190.t002, To find the f constant for tumor growth without therapy (Phase I), first reliable tumor volume values had to be found, since there was no MRI measurement in Phase I. Beside tumor diameters, tumor mass was measured and vascularization area was calculated in the case of the removed tumors. In the case of Phase I and Phase IV, there were no MRI measurements. Tumors were cut into two pieces for sample processing: one piece was stored in formalin, and the other piece was frozen using liquid nitrogen. Clin. We have examined C38 mouse colon adenocarcinoma and HT-29 human colorectal adenocarcinoma. No, Is the Subject Area "Mathematical models" applicable to this article? Figure 17. . The closer the value is to 1, the more precise the data. No, Is the Subject Area "Magnetic resonance imaging" applicable to this article? In Phase IV, eleven weeks old male SCID mice with implanted HT-29 human colorectal adenocarcinoma was used. Case1 group members received one 200 g bevacizumab dose on the 8th day, case2 group members received 1.11 g bevacizumab from the 8th day every day for 15 days. 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]. 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%. These together with the tumor shape and all obtained data can easily be traced and consulted afterwards. 35, 18341840 (2003). Of six different tumour is effective against tumor growth and the effect of the tumor for,! Read the article on why you should not use calipers area is not occupied by the for... 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