No, Is the Subject Area "Magnetic resonance imaging" applicable to this article? Oncol. 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. 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. The lines on the graphs have a slope of 1, signifying that it represents caliper-based measurements in which height equals width. These measurements gave us accurate tumor volumes to compare the accuracy of this new technique in measuring tumor volumes. 17, 905910 (2004). ISSN 0093-7355 (print). Preclinical Imaging Center, Gedeon Richter Plc., Budapest, Hungary, Affiliation Please enable it to take advantage of the complete set of features! There are no further patents, products in development or marketed products to declare. One can find datasets in the last column of Table 2. In addition, the root mean square, R2 values under the linear regression equations in Figure 15. symbolize the precision of the data. Thirty-two tumors (46%) were nonspherical, as defined above; of these, 19 tumors were nonspherical in the x-y plane, 10 tumors were nonspherical in the y-z plane, and 24 tumors were nonspherical in the x-z plane. Better results can be obtained by proper handling of the mice. Lifetime dose-response relationships for mammary tumor induction by a single administration of N-methyl-N-nitrosourea. ), 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. Mammary tumors similar to those observed in women can be induced in rats by intraperitoneal administration of N-methyl-N-nitrosourea. Role of real-time sonography in assessment of breast diseases: a review of 200 cases (Abstr). 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. 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. Our results provide a theoretical background for a much more effective bevacizumab treatment using optimized administration. https://doi.org/10.1038/laban.254. Clarke, R. Animal models of breast cancer: their diversity and role in biomedical research. Figure 7. Med. J. Clin. https://doi.org/10.1371/journal.pone.0142190.t003. Internet J. Surg. Med. Mrio Ginja. . and transmitted securely. This device measures the volume displacement of the water due to any object dipped into a measuring cylinder. PLOS ONE promises fair, rigorous peer review, 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 Int. Watch our 2-minute video overview. recurrent glioblastoma (rGBM) [36]) as a first or second line treatment, usually in combination with chemo- or immunotherapy. Cancer Res. Bevacizumab is an exogenous inhibitor which inhibits the biological activity of human VEGF. Yes Verma, R. et al. One can find datasets in Table 3. The other eight tumors exhibit forms that cannot be compared to a perfect ellipsoid. In Phase IV, the first measurement occurred when the tumors have reached an average volume of 5060 mm3 (according to the xenograft protocol [20]). However, if the treatment is lengthy, the problem of side-effects also has to be considered. A diagram of an ellipsoid, with the derivations of the variables needed to calculate its volume. They then used different formulas to calculate tumor volume from these tumor measurements and compared the calculated tumor volumes with the real tumor volume to identify the formulas that gave the most accurate volume calculations. 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 longitudinal studies, sequential measurements of tumor volume with a non-invasive method are essential. In Phase III/3, MRI-measured tumor volume values are available which can be used as reference values for caliper-measured data. Comparison of volume measurement results between four users. Figure 3. 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.). In each case the reference value is the MRI-measured tumor volume. Repetitive non-typhoidal Salmonella exposure is an environmental risk factor for colon cancer and tumor growth. Physical activity cancer preventionmechanisms. In this study, the authors measured dimensions of rat mammary tumors using a caliper and using real-time . Yes 35, 18341840 (2003). Autopsy revealed only minimal local tumor; however death was not caused by tumor. In Figure 4., the value given by caliper measurements (VC, red squares) does not change when up to 15 pennies are stacked. Scientific Reports Measured data is the MRI-measured tumor volumetumor mass pairs on the 23rd day of Phase III/3 (case and control group). x|jY!==g'{oZ6-JiZ Davis, P.L. Tievsky AL, Ziegler RB, Salhus MR, Weisskoff R. Comparison of diameter and perimeter methods for tumor volume calculation. where f is a constant which belongs to a certain tumor type. In that caseeven though all the three diameters can be measuredthe estimation of the volume has quite a large error. The means of the samples are mpIV_control = 0.65, mpIV_case1 = 0.70, mpIV_case2 = 0.46. 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). & Russo, I.H. 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. In this study, the authors measured dimensions of rat mammary tumors using a caliper and using real-time compound B-mode ultrasonography. In our study, we applied a two-dimensional mathematical model and determined the corresponding tumor- and therapy-specific constants in the three investigated cases (C38 colon adenocarcinoma growth without therapy, C38 colon adenocarcinoma growth with protocol-based bevacizumab therapy and C38 colon adenocarcinoma growth with quasi-continuous bevacizumab therapy). https://doi.org/10.1371/journal.pone.0142190.g002. Caliper Measurement. Estimation of rat mammary tumor volume using caliper and ultrasonography measurements. In Phase IV, approximately 2.9106 cells were injected subcutaneously into each SCID mouse. In one trial, 208 tumors were measured, and 98.94% of those tumors exhibited much smaller heights than widths. The authors declare no competing financial interests. In another, 7,286 tumors were measured and 99.97% of those exhibited smaller heights than widths. The resulted linear curve is 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. 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. Kim DK, Synn CB, Yang SM, Kang S, Baek S, Oh SW, Lee GJ, Kang HW, Lee YS, Park JS, Kim JH, Byeon Y, Kim YS, Lee DJ, Kim HW, Park JD, Lee SS, Lee JY, Lee JB, Kim CG, Hong MH, Lim SM, Kim HR, Pyo KH, Cho BC. CAS Cells should be suspended in a volume so that 300 l contains required number of cells per injection. An official website of the United States government. Mice in Phase I and Phase IV control group received no bevacizumab. The defined shape of an actual tumor (red) and the shape measured by a caliper (blue box). The usual administration is via intravenous infusion; once every 2 or 3 weeks. Ultrasound Med. Because the industrys caliper-based formula allows for these inclusions in nonexistent volumes more often than not, it yields inaccurate measurements, which can confuse. This formula was the starting point of our examination to find an appropriate mathematical model. @L Pk5*Gj@>Sk%SLL4w^c{j[hP(/h8HP_ @Ch( Figure 8. CAS No animals were sacrificed before the experimental endpoint. Figure 19. 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%. Using the above mentioned iterative method, the resulted equation is 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. 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. The height and topography of the tumor is not taken into account in a caliper measurement. 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. Possible mechanisms mediating an association between physical activity and breast cancer. 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. et al. No, Is the Subject Area "Breast cancer" applicable to this article? 1 0 obj P`e+"JF^ : 4:p7]k = Jy}! Yes Tumor volume was measured with digital caliper as well. 41, 16901694 (1981). Cancer Res. Google Scholar. This effect is illustrated in the included video. A 3-D illustration can be found in Fig 7. a) berry-shaped tumor; b) x-diameter of the tumor; c) y-diameter of the tumor; d) z-diameter of the tumor; e) berry-shaped tumor with ellipsoidal estimation. For more information about PLOS Subject Areas, click 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. In several recent studies ([21, 22]), tumor volume is calculated assuming ellipsoid shape: J. Oncol. Analyzed the data: JS ZS PK DG DAD LK. 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; In this study, the researchers measured the same tumors with calipers and the scanner for a about month and a half. This site needs JavaScript to work properly. Breast Cancer Res. Results of this phase can be found in [26]. No, Is the Subject Area "Renal cancer" applicable to this article? Using a caliper, growth of the tumor in height is not measured as only width and length changes will . Evaluation of prostate volume by transabdominal ultrasonography with modified ellipsoid formula at different stages of benign prostatic hyperplasia. In the top-left graph (Figure 19. Using the mathematical model, different dosage algorithms can be designed for antiangiogenic cancer therapy [1619]. 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. 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. Usage of this formula to calculate tumor volume from length and width values resulted in much more precise approximation of the MRI-measured tumor volume than protocol-based calculation. The other way to measure tumor volume is the usage of small animal MRI, a non-invasive in vivo technology giving the possibility of a more precise volume measurement [29]. Faustino-Rocha AI, Gama A, Oliveira PA, Vanderperren K, Saunders JH, Pires MJ, Ferreira R, Ginja M. Life Sci. Tukeys HSD test resuled in significant difference between case1 and case2 groups (p = 0.038). Even the same operator, with different trials or at different moments in time does not always hold the animal in exactly the same way. 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 . Topography of the data: JS ZS PK DG DAD LK a diagram of an ellipsoid with. Be used as reference values for caliper-measured data compare the accuracy of this new technique in tumor! 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