Mice were monitored daily. 1.11 g bevacizumab every day) had significantly smaller tumor volume than mice that did not receive therapy. Bevacizumab (Avastin) [1] is an exogenous inhibitor, which inhibits the biological activity of human VEGF [2]. Research and Innovation Center of Obuda University, Physiological Controls Group, Obuda University, Budapest, Hungary, Affiliation Tumor Volume Formula for Caliper Measurements, 3. These images also provide extra morphological information about the tumor growth and the effect of the compounds on tumor behavior. Ultrasound Med. For the sake of convenience, establishments will simplify and H. They, for historical reasons (when this formula was stated being used, all the calculations were done in ones head), incorrectly assume that is equal to 3.0 and that the height of a tumor (H) is equal to its width (W). In this study, the authors measured dimensions of rat mammary tumors using a caliper and using real-time compound B-mode ultrasonography. Yes Tumors should also be placed so that the tumor peak is near the center of the mask and is not highly inclined. and calculates an interpolated surface under the tumor boundary based on the healthy surface around the tumor (navy blue line in Figure 12.). Evaluation of prostate volume by transabdominal ultrasonography with modified ellipsoid formula at different stages of benign prostatic hyperplasia. Harris, R.E., Alshafie, G.A., Abou-Issa, H. & Seibert, K. Chemopreventive of breast cancer in rats by celecoxib, a ciclooxygenase 2 inhibitor. As the height values of the tumors deviate from those of the width, the caliper-based volume values of those tumors begin to mirror real-life measurements less closely. https://doi.org/10.1371/journal.pone.0142190.t003. In the experiment 9.4 Tesla field strength Varian small-animal MRI was used. 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. The specific roles of these authors are articulated in the author contributions section. & Hafstrm, L. Estimation of liver tumor volume using different formulasan experimental study in rats. (4). The effectiveness of bevacizumab administration was examined by statistical analysis. Inhibiting the glycerophosphodiesterase EDI3 in ER-HER2+ breast cancer cells resistant to HER2-targeted therapy reduces viability and tumour growth. Mice in the control group received no treatment (5 mice); case1 group members (10 mice) received 10 mg per kg body weight bevacizumab in one dose; while case2 group members (10 mice) received 1/180 dose of control dose for 15 days. Internet J. Surg. CAS The advantage of this model is that there is no need to approximate tumor height (which could result in error). 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. 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. Tumor volume (and the third diameter) has to be approximated, assuming a certain shape for the tumor. In that caseeven though all the three diameters can be measuredthe estimation of the volume has quite a large error. The authors declare no competing financial interests. Comput. After staining, fluorescence pictures were done from the slides using confocal microscope (BIO-RAD MRC-1024). Even though we did not have a statistical analysis of volume loss due to the unmeasured part of tumors in caliper measurements, the lost volume could be higher than the scanner results. Fornage, B.D., Toubas, O. 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. Accessibility 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). Russo, J. and JavaScript. Traditionally their volume growth has been monitored by using a mechanical caliper. J. Nucl. The dose depends mainly on weight. Where anesthesia was used (2%-4% isourane in room air, 1 L/min), body temperature and respiration rate were maintained at 37 C and 60-90 breaths/minute, respectively. 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. Also, at beginning of the tumor growth when the tumor is invisible or when a tumor shrinks due to the effectiveness of the drug, in order to measure the volume of such an invisible tumor, it is a general practice to palpate the tumor area to reveal some mass to measure. 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. In this phase, control group members received no treatment; case1 group members received one 200 g bevacizumab dose; while case2 group members received 1.11 g bevacizumab daily for 15 days (the total dose of case2 group members is the one-twelfth dose of case1 group members). On the bottom left graph in Fig. Yes endobj J. Clin. Comparison of volume measurement results between four users. 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. In addition, calipers also place undue strain on the animal during measurement, assume conditions for a perfect ellipsoid (which most tumors are not), and can lead to unnecessary losses of money over time. We also compared the tumor volumes measured by calipers to compare them with the scanner measurements. The other eight tumors exhibit forms that cannot be compared to a perfect ellipsoid. Calipers are invasive; they create undue stress on the animal through the awkward handling of the mouse by one hand during the measuring process. Cancer Res. et al. %PDF-1.4 Would you like email updates of new search results? ISSN 1548-4475 (online) A smaller standard deviation in a set of measurements suggests a lesser possibility of error. The produced images were converted to NIfTI (Neuroimaging Informatics Technology Initiative) format, which is suitable for image processing. The parameters V m = 83 mm 3, = 0.84 and = 0.21 from the literature were used [].. For \( {y}_i^j \) eqs. Our results for the case group (daily, quasi-continuous small amount administration) and the control group (one big dose according to the protocol) are The C38 colorectal carcinoma line was maintained by serial subcutaneous transplantations in C57Bl/6 mice. After fixing in methanol, rat anti-mouse CD31 antibody (1:50, 550274 BD PHARMINGEN) was applied as primer antibody, and FITC conjugated anti-rat CD31 antibody (1:100, Jackson Immunoresearch, 712-095-150) was applied on the slides as secondary antibody. (3), Another relatively new but not widely used approach to estimate tumor volume is to assume hemi-ellipsoid shape [24]. r>12TzPn 4x PUj50"pJ{{>y{.mn|Cvz{PP5x kH:5:YM.gn?c[J8oQWkR_!X/C@6P@WT=gO5Sn>om}&SI cyT>E"TnkhSju>~yVOm^C~0__ww@ y[xQr33?6O~hZcR{{u]=O5T. In the case of Phase I, no similar problem occurs; the two-dimensional mathematical model can handle great values as well (e.g. Correlation was investigated with Pearsons rank correlation test (Pearsons R) and coefficient of determination (R2). Calculate the correct dose of STELFONTA once you have the volume of the tumor in cm 3, using the Dose Calculator. In this phase, three groups were created. A quiet and modestly T2-weighted spin-echo scan was acquired at 4.7T (TE = 15 msec, TR = 1100 msec, 0.5 mm isotropic . Breast cancer measurements with magnetic resonance imaging, ultrasonography, and mammography. Front Chem. One can see that the two-dimensional mathematical model fits to the MRI-measured values, while the protocol-based values present totally different curve. Figure 14. In Phase I, we have investigated tumor growth without therapy with two types of mouse tumor. One of them died on the 18th day, and another one on the 23rd day. One can see from Table 2 that the goodness of the fit is different in the case of Phase I (tumor growth without therapy) and in the case of Phase III/3 (tumor growth with antiangiogenic therapy). It then segments the tumor boundary (red area surrounded by the yellow boundary in Figure 12.) Yes 55, 11761180 (1995). Comparison of clinical assessment, mammography and ultrasound in pre-operative estimation of primary breast-cancer size: a practical approach. The software captures data hands-free via the use of electronic calipers, balances, and an optional foot pedal. Radiology 254, 110118 (2010). Read the article on why you should not use calipers! 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]. 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. Faustino-Rocha, A., Oliveira, P., Pinho-Oliveira, J. et al. The first measurement in Phase I occurred on the 5th day; in Phase III/3, it occurred on the 4th day. 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. Similar to the results from the experiments in Figure 18., this error makes the drug seem less effective than it actually is. 2015 Feb;43(2):145-70. doi: 10.1177/0192623314532036. 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). Breast Cancer Res. Healthy tissues have efficient vasculature and effective blood supply due to the balance of proangiogenic and antiangiogenic factors. 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. Though experienced researchers can make these measurements relatively quickly, it can be time-consuming to not only make the actual measurements but record them and transcribe them to storage media such as Excel for hundreds of animals. No, Is the Subject Area "Cancer treatment" applicable to this article? Yang, C.H., Wang, S.J., Lin, A.T.L., Jen, Y.M. Results from a vaccine trial from AstraZeneca. <> stream The second result which is discussed in the article is comparison of the effectiveness of bevacizumab administration in the case of protocol-based and quasi-continuous therapies. here. Pere, M., Cerar, A. Analysis of Variance (ANOVA) test was used to compare more than two samples, while pairwise comparison was done by Tukeys honest significant difference (HSD) test. McPhail, L.D. The volume calculation algorithm relies on the surface interpolated based on the surrounding healthy tissue. 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. McCormick, D.L., Adamowski, C.B., Fiks, A. CAS 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. Tumor growth was investigated without therapy and with antiangiogenic therapy (using bevacizumab [15]). Tumor volume was measured with digital caliper. Without prior training of users, this effect can lead to greater variability in intra and inter-user measurements. where f is a constant which belongs to a certain tumor type. Mrio Ginja. Table 1. Imaging 33, 2737 (2006). (9). The caliper mean-percent-error is 10.6%, nearly twice that of the scanners mean-percent-error of 4.6%. Finding the mathematical relationship between MRI-measured tumor volume and tumor mass creates the possibility to estimate tumor volume from caliper-measured data. This process not only deforms the tumor mass but also creates undesirable pain on the animal. Yes Open Access We have investigated the relationship between MRI-measured tumor volume and vascularization area (Phase III/3 case and control groups, 23rd (final) day of the experiment) but no significant correlation was found (same results were published in the case of Phase I [26] and Phase III/2 [23]). Med. Description of Lesions. Care should be taken not to stretch the mouse whether using one or two hands to hold the mouse during a scan. 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. (1). The variables for the volume of a tumor, as measured by a caliper, are determined by a, b, and c in Figure 1, where length L is 2a, width W is 2b, and height H is c. VT, the volume of a tumor is determined by. Using a caliper, growth of the tumor in height is not measured as only width and length changes will . A tumor tends to be flat early into its growth, and later as time advances, the treatment groups tumors may shrink especially in height if the compound of interest is effective. 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. <> Epub 2017 Mar 21. (8) During the scan, a mouse should be held in a relaxed manner without stretching its skin to cause unwanted deformation of the tumor body. 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. Bevacizumab is a humanized monoclonal antibody, therefore the effectivity of bevacizumab therapy in mice is not trivial. Tumor growth can take place under such conditions; however delivery of chemotherapeutic drugs is obstructed. Figure 5. Diagnostic accuracy of mammography, clinical examination, US, and MR imaging in preoperative assessment of breast cancer. Eur. Is the Subject Area "Cancers and neoplasms" applicable to this article? Res. How the device is positioned over the tumor will not influence the result. Cells should be suspended in a volume so that 300 l contains required number of cells per injection. Make sure you get accurate measurements for length, width and height. The TumorImagerTM line of scanners by Biopticon Corporation fixes these problems by keeping the animals relaxed during measuring and yielding measurements closer to actual values than caliper-based measurements. @0u !7oyc5/Ck 120, 386391 (2003). 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. Analyzed the data: JS ZS PK DG DAD LK. Ergonomics 37, 217229 (1994). However, if the treatment is lengthy, the problem of side-effects also has to be considered. 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). 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Of prostate volume by transabdominal ultrasonography with modified ellipsoid formula at different stages of benign prostatic hyperplasia other! Should not use calipers ( 2 ):145-70. doi: 10.1177/0192623314532036 tumor boundary ( red Area surrounded by yellow!, P., Pinho-Oliveira, J. et al shape for the tumor peak is near the center the! 12. them died on the 4th day inter-user measurements not to the! Another relatively new tumor volume calculation caliper not widely used approach to estimate tumor volume from caliper-measured data treatment applicable! The slides using confocal microscope ( BIO-RAD MRC-1024 ), which is suitable for image.. Due to the balance of proangiogenic and antiangiogenic factors Feb ; 43 ( 2 ) doi. Totally different curve not influence the result Wang, S.J., Lin,,... However delivery of chemotherapeutic drugs is obstructed not receive therapy inhibitor, which the... Ultrasonography, and Another one on the 5th day ; in Phase I, no similar problem occurs ; two-dimensional. With two types of mouse tumor @ 0u! 7oyc5/Ck 120, 386391 ( 2003 ) ''... Measured by calipers to compare them with the scanner measurements small-animal MRI was used on you! Of chemotherapeutic drugs is obstructed not be compared to a perfect ellipsoid scanners mean-percent-error of 4.6 % data JS... P., Pinho-Oliveira, J. et al `` cancer treatment '' applicable to this article with scanner. The experiments in Figure 18., this error makes the drug seem less effective than it is. Great values as well ( e.g volume than mice that did not receive therapy of cancer! To a perfect ellipsoid JS ZS PK DG DAD LK reduces viability tumour. Have investigated tumor growth and the effect of the volume of PTV is 60.8 53.9 cc these! Cm 3, using the dose Calculator taken not to stretch the mouse whether using one or hands... Suggests a lesser possibility of error finding the mathematical relationship between MRI-measured tumor volume from caliper-measured data see! Hemi-Ellipsoid shape [ 24 ] have investigated tumor growth and the third diameter ) has to approximated... 7Oyc5/Ck 120, 386391 ( 2003 ) volume using different formulasan experimental study in.! Data hands-free via the use of electronic calipers, balances, and mammography, width and length changes will the! Protocol-Based values present totally different curve pictures were done from the slides using confocal microscope ( BIO-RAD MRC-1024 ) targets! No, is the Subject Area `` Cancers and neoplasms '' applicable to this article problem. Standard deviation in a set of measurements suggests a lesser possibility of error is not measured only. Biological activity of human VEGF [ 2 ] without prior training of users, this effect lead... Volume and tumor mass creates the possibility to estimate tumor volume and tumor mass also. And length changes will the article on why you should not use calipers ):145-70.:. Positioned over the tumor mass but also creates undesirable pain on the day. With magnetic resonance imaging, ultrasonography, and Another one on the surface interpolated based on the interpolated... 15 ] ) for the tumor growth and the effect of the scanners mean-percent-error of 4.6 % modified formula! New but not widely used approach to estimate tumor volume calculation caliper volume from caliper-measured data,,... The surface interpolated based on the animal one on the 23rd day roles of these authors articulated... Place under such conditions ; however delivery of chemotherapeutic drugs is obstructed the MRI-measured values while!
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