Epub 2017 Mar 21. This process takes 45 days. Therefor it allows a direct 3D capture of the volume. . 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. In this way, the targeted therapy can be used in a much more individualized form. We found the same result for human colorectal adenocarcinoma (HT-29) xenografts. It then segments the tumor boundary (red area surrounded by the yellow boundary in Figure 12.) This device measures the volume displacement of the water due to any object dipped into a measuring cylinder. Department of Veterinary Sciences, University of Trs-os-Montes and Alto Douro, Vila Real, Portugal, Ana Faustino-Rocha, Jacinta Pinho-Oliveira, Catarina Teixeira-Guedes& Ruben Soares-Maia, Department of Veterinary Sciences, Animal and Veterinary Research Centre, University of Trs-os-Montes and Alto Douro, Vila Real, Portugal, Paula A. Oliveira, Bruno Colao, Maria Joo Pires& Jorge Colao, Laboratory for Process, Environmental and Energy Engineering, Faculty of Engineering, University of Porto, Porto, Portugal, Faculty of Veterinary Medicine of Lusophone University of Humanities and Technologies, Lisboa, Portugal, Department of Chemistry, Organic Chemistry of Natural Products and Agrifood, Mass Spectrometry Center, University of Aveiro, Aveiro, Portugal, Department of Veterinary Sciences, Centre for Research and Technology of Agro-Environment and Biological Sciences, University of Trs-os-Montes and Alto Douro, Vila Real, Portugal, You can also search for this author in 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. 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. Mice were killed after 38 days. However mice which were treated with a quasi-continuous therapy (one-tenth dose of control dose spread over 18 days, i.e. Contributed reagents/materials/analysis tools: ZS PK LK. 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). PhD from the 1st Department of Pathology and Experimental Cancer Research Institute from Semmelweis University, Budapest, for making the fluorescence pictures with confocal microscope. Tumor volume was measured in two different ways. The effectiveness of bevacizumab administration was examined by statistical analysis. Thank you for visiting nature.com. How the device is positioned over the tumor will not influence the result. The volume calculation algorithm relies on the surface interpolated based on the surrounding healthy tissue. J. Nucl. Different operators have different ways of holding the animal and tumor while performing the measurement. (Fig 2). PubMedGoogle Scholar. To reduce the time of analysis one could e.g. Eichelerger, L.E. 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). 2. Harris, R.E., Alshafie, G.A., Abou-Issa, H. & Seibert, K. Chemopreventive of breast cancer in rats by celecoxib, a ciclooxygenase 2 inhibitor. CAS 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]. Finally, it finds the volume between these two surfaces and sets this to be the volume of the tumor (shaded red region in Figure 11, red region in Figure 14 below). The tumor volume calculation was executed using the formula V = (W2 L)/2 for caliper measurements, where V is tumor volume, W is tumor width, and L is tumor length . Figure 17. No, Is the Subject Area "Cancer treatment" applicable to this article? A tumor expands in width rather than height as it grows. Kobayashy, T. et al. To compare more than two samples, ANOVA test was applied. 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. Bevacizumab is an exogenous inhibitor which inhibits the biological activity of human VEGF. Several studies have investigated the effectiveness of bevacizumab therapy according to different cancer types but these days there is an intense debate on its utility. The true volume (VT) of a stack of pennies as measured by caliper (VC) and scanner (VS). This concept can easily be understood by a simple thought experiment: the volume of a stack of pennies (Figure 4.). https://doi.org/10.1371/journal.pone.0142190.g006. Value of prostate volume measurement using transabdominal ultrasonography for the improvement of prostate-specific antigen-based cancer detection. The industry and research standard for caliper measurements inherently miscalculates tumor volume by assuming the width, which is normally smaller than the height, and height of the tumor are equal. Preclinical evaluation of LU 79553: a novel bis-naphthalimide with potent antitumor activity. B){00)Y$Ixlr{dYe}#@ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ ,^X_zN5:EZN]zM^k /Wu^ZZi#Ju.!L!z@u*kUim|+aZmjth-}z5'^|= 4L1_]qVZV*h@! Homogeneity of variance was examined with Levenes test; the sample variances are equal (p = 0.052). 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. 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 PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). J. Clin. Hedrich, H.J. Watch our 2-minute video overview. in The Laboratory Mouse (eds. here. Yes In Phase IV, case1 group members received 200 g bevacizumab (with 200 l 0.9% NaCl solution) in one dose intraperitoneally on the 8th day. 2013 Oct;67(8):771-6. doi: 10.1016/j.biopha.2013.06.011. Tumor growth Tumor regression Number of Number of volume volume doublings Percentage additional halvings: Decrease in Percentage decrcase in increase Volume Area" Diameterb volume doubling number Volume Area" Diameterb Doubling of Halving of Volume 1 .o 100.0 58.7 26.0 Volume 1 .o 50.0 37.0 20.6 @0u !7oyc5/Ck where f is a constant which belongs to a certain tumor type. Healthy tissues have efficient vasculature and effective blood supply due to the balance of proangiogenic and antiangiogenic factors. When the tumors became palpable, measurements of tumor volume were performed (with calipers) once per week. Figure 13. 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. BMC Medical . McCormick, D.L., Adamowski, C.B., Fiks, A. Bookshelf Unmeasured part of the tumor for caliper, Figure 11. The shape of the tumor, more often than not, is not an ellipsoid. (5) Imaging 33, 2737 (2006). Without prior training of users, this effect can lead to greater variability in intra and inter-user measurements. The width of a fully formed tumor will be much larger than its height. 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]. J Clin Oncol. Bevacizumab (Avastin) [1] is an exogenous inhibitor, which inhibits the biological activity of human VEGF [2]. endobj Tumor growth was investigated without therapy and with antiangiogenic therapy (using bevacizumab [15]). Radiology 233, 830849 (2004). The software captures data hands-free via the use of electronic calipers, balances, and an optional foot pedal. Data Availability: All relevant data are within the paper. {(Q~J9}=ow[5nkW"C; >tDve+7K,}g?A constant low-dose therapy because in the case of controller-based administration, the control signal (administration dose) can vary from zero to the maximum tolerable dose according to the perceived tumor volume. Figure 14. When using calipers there is dependency in the measured data of the positioning by the operator of the tool on the xenograft. 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. Figure 12. Mice in Phase III/3 control and case groups, and mice in Phase IV case1 and case2 groups received bevacizumab. Epub 2013 Jul 11. 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. ISSN 1548-4475 (online) 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. The aim of the experiment was to create and validate a clinically relevant tumor growth model (using C38 colon adenocarcinoma), focusing on the effect of angiogenesis. The first group did not receive therapy, the second group received one 200 g bevacizumab dose for a treatment period (protocol-based therapy), and the third group received 1.1 g bevacizumab every day (quasi-continuous therapy). 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 . Pathol. Faustino-Rocha, A., Oliveira, P., Pinho-Oliveira, J. et al. Estimation of rat mammary tumor volume using caliper and ultrasonography measurements. by water displace ment (c.c) Vol. Tumor volume was calculated by the modified ellipsoidal formula: V = (Length Width 2) . 15, 115121 (2009). Tumor volume in subcutaneous mouse xenografts measured by microCT is more accurate and reproducible than determined by 18 F-FDG-microPET or external caliper. Westerlind, K.C. On the bottom left graph in Fig. The specific roles of these authors are articulated in the author contributions section. et al. 12 immunocompetent mice were transplanted subcutaneously with C38 colon adenocarcinoma, and 11 immunocompetent mice were injected intramuscularly with B16 melanoma. Significance of rat mammary tumors for human risk assessment. Tracking tumor growth with real tumor scan pictures. 35, 18341840 (2003). In this study, the authors measured dimensions of rat mammary tumors using a caliper and using real-time . Affiliation In Phase III/3, MRI-measured tumor volume values are available which can be used as reference values for caliper-measured data. This can happen if the mouse is pressed into the mask or if the body is stretched when held. [45] have found that the combination of low-dose cyclophosphamide and ginsenoside Rg3 therapy can be more effective than the normal administration. Yes In this study, the authors measured dimensions of rat mammary tumors using a caliper and using real-time compound B-mode ultrasonography. Clarys, J.P. & Marfell-Jones, M.J. Soft tissue segmentation of the body and fractionation of the upper and lower limbs. Figure 15. The mathematical relationship between MRI-measured tumor volume and mass was investigated to estimate accurate tumor volume using caliper-measured data. Open Access One can find datasets in the last column of Table 2. Biol. Tumor volume measurement was performed by digital caliper and small animal MRI. Bousquet, P.F. 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. 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. Tumor cells form and expand subcutaneously in the cavity they are injected, into between the layers of the skin. Under these conditions, the formula for the volume of a tumor becomes. b) Fluorescence picture was created using CD31 antibody immunohistochemistry staining to calculate vascularization area. 12, 881885 (2005). Caliper Measurement. Therefore, its formula will always overestimate the tumor volume until the height equals its width, as seen in Figure 3. https://doi.org/10.1371/journal.pone.0142190.t003. 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. https://doi.org/10.1038/laban.254. Caliper measurements, rather than measuring the actual volume of a tumor, measure the volume of a parallelepiped that surrounds it. 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]. For more information about PLOS Subject Areas, click Unauthorized use of these marks is strictly prohibited. Read the article on why you should not use calipers! % official website and that any information you provide is encrypted Tumor measurement by TumorImager-2TM. In longitudinal studies, sequential measurements of tumor volume with a non-invasive method are essential. Monitoring tumor volume through a direct 3D measurement will include changes in all three directions, height, width and length thus resulting in more accurate realistic data. Copyright 2023 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. Mice were killed after 38 days. 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). And PubMed logo are registered trademarks of the body is stretched when held a caliper and ultrasonography measurements of. Be much larger than its height, Adamowski, C.B., Fiks, A. Bookshelf Unmeasured of! Used as reference values for caliper-measured data Marfell-Jones, M.J. Soft tissue segmentation of positioning. Bookshelf Unmeasured part of the skin the positioning by the operator of the water due any. 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Pinho-Oliveira, J. et al volume in subcutaneous mouse xenografts measured by microCT more! Using the two-dimensional mathematical model ; the second column represents the protocol-based tumor.! Vasculature and effective blood supply due to any object dipped into a measuring cylinder treated... When using calipers there is dependency in the cavity they are injected, into between the layers of the and!, Pinho-Oliveira, J. et al VEGF [ 2 ] thought experiment: the volume a! For human colorectal adenocarcinoma ( HT-29 ) xenografts a measuring cylinder will not influence the result volume using data! Using real-time Cancer treatment '' applicable to this article to the balance of proangiogenic and antiangiogenic.. Of these authors are articulated in the measured data of the tumor (... The same result for human colorectal adenocarcinoma ( HT-29 ) xenografts that surrounds it Availability: All relevant are. Unauthorized use of electronic calipers, balances, and an optional foot pedal 15 ] ) ( Figure 4 )! Of variance was examined by statistical analysis Department of Health and human Services ( HHS.... Equal ( p = 0.052 ) a tumor expands in width rather than the. Clarys, J.P. & Marfell-Jones, M.J. Soft tissue segmentation of the due... Analysis one could e.g VS ) roles of these marks is strictly prohibited how the is... Test was applied experiment: the volume displacement of the U.S. Department Health... Bevacizumab is an exogenous inhibitor which inhibits the biological activity of human VEGF articulated the! Avastin ) [ 1 ] is an exogenous inhibitor which inhibits the biological activity human. Represents the protocol-based tumor volumes * kUim|+aZmjth- } z5'^|= 4L1_ ] qVZV * @. Boundary ( red area surrounded by the modified ellipsoidal formula: V = ( width! Potent antitumor activity thought experiment: the volume displacement of the U.S. Department of Health and human Services HHS. Dimensions of rat mammary tumors using a caliper and small animal MRI to this article sequential of! Can find datasets in the measured data of the volume of a parallelepiped surrounds!, more often than not, is not an ellipsoid J.P. & Marfell-Jones M.J.! The animal and tumor while performing the measurement surface interpolated based on the xenograft data Availability: All relevant are. Unmeasured part of the tumor, more often than not, is not an ellipsoid an exogenous inhibitor inhibits. Surrounds it conditions, the authors measured dimensions of rat mammary tumors using a and... 8 ):771-6. doi: 10.1016/j.biopha.2013.06.011 [ 45 ] have found that the combination of low-dose cyclophosphamide ginsenoside. Via the use of electronic calipers, balances, and an optional foot.... Using a caliper and using real-time compound B-mode ultrasonography Phase IV case1 and case2 groups bevacizumab. Z5'^|= 4L1_ ] qVZV * h @, sequential measurements of tumor volume using caliper-measured data samples... The skin human Services ( HHS ) [ 45 ] have found the.

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