The Biostatistics, Data Analysis, and Computation (BDAC) Core will provide the following services to the projects of the Dartmouth CCNE: (1) technological and preclinical data analysis of magnetic NanoPartide (mNP) characterization measurements, such as size, heating evaluation, biodistribution, etc., using traditional numeric values data as well as innovative statistical image analyses, (2) statistical analysis of mNP-induced hyperthermia treatment outcomes including toxicity, tumor volume, and survival analysis, (S) modeling and computer simulation of mNP interaction with tissue and cells in vivo under an alternating magnetic field (AMF) and prediction ofthe induced temperature rise in tumors. Model-based statistical techniques will be used for mNP characterization and evaluation. Unlike method driven algorithms, the model-based approach allows the assessment ofthe uncertainty of methods (e.g. through the standard error) and therefore enables statistical significance testing (Projects 1, 3, Nanoparticle Core). The majority of the mNP characterization data, to be derived in the DCCNE will come in the form of images. Methods of Multivariate ANalysis Of VAriance (MANOVA) will be used for modeling and statistical comparison of gray scale and color images. To comply with the normal/Gaussian assumption and to eliminate the differences in images illumination and contrast, the logit transformation will be used (log of the image level intensity with respect to the background). Projects 1, 2, 3, NDPC &TPB cores. The BDAC Core will evaluate the efficacy of the mNP treatment of tumors in the DCCNE Projects through the statistical analysis of tumor regrowth data and survival analysis. A particular emphasis will be given to the statistical significance assessment of the synergy of the treatments, such as mNP hyperthermia and chemotherapy (Projects 1, 2 &4). Modeling and computer simulation of scattering and absorption fields from mNPs will play an important role in choosing the biologically justified conditions for animal experiments, such as the strength of the AMF, injection concentration, magnetic field exposure time, particle size, etc. The numerical assessment of the mNP-induced hyperthermia will precede animal experiments through estimation ofthe specific absorption rate (SAR) inside the tumor and by solving of the bioheat equation on the nanometer scale (Projects 1, 3, and Nanoparticle Core).

Public Health Relevance

The BDAC Core will be intimately involved in all aspects of mNPs production, characterization, implementation, and treatment outcomes assessment over the entire funding period. A comprehensive biostatistical analysis of the mNP-induced hyperthermia treatment outcomes in animal studies lays the ground to its successful translation into clinic environment.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
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Dartmouth College
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Rutkowski, Melanie R; Stephen, Tom L; Svoronos, Nikolaos et al. (2015) Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation. Cancer Cell 27:27-40
Stephen, Tom L; Rutkowski, Melanie R; Allegrezza, Michael J et al. (2014) Transforming growth factor ?-mediated suppression of antitumor T cells requires FoxP1 transcription factor expression. Immunity 41:427-39
Reeves, Daniel B; Weaver, John B (2014) Approaches for modeling magnetic nanoparticle dynamics. Crit Rev Biomed Eng 42:85-93
Toraya-Brown, Seiko; Sheen, Mee Rie; Zhang, Peisheng et al. (2014) Local hyperthermia treatment of tumors induces CD8(+) T cell-mediated resistance against distal and secondary tumors. Nanomedicine 10:1273-85
Tichauer, Kenneth M; Deharvengt, Sophie J; Samkoe, Kimberley S et al. (2014) Tumor endothelial marker imaging in melanomas using dual-tracer fluorescence molecular imaging. Mol Imaging Biol 16:372-82
Tichauer, Kenneth M; Samkoe, Kimberley S; Gunn, Jason R et al. (2014) Microscopic lymph node tumor burden quantified by macroscopic dual-tracer molecular imaging. Nat Med 20:1348-53
Samkoe, Kimberley S; Tichauer, Kenneth M; Gunn, Jason R et al. (2014) Quantitative in vivo immunohistochemistry of epidermal growth factor receptor using a receptor concentration imaging approach. Cancer Res 74:7465-74
Perreard, I M; Reeves, D B; Zhang, X et al. (2014) Temperature of the magnetic nanoparticle microenvironment: estimation from relaxation times. Phys Med Biol 59:1109-19
Ficko, Bradley W; Nadar, Priyanka M; Hoopes, P Jack et al. (2014) Development of a magnetic nanoparticle susceptibility magnitude imaging array. Phys Med Biol 59:1047-71
Russell, Stewart; Samkoe, Kimberley S; Gunn, Jason R et al. (2014) Spatial frequency analysis of anisotropic drug transport in tumor samples. J Biomed Opt 19:15005

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