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, biodistribufion, etc., using traditional numeric values data as well as innovafive statistical image analyses, (2) statistical analysis of mNP-induced hyperthermia treatment outcomes including toxicity, tumor volume, and survival analysis, (S) modeling and computer simulafion of mNP interacfion with fissue and cells in vivo under an alternating magnefic field (AMF) and predicfion ofthe induced temperature rise in tumors. Model-based stafisfical 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 characterizafion data, to be derived in the DCCNE will come in the form of images. Methods of Mulfivariate ANalysis Of VAriance (MANOVA) will be used for modeling and statisfical comparison of gray scale and color images. To comply with the normal/Gaussian assumption and to eliminate the differences in images illuminafion and contrast, the logit transformafion 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 ofthe mNP treatment of tumors in the DCCNE Projects through the stafistical 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 equafion 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 enfire funding period. A comprehensive biostatistical analysis ofthe mNP-induced hyperthermia treatment outcomes in animal studies lays the ground to its successful translation into clinic environment.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA151662-03
Application #
8379366
Study Section
Special Emphasis Panel (ZCA1-GRB-S)
Project Start
Project End
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
3
Fiscal Year
2012
Total Cost
$158,643
Indirect Cost
$83,028
Name
Dartmouth College
Department
Type
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
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