2480 IEEE TRANSACTIONS ON NUCLEAR SCIENCE, VOL. 61, NO. 5, OCTOBER 2014 Feasibility of Small Animal Anatomical and Functional Imaging with Neutrons: A Monte Carlo Simulation Study David C. Medich, Blake H. Currier, and Andrew Karellas Abstract—A novel technique is presented for obtaining a single in-vivo image containing both functional and anatomical informa- tion in a small animal model such as a mouse. This technique, which incorporates appropriate image neutron-scatter rejection and uses a neutron opaque contrast agent, is based on neutron radiographic technology and was demonstrated through a series of Monte Carlo simulations. With respect to functional imaging, this technique can be useful in biomedical and biological research because it could achieve a spatial resolution orders of magnitude better than what presently can be achieved with current functional imaging technologies such as nuclear medicine (PET, SPECT) and fMRI. For these studies, Monte Carlo simulations were performed with thermal (0.025 eV) neutrons in a 3 cm thick phantom using the MCNP5 simulations software. The goals of these studies were to determine: 1) the extent that scattered neutrons degrade image contrast; 2) the contrasts of various normal and diseased tissues under conditions of complete scatter rejection; 3) the concentra- tions of Boron-10 and Gadolinium-157 required for contrast differ- entiation in functional imaging; and 4) the efficacy of collimation for neutron scatter image rejection. Results demonstrate that with proper neutron-scatter rejection, a neutron fluence of n/cm will provide a signal to noise ratio of at least one ( ) when attempting to image various m thick tissues placed in a 3 cm thick phantom. Similarly, a neutron fluence of only n/cm is required to differentiate a m thick diseased tissue relative to its normal tissue counterpart. The utility of a B-10 contrast agent was demonstrated at a concentration of g/g to achieve in 0.3 mm thick tissues while Gd-157 requires only slightly more than g/g to achieve the same level of differentiation. Lastly, neutron collimator with an L/D ratio from 50 to 200 were calcu- lated to provide appropriate scatter rejection for thick tissue bio- logical imaging with neutrons. Index Terms—Anatomical imaging, functional imaging, Monte Carlo, neutron biological imaging, neutron scatter. I. INTRODUCTION A. Introduction to functional diagnostic imaging I N-VIVO FUNCTIONAL IMAGING is an invaluable clinical and biomedical research tool used for measuring metabolic processes and tissue activity; unfortunately, a shared Manuscript received August 27, 2013; revised December 06, 2013; accepted June 22, 2014. Date of publication July 31, 2014; date of current version October 09, 2014. D. C. Medich and B. H. Currier are with the Department of Physics, Worcester Polytechnic Institute, Worcester, MA 01609 USA (e-mail: dcmedich@wpi.edu; bhcurrier@wpi.edu). A. Karellas is at the Department of Radiology, University of Massa- chusetts Medical School, Worcester, MA 01655 USA (e-mail: Andrew. Karellas@umassmed.edu). Color versions of one or more of the figures in this paper are available online at http://ieeexplore.ieee.org. Digital Object Identifier 10.1109/TNS.2014.2334593 disadvantage of current functional imaging technologies is their poor spatial resolution over a reasonable field of view. As an example, fMRI, PET, and SPECT have a spatial resolution of 2 mm, 3-5 mm, and 5-10 mm respectively [1] while Magnetic Particle Imaging, an emerging functional imaging technology, has been characterized to have a spatial resolution mm at 2.35 T/m [2], [3]. This resolution is orders of magnitude worse than that achievable with anatomical imaging technology (0.05 - 0.3 mm [1]), which limits the analytical quality of a functional image and the types of studies that can be performed with it. Therefore, researchers actively have been investigating methods to increase the spatial resolution of current functional imaging technology. Another issue with current functional imaging technologies is that they do not obtain information on anatomical structure. Therefore, to provide an anatomic context for location, a functional image often is merged with a separate anatomic image in a process called image fusion [4], [5]. This process can degrade image quality since the quality of the fused image closely depends on the computational constraints used in the fusion process [6]. To address the low resolution of current functional imaging technology, magnetic resonance based imaging technologies (fMRI and MRI) were able to increase spatial resolution to approximately 0.6 mm by increasing the device’s magnetic field from 1.5 to 7 T/m [7]. Unfortunately, these images had a very limited field of view due to inhomogeneities in the mag- netic field and displayed reduced image quality from in-plane de-phasing, increased production of artifacts, nonuniform tissue contrast variations, and occasional excessive RF SAR body heating [7]. Alternatively, the CLARITY [8] optically transparent brain was developed to enable high resolution optical brain imaging for invasive or ex-vivo neurological research. Unfortunately, because CLARITY uses visible light as an imaging source, CLARITY based imaging cannot be performed noninvasively in an in-vivo biological model. In an attempt to overcome these issues and enhance biolog- ical and biomedical research capabilities, the authors present a novel technique which simultaneously could obtain functional and anatomic information in a single image and at high resolu- tion in a small animal model, such as a mouse. This would be accomplished by using thermal energy (0.025 eV) neutrons as the imaging source, appropriate neutron scatter rejection during image formation, and through use of a nonradioactive and neu- tron-opaque contrast agent. B. Anatomical and Functional Imaging with Neutrons Neutron imaging is a well-developed nondestructive radio- graphic technology [9]–[11] that is known for providing infor- mation complementary to that obtained using x-rays and for pro- 0018-9499 © 2014 IEEE. Personal use is permitted, but republication/redistribution requires IEEE permission. See http://www.ieee.org/publications_standards/publications/rights/index.html for more information.