Neutron Microscope for In-Vivo Imaging

The objective of the proposed research is to design an inexpensive, compact neutron microscope capable of imaging biological material that can meet specific medical research and clinical needs. One particular clinical application for the thermal or cold neutron microscope that we will address in the proposed program is to provide a new imaging modality in boron neutron capture therapy (BNCT) for the treatment of glioblastomas and anaplastic astrocytomas. We believe that our microscope would be useful as a high-resolution quantitative imaging tool for optimizing the delivery of boron-containing drug (BSH), and for development of tumor-targeting boron compounds. Specifically, in Phase I we will image a phantom containing the standard concentration of BSH in localized regions, which is a precursor to imaging a mouse model with a transplanted glioma in Phase II. Indeed, the neutron microscope strengths and weaknesses match this application's needs and limitations well. Under phase I we will concentrate on the development of the neutron microscope as a complete system. Adelphi Technology has developed compound refractive lenses that have imaged mechanical objects and, most recently, hydrogen-rich plastic materials, and biological samples using cold neutrons. These magnified neutron images have been achieved using moderated reactor sources. Such a source would limit the use of a neutron microscope to only national facilities; therefore, with researchers at the Lawrence Berkeley Laboratory, we are developing a compact neutron source and moderator that will permit both laboratory and clinical use. This device has the possibility of revolutionizing radiology: neutron microscopy can be a valuable complement and extension of already mature light, x-ray and electron imaging techniques. Unlike these other sources, neutron propagation in matter is defined by strong neutron-nucleus interaction. Thus neutrons can provide a means to probe into materials with a completely different "light" allowing visualization of objects otherwise concealed. Thicker, unstained, unfixed, in vivo samples may be imaged with neutrons since they are less affected by attenuation than other sources. The research will proceed by (1) improving the image resolution and contrast, (2) obtaining images using thermal neutrons, (3) design lens pairs to overcome chromatic aberration and (4) determining the required dose. The potential for successful development of the prototype imaging system is very high because (1) our compound refractive lenses have demonstrated magnified imaging of biological and hydrogenous containing materials; (2) a simple lens/filter arrangement has demonstrated bandwidths required for improved resolution; and (3) the proposed neutron source has been demonstrated to produce high flux neutrons comparable to that of reactors.