FY2010 - Oak Ridge National Laboratory

Seed Money Fund—
Measurement Science and Systems Engineering Division
05878
Neutron Imaging for the Determination of Tumor Margins
Trent L. Nichols , Hassina Z. Bilheux. Philip R. Bingham, ; Jack S. Brenizer, Jr.; George W. Kabalka.;
Amy K. LeBlanc.; Alfred M. Legendre; Robert L. Donnell.; Maria Cekanova;
Anton S. Tremsin; Kenneth L. Watkin.; and Laurentia M. Nodit
Project Description
The project will produce a proof of principle that a low-energy neutron imaging system with 10–15 m
spatial resolution and boronated tissue stains will result in a clear delineation of normal and malignant
cells not seen in standard optical approaches. This research explores the application of neutron imaging to
enhance medical pathological specimen analysis using the cold guide (CG-1) beamline at the High Flux
Isotope Reactor (HFIR). Neutron images will be obtained with a resolution of 10–15 m by collimating
the beam with a pinhole or micropore neutron collimator. Specimens of melanoma, sarcoma, and breast
cancer will be examined to evaluate the efficacy of neutron radiography as a tool for the determination of
tumor margins. While previous research has indicated that neutron radiography may provide additional
contrast as compared to the traditional methods, the spatial resolution of neutron radiography systems has
only recently reached a level that would provide an image suitable for determination of tumor margins.
Normal cell sizes vary considerably depending upon the tissue but are typically on the order of 10–20 m
in diameter with nuclei of 5–8 m. Malignant cells are typically at 2–5 m larger than the normal
counterpart from the same original tissue type. A common method to improve contrast for radiographic
studies is to incorporate a contrast agent into the sample for improved delineation between areas of
interest. One novel aspect of the proposed effort is the attempt to use boron and deuterated water to
improve contrast between healthy and tumor tissue. Specially prepared histochemical stains will be
prepared by boronation with 10 B to improve the neutron image contrast and with deuterated water or
alcohol as fixatives to decrease neutron scattering. Since tumor cells have a different biochemical milieu
(environment) than surrounding normal cells of origin, there are expected to be contrast differences that
can be exploited in addition to the boronated stains.
Mission Relevance
This project melds two of ORNL’s primary mission foci: neutron science and systems biology. Using
neutrons to image malignant tumor margins is both novel and innovative. It requires extending the field of
neutron imaging to higher resolution images and incorporates boronated stains to increase the contrast
between normal and malignant tissues. The neutron images are likely to distinguish the small differences
in biochemical milieu that exist between normal and abnormal cells. The improved delineation of tumor
margins will have significant impact on the major public health problem of cancer through systems
biological application of the results of neutron imaging of these biological materials.
Results and Accomplishments
Work on this project started in June with discussions with colleagues on how best to perform the
experiments at the CG-1 beamline at HFIR. There are many technical issues to address in order to
improve the resolution to 10–15 m or perhaps down to 1–2 m. These are being actively pursued with
calculations and simulations. At this point, the best resolution can be obtained by mounting high
resolution film next to the specimens with a thin gadolinium film in between. This would provide a
resolution of approximately 2 m, which should be adequate for the current experiment. This assembly
will be held in place between two thin aluminum plates held together with a vacuum supplied by a
roughing pump.
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