140 IEEE TRANSACTIONS ON NUCLEAR SCIENCE, VOL. 50, NO. 1, FEBRUARY 2003 High-Resolution X-ray Imaging Based on Curved Bragg Mirrors: First Results Uwe Bergmann, Marijana Ivanovic, Member, IEEE, Pieter Glatzel, and Stephen P. Cramer Abstract—Small animal cancer imaging has drawn increased attention over the last few years due to greater availability of genetically modified mice, permitting the study of human diseases in animal models. Submillimeter resolution would be of great value to provide the fine detail needed in the imaging of small tumors traced by radio-labeled agents. Despite extensive research and improvements in instrumentation and imaging reconstruction, until now, there has been no efficient technology for this task. The limitations of scintillation cameras with pin- hole collimators, currently the highest resolution devices, are fundamental in nature. They include image blurring through edge effects, scattering at the pinhole, and inelastic Compton scattering. Furthermore, such devices often yield low efficiency. In this paper, a new approach to high-resolution imaging of radio-labeled agents is introduced and first results are shown. The technique is based on curved perfect-crystal X-ray mirrors applied in a one-to-one focusing geometry. Such Bragg diffraction optics yields high reflectivity and excellent energy resolution and it has been applied in X-ray spectroscopy for many years. Today large perfect-crystal mirrors are commercially available and efficient devices covering a substantial solid angle can be envisioned. The potential advantage over conventional pinhole cameras is twofold. First, focusing diffraction optics provides a “virtual” pinhole, which can effectively be inside the object under investigation and does not suffer from edge effects. Second, Bragg optics has an energy resolution of a few eV and discriminates against Compton scattering. The fundamentals of Bragg optics are dicussed and first results using Fe and Tc phantoms are presented. Our data show spatial resolutions of less than 1 and 2 mm, respectively. Current limitations of this new technique and possible future designs are discussed. Index Terms—Biomedical imaging, Bragg reflection, small an- imal cancer imaging, X-rays, X-ray detectors, X-ray scattering. I. INTRODUCTION H IGHER spatial resolution and sensitivity for small animal imaging is continuously sought to improve the spatial detail and image quality that can be obtained in radionuclide imaging. Radionuclide imaging has profited from greater tissue specificity and highly selective uptake of many of the new labeled monoclonal antibodies, receptor specific molecules, peptides, and other new radiopharmaceuticals [1]–[4]. These Manuscript received January 3, 2002; revised August 15, 2002. This work was supported in part by the Department of Health and Human Services, NIH National Cancer Institute1 R21, under Grant 87499-01. U. Bergmann and S. P. Cramer are with the Lawrence Berkley National Laboratory, Berkley, CA 94720, USA, and also with the Department of Applied Science, University of California, Davis, Davis, CA 95616 USA (e-mail: ubergmann@lbl.gov). M. Ivanovic is with the Department of Radiology, University of North Car- olina, Chapel Hill, NC 27514 USA. P. Glatzel is with the Department of Applied Science, University of California Davis, Davis, CA 95616 USA. Digital Object Identifier 10.1109/TNS.2002.807884 advances also place new demands on imaging with high spatial resolution in order to characterize regional localization and turnover properties. Planar imaging of the activity distribution of radiopharma- ceuticals in small animals has been conventionally performed using scintillation cameras with high-resolution, parallel hole collimators or pinhole collimators. Although good spatial reso- lution can be achieved with these techniques, only two-dimen- sional images of three-dimensional activity distributions are ob- tained and spatial detail and contrast are limited due to crosstalk from activity in overlying or underlying tissues. Spatial reso- lution of the order of 6–10 mm is obtained with high-resolu- tion parallel hole collimators and 2–5 mm with pinhole colli- mators. SPECT imaging with conventional parallel hole, fan, or cone beam collimators can provide tomograms of the activity distribution in three dimensions, however, the spatial resolution achieved with these collimators is usually not adequate to pro- vide the fine detail needed for many tissues and organs in small laboratory animals. Spatial resolution of 1–3 mm is often sought for these studies. As a result, considerable effort has been given to identify and characterize new detectors and to modify more conventional detectors to achieve greater spatial resolution and adequate sensitivity [5]–[10]. In this work, we present first studies of a new approach to high-resolution imaging of radio-labeled agents. The technique is based on focusing X-ray optics using perfect crystal Bragg mirrors. In the visible range imaging devices such as mirrors, lenses, and wave-guides rely on the large refraction index of glass or other materials. Due to the short wavelength of hard X-rays and -rays condensed matter has, at these high frequen- cies, generally an index of refraction somewhat smaller than, but very close to one. As a consequence the critical angle for total reflection is very small (of order mrad). Considering absorption and stringent requirements on surface quality, focusing X-ray optics based on many total reflections are not very efficient in the hard X-ray regime. (Although there is an increased use of capillary X-ray optics based on total reflection in the soft and medium X-ray range). A different way to reflect X-rays at much larger angles makes use of diffraction from crystalline material. This so-called Bragg optics is commonly used in X-ray spectroscopy. Large perfect single crystals such as Si or Ge are grown routinely nowadays, and curved X-ray Bragg mirrors have become larger as well [11]. Due to the nature of Bragg reflections a curved Bragg mirror can act like a monochromator and lens at the same time. Thus, different from a -camera based on a real pinhole, a fo- cusing Bragg mirror can provide a “virtual” pinhole. In the fol- lowing section, we describe the principle of Bragg optics and in 0018-9499/03$17.00 © 2003 IEEE