U-SPECT-I: a novel system for submillimeter-resolution tomography with radiolabeled molecules in mice

A major advance in biomedical science and diagnosis was accomplished with the development of in vivo techniques to image radiolabeled molecules, but limited spatial resolution has slowed down applications to small experimental animals. Here, we present a SPECT system (U-SPECT-I) dedicated to radionuclide imaging of murine organs at a submillimeter resolution.

The high performance of U-SPECT-I is based on a static triangular detector setup, with a cylindric imaging cavity in the center and 75 gold micropinhole apertures in the cavity wall. The pinholes are focused on a small volume of interest such as the mouse heart or spine to maximize the detection yield of gamma-photons. Three-dimensional molecular distributions are iteratively estimated using the detector data and a statistical reconstruction algorithm that takes into account system blurring and data noise to increase resolution and reduce image noise.

With 0.6-mm-diameter pinholes, the maximum fraction of detected photons emitted by a point source (peak sensitivity) is 0.22% for a 15%-wide energy window and remains higher than 0.12% in the central 12 mm of the central plane. In a resolution phantom, radioactively filled capillaries as small as 0.5 mm and separated by 0.5 mm can be distinguished clearly in reconstructions. Projection data needed for the reconstruction of cross sections of molecular distributions in mouse organs can readily be obtained without the need for any mechanical movements. Images of a mouse spine show 99mTc-hydroxymethylene diphosphonate uptake down to the level of tiny parts of vertebral processes. These are separated clearly from the vertebral and intervertebral foramina. Using another tracer, one can monitor myocardial perfusion in the left and right ventricular walls, even in structures as small as the papillary muscles.

U-SPECT-I allows discrimination between molecular concentrations in adjacent volumes of as small as about 0.1 muL, which is significantly smaller than can be imaged by any existing SPECT or PET system. Our initial in vivo images of the mouse heart and spine show that U-SPECT-I can be used for novel applications in the study of dynamic biologic systems with a clear projection to clinical applications. The combination of high resolution and detection efficiency of U-SPECT-I opens up new possibilities for the suborgan-level study of radiotracers in mouse models.