Development and Evaluation of an EMCCD Based Gamma Camera for Preclinical SPECT Imaging

Pinhole collimation is extremely well suited for imaging radiopharmaceuticals in murine models of human disease. With pinhole collimation, SPECT systems are able to achieve sub-millimeter spatial resolutions. Data from such detailed images are extremely useful for preclinical studies in biomedical research including mapping in vivo gene expression, infectious disease modeling, drug development, and cancer diagnosis and therapy. Although high spatial resolutions can be reached with pinhole collimation, the sensitivity (cps/μCi) is still low when compared to clinical SPECT systems. An increase in pinhole SPECT sensitivity would allow for shorter scan times, higher animal throughput, and reduced dose levels. Both the sensitivity and resolution of preclinical SPECT systems can be improved using an electron-multiplying charge-coupled device (EMCCD). The EMCCD offers improved quantum efficiencies (35 to 95%) over a broader range of wavelengths (400 to 900 nm) and a higher intrinsic resolution (< 100 μ using photon counting) when compared to photomultiplier tubes. The electron gain achieved in the multiplication register of an EMCCD effectively reduces the readout noise to less than 1 electron/pixel (e/p), making them sensitive to single photoelectrons. Both homemade and commercial systems were used to investigate the application of EMCCDs to preclinical SPECT. The homemade prototype system used the Texas Instruments ImpactronTM EMCCD model TC253SPD-B0 (7.4 μ square pixels) which was cooled under vacuum to -50°C using a four stage Peltier and liquid heat exchanger. Shuttered lens-coupling was used to image the optical light from a 3 mm thick monolithic CsI(Tl) crystal. Precise clocking for the EMCCD was provided by a National Instruments FPGA controller (PCI-7811R) and LabVIEW FPGA module (version 8.0). A custom built electronics box contained the clock driver circuitry and 16-bit video board for digital conversion of the video signal. TC253 characterization tests measured a maximum gain just over 1000x, dark current rate of 0.14 e/p/s, read noise of 18.2 e/p, and spurious charge generation of 4 e/p. A light integration intrinsic resolution of 110 μ FWHM was measured. Light integration images of a line phantom using a single pinhole collimator were used for SPECT reconstruction. We found the relatively high spurious charge generation and low quantum efficiency (35% at 560 nm) of the inexpensive TC253 made it incapable of photon counting for low energy sources using lens coupling. Photon counting with the TC253 was demonstrated using fiber optic coupling. The commercially available PhotonMAX 512B system used the e2v CCD97 EMCCD (16 μ square pixels). The improved quantum efficiency (95% at 560 nm) and low spurious charge generation (< 0.01 e/p) made photon counting with lens coupling possible for both 99mTc and 125I sources. A photon counting algorithm written with LabVIEW software was used with the PhotonMAX system to take list-mode data. A photon counting intrinsic resolution of 56 μ FWHM was measured. An energy resolution of 50% was measured for 57Co. Photon counting images of 99mTc-MDP uptake within a mouse using single pinhole collimation showed an improved SNR over integration images. This optical coupling method differs from other EMCCD SPECT systems by using lenses rather than fiber optic bundles for transfer. Although the optical coupling efficiency for lens coupling is lower than fiber coupling, it has been shown that photon counting can still be achieved provided a high quality EMCCD is used.