Un-collimated single-photon imaging system for high-sensitivity small animal and plant imaging

Abstract

In preclinical single-photon emission computed tomography (SPECT) system development the primary objective has been to improve spatial resolution by using novel parallel-hole or multi-pinhole collimator geometries. However, such high-resolution systems have relatively poor sensitivity (typically 0.01% to 0.1%). In contrast, a system that does not use collimators can achieve very high-sensitivity. Here we present a high-sensitivity un-collimated detector single-photon imaging (UCD-SPI) system for the imaging of both small animals and plants. This scanner consists of two thin, closely spaced, pixelated scintillator detectors that use NaI(Tl), CsI(Na), or BGO. The performance of the system has been characterized by measuring sensitivity, spatial resolution, linearity, detection limits, and uniformity. With 99mTc (140 keV) at the center of the field of view (20 mm scintillator separation), the sensitivity was measured to be 31.8% using the NaI(Tl) detectors and 40.2% with CsI(Na). The best spatial resolution (FWHM when the image formed as the geometric mean of the two detector heads, 20 mm scintillator separation) was 19.0 mm for NaI(Tl) and 11.9 mm for CsI(Na) at 140 keV, and 19.5 mm for BGO at 1116 keV, which is somewhat degraded compared to the cm-scale resolution obtained with only one detector head and a close source. The quantitative accuracy of the system’s linearity is better than 2% with detection down to activity levels of 100 nCi. Two in vivo animal studies (a renal scan using 99mTc MAG-3 and a thyroid scan with 123I) and one plant study (a 99mTcO4− xylem transport study) highlight the unique capabilities of this UCD-SPI system. From the renal scan, we observe approximately a one thousand-fold increase in sensitivity compared to the Siemens Inveon SPECT/CT scanner. UCD-SPI is useful for many imaging tasks that do not require excellent spatial resolution, such as high-throughput screening applications, simple radiotracer uptake studies in tumor xenografts, dynamic studies where very good temporal resolution is critical, or in planta imaging of radioisotopes at low concentrations.

Real‐time whole‐plant dynamics of heavy metal transport inArabidopsis halleriandArabidopsis thalianaby gamma‐ray imaging

“…Absolute sensitivity of the system is known from measurement with a centrifuge tube containing known 65 Zn activity. The calibrated system performance as measured with point gamma ray sources of a variety of energies broadly agrees with expectations from detailed calculations and simulations (Walker, Cherry, & Mitchell, ; Walker et al., ).…”

“…These results are in line with previous reports for rice (Suzui et al., ). This contrasts strongly with the faster speed of the other xylem‐transported compounds, such as water in A. thaliana (Park et al., ), Cd in A. halleri (Ueno et al., ) and pertechnetate in sunflower (Walker et al., ), all measured to reach the shoot in 30 min. It should be noted, however, that the experiments demonstrating water transport (Park et al., ) and Cd transport (Ueno et al., ) were carried out using decapitated stems and are thus destructive in nature, but also far more sensitive to small quantities than the method used here.…”

“…After xylem loading, the mass flow‐mediated movement of Zn into the shoot inside the xylem is expected to occur within 30 min in Arabidopsis , as previously shown for water (Park et al., ) and Cd in xylem sap (Ueno et al., ). From previous SPECT imaging, we have shown that a pulse of radiolabelled pertechnetate ( 99m TcO 4 − ) moving in the xylem stream reaches the shoot apical meristem of a 2 week old sunflower already in 5 min (Walker et al., ).…”

“…To complement these often spatially narrow or invasive studies, whole plant imaging enables direct large‐scale material transport studies, addressing spatiotemporal transport within the context of the entire intact plant, from root to shoot for a period of up to several days. Here, we use a high‐sensitivity uncollimated detector single photon emission computed tomography (SPECT)‐type imaging system (UCD‐SPI (Walker, Judenhofer, Cherry, & Mitchell, )), to study Zn metal transport in a hyperaccumulator, A. halleri, and in a non‐accumulator A. thaliana . We further examine the influence of the HMA4 transporter on Zn transport in A. halleri by use of an HMA4 knockdown line.…”

Plant-PET Scans: In Vivo Mapping of Xylem and Phloem Functioning

“…While its technical applicability has been proven in a few plant studies with 99m Tc as a proxy for water transport [58,59], no plant physiological insights have yet been derived from SPECT because most biological molecules of interest are covered by PET (Box 1) whereas SPECT employs non-biological tracers [58][59][60].…”