Gail D. Stevenson

Tomographic small-animal imaging using a high-resolution semiconductor camera

We have developed a high-resolution, compact semiconductor camera for nuclear medicine applications. The modular unit has been used to obtain tomographic images of phantoms and mice. The system consists of a 64 x 64 CdZnTe detector array and a parallel-hole tungsten collimator mounted inside a 17 cm x 5.3 cm x 3.7 cm tungsten-aluminum housing. The detector is a 2.5 cm x 2.5 cm x 0.15 cm slab of CdZnTe connected to a 64 x 64 multiplexer readout via indium-bump bonding. The collimator is 7 mm thick, with a 0.38 mm pitch that matches the detector pixel pitch. We obtained a series of projections by rotating the object in front of the camera. The axis of rotation was vertical and about 1.5 cm away from the collimator face. Mouse holders were made out of acrylic plastic tubing to facilitate rotation and the administration of gas anesthetic. Acquisition times were varied from 60 sec to 90 sec per image for a total of 60 projections at an equal spacing of 6 degrees between projections. We present tomographic images of a line phantom and mouse bone scan and assess the properties of the system. The reconstructed images demonstrate spatial resolution on the order of 1-2 mm.

Gamma-ray imaging using a CdZnTe pixel array and a high-resolution, parallel-hole collimator

The poor performance of current parallel-hole collimators is an impediment to planar high-resolution gamma-ray imaging, even when high-resolution semiconductor detector arrays are available. High-resolution parallel-hole collimators are possible but have not been fabricated because conventional collimator construction techniques severely limit achievable bore size and septal thickness. We describe development and testing of a high-resolution collimator with 4096 260-/spl mu/m square bores and 380 /spl mu/-m pitch, matched to our existing 2.5 cm/spl times/2.5 cm hybrid 64/spl times/64 CdZnTe arrays with multiplexer readout. The collimator is a laminar composite of about 100 layers of W sheets produced by photolithography and has an efficiency of 5/spl times/10/sup -5/. We have demonstrated sub-millimeter spatial resolution at 140 keV in both phantom and animal imaging using this system. We present images of resolved individual vertebrae in the spine of a mouse and lymphatic channels and nodes in a rat. The collimator and semiconductor array could form a compact module for use in a wide variety of gamma-ray imaging systems.

Imaging recognition of multidrug resistance in human breast tumors using 99mTc-labeled monocationic agents and a high-resolution stationary SPECT system.

Imaging recognition of multidrug-resistance by 99mTc-labeled sestamibi, tetrofosmin and furifosmin in mice bearing human breast tumors was evaluated using a high-resolution SPECT, FASTSPECT. Imaging results showed that the washout rates in drug-resistant MCF7/D40 tumors were significantly greater than that in drug-sensitive MCF7/S tumors. Furifosmin exhibited greater washout from both MCF7/S and MCF7/D40 than sestamibi, while tetrofosmin washout was greater than sestamibi in MCF7/D40 only. Feasibility of the monocationic agents for characterizing MDR expression was well clarified with FASTSPECT imaging.

Imaging of rat cerebral ischemia-reperfusion injury using99mTc-labeled duramycin

OBJECTIVES Prompt identification of necrosis and apoptosis in the infarct core and penumbra region is critical in acute stroke for delineating the underlying ischemic/reperfusion molecular pathologic events and defining therapeutic alternatives. The objective of this study was to investigate the capability of (99m)Tc-labeled duramycin in detecting ischemia-reperfusion injury in rat brain after middle cerebral artery (MCA) occlusion. METHODS Ischemic cerebral injury was induced in ten rats by vascular insertion of a nylon suture in the left MCA for 3 hr followed by 21-24hr reperfusion. After i.v. injection of (99m)Tc-duramycin (1.0-3.5 mCi), dynamic cerebral images were acquired for 1 hr in six rats using a small-animal SPECT imager. Four other rats were imaged at 2 hr post-injection. Ex vivo images were obtained by autoradiography after sacrifice. Histologic analyses were performed to assess cerebral infarction and apoptosis. RESULTS SPECT images showed that (99m)Tc-duramycin uptake in the left cerebral hemisphere was significantly higher than that in the right at 1 and 2 hr post-injection. The level of radioactive uptake in the ischemic brain varied based on ischemic severity. The average ratio of left cerebral hot-spot uptake to right hemisphere radioactivity, as determined by computerized ROI analysis, was 4.92±0.79. Fractional washout at 1 hr was 38.2±4.5% of peak activity for left cerebral hot-spot areas and 80.9±2.0% for remote control areas (P<0.001). Based on triphenyltetrazolium chloride staining and autoradiograph image data, the hotspot uptake may be associated primarily with the ischemic penumbra, in which high apoptotic activity was observed by cleaved caspase-3 immunocytochemical staining. CONCLUSIONS (99m)Tc-duramycin SPECT imaging may be useful for detecting and quantifying ongoing apoptotic neuronal cell loss induced by ischemia-reperfusion injury.

Evaluating the protective role of ischaemic preconditioning in rat hearts using a stationary small-animal SPECT imager and 99mTc-glucarate

ObjectiveTo examine the protective role of ischaemic preconditioning (IPC) in rat hearts using 99mTc-glucarate (GLA) and a stationary SPECT imager, FastSPECT. MethodsTwenty-four rats with 30 min myocardial ischaemia and 150 min reperfusion (IR) were studied as follows. The IPC group (n=6) underwent IPC (five cycles of 4 min ligation of the left coronary artery and reflow) before IR. The control group (n=7) was treated by IR without IPC. The SPT group (n=6) was subjected to IPC and an adenosine antagonist, 8-(p-sulfophenyl)-theophylline (SPT). The vehicle group (n=5) received IPC and SPT carrier vehicle. GLA was delivered intravenously 30 min post-reperfusion, and 2-h dynamic cardiac images were acquired by FastSPECT. ResultsGLA showed ‘hot-spot’ accumulation in the ischaemic area-at-risk (IAR) and exhibited lower retention (% 5 min peak) in the IPC and vehicle groups (33.8±2.6 vs. 35.7±9.2, P>0.05) than in the control and SPT groups (63.1±5.3 vs. 54.8±4.8, P>0.05). The infarct size (% IAR) was larger in the control and SPT groups (48.2±6.3 vs. 41.7±6.3, P>0.05) than that in the IPC and vehicle groups (21.0±1.9 vs. 19.1±4.6, P>0.05). In terms of the ex-vivo IAR-to-normal radioactivity ratio, there was a statistical difference between the control and IPC groups (7.4±0.9 vs. 3.0±0.4), as well as the SPT and vehicle groups (7.4±1.0 vs. 3.4±0.5). ConclusionIPC offers cardioprotection and relates to the activation of adenosine receptors in rat hearts. FastSPECT GLA imaging is not only useful in detecting early ischaemia–reperfusion injury, but also valuable in evaluating cardioprotection.

The Animal in Animal Imaging

With the development of new imaging modalities, techniques,and radiotracers, it is easy to get caught up in the excitement of the equipment and the pictures. Yet the value in imaging lies primarily in the benefit it brings to human lives. That potential value is determined first by studies in animals. This paper will focus on the care and handling of rodents as they make up over 90% of the animal research done. However,many of the concepts we will be discussing could be applied to any species. Whatever species you work with, take time to learn about them and their specific needs; it will pay compounding dividends.

Molecular Imaging in the College of Optical Sciences - An Overview of Two Decades of Instrumentation Development.

During the past two decades, researchers at the University of Arizona’s Center for Gamma-Ray Imaging (CGRI) have explored a variety of approaches to gamma-ray detection, including scintillation cameras, solid-state detectors, and hybrids such as the intensified Quantum Imaging Device (iQID) configuration where a scintillator is followed by optical gain and a fast CCD or CMOS camera. We have combined these detectors with a variety of collimation schemes, including single and multiple pinholes, parallel-hole collimators, synthetic apertures, and anamorphic crossed slits, to build a large number of preclinical molecular-imaging systems that perform Single-Photon Emission Computed Tomography (SPECT), Positron Emission Tomography (PET), and X-Ray Computed Tomography (CT). In this paper, we discuss the themes and methods we have developed over the years to record and fully use the information content carried by every detected gamma-ray photon.

An Implantable Synthetic SPECT Lesion : A Bridge from Phantom to Reality

Small-animal imaging systems are often characterized using phantoms, which may not predict performance in clinical applications. An implantable synthetic SPECT lesion would facilitate characterization of lesion detectability in a living animal. Methods: Anion-exchange columns with bed volumes of 100–300 nL were constructed from medical-grade polyvinyl chloride tubing and resin. The columns were tested in an excised mouse femur and implanted in the femur of a living mouse. Imaging was performed using a prototype dual-modality SPECT/CT system. Results: Activity of 7.4–22.2 MBq (0.2–0.6 mCi) localized within the synthetic lesion. The synthetic lesions were reused multiple times. Mice tolerated the implanted columns without complications for up to 8 wk. Conclusion: A reusable, synthetic SPECT lesion was constructed and implanted in the femur of a living mouse. The synthetic lesion is useful for the development of imaging schemes and for more realistically evaluating imaging-system performance in the context of a living animal.