Development and characterization of a scintillating cell imaging dish for radioluminescence microscopy.

Radioluminescence microscopy is an emerging modality that can be used to image radionuclide probes with micron-scale resolution. This technique is particularly useful as a way to probe the metabolic behavior of single cells and to screen and characterize radiopharmaceuticals, but the quality of the images is critically dependent on the scintillator material used to image the cells. In this paper, we detail the development of a microscopy dish made of a thin-film scintillating material, Lu2O3:Eu, that could be used as the blueprint for a future consumable product. After developing a simple quality control method based on long-lived alpha and beta sources, we characterize the radioluminescence properties of various thin-film scintillator samples. We find consistent performance for most samples, but also identify a few samples that do not meet the specifications, thus stressing the need for routine quality control prior to biological experiments. In addition, we test and quantify the transparency of the material, and demonstrate that transparency correlates with thickness. Finally, we evaluate the biocompatibility of the material and show that the microscopy dish can produce radioluminescent images of live single cells.

Compressive x-ray phase tomography based on the transport of intensity equation.

We develop and implement a compressive reconstruction method for tomographic recovery of refractive index distribution for weakly attenuating objects in a microfocus x-ray system. This is achieved through the development of a discretized operator modeling both the transport of intensity equation and the x-ray transform that is suitable for iterative reconstruction techniques.

High-speed detector for time-resolved diffraction studies.

There are a growing number of high brightness synchrotron sources that require high-frame-rate detectors to provide the time-scales required for performing time-resolved diffraction experiments. We report on the development of a very high frame rate CMOS X-ray detector for time-resolved muscle diffraction and time-resolved solution scattering experiments. The detector is based on a low-afterglow scintillator, provides a megapixel resolution with frame rates of up to 120,000 frames per second, an effective pixel size of 64 µm, and can be adapted for various X-ray energies. The paper describes the detector design and initial results of time-resolved diffraction experiments on a synchrotron beamline.

Depth-of-Interaction Compensation Using a Focused-Cut Scintillator for a Pinhole Gamma Camera.

Preclinical SPECT offers a powerful means to understand the molecular pathways of drug interactions in animal models by discovering and testing new pharmaceuticals and therapies for potential clinical applications. A combination of high spatial resolution and sensitivity are required in order to map radiotracer uptake within small animals. Pinhole collimators have been investigated, as they offer high resolution by means of image magnification. One of the limitations of pinhole geometries is that increased magnification causes some rays to travel through the detection scintillator at steep angles, introducing parallax errors due to variable depth-of-interaction in scintillator material, especially towards the edges of the detector field of view. These parallax errors ultimately limit the resolution of pinhole preclinical SPECT systems, especially for higher energy isotopes that can easily penetrate through millimeters of scintillator material. A pixellated, focused-cut (FC) scintillator, with its pixels laser-cut so that they are collinear with incoming rays, can potentially compensate for these parallax errors and thus improve the system resolution. We performed the first experimental evaluation of a newly developed focused-cut scintillator. We scanned a Tc-99m source across the field of view of pinhole gamma camera with a continuous scintillator, a conventional "straight-cut" (SC) pixellated scintillator, and a focused-cut scintillator, each coupled to an electron-multiplying charge coupled device (EMCCD) detector by a fiber-optic taper, and compared the measured full-width half-maximum (FWHM) values. We show that the FWHMs of the focused-cut scintillator projections are comparable to the FWHMs of the thinner SC scintillator, indicating the effectiveness of the focused-cut scintillator in compensating parallax errors.

Suppression of Afterglow in Microcolumnar CsI:Tl by Codoping With Sm: Recent Advances.

Microcolumnar CsI:Tl remains a highly desirable sensor for digital X-ray imaging due to its superior spatial resolution, bright emission, high absorption efficiency, and ready availability. Despite such obvious advantages, two characteristic properties of CsI:Tl undermine their use in clinical and high speed imaging: a persistent afterglow in its scintillation decay, and a hysteresis effect that distorts the scintillation yield after exposure to high radiation doses.In our earlier work we have discovered that the addition of 0.05 to 0.5 mol percent of Sm(2+) to crystals of CsI:Tl suppresses their afterglow by a factor of up to 50, even when subjected to a very high exposure of 120 R. This additive also diminishes hysteresis by an order of magnitude, which is a major accomplishment. Consequent- ly, our work is now focused on developing codoped microcolumnar CsI:Tl, Sm films that can potentially combine excellent properties of the current state-of-the-art CsI:Tl films with the reduced afterglow and hysteresis observed in codoped crystals. While our earlier attempts in CsI:Tl, Sm film fabrication, reported at the previous IEEE meeting, demonstrated obvious advantages of the approach, the recent work has succeeded in producing films that show improvement by at least a factor of 7 in afterglow and 150% in brightness compared to the standard CsI:Tl films. We report these important results in this paper, along with other recent advances in film growth and new imaging results.

Bright Lu2 O3 :Eu Thin-Film Scintillators for High-Resolution Radioluminescence Microscopy.

The performance of a new thin-film Lu2 O3 :Eu scintillator for single-cell radionuclide imaging is investigated. Imaging the metabolic properties of heterogeneous cell populations in real time is an important challenge with clinical implications. An innovative technique called radioluminescence microscopy has been developed to quantitatively and sensitively measure radionuclide uptake in single cells. The most important component of this technique is the scintillator, which converts the energy released during radioactive decay into luminescent signals. The sensitivity and spatial resolution of the imaging system depend critically on the characteristics of the scintillator, that is, the material used and its geometrical configuration. Scintillators fabricated using conventional methods are relatively thick and therefore do not provide optimal spatial resolution. A thin-film Lu2 O3 :Eu scintillator is compared to a conventional 500 µm thick CdWO4 scintillator for radioluminescence imaging. Despite its thinness, the unique scintillation properties of the Lu2 O3 :Eu scintillator allow us to capture single-positron decays with fourfold higher sensitivity, which is a significant achievement. The thin-film Lu2 O3 :Eu scintillators also yield radioluminescence images where individual cells appear smaller and better resolved on average than with the CdWO4 scintillators. Coupled with the thin-film scintillator technology, radioluminescence microscopy can yield valuable and clinically relevant data on the metabolism of single cells.

A comparison of x-ray detectors for mouse CT imaging.

There is significant interest in using computed tomography (CT) for in vivo imaging applications in mouse models of disease. Most commercially available mouse x-ray CT scanners utilize a charge-coupled device (CCD) detector coupled via fibre optic taper to a phosphor screen. However, there has been little research to determine if this is the optimum detector for the specific task of in vivo mouse imaging. To investigate this issue, we have evaluated four detectors, including an amorphous selenium (a-Se) detector, an amorphous silicon (a-Si) detector with a gadolinium oxysulphide (GOS) screen, a CCD with a 3:1 fibre taper and a GOS screen, and a CCD with a 2:1 fibre taper and both GOS and thallium-doped caesium iodide (CsI:Tl) screens. The detectors were evaluated by measuring the modulation transfer function (MTF), noise power spectrum (NPS), detective quantum efficiency (DQE), stability over multiple exposures, and noise in reconstructed CT images. The a-Se detector had the best MTF and the highest DQE (0.6 at 0 lp mm(-1)) but had the worst stability (45% reduction after 2000 exposure frames). The a-Si detector and the CCD with the 3:1 fibre, both of which used the GOS screen, had very similar performance with a DQE of approximately 0.30 at 0 lp mm(-1). For the CCD with the 2:1 fibre, the CsI:Tl screen resulted in a nearly two-fold improvement in DQE over the GOS screen (0.4 versus 0.24 at 0 lp mm(-1)). The CCDs both had the best stability, with less than a 1% change in pixel values over multiple exposures. The pixel values of the a-Si detector increased 5% over multiple exposures due to the effects of image lag. Despite the higher DQE of the a-Se detector, the reconstructed CT images acquired with the a-Si detector had lower noise levels, likely due to the blurring effects from the phosphor screen.

A New Columnar CsI(Tl) Scintillator for iQID detectors.

A 1650 µm thick columnar CsI(Tl) scintillator for upgrading iQID detectors, which is a high-resolution photon-counting gamma-ray and x-ray detector recently developed at the Center for Gamma-Ray Imaging (CGRI), has been studied in terms of sensitivity, spatial resolution and depth-of-interaction effects. To facilitate these studies, a new frame-parsing algorithm for processing raw event data is also proposed that has more degrees of freedom in data processing and can discriminate against a special kind of noise present in some low-cost intensifiers. The results show that in comparison with a 450 µm-thickness columnar CsI(Tl) scintillator, the 1650 µm thick CsI(Tl) scintillator provides more than twice the sensitivity at the expense of some spatial resolution degradation. The depth-of-interaction study also shows that event size and amplitude vary with scintillator thickness, which can assist in future detector simulations and 3D-interaction-position estimation.

Imaging properties of pixellated scintillators with deep pixels.

We have investigated the light-transport properties of scintillator arrays with long, thin pixels (deep pixels) for use in high-energy gamma-ray imaging. We compared 10×10 pixel arrays of YSO:Ce, LYSO:Ce and BGO (1mm × 1mm × 20 mm pixels) made by Proteus, Inc. with similar 10×10 arrays of LSO:Ce and BGO (1mm × 1mm × 15mm pixels) loaned to us by Saint-Gobain. The imaging and spectroscopic behaviors of these scintillator arrays are strongly affected by the choice of a reflector used as an inter-pixel spacer (3M ESR in the case of the Proteus arrays and white, diffuse-reflector for the Saint-Gobain arrays). We have constructed a 3700-pixel LYSO:Ce Prototype NIF Gamma-Ray Imager for use in diagnosing target compression in inertial confinement fusion. This system was tested at the OMEGA Laser and exhibited significant optical, inter-pixel cross-talk that was traced to the use of a single-layer of ESR film as an inter-pixel spacer. We show how the optical cross-talk can be mapped, and discuss correction procedures. We demonstrate a 10×10 YSO:Ce array as part of an iQID (formerly BazookaSPECT) imager and discuss issues related to the internal activity of 176Lu in LSO:Ce and LYSO:Ce detectors.

A hand-held beta imaging probe for FDG.

OBJECTIVES: Advances in radiopharmaceuticals and clinical understanding have escalated the use of intraoperative gamma probes in surgery. However, most probes on the market are non-imaging gamma probes that suffer from the lack of ancillary information of the surveyed tissue area. We have developed a novel, hand-held digital Imaging Beta Probe™ (IBP™) to be used in surgery in conjunction with beta-emitting radiopharmaceuticals such as (18)FDG, (131)I and (32)P for real-time imaging of a surveyed area with higher spatial resolution and sensitivity and greater convenience than existing instruments. METHODS: We describe the design and validation of a hand-held beta probe intended to be used as a visual mapping device to locate and confirm excision of (18)FDG-avid primary tumors and metastases in an animal model. RESULTS: We have demonstrated a device which can generate beta images from (18)FDG avid lesions in an animal model. CONCLUSIONS: It is feasible to image beta irradiation in animal models of cancer given (18)FDG. This technology may be applied to clinical mapping of tumors and/or their metastases in the operating room. Visual image depiction of malignancy may aid the surgeon in localization and excision of lesions of interest.

Orthotopic VX rabbit tongue cancer model with FDG-PET and histologic characterization.

BACKGROUND: We present our experience with the use of an immunocompetent medium-sized animal model of tongue cancer that may be suitable for imaging and surgical studies. METHODS: A New Zealand white rabbit model of tongue cancer was created by injecting a VX tumor cell suspension grown in culture into the tongue of our model. The tumor was examined 7 days following implantation by physical examination, photography, and (18) fluoro 2-deoxyglucose-positron emission tomography (FDG-PET). At 12 days postimplantation, the model was again studied as described above prior to euthanization, and then tongue excision and bilateral neck dissections were performed. All tissue was examined by histology. RESULTS: We confirmed a successful orthotopic tongue cancer model that resulted in cervical nodal metastases. CONCLUSION: This model may be a useful model of orthotopic head and neck cancer for future surgical or imaging research.

Progress in BazookaSPECT: High-Resolution, Dynamic Scintigraphy with Large-Area Imagers.

We present recent progress in BazookaSPECT, a high-resolution, photon-counting gamma-ray detector. It is a new class of scintillation detector that combines columnar scintillators, image intensifiers, and CCD (charge-coupled device) or CMOS (complementary metal-oxide semiconductors) sensors for high-resolution imaging. A key feature of the BazookaSPECT paradigm is the capability to easily design custom detectors in terms of the desired intrinsic detector resolution and event detection rate. This capability is possible because scintillation light is optically amplified by the image intensifier prior to being imaging onto the CCD/CMOS sensor, thereby allowing practically any consumer-grade CCD/CMOS sensor to be used for gamma-ray imaging. Recent efforts have been made to increase the detector area by incorporating fiber-optic tapers between the scintillator and image intensifier, resulting in a 16× increase in detector area. These large-area BazookaSPECT detectors can be used for full-body imaging and we present preliminary results of their use as dynamic scintigraphy imagers for mice and rats. Also, we discuss ongoing and future developments in BazookaSPECT and the improved event-detection rate capability that is achieved using Graphics Processing Units (GPUs), multi-core processors, and new high-speed, USB 3.0 CMOS cameras.

CdTe quantum dots and polymer nanocomposites for x-ray scintillation and imaging.

Investigations are reported on the x-ray scintillation and imaging application of CdTe quantum dots (QDs) and their polymer nanocomposites. Aqueous CdTe QDs with emissions ranging between 510 and 680 nm were prepared and incorporated into polyvinyl alcohol or polymethyl methacrylate polymer matrices. The x-ray luminescent properties were evaluated and a resolution of 5 lines∕mm was obtained from the nanocomposite films. Additionally, the fast decay time, nonafterglow, and superior spectral match to conventional charge coupled devices, show that CdTe QD nanocomposites have high promise for x-ray imaging applications.

Modular high frame rate detector for synchrotron applications.

The development of detectors often lags the development in X-ray sources. However, advanced detectors are critical for fully utilizing and exploiting the capabilities of the new bright sources. We report on the development of a modular high frame rate detector for synchrotron applications such as small angle X-ray scattering (SAXS) and wide angle X-ray scattering (WAXS). The detector consists of four modules, each providing an imaging area of 5×5 cm(2) and capable of frame rates of 200 frames per second (fps) with full resolution, and 650 fps with smaller region of interest (ROI). Details of the detector design and experiments at synchrotron beamlines are discussed in the paper.

System Integration of FastSPECT III, a Dedicated SPECT Rodent-Brain Imager Based on BazookaSPECT Detector Technology.

FastSPECT III is a stationary, single-photon emission computed tomography (SPECT) imager designed specifically for imaging and studying neurological pathologies in rodent brain, including Alzheimer's and Parkinsons's disease. Twenty independent BazookaSPECT [1] gamma-ray detectors acquire projections of a spherical field of view with pinholes selected for desired resolution and sensitivity. Each BazookaSPECT detector comprises a columnar CsI(Tl) scintillator, image-intensifier, optical lens, and fast-frame-rate CCD camera. Data stream back to processing computers via firewire interfaces, and heavy use of graphics processing units (GPUs) ensures that each frame of data is processed in real time to extract the images of individual gamma-ray events. Details of the system design, imaging aperture fabrication methods, and preliminary projection images are presented.

Cost-effective EMCCD-based detector for time-resolved biological SAXS applications.

Third generation synchrotron sources such as the Advanced Photon Source at Argonne National Laboratory, Argonne, IL, are outstanding tools for X-ray diffraction and scattering studies of non-crystalline biological materials. However, these studies are hindered by the lack of adequate detectors that can provide multiple frames of detailed structural information on the required millisecond time scale at the extremely high count rates available at the APS. RMD is developing a cost effective detector for time-resolved small angle X-ray scattering, using a cooled, 512x512 pixel electron multiplying CCD (EMCCD). This paper describes the detector design, its efficacy for time-resolved SAXS studies, and its imaging performance with frame rates of 30 to 500 fps.