Fast X-ray/γ-ray imaging using electron multiplying CCD-based detector

Nagarkar, Vivek V.; Shestakova, I.; Gaysinskiy, V.; Singh, Bipin; Miller, Brian W.; Barber, H. Bradford

doi:10.1016/j.nima.2006.01.063

Cited by 28 publications

(28 citation statements)

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“…Highly sensitive CCD cameras with high internal gain, comparable to the one used in this work, have in recent years found application in high-resolution SPECT imaging (15)(16)(17)(18). These SPECT systems image the ionization track produced by low-energy g rays interacting in a thin scintillator screen.…”

Section: Discussionmentioning

confidence: 99%

High-Resolution Radioluminescence Microscopy of ¹⁸F-FDG Uptake by Reconstructing the β-Ionization Track

et al. 2013

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Radioluminescence microscopy is a new method for imaging radionuclide uptake by single live cells with a fluorescence microscope. Here, we report a particle-counting scheme that improves spatial resolution by overcoming the b-range limit. Methods: Short frames (10 ms21 s) were acquired using a high-gain camera coupled to a microscope to capture individual ionization tracks. Optical reconstruction of the b-ionization track (ORBIT) was performed to localize individual b decays, which were aggregated into a composite image. The new approach was evaluated by imaging the uptake of 18 F-FDG in nonconfluent breast cancer cells. Results: After image reconstruction, ORBIT resulted in better definition of individual cells. This effect was particularly noticeable in small clusters (2-4 cells), which occur naturally even for nonconfluent cell cultures. The annihilation and Bremsstrahlung photon background signal was markedly lower. Single-cell measurements of 18 F-FDG uptake that were computed from ORBIT images more closely matched the uptake of the fluorescent glucose analog (Pearson correlation coefficient, 0.54 vs. 0.44, respectively). Conclusion: ORBIT can image the uptake of a radiotracer in living cells with spatial resolution better than the b range. In principle, ORBIT may also allow for greater quantitative accuracy because the decay rate is measured more directly, with no dependency on the b-particle energy.Key Words: radionuclide imaging instrumentation; single-cell analysis; microscopy; autoradiography Nucl Med 2013; 54:1841 54: -1846 54: DOI: 10.2967 Aut oradiography is a well-established method for high-resolution imaging of radionuclide probes in tissues. Film and emulsion methods have the highest spatial resolution but poor sensitivity, dynamic range, and quantitative accuracy and require tedious sample preparation (1,2). Other autoradiography methods (e.g., storage phosphor (3), solid-state detection (4,5), gaseous detectors (6), and thin phosphor (7)) have higher sensitivity and dynamic range but spatial resolution worse than 50 mm. Only a few methods have demonstrated the ability to visualize the uptake of radionuclide probes with single-cell resolution. One of these methods uses a bsensitive avalanche photodiode to measure radionuclide uptake in small groups of cells, cultured in 16 microfluidic chambers (8). An experiment showed that the avalanche photodiode could measure signal from a single cell in the chamber. Another device, the MicroImager, achieved 15-mm spatial resolution for 35 S, which was used to detect in situ hybridization in single neurons (9). A third device, the radioluminescence microscope, was developed to visualize radionuclide uptake in live cells during fluorescence microscopy (10). Radioluminescence microscopy can be used to measure fluorescent and radionuclide signals emanating from a collection of living cells, in a relatively short time. Here we propose a new particlecounting scheme for radioluminescence microscopy with higher spatial resolution and, in principle, quantitative ...

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Section: Discussionmentioning

confidence: 99%

High-Resolution Radioluminescence Microscopy of ¹⁸F-FDG Uptake by Reconstructing the β-Ionization Track

et al. 2013

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“…[1][2][3][4][5][6][7] These detectors show great promise in small-animal SPECT and molecular imaging and exist in a variety of configurations. Typically, a columnar CsI(Tl) scintillator or a radiography screen (Gd 2 O 2 S:Tb) is imaged onto the CCD.…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3][4][5][6][7]13 Such detectors have intrinsic resolutions better than 100 μm and employ scintillators such as columnar CsI(Tl) 14 or terbium-doped gadolinium oxysulfide (Gd 2 O 2 S:Tb) phosphor screens. Gamma-ray interactions in columnar CsI(Tl) scintillators or in radiography screens are imaged onto a CCD as clusters of signal.…”

Section: Introductionmentioning

confidence: 99%

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Photon-counting gamma camera based on columnar CsI(Tl) optically coupled to a back-illuminated CCD

et al. 2007

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Recent advances have been made in a new class of CCD-based, single-photon-counting gamma-ray detectors which offer sub-100 μm intrinsic resolutions. [1][2][3][4][5][6][7] These detectors show great promise in small-animal SPECT and molecular imaging and exist in a variety of configurations. Typically, a columnar CsI(Tl) scintillator or a radiography screen (Gd 2 O 2 S:Tb) is imaged onto the CCD. Gammaray interactions are seen as clusters of signal spread over multiple pixels. When the detector is operated in a charge-integration mode, signal spread across pixels results in spatial-resolution degradation. However, if the detector is operated in photon-counting mode, the gamma-ray interaction position can be estimated using either Anger (centroid) estimation or maximumlikelihood position estimation resulting in a substantial improvement in spatial resolution. 2 Due to the low-light-level nature of the scintillation process, CCD-based gamma cameras implement an amplification stage in the CCD via electron multiplying (EMCCDs) [8][9][10] or via an image intensifier prior to the optical path. 1 We have applied ideas and techniques from previous systems to our high-resolution LumiSPECT detector. 11,12 LumiSPECT is a dual-modality optical/SPECT small-animal imaging system which was originally designed to operate in charge-integration mode. It employs a cryogenically cooled, high-quantum-efficiency, back-illuminated large-format CCD and operates in single-photoncounting mode without any intermediate amplification process. Operating in photon-counting mode, the detector has an intrinsic spatial resolution of 64 μm compared to 134 μm in integrating mode.

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“…The resulting X-ray beam has central wavelength λ = 0.062nm. Intensity images were taken with a custom designed EMCCD based X-ray camera, where a 150µm thick RMD CsI:Tl scintillator was fiber optically coupled to an EMCCD [Andor, ixon, 512×512 pixels (N = 512), 16µm pixel size] with a 6:1 taper [19]; the effective pixel size at the scintillator is 96µm. The scintillator was at d = 1.711m (M s = 3.24, ∆ ≈ 30µm).…”

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

et al. 2013

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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 X-ray transform that is suitable for iterative reconstruction techniques.Traditional tomography with hard X-rays recovers the attenuation of an object. Attenuation does not always provide good contrast when imaging objects made of materials with low electron density, e.g. soft tissues. In these cases, richer information is often contained in the phase, i.e. the optical thickness of the sample [1][2][3]. Propagation based techniques are particularly suitable for X-ray phase imaging because they allow phase to be recovered from intensity images taken at multiple propagation distances without the need for optical elements [4,5]. Here we adopt the transport of intensity equation (TIE) which relates the measured intensity to the Laplacian of the phase under a weakly-attenuating sample approximation. Implementing TIE at many angles while rotating the object allows tomographic reconstruction of the refractive index distribution.TIE tomographic reconstruction first requires a suitable forward model, consisting of 1) a projection of refractive index through the sample and 2) modeling diffraction after the sample with the TIE. Recovering the phase then amounts to inverting these operations on the measured data. A straightforward method of reconstruction is to invert the forward model in two steps [7]. For the first step, the TIE can be solved by a Poisson equation solver. The TIE is ill-posed because the transfer function relating the intensity measurement to the phase tends to zero as the spatial frequency decreases. As a result, reconstructions are often corrupted by significant low-frequency noise, requiring regularization. Tikhonov regularization is most commonly employed to reduce these artifacts [7,8]. For the second step, a standard tomographic reconstruction is carried out, e.g. using the filtered back-projection (FBP) method. In order for FBP to yield a result free from high-frequency "streaking" artifacts, projections must be taken at many angles. It is often desirable to use fewer projections in order to reduce dose or acquisition time, in which case the tomographic inversion problem is underdetermined. Rather than solve these two inverse problems independently, the forward and inverse models may be adapted into a single-step op- Fig. 1: Imaging geometry for TIE tomography eration combining TIE and tomography [6,[9][10][11]. However, a single step inversion still requires many projection angles in order to avoid artifacts. Iterative solvers have recently been proposed to reduce these artifacts when attempting a reconstruction from a small number of projections. Myers et. al. propose inversion of TIE tomography measurements to obtain a sample distribution using prior knowledge that the sample consists of a single mat...

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Fast X-ray/γ-ray imaging using electron multiplying CCD-based detector

Cited by 28 publications

References 9 publications

High-Resolution Radioluminescence Microscopy of ¹⁸F-FDG Uptake by Reconstructing the β-Ionization Track

High-Resolution Radioluminescence Microscopy of ¹⁸F-FDG Uptake by Reconstructing the β-Ionization Track

Photon-counting gamma camera based on columnar CsI(Tl) optically coupled to a back-illuminated CCD

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

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Fast X-ray/γ-ray imaging using electron multiplying CCD-based detector

Cited by 28 publications

References 9 publications

High-Resolution Radioluminescence Microscopy of 18F-FDG Uptake by Reconstructing the β-Ionization Track

High-Resolution Radioluminescence Microscopy of 18F-FDG Uptake by Reconstructing the β-Ionization Track

Photon-counting gamma camera based on columnar CsI(Tl) optically coupled to a back-illuminated CCD

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

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High-Resolution Radioluminescence Microscopy of ¹⁸F-FDG Uptake by Reconstructing the β-Ionization Track

High-Resolution Radioluminescence Microscopy of ¹⁸F-FDG Uptake by Reconstructing the β-Ionization Track