Photon-counting Level Research Articles

Deep learning generation of preclinical positron emission tomography (PET) images from low-count PET with task-based performance assessment.

Preclinical low-count positron emission tomography (LC-PET) imaging offers numerous advantages such as facilitating imaging logistics, enabling longitudinal studies of long- and short-lived isotopes as well as increasing scanner throughput. However, LC-PET is characterized by reduced photon-count levels resulting in low signal-to-noise ratio (SNR), segmentation difficulties, and quantification uncertainties. We developed and evaluated a novel deep-learning (DL) architecture-Attention based Residual-Dilated Net (ARD-Net)-to generate standard-count PET (SC-PET) images from LC-PET images. The performance of the ARD-Net framework was evaluated for numerous low count realizations using fidelity-based qualitative metrics, task-based segmentation, and quantitative metrics. Patient Derived tumor Xenograft (PDX) with tumors implanted in the mammary fat-pad were subjected to preclinical [18F]-Fluorodeoxyglucose (FDG)-PET/CT imaging. SC-PET images were derived from a 10min static FDG-PET acquisition, 50min post administration of FDG, and were resampled to generate four distinct LC-PET realizations corresponding to 10%, 5%, 1.6%, and 0.8% of SC-PET count-level. ARD-Net was trained and optimized using 48 preclinical FDG-PET datasets, while 16 datasets were utilized to assess performance. Further, the performance of ARD-Net was benchmarked against two leading DL-based methods (Residual UNet, RU-Net; and Dilated Network, D-Net) and non-DL methods (Non-Local Means, NLM; and Block Matching 3D Filtering, BM3D). The performance of the framework was evaluated using traditional fidelity-based image quality metrics such as Structural Similarity Index Metric (SSIM) and Normalized Root Mean Square Error (NRMSE), as well as human observer-based tumor segmentation performance (Dice Score and volume bias) and quantitative analysis of Standardized Uptake Value (SUV) measurements. Additionally, radiomics-derived features were utilized as a measure of quality assurance (QA) in comparison to true SC-PET. Finally, a performance ensemble score (EPS) was developed by integrating fidelity-based and task-based metrics. Concordance Correlation Coefficient (CCC) was utilized to determine concordance between measures. The non-parametric Friedman Test with Bonferroni correction was used to compare the performance of ARD-Net against benchmarked methods with significance at adjusted p-value ≤0.01. ARD-Net-generated SC-PET images exhibited significantly better (p ≤ 0.01 post Bonferroni correction) overall image fidelity scores in terms of SSIM and NRMSE at majority of photon-count levels compared to benchmarked DL and non-DL methods. In terms of task-based quantitative accuracy evaluated by SUVMeanand SUVPeak, ARD-Net exhibited less than 5% median absolute bias for SUVMean compared to true SC-PET and lower degree of variability compared to benchmarked DL and non-DL based methods in generating SC-PET. Additionally, ARD-Net-generated SC-PET images displayed higher degree of concordance to SC-PET images in terms of radiomics features compared to non-DL and other DL approaches. Finally, the ensemble score suggested that ARD-Net exhibited significantly superior performance compared to benchmarked algorithms (p ≤ 0.01 post Bonferroni correction). ARD-Net provides a robust framework to generate SC-PET from LC-PET images. ARD-Net generated SC-PET images exhibited superior performance compared other DL and non-DL approaches in terms of image-fidelity based metrics, task-based segmentation metrics, and minimal bias in terms of task-based quantification performance for preclinical PET imaging.

Studies of DNA breathing in exciton-coupled (iCy3)2 dimer-labeled DNA constructs by polarization-sweep single-molecule fluorescence (PS-SMF) microscopy.

Local fluctuations of the sugar-phosphate backbones and bases of DNA (a form of DNA 'breathing') play a central role in the assembly of protein-DNA complexes. We present a single-molecule fluorescence method to sensitively measure the local conformational fluctuations of exciton-coupled cyanine [(iCy3)2] dimer-labeled DNA fork constructs in which the dimer probes are placed at varying positions relative to the DNA fork junction. These systems exhibit spectroscopic signals that are sensitive to the local conformations adopted by the sugar-phosphate backbones and bases immediately surrounding the dimer probe label positions. The (iCy3)2 dimer has one symmetric (+) and one anti-symmetric (-) exciton with respective transition dipole moments oriented perpendicular to one another. We excite single molecule samples using a continuous-wave, linearly polarized laser with its polarization direction rotated at a frequency of 1 MHz. The ensuing fluorescence signal is modulated as the laser polarization alternately excites the symmetric and anti-symmetric excitons of the (iCy3)2 dimer probe. Phase-sensitive detection of the signal at the photon-counting level provides information about the distribution of local conformations and conformational dynamics. We analyze our data using a kinetic network model, which we use to parametrize the free energy surface of the system. In addition to observing DNA breathing at and near ss-dsDNA junctions, the approach can be used to study the effects of proteins that bind and function at these sites.

Effect of reduced photon count levels and choice of normal data on semi-automated image assessment in cardiac SPECT

BackgroundThe SMARTZOOM multifocal collimator from Siemens Healthcare was developed to improve the γ-photon sensitivity in myocardial perfusion imaging without truncating the field of view. As part of the IQ-SPECT package, it may be used to reduce radiopharmaceutical dose to patients, as well as acquisition time. The aim of this study was twofold: (1) to evaluate the influence of dose reduction in semi-automated MPI scoring, with focus on different strategies for the choice of normal data (count-matched, full-count), and (2) to evaluate the effect of dose reduction afforded by Siemens’ IQ-SPECT package. Methods50 patients underwent Tc-99m-sestamibi one-day stress/rest SPECT/CT. Multiple levels of count reduction were generated using binomial thinning. Using Corridor 4DM, summed stress score (SSS) was calculated using either count-matched or full-count normal data. Studies were classified as low-risk (SSS < 4) or intermediate/high-risk (SSS ≥ 4). ResultsCount reduction using count-matched normal data increases false-normal rate and decreases sensitivity. With full-count normal data, count reduction increases false-hypoperfusion rate, leading to decreased specificity. Altogether, rate of reclassification was significant at roughly 67% dose and below. ConclusionSignificant bias results from count level of normal data relative to actual patient data. Compared to standard LEHR, IQ-SPECT should allow for significant dose reduction.

Study on relative collection efficiency of PMTs with spotlight

Photon detection efficiency is a key parameter of PMTs in high-precision neutrino and dark matter experiments, while normally the quantum efficiency is used with a normalization factor and angular response as the detection efficiency, where it is always coupled with detector response from the calibration normalization. Here, the absolute photon detection efficiency of 20′′ PMTs in photon-counting level is further considered rather than the combination of quantum efficiency and normalization factors. In order to have a good understanding of photon detection efficiency of the large-area PMT, we conduct a detailed comparison of relative collection efficiencies of a series of PMTs with spotlight. This study is based on the tests of relative quantum efficiency and relative detection efficiency, checked with several light intensities. All the results are consistent in relative QE and DE measurement with different light intensities, and the error of each parameter is coupled in our studies. Based on the measurements, Hamamatsu R12860 shows the maximum collection efficiency with spotlight at PMT center, and Hamamatsu R12199, R1355 and HZC XP72B22 have the same level of CE within the uncertainty. Following the configuration on incident light and DE definition, we can further define the DE of a large-area PMT with similar algorithms, which will also be used for detector simulation in JUNO.

Free-Space Remote Sensing of Rotation at the Photon-Counting Level

In principle the rotational Doppler effect could be used to detect the turning of a distant object, but the approach has not progressed beyond the laboratory, due to low photon-collection efficiency and orbital angular momentum (OAM) mode crosstalk. The authors address these challenges and successfully observe the effect over a 120-m free-space link between two rooftops. By analyzing the photon counts for the relevant OAM components, they deduce the speed and symmetry of rotating bodies, even at the photon-counting level. This work is a significant step toward remote sensing in a realistic environment based on the rotational Doppler effect of ``twisted light''.

Feasibility of estimating volumetric breast density from mammographic x-ray spectra using a cadmium telluride photon-counting detector.

Mammographic density of glandular breast tissue has a masking effect that can reduce lesion detection accuracy and is also a strong risk factor for breast cancer. Therefore, accurate quantitative estimation of breast density is clinically important. In this study, we investigate experimentally the feasibility of quantifying volumetric breast density with spectral mammography using a CdTe-based photon-counting detector. To demonstrate proof-of-principle, this study was carried out using the single pixel Amptek XR-100T-CdTe detector. The total number of x rays recorded by the detector from a single pencil-beam projection through 50%/50% of adipose/glandular mass fraction-equivalent phantoms was measured. Material decomposition assuming two, four, and eight energy bins was then applied to characterize the inspected phantom into adipose and glandular using log-likelihood estimation, taking into account the polychromatic source, the detector response function, and the energy-dependent attenuation. Measurement tests were carried out for different doses, kVp settings, and different breast sizes. For dose of 1 mGy and above, the percent relative root mean square (RMS) errors of the estimated breast density was measured below 7% for all three phantom studies. It was also observed that some decrease in RMS errors was achieved using eight energy bins. For 3 and 4 cm thick phantoms, performance at 40 and 45 kVp showed similar performance. However, it was observed that 45 kVp showed better performance for a phantom thickness of 6 cm at low dose levels due to increased statistical variation at lower photon count levels with 40 kVp. The results of the current study suggest that photon-counting spectral mammography systems using CdTe detectors have the potential to be used for accurate quantification of volumetric breast density on a pixel-to-pixel basis, with an RMS error of less than 7%.

Absolute optical responsivity down to the photon counting level with a photomultiplier tube.

A novel method is presented for evaluation of the absolute optical responsivity of a photomultiplier tube (PMT) at optical powers down to the photon counting level under visible light. This method is based on a combination of the calibrated responsivity and nonlinearity corrections using a silicon photodiode and a PMT. The evaluation results with the PMT enable accurate determination of the absolute optical responsivity over a wide power range of 10-11 W to 10-16 W under visible light. This method provides validation of both the photon counting efficiency of a PMT and of accurate optical measurement with attenuators at the photon counting level.

Conditional operation using three degrees of freedom of a laser beam for application in quantum information

We propose and experimentally demonstrate a conditional operation by using three degrees of freedom of a classical laser beam that simulates the operations of the quantum Toffoli gate. A tripartite non-separable mode, a classical analog of the entangled Greenberger–Horne–Zeilinger (GHZ) state, can be produced in a very simple way. In addition, we present a discussion showing the possibility to perform a quantum Toffoli gate by using the quantum counterpart of our experiment, i.e., by attenuating the laser beam to a photon counting level.

High-security communication by coherence modulation at the photon-counting level.

We show that key-specified interferometer path-length difference modulation (often referred to as coherence modulation), operating in the photon-counting regime with a broadband source, can provide a quantifiably high level of physics-guaranteed security for binary signal transmission. Each signal bit is associated with many photocounts, perhaps numbering in the thousands. Of great importance, the presence of an eavesdropper can be quickly detected. We first review the operation of key-specified coherence modulation at high light levels, illustrating by means of an example its lack of security against attack. We then show, using the same example, that, through the reduction of light intensities to photon-counting levels, a high level of security can be attained. A particular attack on the system is analyzed to demonstrate the quantifiability of the scheme's security, and various remaining research issues are discussed. A potential weakness of the scheme lies in a possible vulnerability to light amplification by an attacker.

Coherence modulation at the photon-counting level: A new scheme for secure communication

When operated at the photon-counting level, coherence modulation can provide quantifiably secure binary signal transmission between two entities, security being based on the nonclonability of photons.

Correlated Photon-Pair Source for Secured $C$-Band Quantum Communications

We have experimentally investigated and shown evidence of correlated photon-pair generation based on coupled intracavity four-wave mixing (FWM) in a dual-wavelength erbium-doped fiber ring laser operating in the fiber-optic communication <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">C</i> -band regime. In the coupled FWM process, the pump photons are both involved in the absorption and stimulated emission, which generate signal and idler wavelengths simultaneously. The correlation experiment was performed with various photon count levels in the order of hundreds of photons/s at each channel. The photon number of channel was less than 0.1/pulse and the maximum coincidence to single counts ratio was approximately 12% with a Gaussian profile in the accumulated counts.

Latest bialkali photocathode with ultra high sensitivity

Among photosensitive devices in use today, the photomultiplier tube (PMT) is a versatile device providing extremely high sensitivity, exceptionally low noise and ultra-fast response. It can detect photons at ultra low light level such as single photon counting level. One of the most important characteristics of the PMT is the quantum efficiency (QE) of the photocathode. Among various kinds of photocathodes, a bialkali photocathode is commonly used for particle physics experiments since it has higher sensitivity and lower dark current than other photocathodes. QE of the conventional bialkali photocathode is 27%.Since 2007, we have made a significant improvement in the QE of the bialkali photocathode, achieving as high as 43% at peak wavelength by precise control of the photocathode activation process. This photocathode was named ultra bialkali (UBA) and was incorporated into PMTs successfully.Additionally, we have developed another new kind of bialkali photocathode for very low-temperature environments. At −175°C, the new bialkali photocathode shows good cathode linearity up to 300nA, and it has 28% QE and lower dark current than the UBA photocathode. A PMT with the new photocathode is expected to be an ideal detector for Dark Matter experiments or double-beta decay.

Providing reference standards and metrology for the few photon–photon counting community

The main drivers for developing few-photon metrological techniques are the rapidly progressing field of quantum information processing, which requires the development of high-efficiency photon-counting detectors, and the wider use of photon-counting technology in biology, medical physics and nuclear physics. This paper will focus on the provision of standards for the few photon community and the development of techniques for the characterisation of photon-counting detectors. At the high-power end, microwatts, we are developing a low-power absolute radiometer as a primary standard that will be used to provide traceability over a much broader spectral range. At the few photon–photon-counting level we are developing a conventional calibration technique, which is traceable to the primary standard through a reference trap detector. This method can be used in both analogue and photon-counting modes and provides a convenient route for providing customer calibration at few-photon levels across the optical spectrum. At the photon-counting/single-photon level we are developing a technique based on correlated photons. These are produced via parametric downconversion and can be used to measure directly the detection efficiency of photon-counting detectors. A cross-validation of the correlated photon and conventional technique is reported. Finally we discuss this work in the context of an EU project, that is aimed at establishing the route towards the re-definition of the candela, the SI unit for optical radiation.

Variable-load quenching circuit for single-photon avalanche diodes

We present a compact 50 microm x 100 microm cell for single-photon detection, based on a new circuitry monolithically integrated together with a 20 microm-diameter CMOS Single-Photon Avalanche Diode (SPAD). The detector quenching relies on a novel mechanism based on starving the avalanche current till quenching through a variable-load (VLQC, Variable- Load Quenching Circuit). Fabricated in a standard 0.35 microm CMOS technology, the topology allows a SPAD bias voltage higher than the chip supply voltage to be used. Moreover it preserves the advantages of active quenching circuits, in terms of hold-off capability (from 40 ns to 2 micros) and fast reset (</=2 ns), while maintaining the low avalanche charge (</=1.6 pC/avalanche) and extremely small dimensions of passive quenching circuits. The cell enables the development of large-dimension dense arrays of SPADs, for two-dimensional imaging at the photon counting level with photon-timing jitter better than 40 ps.

Coincident Measurement of a Weakly Backscattered X-ray with a CPA Laser-Produced X-ray Pulse

Backscattered X-ray intensity was measured coincidently with a CPA laser-produced X-ray pulse. Results show that the coincident measurement is useful in reducing the effect of natural radiation. Even for signals at the photon counting level, we can distinguish the scattering materials and their thickness from the difference in backscattered X-ray counts. These results suggest that the backscattered X-ray can be used for imaging any distant object.

Comparison of photon counting and analog techniques for the measurement of photon pair generation in a PPLN waveguide

We present two independent measurements of the photon pairs production efficiency (PPPE) at 1572 nm, generated in a noncommercial periodically poled lithium-niobate waveguide fabricated in our laboratory. The first measurement, referred to as direct measurement, is performed at the photon-counting level (light power at the level of a few picowatts), exploiting a typical coincidence detection technique and a dedicated statistical model. In this case the measured PPPE is (4.1±1.1)1011 pairs/(s W). The same parameter was estimated independently by a well-established indirect measurement, based on a difference frequency generation experiment (typical light power level of a few microwatts). This other measurement yields (5.0±2.4)1011 pairs/(s W). Despite the large uncertainty of this second measurement, we observe that the two results are in good agreement even considering only the lower uncertainty value. To our knowledge, it is the first realization of a comparison between these two measurement techniques, working at so different light levels.

THz imaging of cyclotron emission in quantum Hall conductors

Recent studies of cyclotron emission microscopy on quantum Hall related states are reported. The topics include non-equilibrium between edge and bulk states, current-induced breakdown of the quantum Hall effect, and the emission threshold at hot spots. Experimental method of scanning-type terahertz microscopes developed towards photon-counting level sensitivity is also described.

Excitonic and biexcitonic decoherence in self-assembled GaAs quantum dots as observed by phase-locked interferography

We observe single-photon interferograms for emission of a single self-assembled GaAs quantum dot. A phase stabilizer is applied to the interferometer, enabling us to trace autocorrelations of weak emissions with a photon-counting level. At low excitation, where the average number of excitons in a dot is less than one, interferography reveals a single exponential decay, reflecting excitonic decoherence. At moderately high excitation, polarization interference between the exciton-biexciton transitions is found to appear on the interferogram. The decoherence time and the binding energy of biexcitons are determined simultaneously.

Impact of System Design Parameters on Image Figures of Merit for a Mouse PET Scanner

In this study, an analytical simulation model was developed to investigate how system design parameters affect image figures of merit and task performance for small animal positron emission tomography (PET) scanners designed to image mice. For a very high resolution imaging system, important physical effects that may impact image quality are positron range, annihilation photon acollinearity, detector point-spread function (PSF) and coincident photon count levels (i.e., statistical noise). Modeling of these effects was included in an analytical simulation that generated multiple realizations of sinograms with varying levels of each effect. To evaluate image quality with respect to quantitation and detection task performance, four different figures of merit were measured: 1) root mean square error (RMSE); 2) a region of interest SNR (SNR/sub ROI/); 3) nonprewhitening matched filter SNR (SNR/sub NPW/); and 4) recovery coefficient. The results indicate that for very high resolution imaging systems, the increase in positron range of C-11 compared to F-18 radiolabeling causes a significant reduction of quantitation (SNR/sub ROI/) and detection (SNR/sub NPW/) accuracy for small regions. In addition, changing the shape of the detector PSF, which depends on crystal thickness, causes significant variations in quantitation and detection performance. However, while increasing noise levels significantly increase RMSE and decrease detectability (SNR/sub NPW/), the quantitation task performance (SNR/sub ROI/), is less sensitive to noise levels. These results imply that resolution is more important than sensitivity for quantitation task performance, while sensitivity is a more significant issue for detection. The analytical simulation model can be used for estimating task performance of small animal PET systems more rapidly than existing full Monte Carlo methods, although Monte Carlo methods are needed to estimate system parameters.

Multiple-image radiography

Conventional radiography produces a single image of an object by measuring the attenuation of an x-ray beam passing through it. When imaging weakly absorbing tissues, x-ray attenuation may be a suboptimal signature of disease-related information. In this paper we describe a new phase-sensitive imaging method, called multiple-image radiography (MIR), which is an improvement on a prior technique called diffraction-enhanced imaging (DEI). This paper elaborates on our initial presentation of the idea in Wernick et al (2002 Proc. Int. Symp. Biomed. Imaging pp 129–32). MIR simultaneously produces several images from a set of measurements made with a single x-ray beam. Specifically, MIR yields three images depicting separately the effects of refraction, ultra-small-angle scatter and attenuation by the object. All three images have good contrast, in part because they are virtually immune from degradation due to scatter at higher angles. MIR also yields a very comprehensive object description, consisting of the angular intensity spectrum of a transmitted x-ray beam at every image pixel, within a narrow angular range. Our experiments are based on data acquired using a synchrotron light source; however, in preparation for more practical implementations using conventional x-ray sources, we develop and evaluate algorithms designed for Poisson noise, which is characteristic of photon-limited imaging. The results suggest that MIR is capable of operating at low photon count levels, therefore the method shows promise for use with conventional x-ray sources. The results also show that, in addition to producing new types of object descriptions, MIR produces substantially more accurate images than its predecessor, DEI. MIR results are shown in the form of planar images of a phantom and a biological specimen. A preliminary demonstration of the use of MIR for computed tomography is also presented.