Design and development of the DE-SPECT system: a clinical SPECT system for broadband multi-isotope imaging of peripheral vascular disease.

Objective Peripheral Vascular Disease (PVD) affects more than 230 million people worldwide and is one of the leading causes of disability among people over age 60. Nowadays, PVD remains largely underdiagnosed and undertreated, and requires the development of tailored diagnostic approaches. We present the full design of the Dynamic Extremity SPECT (DE-SPECT) system, the first organ-dedicated SPECT system for lower extremity imaging, based on 1-cm thick Cadmium Zinc Telluride (CZT) spectrometers and a dynamic dual field-of-view (FOV) synthetic compound-eye collimator. Approach The proposed DE-SPECT detection system consists of 48 1-cm thick 3D-position-sensitive CZT spectrometers arranged in a partial ring of 59 cm in diameter in a checkerboard pattern. The detection system is coupled with a compact dynamic synthetic compound-eye (SCE) collimator that allows the user to select between two different FOVs at any time during an imaging study: a wide-FOV (28-cm diameter) configuration for dual-leg or scout imaging or a high-resolution and high-sensitivity (HR-HS) FOV (16-cm diameter) for single-leg or focused imaging. Main Results The preliminary experimental data show that the CZT spectrometer achieves a 3D intrinsic spatial resolution of <0.75 mm FWHM and an excellent energy resolution over a broad energy range (2.6 keV FWHM at 218 keV, 3.3 keV at 440 keV). From simulations, the wide-FOV configuration offers a 0.034% averaged sensitivity at 140 keV and <8 mm spatial resolution, whereas the HR-HS configuration presents a peak central sensitivity of 0.07% at 140 keV and a ~5 mm spatial resolution. The dynamic SCE collimator enables the capability to perform joint reconstructions that would ensure an overall improvement in imaging performance. Significance The DE-SPECT system is a stationary and high-performance SPECT system that offers an excellent spectroscopic performance with a unique computer-controlled dual-FOV imaging capability, and a relatively high sensitivity for multi-tracer and multi-functional SPECT imaging of the extremities.

A High-Sensitivity Benchtop X-Ray Fluorescence Emission Tomography (XFET) System With a Full-Ring of X-Ray Imaging-Spectrometers and a Compound-Eye Collimation Aperture.

The advent of metal-based drugs and metal nanoparticles as therapeutic agents in anti-tumor treatment has motivated the advancement of X-ray fluorescence computed tomography (XFCT) techniques. An XFCT imaging modality can detect, quantify, and image the biodistribution of metal elements using the X-ray fluorescence signal emitted upon X-ray irradiation. However, the majority of XFCT imaging systems and instrumentation developed so far rely on a single or a small number of detectors. This work introduces the first full-ring benchtop X-ray fluorescence emission tomography (XFET) system equipped with 24 solid-state detectors arranged in a hexagonal geometry and a 96-pinhole compound-eye collimator. We experimentally demonstrate the system's sensitivity and its capability of multi-element detection and quantification by performing imaging studies on an animal-sized phantom. In our preliminary studies, the phantom was irradiated with a pencil beam of X-rays produced using a low-powered polychromatic X-ray source (90kVp and 60W max power). This investigation shows a significant enhancement in the detection limit of gadolinium to as low as 0.1 mg/mL concentration. The results also illustrate the unique capabilities of the XFET system to simultaneously determine the spatial distribution and accurately quantify the concentrations of multiple metal elements.

Exploration of Coincidence Detection of Cascade Photons to Enhance Preclinical Multi-Radionuclide SPECT Imaging.

We proposed a technique of coincidence detection of cascade photons (CDCP) to enhance preclinical SPECT imaging of therapeutic radionuclides emitting cascade photons, such as Lu-177, Ac-225, Ra-223, and In-111. We have carried out experimental studies to evaluate the proposed CDCP-SPECT imaging of low-activity radionuclides using a prototype coincidence detection system constructed with large-volume cadmium zinc telluride (CZT) imaging spectrometers and a pinhole collimator. With In-111 in experimental studies, the CDCP technique allows us to improve the signal-to-contamination in the projection (Projection-SCR) by ~53 times and reduce ~98% of the normalized contamination. Compared to traditional scatter correction, which achieves a Projection-SCR of 1.00, our CDCP method boosts it to 15.91, showing enhanced efficacy in reducing down-scattered contamination, especially at lower activities. The reconstructed images of a line source demonstrated the dramatic enhancement of the image quality with CDCP-SPECT compared to conventional and triple-energy-window-corrected SPECT data acquisition. We also introduced artificial energy blurring and Monte Carlo simulation to quantify the impact of detector performance, especially its energy resolution and timing resolution, on the enhancement through the CDCP technique. We have further demonstrated the benefits of the CDCP technique with simulation studies, which shows the potential of improving the signal-to-contamination ratio by 300 times with Ac-225, which emits cascade photons with a decay constant of ~0.1 ns. These results have demonstrated the potential of CDCP-enhanced SPECT for imaging a super-low level of therapeutic radionuclides in small animals.

Experimental Evaluation of a 3-D CZT Imaging Spectrometer for Potential Use in Compton-Enhanced PET Imaging.

We constructed a prototype positron emission tomography (PET) system and experimentally evaluated large-volume 3-D cadmium zinc telluride (CZT) detectors for potential use in Compton-enhanced PET imaging. The CZT spectrometer offers sub-0.5-mm spatial resolution, an ultrahigh energy resolution (~1% @ 511 keV), and the capability of detecting multiple gamma-ray interactions that simultaneously occurred. The system consists of four CZT detector panels with a detection area of around 4.4 cm × 4.4 cm. The distance between the front surfaces of the two opposite CZT detector panels is ~80 mm. This system allows us to detect coincident annihilation photons and Compton interactions inside the detectors and then, exploit Compton kinematics to predict the first Compton interaction site and reject chance coincidences. We have developed a numerical integration technique to model the near-field Compton response that incorporates Doppler broadening, detector's finite resolutions, and the distance between the first and second interactions. This method was used to effectively reject random and scattered coincidence events. In the preliminary imaging studies, we have used point sources, line sources, a custom-designed resolution phantom, and a commercial image quality (IQ) phantom to demonstrate an imaging resolution of approximately 0.75 mm in PET images, and Compton-based enhancement.

Joint Estimation of Metal Density and Attenuation Maps with Pencil Beam XFET.

X-ray fluorescence emission tomography (XFET) is an emerging imaging modality that images the spatial distribution of metal without requiring biochemical modification or radioactivity. This work investigates the joint estimation of metal and attenuation maps with a pencil-beam XFET system that allows for direct metal measurement in the absence of attenuation. Using singular value decomposition on a simplified imaging model, we show that reconstructing metal and attenuation voxels far from the detector is an ill-conditioned problem. Using simulated data, we develop and compare two image reconstruction methods for joint estimation. The first method alternates between updating the attenuation map with a separable paraboloidal surrogates algorithm and updating the metal map with a closed-form solution. The second method performs simultaneous joint estimation with conjugate gradients based on a linearized imaging model. The alternating approach outperforms the linearized approach for iron and gold numerical phantom reconstructions. Reconstructing an (8 cm)3 object containing gold concentrations of 5 mg/cm3 and an unknown beam attenuation map using the alternating approach yields an accurate gold map (NRMSE = 0.19) and attenuation map (NRMSE = 0.14). This simulation demonstrates an accurate joint reconstruction of metal and attenuation maps, from emission data, without previous knowledge of any attenuation map.

Joint estimation of interaction position and energy deposition in semiconductor SPECT imaging sensors using fully connected neural network.

Objective.Pixelated semiconductor detectors such as CdTe and CZT sensors suffer spatial resolution and spectral performance degradation induced by charge-sharing effects. It is critical to enhance the detector property through recovering the energy-deposition and position estimation.Approach.In this work, we proposed a fully-connected-neural-network-based charge-sharing reconstruction algorithm to correct the charge-loss and estimate the sub-pixel position for every multi-pixel charge-sharing event.Main results.Evident energy resolution improvement can be observed by comparing the spectrum produced by a simple charge-sharing addition method and the proposed energy correction methods. We also demonstrate that sub-pixel resolution can be achieved in projections obtained with a small pinhole collimator and an innovative micro-ring collimator.Significance.These achievements are crucial for multiple-tracer SPECT imaging applications, and for other semiconductor detector-based imaging modalities.

Design Study of an Ultrahigh Resolution Brain SPECT System Using a Synthetic Compound-Eye Camera Design With Micro-Slit and Micro-Ring Apertures.

In this paper, we discuss the design study for a brain SPECT imaging system, referred to as the HelmetSPECT system, based on a spherical synthetic compound-eye (SCE) gamma camera design. The design utilizes a large number (  âˆ¼ 500 ) of semiconductor detector modules, each coupled to an aperture with a very narrow opening for high-resolution SPECT imaging applications. In this study, we demonstrate that this novel system design could provide an excellent spatial resolution, a very high sensitivity, and a rich angular sampling without scanning motion over a clinically relevant field-of-view (FOV). These properties make the proposed HelmetSPECT system attractive for dynamic imaging of epileptic patients during seizures. In ictal SPECT, there is typically no prior information on where the seizures would happen, and both the imaging resolution and quantitative accuracy of the dynamic SPECT images would provide critical information for staging the seizures outbreak and refining the plans for subsequent surgical intervention.We report the performance evaluation and comparison among similar system geometries using non-conventional apertures, such as micro-ring and micro-slit, and traditional lofthole apertures. We demonstrate that the combination of ultrahigh-resolution imaging detectors, the SCE gamma camera design, and the micro-ring and micro-slit apertures would offer an interesting approach for the future ultrahigh-resolution clinical SPECT imaging systems without sacrificing system sensitivity and FOV.

Development of a multi-detector readout circuitry for ultrahigh energy resolution single-photon imaging applications.

In this paper, we present the design and preliminary performance evaluation of a novel external multi-channel readout circuitry for small-pixel room-temperature semiconductor detectors, namely CdZnTe (CZT) and CdTe, that provide an excellent intrinsic spatial (250 and 500 µm pixel size) and an ultrahigh energy resolution (~1% at 122 keV) for X-ray and gamma-ray imaging applications. An analog front-end printed circuit board (PCB) was designed and developed for data digitization, data transfer and ASIC control of pixelated CZT or CdTe detectors. Each detector unit is 2 cm × 2 cm in size and 1 or 2 mm in thickness, being bump-bonded onto a HEXITEC ASIC, and wire-bonded to a readout detector module PCB. The detectors' front-end is then connected, through flexible cables of up to 10 m in length, to a remote data acquisition system that interfaces with a PC through USB3.0 connection. We present the design and performance of a prototype multi-channel readout system that can read out up to 24 detector modules synchronously. Our experimental results demonstrated that the readout circuitry offers an ultrahigh spectral resolution (0.8 keV at 60 keV and 1.05 keV at 122 keV) with the Cd(Zn)Te/HEXITEC ASIC modules tested. This architecture was designed to allow easy expansion to accommodate a larger number of detector modules, and the flexibility of arranging the detector modules in a large and deformable detector array without degrading the excellent energy resolution.

System Modeling and Evaluation of a Prototype Inverted-Compound Eye Gamma Camera for the Second Generation MR Compatible SPECT.

We have reported the design of the MRC-SPECT-II system based on the inverted-compound-eye (ICE) gamma camera to offer a > 1% detection efficiency while maintaining a sub-500 µm imaging resolution [1]. One of the key challenges of using the ICE camera for SPECT imaging is whether one could develop an accurate point response function (PRF), given its complex aperture design and low fractionation accuracy of 3D printing. In this work, we will discuss (I) a combined experimental and analytical approach for deriving the precise PRF, and (II) an experimental imaging study to demonstrate the feasibility of using the ICE-camera for acquiring high-quality SPECT images with a sub-500 µm resolution. These studies would help to overcome one of the major hurdles for implement ICE-cameras for practical SPECT imaging.

[Changes in serum human cartilage glycoprotein-39 and high-mobility group box 1 in preterm infants with bronchopulmonary dysplasia].

OBJECTIVE: To study the association of the dynamic changes of peripheral blood human cartilage glycoprotein-39 (YKL-40) and high-mobility group box 1 (HMGB1) with bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: Preterm infants, with a gestational age of 28-32 weeks and a birth weight of <1 500 g, who were admitted to the neonatal intensive care unit from July 2017 to August 2019 were prospectively selected and divided into a BPD group with 35 infants and a non-BPD group with 51 infants. ELISA was used to measure the serum concentrations of YKL-40 and HMGB1 in preterm infants on days 3, 7, and 14 after birth. RESULTS: The BPD group had a significantly lower serum YKL-40 concentration and a significantly higher serum HMGB1 concentration than the non-BPD group on days 3, 7, and 14 (P<0.001). The serum concentrations of YKL-40 and HMGB1 on days 7 and 14 were significantly higher than those on day 3 in both groups (P<0.017). In the BPD group, HMGB1 concentration on day 14 was significantly higher than that on day 7 (P<0.017), while there was no significant change in YKL-40 concentration from day 7 to day 14 (P>0.017). In the non-BPD group, YKL-40 concentration on day 14 was significantly higher than that on day 7 (P<0.017), while there was no significant change in HMGB1 concentration from day 7 to day 14 (P>0.017). CONCLUSIONS: There are significant differences in the levels of YKL-40 and HMGB1 in peripheral blood between the preterm infants with BPD and those without BPD on days 3, 7, and 14 after birth, suggesting that YKL-40 and HMGB1 might be associated with the development of BPD.

[A comparative study of two ventilation modes in the weaning phase of preterm infants with respiratory distress syndrome].

OBJECTIVE: To compare the efficacy between synchronized intermittent mandatory ventilation (SIMV) and pressure support ventilation with volume guarantee (PSV+VG) in the weaning phase of preterm infants with respiratory distress syndrome (RDS). METHODS: Forty preterm infants with RDS who were admitted to the neonatal intensive care unit between March 2016 and May 2017 were enrolled as subjects. All infants were born at less than 32 weeks' gestation and received mechanical ventilation. These patients were randomly and equally divided into SIMV group and PSV+VG group in the weaning phase. Ventilator parameters, arterial blood gas, weaning duration (from onset of weaning to extubation), duration of nasal continuous positive airway pressure (NCPAP) after extubation, extubation failure rate, the incidence rates of pneumothorax, patent ductus arteriosus (PDA) and bronchopulmonary dysplasia (BPD), and the mortality rate were compared between the two groups. RESULTS: The PSV+VG group had significantly decreased mean airway pressure, weaning duration, duration of NCPAP after extubation, and extubation failure rate compared with the SIMV group (P<0.05). There were no significant differences in arterial blood gas, mortality, or incidence rates of pneumothorax, PDA and BPD between the two groups (P>0.05). CONCLUSIONS: For preterm infants with RDS, the PSV+VG mode may be a relatively safe and effective mode in the weaning phase. However, multi-center clinical trials with large sample sizes are needed to confirm the conclusion.

A novel depth-of-interaction rebinning strategy for ultrahigh resolution PET.

Small animal positron emission tomography (PET) imaging often requires high resolution (∼few hundred microns) to enable accurate quantitation in small structures such as animal brains. Recently, we have developed a prototype ultrahigh resolution depth-of-interaction (DOI) PET system that uses CdZnTe detectors with a detector pixel size of 350 µm and eight DOI layers with a 250 µm depth resolution. Due to the large number of line-of-response (LOR) combinations of DOIs, the system matrix for reconstruction is 64 times larger than that without DOI. While a high resolution virtual ring geometry can be employed to simplify the system matrix and create a sinogram, the LORs in such a sinogram tend to be sparse and irregular, leading to potential degradation of the reconstructed image quality. In this paper, we propose a novel high resolution sinogram rebinning method in which a uniform sub-sampling DOI strategy is employed. However, even with the high resolution rebinning strategy, the reconstructed image tends to be very noisy due to insufficient photon counts in many high resolution sinogram pixels. To reduce noise effects, we developed a penalized maximum likelihood reconstruction framework with the Poisson log-likelihood and a non-convex total variation penalty. Here, an ordered subsets separable quadratic surrogate and alternating direction method of multipliers are utilized to solve the optimization. To evaluate the performance of the proposed sub-sampling method and the penalized maximum likelihood reconstruction technique, we perform simulations and preliminary point source experiments. By comparing the reconstructed images and profiles based on sinograms without DOI, with rebinned DOI and with sub-sampled DOI, we demonstrate that the proposed method with sub-sampled DOIs can significantly improve the image quality with lower dose and yield a high resolution of <300 µm.

[Percentages of peripheral blood γδ T cells and regulatory T cells and expression of associated cytokines in infants with human cytomegalovirus infection].

OBJECTIVE: To investigate the percentages of peripheral blood γδ T cells and regulatory T cells (Treg) and the expression of associated cytokines, interleukin 17 (IL-17) and transforming growth factor-ß1 (TGF-ß1), in infants with human cytomegalovirus (HCMV) infection. METHODS: Twenty-two infants with HCMV infection (HCMV group) and 22 healthy infants who underwent physical examination (control group) were enrolled in this study. The percentages of peripheral blood γδ T cells and Treg cells were determined by flow cytometry. The levels of IL-17 and TGF-ß1 in plasma were measured using ELISA. RESULTS: Compared with the control group, the HCMV group had significantly higher percentage of γδ T cells and IL-17 level (P<0.01) and significantly lower percentage of Treg cells and TGF-ß1 level (P<0.01). In the HCMV group, the percentage of γδ T cells was negatively correlated with the percentage of Treg cells and TGF-ß1 level (P<0.05), but positively correlated with IL-17 level (P<0.05); the percentage of Treg cells was positively correlated with TGF-ß1 level (P<0.05), but negatively correlated with IL-17 level (P<0.05); there was no correlation between IL-17 level and TGF-ß1 level (P>0.05). CONCLUSIONS: There is an imbalance between γδ T cells and Treg cells in the peripheral blood of infants with HCMV infection, and γδ T cells may be involved in the secretion of IL-17.

Simulation study of the second-generation MR-compatible SPECT system based on the inverted compound-eye gamma camera design.

In this paper, we present simulation studies for the second-generation MRI compatible SPECT system, MRC-SPECT-II, based on an inverted compound eye (ICE) gamma camera concept. The MRC-SPECT-II system consists of a total of 1536 independent micro-pinhole-camera-elements (MCEs) distributed in a ring with an inner diameter of 6 cm. This system provides a FOV of 1 cm diameter and a peak geometrical efficiency of approximately 1.3% (the typical levels of 0.1%-0.01% found in modern pre-clinical SPECT instrumentations), while maintaining a sub-500 µm spatial resolution. Compared to the first-generation MRC-SPECT system (MRC-SPECT-I) (Cai 2014 Nucl. Instrum. Methods Phys. Res. A 734 147-51) developed in our lab, the MRC-SPECT-II system offers a similar resolution with dramatically improved sensitivity and greatly reduced physical dimension. The latter should allow the system to be placed inside most clinical and pre-clinical MRI scanners for high-performance simultaneous MRI and SPECT imaging.

MRC-SPECT: A sub-500 µm resolution MR-compatible SPECT system for simultaneous dual-modality study of small animals.

In this paper, we will report the development of an ultrahigh resolution MR-compatible SPECT system that can be operated inside a pre-existing clinical MR scanner for simultaneous dual-modality imaging of small animals. This system is constructed with 40 small-pixel CdTe detector modules assembled in a fully stationary ring SPECT geometry. We have experimentally demonstrated that this system is capable of providing an imaging resolution of <500 µm when operating inside MR scanners. We will report the design, construction of the MRI-compatible SPECT system, including the detector technology, collimator, system development and so on. The first imaging results obtained with this newly constructed SPECT system will also be reported.

Hybrid pixel-waveform CdTe/CZT detector for use in an ultrahigh resolution MRI compatible SPECT system.

In this paper, we will present a new small pixel CdTe/CZT detector for sub-500 µm resolution SPECT imaging application inside MR scanner based on a recently developed hybrid pixel-waveform (HPWF) readout circuitry. The HPWF readout system consists of a 2-D multi-pixel circuitry attached to the anode pixels to provide the X-Y positions of interactions, and a high-speed digitizer to read out the pulse-waveform induced on the cathode. The digitized cathode waveform could provide energy deposition information, precise timing and depth-of-interaction information for gamma ray interactions. Several attractive features with this HPWF detector system will be discussed in this paper. To demonstrate the performance, we constructed several prototype HPWF detectors with pixelated CZT and CdTe detectors of 2-5 mm thicknesses, connected to a prototype readout system consisting of energy-resolved photon-counting ASIC for readout anode pixels and an Agilent high-speed digitizer for digitizing the cathode signals. The performances of these detectors based on HPWF are discussed in this paper.

[Changes of hearing threshold and calcium/calmodulin in the cochlear nucleus cells of mice with cytomegalovirus intracranial infection].

OBJECTIVE: To explore the changes in the threshold of auditory brainstem response (ABR) and [Ca(2+)]I and calmodulin (CaM) in cochlear nucleus of newborn mice infected by murine cytomegalovirus (MCMV) in the brain. METHODS: Sixty-nine newborn mice were randomized into model group and control group. The model group (54 mice) was established by intracranial injection with MCMV viral suspension 20 l and the same volume of 0.9% sodium chloride was injected in the control group (15 mice). After 1 month, the ABR was tested in a sound-electric screen environment and the threshold was recorded. Then intracellular free calcium [Ca(2+)]i and the mRNA level of CaM in the cochlear nucleus were assayed by flow cytometry and RT-PCR. RESULTS: Compare to the control group [(64.0 ± 1.3) dBSPL], the threshold of ABR in the model group [(84.5 ± 2.7) dBSPL] was increased (F = 2.789,P = 0.000). Moreover, in the model group the intracellular free calcium [Ca(2+)]i and the mRNA level of CaM in the cochlear nucleus were increased (F = 1.290, P = 0.000; F = 4.252, P = 0.023), and the differences were statistically significant. CONCLUSIONS: The intracranial injection of MCMV can lead to abnormal changes in the threshold of ABR in mice, and the change of [Ca(2+) ]I/CaM in cochlear nucleus may be the important pathological basis of sensorineural hearing loss induced by MCMV infection.

Experimental demonstration of novel imaging geometries for x-ray fluorescence computed tomography.

PURPOSE: X-ray fluorescence computed tomography (XFCT) is an emerging imaging modality that maps the three-dimensional distribution of elements, generally metals, in ex vivo specimens and potentially in living animals and humans. At present, it is generally performed at synchrotrons, taking advantage of the high flux of monochromatic x rays, but recent work has demonstrated the feasibility of using laboratory-based x-ray tube sources. In this paper, the authors report the development and experimental implementation of two novel imaging geometries for mapping of trace metals in biological samples with ∼50-500 µm spatial resolution. METHODS: One of the new imaging approaches involves illuminating and scanning a single slice of the object and imaging each slice's x-ray fluorescent emissions using a position-sensitive detector and a pinhole collimator. The other involves illuminating a single line through the object and imaging the emissions using a position-sensitive detector and a slit collimator. They have implemented both of these using synchrotron radiation at the Advanced Photon Source. RESULTS: The authors show that it is possible to achieve 250 eV energy resolution using an electron multiplying CCD operating in a quasiphoton-counting mode. Doing so allowed them to generate elemental images using both of the novel geometries for imaging of phantoms and, for the second geometry, an osmium-stained zebrafish. CONCLUSIONS: The authors have demonstrated the feasibility of these two novel approaches to XFCT imaging. While they use synchrotron radiation in this demonstration, the geometries could readily be translated to laboratory systems based on tube sources.

3-D Spatial Resolution of 350 µm Pitch Pixelated CdZnTe Detectors for Imaging Applications.

We are currently investigating the feasibility of using highly pixelated Cadmium Zinc Telluride (CdZnTe) detectors for sub-500 µm resolution PET imaging applications. A 20 mm × 20 mm × 5 mm CdZnTe substrate was fabricated with 350 µm pitch pixels (250 µm anode pixels with 100 µm gap) and coplanar cathode. Charge sharing among the pixels of a 350 µm pitch detector was studied using collimated 122 keV and 511 keV gamma ray sources. For a 350 µm pitch CdZnTe detector, scatter plots of the charge signal of two neighboring pixels clearly show more charge sharing when the collimated beam hits the gap between adjacent pixels. Using collimated Co-57 and Ge-68 sources, we measured the count profiles and estimated the intrinsic spatial resolution of 350 µm pitch detector biased at -1000 V. Depth of interaction was analyzed based on two methods, i.e., cathode/anode ratio and electron drift time, in both 122 keV and 511 keV measurements. For single-pixel photopeak events, a linear correlation between cathode/anode ratio and electron drift time was shown, which would be useful for estimating the DOI information and preserving image resolution in CdZnTe PET imaging applications.