Semi-monolithic scintillation detectors have recently proven to be a promising compromise between pixelated and monolithic crystals. This geometry is particularly suitable for preclinical Positron Emission Tomography (PET) systems, as it provides high spatial resolution while enabling Depth of Interaction (DOI) capabilities. While prior detector developments have almost exclusively focused on lutetium-based scintillators, BGO has re-gained attention for PET applications given its lower cost, higher stopping power, larger photo-fraction and absence of intrinsic radioactivity. In this work, we propose a semi-monolithic detector composed of 44 BGO slabs of 1 mm × 24.2 mm × 10 mm each, designed for preclinical PET systems. We focus on evaluating its spatial and energy performance and directly compare it with a LYSO semi-monolithic block of identical dimensions. The x-monolithic direction and DOI resolutions were evaluated using neural networks, while the y-pixelated direction was evaluated with an analytical method. Average FWHM spatial resolutions of 1.6 ± 0.2 mm and 1.2 ± 0.3 mm were achieved for the BGO and LYSO, respectively, along the x-monolithic direction. Regarding DOI, average FWHM resolution values of 3.0 ± 0.6 mm and 2.0 ± 0.5 mm were obtained for BGO and LYSO, respectively. A FWHM spatial resolution of around 1 mm was estimated for both crystal types along the y-pixelated direction. Finally, mean energy resolutions of 23.7% and 18.5% were found for the BGO and LYSO, respectively. These results show that the proposed BGO block is a viable alternative for high spatial resolution, high sensitivity and low-cost preclinical PET scanners.

Most preclinical PET scanners are based on pixelated detectors without Depth of Interaction (DOI) capabilities, which is crucial to correct for parallax errors. Semi-monolithic crystals have the potential to combine the timing capabilities of pixelated crystals and the 3D positioning accuracy of monolithic scintillators. In this work, we present a preclinical PET prototype consisting of 2 rings defining an inner diameter of 106 mm and an axial length of 52 mm. Each ring contains 14 arrays of 1 × 22 LYSO slabs of 0.97 mm × 25.6 mm × 12 mm, coupled to 8 × 8 SiPMs arrays. The sensitivity, spatial resolution, count rate performance and image quality were studied using the NEMA NU 4-2008 protocol. All images were reconstructed using the MLEM algorithm with 0.5 mm voxel size, including DOI information and normalization correction. A mean spatial resolution for all measured positions and across the three directions (axial, transaxial and radial) of 1.61 ± 0.19 mm was obtained at the center of the FOV. A peak sensitivity of 3.5% was obtained at the center of the scanner, for an energy window (EW) between 358 keV -664 keV. The noise equivalent count rate peak reached 106.9 kcps for an activity of 11.7 MBq using the mouse-sized phantom, the same EW window and a time coincidence window of 10 ns. For the image quality phantom, contrast recovery coefficients of 0.20, 0.62, 0.75, 0.81 and 0.85 were found for the 1, 2, 3, 4 and 5 mm rods, respectively. Spill-over-ratio values of 0.10 for air-filled and 0.23 for water-filled cylinders were measured. Also, according to the Rayleigh criterion, 1.5, 1.2 and 1 mm hot spots of a micro-Derenzo phantom were well distinguished.

The use of monolithic scintillator-based photon detectors in positron emission tomography (PET) has emerged as an attractive alternative to traditional pixelated array designs. Monolithic-based detector designs employ the scintillation light distribution (LD) shape to provide a single 3-D photon interaction position per event, enabling high spatial resolution throughout the crystal volume. Since there are no intercrystal gaps, monolithic designs provide higher intrinsic detection efficiency compared to pixelated designs. However, in order to make the monolithic detector design practical for clinical PET systems, some major drawbacks need to be addressed, such as the time-consuming and complex calibration procedures to obtain precise spatial and timing information. This article gives a historical review of monolithic-based PET detectors, a description of their main advantages and challenges, describes the state-of-the-art, including their use in current commercial system, and ends with a future prospective.

3123 Objectives: Multimodal PET/MR imaging is a powerful molecular imaging tool widely used in research and clinical practice for a broad variety of applications. Small animal PET inserts are an instrumentation tool that can be used in combination with already installed MRI systems. This work shows the initial performance and MRI compatibility of a small animal PET insert for mouse applications, based on monolithic LYSO scintillation crystals. Methods: The PET system is based on LYSO cuboids of 25x33x10 mm, laterally black painted and include a retroreflector layer at the entrance face. This layer improves the detectability of the gamma ray position interaction. The crystals are coupled to custom made 10x8 SiPM arrays with 3x3 mm active area each. 24 crystals are distributed in 3 rings defining an axial and transaxial FOV of 100 mm and 40 mm, respectively. The SiPM photosensor and readout electronics are mounted on high performance boards that avoid the generation of eddy current by the switching gradient fields.This work shows the results carried out within a Bruker BioSpec 94/20 MRI imaging instrument using a 35 mm volume RF coil. The PET insert includes an RF shielding based on carbon fiber structures. We report here the average performance of the detector blocks, and some of the most important parameters regarding PET imagingand MR compatibility. Results: After calibration of each detector block using a novel approach based on Voronoi diagrams [1], the average energy resolution of the whole system is about 13.5%, together with an impact precision determination in 2D below 1.5 mm, and about 2 mm depth of interaction (DOI) resolution.Regarding MR compatibility, the PET insert has been run under several MRI sequences including EPI with high duty cycles. No significant change in MRI performance was observed when compared to the case without the PET. The PET detector performance is not affected by interferences that could arise from different MRI imaging sequences, concerning impact determination, energy or any other parameter [2,3]. Therefore, the reconstructed images did not exhibit any degradation.The initial performance evaluation resulted in a peak sensitivity of nearly 12% at CFOV, and a NECR mouse peak of 481 kcps at 25.7 MBq . The PSF-corrected spatial resolution has been determined to be about 0.7 mm FWHM for all three space components. Using DOI allows to reach similar spatial resolution performance for the entire FOV. The good spatial resolution of the device allows to distinguish 0.8mm rods of a micro-Derenzo phantom when using 0.25 mm voxels, 1 mm virtual pixels and 25 iterations (MLEM). Conclusions: This works provides design principles needed for the realization of small PET/MR inserts for mice. The initial study has shown that the requirements for simultaneous PET/MR mouse imaging applications can be reached, thus high spatial PET imaging resolution and the absence of any interference effects for PET and MRI.The PET insert reaches an unprecedented image performance resolving well 0.8 mm Derenzo rods while simultaneously imaging MRI with EPI sequences. The high spatial resolution is obtained across the entire PET FOV, thus helping researchers for a more reliable quantification during their investigations. Bibliography: [1] M. Freire, IEEE TRPMS, 2019, doi: 0.1109/TRPMS.2019.2947716. [2] A.J. Gonzalez, IEEE TRPMS 3, 343, 2019. [3] W. Gsell, to be submitted to EJNMMI, 2020.

The main aim of this work is to provide a method to retrieve the intrinsic spatial resolution of a gamma-ray detector block based on monolithic crystals within an assembled scanner. This method consists on a discrimination of the data using a software collimation process. The results are compared with an alternative method of separating two detector blocks far enough to produce a "virtual" source collimation due to the geometric constraints on the allowed coincidence event angles. A theoretical model has been deduced to fit the measured light distribution profiles, allowing estimating the detector intrinsic spatial resolution. The detector intrinsic spatial resolution is expected to follow a Gaussian distribution and the positron-emitter source shape, given the small size of a Na-22 source with 0.25 mm in diameter, can be assumed to follow a Lorentzian profile. However, the collimation of the data modifies the source shape that is no longer a pure Lorentzian distribution. Therefore, the model is based on the convolution of a Gaussian shaped distribution (contribution of the detector) and a modified Lorentzian distribution (contribution of the collimated source profile) that takes into account the collimation effect. Three LYSO crystals geometries have been studied in the present work, namely a 10 mm thick trapezoidal monolithic block, and two rectangular monolithic blocks with thicknesses of 15 mm and 20 mm, respectively. All the blocks have size dimensions of 50 mm x 50 mm. The experimental results yielded an intrinsic detector spatial resolution of 0.64 +/- 0.02 mm, 0.82 +/- 0.02 and 1.07 +/- 0.03 mm, for the 10 mm, 15 mm and 20 mm thick blocks, respectively, when the source was placed at the center of the detector. The detector intrinsic spatial resolution was moreover evaluated across one of the axis of each crystal. These values worsen to an average value of 0.68 +/- 0.04 mm, 0.90 +/- 0.14 and 1.29 +/- 0.19 mm, respectively, when the whole crystal size is considered, as expected. These tests show an accurate method to determine the intrinsic spatial resolution of monolithic-based detector blocks, once assembled in the PET system.

The main aim of this work is to provide a method to retrieve the intrinsic resolution of detector blocks based on monolithic crystals in a fully assembled scanner. This method suggests a software collimation to the original data. The results are compared with the traditional approach of separating two detector blocks far enough, resulting in geometrical collimation.An empirical equation has been deduced to fit the experimental data in which the detector intrinsic resolution follows a Gaussian distribution and the contribution of the source, given the small size of 0.25 mm in diameter, follows a Lorentzian profile. The experiments resulted in an average detector intrinsic spatial resolution of 0.6 mm FWHM, with a standard deviation error of 0.1 mm. These tests show a method to determine the intrinsic resolution of monolithic-based detector blocks, once assembled in the PET system, with high accuracy.

A new small animal PET based on SiPM and monolithic LYSO crystals has been developed. Eight detector modules form the PET ring, each mounting an array of 12 × 12 SiPMs coupled to a readout providing the summed signals of the pixels on each of the 12 rows and 12 columns of the SiPM array. This design makes it possible to accurately determine the centroid of the scintillation light distribution with about 1.6 mm full width at half maximum (FWHM) resolution without correction for the 1 mm source size, and the photon depth of interaction (DOI) with nearly 2 mm FWHM. This single ring PET system has a homogeneous spatial resolution across the entire 80 mm transaxial field of view (FOV) of about 1 mm FWHM. The noise equivalent count rate (NECR) peak is estimated to occur at around 39.2 MBq with a rate of approximately 82.7 kcps for the mouse-like phantom and 22 kcps at 48.1 MBq for the rat-like phantom. Following the NEMA protocol, the peak absolute sensitivity in the center of the FOV is 2.8% for a 30% peak energy window. A pilot test injecting NaF to a mouse of 20 grams is also presented. Finally, the PET ring has been tested in front of a high field 15.2 T Magnetic Resonance (MR). No significant variation on energy and spatial resolution across the FOV has been observed due to the presence of the magnetic field.

Before microcomputed tomography (micro-CT) can be exploited to its full potential for longitudinal monitoring of transgenic and experimental mouse models of lung diseases, radiotoxic side effects such as inflammation or fibrosis must be considered. We evaluated dose and potential radiotoxicity to the lungs for long-term respiratory-gated high-resolution micro-CT protocols. Free-breathing C57Bl/6 mice underwent four different retrospectively respiratory gated micro-CT imaging schedules of repeated scans during 5 or 12 wk, followed by ex vivo micro-CT and detailed histological and biochemical assessment of lung damage. Radiation exposure, dose, and absorbed dose were determined by ionization chamber, thermoluminescent dosimeter measurements and Monte Carlo calculations. Despite the relatively large radiation dose delivered per micro-CT acquisition, mice did not show any signs of radiation-induced lung damage or fibrosis when scanned weekly during 5 and up to 12 wk. Doubling the scanning frequency and once tripling the radiation dose as to mimic the instant repetition of a failed scan also stayed without detectable toxicity after 5 wk of scanning. Histological analyses confirmed the absence of radiotoxic damage to the lungs, thereby demonstrating that long-term monitoring of mouse lungs using high-resolution micro-CT is safe. This opens perspectives for longitudinal monitoring of (transgenic) mouse models of lung diseases and therapeutic response on an individual basis with high spatial and temporal resolution, without concerns for radiation toxicity that could potentially influence the readout of micro-CT-derived lung biomarkers. This work further supports the introduction of micro-CT for routine use in the preclinical pulmonary research field where postmortem histological approaches are still the gold standard.

In the field of biomedical X-ray imaging, novel techniques, such as phase-contrast and dark-field imaging, have the potential to enhance the contrast and provide complementary structural information about a specimen. In this paper, a first prototype of a preclinical X-ray phase-contrast CT scanner based on a Talbot-Lau interferometer is characterized. We present a study of the contrast-to-noise ratios for attenuation and phase-contrast images acquired with the prototype scanner. The shown results are based on a series of projection images and tomographic data sets of a plastic phantom in phase and attenuation-contrast recorded with varying acquisition settings. Subsequently, the signal and noise distribution of different regions in the phantom were determined. We present a novel method for estimation of contrast-to-noise ratios for projection images based on the cylindrical geometry of the phantom. Analytical functions, representing the expected signal in phase and attenuation-contrast for a circular object, are fitted to individual line profiles of the projection data. The free parameter of the fit function is used to estimate the contrast and the goodness of the fit is determined to assess the noise in the respective signal. The results depict the dependence of the contrast-to-noise ratios on the applied source voltages, the number of steps of the phase stepping routine, and the exposure times for an individual step. Moreover, the influence of the number of projection angles on the image quality of CT slices is investigated. Finally, the implications for future imaging purposes with the scanner are discussed.

We have investigated available approaches for the non-destructive 3D mineralogical analysis of reservoir rocks. The applicability of the classical X-ray micro-computed tomography technique is reviewed together with an analysis of the results from a newly developed combined microCT and micro-X-ray fluorescence system. The advantages and limitations of these different approaches are discussed using the example of a sandstone reservoir rock study. acknowledgements The authors thank Alexander Sasov, CEO of Bruker Micro-CT, for fruitful discussions. corresponding author details Dr Albina Mutina Schlumberger Surenco, SA Calle 100, No. 13-21 Bogotá D.C., Colombia Tel: +57 321 44

The grating based approach to phase contrast imaging is rather inefficient in the use of the available x-ray flux due to the presence of two absorption gratings and it requires longer scan times compared to conventional CT because multiple images are needed at each projection angle. To avoid these drawbacks, a proof-of-principle experiment was developed to obtain absorption, phase contrast (DPC) and dark field images (DCI) in a single exposure using only a non-absorbing phase grating, a micro-focus source in cone-beam geometry and a highresolution x-ray detector.

Novel radiography approaches based on the wave nature of x-rays when propagating through matter have a great potential for improved future x-ray diagnostics in the clinics. Here, we present a significant milestone in this imaging method: in-vivo multi-contrast x-ray imaging of a mouse using a compact scanner. Of particular interest is the enhanced contrast in regions related to the respiratory system, indicating a possible application in diagnosis of lung diseases (e.g. emphysema).

To explore the future clinical potential of improved soft-tissue visibility with grating-based X-ray phase contrast (PC), we have developed a first preclinical computed tomography (CT) scanner featuring a rotating gantry. The main challenge in the transition from previous bench-top systems to a preclinical scanner are phase artifacts that are caused by minimal changes in the grating alignment during gantry rotation. In this paper, we present the first experimental results from the system together with an adaptive phase recovery method that corrects for these phase artifacts. Using this method, we show that the scanner can recover quantitatively accurate Hounsfield units in attenuation and phase. Moreover, we present a first tomography scan of biological tissue with complementary information in attenuation and phase contrast. The present study hence demonstrates the feasibility of grating-based phase contrast with a rotating gantry for the first time and paves the way for future in vivo studies on small animal disease models (in the mid-term future) and human diagnostics applications (in the long-term future).

Cramér–Rao theory can be used to derive the lower bound on the spatial resolution achievable with position-sensitive scintillation detectors as a function of the detector geometry and the pertinent physical properties of the scintillator, the photosensor and the readout electronics. Knowledge of the Cramér–Rao lower bound (CRLB) can for example be used to optimize the detector design and to test the performance of the method used to derive position information from the detector signals. Here, this approach is demonstrated for monolithic scintillator detectors for positron emission tomography. Two detector geometries are investigated: a 20 × 10 × 10 mm3 and a 20 × 10 × 20 mm3 monolithic LYSO:Ce3+ crystal read out by one or two Hamamatsu S8550SPL avalanche photodiode (APD) arrays, respectively. The results indicate that in these detectors the CRLB is primarily determined by the APD excess noise factor and the number of scintillation photons detected. Furthermore, it is shown that the use of a k-nearest neighbor (k-NN) algorithm for position estimation allows the experimentally obtained spatial resolution to closely approach the CRLB. The approach outlined in this work can in principle be applied to any scintillation detector in which position information is encoded in the distribution of the scintillation light over multiple photosensor elements.

In our dual-modality microCT/microXRF system, the two sub-systems are combined in one machine, sharing a travelling sample holder. The microXRF, based on a pin-hole collimator and a photon-counting energysensitive 2D-detector, obtains 3D chemical composition maps of a sample. These images often lack structural information. With the built-in microCT, 3D structural information of the sample can be obtained. The two subsystems need to be properly calibrated and aligned. This calibration and alignment procedure needs to be done for all pin-hole collimators, but only need to be performed once after the system is assembled. The two modalities are calibrated separately, by analyzing projection images of a 3-ball phantom. The phantom is made of a very thin plastic cylinder, on which 3 copper balls are attached at well-chosen locations. The same phantom is used for both sub-systems and is scanned sequentially. We have evaluated this calibration method on various CT scanners and it has proven to be very effective. But it is more challenging for the XRF subsystem due to the strong absorptions. The two imaging spaces are calibrated relative to their own coordinate systems. To align the two sub-systems, the centers of the balls in reconstructed volumes are determined and then aligned using a rigid transformation. Repeated tests have shown that the mechanical movements are stable and the reconstructed image volumes can be well co-registered.

We have developed a compact grating-based in-vivo phase-contrast micro-CT system with a rotating gantry. The 50 W microfocus x-ray source operates with 20 to 50 kV peak energy. The length of the rotating interferometer is around 47 cm. Pixel size in the object is 30 micron; the field of view is approx. 35 mm in diameter, suited to image a mouse. The interferometer consists of three gratings: an absorption grating close to the x-ray source, a phase grating to introduce a pi/2 phase shift and an absorption analyzer grating positioned at the first fractional Talbot distance. Numerous drives and actuators are used to provide angular and linear grating alignment, phase stepping and object/gantry precision positioning.Phantom studies were conducted to investigate performance, accuracy and stability of the scanner. In particular, the influences of gantry rotation and of temperature fluctuations on the interferometric image acquisition were characterized. Also dose measurements were performed. The first imaging results obtained with the system show the complementary nature of phase-contrast micro-CT images with respect to absorption-based micro-CT. Future improvements, necessary to optimize the scanner for in-vivo small-animal CT scanning on a regular and easy-to-use basis, are also discussed.

After successful demonstrations of soft-tissue phase-contrast imaging with grating interferometers at synchrotron radiation sources and at laboratory based x-ray tubes, a first preclinical CT scanner with grating based phase contrast imaging modality has been constructed. The rotating gantry is equipped with a three-grating interferometer, a 50 watt tungsten anode source and a Hamamatsu flat panel detector. The total length of the interferometer is 45 cm, and the bed of the scanner is optimized for mice, with a scanning diameter of 35 mm. From one single scan both phase-contrast and standard attenuation based tomography can be attained, providing an overall gain in image contrast.

Purpose: One of the main limitations of absorption‐based x‐ray imaging of biomedical specimen is the weak soft‐tissue contrast. This limitation can be addressed by phase‐sensitive imaging methods facilitating considerably improved density resolution. During the last decades various approaches have been investigated ‐ amongst them grating‐based interferometric methods with laboratory x‐ray sources. As a first step towards clinical applications, we have developed a grating‐based compact preclinical phase‐contrast CT scanner, from which we present the first commissioning results. Methods: The grating interferometer translates a small local refraction signal of x‐rays in the sample to intensity modulations that can be detected with a conventional x‐ray detector. Using a generalized filtered backprojection based reconstruction algorithm to account for the cone‐beam geometry, phase‐sensitive tomographic imaging of whole rodents is possible. A first phantom study was performed to investigate the performance, quantitativeness and accuracy of phase‐contrast and absorption‐based computed tomography scans. These scans yield the three‐dimensional distribution of attenuation coefficient mu and refractive index decrement delta of the different liquids contained in the phantom. Further performance experiments were conducted to assess the rotation stability and to optimize the phase‐contrast acquisition protocol of the compact gantry system. Results: The experimental phantom data for mu and delta match accurately with tabulated data, and demonstrate that the compact gantry performs well in both absorption and phase contrast. In addition, first imaging results from small‐animal models will be presented. Conclusions: We show results of the first implementation of phase‐contrast imaging into a compact, rotating x‐ray CT gantry system. We believe that this work represents an important milestone in translating phase‐contrast from bench to bedside.

A prototype micro-XRF laboratory system based on pinhole imaging was developed to produce 3D elemental maps. The fluorescence x-rays are detected by a deep-depleted CCD camera operating in photon-counting mode. A charge-clustering algorithm, together with dynamically adjusted exposure times, ensures a correct energy measurement. The XRF component has a spatial resolution of 70 mu m and an energy resolution of 180 eV at 6.4 keV. The system is augmented by a micro-CT imaging modality. This is used for attenuation correction of the XRF images and to co-register features in the 3D XRF images with morphological structures visible in the volumetric CT images of the object.

X‐ray optics, such as zone plates, are often used to obtain a spatial resolution better than 100 nm in x‐ray projection images. Such types of optics are not always suited for tomographic imaging due to their limited depth of focus, which restricts the size of the specimen to a few microns. To overcome these limitations, we developed a new lens‐free setup for a nano‐CT system. Spatial resolution of nano‐CT systems is mainly defined by x‐ray source performance. It is dependent on target shape and focusing of the electron beam. The typical way to improve spatial resolution is based on replacement of the bulk metal target to thin film. It allows getting submicron spot size, but significantly reduces x‐ray flux. To overcome flux limitation without compromising with spatial resolution, we invented a new type of target shaped as a rod or needle towards the camera. It allows us to reach 50‐nm resolution with reasonable flux.