Development of an MRI-compatible digital SiPM detector stack for simultaneous PET/MRI.

Advances in solid-state photon detectors paved the way to combine positron emission tomography (PET) and magnetic resonance imaging (MRI) into highly integrated, truly simultaneous, hybrid imaging systems. Based on the most recent digital SiPM technology, we developed an MRI-compatible PET detector stack, intended as a building block for next generation simultaneous PET/MRI systems. Our detector stack comprises an array of 8 × 8 digital SiPM channels with 4 mm pitch using Philips Digital Photon Counting DPC 3200-22 devices, an FPGA for data acquisition, a supply voltage control system and a cooling infrastructure. This is the first detector design that allows the operation of digital SiPMs simultaneously inside an MRI system. We tested and optimized the MRI-compatibility of our detector stack on a laboratory test bench as well as in combination with a Philips Achieva 3 T MRI system. Our design clearly reduces distortions of the static magnetic field compared to a conventional design. The MRI static magnetic field causes weak and directional drift effects on voltage regulators, but has no direct impact on detector performance. MRI gradient switching initially degraded energy and timing resolution. Both distortions could be ascribed to voltage variations induced on the bias and the FPGA core voltage supply respectively. Based on these findings, we improved our detector design and our final design shows virtually no energy or timing degradations, even during heavy and continuous MRI gradient switching. In particular, we found no evidence that the performance of the DPC 3200-22 digital SiPM itself is degraded by the MRI system.

Software-Based Real-Time Acquisition and Processing of PET Detector Raw Data.

In modern positron emission tomography (PET) readout architectures, the position and energy estimation of scintillation events (singles) and the detection of coincident events (coincidences) are typically carried out on highly integrated, programmable printed circuit boards. The implementation of advanced singles and coincidence processing (SCP) algorithms for these architectures is often limited by the strict constraints of hardware-based data processing. In this paper, we present a software-based data acquisition and processing architecture (DAPA) that offers a high degree of flexibility for advanced SCP algorithms through relaxed real-time constraints and an easily extendible data processing framework. The DAPA is designed to acquire detector raw data from independent (but synchronized) detector modules and process the data for singles and coincidences in real-time using a center-of-gravity (COG)-based, a least-squares (LS)-based, or a maximum-likelihood (ML)-based crystal position and energy estimation approach (CPEEA). To test the DAPA, we adapted it to a preclinical PET detector that outputs detector raw data from 60 independent digital silicon photomultiplier (dSiPM)-based detector stacks and evaluated it with a [(18)F]-fluorodeoxyglucose-filled hot-rod phantom. The DAPA is highly reliable with less than 0.1% of all detector raw data lost or corrupted. For high validation thresholds (37.1 ± 12.8 photons per pixel) of the dSiPM detector tiles, the DAPA is real time capable up to 55 MBq for the COG-based CPEEA, up to 31 MBq for the LS-based CPEEA, and up to 28 MBq for the ML-based CPEEA. Compared to the COG-based CPEEA, the rods in the image reconstruction of the hot-rod phantom are only slightly better separable and less blurred for the LS- and ML-based CPEEA. While the coincidence time resolution (∼ 500 ps) and energy resolution (∼12.3%) are comparable for all three CPEEA, the system sensitivity is up to 2.5 × higher for the LS- and ML-based CPEEA.

Initial PET performance evaluation of a preclinical insert for PET/MRI with digital SiPM technology.

Hyperion-II(D) is a positron emission tomography (PET) insert which allows simultaneous operation in a clinical magnetic resonance imaging (MRI) scanner. To read out the scintillation light of the employed lutetium yttrium orthosilicate crystal arrays with a pitch of 1 mm and 12 mm in height, digital silicon photomultipliers (DPC 3200-22, Philips Digital Photon Counting) (DPC) are used. The basic PET performance in terms of energy resolution, coincidence resolution time (CRT) and sensitivity as a function of the operating parameters, such as the operating temperature, the applied overvoltage, activity and configuration parameters of the DPCs, has been evaluated at system level. The measured energy resolution did not show a large dependency on the selected parameters and is in the range of 12.4%-12.9% for low activity, degrading to ∼13.6% at an activity of ∼100 MBq. The CRT strongly depends on the selected trigger scheme (trig) of the DPCs, and we measured approximately 260 ps, 440 ps, 550 ps and 1300 ps for trig 1-4, respectively. The trues sensitivity for a NEMA NU 4 mouse-sized scatter phantom with a 70 mm long tube of activity was dependent on the operating parameters and was determined to be 0.4%-1.4% at low activity. The random fraction stayed below 5% at activity up to 100 MBq and the scatter fraction was evaluated as ∼6% for an energy window of 411 keV-561 keV and ∼16% for 250 keV-625 keV. Furthermore, we performed imaging experiments using a mouse-sized hot-rod phantom and a large rabbit-sized phantom. In 2D slices of the reconstructed mouse-sized hot-rod phantom (∅ = 28 mm), the rods were distinguishable from each other down to a rod size of 0.8 mm. There was no benefit from the better CRT of trig 1 over trig 3, where in the larger rabbit-sized phantom (∅ = 114 mm) we were able to show a clear improvement in image quality using the time-of-flight information. The findings will allow system architects-aiming at a similar detector design using DPCs-to make predictions about the design requirements and the performance that can be expected.

PET performance and MRI compatibility evaluation of a digital, ToF-capable PET/MRI insert equipped with clinical scintillators.

We evaluate the MR compatibility of the Hyperion-II(D) positron emission tomography (PET) insert, which allows simultaneous operation in a clinical magnetic resonance imaging (MRI) scanner. In contrast to previous investigations, this work aims at the evaluation of a clinical crystal configuration. An imaging-capable demonstrator with an axial field-of-view of 32 mm and a crystal-to-crystal spacing of 217.6 mm was equipped with LYSO scintillators with a pitch of 4 mm which were read out in a one-to-one coupling scheme by sensor tiles composed of digital silicon photomultipliers from Philips Digital Photon Counting (DPC 3200-22). The PET performance degradation (energy resolution and coincidence resolution time (CRT)) was evaluated during simultaneous operation of the MRI scanner. We used clinically motivated imaging sequences as well as synthetic gradient stress test sequences. Without activity of the MRI scanner, we measured for trigger scheme 1 (first photon trigger) an energy resolution of 11.4% and a CRT of 213 ps for a narrow energy (NE) window using five (22)Na point-like sources. When applying the synthetic gradient sequences, we found worst-case relative degradations of the energy resolution by 5.1% and of the CRT by 33.9%. After identifying the origin of the degradations and implementing a fix to the read-out hardware, the same evaluation revealed no degradation of the PET performance anymore even when the most demanding gradient stress tests were applied. The PET performance of the insert was initially evaluated using the point sources, a high-activity phantom and hot-rod phantoms in order to assess the spatial resolution. Trigger schemes 2-4 delivered an energy resolution of 11.4% as well and CRTs of 279 ps, 333 ps and 557 ps for the NE window, respectively. An isocenter sensitivity of 0.41% using the NE window and 0.71% with a wide energy window was measured. Using a hot-rod phantom, a spatial resolution in the order of 2 mm was demonstrated and the benefit of time-of-flight PET was shown with a larger rabbit-sized phantom. In conclusion, the Hyperion architecture is an interesting platform for clinically driven hybrid PET/MRI systems.

A Digital Preclinical PET/MRI Insert and Initial Results.

Combining Positron Emission Tomography (PET) with Magnetic Resonance Imaging (MRI) results in a promising hybrid molecular imaging modality as it unifies the high sensitivity of PET for molecular and cellular processes with the functional and anatomical information from MRI. Digital Silicon Photomultipliers (dSiPMs) are the digital evolution in scintillation light detector technology and promise high PET SNR. DSiPMs from Philips Digital Photon Counting (PDPC) were used to develop a preclinical PET/RF gantry with 1-mm scintillation crystal pitch as an insert for clinical MRI scanners. With three exchangeable RF coils, the hybrid field of view has a maximum size of 160 mm × 96.6 mm (transaxial × axial). 0.1 ppm volume-root-mean-square B 0-homogeneity is kept within a spherical diameter of 96 mm (automatic volume shimming). Depending on the coil, MRI SNR is decreased by 13% or 5% by the PET system. PET count rates, energy resolution of 12.6% FWHM, and spatial resolution of 0.73 mm (3) (isometric volume resolution at isocenter) are not affected by applied MRI sequences. PET time resolution of 565 ps (FWHM) degraded by 6 ps during an EPI sequence. Timing-optimized settings yielded 260 ps time resolution. PET and MR images of a hot-rod phantom show no visible differences when the other modality was in operation and both resolve 0.8-mm rods. Versatility of the insert is shown by successfully combining multi-nuclei MRI ((1)H/(19)F) with simultaneously measured PET ((18)F-FDG). A longitudinal study of a tumor-bearing mouse verifies the operability, stability, and in vivo capabilities of the system. Cardiac- and respiratory-gated PET/MRI motion-capturing (CINE) images of the mouse heart demonstrate the advantage of simultaneous acquisition for temporal and spatial image registration.

USPIO-labeled textile materials for non-invasive MR imaging of tissue-engineered vascular grafts.

Non-invasive imaging might assist in the clinical translation of tissue-engineered vascular grafts (TEVG). It can e.g. be used to facilitate the implantation of TEVG, to longitudinally monitor their localization and function, and to provide non-invasive and quantitative feedback on their remodeling and resorption. We here incorporated ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles into polyvinylidene fluoride (PVDF)-based textile fibers, and used them to prepare imageable tissue-engineered vascular grafts (iTEVG). The USPIO-labeled scaffold materials were molded with a mixture of fibrin, fibroblasts and smooth muscle cells, and then endothelialized in a bioreactor under physiological flow conditions. The resulting grafts could be sensitively detected using T1-, T2- and T2*-weighted MRI, both during bioreactor cultivation and upon surgical implantation into sheep, in which they were used as an arteriovenous shunt between the carotid artery and the jugular vein. In vivo, the iTEVG were shown to be biocompatible and functional. Post-mortem ex vivo analyses provided evidence for efficient endothelialization and for endogenous neo-vascularization within the biohybrid vessel wall. These findings show that labeling polymer-based textile materials with MR contrast agents is straightforward and safe, and they indicate that such theranostic tissue engineering approaches might be highly useful for improving the production, performance, personalization and translation of biohybrid vascular grafts.

PET/MRI insert using digital SiPMs: Investigation of MR-compatibility.

In this work, we present an initial MR-compatibility study performed with the world's first preclinical PET/MR insert based on fully digital silicon photo multipliers (dSiPM). The PET insert allows simultaneous data acquisition of both imaging modalities and thus enables the true potential of hybrid PET/MRI. Since the PET insert has the potential to interfere with all of the MRI's subsystems (strong magnet, gradients system, radio frequency (RF) system) and vice versa, interference studies on both imaging systems are of great importance to ensure an undisturbed operation. As a starting point to understand the interference, we performed signal-to-noise ratio (SNR) measurements as well as dedicated noise scans on the MRI side to characterize the influence of the PET electronics on the MR receive chain. Furthermore, improvements of sub-components' shielding of the PET system are implemented and tested inside the MRI. To study the influence of the MRI on the PET performance, we conducted highly demanding stress tests with gradient and RF dominated MR sequences. These stress tests unveil a sensitivity of the PET's electronics to gradient switching.

MR compatibility aspects of a silicon photomultiplier-based PET/RF insert with integrated digitisation.

The combination of Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) into a single device is being considered a promising tool for molecular imaging as it combines the high sensitivity of PET with the functional and anatomical images of MRI. For highest performance, a scalable, MR compatible detector architecture with a small form factor is needed, targeting at excellent PET signal-to-noise ratios and time-of-flight information. Therefore it is desirable to use silicon photo multipliers and to digitize their signals directly in the detector modules inside the MRI bore. A preclinical PET/RF insert for clinical MRI scanner was built to demonstrate a new architecture and to study the interactions between the two modalities.The disturbance of the MRI's static magnetic field stays below 2 ppm peak-to-peak within a diameter of 56 mm (90 mm using standard automatic volume shimming). MRI SNR is decreased by 14%, RF artefacts (dotted lines) are only visible in sequences with very low SNR. Ghosting artefacts are visible to the eye in about 26% of the EPI images, severe ghosting only in 7.6%. Eddy-current related heating effects during long EPI sequences are noticeable but with low influence of 2% on the coincidences count rate. The time resolution of 2.5 ns, the energy resolution of 29.7% and the volumetric spatial resolution of 1.8 mm(3) in the PET isocentre stay unaffected during MRI operation. Phantom studies show no signs of other artefacts or distortion in both modalities. A living rat was simultaneously imaged after the injection with (18)F-Fluorodeoxyglucose (FDG) proving the in vivo capabilities of the system.