David Schug

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

In this work, we present an initial MR-compatibility study performed with the worlds 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 MRIs 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 PETs electronics to gradient switching.

MR-compatibility assessment of the first preclinical PET-MRI insert equipped with digital silicon photomultipliers

PET (positron emission tomography) with its high sensitivity in combination with MRI (magnetic resonance imaging) providing anatomic information with good soft-tissue contrast is considered to be a promising hybrid imaging modality. However, the integration of a PET detector into an MRI system is a challenging task since the MRI system is a sensitive device for external disturbances and provides a harsh environment for electronic devices. Consequently, the PET detector has to be transparent for the MRI system and insensitive to electromagnetic disturbances. Due to the variety of MRI protocols imposing a wide range of requirements regarding the MR-compatibility, an extensive study is mandatory to reliably assess worst-case interference phenomena between the PET detector and the MRI scanner. We have built the first preclinical PET insert, designed for a clinical 3 T MRI, using digital silicon photomultipliers (digital SiPM, type DPC 3200-22, Philips Digital Photon Counting). Since no thorough interference investigation with this new digital sensor has been reported so far, we present in this work such a comprehensive MR-compatibility study. Acceptable distortion of the B0 field homogeneity (volume RMS = 0.08 ppm, peak-to-peak value = 0.71 ppm) has been found for the PET detector installed. The signal-to-noise ratio degradation stays between 2-15% for activities up to 21 MBq. Ghosting artifacts were only found for demanding EPI (echo planar imaging) sequences with read-out gradients in Z direction caused by additional eddy currents originated from the PET detector. On the PET side, interference mainly between the gradient system and the PET detector occurred: extreme gradient tests were executed using synthetic sequences with triangular pulse shape and maximum slew rate. Under this condition, a relative degradation of the energy (⩽10%) and timing (⩽15%) resolution was noticed. However, barely measurable performance deterioration occurred when morphological MRI protocols are conducted certifying that the overall PET performance parameters remain unharmed.

Development of an MRI compatible digital SiPM based PET detector stack for simultaneous preclinical PET/MRI

We developed the worlds first MRI compatible PET detector based on digital silicon photomultiplier technology (digital SiPM). In this work we present our stack design and initial measurement results. The design of the detector stack considers all aspects of MRI compatibility and allows for the first time to operate digital SiPMs inside an MRI. The detector stack is composed of two layers. The top layer contains an 8 x 8 channel digital SiPM array with 4 mm pitch. The bottom layer hosts an FPGA for data acquisition and configuration as well as a circuit to control and monitor the bias voltage. We tested the detector stack in combination with an L YSO scintillator array containing 30 × 30 crystals with a pitch of 1 mm and 12 mm length. We build up highly integrated detector modules and tested the detector stack in a clinical 3 Tesla Philips Achieva MRI system. Our measurements indicate that the performance of the digital SiPM is unaffected by the MRI system even under extreme conditions. The presented detector stack is used to build up the Hyperion IID preclinical simultaneous PET/MRI insert for rodent studies within MEC and ForSaTum project.

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.

Data Processing for a High Resolution Preclinical PET Detector Based on Philips DPC Digital SiPMs

In positron emission tomography (PET) systems, light sharing techniques are commonly used to readout scintillator arrays consisting of scintillation elements, which are smaller than the optical sensors. The scintillating element is then identified evaluating the signal heights in the readout channels using statistical algorithms, the center of gravity (COG) algorithm being the simplest and mostly used one. We propose a COG algorithm with a fixed number of input channels in order to guarantee a stable calculation of the position. The algorithm is implemented and tested with the raw detector data obtained with the Hyperion-II D preclinical PET insert which uses Philips Digital Photon Countings (PDPC) digitial SiPMs. The gamma detectors use LYSO scintillator arrays with 30 ×30 crystals of 1 ×1 ×12 mm3 in size coupled to 4 ×4 PDPC DPC 3200-22 sensors (DPC) via a 2-mm-thick light guide. These self-triggering sensors are made up of 2 ×2 pixels resulting in a total of 64 readout channels. We restrict the COG calculation to a main pixel, which captures most of the scintillation light from a crystal, and its (direct and diagonal) neighboring pixels and reject single events in which this data is not fully available. This results in stable COG positions for a crystal element and enables high spatial image resolution. Due to the sensor layout, for some crystals it is very likely that a single diagonal neighbor pixel is missing as a result of the low light level on the corresponding DPC. This leads to a loss of sensitivity, if these events are rejected. An enhancement of the COG algorithm is proposed which handles the potentially missing pixel separately both for the crystal identification and the energy calculation. Using this advancement, we show that the sensitivity of the Hyperion-II D insert using the described scintillator configuration can be improved by 20-100% for practical useful readout thresholds of a single DPC pixel ranging from 17-52 photons. Furthermore, we show that the energy resolution of the scanner is superior for all readout thresholds if singles with a single missing pixel are accepted and correctly handled compared to the COG method only accepting singles with all neighbors present by 0-1.6% (relative difference). The presented methods can not only be applied to gamma detectors employing DPC sensors, but can be generalized to other similarly structured and self-triggering detectors, using light sharing techniques, as well.

First evaluations of the neighbor logic of the digital SiPM tile

For a high resolution PET/MRI insert, we are using pixelated scintillator arrays with 1 mm pitch in combination with digital SiPM arrays. The pitch of the digital SiPM arrays is 4 mm. Therefore, a light-sharing technique is used to identify individual crystals. Information from several sensors, a cluster, is needed to identify the crystal in which a gamma photon has been converted to scintillation photons. We present first evaluations of the neighbor logic (NL) of the PDPe DLS 3200-22 dSiPM. The NL allows the use of strict trigger validation criteria while delivering the complete light distribution on the sensor tile. Measurements are performed at ~10°C sensor temperature. We compare the measurement with enabled NL to a standard triggering scheme which needs to use low trigger validation thresholds in order to achieve the same performance. Positioning of clusters is performed using a center-of-gravity algorithm. We show that the NL trigger scheme allows to achieve a better energy resolution and improved crystal identification. Furthermore, we show that the NL allows to recover more clusters containing light distributions with less missing relevant information while reducing the noise level in the data by more than one order of magnitude.

Longitudinal imaging of the ageing mouse.

Several non-invasive imaging techniques are used to investigate the effect of pathologies and treatments over time in mouse models. Each preclinical in vivo technique provides longitudinal and quantitative measurements of changes in tissues and organs, which are fundamental for the evaluation of alterations in phenotype due to pathologies, interventions and treatments. However, it is still unclear how these imaging modalities can be used to study ageing with mice models. Almost all age related pathologies in mice such as osteoporosis, arthritis, diabetes, cancer, thrombi, dementia, to name a few, can be imaged in vivo by at least one longitudinal imaging modality. These measurements are the basis for quantification of treatment effects in the development phase of a novel treatment prior to its clinical testing. Furthermore, the non-invasive nature of such investigations allows the assessment of different tissue and organ phenotypes in the same animal and over time, providing the opportunity to study the dysfunction of multiple tissues associated with the ageing process. This review paper aims to provide an overview of the applications of the most commonly used in vivo imaging modalities used in mouse studies: micro-computed-tomography, preclinical magnetic-resonance-imaging, preclinical positron-emission-tomography, preclinical single photon emission computed tomography, ultrasound, intravital microscopy, and whole body optical imaging.

Initial PET Performance Evaluation of a Preclinical Insert for PET/MRI with Digital SiPM Technology

Abstract Hyperion-IID 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.

ToF Performance Evaluation of PET Modules With Digital Silicon Photomultiplier Technology During MR Operation

In 2012, we presented the Hyperion-II D preclinical PET insert which uses Philips Digital Photon Countings digital SiPMs and is designed to be operated in a 3-T MRI. In this work we use the same platform equipped with scintillators having dimensions closer to a clinical application. This allows an investigation of the time of flight (ToF) performance of the platform and its behavior during simultaneous MR operation. We employ LYSO crystal arrays of 4×4 ×10 mm3 coupled to 4 ×4 PDPC DPC 3200-22 sensors (DPC) resulting in a one-to-one coupling of crystals to read-out channels. Six sensor stacks are mounted onto a singles processing unit in a 2 ×3 arrangement. Two modules are mounted horizontally facing each other on a gantry with a crystal-to-crystal spacing of 217.6 mm (gantry position). A second arrangement places the modules at the maximum distance of approximately 410 mm inside the MR bore (maximum distance position) which brings each module close to the gradient system. The DPCs are cooled down to approximately 5-10° C under operation. We disable 20% of the worst cells and use an overvoltage of Vov = 2.0 V and 2.5 V. To obtain the best time stamps, we use the trigger scheme 1 (first photon trigger), a narrow energy window of 511 ±50 keV and a minimum required light fraction of the main pixel of more than 65% to reject intercrystal scatter. By using a 22Na point source in the isocenter of the modules, the coincidence resolution time (CRT) of the two modules is evaluated inside the MRI system without MR activity and while using highly demanding gradient sequences. Inside the B0 field without any MR activity at an overvoltage of Vov = 2.0 V, the energy resolution is 11.45% (FWHM) and the CRT is 250 ps (FWHM). At an overvoltage of Vov = 2.5 V, the energy resolution is 11.15% (FWHM) and the CRT is 240 ps (FWHM). During a heavy z-gradient sequence (EPI factor: 49, gradient strength: 30 mT/m, slew rate: 192.3 mT/m/ms, TE/TR: 12/25 ms and switching duty cycle: 67%) at the gantry position and an overvoltage of Vov = 2.0 V, the energy resolution is degraded relatively by 4.1% and the CRT by 25%. Using the same sequence but at the maximum distance position and an overvoltage of Vov = 2.5 V, we measure a degradation of the energy resolution of 9.2% and a 52% degradation of the CRT. The Hyperion-IID platform proofs to deliver good timing performance and energy resolution inside the MRI system even under highly demanding gradient sequences.

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 leastsquares (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 [18F]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 LSand ML-based CPEEA. While the coincidence time resolution (~550 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.