Simulation study on the performance of time-over-threshold based positioning in monolithic PET detectors.

The vast majority of PET detectors in the field today are based on pixelated scintillators. Yet, the resolution of this type of detector is limited by the pixel size. To overcome this limitation, one can use monolithic detectors. However, this detector architecture demands specific and high-speed detector readout of the photodetector array. A commonly used approach is to integrate the current pulses generated by every pixel but such circuitry quickly becomes bulky, power consuming and expensive. The objective of this work is to investigate a novel readout and event positioning scheme for monolithic PET detectors, based on time-over-threshold (ToT). In this case, we measure the time that the pulse is above a certain threshold through a comparator. The pulse widths are used for event positioning using a mean nearest neighbour approach (mNNToT). For energy determination one integrating multiplexed channel is foreseen. We evaluate the positioning accuracy and uniformity of such a ToT detector by means of Monte Carlo simulations. The impact of the threshold value is investigated and the results are compared to a detector using mean nearest neighbour with pulse-integration (mNNint), which has already proven to allow sub-mm resolution. We show minimal degradation in spatial resolution and bias performance compared to mNNint. The highest threshold results in the worst resolution performance but degradation remains below 0.1 mm. Bias is largely constant over different thresholds for mNNToTand close to identical to mNNint. Furthermore we show that ToT performs well in terms of detector uniformity and that scattered photons can be positioned inside the crystal with high accuracy. We conclude from this work that ToT is a valuable alternative to pulse-integration for monolithic PET detectors. This novel approach has an impact on PET detector development since it has the advantage of lower power consumption, compactness and inherent amplitude-to-time conversion.

Species-dependent extracranial manifestations of a brain seeking breast cancer cell line.

PURPOSE: Metastatic brain tumors pose a severe problem in the treatment of patients with breast carcinoma. Preclinical models have been shown to play an important role in unraveling the underlying mechanisms behind the metastatic process and evaluation of new therapeutic approaches. As the size of the rat brain allows improved in vivo imaging, we attempted to establish a rat model for breast cancer brain metastasis that allows follow-up by 7 tesla (7T) preclinical Magnetic Resonance Imaging (MRI). PROCEDURES: Green fluorescent protein-transduced (eGFP) MDA-MB-231br breast cancer cells were labeled with micron-sized particles of iron oxide (MPIOs) and intracardially injected in the left ventricle of female nude rats and mice. 7T preclinical MRI was performed to show the initial distribution of MPIO-labeled cancer cells and to visualize metastasis in the brain. Occurrence of potential metastasis outside the brain was evaluated by 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET)/computed tomography (CT) and potential bone lesions were assessed using [18F]sodium fluoride ([18F]NaF) PET/CT. RESULTS: The first signs of brain metastasis development were visible as hyperintensities on T2-weighted (T2w) MR images acquired 3 weeks after intracardiac injection in rats and mice. Early formation of unexpected bone metastasis in rats was clinically observed and assessed using PET/CT. Almost no bone metastasis development was observed in mice after PET/CT evaluation. CONCLUSIONS: Our results suggest that the metastatic propensity of the MDA-MB-231br/eGFP cancer cell line outside the brain is species-dependent. Because of early and abundant formation of bone metastasis with the MDA-MB-231br/eGFP cancer cell line, this rat model is currently not suitable for investigating brain metastasis as a single disease model nor for evaluation of novel brain metastasis treatment strategies.

Performance evaluation of the MOLECUBES ß-CUBE-a high spatial resolution and high sensitivity small animal PET scanner utilizing monolithic LYSO scintillation detectors.

The MOLECUBES ß-CUBE scanner is the newest amongst commercially available preclinical PET scanners for dedicated small animal imaging. The scanner is compact, lightweight and utilizes a small footprint to facilitate bench-top imaging. It can be used individually, or in combination with the X-CUBE CT scanner, which provides the ability to perform all necessary PET data corrections and provide fully quantitative PET images. The PET detector comprises of an 8 mm thick monolithic LYSO scintillator read-out by an array of 3 mm × 3 mm Hamamatsu silicon photomultipliers. The monolithic scintillator provides the ability to measure depth-of-interaction which aids in the development of such a compact scanner. With a scanner diameter of 7.6 cm and axial length of 13 cm it is suitable for imaging both whole-body mice and rats. This paper presents the design and imaging performance of the ß-CUBE scanner. NEMA NU4-2008 characterization and a variety of phantom and animal imaging studies to demonstrate the quantitative imaging performance of the PET scanner are presented. Spatial resolution of 1 mm is measured with a filtered-back projection reconstruction algorithm at the center of the scanner and DOI measurement helps maintain the excellent spatial resolution over the entire imaging FOV. An absolute peak sensitivity of 12.4% is measured with a 255-765 keV energy window. The scanner demonstrates good count-rate performance, with a peak NEC of 300 kcps and 160 kcps measured with ~900 µCi in the NEMA mouse and rat phantoms, respectively. Imaging data with the NEMA image quality phantom and Micro Derenzo phantoms demonstrate the ability to achieve good image quality and accurate quantitative data. Image uniformity of 7.4% and spill-over ratio of 8% were measured. The superior spatial resolution, excellent energy resolution and sensitivity also provide superior contrast recovery, with ~70% recovery for the 2 mm rods. While current commercial preclinical PET scanners have spatial resolution in the 1-2 mm range, the 1 mm3 volumetric resolution presents significant improvement over current commercially available preclinical PET scanners. In combination with the X-CUBE scanner it provides the ability to perform fully quantitative imaging with spatially co-registered high-resolution 3D PET-CT images.

Optimization of an ultralow-dose high-resolution pediatric PET scanner design based on monolithic scintillators with dual-sided digital SiPM readout: a simulation study.

The goal of this simulation study is the performance evaluation and comparison of six potential designs for a time-of-flight PET scanner for pediatric patients of up to about 12 years of age. It is designed to have a high sensitivity and provide high-contrast and high-resolution images. The simulated pediatric PET is a full ring scanner, consisting of 32 × 32 mm2 monolithic LYSO:Ce crystals coupled to digital silicon photomultiplier arrays. The six considered designs differ in axial lengths (27.2 cm, 54.4 cm and 102 cm) and crystal thicknesses (22 mm and 11 mm). The simulations are based on measured detector response data. We study two possible detector arrangements: 22 mm-thick crystals with dual-sided readout and 11 mm-thick crystals with back-sided readout. The six designs are simulated by means of the GEANT4 application for tomographic emission software, using the measured spatial, energy and time response of the monolithic scintillator detectors as input. The performance of the six designs is compared on the basis of four studies: (1) spatial resolution; (2) NEMA NU2-2012 sensitivity and scatter fraction (SF) tests; (3) non-prewhitening signal-to-noise ratio observer study; and (4) receiver operating characteristics analysis. Based on the results, two designs are identified as cost-effective solutions for fast and efficient imaging of children: one with 54.4 cm axial field-of-view (FOV) and 22 mm-thick crystals, and another one with 102 cm axial FOV and 11 cm-thick crystals. The first one has a higher center point sensitivity than the second one, but requires dual-sided readout. The second design has the advantage of allowing a whole-body scan in a single bed position acquisition. Both designs have the potential to provide an excellent spatial resolution (∼2 mm) and an ultra-high sensitivity (>100 cps [Formula: see text]).

Sub-millimetre DOI detector based on monolithic LYSO and digital SiPM for a dedicated small-animal PET system.

The mouse model is widely used in a vast range of biomedical and preclinical studies. Thanks to the ability to detect and quantify biological processes at the molecular level in vivo, PET has become a well-established tool in these investigations. However, the need to visualize and quantify radiopharmaceuticals in anatomic structures of millimetre or less requires good spatial resolution and sensitivity from small-animal PET imaging systems.In previous work we have presented a proof-of-concept of a dedicated high-resolution small-animal PET scanner based on thin monolithic scintillator crystals and Digital Photon Counter photosensor. The combination of thin monolithic crystals and MLE positioning algorithm resulted in an excellent spatial resolution of 0.7 mm uniform in the entire field of view (FOV). However, the limitation of the scanner was its low sensitivity due to small thickness of the lutetium-yttrium oxyorthosilicate (LYSO) crystals (2 mm).Here we present an improved detector design for a small-animal PET system that simultaneously achieves higher sensitivity and sustains a sub-millimetre spatial resolution. The proposed detector consists of a 5 mm thick monolithic LYSO crystal optically coupled to a Digital Photon Counter. Mean nearest neighbour (MNN) positioning combined with depth of interaction (DOI) decoding was employed to achieve sub-millimetre spatial resolution. To evaluate detector performance the intrinsic spatial resolution, energy resolution and coincidence resolving time (CRT) were measured. The average intrinsic spatial resolution of the detector was 0.60 mm full-width-at-half-maximum (FWHM). A DOI resolution of 1.66 mm was achieved. The energy resolution was 23% FWHM at 511 keV and CRT of 529 ps were measured. The improved detector design overcomes the sensitivity limitation of the previous design by increasing the nominal sensitivity of the detector block and retains an excellent intrinsic spatial resolution.

Improvement of attenuation correction in time-of-flight PET/MR imaging with a positron-emitting source.

UNLABELLED: Quantitative PET imaging relies on accurate attenuation correction. Recently, there has been growing interest in combining state-of-the-art PET systems with MR imaging in a sequential or fully integrated setup. As CT becomes unavailable for these systems, an alternative approach to the CT-based reconstruction of attenuation coefficients (µ values) at 511 keV must be found. Deriving µ values directly from MR images is difficult because MR signals are related to the proton density and relaxation properties of tissue. Therefore, most research groups focus on segmentation or atlas registration techniques. Although studies have shown that these methods provide viable solutions in particular applications, some major drawbacks limit their use in whole-body PET/MR. Previously, we used an annulus-shaped PET transmission source inside the field of view of a PET scanner to measure attenuation coefficients at 511 keV. In this work, we describe the use of this method in studies of patients with the sequential time-of-flight (TOF) PET/MR scanner installed at the Icahn School of Medicine at Mount Sinai, New York, NY. METHODS: Five human PET/MR and CT datasets were acquired. The transmission-based attenuation correction method was compared with conventional CT-based attenuation correction and the 3-segment, MR-based attenuation correction available on the TOF PET/MR imaging scanner. RESULTS: The transmission-based method overcame most problems related to the MR-based technique, such as truncation artifacts of the arms, segmentation artifacts in the lungs, and imaging of cortical bone. Additionally, the TOF capabilities of the PET detectors allowed the simultaneous acquisition of transmission and emission data. Compared with the MR-based approach, the transmission-based method provided average improvements in PET quantification of 6.4%, 2.4%, and 18.7% in volumes of interest inside the lung, soft tissue, and bone tissue, respectively. CONCLUSION: In conclusion, a transmission-based technique with an annulus-shaped transmission source will be more accurate than a conventional MR-based technique for measuring attenuation coefficients at 511 keV in future whole-body PET/MR studies.

Influence of detector pixel size, TOF resolution and DOI on image quality in MR-compatible whole-body PET.

The optimization of a whole-body PET system remains a challenging task, as the imaging performance is influenced by a complex interaction of different design parameters. However, it is not always clear which parameters have the largest impact on image quality and are most eligible for optimization. To determine this, we need to be able to assess their influence on image quality. We performed Monte-Carlo simulations of a whole-body PET scanner to predict the influence on image quality of three detector parameters: the TOF resolution, the transverse pixel size and depth-of-interaction (DOI)-correction. The inner diameter of the PET scanner was 65 cm, small enough to allow physical integration into a simultaneous PET-MR system. Point sources were used to evaluate the influence of transverse pixel size and DOI-correction on spatial resolution as function of radial distance. To evaluate the influence on contrast recovery and pixel noise a cylindrical phantom of 35 cm diameter was used, representing a large patient. The phantom contained multiple hot lesions with 5 mm diameter. These lesions were placed at radial distances of 50, 100 and 150 mm from the center of the field-of-view, to be able to study the effects at different radial positions. The non-prewhitening (NPW) observer was used for objective analysis of the detectability of the hot lesions in the cylindrical phantom. Based on this analysis the NPW-SNR was used to quantify the relative improvements in image quality due to changes of the variable detector parameters. The image quality of a whole-body PET scanner can be improved significantly by reducing the transverse pixel size from 4 to 2.6 mm and improving the TOF resolution from 600 to 400 ps and further from 400 to 200 ps. Compared to pixel size, the TOF resolution has the larger potential to increase image quality for the simulated phantom. The introduction of two layer DOI-correction only leads to a modest improvement for the spheres at radial distance of 150 mm from the center of the transaxial FOV.

Challenges and current methods for attenuation correction in PET/MR.

Quantitative PET imaging requires an attenuation map to correct for attenuation. In stand-alone PET or PET/CT, the attenuation map is usually derived from a transmission scan or CT image, respectively. In PET/MR, these methods will most likely not be used. Therefore, attenuation correction has long been regarded as one of the major challenges in the development of PET/MR. In the past few years, much progress has been made in this field. In this review, the challenges faced in attenuation correction for PET/MR are discussed. Different methods have been proposed to overcome these challenges. An overview of the MR-based (template-based and voxel-based), transmission-based and emission-based methods and the results that have been obtained is provided. Although several methods show promising results, no single method fulfils all of the requirements for the ideal attenuation correction method for PET/MR. Therefore, more work is still necessary in this field. To allow implementation in routine clinical practice, extensive evaluation of the proposed methods is necessary to demonstrate robustness and automation.

Simultaneous MR-compatible emission and transmission imaging for PET using time-of-flight information.

Quantitative positron emission tomography (PET) imaging relies on accurate attenuation correction. Predicting attenuation values from magnetic resonance (MR) images is difficult because MR signals are related to proton density and relaxation properties of tissues. Here, we propose a method to derive the attenuation map from a transmission scan. An annulus transmission source is positioned inside the field-of-view of the PET scanner. First a blank scan is acquired. The patient is injected with FDG and placed inside the scanner. 511-keV photons coming from the patient and the transmission source are acquired simultaneously. Time-of-flight information is used to extract the coincident photons originating from the annulus. The blank and transmission data are compared in an iterative reconstruction method to derive the attenuation map. Simulations with a digital phantom were performed to validate the method. The reconstructed attenuation coefficients differ less than 5% in volumes of interest inside the lungs, bone, and soft tissue. When applying attenuation correction in the reconstruction of the emission data a standardized uptake value error smaller than 9% was obtained for all tissues. In conclusion, our method can reconstruct the attenuation map and the emission data from a simultaneous scan without prior knowledge about the anatomy or the attenuation coefficients of the tissues.

The effect of errors in segmented attenuation maps on PET quantification.

PURPOSE: Accurate attenuation correction is important for PET quantification. Often, a segmented attenuation map is used, especially in MRI-based attenuation correction. As deriving the attenuation map from MRI images is difficult, different errors can be present in the segmented attenuation map. The goal of this paper is to determine the effect of these errors on quantification. METHODS: The authors simulated the digital XCAT phantom using the GATE Monte Carlo simulation framework and a model of the Philips Gemini TF. A whole body scan was simulated, spanning an axial field of view of 70 cm. A total of fifteen lesions were placed in the lung, liver, spine, colon, prostate, and femur. The acquired data were reconstructed with a reference attenuation map and with different attenuation maps that were modified to reflect common segmentation errors. The quantitative difference between reconstructed images was evaluated. RESULTS: Segmentation into five tissue classes, namely cortical bone, spongeous bone, soft tissue, lung, and air yielded errors below 5%. Large errors were caused by ignoring lung tissue (up to 45%) or cortical bone (up to 17%). The interpatient variability of lung attenuation coefficients can lead to errors of 10% and more. Up to 20% tissue misclassification from bone to soft tissue yielded errors below 5%. The same applies for up to 10% misclassification from lung to air. CONCLUSIONS: When using a segmented attenuation map, at least five different tissue types should be considered: cortical bone, spongeous bone, soft tissue, lung, and air. Furthermore, the interpatient variability of lung attenuation coefficients should be taken into account. Limited misclassification from bone to soft tissue and from lung to air is acceptable, as these do not lead to relevant errors.