Pieter Mollet

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.

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.

Fast generation of 4D PET-MR data from real dynamic MR acquisitions

We have implemented and evaluated a framework for simulating simultaneous dynamic PET-MR data using the anatomic and dynamic information from real MR acquisitions. PET radiotracer distribution is simulated by assigning typical FDG uptake values to segmented MR images with manually inserted additional virtual lesions. PET projection data and images are simulated using analytic forward projections (including attenuation and Poisson statistics) implemented within the image reconstruction package STIR. PET image reconstructions are also performed with STIR. The simulation is validated with numerical simulation based on Monte Carlo (GATE) which uses more accurate physical modelling, but has 150× slower computation time compared to the analytic method for ten respiratory positions and is 7000× slower when performing multiple realizations. Results are validated in terms of region of interest mean values and coefficients of variation for 65 million coincidences including scattered events. Although some discrepancy is observed, agreement between the two different simulation methods is good given the statistical noise in the data. In particular, the percentage difference of the mean values is 3.1% for tissue, 17% for the lungs and 18% for a small lesion. The utility of the procedure is demonstrated by simulating realistic PET-MR datasets from multiple volunteers with different breathing patterns. The usefulness of the toolkit will be shown for performance investigations of the reconstruction, motion correction and attenuation correction algorithms for dynamic PET-MR data.

Recent developments in time-of-flight PET

While the first time-of-flight (TOF)-positron emission tomography (PET) systems were already built in the early 1980s, limited clinical studies were acquired on these scanners. PET was still a research tool, and the available TOF-PET systems were experimental. Due to a combination of low stopping power and limited spatial resolution (caused by limited light output of the scintillators), these systems could not compete with bismuth germanate (BGO)-based PET scanners. Developments on TOF system were limited for about a decade but started again around 2000. The combination of fast photomultipliers, scintillators with high density, modern electronics, and faster computing power for image reconstruction have made it possible to introduce this principle in clinical TOF-PET systems. This paper reviews recent developments in system design, image reconstruction, corrections, and the potential in new applications for TOF-PET. After explaining the basic principles of time-of-flight, the difficulties in detector technology and electronics to obtain a good and stable timing resolution are shortly explained. The available clinical systems and prototypes under development are described in detail. The development of this type of PET scanner also requires modified image reconstruction with accurate modeling and correction methods. The additional dimension introduced by the time difference motivates a shift from sinogram- to listmode-based reconstruction. This reconstruction is however rather slow and therefore rebinning techniques specific for TOF data have been proposed. The main motivation for TOF-PET remains the large potential for image quality improvement and more accurate quantification for a given number of counts. The gain is related to the ratio of object size and spatial extent of the TOF kernel and is therefore particularly relevant for heavy patients, where image quality degrades significantly due to increased attenuation (low counts) and high scatter fractions. The original calculations for the gain were based on analytical methods. Recent publications for iterative reconstruction have shown that it is difficult to quantify TOF gain into one factor. The gain depends on the measured distribution, the location within the object, and the count rate. In a clinical situation, the gain can be used to either increase the standardized uptake value (SUV) or reduce the image acquisition time or administered dose. The localized nature of the TOF kernel makes it possible to utilize local tomography reconstruction or to separate emission from transmission data. The introduction of TOF also improves the joint estimation of transmission and emission images from emission data only. TOF is also interesting for new applications of PET-like isotopes with low branching ratio for positron fraction. The local nature also reduces the need for fine angular sampling, which makes TOF interesting for limited angle situations like breast PET and online dose imaging in proton or hadron therapy. The aim of this review is to introduce the reader in an educational way into the topic of TOF-PET and to give an overview of the benefits and new opportunities in using this additional information.

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.

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

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.

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.

Experimental evaluation of simultaneous emission and transmission imaging using TOF information

Attenuation correction is one of the major challenges in the development of PET-MR scanners. Predicting attenuation values from MR images is difficult because MR signals are not related to electron densities and in most MRI sequences, air, bone and lung do not produce any signal, while their attenuation coefficients are completely different. Here we investigate a method to obtain the necessary transmission data simultaneously with the emission data in a existing Time-Of-Flight PET system. An annulus shaped transmission source filled with 18F-FDG is placed inside the FOV of a TOF-PET scanner. A blank PET scan is acquired followed by an acquisition of a phantom containing 18F-FDG. During the second acquisition, photons originating from the transmission source as well as from the phantom are detected. TOF information is used to separate the transmission data from the annulus source and the emission data from the phantom. An iterative gradient descent method is then applied to the transmission data to reconstruct an attenuation map yielding attenuation coefficients at 511 keV. The method was validated with phantom studies on the Gemini TF PET scanner using an anthropomorphic torso phantom and a cylindrical phantom containing bone, lung, water and two hot spheres. The torso phantom contained no activity. Data were corrected for randoms during reconstruction using a delayed window method. A method is presented to derive a global count rate correction factor. No scatter correction was implemented. The reconstructed attenuation maps of both phantom studies show good contrast between different tissues. An underestimation of attenuation coefficients is noticed caused by scattered events. The emission data acquired during the cylindrical phantom study were reconstructed and corrected using the transmission-based attenuation map. A Contrast Recovery Coefficient of 62% and 73% was obtained for the two hot spheres respectively. This work shows how an attenuation map can be reconstructed from a simultaneous transmission/emission scan. In order to obtain accurate attenuation coefficients, corrections for random coincidences, count rate and scatter are needed. The reconstructions presented in this work were only corrected for randoms and the count rate performance mismatch between the blank and transmission scan.

Design of a realistic PET-CT-MRI phantom

The validation of the PET image quality of new PET-MRI systems should be done against the image quality of currently available PET-CT systems. This includes the validation of new attenuation correction methods. Such validation studies should preferentially be done using a phantom. There are currently no phantoms that have a realistic appearance on PET, CT and MRI. In this work we present the design and evaluation of such a phantom.

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]).