First experimental results of time-of-flight reconstruction on an LSO PET scanner

Time-of-flight (TOF) positron emission tomography (PET) was studied and preliminarily developed in the 1980s, but the lack of a scintillator able to deliver at the same time proper time resolution and stopping power has prevented this technique from becoming widespread and commercially available. With the introduction of LSO in PET, TOF is now a feasible option. TOF reconstruction has been implemented in the CPS Hi-Rez PET scanner, both with 2D filtered-back-projection (FBP2D) and 3D ordered subset expectation maximization (OSEM3D). A new procedure has been introduced in the time alignment to compensate for the limited digital time resolution of the present electronics. A preliminary version of scatter correction for TOF has been devised and is presented. The measured time resolution of 1.2 ns (FWHM) allowed for a signal-to-noise ratio increase of about 50% in phantoms of about 40 cm transaxial size, or a gain larger than 2 in noise equivalent counts (NEC). TOF reconstruction has shown the expected improvement in SNR, both in simulation and experimental data. First experimental results show two improvements of TOF reconstruction over conventional (non-TOF) reconstruction: a lower noise level and a better capability to resolve structures deep inside large objects.     

Lutetium oxyorthosilicate (LSO) intrinsic activity correction and minimal detectable target activity study for SPECT imaging with a LSO-based animal PET scanner

This work is part of a feasibility study to develop SPECT imaging capability on a lutetium oxyorthosilicate (LSO) based animal PET system. The SPECT acquisition was enabled by inserting a collimator assembly inside the detector ring and acquiring data in singles mode. The same LSO detectors were used for both PET and SPECT imaging. The intrinsic radioactivity of (176)Lu in the LSO crystals, however, contaminates the SPECT data, and can generate image artifacts and introduce quantification error. The objectives of this study were to evaluate the effectiveness of a LSO background subtraction method, and to estimate the minimal detectable target activity (MDTA) of image object for SPECT imaging. For LSO background correction, the LSO contribution in an image study was estimated based on a pre-measured long LSO background scan and subtracted prior to the image reconstruction. The MDTA was estimated in two ways. The empirical MDTA (eMDTA) was estimated from screening the tomographic images at different activity levels. The calculated MDTA (cMDTA) was estimated from using a formula based on applying a modified Currie equation on an average projection dataset. Two simulated and two experimental phantoms with different object activity distributions and levels were used in this study. The results showed that LSO background adds concentric ring artifacts to the reconstructed image, and the simple subtraction method can effectively remove these artifacts-the effect of the correction was more visible when the object activity level was near or above the eMDTA. For the four phantoms studied, the cMDTA was consistently about five times of the corresponding eMDTA. In summary, we implemented a simple LSO background subtraction method and demonstrated its effectiveness. The projection-based calculation formula yielded MDTA results that closely correlate with that obtained empirically and may have predicative value for imaging applications.     

Progress in the development of a PET scanner based on BaF2 scintillator and photosensitive wire chambers.

The work presented is part of a design study for a Positron Emission Tomograph (PET) scanner based on the use of BaF2 scintillator and photosensitive wire chambers. The detection efficiency for gamma radiation of 511 keV is found close to 100% for a sufficiently large crystal. For a matrix of small and elongated crystals as one would use in a PET scanner (5 x 5 x 50 mm3) we obtained 6 photoelectrons per 511 keV deposited. The following variants and alternatives were also studied: operation of the wire chamber at atmospheric pressure; double readout where the crystals are read on one side with a photomultiplier to give time and energy resolution, and on the other side with a wire chamber to localise the event; and Csl photocathodes. Encouraging results have been obtained for each of these, but particularly the Csl photocathodes look very promising.     

Analytical study of performance in a 3D PET scanner.

The use of arrays of small discrete detectors and thin slices to achieve a high isotropic spatial resolution in positron emission tomography (PET) results in systems with a low ring sensitivity. In a multi-ring system, the overall sensitivity can be considerably improved by removing the interslice collimators to make full use of all cross slices coincidences, but this is achieved at the expense of increased scatter and accidental rates in the image. For imaging of small laboratory animals (diameter of 10 cm or less), the relieved burden of scatters, and to some extent accidentals, suggests that volumetric imaging may be of particular value. In order to evaluate the performance to be expected from a small animal PET scanner (10 cm diameter field) with and without the interplane collimators, the incident event rates for singles (unscattered and single scattered) and true, scatter and accidental coincidences were evaluated analytically. The performance was evaluated for various source sizes and activities in terms of five criteria: true/single ratio, scatter fraction, accidental fraction, image contrast and noise effective sensitivity. As a result of a 3-fold increase in scatter fraction and of a significant increase in accidental fraction for larger sources, the image contrast (true/(scatter+accidental)) is observed to always be inferior with the collimators removed. However, a significant improvement in noise effective sensitivity is obtained with the volumetric configuration, especially for small size sources placed at the centre of the field of view. It is concluded that the volumetric configuration is more advantageous than the multislice configuration to image small animals because the gain in sensitivity overcomes the loss of accuracy due to higher scatter and accidental rates.     

Design and evaluation of an LSO PET detector for breast cancer imaging

Functional imaging with positron emission tomography (PET) may be a promising technique in conjunction with x-ray mammography for breast cancer patient management. Conventional whole body PET scanners provide metabolic images of breast cancer patients with several shortcomings related to the general-purpose nature of these systems. In whole body scanners, the detectors are typically 20-30 cm away from the breast or axilla, reducing sensitivity, and these scanners have relatively large detector elements (> 4 mm), limiting spatial resolution. Dedicated PET systems for breast imaging aim to overcome these limitations and improve the overall diagnostic quality of the images by bringing the detectors closer to the area to be imaged, thereby improving sensitivity, and by using smaller detector elements to improve the spatial resolution. We have designed and developed a modular PET detector that is composed of a 9x9 array of 3x3x20 mm3 lutetium oxyorthosilicate (LSO) scintillator crystals coupled to an optical fiber taper, which in turn is coupled to a Hamamatsu R5900-C8 position-sensitive photomultiplier tube. These detectors can be tiled together without gaps to construct large area detector arrays to form a dedicated PET breast cancer imaging system. Two complete detector modules have been built and tested. All detector elements are clearly visualized upon flood irradiation of the module. The intrinsic spatial resolution (full-width at half-maximum) was measured to be 2.26 mm (range 1.8-2.6 mm). The average energy resolution was 19.5% (range 17%-24%) at 511 keV. The coincidence time resolution was measured to be 2.4 ns. The detector efficiency for 511 keV gamma rays was 53% using a 350 keV energy threshold. These promising results support the feasibility of developing a high resolution, high sensitivity dedicated PET scanner for breast cancer applications.     

A study of artefacts in simultaneous PET and MR imaging using a prototype MR compatible PET scanner.

We have assessed the possibility of artefacts that can arise in attempting to perform simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) using a small prototype MR compatible PET scanner (McPET). In these experiments, we examine MR images for any major artefacts or loss in image quality due to inhomogeneities in the magnetic field, radiofrequency interference or susceptibility effects caused by operation of the PET system inside the MR scanner. In addition, possible artefacts in the PET images caused by the static and time-varying magnetic fields or radiofrequency interference from the MR system were investigated. Biological tissue and a T2-weighted spin echo sequence were used to examine susceptibility artefacts due to components of the McPET scanner (scintillator, optical fibres) situated in the MR field of view. A range of commonly used MR pulse sequences was studied while acquiring PET data to look for possible artefacts in either the PET or MR images. Other than a small loss in signal-to-noise using gradient echo sequences, there was no significant interaction between the two imaging systems. Simultaneous PET and MR imaging of simple phantoms was also carried out in different MR systems with field strengths ranging from 0.2 to 4.7 T. The results of these studies demonstrate that it is possible to acquire PET and MR images simultaneously, without any significant artefacts or loss in image quality, using our prototype MR compatible PET scanner.     

Figures of merit for comparing reconstruction algorithms with a volume-imaging PET scanner

For volume-imaging PET scanners, no septa are used to maximize the sensitivity by collecting events oblique to the scanner axis. We answer two questions: (i) how does the performance of an image reconstruction algorithm for a volume-imaging PET scanner depend on its general dimensions? and (ii) at what point is a three-dimensional (3D) reconstruction algorithm needed for a volume-imaging scanner, as the axial extent is increased? A 3D reconstruction algorithm will accurately incorporate the oblique events in a reconstruction of the original source distribution. From simulations of an existing volume PET scanner with a maximum axial acceptance angle (+/-alpha) of alpha = 9 degrees, however, we show that the single-slice rebinning algorithm is a good compromise between sensitivity, speed, and accuracy when compared to standard two-dimensional reconstruction (alpha = 1 degrees), and a 3D reconstruction with alpha = 9 degrees. We also show with simulations that a new scanner with alpha = 27 degrees requires 3D reconstruction in order to achieve maximum sensitivity without unacceptable losses in accuracy. Measurements of scanner performance are based on a series of figures of merit that characterize image quality and quantitative accuracy measured from a set of simulated test phantoms.     

Design study of an in situ PET scanner for use in proton beam therapy

Proton beam therapy can deliver a high radiation dose to a tumor without significant damage to surrounding healthy tissue or organs. One way of verifying the delivered dose distribution is to image the short-lived positron emitters produced by the proton beam as it travels through the patient. A potential solution to the limitations of PET imaging in proton beam therapy is the development of a high sensitivity, in situ PET scanner that starts PET imaging almost immediately after patient irradiation while the patient is still lying on the treatment bed. A partial ring PET design is needed for this application in order to avoid interference between the PET detectors and the proton beam, as well as restrictions on patient positioning on the couch. A partial ring also allows us to optimize the detector separation (and hence the sensitivity) for different patient sizes. Our goal in this investigation is to evaluate an in situ PET scanner design for use in proton therapy that provides tomographic imaging in a partial ring scanner design using time-of-flight (TOF) information and an iterative reconstruction algorithm. GEANT4 simulation of an incident proton beam was used to produce a positron emitter distribution, which was parameterized and then used as the source distribution inside a water-filled cylinder for EGS4 simulations of a PET system. Design optimization studies were performed as a function of crystal type and size, system timing resolution, scanner angular coverage and number of positron emitter decays. Data analysis was performed to measure the accuracy of the reconstructed positron emitter distribution as well as the range of the positron emitter distribution. We simulated scanners with varying crystal sizes (2-4 mm) and type (LYSO and LaBr(3)) and our results indicate that 4 mm wide LYSO or LaBr(3) crystals (resulting in 4-5 mm spatial resolution) are adequate; for a full-ring, non-TOF scanner we predict a low bias (<0.6 mm) and a good precision (<1 mm) in the estimated range relative to the simulated positron distribution. We then varied the angular acceptance of the scanner ranging from 1/2 to 2/3 of 2π; a partial ring TOF imaging with good timing resolution (≤600 ps) is necessary to produce accurate tomographic images. A two-third ring scanner with 300 ps timing resolution leads to a bias of 1.0 mm and a precision of 1.4 mm in the range estimate. With a timing resolution of 600 ps, the bias increases to 2.0 mm while the precision in the range estimate is similar. For a half-ring scanner design, more distortions are present in the image, which is characterized by the increased error in the profile difference estimate. We varied the number of positron decays imaged by the PET scanner by an order of magnitude and we observe some decrease in the precision of the range estimate for lower number of decays, but all partial ring scanner designs studied have a precision ≤1.5 mm. The largest number tested, 150 M total positron decays, is considered realistic for a clinical fraction of delivered dose, while the range of positron decays investigated in this work covers a variable number of situations corresponding to delays in scan start time and the total scan time. Thus, we conclude that for partial ring systems, an angular acceptance of at least 1/2 (of 2π) together with timing resolution of 300 ps is needed to achieve accurate and precise range estimates. With 600 ps timing resolution an angular acceptance of 2/3 (of 2π) is required to achieve satisfactory range estimates. These results indicate that it would be feasible to develop a partial-ring dedicated PET scanner based on either LaBr(3) or LYSO to accurately characterize the proton dose for therapy planning.     

Evaluation of spatial resolution of a PET scanner through the simulation and experimental measurement of the recovery coefficient

Purpose: In order to measure spatial resolution of a PET tomograph in clinical conditions, this study describes and validates a method based on the recovery coefficient, a factor required to compensate underestimation in measured radioactivity concentration for small structures.Methods: In a PET image, the recovery factors of radioactive spheres were measured and their comparison with simulated recovery coefficients yielded the tomographic spatial resolution. Following this methodology, resolution was determined in different surrounding media and several conditions for reconstruction, including clinical conditions for brain PET studies. All spatial resolution values were compared with those obtained using classical methods with point and line sources.Results: In each considered condition, spatial resolution of the PET image estimated using the recovery coefficient showed good agreement with classical methods measurements, validating the procedure.Conclusion: Measurement of the recovery coefficient provides an assessment of tomographic spatial resolution, particularly in clinical studies conditions.     

Detector development for microPET II: a 1 microl resolution PET scanner for small animal imaging.

We are currently developing a small animal positron emission tomography (PET) scanner with a design goal of 1 microlitre (1 mm3) image resolution. The detectors consist of a 12 x 12 array of 1 x 1 x 10 mm lutetium oxyorthosilicate (LSO) scintillator crystals coupled to a 64-channel photomultiplier tube (PMT) via 5 cm long optical fibre bundles. The optical fibre connection allows a high detector packing fraction despite the dead space surrounding the active region of the PMT. Optical fibre bundles made from different types of glass were tested for light transmission, and also their effects on crystal identification and energy resolution, and compared to direct coupling of the LSO arrays to the PMTs. We also investigated the effects of extramural absorber (EMA) in the fibre bundles. Based on these results, fibre bundles manufactured from F2 glass were selected. We built three pairs of prototype detectors (directly coupled LSO array, fibre bundle without EMA and fibre bundle with EMA) and measured flood histograms, energy resolution, intrinsic spatial resolution and timing resolution. The results demonstrated an intrinsic spatial resolution (FWHM) of 1.12 mm (directly coupled), 1.23 mm (fibre bundle without EMA coupling) and 1.27 mm (fibre bundle with EMA coupling) using an approximately 500 microm diameter Na-22 point source. Using a 330 microm outer diameter steel needle line source filled with F-18, spatial resolution for the detector with the EMA optical fibre bundle improved to 1.05 mm. The respective timing and energy FWHM values were 1.96 ns, 21% (directly coupled), 2.20 ns, 23% (fibre bundle without EMA) and 2.99 ns, 30% (fibre bundle with EMA). The peak-to-valley ratio in the flood histograms was better with EMA (5:1) compared to the optical fibre bundle without EMA (2.5:1), due to the decreased optical cross-talk. In comparison to the detectors used in our current generation microPET scanner, these detectors substantially improve on the spatial resolution, preserve the timing resolution and provide adequate energy resolution for a modern high-resolution animal PET tomograph.     

Characterization of a high-resolution hybrid DOI detector for a dedicated breast PET/CT scanner

The aim of this study is to design and test a new high-resolution hybrid depth of interaction (DOI) detector for a dedicated breast PET/CT scanner. Two detectors have been designed and built. The completed detectors are based on a 14 × 14 array of 1.5 × 1.5 × 20 mm(3) unpolished lutetium orthosilicate scintillation crystals, with each element coated in a 50 μm layer of reflective material. The detector is read out from both ends using a position-sensitive photomultiplier tube (PSPMT) and a large active area (20 × 20 mm(2)) avalanche photodiode (APD) to enable acquisition of DOI information. Nuclear instrumentation modules were used to characterize the detectors' performances in terms of timing, intrinsic spatial resolution (ISR) and energy resolution, as well as DOI resolution with a dual-ended readout configuration. Measurements with the APD were performed at a temperature of 10 °C. All crystals were identified at all depths, even though the signal amplitude from the PSPMT decreases with depth away from it. We measured a timing resolution of 2.4 ns, and an average energy resolution of 19%. The mean ISR was measured to be 1.2 mm for crystals in the central row of the array for detectors in the face-to-face position. Two off-center positions were measured corresponding to 26° and 51° oblique photon incidence, and the mean ISR at these positions was 1.5 and 1.7 mm, respectively. The average DOI resolution across all crystals and depths was measured to be 2.9 mm (including the beam width of 0.6 mm). This detector design shows good promise as a high-resolution detector for a dedicated breast PET/CT scanner.     

Design considerations for a limited angle, dedicated breast, TOF PET scanner

Development of partial ring, dedicated breast positron emission tomography (PET) scanners is an active area of research. Due to the limited angular coverage, generation of distortion and artifact-free, fully 3D tomographic images is not possible without rotation of the detectors. With time-of-flight (TOF) information, it is possible to achieve the 3D tomographic images with limited angular coverage and without detector rotation. We performed simulations for a breast scanner design with a ring diameter and an axial length of 15 cm and comprising a full (180 degrees in-plane angular coverage), 2/3 (120 degrees in-plane angular coverage) or 1/2 (90 degrees in-plane angular coverage) ring detector. Our results show that as the angular coverage decreases, improved timing resolution is needed to achieve distortion-free and artifact-free images with TOF. The contrast recovery coefficient (CRC) value for small hot lesions in a partial ring scanner is similar to a full ring non-TOF scanner. Our results indicate that a timing resolution of 600 ps is needed for a 2/3 ring scanner, while a timing resolution of 300 ps is needed for a 1/2 ring scanner. We also analyzed the ratio of lesion CRC to the background pixel noise (SNR) and concluded that TOF improves the SNR values of the partial ring scanner, and helps to compensate for the loss in sensitivity due to reduced geometric sensitivity in a limited angle coverage PET scanner. In particular, it is possible to maintain similar SNR characteristic in a 2/3 ring scanner with a timing resolution of 300 ps as in a full ring non-TOF scanner.     

A practical method for depth of interaction determination in monolithic scintillator PET detectors

Several new methods for determining the depth of interaction (DOI) of annihilation photons in monolithic scintillator detectors with single-sided, multi-pixel readout are investigated. The aim is to develop a DOI decoding method that allows for practical implementation in a positron emission tomography system. Specifically, calibration data, obtained with perpendicularly incident gamma photons only, are being used. Furthermore, neither detector modifications nor a priori knowledge of the light transport and/or signal variances is required. For this purpose, a clustering approach is utilized in combination with different parameters correlated with the DOI, such as the degree of similarity to a set of reference light distributions, the measured intensity on the sensor pixel(s) closest to the interaction position and the peak intensity of the measured light distribution. The proposed methods were tested experimentally on a detector comprised of a 20 mm × 20 mm × 12 mm polished LYSO:Ce crystal coupled to a 4 × 4 multi-anode photomultiplier. The method based on the linearly interpolated measured intensities on the sensor pixels closest to the estimated (x, y)-coordinate outperformed the other methods, yielding DOI resolutions between ～1 and ～4.5 mm FWHM depending on the DOI, the (x, y) resolution and the amount of reference data used.     

Application of a capacitive-coupling interstitial hyperthermia system at 27 MHz: study of different applicator configurations

A 27 MHz capacitive-coupling interstitial hyperthermia system has been developed. It uses thin flexible applicators which can easily be inserted in standard brachytherapy catheters. The system can be operated in two different configurations. In the external ground return configuration tissue is heated by currents passing from the catheters to external ground returns; in the balanced configuration, by currents passing between applicators with a phase difference of 180 degrees. The purpose of this study was to find out which configuration is preferable, in terms of temperature homogeneity and clinical usefulness. Model calculations show that, due to the high impedance associated with capacitive coupling, the applicators can be represented as current sources, in contrast to local current field electrodes which are voltage sources. SAR measurements in muscle-equivalent phantoms illustrate that homogeneous heating patterns along the catheters can be expected in both configurations in regular as well as in irregular implants. Using the external ground return configuration the power of each applicator can be controlled individually. Calculations and measurements show that cross-talk cannot be avoided completely in this configuration, but that it can be minimized by using applicators operating in phase.     

3D reconstruction for a multi-ring PET scanner by single-slice rebinning and axial deconvolution

A three-dimensional (3D) image reconstruction method, which was originally developed for a positron emission tomography (PET) system consisting of two rotating scintillation cameras, has now been implemented for a multi-ring PET scanner with retractable septa. The method is called 'single-slice rebinning with axial deconvolution' (SSAD), and can be described as follows. The projection data are sorted into transaxial 2D sinograms. Correction for the axial blurring is made by deconvolution in the sinograms. To obtain the axial spread functions, which depend on the activity distribution, 2D reconstruction is first made using a limited axial acceptance angle. The final 3D image is obtained by 2D reconstruction of transaxial planes. The method is simple but not approximate, has a modest memory requirement, and can be combined with different 2D techniques. Evaluations by Monte Carlo simulations and phantom studies have been made.     

Construction of a modified capacitive overlap MR coil for imaging of small animals and objects in a clinical whole-body scanner

During the last two decades, there has been an explosive increase in the number of MR investigations involving genetically manipulated mice and rats. Many of the animal studies are performed in a more or less clinical environment, where whole-body MR scanners are the only option available. The quality and acquisition time of MR images have improved with the development of novel RF coil technologies. This communication describes the construction of a small inductively coupled capacitive overlap transmit-receive MR coil for imaging of small animals and objects in a clinical MR scanner. The MR coil presented here is a modified version of the bridged loop-gap coil and consists of two tube-shaped coupled resonance circuits, where the primary circuit partly encapsulates the imaging (secondary) circuit. By rotating the concentric primary coil relative to the secondary coil tuning over a range of several hundred kilohertz is obtained. The coil performance was characterized experimentally by acquiring high-resolution anatomical, diffusion and perfusion MR images as well as the acquisition of proton spectra of a mouse tumour.