Bernard Bendriem

Physical and clinical performance of the mCT time-of-flight PET/CT scanner

Time-of-flight (TOF) measurement capability promises to improve PET image quality. We characterized the physical and clinical PET performance of the first Biograph mCT TOF PET/CT scanner (Siemens Medical Solutions USA, Inc.) in comparison with its predecessor, the Biograph TruePoint TrueV. In particular, we defined the improvements with TOF. The physical performance was evaluated according to the National Electrical Manufacturers Association (NEMA) NU 2-2007 standard with additional measurements to specifically address the TOF capability. Patient data were analyzed to obtain the clinical performance of the scanner. As expected for the same size crystal detectors, a similar spatial resolution was measured on the mCT as on the TruePoint TrueV. The mCT demonstrated modestly higher sensitivity (increase by 19.7 ± 2.8%) and peak noise equivalent count rate (NECR) (increase by 15.5 ± 5.7%) with similar scatter fractions. The energy, time and spatial resolutions for a varying single count rate of up to 55 Mcps resulted in 11.5 ± 0.2% (FWHM), 527.5 ± 4.9 ps (FWHM) and 4.1 ± 0.0 mm (FWHM), respectively. With the addition of TOF, the mCT also produced substantially higher image contrast recovery and signal-to-noise ratios in a clinically-relevant phantom geometry. The benefits of TOF were clearly demonstrated in representative patient images.

The theory and practice of 3D PET

Foreword T. Jones. Preface. 1. Introduction to 3D PET D.W. Townsend, B. Bendriem. 2. Data Acquisition and Image Reconstruction for 3D PET M. Defrise, P.E. Kinahan. 3. Quantitative Procedures in 3D PET D.L. Bailey, et al. 4. Volume Imaging Tomographs D.W. Townsend, et al. 5. Applications of 3D PET K. Wienhard, et al.

Method for transforming CT images for attenuation correction in PET/CT imaging

A tube-voltage-dependent scheme is presented for transforming Hounsfield units (HU) measured by different computed tomography (CT) scanners at different x-ray tube voltages (kVp) to 511 keV linear attenuation values for attenuation correction in positron emission tomography (PET) data reconstruction. A Gammex 467 electron density CT phantom was imaged using a Siemens Sensation 16-slice CT, a Siemens Emotion 6-slice CT, a GE Lightspeed 16-slice CT, a Hitachi CXR 4-slice CT, and a Toshiba Aquilion 16-slice CT at kVp ranging from 80 to 140 kVp. All of these CT scanners are also available in combination with a PET scanner as a PET/CT tomograph. HU obtained for various reference tissue substitutes in the phantom were compared with the known linear attenuation values at 511 keV. The transformation, appropriate for lung, soft tissue, and bone, yields the function 9.6 x 10(-5). (HU+ 1000) below a threshold of approximately 50 HU and a (HU+ 1000)+b above the threshold, where a and b are fixed parameters that depend on the kVp setting. The use of the kVp-dependent scaling procedure leads to a significant improvement in reconstructed PET activity levels in phantom measurements, resolving errors of almost 40% otherwise seen for the case of dense bone phantoms at 80 kVp. Results are also presented for patient studies involving multiple CT scans at different kVp settings, which should all lead to the same 511 keV linear attenuation values. A linear fit to values obtained from 140 kVp CT images using the kVp-dependent scaling plotted as a function of the corresponding values obtained from 80 kVp CT images yielded y = 1.003 x -0.001 with an R2 value of 0.999, indicating that the same values are obtained to a high degree of accuracy.

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.

Quantification of benzodiazepine receptors in human brain using PET, [11C]flumazenil, and a single-experiment protocol

A kinetic method using a multiinjection protocol, positron emission tomography (PET), and [11C]flumazenil as a specific ligand was used to study in vivo the flumazenil-benzodiazepine receptor interactions in the human brain. The model structure is composed of three compartments (plasma, free, and bound ligand) and five parameters (including the benzodiazepine receptor concentration). The arterial plasma concentration, after correction for metabolites, was used as the input function. The experimental protocol, which consisted of three injections of labeled and/or unlabeled ligand, allowed the evaluation of the five model parameters in various brain regions from a single experiment. In particular, the concentration of receptor sites available for binding (B′max) and the equilibrium dissociation constant (KDVK, VR being the volume of reaction) were estimated in five brain regions, including the pons, in which these parameters are identified for the first time (B′max = 4.7 ± 1.7 pmol/ml and KDVR = 4.4 ± 1.3 pmol/ml). Due to the large range of measured receptor concentrations, a linear correlation between B′max and KDVR was pointed out (r = 0.88, p < 0.0005) and was interpreted as a linear relationship between B′max and VR, the parameter KD being assumed constant. This result and its concordance with the published data are discussed. Simulation of the usual two-experiment Scatchard analysis, using the pons as a reference region, showed that the bias on the receptor concentration estimates introduced by this method is significant (from 20 to 40%) but can be corrected using an estimate of the receptor concentration in the pons. Furthermore, we propose a new experimental protocol, based on a Scatchard analysis of the PET data obtained with a partial-saturation experiment. This single-injection protocol is entirely noninvasive, and thus the estimation of the benzodiazepine receptor concentration and of the flumazenil affinity is now possible in human patients using a single 1-h experiment without blood sampling.

Fast Nonsupervised 3D Registration of PET and MR Images of the Brain

We propose a fully nonsupervised methodology dedicated to the fast registration of positron emission tomography (PET) and magnetic resonance images of the brain. First, discrete representations of the surfaces of interest (head or brain surface) are automatically extracted from both images. Then, a shape-independent surface-matching algorithm gives a rigid body transformation, which allows the transfer of information between both modalities. A three-dimensional (3D) extension of the chamfer-matching principle makes up the core of this surface-matching algorithm. The optimal transformation is inferred from the minimization of a quadratic generalized distance between discrete surfaces, taking into account between-modality differences in the localization of the segmented surfaces. The minimization process is efficiently performed via the precomputation of a 3D distance map. Validation studies using a dedicated brain-shaped phantom have shown that the maximum registration error was of the order of the PET pixel size (2 mm) for the wide variety of tested configurations. The software is routinely used today in a clinical context by the physicians of the Service Hospitalier Frédéric Joliot (>150 registrations performed). The entire registration process requires ∼5 min on a conventional workstation.

Performance Characteristics of a New LSO PET/CT Scanner With Extended Axial Field-of-View and PSF Reconstruction

A new combined lutetium oxyorthosilicate (LSO) PET/CT scanner with an extended axial field-of-view (FOV) of 21.8 cm has been developed (Biograph TruePoint PET/CT with TrueV; Siemens Molecular Imaging) and introduced into clinical practice. The scanner includes the recently announced point spread function (PSF) reconstruction algorithm. The PET components incorporate four rings of 48 detector blocks, 5.4 cm times 5.4 cm in cross-section. Each block comprises a 13 times 13 matrix of 4 times 4 times 20 mm3 elements. Data are acquired with a 4.5 ns coincidence time window and an energy window of 425-650 keV. The physical performance of the new scanner has been evaluated according to the recently revised National Electrical Manufacturers Association (NEMA) NU 2-2007 standard and the results have been compared with a previous PET/CT design that incorporates three rings of block detectors with an axial coverage of 16.2 cm (Biograph TruePoint PET/CT; Siemens Molecular Imaging). In addition to the phantom measurements, patient Noise Equivalent Count Rates (NECRs) have been estimated for a range of patients with different body weights (42-154 kg). The average spatial resolution is the same for both scanners: 4.4 mm (FWHM) and 5.0 mm (FWHM) at 1 cm and 10 cm respectively from the center of the transverse FOV. The scatter fractions of the Biograph TruePoint and Biograph TruePoint TrueV are comparable at 32%. Compared to the three ring design, the system sensitivity and peak NECR with smoothed randoms correction (1R) increase by 82% and 73%, respectively. The increase in sensitivity from the extended axial coverage of the Biograph TruePoint PET/CT with TrueV should allow a decrease in either scan time or injected dose without compromising diagnostic image quality. The contrast improvement with the PSF reconstruction potentially offers enhanced detectability for small lesions.

Modeling Analysis of [11C]Flumazenil Kinetics Studied by PET: Application to a Critical Study of the Equilibrium Approaches

The multi-injection modeling approach was used for the in vivo quantitation of benzodiazepine receptors in baboon brain using positron emission tomography (PET) and [11C]flumazenil (RO 15-1788) as a specific ligand. The model included three compartments (plasma, free, and bound ligand) and five parameters (including the benzodiazepine receptor concentration). The plasma concentration after correction for the metabolites was used as the input function. The experimental protocol consisted of four injections of labeled and/or unlabeled ligand. This protocol allows the evaluation, from a single experiment, of the five model parameters in various regions of interest. For example, in the temporal cortex, the concentration of receptor sites available for binding (B′max) and the equilibrium dissociation constant (Kd) were estimated to be 70 ± 15 pmol/ml and 15.8 ± 2.2 nM, respectively. The validity of the equilibrium approach, which is the most often used quantitation method, has been studied from simulated data calculated using these model parameters. The equilibrium approaches consist of reproducing in PET studies the experimental conditions that permit the use of the usual in vitro methods such as Scatchard analysis. These approaches are often open to criticism because of the difficulty of defining the notion of equilibrium in in vivo studies. However, it appears that the basic relation of Scatchard analysis is valid over a broader range of conditions than those normally used, such as the requirement of a constant bound/free ratio. Simulations showed that the values of the receptor concentration (B′max) and the equilibrium dissociation constant (Kd) found using Scatchard analysis are always underestimated. These simulations also suggest an explanation concerning the dependency of B′max and Kd on the time point employed for the Scatchard analysis, a phenomenon found by several authors. To conclude, we propose new protocols that allow the estimation of the B′max and Kd parameters using a Scatchard analysis but based on a protocol including only one or two injections. These protocols being entirely noninvasive, it thus becomes possible to investigate possible changes in receptor density and/or affinity in patients.

Advances in scatter correction for 3D PET/CT

We report on several significant improvements to the implementation of image-based scatter correction for 3D PET and PET/CT. Among these advances are: a new algorithm to scale the estimated scatter sinogram to the measured data, thereby largely compensating for external scatter; the ability to handle CT image truncation during this scaling; the option to iterate the scatter calculation for improved accuracy; the use of ordered subset estimation maximization (OSEM) reconstruction for the estimated emission images from which the scatter contributions are simulated; reporting of data quality parameters such as scatter and randoms fractions, and noise equivalent count rate (NECR), for each patient bed position; and extensive quality control output. Scatter correction (2 iterations, OSEM) typically requires 15-45 sec per bed. Very good agreement between the estimated scatter and measured emission data for several typical clinical scans is reported for CPS Pico-3D and HiRez LSO PET/CT systems. The data characteristics extracted during scatter correction are useful for patient specific count rate modeling and scan optimization

A PET scatter correction using simultaneous acquisitions with low and high lower energy thresholds

The authors propose a new method for scatter correction using two sinograms acquired simultaneously with a low and a high lower energy threshold (LLD). The high LLD is chosen such that the corresponding sinogram contains no or few scatter counts. The information in each data set are combined to produce a sinogram corrected for scatter. The method is described in detail and evaluated on various phantom measurements.<<ETX>>