Alberto Del Guerra

From PET detectors to PET scanners

This review describes the properties of available and emerging radiation detector and read-out technologies and discusses how they may affect PET scanner performance. After a general introduction, there is a section in which the physical properties of several different detector scintillators are compared. This is followed by a discussion of recent advances in read-out electronics. Finally, the physical performance of the several commercial PET scanners is summarized.

Age dependence of cerebral perfusion assessed by magnetic resonance continuous arterial spin labeling.

To study the normal dependence of cerebral perfusion changes on age, to measure values of perfusion early in life, and to create a reference dataset.

An outlook on future design of hybrid PET/MRI systems

Early diagnosis and therapy increasingly operate at the cellular, molecular, or even at the genetic level. As diagnostic techniques transition from the systems to the molecular level, the role of multimodality molecular imaging becomes increasingly important. Positron emission tomography (PET) and magnetic resonance imaging (MRI) are powerful techniques for in vivo molecular imaging. The inability of PET to provide anatomical information is a major limitation of standalone PET systems. Combining PET and CT proved to be clinically relevant and successfully reduced this limitation by providing the anatomical information required for localization of metabolic abnormalities. However, this technology still lacks the excellent soft-tissue contrast provided by MRI. Standalone MRI systems reveal structure and function but cannot provide insight into the physiology and/or the pathology at the molecular level. The combination of PET and MRI, enabling truly simultaneous acquisition, bridges the gap between molecular and systems diagnosis. MRI and PET offer richly complementary functionality and sensitivity; fusion into a combined system offering simultaneous acquisition will capitalize the strengths of each, providing a hybrid technology that is greatly superior to the sum of its parts. A combined PET/MRI system provides both the anatomical and structural description of MRI simultaneously with the quantitative capabilities of PET. In addition, such a system would allow exploiting the power of MR spectroscopy (MRS) to measure the regional biochemical content and to assess the metabolic status or the presence of neoplasia and other diseases in specific tissue areas. This paper briefly summarizes state-of-the-art developments and latest advances in dedicated hybrid PET/MRI instrumentation. Future prospects and potential clinical applications of this technology will also be discussed.

A detector head design for small-animal PET with silicon photomultipliers (SiPM)

Small-animal PET systems are now striving for sub-millimetre resolution. Current systems based upon PSPMTs and finely pixellated scintillators can be pushed to higher resolution, but at the expense of other performance parameters and a rapidly escalating cost. Moreover, depth of interaction (DOI) information is usually difficult to assess in such systems, even though this information is highly desirable to reduce the parallax error, which is often the dominant error for such high-resolution systems. In this study we propose a high-resolution detector head for a small-animal PET imaging system with intrinsic DOI information. Instead of a pixellated scintillator, our design is based upon the classic Anger camera principle, i.e. the head is constructed of modular layers each consisting of a continuous slab of scintillator, viewed by a new type of compact silicon photodetector. The photodetector is the recently developed silicon photomultiplier (SiPM) that as well as being very compact has many other attractive properties: high gain at low bias voltage, excellent single-photoelectron resolution and fast timing. A detector head of about 4 x 4 cm2 in area is proposed, constructed from three modular layers of the type described above. We perform a simulation study, using the Monte Carlo simulation package Geant4. The simulation results are used to optimize the geometry of the detector head and characterize its performance. Additionally, hit estimation algorithms are studied to determine the interaction position of annihilation photons correctly over the whole detector surface. The resulting detector has a nearly uniform efficiency for 511 keV photons of approximately 70% and an intrinsic spatial resolution of less than approximately 0.4 mm full width at half maximum (fwhm).

Multi-ray-based system matrix generation for 3D PET reconstruction.

Iterative image reconstruction algorithms for positron emission tomography (PET) require a sophisticated system matrix (model) of the scanner. Our aim is to set up such a model offline for the YAP-(S)PET II small animal imaging tomograph in order to use it subsequently with standard ML-EM (maximum-likelihood expectation maximization) and OSEM (ordered subset expectation maximization) for fully three-dimensional image reconstruction. In general, the system model can be obtained analytically, via measurements or via Monte Carlo simulations. In this paper, we present the multi-ray method, which can be considered as a hybrid method to set up the system model offline. It incorporates accurate analytical (geometric) considerations as well as crystal depth and crystal scatter effects. At the same time, it has the potential to model seamlessly other physical aspects such as the positron range. The proposed method is based on multiple rays which are traced from/to the detector crystals through the image volume. Such a ray-tracing approach itself is not new; however, we derive a novel mathematical formulation of the approach and investigate the positioning of the integration (ray-end) points. First, we study single system matrix entries and show that the positioning and weighting of the ray-end points according to Gaussian integration give better results compared to equally spaced integration points (trapezoidal integration), especially if only a small number of integration points (rays) are used. Additionally, we show that, for a given variance of the single matrix entries, the number of rays (events) required to calculate the whole matrix is a factor of 20 larger when using a pure Monte-Carlo-based method. Finally, we analyse the quality of the model by reconstructing phantom data from the YAP-(S)PET II scanner.

Expression analysis of facilitative glucose transporters (GLUTs) in human thyroid carcinoma cell lines and primary tumors

Fluorine-18-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) is based on cell capability to take-up glucose. While a significantly higher expression of the glucose transporter GLUT1 has been reported in thyroid tumors only few data are available on the expression of other GLUT isoforms. We studied several GLUT isoforms expression in thyroid tumor cell lines deriving from anaplastic (ARO, FRO), papillary (NPA), follicular (WRO) and medullary (TT) human thyroid carcinoma. GLUT1 and GLUT3 were also studied in 157 human thyroid malignant and benign tissues. Quantitative Real-time RT-PCR analysis revealed that GLUT1 mRNA levels were higher in less-differentiated cells (ARO, FRO) while GLUT3 mRNA levels were prevalent in well-differentiated cells (NPA, WRO). Accordingly, Western blot showed high expression and correct membrane targeting of GLUT1 protein in ARO and FRO and of GLUT3 protein in NPA and WRO. All cell lines were able to take-up different rates of (3)H-deoxy-glucose. The analysis of GLUT1 and GLUT3 mRNA expression in human thyroid tissues showed the prevalence of GLUT1, but not of GLUT3, in malignant with respect to normal tissues. Finally, both GLUT1 and GLUT3 showed a slightly higher expression in anaplastic than in well-differentiated tumors. In conclusion, we showed that GLUT1 and GLUT3 were the most important glucose transporters in the thyroid tumoral cells. In particular GLUT1 was the most prevalent in less-differentiated cells (ARO and FRO) while GLUT3 was the most prevalent in well-differentiated cells (NPA and WRO). A similar pattern of expression was found for GLUT1 but not for GLUT3 in human thyroid tumors.

ASIC development for SiPM readout

The design of CMOS front-end electronics suitable for Silicon Photo-Multipliers (SiPM) is described in this paper, starting with the specification of an accurate electrical model of the detector and its experimental validation. A novel current-mode solution is proposed for the preamplifier and the discriminator, to cope with the large dynamic range and the extremely fast rise time of the detector signal. Experimental results achieved from front-end prototypes designed according to this current-mode approach demonstrate its effectiveness: dynamic range of the order of 50 pC and timing accuracy of the electronics alone of about 30 ps have been measured.

A Time Efficient Optical Model for GATE Simulation of a LYSO Scintillation Matrix Used in PET Applications

A time efficient optical model is proposed for GATE simulation of a LYSO scintillation matrix coupled to a photomultiplier. The purpose is to avoid the excessively long computation time when activating the optical processes in GATE. The usefulness of the model is demonstrated by comparing the simulated and experimental energy spectra obtained with the dual planar head equipment for dosimetry with a positron emission tomograph (DoPET). The procedure to apply the model is divided in two steps. Firstly, a simplified simulation of a single crystal element of DoPET is used to fit an analytic function that models the optical attenuation inside the crystal. In a second step, the model is employed to calculate the influence of this attenuation in the energy registered by the tomograph. The use of the proposed optical model is around three orders of magnitude faster than a GATE simulation with optical processes enabled. A good agreement was found between the experimental and simulated data using the optical model. The results indicate that optical interactions inside the crystal elements play an important role on the energy resolution and induce a considerable degradation of the spectra information acquired by DoPET. Finally, the same approach employed by the proposed optical model could be useful to simulate a scintillation matrix coupled to a photomultiplier using single or dual readout scheme.

Spatial resolution measurements in quasimonochromatic x rays with mosaic crystals for mammography application

A novel x-ray source for mammography application is being investigated. Quasimonochromatic x rays have been produced via Bragg diffraction with a W-anode x-ray tube and a graphite mosaic crystal array. The system provides 18 keV x rays with an energy resolution deltaE/E approximately equals 0.12. A thorough analysis of the spatial resolution of the system has been performed in order to understand and quantify the effect of the introduction of an active optical element such as a mosaic crystal in the x-ray path. The focal spot of the source and its emission properties have been studied by using the slit camera method. Experiments have shown that the introduction of a mosaic crystal in the optical path modifies the resolution properties of the Bragg diffraction-based radiography system. Along the direction perpendicular to the diffraction plane the resolution properties of the imaging system mainly depend on the x-ray tube focal spot size and position. Along the diffraction plane the focal spot size depends on mosaic characteristics and on the geometrical setup. Hence, it could be modified by setting the appropriate experimental conditions.

Brain Glucose Overexposure and Lack of Acute Metabolic Flexibility in Obesity and Type 2 Diabetes: A PET-[18F]FDG Study in Zucker and ZDF Rats

Brain glucose exposure may complicate diabetes and obesity. We used positron emission tomography with 18F-fluorodeoxyglucose in Zucker obese, diabetic, and control rats to determine the contributions of blood glucose mass action versus local mechanisms in regulating central glucose disposal in fasted and acutely glucose-stimulated states, and their adaptations in obesity and diabetes. Our study data indicate that brain glucose uptake is dependent on both local and mass action components, and is stimulated by acute glucose intake in healthy rats. In diseased animals, the organ was chronically overexposed to glucose, due to high fasting glucose uptake, almost abolishing the physiologic response to glucose loading.