Enrico Preziosi

Preliminary evaluation of a monolithic detector module for integrated PET/MRI scanner with high spatial resolution

The proposal of Mindview European Project concerns with the development of a very high resolution and high efficiency brain dedicated PET scanner simultaneously working with a Magnetic Resonance scanner, that expects to visualize neurotransmitter pathways and their disruptions in the quest to better diagnose schizophrenia. On behalf of this project, we propose a low cost PET module for the first prototype, based on monolithic crystals, suitable to be integrated with a head Radio Frequency (RF) coil. The aim of the suggested module is to achieve high performances in terms of efficiency, planar spatial resolution (expected about 1 mm) and discrimination of gamma Depth Of Interaction (DOI) in order to reduce the parallax error. Our preliminary results are very promising: a DOI resolution of about 3 mm, a spatial resolution ranging from about 1 to 1.5 mm and a good position linearity.

Position algorithm for monolithic scintillation crystals based on charge projection readout

Nuclear medicine imaging devices commonly use multi-element photo detection systems, composed of an array of N × N elements, each one providing an individual signal. Many strategies have been developed to reduce the number of readout channels, one of the main approaches is the Rows and Columns (R/C) projection logic. In this paper we proposed a modified version of Raised To the Power (RTP) algorithm adapted to R/C logic. In order to validate its efficiency a linear scanning irradiation on two 49× 49 mm2 LaBr3:Ce (0.5%) crystals with different thickness (4 mm and 10 mm) was carried out. Imaging performance analysis was made in terms of position linearity, Field-of-View (FoV) enlargement and spatial resolution. Imaging results from Anger Logic, RTP algorithm based on single element readout and RTP algorithm based on R/C readout were compared. A notable advantage of using RTP algorithms instead of Anger Logic was found: the FoV widens from about 30% to more than 70% of the detector area whereas the spatial resolution is highly improved, especially for off-center interactions, both for 4 mm-thick and 10 mm-thick crystals. Furthermore, imaging performance with the R/C readout is just slightly different from the single element one (FoV reduction less than 7% and SR worsening less than 10%). The R/C adapted RTP algorithm opens doors to high imaging performance with a substantial reduction of complexity and cost in the readout electronics.

A Novel Method for

Achieved spatial resolution of the PET systems is often limited by the parallax error due to the lack of information about the Depth of Interaction (DoI) inside the crystal of the incoming 511 keV annihilation photons. The smaller the diameter of the PET ring and the thicker the scintillator are, the more this error affects imaging performance. In this work, a DoI calculator suitable for monolithic scintillation crystals and based on the shape of the scintillation light distribution at the photodetector surface has been proposed. To test the estimator performance, a test PET module with a 50 × 50 × 20 mm monolithic LYSO crystal coupled to a 12 × 12 SiPM array has been employed. In addition, for calibration and validation of the method, Geant4 simulations have been also used. The key result of the application of the proposed DoI estimator is obtaining a continuous DoI estimation with an average DoI resolution of about 5 mm in the 20 mm-thick crystal. Benefiting from the DoI estimation capabilities of the method, it has been also possible to achieve additional important goals, first of all reducing the parallax error. First, because the scintillation light collection varies as a function of the 3D position of the interaction of the annihilation photon inside the crystal, a method to correct this response variation via a proper 3D look-up-table is proposed. This has led to an improvement of about 35% in energy resolution. Moreover, a DoI-dependent position algorithm has been proposed, allowing an improvement of both planar (X-Y) position linearity and planar spatial resolution. This algorithm is specifically developed for the rows/columns multi-channel readout logic, that reduces the number of independent channels from N × N to N + N, where N is the number of SiPM photodetection elements (12 in our case) in each row and column. This development was performed in the framework of the MindView PET/MilI brain imaging project.

\gamma - \text{photons}

One of the technical objectives of the MindView project is developing a brain-dedicated PET insert based on monolithic scintillation crystals. It will be inserted in MRI systems with the purpose to obtain simultaneous PET and MRI brain images. High sensitivity, high image quality performance and accurate detection of the Depth-of-Interaction (DoI) of the 511keV photons are required. We have developed a DoI estimation method, dedicated to monolithic scintillators, allowing continuous DoI estimation and a DoI-dependent algorithm for the estimation of the photon planar impact position, able to improve the single module imaging capabilities. In this work, through experimental measurements, the proposed methods have been used for the estimation of the impact positions within the monolithic crystal block. We have evaluated the PET system performance following the NEMA NU 4-2008 protocol by reconstructing the images using the STIR 3D platform. The results obtained with two different methods, providing discrete and continuous DoI information, are compared with those obtained from an algorithm without DoI capabilities and with the ideal response of the detector. The proposed DoI-dependent imaging methods show clear improvements in the spatial resolution (FWHM) of reconstructed images, allowing to obtain values from 2mm (at the center FoV) to 3mm (at the FoV edges).

Depth-of-Interaction Detection in Monolithic Scintillation Crystals

A whole-body PET device is sometimes not suitable for brain studies because the achieved image resolution is typically not sufficient to investigate small size structures. Thus, a dedicated brain PET insert system with high performance would overcome such limitations. Moreover, these functional studies lack of anatomical information. It is shown elsewhere the convenience of simultaneously acquisition of PET and MR data. In this work we show the final design and first pilot evaluation tests of a novel brain PET insert. Each detector block is based on a monolithic scintillation crystal, an array of SiPMs and a readout allowing characterizing the scintillation light distribution in the X and Y detector axes. The scintillators have a parallelepiped geometry with dimensions of 50×50×20 mm3. Their lateral walls are black painted and with the entrance face coupled to a retroreflector optical layer. We have determined an average (XYZ) detector spatial resolution through the FWHM of 1.2 mm (whole scintillator volume). The DOI resolution was measured with lateral incidence experiments and found to be about 3.5 mm, also on average for all photons depth of interactions and crystal positions. Thanks to the retroreflector, the energy resolution improves when compared to a case with all surfaces black painted, resulting on an average value of 13%. The tomographic reconstruction of the data was evaluated using different algorithms, including analytical (FBP STIR-3D), iterative (MLEM and List Mode OS) and a novel method that provides images by directly tracing the measured LORs. The minimum pixel/voxel sizes that were tried are 0.8/0.4 mm, 1.0/0.5 mm and 0.16/0.16 mm, respectively. All methods made it possible to show the PET system capabilities to resolve 1.6 mm rods in a Derenzo-like phantom filled with 150 uCi and scanned for 20 minutes. Pilot tests of the PET insert inside a clinical 3T MR showed a good system performance for most of the sequences typically used for brain imaging.

Performance study of a PET scanner based on monolithic scintillators for different DoI-dependent methods

We present the first results of the MINDVIEW project. An innovative imaging system for the human brain examination, allowing simultaneous acquisition of PET/MRI images, has been designed and constructed. It consists of a high sensitivity and high resolution PET scanner integrated in a novel, head-dedicated, radio frequency coil for a 3T MRI scanner. Preliminary measurements from the PET scanner show sensitivity 3 times higher than state-of-the-art PET systems that will allow safe repeated studies on the same patient. The achieved spatial resolution, close to 1 mm, will enable differentiation of relevant brain structures for schizophrenia. A cost-effective and simple method of radiopharmaceutical production from 11C-carbon monoxide and a mini-clean room has been demonstrated. It has been shown that 11C-raclopride has higher binding potential in a new VAAT null mutant mouse model of schizophrenia compared to wild type control animals. A significant reduction in TSPO binding has been found in gray matter in a small sample of drug-naïve, first episode psychosis patients, suggesting a reduced number or an altered function of immune cells in brain at early stage schizophrenia.

A brain PET insert MR compatible: Final design and first results

In recent years, a new generation of compact gamma cameras, based on monolithic scintillation crystals, has become increasingly widespread. The main advantages of small FoV gamma cameras with respect to the standard ones are high portability, low cost and low weight, allowing several clinical applications, from scintimammography to intraoperative tumor localization. In gamma cameras based on continuous scintillation crystals, intrinsic Spatial Resolution (SR) is mainly affected by two factors: scintillation light collection efficiency and overall crystal thickness. The first affects the counting statistics, the latter impacts on the light distribution width. To fully investigate the potentiality of these devices we took advantage of Monte Carlo simulations as a valuable tool to physically characterize the imaging systems and to establish a priori reference values. GEANT4 toolkit allows to completely describe the phenomenon of light emission and propagation through the media, providing control to all second-order factors existing in real systems. Results show clearly that SR is dependent on the number of photoelectrons produced and on the light spread. Furthermore, the role of refractive index has been unambiguously identified as an important factor affecting light collection and consequently SR.

The MINDVIEW project: First results

The MindView European Project pursues the development of a high efficiency and high resolution brain dedicated PET detector, simultaneously working with a Magnetic Resonance Imaging (MRI) system. Since the PET scanner is based on a small diameter ring and on thick monolithic scintillation crystals to assess high efficiency, the parallax error related to off-center positron annihilation is a critical issue. The Depth of Interaction (DoI) discrimination can reduce the blurring due to this phenomenon. In this work, we propose a novel DoI estimator, based on the ratio of the integral of scintillation light distribution to its maximum (named N/I). In a preliminary way, by means of Monte Carlo simulation, we have validated the correlation between this parameter and the DoI. Furthermore, we have experimentally tested the capability of such DoI estimator on a monolithic 20 mm-thick LYSO crystal optically coupled to a 12x12 silicon photomultipliers (SiPMs) array. Thanks to the proposed method, it is possible to select interaction events coming from different depths of the crystal. The DoI discrimination capability has been confirmed by using a collimated slanted pencil-beam: the proposed estimator allows to produce different images coming from events belonging to different depths of the crystal. From the experimental results a DoI discrimination resolution ranging from 4 mm to 6 mm has been obtained. The proposed method is expected to reduce the parallax error and, consequently, the width of lines of response coming from off- center positron annihilation of about 70% respect to the method without DoI discrimination.

Monte Carlo simulation to evaluate factors affecting imaging performances of compact scintillation gamma camera

Dynamic contrast-enhanced cardiovascular magnetic resonance imaging can be used to quantitatively assess the myocardial blood flow (MBF), recovering the tissue impulse response function for the transit of a gadolinium bolus through the myocardium. Several deconvolution techniques are available, using various models for the impulse response. The method of choice may influence the results, producing differences that have not been deeply investigated yet. Three methods for quantifying myocardial perfusion have been compared: Fermi function modelling (FFM), the Tofts model (TM) and the gamma function model (GF), with the latter traditionally used in brain perfusion MRI. Thirty human subjects were studied at rest as well as under cold pressor test stress (submerging hands in ice-cold water), and a single bolus of gadolinium weighing 0.1  ±  0.05 mmol kg-1 was injected. Perfusion estimate differences between the methods were analysed by paired comparisons with Students t-test, linear regression analysis, and Bland-Altman plots, as well as also using the two-way ANOVA, considering the MBF values of all patients grouped according to two categories: calculation method and rest/stress conditions. Perfusion estimates obtained by various methods in both rest and stress conditions were not significantly different, and were in good agreement with the literature. The results obtained during the first-pass transit time (20 s) yielded p-values in the range 0.20-0.28 for Students t-test, linear regression analysis slopes between 0.98-1.03, and R values between 0.92-1.01. From the Bland-Altman plots, the paired comparisons yielded a bias (and a 95% CI)-expressed as ml/min/g-for FFM versus TM, -0.01 (-0.20, 0.17) or 0.02 (-0.49, 0.52) at rest or under stress respectively, for FFM versus GF, -0.05 (-0.29, 0.20) or  -0.07 (-0.55, 0.41) at rest or under stress, and for TM versus GF, -0.03 (-0.30, 0.24) or  -0.09 (-0.43, 0.26) at rest or under stress. With the two-way ANOVA, the results were p  =  0.20 for the method effect (not significant), p  <  0.0001 for the rest/stress condition effect (highly significant, as expected), whereas no interaction resulted between the rest/stress condition and method (p  =  0.70, not significant). Considering a wider time-frame (60 s), the estimates for both rest and stress conditions were 25%-30% higher (p in the range 0.016-0.025) than those obtained in the 20 s time-frame. MBF estimates obtained by various methods under rest/stress conditions were not significantly different in the first-pass transit time, encouraging quantitative perfusion estimates in DCE-CMRI with the used methods.

A novel method for γ photons depth of interaction discrimination on monolithic LYSO crystals for brain PET/MRI.

Magnetic Resonance (MR) guided Focused Ultrasound Surgery (MRgFUS) technology, combined with High Intensity Focused Ultrasound (HIFU) beams, has opened to new therapeutic protocols for various pathological conditions. The success of this therapy relies on the accuracy of the guidance for therapy provided by thermal mapping of sonication, which is obtained with MR imaging. In addition, in recent years, multimodality Positron Emission Tomography and Magnetic Resonance Imaging (PET/MRI) imaging has been developed. This technique is able to provide simultaneous functional and soft tissue morphological imaging and, for this reason, it is particularly engaging for brain imaging. The key concept behind this work is to assess the feasibility of a brain-dedicated PET- and MRI-guided FUS device providing real-time evaluation of the outcome of the HIFU therapy. At first, a method to improve imaging capabilities of small-ring PET scanners will be presented. It will be showed that thanks to this method it is possible to obtain high tomographic spatial resolution with an affordable, brain-dedicated, PET scanner based on monolithic scintillation crystals and able to work as an insert in a MRI system. Moreover, simulations of an anthropomorphic phantom will be made in order to evaluate the effect of different HIFU protocols and, in addition, to investigate the capability of thermal maps provided by MRI for assessing the effect of the HIFU treatment. Finally, from the comparison of the spatial resolutions provided by each imaging technique (PET, MRI and thermal MRI) and the HIFU therapy, it will be possible to assess the feasibility of the proposed multimodality device. The system suggested in this work should be composed of a MRI scanner with a PET insert and a customized MRI-compatible focused ultrasound applicator. It could be very useful for the diagnosis and therapy of brain tumors thanks to the possibility of a real-time evaluation of the effect of the HIFU treatment. The protocol for the therapy could be executed in three main steps: the diagnosis of the pathological condition by means of fused anatomical imaging from MRI and functional imaging from PET (with different radiotracers) that allow to identify the region where apply the therapy, the ablation of the tumor by means of HIFU beams and the simultaneous evaluation of the thermal response of the tissues by means MRI thermal maps and, finally, the assessment of the outcome of the therapy by means, again, of PET/MRI hybrid imaging. The results suggest that PET-and MRI-guided focused ultrasound surgery (PET/MRgFUS) could be an innovative, feasible and engaging technique for tumor ablation in the brain.