Cristian Borrazzo

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}

BackgroundA new transcranial focused ultrasound device has been developed that can induce hyperthermia in a large tissue volume. The purpose of this work is to investigate theoretically how glioblastoma multiforme (GBM) can be effectively treated by combining the fast hyperthermia generated by this focused ultrasound device with external beam radiotherapy.Methods/DesignTo investigate the effect of tumor growth, we have developed a mathematical description of GBM proliferation and diffusion in the context of reaction–diffusion theory. In addition, we have formulated equations describing the impact of radiotherapy and heat on GBM in the reaction–diffusion equation, including tumor regrowth by stem cells. This formulation has been used to predict the effectiveness of the combination treatment for a realistic focused ultrasound heating scenario.Our results show that patient survival could be significantly improved by this combined treatment modality.DiscussionHigh priority should be given to experiments to validate the therapeutic benefit predicted by our model.

Depth-of-Interaction Detection in Monolithic Scintillation Crystals

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).

Fast and high temperature hyperthermia coupled with radiotherapy as a possible new treatment for glioblastoma

PURPOSE Cardiac magnetic resonance (CMR) is a useful non-invasive tool for characterizing tissues and detecting myocardial fibrosis and edema. Estimation of extracellular volume fraction (ECV) using T1 sequences is emerging as an accurate biomarker in cardiac diseases associated with diffuse fibrosis. In this study, automatic software for T1 and ECV map generation consisting of an executable file was developed and validated using phantom and human data. METHODS T1 mapping was performed in phantoms and 30 subjects (22 patients and 8 healthy subjects) on a 1.5T MR scanner using the modified Look-Locker inversion-recovery (MOLLI) sequence prototype before and 15 min after contrast agent administration. T1 maps were generated using a Fast Nonlinear Least Squares algorithm. Myocardial ECV maps were generated using both pre- and post-contrast T1 image registration and automatic extraction of blood relaxation rates. RESULTS Using our software, pre- and post-contrast T1 maps were obtained in phantoms and healthy subjects resulting in a robust and reliable quantification as compared to reference software. Coregistration of pre- and post-contrast images improved the quality of ECV maps. Mean ECV value in healthy subjects was 24.5%±2.5%. CONCLUSIONS This study demonstrated that it is possible to obtain accurate T1 maps and informative ECV maps using our software. Pixel-wise ECV maps obtained with this automatic software made it possible to visualize and evaluate the extent and severity of ECV alterations.

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

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.

A feasible and automatic free tool for T1 and ECV mapping

Spatial localization of radioactive sources is currently a main issue interesting different fields, including nuclear industry, homeland security as well as medical imaging. It is currently achieved using different systems, but the development of technologies for detecting and characterizing radiation is becoming important especially in medical imaging. In this latter field, radiation detection probes have long been used to guide surgery, thanks to their ability to localize and quantify radiopharmaceutical uptake even deep in tissue. Radiolabelled colloid is injected into, or near to, the tumor and the surgeon uses a hand-held radiation detector, the gamma probe, to identify lymph nodes with radiopharmaceutical uptkake. The present work refers to a novel scintigraphic goniometric probe to identify gamma radiation and its direction. The probe incorporates several scintillation crystals joined together in a particular configuration to provide data related to the position of a gamma source. The main technical characteristics of the gamma locator prototype, i.e. sensitivity, spatial resolution and detection efficiency, are investigated. Moreover, the development of a specific procedure applied to the images permits to retrieve the source position with high precision with respect to the currently used gamma probes. The presented device shows a high sensitivity and efficiency to identify gamma radiation taking a short time (from 30 to 60 s). Even though it was designed for applications in radio-guided surgery, it could be used for other purposes, as for example homeland security.

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

BACKGROUND High Intensity Focused Ultrasound (HIFU) is a noninvasive treatment for therapeutic applications, in particular the treatment of either benign or malignant tumor lesions. HIFU treatment is based on the power of a focused ultrasound beam to locally heat biological tissues over a necrotic level with minimal impact on the surrounding tissues. Therapies based on HIFU are becoming widely spread in the panorama of options offered by the Health Care System. Consequently, there is an ever increasing need to standardise quality assurance protocols and to develop computational tools to evaluate the output of clinical HIFU devices and ensuring safe delivery of HIFU treatment. AIMS Goal of this study is the development of a computational tool for HIFU ablation therapy to assure safety of the patient and effectiveness of the treatment. RESULTS The simulated results provide information about the behaviour of the focalized ultrasound in their interaction with different biological tissues. CONCLUSIONS Numerical simulation represents a useful approach to predict the heath deposition and, consequently, to assess the safety and effectiveness of HIFU devices.

Development of a novel gamma probe for detecting radiation direction

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.