Few-seconds range verification with short-lived positron emitters in carbon ion therapy.

In-beam PET (Positron Emission Tomography) is one of the most precise techniques for in-vivo range monitoring in hadron therapy. Our objective was to demonstrate the feasibility of a short irradiation run for range verification before a carbon-ion treatment. To do so a PMMA target was irradiated with a 220 MeV/u carbon-ion beam and annihilation coincidences from short-lived positron emitters were acquired after irradiations lasting 0.6 s. The experiments were performed at the synchrotron-based facility CNAO (Italian National Center of Oncological Hadrontherapy) by using the INSIDE in-beam PET detector. The results show that, with 3·107 carbon ions, the reconstructed positron emitting nuclei distribution is in good agreement with the predictions of a detailed FLUKA Monte Carlo study. Moreover, the radio-nuclei production is sufficiently abundant to determine the average ion beam range with a σ of 1 mm with a 6 s measurement of the activity distribution. Since the data were acquired when the beam was off, the proposed rapid calibration method can be applied to hadron beams extracted from accelerators with very different time structures.

A Monte Carlo detector response model for the IRIS PET preclinical scanner.

PET preclinical studies require high spatial resolution due to the limited size of the animal under investigation. To achieve this target, iterative image reconstruction algorithms are commonly preferred over the analytical methods because they offer the possibility of accurately modeling the whole imaging process. In this work, we propose an accurate factorized system matrix for the INVISCAN IRIS preclinical PET scanner to be used with an iterative algorithm. The model includes two components: the geometric component and the detector response of the system. The main innovative aspect of the work is the creation of the detector matrix using a Monte Carlo simulation, with a particular focus on the optimization of the simulation process to reduce the calculation time. The new system model is compared with the current IRIS model to evaluate the image quality, following the NEMA Standards NU 4-2008. The comparison showed an enhancement of the image quality, in terms of uniformity and recovery coefficients. This work confirms that the inclusion of the detector response into the system model leads to improved reconstruction results.

Online proton therapy monitoring: clinical test of a Silicon-photodetector-based in-beam PET.

Particle therapy exploits the energy deposition pattern of hadron beams. The narrow Bragg Peak at the end of range is a major advantage but range uncertainties can cause severe damage and require online verification to maximise the effectiveness in clinics. In-beam Positron Emission Tomography (PET) is a non-invasive, promising in-vivo technique, which consists in the measurement of the ß+ activity induced by beam-tissue interactions during treatment, and presents the highest correlation of the measured activity distribution with the deposited dose, since it is not much influenced by biological washout. Here we report the first clinical results obtained with a state-of-the-art in-beam PET scanner, with on-the-fly reconstruction of the activity distribution during irradiation. An automated time-resolved quantitative analysis was tested on a lacrimal gland carcinoma case, monitored during two consecutive treatment sessions. The 3D activity map was reconstructed every 10 s, with an average delay between beam delivery and image availability of about 6 s. The correlation coefficient of 3D activity maps for the two sessions (above 0.9 after 120 s) and the range agreement (within 1 mm) prove the suitability of in-beam PET for online range verification during treatment, a crucial step towards adaptive strategies in particle therapy.

TRIMAGE: A dedicated trimodality (PET/MR/EEG) imaging tool for schizophrenia.

Simultaneous PET/MR/EEG (Positron Emission Tomography - Magnetic Resonance - Electroencephalography), a new tool for the investigation of neuronal networks in the human brain, is presented here within the framework of the European Union Project TRIMAGE. The trimodal, cost-effective PET/MR/EEG imaging tool makes use of cutting edge technology both in PET and in MR fields. A novel type of magnet (1.5T, non-cryogenic) has been built together with a PET scanner that makes use of the most advanced photodetectors (i.e., SiPM matrices), scintillators matrices (LYSO) and digital electronics. The combined PET/MR/EEG system is dedicated to brain imaging and has an inner diameter of 260 mm and an axial Field-of-View of 160 mm. It enables the acquisition and assessment of molecular metabolic information with high spatial and temporal resolution in a given brain simultaneously. The dopaminergic system and the glutamatergic system in schizophrenic patients are investigated via PET, the same physiological/pathophysiological conditions with regard to functional connectivity, via fMRI, and its electrophysiological signature via EEG. In addition to basic neuroscience questions addressing neurovascular-metabolic coupling, this new methodology lays the foundation for individual physiological and pathological fingerprints for a wide research field addressing healthy aging, gender effects, plasticity and different psychiatric and neurological diseases. The preliminary performances of two components of the imaging tool (PET and MR) are discussed. Initial results of the search of possible candidates for suitable schizophrenia biomarkers are also presented as obtained with PET/MR systems available to the collaboration.

Improving fMRI in signal drop-out regions at 7 T by using tailored radio-frequency pulses: application to the ventral occipito-temporal cortex.

OBJECTIVE: Signal drop-off occurs in echo-planar imaging in inferior brain areas due to field gradients from susceptibility differences between air and tissue. Tailored-RF pulses based on a hyperbolic secant (HS) have been shown to partially recover signal at 3 T, but have not been tested at higher fields. MATERIALS AND METHODS: The aim of this study was to compare the performance of an optimized tailored-RF gradient-echo echo-planar imaging (TRF GRE-EPI) sequence with standard GRE-EPI at 7 T, in a passive viewing of faces or objects fMRI paradigm in healthy subjects. RESULTS: Increased temporal-SNR (tSNR) was observed in the middle and inferior temporal lobes and orbitofrontal cortex of all subjects scanned, but elsewhere tSNR decreased relative to the standard acquisition. In the TRF GRE-EPI, increased functional signal was observed in the fusiform, lateral occipital cortex, and occipital pole, regions known to be part of the visual pathway involved in face-object perception. CONCLUSION: This work highlights the potential of TRF approaches at 7 T. Paired with a reversed-gradient distortion correction to compensate for in-plane susceptibility gradients, it provides an improved acquisition strategy for future neurocognitive studies at ultra-high field imaging in areas suffering from static magnetic field inhomogeneities.

Characterization of high-resolution Gradient Echo and Spin Echo EPI for fMRI in the human visual cortex at 7T.

The increased signal-to-noise ratio (SNR) offered by functional Magnetic Resonance Imaging (fMRI) at 7T allows the acquisition of functional data at sub-millimetric spatial resolutions. However, simply reducing partial volume effects is not sufficient to precisely localize task-induced activation due to the indirect mechanisms that relate brain function and the changes in the measured signal. In this work T2* and T2 weighted Echo Planar Imaging (EPI) schemes based on Gradient Recalled Echo (GRE) and Spin Echo (SE) were evaluated in terms of temporal SNR, percent signal change, contrast to noise ratio (CNR), activation volume, and sensitivity and specificity to gray matter. Datasets were acquired during visual stimulation at in-plane resolutions ranging between 1.5×1.5mm2 and 0.75×0.75mm2 targeting the early visual cortex. While similar activation foci were obtained in all acquisitions, at in-plane resolutions of 1.0×1.0mm2 and larger voxel sizes the T2 weighted contrast of SE-EPI allowed the identification of the activation site with better spatial accuracy. However, at sub-millimetric resolutions the decrease in temporal SNR significantly hampered the sensitivity and the extent of the activation site. On the other hand, high resolution T2* weighted data collected with GRE-EPI provided higher CNR and sensitivity, benefiting from the decreased physiological and partial volume effects. However, spurious activations originating from regions of blood drainage were still present in GRE data, and simple thresholding techniques were found to be inadequate for the removal of such contributions. The combination of 2-class and 3-class automated segmentations, performed directly in EPI space, allowed the selection of active voxels in gray matter. This approach could enable GRE-EPI to accurately map functional activity with satisfactory CNR and specificity to the true site of activation.

Depth of interaction determination in monolithic scintillator with double side SiPM readout.

BACKGROUND: Monolithic scintillators read out by arrays of photodetectors represent a promising solution to obtain high spatial resolution and the depth of interaction (DOI) of the annihilation photon. We have recently investigated a detector geometry composed of a monolithic scintillator readout on two sides by silicon photomultiplier (SiPM) arrays, and we have proposed two parameters for the DOI determination: the difference in the number of triggered SiPMs on the two sides of the detector and the difference in the maximum collected signal on a single SiPM on each side. This work is focused on the DOI calibration and on the determination of the capability of our detector. For the DOI calibration, we studied a method which can be implemented also in detectors mounted in a full PET scanner. We used a PET detector module composed of a monolithic 20 × 20 × 10 mm3 LYSO scintillator crystal coupled on two opposite faces to two arrays of SiPMs. On each side, the scintillator was coupled to 6 × 6 SiPMs. In this paper, the two parameters previously proposed for the DOI determination were calibrated with two different methods. The first used a lateral scan of the detector with a collimated 511 keV pencil beam at steps of 0.5 mm to study the detector DOI capability, while the second used the background radiation of the 176Lu in the scintillator. The DOI determination capability was tested on different regions of the detector using each parameter and the combination of the two. RESULTS: With both parameters for the DOI determination, in the lateral scan, the bias between the mean reconstructed DOI and the real beam position was lower than 0.3 mm, and the DOI distribution had a standard deviation of about 1.5 mm. When using the calibration with the radioactivity of the LYSO, the mean bias increased of about 0.2 mm but with no degradation of the standard deviation of the DOI distribution. CONCLUSIONS: The two parameters allow to achieve a DOI resolution comparable with the state of the art, giving a continuous information about the three-dimensional interaction position of the scintillation. These results were obtained by using simple estimators and a detector scalable to a whole PET system. The DOI calibration obtained using lutetium natural radioactivity gives results comparable to the other standard method but appears more readily applicable to detectors mounted in a full PET scanner.

INSIDE in-beam positron emission tomography system for particle range monitoring in hadrontherapy.

The quality assurance of particle therapy treatment is a fundamental issue that can be addressed by developing reliable monitoring techniques and indicators of the treatment plan correctness. Among the available imaging techniques, positron emission tomography (PET) has long been investigated and then clinically applied to proton and carbon beams. In 2013, the Innovative Solutions for Dosimetry in Hadrontherapy (INSIDE) collaboration proposed an innovative bimodal imaging concept that combines an in-beam PET scanner with a tracking system for charged particle imaging. This paper presents the general architecture of the INSIDE project but focuses on the in-beam PET scanner that has been designed to reconstruct the particles range with millimetric resolution within a fraction of the dose delivered in a treatment of head and neck tumors. The in-beam PET scanner has been recently installed at the Italian National Center of Oncologic Hadrontherapy (CNAO) in Pavia, Italy, and the commissioning phase has just started. The results of the first beam test with clinical proton beams on phantoms clearly show the capability of the in-beam PET to operate during the irradiation delivery and to reconstruct on-line the beam-induced activity map. The accuracy in the activity distal fall-off determination is millimetric for therapeutic doses.

Accurate and efficient modeling of the detector response in small animal multi-head PET systems.

In fully three-dimensional PET imaging, iterative image reconstruction techniques usually outperform analytical algorithms in terms of image quality provided that an appropriate system model is used. In this study we concentrate on the calculation of an accurate system model for the YAP-(S)PET II small animal scanner, with the aim to obtain fully resolution- and contrast-recovered images at low levels of image roughness. For this purpose we calculate the system model by decomposing it into a product of five matrices: (1) a detector response component obtained via Monte Carlo simulations, (2) a geometric component which describes the scanner geometry and which is calculated via a multi-ray method, (3) a detector normalization component derived from the acquisition of a planar source, (4) a photon attenuation component calculated from x-ray computed tomography data, and finally, (5) a positron range component is formally included. This system model factorization allows the optimization of each component in terms of computation time, storage requirements and accuracy. The main contribution of this work is a new, efficient way to calculate the detector response component for rotating, planar detectors, that consists of a GEANT4 based simulation of a subset of lines of flight (LOFs) for a single detector head whereas the missing LOFs are obtained by using intrinsic detector symmetries. Additionally, we introduce and analyze a probability threshold for matrix elements of the detector component to optimize the trade-off between the matrix size in terms of non-zero elements and the resulting quality of the reconstructed images. In order to evaluate our proposed system model we reconstructed various images of objects, acquired according to the NEMA NU 4-2008 standard, and we compared them to the images reconstructed with two other system models: a model that does not include any detector response component and a model that approximates analytically the depth of interaction as detector response component. The comparisons confirm previous research results, showing that the usage of an accurate system model with a realistic detector response leads to reconstructed images with better resolution and contrast recovery at low levels of image roughness.

Development of a new, fast, user friendly, ray tracing program "CSIM" for the simulation of parallelhole collimators.

We have developed a fast, user friendly, ray-tracing program, "CSIM" for low-energy gamma rays (up to ∼200keV) to simulate the performance characteristics of parallelhole collimators. We have used a ray-tracing approach to find the sensitivity and resolution of the parallelhole collimator by including the penetration of photons through the collimator due to the finite attenuation of the collimator material. "CSIM" can calculate the sensitivity of the collimator, the geometric and penetrating photon ratios, and the 1D and 2D point source response functions (PSF) with the statistical uncertainty for different hole shapes (e.g. square, hexagonal, and cylindrical). We have used "CSIM" to simulate the collimator of the YAP-(S)PETII small animal scanner. We present the analysis of the YAP-(S)PETII scanner round-hole parallel collimator designed for nuclear medicine imaging at 140keV. For this aim, different designs have been considered for a variety of source-collimator distances (b=5, 10, 15, 20cm). Resolution and sensitivity characteristics have been plotted as a function of the collimator thickness and the diameter of the hole. For each value of the source-collimator distance, and for each collimator thickness investigated, the trade-off between sensitivity and spatial resolution has been given as a series of characteristic curves. Then, we compare our simulated resolution and sensitivity results to the analytically calculated ones and found that the analytically calculated results for the YAP-(S)PETII scanner collimator are not far away the results predicted by CSIM and also with the experimentally measured resolution values.

Curriculum for education and training of medical physicists in nuclear medicine: recommendations from the EANM Physics Committee, the EANM Dosimetry Committee and EFOMP.

PURPOSE: To provide a guideline curriculum covering theoretical and practical aspects of education and training for Medical Physicists in Nuclear Medicine within Europe. MATERIAL AND METHODS: National training programmes of Medical Physics, Radiation Physics and Nuclear Medicine physics from a range of European countries and from North America were reviewed and elements of best practice identified. An independent panel of experts was used to achieve consensus regarding the content of the curriculum. RESULTS: Guidelines have been developed for the specialist theoretical knowledge and practical experience required to practice as a Medical Physicist in Nuclear Medicine in Europe. It is assumed that the precondition for the beginning of the training is a good initial degree in Medical Physics at master level (or equivalent). The Learning Outcomes are categorised using the Knowledge, Skill and Competence approach along the lines recommended by the European Qualifications Framework. The minimum level expected in each topic in the theoretical knowledge and practical experience sections is intended to bring trainees up to the requirements expected of a Medical Physicist entering the field of Nuclear Medicine. CONCLUSIONS: This new joint EANM/EFOMP European guideline curriculum is a further step to harmonise specialist training of Medical Physicists in Nuclear Medicine within Europe. It provides a common framework for national Medical Physics societies to develop or benchmark their own curricula. The responsibility for the implementation and accreditation of these standards and guidelines resides within national training and regulatory bodies.

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.