Francesca Attanasi

Extension and validation of an analytical model for in vivo PET verification of proton therapy--a phantom and clinical study

The interest in positron emission tomography (PET) as a tool for treatment verification in proton therapy has become widespread in recent years, and several research groups worldwide are currently investigating the clinical implementation. After the first off-line investigation with a PET/CT scanner at MGH (Boston, USA), attention is now focused on an in-room PET application immediately after treatment in order to also detect shorter-lived isotopes, such as O15 and N13, minimizing isotope washout and avoiding patient repositioning errors. Clinical trials are being conducted by means of commercially available PET systems, and other tests are planned using application-dedicated tomographs. Parallel to the experimental investigation and new hardware development, great interest has been shown in the development of fast procedures to provide feedback regarding the delivered dose from reconstructed PET images. Since the thresholds of inelastic nuclear reactions leading to tissue β+ -activation fall within the energy range of 15-20 MeV, the distal activity fall-off is correlated, but not directly matched, to the distal fall-off of the dose distribution. Moreover, the physical interactions leading to β+ -activation and energy deposition are of a different nature. All these facts make it essential to further develop accurate and fast methodologies capable of predicting, on the basis of the planned dose distribution, expected PET images to be compared with actual PET measurements, thus providing clinical feedback on the correctness of the dose delivery and of the irradiation field position. The aim of this study has been to validate an analytical model and to implement and evaluate it in a fast and flexible framework able to locally predict such activity distributions directly taking the reference planning CT and planned dose as inputs. The results achieved in this study for phantoms and clinical cases highlighted the potential of the implemented method to predict expected activity distributions with great accuracy. Thus, the analytical model can be used as a powerful substitute method to the sensitive and time-consuming Monte Carlo approach.

Reprogrammable Acquisition Architecture for Dedicated Positron Emission Tomography

We have developed a flexible, cost-efficient PET architecture adaptPositron Emission Tomographyable to different applications and system geometries, such as positron emission mammography (PEM) and in-beam PET for dose delivery monitoring (ibPET). The acquisition system has been used to implement modularized dual planar detectors with very low front-end dead time, as required in PEM or in ibPET. The flexibility is obtained thanks to the FPGA-based, reprogrammable, TDC-less coincidence processor. The final goal is to propose an effective acquisition methodology and the construction of a compact, low-cost instrument able to provide early diagnosis and to improve the effectiveness of follow-up studies for smaller tumours with respect to those studied with present clinical equipment (e.g., whole-body PET, SPECT, or scintigraphy).

Experimental validation of the filtering approach for dose monitoring in proton therapy at low energy

The higher physical selectivity of proton therapy demands higher accuracy in monitoring of the delivered dose, especially when the target volume is located next to critical organs and a fractionated therapy is applied. A method to verify a treatment plan and to ensure the high quality of the hadrontherapy is to use Positron Emission Tomography (PET), which takes advantage of the nuclear reactions between protons and nuclei in the tissue during irradiation producing beta(+)-emitting isotopes. Unfortunately, the PET image is not directly proportional to the delivered radiation dose distribution; this is the reason why, at the present time, the verification of depth dose profiles with PET techniques is limited to a comparison between the measured activity and the one predicted for the planned treatment by a Monte Carlo model. In this paper we test the feasibility of a different scheme, which permits to reconstruct the expected PET signal from the planned radiation dose distribution along beam direction in a simpler and more direct way. The considered filter model, based on the description of the PET image as a convolution of the dose distribution with a filter function, has already demonstrated its potential applicability to beam energies above 70 MeV. Our experimental investigation provides support to the possibility of extending the same approach to the lower energy range ([40, 70] MeV), in the perspective of its clinical application in eye proton therapy.

A PET Prototype for “In-Beam” Monitoring of Proton Therapy

The in-beam PET is a novel PET application to image the beta+ activity induced in biological tissues by hadronic therapeutic beams. Thanks to the correlation existing between beam-delivered dose profiles and beam-induced activity profiles, in vivo information about the effective ion paths can be extracted from the in-beam pet image. in situ measurements, immediately after patient irradiation, are recommended in order to exploit the maximum statistics, by also detecting the contribution provided by the very short lived isotopes, e.g. 15O. A compact, dedicated tomograph should then be developed for such an application, so as to be used in the treatment room. We developed a small PET prototype in order to demonstrate the feasibility of such a technique for the monitoring of proton therapy of ocular tumors at the CATANA facility (Catania, Italy). The prototype consists of two planar heads with an active area of about 5 cm times 5 cm. Each head is made up of a square position sensitive photomultiplier (Hamamatsu H8500) coupled to a matrix of the same size of LYSO scintillating crystals (2 mm times 2 mm times 18 mm pixel dimensions). Dedicated, compact electronic boards are used for the signal multiplexing, amplification and digitization. The distance between the pair can be varied from 10 cm up to a maximum of about 20 cm. The validation of the prototype was performed on plastic phantoms using 62 MeV protons at the CATANA beam line. Different dose distributions were delivered and a good correlation between the distal fall-off of the activity profiles and of the dose profiles was found, i.e., better than 2 mm along the beam direction.

Characterization of an in-beam PET prototype for proton therapy with different target composition

Positron emission tomography is a valuable method for in situ and non invasive monitoring of the accuracy of the treatment in hadron therapy. It takes advantage of short lived β+- emitters spontaneously produced in the biological tissues during irradiation, by means of projectile and/or target nuclei fragmentations. Although β+- emitter production cross-sections and hadron stopping power exhibit a different dependence on the hadron energy, it is still possible to extract non invasively in vivo information about dose localization reconstructing the distribution of positron annihilation points.

Characterization of an In-Beam PET Prototype for Proton Therapy With Different Target Compositions

At the University of Pisa, the DoPET (Dosimetry with a Positron Emission Tomograph) project has focused on the development and characterization of an ad hoc, scalable, dual-head PET prototype for in-beam treatment planning verification of the proton therapy. In this paper we report the first results obtained with our current prototype, consisting of two opposing lutetium yttrium orthosilicate (LYSO) detectors, each one covering an area of 4.5 × 4.5 cm2. We measured the β+-activation induced by 62 MeV proton beams at Catana facility (LNS, Catania, Italy) in several plastic phantoms. Experiments were performed to evaluate the possibility to extract accurate phantom geometrical information from the reconstructed PET images. The PET prototype proved its capability of locating small air cavities in homogeneous PMMA phantoms with a submillimetric accuracy and of distinguishing materials with different 16O and 12C content by back mapping phantom geometry through the separation of the isotope contributions. This could be very useful in the clinical practice as a tool to highlight anatomical or physiological organ variations among different treatment sessions and to discriminate different tissue types, thus providing feedbacks for the accuracy of dose deposition.

A novel random counts estimation method for PET using a symmetrical delayed window technique and random single event acquisition

We have developed a novel logic scheme for the estimation of the random count distribution based on a dual symmetrical delayed window technique. The solution has been applied to a dual head PET case. We have also implemented a new method for noise variance reduction in the random count distribution.

A flexible acquisition system for modular dual head Positron Emission Mammography

We have developed a dedicated scanner for Positron Emission Mammography, equipped with a new detection architecture that enhances its flexibility and reduces dead time. The scanner is going to use Luthetium based scintillators, which offer good detection efficiency, and a novel modular acquisition system, capable of sustaining the high scintillation rate and being less sensitive to background radiation. The final goal is the construction of an instrument able to provide an early diagnosis and to improve the effectiveness of follow-up studies for smaller tumours with respect to those studied with present clinical equipment (e.g. PET, SPECT o scintigraphy) so as to be able to visualize and characterize breast lesions with diameters < 5 mm.

Clinical validation of an analytical procedure for in vivo PET range verification in proton therapy

Proton therapy is a treatment modality of increasing interest in clinical radiation oncology mostly because its dose distribution allows high dose conformality and a reduced integral dose compared to conventional radiation therapy based on X-rays and electrons. Its advantages are centered on the characteristic proton Bragg peak: a sharp maximum in the linear energy transfer of the projectile, that, if rightly positioned, makes the effect of the irradiation on the tissue more localized, thus increasing therapy efficacy and reducing side effects. The potential benefits of such physical selectivity have led to multiple studies addressed to the evaluation of uncertainty sources in the radiation therapy treatment process, from the initial treatment planning to the real patient dose delivery, thus providing insights into ways in which new imaging strategies are necessary to monitor, correct and adapt for possible errors. An interesting method to assess the geometric accuracy of the planned treatment delivery and to ensure the high quality of the proton therapy is to use Positron Emission Tomography (PET), which takes advantage of the nuclear inelastic reactions between protons and nuclei in the tissue during irradiation, producing small amounts of short-lived β+-emitting isotopes detectable soon after the irradiation. Verification of the therapy can be achieved by comparing and then quantifying differences between the PET images and the yield of the positron emitters predicted on the basis of the treatment planning system. The purpose of this study has been to extend an existing model and to implement and evaluate it in a fast and flexible framework to predict locally such activity distributions taking directly the reference planning CT and planned dose as inputs. The results achieved in this patient study highlighted the potential of the implemented analytical model, to monitor the dose delivery, proposing as a powerful substitution method to the sensitive and time-consuming Monte Carlo (MC) approach for the calculation of expected activity distributions.

TH‐D‐303A‐03: Validation of An Analytical 1D Filtering of the Dose Distribution for the Calculation of the Expected PET Distributions in Proton Therapy.

Purpose: A non‐invasive method for verification of treatment delivery to ensure the high quality of proton therapy is offered by Positron Emission Tomography(PET), which takes advantage of the β+‐activation produced via nuclear reactions between the protons and the nuclei of the tissue during irradiation,. Since dose distributions and measured PETimages are correlated but not identical, a procedure to provide clinical feedback on the correct dose delivery and irradiation field position is necessary. This study aims to validate the measured activity patterns by means of activity distributions calculated using a novel and fast one‐dimensional filtering model recently proposed. This way the actual dose delivery can be validated without reverting to Monte Carlo simulated PET distributions. Method: We derived the analytical expressions of the filters by converting the dose into the specific isotope profiles along the penetration depth, for all the main reaction channels which yield positron emitters in biological tissue. For the application to inhomogeneous targets a dedicated MATLAB®‐based code has been developed. Results: The new filters were first applied to monoenergetic depth dose distributions at different beam energies and the results were validated against FLUKA‐MC β+isotope distributions. All resulting distributions were found in agreement with the MC distributions, confirming filter independence from the proton beam energy. The filter functions were then applied to more realistic spread out Bragg peaks, simulated in simple inhomogeneous targets consisting of PMMA, lung and bone equivalent inserts. Conclusion: Results have shown a fairly good agreement in terms of both 50% distal fall‐off position (<1mm) and absolute value between simulated depth activity profiles and filter predictions (few percent), demonstrating how a proper filtering of the MC depth dose distribution can be used to predict in a simple and fast manner all the possible β+ activations of an arbitrary target.