Contrast enhanced proton range verification via PET emission

In Madrid they have been confirmed two facilities for proton therapy, delivering their first proton in late 2019, early 2020. One powered by IBA and another with HITACHI accelerators, gantry and delivery rooms. In total four treatment rooms and one physics line will be available soon. The GFN group is establishing collaborations with both facilities in order to put in play all the knowledge in nuclear instrumentation and simulation available at the group.

Activity

Prior to the development of the instrumentation, in the group we have been performing estimations of integral activity produced by protons in biological tissues, and the enhancement one can obtain with the use of suitable contrast agents. For instance, in the figure it is shown a tube of 1 cm2 cross-section after proton irradiation near the Bragg peak in pure water (red line), and with a contrast based on natural Zn (green line) at a tissue concentration of 5% 120 seconds right after irradiation. Very similar values are obtained for the first few seconds after irradiation. Gallium obtained from activated Zn is interesting also as a nuclear imaging isotope and shows potential for use in hadrontherapy range [4]. The presence of the Zn contrast greatly enhances the activity produced up to 2 mm close to the Bragg peak, and would gain great confidence with regards to range verification. A systematic study of many other potential contrast agents is being performed, and also a plan of experimental proposals to fill in the gaps in the knowledge of cross-sections needed to perform estimations of the activations of possible contrast agents.

Acoustic range verification of proton beams

At GFN we have been working on a prototype system for ionoacoustic range verification of proton beams, using low-noise hydrophones and amplifiers and a digital treatment of the acquired signals. The development of the prototype hardware has been complemented with detailed simulations of the system (using both Monte Carlo particle transport codes and analytical acoustic wave transport software) and with an analysis of available image reconstruction methods, which can improve the spatial accuracy of the detection system in environments with a low signal-to-noise ratio, as it is the case for protoacoustic range verification. The system prototype has been tested in local photon LINACs and radiosurgery beams and will soon be irradiated with a clinical proton beams. The results of the initial experimental tests and the development of the dose reconstruction algorithms will soon be published in relevant peer-reviewed journals.

The information exchange with other groups with relevant expertise in range verification (especially, the LMU group in Munich, with ample experience in ionoacoustics) has been fluid and helpful for the progress of our project. At GFN we have been combining this with our expertise in image reconstruction from ultrasound, in tomographic fashion. This way we intend to gain experience to use the ultrasound shock wave generated during hadrontherapy irradiation, which can be used for range verification. This ionoacoustic area is of current interest [5].

Radiobiological optimization of protontherapy plans

We have developed a new planning algorithm (MultiRBE) including a dual modeling of the radiobiological effectiveness (RBE) in tumor and healthy tissues with which we expect to reduce potential side effects caused by radiobiological uncertainties while maintaining coverage of physical dose to target volumes. The model was presented at the II Spanish Workshop in Proton Therapy and is now awaiting publication in a peer-reviewed journal.

Nuclear instrumentation of interest in protontherapy

The expertise of the GFN in designing and operating fast inorganic scintillators comes also very handy for the proton range verification with prompt gammas. The fast decay time of BrLa(Ce) and BrCe (<20 ns), scintillators routinely used in the group, together with its good efficiency and excellent energy resolution will make it possible to build detectors with high rate capability (in excess of 10 Mcps) and unparalleled spectroscopic capabilities, extremely interesting for proton range verification with prompt gamma emissions. Paving the way towards this goal, tests with one of the detectors of the group were performed [6] in at the CyberknifeTM unit (Accuray Technologies, Sunnyvale CA, USA) at of Hospital Ruber Internacional (Madrid, Spain). The time structure of the pulses were perfectly resolved with the detector (left part of the figure below), where the number of pulses against time is plotted against the trigger signal taken from the accelerator, and the spectra of photons coming from the head of the Cyberknife from different orientations, for the energy setting of 6 MV, has also been measured (right part of the figure).

The high rates that such a detector can sustain constitute a demanding challenge for conventional acquisition electronics, if both good energy, timing capabilities and high rates are desired. The conventional combination of integrating filter, Gaussian shaper and peak ADC will not be enough at rates in excess of 2 Mcps. However, current fully digital acquisition systems can handle >1 Gs/s with 12 bits of vertical resolution or better, and by means of PCIe or other fast connections, feed the data to the PC which, with the aid of GPUs and/o multicore computer can process the data on-the-fly, avoiding this way the huge storage required by off-line processing at these rates, nor the relatively specialized task of programming the algorithms in the embedded FPGA or DSP of the acquisition boards. The GFN has developed specific in-silico algorithms to process fully digitized nuclear detector pulses. Fully digitization of the pulses makes them amenable to all kind of digital algorithms and to try on deep learning approaches [7].  Compared to the conventional DAQ, the fully digital approach performed equally or better than the conventional one in timing and energy resolution capabilities, while holding the potential to handle much larger rates [7]. These achievements will proof useful both in protontherapy range verification as well as in the nuclear experiments that the group conducts in several facilities worldwide.

REFERENCES

1. Bauer, J., Unholtz, D., Sommerer, F., Kurz, C., Haberer, T., Herfarth, K., ... & Parodi, K. (2013). Implementation and initial clinical experience of offline PET/CT-based verification of scanned carbon ion treatment. Radiotherapy and Oncology, 107(2), 218-226.
2. Nishio, T., Ogino, T., Nomura, K., & Uchida, H. (2006). Dose‐volume delivery guided proton therapy using beam on‐line PET system. Medical physics, 33(11), 4190-4197.
3. Parodi, K., Paganetti, H., Shih, H. A., Michaud, S., Loeffler, J. S., DeLaney, T. F., ... & Bortfeld, T. (2007). Patient study of in vivo verification of beam delivery and range, using positron emission tomography and computed tomography imaging after proton therapy. International Journal of Radiation Oncology* Biology* Physics, 68(3), 920-934.
4. Fraile LM, Herraiz JL, Udías JM, Cal-González J, Corzo PMG, España S, herranz E, Pérez-Liva M, Picado E, Vicente E, Muñoz-Martín A, Vaquero JJ; Experimental validation of gallium production and isotope-dependent positron range correction in PET; Nuclear Instruments and Methods in Physics research A 814, 110-116 (2017)DOI: 10.1016/j.nima.2016.01.013
5. Pérez-Liva M, Herraiz JL, Udias JM; Time domain reconstruction of sound speed and attenuation in ultrasound computed tomography using full wave inversion; J Acoust Soc Am, 141(3),  1595- 1604 (2017) DOI: dx.doi.org/10.1121/1.4976688
6. Víctor Sánchez-Tembleque, Daniel Sánchez-Parcerisa, Víctor Valladolid-Onecha, Luis Mario Fraile, José Manuel Udías, Simultaneous measurement of the spectral and temporal properties of a LINAC pulse from outside the treatment room (submitted)
7. V. Sánchez-Tembleque, V. Vedia, L. M. Fraile, S. Ritt, J. M. Udías, Optimizing Time-Pickup Algorithms in Radiation Detectors with a Genetic Algorithm (submitted)