Periodic Reporting for period 1 - AMA (Advanced imaging system for Medical Applications)
Berichtszeitraum: 2023-11-01 bis 2025-12-31
Cancer remains one of the greatest global health challenges, with aggressive tumors like glioblastoma, head and neck cancers, and melanoma particularly difficult to treat. Boron Neutron Capture Therapy (BNCT) offers promising prospects by administering boron-enriched compounds that accumulate in tumor cells, then irradiating patients with neutrons that trigger nuclear reactions destroying cancer cells within cellular dimensions.
Despite BNCT's therapeutic promise, clinical adoption faces a critical obstacle: absence of real-time monitoring during treatment. Doctors rely entirely on pre-treatment imaging and blood analysis to estimate radiation doses, introducing 30-40% uncertainties that risk under-treating tumors or over-exposing healthy organs. Boron uptake varies significantly between patients and changes over time, making pretreatment predictions unreliable. With several operational accelerator-based BNCT facilities worldwide and more under development across Europe and Asia, accurate real-time dosimetry is increasingly urgent.
The AMA project transformed detector technology originally developed for nuclear physics research at CERN into a practical medical device addressing BNCT's dosimetry challenge. Building on the ERC Consolidator Grant HYMNS, the project demonstrated preclinical applicability of the i-TED Compton camera system for real-time boron monitoring in laboratory measurements emulating simplified BNCT treatments. Primary objectives included advancing technology readiness from laboratory prototype to demonstration in relevant environment (TRL6), validating sensitivity at clinical boron concentrations, linear system response, developing real-time image processing compatible with treatment durations, and establishing commercialization strategy with patent protection. The project strategically focused on leveraging i-TED's unique advantages: intrinsically low neutron background sensitivity, high efficiency for characteristic 478 keV gamma-rays from boron neutron capture, compact modular clinical design, and dual-modality capability (TRL4) detecting both gamma-rays and thermal neutrons simultaneously.
Despite BNCT's therapeutic promise, clinical adoption faces a critical obstacle: absence of real-time monitoring during treatment. Doctors rely entirely on pre-treatment imaging and blood analysis to estimate radiation doses, introducing 30-40% uncertainties that risk under-treating tumors or over-exposing healthy organs. Boron uptake varies significantly between patients and changes over time, making pretreatment predictions unreliable. With several operational accelerator-based BNCT facilities worldwide and more under development across Europe and Asia, accurate real-time dosimetry is increasingly urgent.
The AMA project transformed detector technology originally developed for nuclear physics research at CERN into a practical medical device addressing BNCT's dosimetry challenge. Building on the ERC Consolidator Grant HYMNS, the project demonstrated preclinical applicability of the i-TED Compton camera system for real-time boron monitoring in laboratory measurements emulating simplified BNCT treatments. Primary objectives included advancing technology readiness from laboratory prototype to demonstration in relevant environment (TRL6), validating sensitivity at clinical boron concentrations, linear system response, developing real-time image processing compatible with treatment durations, and establishing commercialization strategy with patent protection. The project strategically focused on leveraging i-TED's unique advantages: intrinsically low neutron background sensitivity, high efficiency for characteristic 478 keV gamma-rays from boron neutron capture, compact modular clinical design, and dual-modality capability (TRL4) detecting both gamma-rays and thermal neutrons simultaneously.
Computational studies using GEANT4 and MCNP6.3 optimized detector configurations, crystal geometries and characteristics. Clinical scenario modeling with B-loaded phantoms characterized performance under realistic conditions. GPU-accelerated 3D reconstruction algorithms were developed using CUDA and SYCL programming for hardware portability, with List-Mode MLEM algorithms enabling convergence within clinical timeframes.
Detector integration focused on electronic-collimation techniques with PETsys TOFPET2 ASIC electronics, developing signal amplification for 8×8 SiPM arrays and firmware modifications for neutron/gamma discrimination. CLYC-6 characterization demonstrated neutron-gamma discrimination (FoM 2.9) and sub-pixel resolution (5 mm), but revealed count-rate limitations. Strategic pivot to CLLBC scintillators achieved 6.5% energy resolution at 662 keV and count-rate handling above 200 kHz.
AIMPLAS developed Li-enriched polyethylene collimators (20 mm thickness, 2.5 mm aperture) with quality protocols achieving ±0.1 mm tolerances. Advanced coded-aperture designs using MURA patterns demonstrated 15.6-fold efficiency improvement through Monte Carlo simulations. Universidad de Granada prepared biological samples using cancer cell lines achieving 80 ppm boron concentrations and procured calibration references spanning 0.6-500 μg ¹⁰B.
Three experimental campaigns validated performance: ILL-Grenoble October 2023 deployed single i-TED module achieving sub-microgram sensitivity and biological sample validation; June 2024 deployed four-module array identifying count rate limitations with monolithic crystals and validating clinical concentrations (65-100 ppm); LENA Reactor November 2025 enabled system tests with new detector geometry at high neutron fluence demonstrating higher count rate capability and using mobile phantoms for 3D dose mapping.
Key achievements include optimized detector geometry reducing count rate limitations, GPU-accelerated processing achieving 120-fold speedup (8.25 seconds for 70,000 events), CLLBC integration extending count-rate capability for dual neutron-gamma imaging, clinical sensitivity validation detecting <1 μg ¹⁰B, spatial resolution of 20 mm FWHM at 100 mm distance, dual-modality concept validation with 26-34% neutron absorption measurement, and TRL advancement to level 6. The project produced five peer-reviewed publications, filed patent ES3049604, and established foundations for spin-off company commercialization.
Detector integration focused on electronic-collimation techniques with PETsys TOFPET2 ASIC electronics, developing signal amplification for 8×8 SiPM arrays and firmware modifications for neutron/gamma discrimination. CLYC-6 characterization demonstrated neutron-gamma discrimination (FoM 2.9) and sub-pixel resolution (5 mm), but revealed count-rate limitations. Strategic pivot to CLLBC scintillators achieved 6.5% energy resolution at 662 keV and count-rate handling above 200 kHz.
AIMPLAS developed Li-enriched polyethylene collimators (20 mm thickness, 2.5 mm aperture) with quality protocols achieving ±0.1 mm tolerances. Advanced coded-aperture designs using MURA patterns demonstrated 15.6-fold efficiency improvement through Monte Carlo simulations. Universidad de Granada prepared biological samples using cancer cell lines achieving 80 ppm boron concentrations and procured calibration references spanning 0.6-500 μg ¹⁰B.
Three experimental campaigns validated performance: ILL-Grenoble October 2023 deployed single i-TED module achieving sub-microgram sensitivity and biological sample validation; June 2024 deployed four-module array identifying count rate limitations with monolithic crystals and validating clinical concentrations (65-100 ppm); LENA Reactor November 2025 enabled system tests with new detector geometry at high neutron fluence demonstrating higher count rate capability and using mobile phantoms for 3D dose mapping.
Key achievements include optimized detector geometry reducing count rate limitations, GPU-accelerated processing achieving 120-fold speedup (8.25 seconds for 70,000 events), CLLBC integration extending count-rate capability for dual neutron-gamma imaging, clinical sensitivity validation detecting <1 μg ¹⁰B, spatial resolution of 20 mm FWHM at 100 mm distance, dual-modality concept validation with 26-34% neutron absorption measurement, and TRL advancement to level 6. The project produced five peer-reviewed publications, filed patent ES3049604, and established foundations for spin-off company commercialization.
The i-TED adapted system represents a potential solution for real-time BNCT dosimetry with no competing commercial systems available. The dual-modality capability—simultaneously mapping boron reaction rates and thermal neutron flux— could provide comprehensive dosimetric information enabling precise correlation between delivered dose and biological effects. Sub-microgram detection sensitivity enables non-destructive boron uptake measurement in cell cultures and tissue samples, accelerating BNCT drug development. Preclinical in-vitro validations demonstrated reduction of dose uncertainties, allowing to verify actual boron distributions during treatment and adjust parameters to maximize tumor dose while protecting critical organs. Scientific impact includes improvements in treatment planning algorithms and patient selection criteria.