Computational Nuclear Oncology Toward Precision Radiopharmaceutical Therapies: Ethical, Regulatory, and Socioeconomic Dimensions of Theranostic Digital Twins.

Computational nuclear oncology for precision radiopharmaceutical therapy (RPT) is a new frontier for theranostic treatment personalization. A key strategy relies on the possibility to incorporate clinical, biomarker, image-based, and dosimetric information in theranostic digital twins (TDTs) of patients to move beyond a one-size-fits-all approach. The TDT framework enables treatment optimization by real-time monitoring of the real-world system, simulation of different treatment scenarios, and prediction of resulting treatment outcomes, as well as facilitating collaboration and knowledge sharing among health care professionals adopting a harmonized TDT.

Embracing the Future of Clinical Trials in Radiotherapy: An NRG Oncology CIRO Technology Retreat Whitepaper on Pioneering Technologies and AI-Driven Solutions.

This white paper examines the potential of pioneering technologies and artificial intelligence (AI)-driven solutions in advancing clinical trials involving radiotherapy. As the field of radiotherapy evolves, the integration of cutting-edge approaches such as radiopharmaceutical dosimetry, FLASH radiotherapy, image-guided radiation therapy (IGRT), and AI promises to improve treatment planning, patient care, and outcomes. Additionally, recent advancements in quantum science, linear energy transfer/relative biological effect (LET/RBE), and the combination of radiotherapy and immunotherapy create new avenues for innovation in clinical trials.

Liver Radioembolization: Predicting Lung Shunt Fraction with Contrast-Enhanced CT, Eliminating the Need for 99mTc-MAA.

Unlabelled: Accurate estimation of the Lung Shunt Fraction (LSF) is a standard of care in yttrium-90 ( Y) radioembolization treatment planning to prevent excessive lung irradiation due to arterio-venous shunting in the liver. LSF is assessed using Tc macroaggregated albumin ( Tc-MAA) imaging, but this approach adds risk, complexity, and expense to the treatment planning. This study investigates the potential of Contrast-Enhanced Computed Tomography (CECT) as a non-invasive alternative for LSF estimation.

Translating contrast enhanced computed tomography images to liver radioembolization dose distribution for more comprehensively indicating patients.

Contrast-enhanced computed tomography (CECT) is commonly used in the pre-treatment evaluation of liver Y-90 radioembolization feasibility. CECT provides detailed imaging of the liver and surrounding structures, allowing healthcare providers to assess the size, location, and characteristics of liver tumors prior to the treatment. Here we propose a method for translating CECT images to an expected dose distribution for tumor(s) and normal liver tissue.

GPU optimization techniques to accelerate optiGAN-a particle simulation GAN.

The demand for specialized hardware to train AI models has increased in tandem with the increase in the model complexity over the recent years. Graphics processing unit (GPU) is one such hardware that is capable of parallelizing operations performed on a large chunk of data. Companies like Nvidia, AMD, and Google have been constantly scaling-up the hardware performance as fast as they can.

Ultrasensitive and multiplexed tracking of single cells using whole-body PET/CT.

In vivo molecular imaging tools are crucially important for elucidating how cells move through complex biological systems; however, achieving single-cell sensitivity over the entire body remains challenging. Here, we report a highly sensitive and multiplexed approach for tracking upward of 20 single cells simultaneously in the same subject using positron emission tomography (PET). The method relies on a statistical tracking algorithm (PEPT-EM) to achieve a sensitivity of 4 becquerel per cell and a streamlined workflow to reliably label single cells with over 50 becquerel per cell of F-fluorodeoxyglucose (FDG).

Cherenkov Light Emission in Pure Cherenkov Emitters for Prompt Gamma Imaging.

Proton range verification (PRV) in proton therapy by means of prompt-gamma detection is a promising but challenging approach. High count rates, energies ranging between 1 MeV and 7 MeV, and a strong background complicate the detection of such particles. In this work, the Cherenkov light generated by prompt-gammas in the pure Cherenkov emitters TlBr, TlCl and PbF was studied.

Efficient and multiplexed tracking of single cells using whole-body PET/CT.

molecular imaging tools are crucially important for elucidating how cells move through complex biological systems, however, achieving single-cell sensitivity over the entire body remains challenging. Here, we report a highly sensitive and multiplexed approach for tracking upwards of 20 single cells simultaneously in the same subject using positron emission tomography (PET). The method relies on a new tracking algorithm (PEPT-EM) to push the cellular detection threshold to below 4 Bq/cell, and a streamlined workflow to reliably label single cells with over 50 Bq/cell of F-fluorodeoxyglucose (FDG).

Potential of Depth-of-Interaction-Based Detection Time Correction in Cherenkov Emitter Crystals for TOF-PET.

Cherenkov light can improve the timing resolution of Positron Emission Tomography (PET) radiation detectors, thanks to its prompt emission. Coincidence time resolutions (CTR) of ~30 ps were recently reported when using 3.2 mm-thick Cherenkov emitters.

The SNR of Positron Emission Data With Gaussian and Non-Gaussian Time-of-Flight Kernels, With Application to Prompt Photon Coincidence.

It is well known that measurement of the time-of-flight (TOF) increases the information provided by coincident events in positron emission tomography (PET). This information increase propagates through the reconstruction and improves the signal-to-noise ratio in the reconstructed images. Takehiro Tomitani has analytically computed the gain in variance in the reconstructed image, provided by a particular TOF resolution, for the center of a uniform disk and for a Gaussian TOF kernel.

Preclinical Evaluation of Ga- and Lu-Labeled Integrin αβ-Targeting Radiotheranostic Peptides.

The integrin αβ, an epithelium-specific cell surface receptor, is overexpressed on numerous malignancies, including the highly lethal pancreatic ductal adenocarcinomas. Here, we developed and tested a novel αβ-targeting peptide, DOTA-5G () radiolabeled with Ga, for PET/CT imaging and Lu for treatment. With the goal to develop a radiotheranostic, further modifications were made for increased circulation time, renal recycling, and tumor uptake, yielding DOTA-albumin-binding moiety-5G ().

The OpenGATE ecosystem for Monte Carlo simulation in medical physics.

This paper reviews the ecosystem of GATE, an open-source Monte Carlo toolkit for medical physics. Based on the shoulders of Geant4, the principal modules (geometry, physics, scorers) are described with brief descriptions of some key concepts (Volume, Actors, Digitizer). The main source code repositories are detailed together with the automated compilation and tests processes (Continuous Integration).

The Impact of Injection Distance to Bifurcations on Yttrium-90 Distribution in Liver Cancer Radioembolization.

Purpose: To model the effect of the injection location on the distribution of yttrium-90 (Y) microspheres in the liver during radioembolization using computational simulation and to determine the potential effects of radial movements of the catheter tip.

Materials And Methods: Numerical studies were conducted using images from a representative patient with hepatocellular carcinoma. The right hepatic artery (RHA) was segmented from contrast-enhanced cone-beam computed tomography scans.

Effect of crystal-photodetector interface extraction efficiency on Cerenkov photons' detection time.

Using Cerenkov photons to improve detector timing resolution in time-of-flight positron emission tomography scanners is promising since they constitute most of the signal rising edge. The main challenge in using Cerenkov light is its low yield per photoelectric interaction, which requires optimizing their complex optical transport in the detector. Monte Carlo simulations unlock information unavailable through benchtop measurements and help better understand the Cerenkov photon behavior.

The Accuracy of Cerenkov Photons Simulation in Geant4/Gate Depends on the Parameterization of Primary Electron Propagation.

Energetic electrons traveling in a dispersive medium can produce Cerenkov radiation. Cerenkov photons' prompt emission, combined with their predominantly forward emission direction with respect to the parent electron, makes them extremely promising to improve radiation detector timing resolution. Triggering gamma detections based on Cerenkov photons to achieve superior timing resolution is challenging due to the low number of photons produced per interaction.

Radioembolization Dosimetry with Total-Body Y PET.

Transarterial radioembolization (TARE) is a locoregional radiopharmaceutical therapy based on the delivery of radioactive Y microspheres to liver tumors. The importance of personalized dosimetry to make TARE safer and more effective has been demonstrated in recent clinical studies, stressing the need for quantification of the dose-response relationship to ultimately optimize the administered activity before treatment and image it after treatment. Y dosimetric studies are challenging because of the lack of accurate and precise methods but are best realized with PET combined with Monte Carlo simulations and other image modalities to calculate a segmental dose distribution.

Integration of polarization in the LUTDavis model for optical Monte Carlo simulation in radiation detectors.

Objective: Cerenkov photons have distinctive features from scintillation photons. Among them is their polarization: their electric field is always perpendicular to the direction of propagation of light and parallel to the plane of incidence. Scintillation photons are instead considered unpolarized.

Study of Čerenkov Light Emission in the Semiconductors TlBr and TlCl for TOF-PET.

Thallium bromide (TlBr) and thallium chloride (TlCl) are semiconductor materials with high transparency to visible light, high index of refraction, and high detection efficiency for gamma rays and annihilation photons. This manuscript reports on measurements of the light intensity and timing response of Čerenkov light emitted in one 3 mm × 3 mm × 5 mm slab of each of these materials operated in coincidence with a lutetium fine silicate (LFS) crystal with dimensions of 3 mm × 3 mm × 20 mm. A Na radioactive source was used.

Optimization of scintillator-reflector optical interfaces for the LUT Davis model.

Purpose: Designing and optimizing scintillator-based gamma detector using Monte Carlo simulation is of great importance in nuclear medicine and high energy physics. In scintillation detectors, understanding the light transport in the scintillator and the light collection by the photodetector plays a crucial role in achieving high performance. Thus, accurately modeling them is critical.

Realistic boundary conditions in SimVascular through inlet catheter modeling.

Objective: This study aims at developing a pipeline that provides the capability to include the catheter effect in the computational fluid dynamics (CFD) simulations of the cardiovascular system and other human vascular flows carried out with the open-source software SimVascular. This tool is particularly useful for CFD simulation of interventional radiology procedures such as tumor embolization where estimation of a therapeutic agent distribution is of interest.

Results: A pipeline is developed that generates boundary condition files which can be used in SimVascular CFD simulations.

Technical Note: Standalone application to generate custom reflectance Look-Up Table for advanced optical Monte Carlo simulation in GATE/Geant4.

Purpose: The need for high-fidelity modeling of radiation detectors to perform reliable detector performance optimization using Monte Carlo simulations requires to accurately simulate the light transport in the scintillator and the light collection by the photodetector. In this work, we implement our well-validated crystal reflectance model computed from three-dimensional (3D) crystal surface measurement in a standalone open-source application to allow researchers to generate fully customized crystal reflectance look-up-tables (LUTs) to be used in optical Monte Carlo simulation.

Methods: The LUTDavisModel application can be installed in a few minutes on Windows, macOS, and Linux, using 26 MB of space.

Advanced Monte Carlo simulations of emission tomography imaging systems with GATE.

Built on top of the Geant4 toolkit, GATE is collaboratively developed for more than 15 years to design Monte Carlo simulations of nuclear-based imaging systems. It is, in particular, used by researchers and industrials to design, optimize, understand and create innovative emission tomography systems. In this paper, we reviewed the recent developments that have been proposed to simulate modern detectors and provide a comprehensive report on imaging systems that have been simulated and evaluated in GATE.

Quantitative PET in the 2020s: a roadmap.

Positron emission tomography (PET) plays an increasingly important role in research and clinical applications, catalysed by remarkable technical advances and a growing appreciation of the need for reliable, sensitive biomarkers of human function in health and disease. Over the last 30 years, a large amount of the physics and engineering effort in PET has been motivated by the dominant clinical application during that period, oncology. This has led to important developments such as PET/CT, whole-body PET, 3D PET, accelerated statistical image reconstruction, and time-of-flight PET.