A feasibility study of enhanced prompt gamma imaging for range verification in proton therapy using deep learning.

. Range uncertainty is a major concern affecting the delivery precision in proton therapy. The Compton camera (CC)-based prompt-gamma (PG) imaging is a promising technique to provide 3Drange verification.

Pancreatic cancer derived 3D organoids as a clinical tool to evaluate the treatment response.

Background And Purpose: Pancreatic cancer (PC) is the fourth leading cause of cancer death in both men and women. The standard of care for patients with locally advanced PC of chemotherapy, stereotactic radiotherapy (RT), or chemo-radiation-therapy has shown highly variable and limited success rates. However, three-dimensional (3D) Pancreatic tumor organoids (PTOs) have shown promise to study tumor response to drugs, and emerging treatments under conditions.

Applications of Machine Learning to Improve the Clinical Viability of Compton Camera Based Range Verification in Proton Radiotherapy.

We studied the application of a deep, fully connected Neural Network (NN) to process prompt gamma (PG) data measured by a Compton camera (CC) during the delivery of clinical proton radiotherapy beams. The network identifies 1) recorded "bad" PG events arising from background noise during the measurement, and 2) the correct ordering of PG interactions in the CC to help improve the fidelity of "good" data used for image reconstruction. PG emission from a tissue-equivalent target during irradiation with a 150 MeV proton beam delivered at clinical dose rates was measured with a prototype CC.

The effects of Compton camera data acquisition and readout timing on PG imaging for proton range verification.

The purpose of this study was to determine how the characteristics of the data acquisition (DAQ) electronics of a Compton camera (CC) affect the quality of the recorded prompt gamma (PG) interaction data and the reconstructed images, during clinical proton beam delivery. We used the Monte-Carlo-plus-Detector-Effect (MCDE) model to simulate the delivery of a 150 MeV clinical proton pencil beam to a tissue-equivalent plastic phantom. With the MCDE model we analyzed how the recorded PG interaction data changed as two characteristics of the DAQ electronics of a CC were changed: (1) the number of data readout channels; and (2) the active charge collection, readout, and reset time.

Use of CBCT plus plan robustness for reducing QACT frequency in intensity-modulated proton therapy: Head-and-neck cases.

Purpose: Anatomic variation has a significant dosimetric impact in intensity-modulated proton therapy. Weekly or biweekly computed tomography (CT) scans, called quality assurance CTs (QACTs), are used to monitor anatomic and resultant dose changes to determine whether adaptive plans are needed. Frequent CT scans result in unwanted QACT dose and increased clinical workloads.

Comparison of reconstructed prompt gamma emissions using maximum likelihood estimation and origin ensemble algorithms for a Compton camera system tailored to proton range monitoring.

Compton-based prompt gamma (PG) imaging is being investigated by several groups as a potential solution for in vivo range monitoring in proton therapy. The performance of this technique depends on the detector system as well as the ability of the reconstruction method to obtain good spatial resolution to establish a quantitative correlation between the PG emission and the proton beam range in the patient. To evaluate the feasibility of PG imaging for range monitoring, we quantitatively evaluated the emission distributions reconstructed by a Maximum Likelihood Expectation Maximization (MLEM) and a Stochastic Origin Ensemble (SOE) algorithm.

Therapeutic Efficacy of Variable Biological Effectiveness of Proton Therapy in U-CH2 and MUG-Chor1 Human Chordoma Cell Death.

Chordoma is a cancer of spinal cord, skull base, and sacral area. Currently, the standard of care to treat chordoma is resection followed by radiation therapy. Since, chordoma is present in the spinal cord and these are very sensitive structures and often complete removal by surgery is not possible.

Secondary Particle Interactions in a Compton Camera Designed for Range Verification of Proton Therapy.

The purpose of this study was to determine the types, proportions, and energies of secondary particle interactions in a Compton camera (CC) during the delivery of clinical proton beams. The delivery of clinical proton pencil beams ranging from 70 to 200 MeV incident on a water phantom was simulated using Geant4 software (version 10.4).

Initial Validation of Proton Dose Calculations on SPR Images from DECT in Treatment Planning System.

Purpose: To investigate and quantify the potential benefits associated with the use of stopping-power-ratio (SPR) images created from dual-energy computed tomography (DECT) images for proton dose calculation in a clinical proton treatment planning system (TPS).

Materials And Methods: The DECT and single-energy computed tomography (SECT) scans obtained for 26 plastic tissue surrogate plugs were placed individually in a tissue-equivalent plastic phantom. Relative-electron density (ρ) and effective atomic number ( ) images were reconstructed from the DECT scans and used to create an SPR image set for each plug.

Impact of bowel and rectum air on target dose with robustly optimized intensity-modulated proton therapy plans.

Purpose: Pelvic target dose from intensity-modulated proton therapy (IMPT) is sensitive to patient bowel motion. Robustly optimized plans in regard to bowel filling may improve the dose coverage in the treatment course. Our purpose is to investigate the effect of air volume in large and small bowel and rectum on target dose from IMPT plans.

Computational model for detector timing effects in Compton-camera based prompt-gamma imaging for proton radiotherapy.

This paper describes a realistic simulation of a Compton-camera (CC) based prompt-gamma (PG) imaging system for proton range verification for a range of clinical dose rates, and its comparison to PG measured data with a pre-clinical CC. We used a Monte Carlo plus Detector Effects (MCDE) model to simulate the production of prompt gamma-rays (PG) and their energy depositions in the CC. With Monte Carlo, we simulated PG emission resulting from irradiation of a high density polyethylene phantom with a 150 MeV proton pencil beam at dose rates of 5.

Evaluation of Computed Tomography Scanners for Feasibility of Using Averaged Hounsfield Unit-to-Stopping Power Ratio Calibration Curve.

Purpose: The purpose of this study was to quantify the variability of stoichiometric calibration curves for different computed tomography (CT) scanners and determine whether an averaged Hounsfield unit (HU)-to-stopping power ratio (SPR) calibration curve can be used across multiple CT scanners.

Materials And Methods: Five CT scanners were used to scan an electron density phantom to establish HU values of known material plugs. A stoichiometric calibration curve was calculated for CT scanners and for the average curve.

A Monte Carlo model for organ dose reconstruction of patients in pencil beam scanning (PBS) proton therapy for epidemiologic studies of late effects.

Significant efforts such as the Pediatric Proton/Photon Consortium Registry (PPCR) involving multiple proton therapy centers have been made to conduct collaborative studies evaluating outcomes following proton therapy. As a groundwork dosimetry effort for the late effect investigation, we developed a Monte Carlo (MC) model of proton pencil beam scanning (PBS) to estimate organ/tissue doses of pediatric patients at the Maryland Proton Treatment Center (MPTC), one of the proton centers involved in the PPCR. The MC beam modeling was performed using the TOPAS (TOol for PArticle Simulation) MC code and commissioned to match measurement data within 1% for range, and 0.

Spectroscopic Compton imaging of prompt gamma emission at the MeV energy range.

This work explores a novel tomographic approach to PGAA that is both quantitative and spatially resolved, adapted from a clinical "proton beam range finder" in which MeV gamma rays are imaged by coincidence measurements of Compton scattered gamma rays with multi-detector arrays. We performed preliminary measurements using a Compton camera made with CdZnTe detector arrays on a series of test samples with high-energy (> 1 MeV) gamma emission lines. 3D image reconstructions were performed on the 2.

Determination of proton stopping power ratio with dual-energy CT in 3D-printed tissue/air cavity surrogates.

Purpose: To study the accuracy with which proton stopping power ratio (SPR) can be determined with dual-energy computed tomography (DECT) for small structures and bone-tissue-air interfaces like those found in the head or in the neck.

Methods: Hollow cylindrical polylactic acid (PLA) plugs (3 cm diameter, 5 cm height) were 3D printed containing either one or three septa with thicknesses t  = 0.8, 1.

In vivo range verification in particle therapy.

Exploitation of the full potential offered by ion beams in clinical practice is still hampered by several sources of treatment uncertainties, particularly related to the limitations of our ability to locate the position of the Bragg peak in the tumor. To this end, several efforts are ongoing to improve the characterization of patient position, anatomy, and tissue stopping power properties prior to treatment as well as to enable in vivo verification of the actual dose delivery, or at least beam range, during or shortly after treatment. This contribution critically reviews methods under development or clinical testing for verification of ion therapy, based on pretreatment range and tissue probing as well as the detection of secondary emissions or physiological changes during and after treatment, trying to disentangle approaches of general applicability from those more specific to certain anatomical locations.

Liposomes: Clinical Applications and Potential for Image-Guided Drug Delivery.

Liposomes have been extensively studied and are used in the treatment of several diseases. Liposomes improve the therapeutic efficacy by enhancing drug absorption while avoiding or minimizing rapid degradation and side effects, prolonging the biological half-life and reducing toxicity. The unique feature of liposomes is that they are biocompatible and biodegradable lipids, and are inert and non-immunogenic.

Rectal dose to prostate cancer patients treated with proton therapy with or without rectal spacer.

The purpose of this study was to evaluate whether a spacer inserted in the prerectal space could reduce modeled rectal dose and toxicity rates for patients with prostate cancer treated in silico with pencil beam scanning (PBS) proton therapy. A total of 20 patients were included in this study who received photon therapy (12 with rectal spacer (DuraSeal™ gel) and 8 without). Two PBS treatment plans were retrospectively created for each patient using the following beam arrangements: (1) lateral-opposed (LAT) fields and (2) left and right anterior oblique (LAO/RAO) fields.

Reply to Comment on 'Imaging of prompt gamma rays emitted during delivery of clinical proton beams with a Compton camera: feasibility studies for range verification'.

A reply is provided to the points raised in the comment by Dr Sitek (2016 Phys. Med. Biol.

Anteriorly Oriented Beam Arrangements with Daily in Vivo Range Verification for Proton Therapy of Prostate Cancer: Rectal Toxicity Rates.

Purpose: To model whether in vivo range verification could reduce high-grade rectal toxicity for patients with prostate cancer treated with pencil beam scanning proton therapy by allowing novel proton beam arrangements compared to standard lateral opposed beams.

Materials And Methods: Proton plans were generated for 8 patients with prostate cancer previously treated with photons by volumetric-modulated arc therapy (VMAT). The VMAT plans were generated by using a uniform 6-mm planning target volume (PTV) expansion.

Imaging of prompt gamma rays emitted during delivery of clinical proton beams with a Compton camera: feasibility studies for range verification.

The purpose of this paper is to evaluate the ability of a prototype Compton camera (CC) to measure prompt gamma rays (PG) emitted during delivery of clinical proton pencil beams for prompt gamma imaging (PGI) as a means of providing in vivo verification of the delivered proton radiotherapy beams. A water phantom was irradiated with clinical 114 MeV and 150 MeV proton pencil beams. Up to 500 cGy of dose was delivered per irradiation using clinical beam currents.

Detecting prompt gamma emission during proton therapy: the effects of detector size and distance from the patient.

Recent studies have suggested that the characteristics of prompt gammas (PGs) emitted from excited nuclei during proton therapy are advantageous for determining beam range during treatment delivery. Since PGs are only emitted while the beam is on, the feasibility of using PGs for online treatment verification depends greatly on the design of highly efficient detectors. The purpose of this work is to characterize how PG detection changes as a function of distance from the patient as a means of guiding the design and usage of clinical PG imaging detectors.

Tumor Spheroids as an in vitro model for determining the therapeutic response to proton beam radiotherapy and thermally sensitive nanocarriers.

Multicellular Tumor Spheroids (MCTS) strongly resemble tumor tissues, which makes them useful tools for radiation biology studies and screening of various chemotherapeutics. The goal of this pilot study was to use MCTS as an in vitro model to determine the response of cells to low temperature-sensitive liposomes (LTSLs) encapsulating doxorubicin (Dox) and proton beam radiotherapy (PBRT). Prior to treatment, MCTS were characterized for morphology and LTSLs were characterized for size, encapsulation efficiency, and ability to thermally release Dox (a model anticancer agent).

Measurement of characteristic prompt gamma rays emitted from oxygen and carbon in tissue-equivalent samples during proton beam irradiation.

The purpose of this work was to characterize how prompt gamma (PG) emission from tissue changes as a function of carbon and oxygen concentration, and to assess the feasibility of determining elemental concentration in tissues irradiated with proton beams. For this study, four tissue-equivalent water-sucrose samples with differing densities and concentrations of carbon, hydrogen, and oxygen were irradiated with a 48 MeV proton pencil beam. The PG spectrum emitted from each sample was measured using a high-purity germanium detector, and the absolute detection efficiency of the detector, average beam current, and delivered dose distribution were also measured.

The effects of Doppler broadening and detector resolution on the performance of three-stage Compton cameras.

Purpose: The authors investigated how the characteristics of the detectors used in a three-stage Compton camera (CC) affect the CC's ability to accurately measure the emission distribution and energy spectrum of prompt gammas (PG) emitted by nuclear de-excitations during proton therapy. The detector characteristics they studied included the material (high-purity germanium [HPGe] and cadmium zinc telluride [CZT]), Doppler broadening (DB), and resolution (lateral, depth, and energy).

Methods: The authors simulated three-stage HPGe and CZT CCs of various configurations, detecting gammas from point sources with energies ranging from 0.