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. As the proton beam dose rate increased, the number of recorded PG single-, double-, and triple-scatter events decreased by a factor of 60× for the current DAQ configuration of the CC. However, as the DAQ readout channels were increased and the readout/reset timing decreased, the number of recorded events decreased by <5× at the highest clinical dose rate. The increased number of readout channels and reduced readout/reset timing also resulted in higher quality recorded data. That is, a higher percentage of the recorded double- and triple-scatters were "true" events (caused by a single incident gamma) and not "false" events (caused by multiple incident gammas). The increase in the number and the quality of recorded data allowed higher quality PG images to be reconstructed even at the highest clinical dose rates.

Secondary Particle Interactions in a Compton Camera Designed for in vivo 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). The simulation included a CC similar to the configuration of a Polaris J3 CC designed to image prompt gammas (PGs) emitted during proton beam irradiation for the purpose of in vivo range verification. The interaction positions and energies of secondary particles in each CC detector module were scored. For a 150-MeV proton beam, a total of 156,688(575) secondary particles per 108 protons, primarily composed of gamma rays (46.31%), neutrons (41.37%), and electrons (8.88%), were found to reach the camera modules, and 79.37% of these particles interacted with the modules. Strategies for using CCs for proton range verification should include methods of reducing the large neutron backgrounds and low-energy non-PG radiation. The proportions of interaction types by module from this study may provide information useful for background suppression.

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 (ρe) and effective atomic number (Z eff) images were reconstructed from the DECT scans and used to create an SPR image set for each plug. Next, the SPR for each plug was measured in a clinical proton beam for comparison of the calculated values in the SPR images. The SPR images and SECTs were then imported into a clinical TPS, and treatment plans were developed consisting of a single field delivering a 10 × 10 × 10-cm3 spread-out Bragg peak to a clinical target volume that contained the plugs. To verify the accuracy of the TPS dose calculated from the SPR images and SECTs, treatment plans were delivered to the phantom containing each plug, and comparisons of point-dose measurements and 2-dimensional γ-analysis were performed. RESULTS: For all 26 plugs considered in this study, SPR values for each plug from the SPR images were within 2% agreement with measurements. Additionally, treatment plans developed with the SPR images agreed with the measured point dose to within 2%, whereas a 3% agreement was observed for SECT-based plans. γ-Index pass rates were > 90% for all SECT plans and > 97% for all SPR image-based plans. CONCLUSION: Treatment plans created in a TPS with SPR images obtained from DECT scans are accurate to within guidelines set for validation of clinical treatment plans at our center. The calculated doses from the SPR image-based treatment plans showed better agreement to measured doses than identical plans created with standard SECT scans.

Targeted Osmotic Lysis of Highly Invasive Breast Carcinomas Using Pulsed Magnetic Field Stimulation of Voltage-Gated Sodium Channels and Pharmacological Blockade of Sodium Pumps.

Abstract: Concurrent activation of voltage-gated sodium channels (VGSCs) and blockade of Na+ pumps causes a targeted osmotic lysis (TOL) of carcinomas that over-express the VGSCs. Unfortunately, electrical current bypasses tumors or tumor sections because of the variable resistance of the extracellular microenvironment. This study assesses pulsed magnetic fields (PMFs) as a potential source for activating VGSCs to initiate TOL in vitro and in vivo as PMFs are unaffected by nonconductive tissues. In vitro, PMFs (0-80 mT, 10 msec pulses, 15 pps for 10 min) combined with digoxin-lysed (500 nM) MDA-MB-231 breast cancer cells stimulus-dependently. Untreated, stimulation-only, and digoxin-only control cells did not lyse. MCF-10a normal breast cells were also unaffected. MDA-MB-231 cells did not lyse in a Na+-free buffer. In vivo, 30 min of PMF stimulation of MDA-MB-231 xenografts in J/Nu mice or 4T1 homografts in BALB/c mice, concurrently treated with 7 mg/kg digoxin reduced tumor size by 60-100%. Kidney, spleen, skin and muscle from these animals were unaffected. Stimulation-only and digoxin-only controls were similar to untreated tumors. BALB/C mice with 4T1 homografts survived significantly longer than mice in the three control groups. The data presented is evidence that the PMFs to activate VGSCs in TOL provide sufficient energy to lyse highly malignant cells in vitro and to reduce tumor growth of highly malignant grafts and improve host survival in vivo, thus supporting targeted osmotic lysis of cancer as a possible method for treating late-stage carcinomas without compromising noncancerous tissues.

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 5.0 × 108, 2.6 × 109, and 4.6 × 109 p+ s-1. Realistic detector timing effects (e.g. delayed triggering time, event-coincidence, dead time, etc,) were added in post-processing to allow for flexible count rate variations. We acquired PG emission measurements with our pre-clinical CC during irradiation with a clinical 150 MeV proton pencil beam at the same dose rates. For simulations and measurements, three primary changes could be seen in the PG emission data as the dose rate increased: (1) reduction in the total number of detected events due to increased dead-time percentage; (2) increase in false-coincidence events (i.e. multiple PGs interacting, rather than a single PG scatter); and (3) loss of distinct PG emission peaks in the energy spectrum. We used the MCDE model to estimate the quality of our measured PG data, primarily with regards to true and false double-scatters and triple-scatters recorded by the CC. The simulation results showed that of the recorded double-scatter PG interactions 22%, 57%, and 70% were false double-scatters and for triple-scatter interactions 3%, 21%, and 35% were false events at 5.0 × 108, 2.6 × 109, and 4.6 × 109 p+ s-1, respectively. These false scatter events represent noise in the data, and the high percentage of these events in the data represents a major limitation in our ability to produce usable PG images with our prototype CC.

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 tsepta  = 0.8, 1.6, 3.2, and 6.4 mm running along the length of the plug. The cylinders were inserted individually into a tissue-equivalent head phantom (16 cm diameter, 5 cm height). First, DECT scans were obtained using a Siemens SOMATOM Definition Edge CT scanner. Effective atomic number (Zeff ) and electron density (ρe ) images were reconstructed from the DECT to produce SPR-CT images of each plug. Second, independent elemental composition analysis of the PLA plastic was used to determine the Zeff and ρe for calculating the theoretical SPR (SPR-TH) using the Bethe-Bloch equation. Finally, for each plug, a direct measurement of SPR (SPR-DM) was obtained in a clinical proton beam. The values of SPR-CT, SPR-TH, and SPR-DM were compared. RESULTS: The SPR-CT for PLA agreed with SPR-DM for tsepta  ≥ 3 mm (for CT slice thicknesses of 0.5, 1.0, and 3.0 mm). The density of PLA was found to decrease with thickness when tsepta  < 3 mm. As tsepta (and density) decreased, the SPR-CT values also decreased, in good agreement with SPR-DM and SPR-TH. CONCLUSION: Overall, the DECT-based SPR-CT was within 3% of SPR-TH and SPR-DM in the high-density gradient regions of the 3D-printed plugs for septa greater than ~ 3mm in thickness.

Cell-shaped silicon-on-insulator microdosimeters: characterization and response to 239PuBe irradiations.

This work tested the feasibility of a silicon-on-insulator microdosimeter, which mimics the size and shape of specific cells within the human body, to determine dose equivalent from neutron irradiation. The microdosimeters were analyzed in terms of their basic diode characteristics, i.e., leakage current as a function of bias voltage. Lineal energy spectra were acquired using two different converter layers placed atop the microdosimeter: a tissue-substitute converter made from high-density polyethylene, and a boron converter consisting of epoxy coated with boron powder. The spectra were then converted into absorbed dose and dose equivalent. Experimental results were compared to Monte Carlo simulations of the neutron irradiations, revealing good agreement. Uncertainty in the dose equivalent determinations was 7.5% when using the cell-shaped microdosimeter with the tissue-substitute converter and 13.1% when using the boron converter. This work confirmed that the SOI approach to cell-mimicking microdosimetry is feasible.