BACKGROUND:The role of oxygen in "Ultra-High Dose Rate" (UHDR) radiotherapy is currently subject to active debate, due to its importance in the FLASH effect. Radiochemical oxygen depletion (ROD) is used to characterize the removal of oxygen by its interaction with the free radicals produced by the radiation. Currently, there is a need to understand why ROD depends on the radiation dose rate and the initial oxygen pressure. PURPOSE:Development of a kinetic model of ROD that explains its dependence on (i) radiation dose rate and (ii) initial oxygen pressure, O 2 ${{{\mathrm{O}}}_2}$ . METHODS:The current work uses a variety of published ROD studies performed in vitro and in vivo in mice to evaluate the kinetic model prediction of ROD. The in vitro studies include evaluation of ROD in water, bovine serum albumin (BSA), and CELL medium consisting of HEPES ( 10 mM $10\ {\mathrm{mM}}$ ), glycerol ( 1 M $1\ {\mathrm{M}}$ ), glucose ( 5 mM $5\ {\mathrm{mM}}$ ), and glutathione ( 5 mM $5\ {\mathrm{mM}}$ ). Published in vivo studies were performed in C57BL/6 mice (male and female) and NU(Ico)-Foxn1nu mice (female Swiss nude) using proton FLASH and electron, respectively. Oxygen pressure measurements were performed with a variety of different probes such as (i) TROXSP5 sensors, (ii) Oxyphor PtG4, and (iii) Oxylite (NX-BF/OT/E). Two definitions of ROD were used in the current work to represent separately the ROD dependence in "time" ( RO D Time ${\mathrm{RO}}{{{\mathrm{D}}}_{{\mathrm{Time}}}}$ ) and "dose" ( RO D Dose ${\mathrm{RO}}{{{\mathrm{D}}}_{{\mathrm{Dose}}}}$ ). RESULTS:The kinetic model RO D Dose ${\mathrm{RO}}{{{\mathrm{D}}}_{{\mathrm{Dose}}}}$ prediction agreed well with published measurements, yielding reduced χ 2 ${{\chi }^2}$ values near the unity for water, BSA, and CELL medium, and comparably strong agreement for the animal-study datasets, within the reported or estimated uncertainties used in this work. The solvated electron G-value, G e aq - ${{G}_{e_{{\mathrm{aq}}}^ - }}$ , was shown to be dose rate, LET dependent and medium specific. For a medium with radical scavenging capacity (such as BSA and CELL), a higher value of G e aq - ${{G}_{e_{{\mathrm{aq}}}^ - }}$ was observed compared to water, which had a much lower radical scavenging capacity. The kinetic model RO D Dose ${\mathrm{RO}}{{{\mathrm{D}}}_{{\mathrm{Dose}}}}$ dose rate predictions also achieved very good agreement, with the published in vitro in water and BSA medium. The RO D Dose ${\mathrm{RO}}{{{\mathrm{D}}}_{{\mathrm{Dose}}}}$ kinetic model's dose-rate predictions for in vivo mice studies also showed excellent agreement once the raw oxygen consumption data were corrected for oxygen diffusion during radiation delivery. CONCLUSIONS:A systematic review of all published ROD studies was performed and used as the basis for testing the novel kinetic model for ROD. The kinetic model prediction of ROD showed that the radiolysis products, OH • ${\mathrm{OH}} \bullet $ , e aq • - ${\mathrm{e}}_{{\mathrm{aq}}}^{ \bullet - }$ , O 2 • - ${\mathrm{O}}_2^{ \bullet - }$ , HO 2 • - ${\mathrm{HO}}_2^{ \bullet - }$ , play an important role in ROD and provide an explanation why ROD depends on (1) dose rate and (2) initial oxygen pressure.

Stereotactic arrhythmia radioablation (STAR) represents an emerging non-invasive treatment for therapy-refractory ventricular tachycardia. Yet, planning remains challenged by multimodal cardiac imaging integration, electroanatomical mapping (EAM) transfer, and cardiorespiratory motion effects on dose delivery. Current radiotherapy (RT) planning systems offer mainly static visualization and limited access to intramural myocardial structures, hindering communication between cardiology and radiation oncology teams. We present a novel extended reality (XR) simulator designed to dynamically visualize STAR-relevant imaging and planning data. The system integrates diastolic cardiac CT, respiratory-binned 4DCT, anatomical segmentations, EAM data, and phase-recomputed RT dose distributions within an XR environment. Cardiac structures are propagated across respiratory phases using deformable registration, while dose distributions are recomputed on each respiratory-binned CT, enabling phase-specific inspection of dose conformality for both planning target volumes (PTVs) and cardiac target volumes (CardTVs). The resulting time-resolved volumetric dataset is rendered in XR, allowing clinicians to explore cardiac motion, visualize intramural dose deposition, and jointly assess target and organ-at-risk dynamics. This supports qualitative evaluation of dose-motion interplay and interdisciplinary interpretation of intramural targets. The system was tested on three STAR patients enrolled in the RAVENTA trial. Motion analysis revealed PTV centroid displacement amplitudes over the breathing cycle of up to 17.5, 10.2, and 8.9 mm for patients 1, 2, and 3, respectively, with conformity number variations of 0.38, 0.34, and 0.19. Expert evaluation showed positive perceived utility for target-anatomy-dose understanding, motion interpretation, and multidisciplinary communication. This proof-of-concept demonstrates the feasibility and potential clinical value of XR-based motion-aware dose visualization for STAR planning.

Purpose: Our overarching goal is to obtain new information for mechanistic understanding of the FLASH effect. In this study we (1) compared three experimental systems used for quantification of radiochemical oxygen depletion (ROD) induced by electron radiation at conventional (CONV) and ultrahigh (FLASH) dose rates; (2) investigated the dependence of the ROD g-values (gO2) on the baseline oxygen concentration using two methods of sample preparation; (3) evaluated gO2 values as a function of electron pulse repetition frequency (PRF) at varying instantaneous pulse dose rates. Methods and Materials; Oxygen measurements were performed using solid-state phosphorescent oxygen probes TROXSP5 (PyroScience GmbH) and OxyLite™ Pro (Oxford Optronics) and a soluble probe Oxyphor PtG4 (Oxyphor LLC) under electron beam irradiation in 3G buffer (glucose-glycerol-glutathione) as a medium. Samples were either equilibrated with air, sealed and then sequentially irradiated until oxygen was fully depleted, or equilibrated with gas mixtures containing different oxygen levels and irradiated once. gO2-Value dependencies on beam parameters (instantaneous dose rates and PRFs) were investigated using 3G buffer and Oxyphor PtG4. Results:The three experimental systems yielded close results. However, the response time of the solid-state sensors was found to be 3-4 orders of magnitude longer than that of Oxyphor PtG4. The gO2 values showed strong dependence on the baseline oxygen concentration at levels below ~40-50 μM [O2] regardless of the sample preparation method. Additionally, for fixed total dose and instantaneous dose rate (DRp), gO2 values decreased with an increase in PRF, exhibiting inverse correlation with the time-averaged dose rate (DRav). Conclusions: Oxygen measurements using solid-state or soluble phosphorescent probes are appropriate for quantification of ROD under CONV and FLASH dose rates, although solid state devices have limited time resolution, incompatible with observation of fast oxygen transients induced by FLASH. The observed inverse correlation between gO2 values and DRav suggests that the latter could be a predictor of oxygen removal from the environment via its consumption in chemical reactions with organic substrates.

Radiotherapy (RT) transforms tumour tissues into in situ vaccines that trigger antitumor immunity. Immunogenicity depends on how RT is delivered, since heterogeneous RT (spatially fractionated RT, SFRT) elicits more prominent responses than the conventional homogenous one. However, this phenomenon cannot be clinically harnessed, unless the relevant pathways are identified. To gain insights, we developed a hybrid dry-lab/wet-lab approach that integrates systems-level immune phenotypes established by homogenous or heterogenous RT (SFRT) with the transcriptomic profiling of irradiated tumors. By further combining feature extraction with machine-learning, including multilayer perceptron modelling, we ranked predictors of immune infiltration and patient survivability for each RT type. We found that conventional RT induces coordinated upregulation of cytosolic sensors of RNA viruses (OASes and RIG I-like receptors) along with ERV RNAs predominately 400-800 base-pairs long, which might serve as their ligands. For schemes establishing abscopal effects, a coordinated upregulation of the OAS sensors and shared ERV transcripts was observed in both irradiated and distant tumours. Compared to homogenous RT, SFRT triggered earlier and stronger activation of OAS signaling along with NK cell responses. Overall, we show a co-involvement of tumour cell-intrinsic ERVs and their cytosolic RNA sensors in RT-induced antitumor immunity. This key finding could guide mechanistic studies and future precision oncology. ### Competing Interest Statement The authors have declared no competing interest.

BACKGROUND:In proton radiotherapy, the steep dose deposition profile near the end of the proton's track, the Bragg peak, ensures a more conformed deposition of dose to the tumor region when compared with conventional radiotherapy while reducing the probability of normal tissue complications. However, uncertainties, as in the proton range, patient geometry, and positioning pose challenges to the precise and secure delivery of the treatment plan (TP). In vivo range determination and dose distribution are pivotal for mitigation of uncertainties, opening the possibility to reduce uncertainty margins and for adaptation of the TP. PURPOSE:This study aims to explore the feasibility of utilizing gadolinium (Gd), a highly used contrast agent in MRI, as a surrogate for in vivo dosimetry during the course of scanning proton therapy, tracking the delivery of a TP and the impact of uncertainties intra- and inter-fraction in the course of treatment. METHODS:Monte Carlo simulations (Geant4 11.1.1) were performed, where a Gd-filled volume was placed within a water phantom and underwent treatment with a scanning proton TP delivering 4 Gy. The secondary photons emitted upon proton-Gd interaction were recorded and assessed for various tumor displacements. The spectral response of Gd to each pencil beam irradiation is therefore used as a surrogate for dose measurements during treatment. RESULTS:Results show that the deposited dose at the target volume can be tracked for each TP scanning point by correlating it with the recorded Gd signal. The analyzed Gd spectral line corresponded to the characteristic X-ray k α $\text{k}_\alpha$ line at 43 keV. Displacements from the planned geometry could be distinguished by observing changes in the Gd signal induced by each pencil beam. Moreover, the total 43 keV signal recorded subsequently to the full TP delivery reflected deviations from the planned integral dose to the target. CONCLUSIONS:The study suggests that the spectral response of a Gd-based contrast agent can be used for in vivo dosimetry, providing insights into the TP delivery. The Gd 43 keV spectral line was correlated with the dose at the tumor, its volume, and its position. Other variables that can impact the method, such as the kinetic energy of the incident protons and Gd concentration in the target were also discussed.

BACKGROUND:Precise range verification is essential in proton therapy to minimize treatment margins due to the steep dose fall-off of proton beams. The emission of secondary radiation from nuclear reactions between incident particles and tissues stands out as a promising method for range verification. Two prominent techniques are PET and Prompt Gamma-Ray Spectroscopy (PGS). PGS holds significant promise due to its real-time capability for range monitoring. This method allows for prompt detection and quantification of any disparities between planned and actual dose delivery, facilitating adaptive treatment strategies. Given the key role of Monte Carlo (MC) codes in understanding the PGS mechanisms during proton therapy, it is essential to address the current lack of validated codes covering the full energy spectrum of emitted gamma-rays. PURPOSE:Addressing the need for precise range monitoring in proton therapy, our study aims to develop and validate MC codes for PGS. We focus on analyse MCNP6, GEANT4, and FLUKA codes, conducting rigorous validation process by comparing our simulation results with experimental data. Additionally, we propose optimal models and parameters to refine the accuracy of simulations for prompt gamma-ray (PG) spectra. METHODS:Various proton data libraries, models and cross-sections values were used in this study to simulate proton-induced gamma-rays in MCNP6, GEANT4 and FLUKA. To validate these simulations, PGS spectra of 15.0 cm 3 $15.0 \,{\rm cm}^{3}$ PMMA block irradiation were obtained with CeBr 3 ${\rm CeBr}_3$ inorganic scintillator detector for different proton energies, raging from approximately 90 $\hskip.001pt 90$ to 130 MeV $130 \,{\rm MeV}$ . RESULTS:GEANT4 was the only MC code capable of successfully reproducing 10 B $^{10}{\rm B}$ PG lines, while the FLUKA aligned better with experimental data for mid-range energies. At higher energies, FLUKA overestimated the 12 C $^{12}{\rm C}$ PG line ( 2 + → 0 + $2^{+} \rightarrow 0^{+}$ ) at 4.44 MeV $4.44 \,{\rm MeV}$ , whereas GEANT4 underestimated it; MCNP6 provided the closest match. Additionally, GEANT4, FLUKA, and MCNP6 failed to accurately reproduce the 16 O $^{16}{\rm O}$ PG line ( 3 - → 0 + $3^{-} \rightarrow 0^{+}$ ) at 6.13 MeV $6.13 \,{\rm MeV}$ , consistent with previous findings. To address this limitation, a new model based on experimental and theoretical data from literature was developed. CONCLUSIONS:This study emphasizes the need for updates to the data tables in MC simulations and underscores the importance of further theoretical and experimental research on PG de-excitation lines relevant to proton therapy. The newly developed model, designed to address discrepancies in the simulation of 12 C $^{12}{\rm C}$ and 16 O $^{16}{\rm O}$ de-excitation lines across different toolkits, successfully improved the accuracy of the oxygen de-excitation line, which was previously not well-reproduced.

The purpose of this study was to investigate the feasibility of extracting proton beams with two distinct energies within a single synchrotron cycle. The energy difference between the beams should be sufficient to use one beam as a range probe to guide the second therapeutic beam in a synchrotron-based proton therapy facility. A clinical synchrotron-based proton therapy facility with a maximum clinical energy of 250 megaeV (MeV) and an experimental energy capability of 330 MeV was used for the study. The synchrotron's internal diagnostic equipment, including beam orbit monitors, dipole magnetic field sensors, acceleration frequency monitors, and energy measurement devices, was used to characterize the properties of the beams within the synchrotron and during extraction. External dosimetric equipment included a PTW water tank fitted with two ionization chambers and an ionization chamber array. These were used to validate dual-energy extraction at the irradiation isocenter independently. Dual-energy extraction was demonstrated across three defined energy ranges: low (75-110 MeV), intermediate (120-155 MeV), and high (195-230 MeV). Both re-acceleration and de-acceleration modes were tested and validated. This preliminary study achieved an energy difference of 35 MeV between extracted beams across the three evaluated energy ranges. This corresponds to clinical targets used under standard operating conditions and does not require hardware modifications. Future studies should explore adjusting the control software to enable target switching during a single cycle or the use of suboptimal targets for higher-energy beams. This would allow for active, real-time range probing. Combining modified dual-energy extraction parameters with low-intensity extraction for high-energy beams shows great promise in enabling simultaneous proton imaging and therapy within a single synchrotron cycle.

Among the tumors with the highest lethality, gliomas are primary brain tumors associated with common recurrence inclined to metastasize along the neuraxis and occasionally out of the central nervous system. Even though metastasis is the main responsible for death in oncological patients, few dedicated treatments are approved. Therefore, the establishment of effective anti-metastasis agents is the final frontier in cancer research. Interestingly, some copper complexes have demonstrated promising efficacy as antimetastatic agents, but they may cause off-site effects such as the alteration of copper homeostasis in healthy tissues. Thus, the incorporation of copper-based antimetastatic agents in rationally designed nano-architectures can increase the treatment localization reducing the side effects. Here, copper complex loaded hybrid nano-architectures (CuLNAs) are presented and employed to assess the impact of an intracellular copper source on glioma cell invasiveness. The novel CuLNAs are fully characterized and exploited for cell migration modulation in a glioma cell line. The results demonstrate that CuLNAs significantly reduce cell migration without impairing cell proliferation compared to standard gold and copper NAs. A concomitant antimigratory-like regulation of the epithelial-to-mesenchymal transition genes confirmed these results, as the gene encoding for the epithelial protein E-cadherin was upregulated and the other explored mesenchymal genes were downregulated. These findings, together with the intrinsic behaviors of NAs, demonstrate that the inclusion of metal complexes in the nano-architectures is a promising approach for the composition of a family of agents with antimetastatic activity.

Objective.Monolithic active pixel sensors are used for charged particle tracking in many applications, from medical physics to astrophysics. The Bergen pCT collaboration designed a sampling calorimeter for proton computed tomography, based entirely on the ALICE PIxel DEtector (ALPIDE). The same telescope can be used for in-situ range verification in particle therapy. An accurate charge diffusion model is required to convert the deposited energy from Monte Carlo simulations to a cluster of pixels, and to estimate the deposited energy, given an experimentally observed cluster.Approach.We optimize the parameters of different charge diffusion models to experimental data for both proton computed tomography and proton range verification, collected at the Danish Centre for Particle Therapy. We then evaluate the performance of downstream tasks to investigate the impact of charge diffusion modeling.Main results.We find that it is beneficial to optimize application-specific models, with a power law working best for proton computed tomography, and a model based on a 2D Cauchy-Lorentz distribution giving better agreement for range verification. We further highlight the importance of evaluating the downstream tasks with multiple approaches to obtain a range of expected performance metrics for the application.Significance.This work demonstrates the influence of the charge diffusion model on downstream tasks, and recommends a new model for proton range verification with an ALPIDE-based pixel telescope.

Ultra-high dose rate irradiations to water indicate an enhancement of radical-radical reactions, which could potentially correlate with the Flash effect. The purpose of this work was to extend gMicroMC to support multiple pulse simulations and Flash dose rates, and to investigate, in a pure water model, the mechanisms underlying the enhancement of radical-radical reactions under Flash conditions. gMicroMC, a GPU-based Monte Carlo track-structure algorithm, was extended to simulate multiple pulses. Pure water was exposed to multiple 70 MeV protons pulses delivering up to 20 Gy. The pulse dose rate was set to 2 · 105 and 106 Gy/s, while the average dose rate ranged from 0.01 to 100000 Gy/s. The G-values of H2O2 were used to monitor the influence of dose rate on radical-radical reactions. The multiple pulse extension of gMicroMC was validated against Kinetiscope. Multiple pulse simulations indicated an average dose rate threshold. Below it, complete radical depletion occurred within the pulses, leading to constant G-values. Above it, reactive species accumulated throughout the irradiation, resulting in an increase of radical-radical reactions and thus the G-values of H2O2. The average dose rate thresholds were in the order of 10 and 100 Gy/s for pulse dose rates of 2 · 105 and 105 Gy/s, respectively. At ultra-high dose rates, the brief intervals between pulses led to a reactive species build-up, which enhanced radical-radical reactions. This build-up is more likely to promote radical-radical reactions than the inter-track mechanism. The advancements in gMicroMC provide a sophisticated tool to study chemical dose rate dependencies.

BACKGROUND:Minibeam radiotherapy has demonstrated its potential to reduce normal tissue toxicity while maintaining tumor control. However, the underlying mechanisms behind this phenomenon remain unknown. Recent theoretical studies suggest a dose surrogate by diffusion of H 2 O 2 ${\rm H}_2{\rm O}_2$ into the valley regions. PURPOSE:The aim of this study is to experimentally investigate oxygen depletion and diffusion upon minibeam (MB) irradiation. METHODS:A 3D-printed water phantom with four sensors was developed to enable the real-time, simultaneous measurement of oxygen concentration in the peak and valley. Water with 0%-11% O 2 ${\rm O}_2$ and 0.1%/5.0% CO 2 ${\rm CO}_2$ was irradiated with broad beam (BB) and MB characterized by peak and valley widths of 2 mm  × $\times$ 2 mm and 0.5 mm  × $\times$  2 mm. The depletion was further compared in other chemical environments. RESULTS:The oxygen depletion rates per dose in hypoxic water in the valley regions were found to be 3-7 times higher compared to the peaks or BB. This observation was found to be independent of oxygen concentration above 2 %, indicating oxygen depletion saturation. For MB, diffusion between peaks and valleys was observed. After a certain period, an equilibrium between diffusion and dose rate differences was established. Glutathione and HEPES as a medium increased the depletion further and distinguished MB from BB. CONCLUSIONS:A novel way of simultaneously measuring oxygen in the peak and valley of the MB dose pattern was introduced. The observed oxygen depletion saturation and diffusion between the peaks and valleys suggest the importance of oxygen in spatially fractionated radiotherapy studies, which is even greater for 5 mM glutathione compared to water.

Radiotherapy (RT) is a cancer treatment technique that involves exposing cells to ionizing radiation, including X-rays, electrons, or protons. RT offers promise to treat cancer, however, some inherent limitations can hamper its performance. Radio-resistance, whether innate or acquired, refers to the ability of tumor cells to withstand treatment, making it a key factor in RT failure. This perspective hypothesizes that nanoscale surface topography can impact on the topology of cancer cells network under radiation, and that this understanding can possibly advance the assessment of cell radio-resistance in RT applications. An experimental plan is proposed to test this hypothesis, using cancer cells exposed to various RT forms. By examining the influence of 2D surface and 3D scaffold nanoscale architecture on cancer cells, this approach diverges from traditional methodologies, such as clonogenic assays, offering a novel viewpoint that integrates fields such as tissue engineering, artificial intelligence, and nanotechnology. The hypotheses at the base of this perspective not only may advance cancer treatment but also offers insights into the broader field of structural biology. Nanotechnology and label-free Raman phenotyping of biological samples are lenses through which scientists can possibly better elucidate the structure-function relationship in biological systems.

Proton computed tomography (pCT) is an imaging reconstruction technique that uses protons’ positions, directions, and energy loss to generate a map of an object’s relative stopping power. In this work, the trigger-controlling system was designed and constructed to synchronize between components of our proposed pCT prototype and a proton beam at King Chulalongkorn Memorial Hospital (KCMH) in Bangkok. The controlling system can control the proton beam gating, a rotational stage, and ALPIDE sensors, which are parts of a tracker and a proton calorimeter of the pCT prototype. The controlling system was constructed based on the MEGA2560 microcontroller unit. The controlling system was verified by measuring the activated rows of the ALPIDE sensor at different proton extraction times. Additionally, the controlling system can control an array of six ALPIDE sensors, which could provide preliminary results of the proton calorimeter prototype.

PURPOSE:The aim of this work was to establish a procedure that allows the conversion of a standard clinical LINAC into a "FLASH" LINAC capable of delivering ultra-high dose rates above 40 Gy/s, with minimal, fully reversible modifications to the device. A dosimetric characterization of the resulting treatment beam is presented. METHODS:A LINAC was modified to emit a 10 MeV electron FLASH beam. Modifications included the integration of a pulse control unit which consisted out of a scintillation detector and a transistor circuit. Beam parameters were optimized to maximize dose output. Beam characterization measurements were performed with different detectors in water: ionization chamber, diamond detector, radiographic films and scintillation detector. The resulting doses per pulse (DPP) and dose rates at different source-surface-distances (SSD) as well as the output reproducibility were determined. The beam was characterized with depth dose curves and lateral profiles. RESULTS:Conversion of a LINAC to FLASH mode was feasible in less than 30 min. Output was between DPPSSD=56cm = 1.69 ± 0.02 Gy and DPPSSD=100cm = 0.53 ± 0.01 Gy or dose rates between 676 ± 8 Gy/s and 213 ± 4 Gy/s. Reproducibility of DPP was better than 0.8 %. FLASH depth dose curves showed a higher range (R80 = 39.8 mm vs. 34.6 mm) and lateral beam profiles had a reduced flatness (from 5.5 % to 12.7 %) at SSD = 56 cm. CONCLUSION:We present a fully reversible conversion method requiring minimal modifications to a LINAC to produce electron FLASH beams. The achieved DPP and mean dose rates demonstrated high reproducibility, meeting criteria for FLASH applications, and markedly simplifying access to this technology for broader implementation.

Background: Recently, mixed carbon-helium beams were proposed for range verification in carbon ion therapy: Helium, with three times the range of carbon, serves as an on-line range probe, and is mixed into a therapeutic carbon beam. Purpose: Treatment monitoring is of special interest for lung cancer therapy, however the helium range might not always be sufficient to exit the patient distally. Therefore mixed beam use cases of several patient sites are considered. Methods: An extension to the open-source planning toolkit, matRad allows for calculation and optimization of mixed beam treatment plans. The use of the mixed beam method in 15 patients with lung cancer, as well as in a prostate and liver case, for various potential beam configurations was investigated. Planning strategies to optimize the residual helium range considering the sensitive energy range of the imaging detector were developed. A strategy involves adding helium to energies whose range is sufficient. Another one is to use range shifters to increase the helium energy and thus range. Results: In most patient cases, the residual helium range of at least one spot is too low. All investigated planning strategies can be used to ensure a high enough helium range while still keeping a low helium dose and a satisfactory total mixed carbon-helium beam dose. The use of range shifters allows for the detection of more spots. Conclusion: The mixed beam method shows promising results for online motioning. The use of range shifters ensures a high enough helium range and more detectable spots, allowing for a wider-spread application.