Characterization of phenolic pellets for ESR dosimetry in photon beam radiotherapy

This work deals with the dosimetric features of a particular phenolic compound (IRGANOX 1076^®) for dosimetry of clinical photon beams by using electron spin resonance (ESR) spectroscopy. After the optimization of the ESR readout parameters (namely modulation amplitude and microwave power) to maximise the signal without excessive spectrum distortions, basic dosimetric properties of laboratory-made phenolic dosimeters in pellet form, such as reproducibility, dose–response, sensitivity, linearity and dose rate dependence were investigated. The dosimeters were tested by measuring the depth dose profile of a 6 MV photon beam. A satisfactory intra-batch reproducibility of the ESR signal of the manufactured dosimeters was obtained. The ESR signal proved to increase linearly with increasing dose in the investigated dose range 1–13 Gy. The presence of an intrinsic background signal limits the minimum detectable dose to a value of approximately 0.6 Gy. Reliable and accurate assessment of the dose was achieved, independently of the dose rate. Such characteristics, together with the fact that IRGANOX 1076^® is almost tissue-equivalent, and the stability of the ESR signal, make these dosimeters promising materials for ESR dosimetric applications in radiotherapy.     

Versatility of thermoluminescence materials and radiation dosimetry – A review

Thermoluminescence (TL) materials exhibit a wide range of applications in different areas such as personal dosimetry, environmental dosimetry, medical research etc. Doping of different rare earth impurities in different hosts is responsible for changing the properties of materials useful for various applications in different fields. These materials can be irradiated by different types of beams such as γ‐rays, X‐rays, electrons, neutrons etc. Various radiation regimes, as well as their dose–response range, play an important role in thermoluminescence dosimetry. Several TL materials, such as glass, microcrystalline, nanostructured inorganic materials and recently developed materials, are reviewed and described in this article.     

Evaluating the Potential of Q-Band ESR Spectroscopy for Dose Reconstruction of Fossil Tooth Enamel

The potential of Q-band Electron Spin Resonance (ESR) for quantitative measurements has been scarcely evaluated in the literature and its application for dose reconstruction of fossil tooth enamel with dating purposes remains still quite unknown. Hence, we have performed a comparative study based on several Early to Middle Pleistocene fossil tooth samples using both X- and Q-band spectroscopies. Our results show that Q-band offers a significant improvement in terms of sensitivity and signal resolution: it allows not only to work with reduced amounts of valuable samples (< 4 mg), but also to identify different components of the main composite ESR signal. However, inherent precision of the ESR intensity measurements at Q-band is clearly lower than that achieved at X-band, highlighting the necessity to carry out repeated measurements. All dose values derived from X- and Q-band are nevertheless systematically consistent at either 1 or 2 sigma. In summary, our results indicate that Q-band could now be considered as a reliable tool for ESR dosimetry/dating of fossil teeth although further work is required to improve the repeatability of the measurements.     

Development and characterization of optical readout well-type glass gas electron multiplier for dose imaging in clinical carbon beams

The use of carbon ion beams in cancer therapy (also known as hadron therapy) is steadily growing worldwide; therefore, the demand for more efficient dosimetry systems is also increasing because daily quality assurance (QA) measurements of hadron radiotherapy is one of the most complex and time consuming tasks. The aim of this study is to develop a two-dimensional dosimetry system that offers high spatial resolution, a large field of view, quick data response, and a linear dose–response relationship.We demonstrate the dose imaging performance of a novel digital dose imager using carbon ion beams for hadron therapy. The dose imager is based on a newly-developed gaseous detector, a well-type glass gas electron multiplier. The imager is successfully operated in a hadron therapy facility with clinical intensity beams for radiotherapy. It features a high spatial resolution of less than 1 mm and an almost linear dose–response relationship with no saturation and very low linear-energy-transfer dependence. Experimental results show that the dose imager has the potential to improve dosimetry accuracy for daily QA.     

Measurement of absorbed doses from X-ray baggage examinations to tooth enamel by means of ESR and glass dosimetry

The contribution of radiation from X-ray baggage scans at airports on dose formation in tooth samples was investigated by electron spin resonance (ESR) dosimetry and by glass dosimetry. This was considered important, because tooth samples from population around the Semipalatinsk Nuclear Test Site (SNTS), Kazakhstan, had been transported in the past to Hiroshima University for retrospective dose assessment of these residents. Enamel samples and glass dosimeters were therefore examined at check-in time at Kansai airport (Osaka, Japan), Dubai airport (Dubai, United Arab Emirates) and Domodedovo airport (Moscow, Russia). These airports are on the route from Kazakhstan to Japan. Three different potential locations of the samples were investigated: in pocket (without X-ray scans), in a small bag (with four X-ray scans) and in large luggage (with two X-ray scans). The doses obtained by glass and ESR dosimetry methods were cross-compared. As expected, doses from X-ray examinations measured by glass dosimetry were in the μGy range, well below the ESR detection limit and also below the doses measured in enamel samples from residents of the SNTS.     

In vivo dosimetry for lung radiotherapy including SBRT

SBRT for lung cancer is being rapidly adopted as a treatment option in modern radiotherapy centres. This treatment is one of the most complex in common clinical use, requiring significant expertise and resources. It delivers a high dose per fraction (typically ∼6–30 Gy/fraction) over few fractions. The complexity and high dose delivered in only a few fractions make powerful arguments for the application of in vivo dosimetry methods for these treatments to enhance patient safety. In vivo dosimetry is a group of techniques with a common objective – to estimate the dose delivered to the patient through a direct measurement of the treatment beam(s). In particular, methods employing an electronic portal imaging device have been intensely investigated over the past two decades. Treatment verification using in vivo dosimetry approaches has been shown to identify errors that would have been missed with other common quality assurance methods. With the addition of in vivo dosimetry to verify treatments, medical physicists and clinicians have a higher degree of confidence that the dose has been delivered to the patient as intended.In this review, the technical aspects and challenges of in vivo dosimetry for lung SBRT will be presented, focusing on transit dosimetry applications using electronic portal imaging devices (EPIDs). Currently available solutions will be discussed and published clinical experiences, which are very limited to date, will be highlighted.     

The observed relationship between the occurrence of acute radiation effects and leukemia mortality among A-bomb survivors

In an analysis of a follow-up study of a fixed population of 73,330 atomic bomb survivors in Hiroshima and Nagasaki, the slope of an estimated dose response between ionizing radiation and leukemia mortality was found to be steeper (P less than 0.002), by a factor of 2.4, among those who reported epilation within 60 days of the bombings, compared to those who did not experience this sign of acute radiation exposure. The strength of this empirical finding as evidence of biological association in individual radiosensitivity for these two end points is studied here. The major factor complicating the interpretation of this finding as evidence of such an association is the degree of imprecision of the radiation dosimetry system used in assignment of radiation doses to the A-bomb survivors. Using models recently suggested for dealing with dosimetry errors in epidemiological analysis of the A-bomb survivor data, the sensitivity of the apparent association between leukemia mortality and severe epilation to the assumed level of dosimetry error is investigated.     

Three-dimensional quality assurance of IMRT prostate plans using gel dosimetry

Intensity modulated radiotherapy (IMRT) is one of the most modern radiation therapy treatment techniques. Although IMRT can deliver high and complex conformational doses to the tumor volume, its implementation requires rigorous quality assurance (QA) procedures that include a dosimetric pre-treatment verification of individual patient planning. This verification usually involves measuring a small volume of absolute dose with an ionization chamber and checking bi-dimensional fluency with an array of detectors. The planning technique has tri-dimensional characteristics, but no tridimensional dosimetry has been established in the clinical routine. One strategy to perform three-dimensional dosimetry is to use polymeric gels associated with magnetic resonance imaging to evaluate dose distribution. Here, we have compared the results of conventional QA procedures involving one- and two-dimensional dosimetry to the results of three-dimensional dosimetry conducted with MAGIC-f gel in 10 cases of prostate cancer IMRT planning. More specifically, we used the gamma index (3%/3 mm) to compare the results of three-dimensional dosimetry to the expected dose distributions obtained with the treatment planning system. Except for one IMRT treatment plan, the gel dosimetry results agreed with the conventional quality control and provided an overview of dose distribution in the target volume.     

Ammonium formate, a compound for sensitive EPR dosimetry

Alanine EPR dosimetry has been applied successfully when measuring intermediate and high radiation doses. Although the performance of alanine dosimetry is being improved, the sensitivity of the material is too low for a fast and simple low- dose determination. Here we present the results using ammonium formate as an EPR dosimeter material. Ammonium formate is seven times more sensitive than alanine, using spectrometer settings optimized for the latter. Deuterated ammonium formate is found to be more than eight times more sensitive than alanine. Analysis of signal stability with time shows that the ammonium formate signal is stable by 5 min after irradiation and that no change in signal intensity is found during 8 days. The atomic composition of ammonium formate is closer to that of tissue than alanine, and thus the energy dependence is smaller than that of alanine at photon energies below 200 keV. Power saturation studies indicate that the energy transfer between the spins and the lattice is fast in ammonium formate, which gives the possibility of using high microwave power without saturation to further increase the sensitivity. These results suggest that ammonium formate has some important properties required of an EPR dosimeter for applications in dosimetry in the dose range typical for radiation therapy.     

External beam radiation therapy with kilovoltage x-rays

Kilovoltage (kV) x-rays are most commonly used for diagnostic imaging due to their sensitivity to tissue composition. In radiation therapy (RT), due to their fast attenuation, kV x-rays are typically only used for superficial irradiation of skin cancer and for intra-operative RT (IORT). Recently, however, a number of kV RT techniques have emerged. In this review article, we provide a brief overview of the use of kV x-rays for RT.Various kV x-ray source technologies suitable for RT, such as conventional x-ray tubes as well as novel x-ray sources, are first described. This x-ray source section is then followed by a section on their implementation in terms of clinical, veterinary and preclinical applications. Specifically, IORT, superficial RT and dose enhancement with iodine and gold nanoparticles, as well as microbeam RT and FLASH RT are discussed in this context. Then, a number of kV x-ray RT applications in modeling and proof-of-principle stages, such as breast external beam RT with rotational sources, kilovoltage arc therapy and the BriXS Compton pulsed x-ray sources, are reviewed. Finally, some clinical and economic considerations for the development of kV RT techniques are discussed.     

Transversal dose distribution optimization for laser-accelerated proton beam medical applications by means of Geant4

The main purpose of this paper is to quantitatively study the possibility of delivering dose distributions of clinical relevance with laser-driven proton beams. A Monte Carlo application has been developed with the Geant4 toolkit, simulating the ELIMED (MEDical and multidisciplinary application at ELI-Beamlines) transport and dosimetry beam line which is being currently installed at the ELI-Beamlines in Prague (CZ). The beam line will be used to perform irradiations for multidisciplinary studies, with the purpose of demonstrating the possible use of optically accelerated ion beams for therapeutic purposes. The ELIMED Geant4-based application, already validated against reference transport codes, accurately simulates each single element of the beam line, necessary to collect the accelerated beams and to select them in energy. Transversal dose distributions at the irradiation point have been studied and optimized to try to quantitatively answer the question if such kind of beam lines, and specifically the systems developed for ELIMED in Prague, will be actually able to transport ion beams not only for multidisciplinary applications, such as pitcher-catcher nuclear reactions (e.g. neutrons), PIXE analysis for cultural heritage and space radiation, but also for delivering dose patterns of clinical relevance in a future perspective of possible medical applications.     

Validation of Dolphin dosimetry in three dimensional patient-specific quality assurance programme

AimThe aim of this study is to commission and validate Dolphin-Compass dosimetry as a patient-specific Quality Assurance (QA) device.BackgroundThe advancement of radiation therapy in terms of highly conformal delivery techniques demands a novel method of patient-specific QA. Dolphin-Compass system is a dosimetry solution capable of doing different QA in radiation therapy.Materials and methodsDolphin, air-vented ionization detector array mounted on Versa-HD Linear Accelerator (LINAC) was used for measurements. The Compass is a dose computation algorithm which requires modelling of LINAC head similar to other Treatment Planning Systems (TPS). The dosimetry system was commissioned after measuring the required beam data. The validation was performed by comparison of treatment plans generated in Monaco TPS against the measurement data. Different types of simple, complex, static and dynamic radiation fields and highly conformal treatment plans of patients were used in this study.ResultsFor all field sizes, point doses obtained from Dolphin-Compass dosimetry were in good agreement with the corresponding TPS calculated values in most of the regions, except the penumbra, outside field and at build-up depth. The results of gamma passing rates of measurements by using different Multi-leaf Collimator patterns and Intensity Modulated Radiation Therapy fluence were also found to be in good correlation with the corresponding TPS values.ConclusionsThe commissioning and validation of dosimetry was performed with the help of various fields, MLC patterns and complex treatment plans. The present study also evaluated the efficiency of the 3D dosimetry system for the QA of complex treatment plans.     

LED-based interferometric reflectance imaging sensor for quantitative dynamic monitoring of biomolecular interactions

Label-free optical biosensors have been established as proven tools for monitoring specific biomolecular interactions. However, compact and robust embodiments of such instruments have yet to be introduced in order to provide sensitive, quantitative, and high-throughput biosensing for low-cost research and clinical applications. Here we present the Interferometric Reflectance Imaging Sensor (IRIS) using an inexpensive and durable multi-color LED illumination source to monitor protein-protein and DNA-DNA interactions. We demonstrate the capability of this system to dynamically monitor antigen-antibody interactions with a noise floor of 5.2 pg/mm(2) and DNA single mismatch detection under denaturing conditions in an array format. Our experiments show that this platform has comparable sensitivity to high-end label-free biosensors at a much lower cost with the capability to be translated to field-deployable applications.     

Clinical trials using dental stem cells: 2022 update

For nearly 20 years, dental stem cells(DSCs) have been successfully isolated from mature/immature teeth and surrounding tissue, including dental pulp of permanent teeth and exfoliated deciduous teeth, periodontal ligaments, dental follicles, and gingival and apical papilla. They have several properties(such as self-renewal, multidirectional differentiation, and immunomodulation) and exhibit enormous potential for clinical applications. To date, many clinical articles and clinical trials using DS...     

Characterization of the initial carbon-centered pentadienyl radical and subsequent radicals in lipid peroxidation: identification via on-line high performance liquid chromatography/electron spin resonance and mass spectrometry

The previously reported combination of an on-line high-performance liquid chromatography (LC)/electron spin resonance (ESR) system with mass spectrometric analysis (MS) created a unique technique to identify a variety of lipid-derived radicals ((.)L(d)) formed from in vitro lipid peroxidation (Iwahashi et al. [20]). To improve the sensitivity, resolution, and reliability of this method for in vitro and in vivo studies, we have investigated the effects of mobile phase pH, modifiers, and columns on the chromatographic separation of linoleic acid-derived radical adducts. Using tetrahydrofuran (THF) and 0.1% glacial acetic acid (HOAc) in an H(2)O/acetonitrile (ACN) mobile phase greatly increased the resolution and retention reproducibility of lipid radical adducts in LC/ESR. In addition, these modifications allowed the elimination of an ESR tuning problem and the synchronization of UV and ESR detection of radical adducts in on-line LC/ESR, neither of which had been possible previously. Analyte purity was therefore increased, thus increasing the reliability of radical detection via on-line LC/ESR as well as radical identification via MS analysis. For the first time, POBN adducts of linoleic carbon-centered pentadienyl radicals (L(.)) were detected and identified. The optimization of chromatography in the LC/ESR and MS combination provided a reliable and sensitive way for the detection and identification of expected radical adducts in vitro and in vivo.     

Imaging in vivo redox status in high spatial resolution with OMRI

Redox-reactions are playing a significant role in regulation of homeostasis of organism. Disorder of the redox-status is related with the onset and/or propagation of oxidative diseases such as lifestyle-related diseases, including cancers and cardiac diseases, etc. In vivo imaging of redox-status is thereby important in the analysis of mechanisms of oxidative diseases and developments of new medicines for the diseases. Aminoxyl radicals are redox-sensitive reporter molecules, which lose their paramagnetic moiety by reactions of free radicals or reducing compounds. Electron spin resonance (ESR) technique has been used to measure the molecules in vivo. In vivo spatial resolution in ESR imaging is in the range of a few millimeters and is not sufficient for the detailed diagnosis of disease models. Overhauser enhanced MRI (OMRI) is an emerging free radical imaging technique, which utilised electron-proton coupling to image the distribution of free radicals. In vivo imaging of redox-status is applicable with OMRI/aminoxyl radical technique. The detailed imaging analysis was demonstrated in oxidative diseases, such as tumour-bearing, neurodegeneration or gastric ulcer models. The OMRI/aminoxyl radical technique has a large potential as a diagnostic system for biomedical applications in the future.     

Measurement of dose rate at the interface of cell culture medium and glass dishes by means of ESR dosimetry using thin films of alanine.

Previous studies on human cervical cancer cells (NHIK 3025) have indicated that the cells, when X-irradiated in suspension, appeared to be more radiosensitive than when they were irradiated attached to glass dishes. However, this result depends on dosimetry, which is difficult in the situation where cells are attached to glass dishes due to backscattering electrons at the glass-liquid interface. Recently developed dosimetry that is based on detection of radiation-induced stable radicals in alanine and uses ESR spectroscopy offers a possibility for more relevant dosimetry at the glass-liquid interface than the previous estimates of doses based on Fricke dosimetry. Thin alanine films (>/=10 microm) were used to measure dose at the interface by irradiating the films while they were placed tightly against the bottom of dishes and covered with 1 mm of wax simulating the medium above cells. Fricke dosimetry was also performed, with different depths of Fricke solution in the dishes, to elucidate the contribution to the dose delivered by backscattering electrons at the glass-liquid interface. A dose rate of 1.9 Gy/min was measured with a thin layer (0.2-0.3 mm) of Fricke solution in petri dishes made of glass. However, this estimate appears to be too high, due to a contribution to dose by short-ranged electrons generated when the X rays passed through a steel lid 4.5 cm above the dishes. Dosimetry using alanine films resulted in dose rates of 1.15 and 0.87 Gy/min at the interfaces of glass-liquid and plastic- liquid, respectively. Hence there is a significant contribution to dose from backscattering electrons on dishes made of glass. The reason for our previous observation of a difference in radiosensitivity between cells irradiated in suspension and cells irradiated attached to glass appears to be a lack of accurate dosimetry at the glass-liquid interface.     

Generation of clinical 177Lu SPECT/CT images based on Monte Carlo simulation with GATE

PurposePatient-specific dosimetry in MRT relies on quantitative imaging, pharmacokinetic assessment and absorbed dose calculation. The DosiTest project was initiated to evaluate the uncertainties associated with each step of the clinical dosimetry workflow through a virtual multicentric clinical trial. This work presents the generation of simulated clinical SPECT datasets based on GATE Monte Carlo modelling with its corresponding experimental CT image, which can subsequently be processed by commercial image workstations.MethodsThis study considers a therapy cycle of 6.85 GBq ¹⁷⁷Lu-labelled DOTATATE derived from an IAEA-Coordinated Research Project (E23005) on “Dosimetry in Radiopharmaceutical therapy for personalised patient treatment”. Patient images were acquired on a GE Infinia-Hawkeye 4 gamma camera using a medium energy (ME) collimator. Simulated SPECT projections were generated based on experimental time points and validated against experimental SPECT projections using flattened profiles and gamma index. The simulated projections were then incorporated into the patient SPECT/CT DICOM envelopes for processing and their reconstruction within a commercial image workstation.ResultsGamma index passing rate (2% − 1 pixel criteria) between 95 and 98% and average gamma between 0.28 and 0.35 among different time points revealed high similarity between simulated and experimental images. Image reconstruction of the simulated projections was successful on HERMES and Xeleris workstations, a major step forward for the initiation of a multicentric virtual clinical dosimetry trial based on simulated SPECT/CT images.ConclusionsRealistic ¹⁷⁷Lu patient SPECT projections were generated in GATE. These modelled datasets will be circulated to different clinical departments to perform dosimetry in order to assess the uncertainties in the entire dosimetric chain.