Radiotherapy plan evaluation indices: A dosimetrical suitability check.

PURPOSE: To classify the available plan evaluation indices and compare the dosimetric suitability of these indices. MATERIALS AND METHODS: Available published plan evaluation indices were categorized. Conformity index (CI) into two groups, one group contains those CI formulas which do not consider critical structure and other group contains those CI formulas which consider planning target volume (PTV) coverage, normal tissue and critical structure sparing simultaneously. Various homogeneity index (HI) formulas extracted from literature. Structure data sets of 25 patients were taken under consideration comprising of various sites. For each patient, two plans were created using Volumetric Arc Therapy technique. First type of plan (Plan-A) were generated considering all tissue objectives for targets and Organ at Risks (OARs) whereas second type of plan (Plan-B) were generated considering only targets tissue objectives and excluding OARs tissue objectives during plan optimization and dose calculation. Planning evaluation parameters were compared between Plan-A and Plan-B. RESULTS: CI calculated by various formulas in two different scenarios presented <2% variation. Any commonly used CI formula failed to differentiate the two different planning situations. On comparison between HI of two different scenario, it is observed that there are four formulas of HI which showed negligible variation but two formulae: S-index and HI (D) showed marginal variation. It is also observed that when OARs are removed from optimization dose homogeneity improved which is specifically pointed by sigma index formula. CONCLUSION: CI, which has assimilated the presence of OAR in their formulation, shows more reliability in plan evaluation. Sigma index was found to be more efficient formula while evaluating homogeneity of a treatment plan.

Ratiometric Electrochemistry: Improving the Robustness, Reproducibility and Reliability of Biosensors.

Electrochemical biosensors are an increasingly attractive option for the development of a novel analyte detection method, especially when integration within a point-of-use device is the overall objective. In this context, accuracy and sensitivity are not compromised when working with opaque samples as the electrical readout signal can be directly read by a device without the need for any signal transduction. However, electrochemical detection can be susceptible to substantial signal drift and increased signal error. This is most apparent when analysing complex mixtures and when using small, single-use, screen-printed electrodes. Over recent years, analytical scientists have taken inspiration from self-referencing ratiometric fluorescence methods to counteract these problems and have begun to develop ratiometric electrochemical protocols to improve sensor accuracy and reliability. This review will provide coverage of key developments in ratiometric electrochemical (bio)sensors, highlighting innovative assay design, and the experiments performed that challenge assay robustness and reliability.

Improved Patient Dosimetry at Radioiodine Therapy by Combining the ICRP Compartment Model and the EANM Pre-Therapeutic Standard Procedure for Benign Thyroid Diseases.

Radioactive iodine is commonly used for the treatment of different thyroid conditions since the 1940s. The EANM has developed a standard pre-therapeutic procedure to estimate patient specific thyroid uptake at treatment of benign thyroid diseases. The procedure which models the time dependent fractional thyroid uptake is based on a two-compartment fitting system, one representing the thyroid and the other the blood. The absorbed dose is however only estimated for the thyroid and not for any other organ in the body. A more detailed biokinetic model for iodine is given by the ICRP and includes an iodide transport in the whole body. The ICRP model has 30 different compartments and 48 transfer coefficients to model the biokinetics of iodide and to model different transfer for inorganic iodide and organic iodine. The ICRP model is a recirculation iodine model, and the optimization is performed on the whole model and not exclusively on the thyroid as in the EANM procedure. Combining the EANM method and the ICRP model gives both patient specific estimations of thyroid uptake and retention and include most organs in the body. The new software gives both an improved patient specific dosimetry for the thyroid and an estimation of the absorbed dose to non-target organs and tissues like kidneys, urinary bladder, stomach wall, and uterus. Using the method described in this paper, the repercussions on the daily routines will be minimal.

On the inaccuracies of dental radiometers.

This study investigated the accuracy of sixteen models of commercial dental radiometers (DR) in measuring the output of thirty-eight LED light curing units (LCUs) compared with a 'gold standard' laboratory-grade spectrometer integrating-sphere (IS) assembly. Nineteen Type I (fiber-bundle light guide) and nineteen Type II (light source in head) LED LCUs were tested, some using different output modes and light guides, resulting in 61 test subsets per radiometer. Gold standard (GS) output measurements (n = 3) were taken using the IS and confirmed with two types of laboratory-grade power meter (PowerMax-Pro 150 HD and PM10-19C; Coherent). One DR (Bluephase Meter II, Ivoclar; BM II) allowed power (mW) as well as irradiance (mW/cm2) recordings. Irradiance readings (n = 3) for each DR/LCU were compared with the IS derived irradiance. Individual LCU irradiance values were normalized against IS data. The GS method yielded reproducible data with a 0.4% pooled coefficient of variation for the LCUs. Mean power values ranged from 0.19 W to 2.40 W. Overall power values for the laboratory-grade power meters were within 5% of GS values. Individual LCU/DR normalized irradiance values ranged from 7% to 535% of the GS; an order of magnitude greater than previous reports. BM II was the only radiometer to average within 20% of normalized pooled GS irradiance values, whereas other radiometers differed by up to 85%. Ten radiometers failed to provide any reading for 1 LCU. When tested with the PowerMax-Pro in high speed (20 kHz) mode, eight LCUs demonstrated pulsing outputs undetectable at the standard (10 Hz) data acquisition rate. Sufficient light exposure is critical for the successful curing of dental resin-based materials. Substantial discrepancies may occur between actual and estimated radiometric data using current DRs. More accurate DRs need to be developed. Manufacturers' accuracy claims for DRs should specify compatible LCUs and testing parameters.

Reference dosimetry of modulated and dynamic photon beams.

In the late 1980s, a new technique was proposed that would revolutionize radiotherapy. Now referred to as intensity-modulated radiotherapy, it is at the core of state-of-the-art photon beam delivery techniques, such as helical tomotherapy and volumetric modulated arc therapy. Despite over two decades of clinical application, there are still no established guidelines on the calibration of dynamic modulated photon beams. In 2008, the IAEA-AAPM work group on nonstandard photon beam dosimetry published a formalism to support the development of a new generation of protocols applicable to nonstandard beam reference dosimetry (Alfonso et al 2008 Med. Phys. 35 5179-86). The recent IAEA Code of Practice TRS-483 was published as a result of this initiative and addresses exclusively small static beams. But the plan-class specific reference calibration route proposed by Alfonso et al (2008 Med. Phys. 35 5179-86) is a change of paradigm that is yet to be implemented in radiotherapy clinics. The main goals of this paper are to provide a literature review on the dosimetry of nonstandard photon beams, including dynamic deliveries, and to discuss anticipated benefits and challenges in a future implementation of the IAEA-AAPM formalism on dynamic photon beams.

Reference dosimetry in MRI-linacs: evaluation of available protocols and data to establish a Code of Practice.

With the rapid increase in clinical treatments with MRI-linacs, a consistent, harmonized and sustainable ground for reference dosimetry in MRI-linacs is needed. Specific for reference dosimetry in MRI-linacs is the presence of a strong magnetic field. Therefore, existing Code of Practices (CoPs) are inadequate. In recent years, a vast amount of papers have been published in relation to this topic. The purpose of this review paper is twofold: to give an overview and evaluate the existing literature for reference dosimetry in MRI-linacs and to discuss whether the literature and datasets are adequate and complete to serve as a basis for the development of a new or to extend existing CoPs. This review is prefaced with an overview of existing MRI-linac facilities. Then an introduction on the physics of radiation transport in magnetic fields is given. The main part of the review is devoted to the evaluation of the literature with respect to the following subjects: • beam characteristics of MRI-linac facilities; • formalisms for reference dosimetry in MRI-linacs; • characteristics of ionization chambers in the presence of magnetic fields; • ionization chamber beam quality correction factors; and • ionization chamber magnetic field correction factors. The review is completed with a discussion as to whether the existing literature is adequate to serve as basis for a CoP. In addition, it highlights subjects for future research on this topic.

Performance characteristics and validation of alpha particle spectrometers for radiometric analysis of natural and anthropogenic radionuclides of environmental impacts.

Alpha spectrometry is one of the greatest nuclear techniques for identification and quantification of α-emitters in the environment due to nuclear fuel cycle operations, nuclear materials and geochemical studies or forensic medicine investigations. This study was conducted to re-evaluate and optimize the factors affecting the performance of a multi-chamber alpha spectrometer (EG&G Ortec) used in our laboratory using an aged α-source of 232U in equilibrium with its decay products. The results shown that the energy calibration within energy window 4-9 MeV has been done using alpha particle emissions of 232U (t1/2.70.6 y) and its decay products with good linear fitting (R2 > 0.999). At a source to detector spacing of 10 mm, the efficiency of the detectors varied between 15 and 20%; while the better resolution (FWHM) was ~36 keV. These values are lower than those warranted when supplied before 20 years. The minimum detectable activity (MDA) of the detectors varies between 0.8 and 3.1 mBq for the chamber in use. The alpha spectrometer was also verified by certified reference samples to measure activity concentration of alpha emitters (e.g., 238U, 232Th, 226Ra and 241Am) with acceptable coefficient of variance (<10%), ζ-score (<3) and P-test (<25%). As a result, the optimized alpha spectrometer is valid and can be utilized for monitoring and assessment of natural and artificial α-emitters in different environmental compartments.

[Establishment of an On-Site Dosimetric Audit Program with a Plastic Phantom].

The quality assurance (QA) of the output constancy of linear accelerators (linacs) is one of the most basic items for radiation therapy. The necessity and demand of the dosimetric audit is on the rise. We aimed at establishing an on-site dosimetric audit program with a plastic phantom in order to enrich the availability of dosimetric audit in Japan. By this, we developed and evaluated an on-site audit program in multiple institutions in 120 cases for photon and electron standard dosimetry and intensity modulated radiation therapy (IMRT) condition. For photon standard dosimetry, we evaluated the accuracies of institutional measured absorbed dose in 50 cases by this on-site audit program. For the electron standard dosimetry, we evaluated the accuracies of institutional measured absorbed dose in 25 cases. For IMRT condition, we evaluated the accuracies of the institutional calculated dose in radiation treatment planning systems in 45 cases. The agreements of the measured absorbed dose between our audit and the institutions were within±1.1% for photon standard dosimetry. The agreements of the measured absorbed dose between our audit and the institutions were within±2.1% for electron standard dosimetry. The agreements between the measured absorbed dose of our audit and the institutional calculated dose were within±2.1% for IMRT condition. We established an on-site dosimetric audit program with a plastic phantom and this program is suitable with tight criteria similar to criteria required for clinical QA.

Semiconductor dosimetry in modern external-beam radiation therapy.

Semiconductor dosimeters are ubiquitous in modern external-beam radiation therapy. They possess key features. The response, electronically available in real time, is stable and linear with absorbed dose for given irradiation conditions; the radiation-sensitive volume can be rather small in size, while retaining mechanical strength and high sensitivity. We describe three common semiconductor dosimeters: diodes, metal-oxide-semiconductor field-effect transistors and diamonds. We discuss in detail their operation principles and applications in modern external-beam radiation therapy, primarily with megavoltage photon beams. We also explore their use in proton and heavy ion therapy, and in experimental radiotherapy techniques such as synchrotron-based micro-beam radiation therapy.

Stanford DRO Toolkit: Digital Reference Objects for Standardization of Radiomic Features.

Several institutions have developed image feature extraction software to compute quantitative descriptors of medical images for radiomics analyses. With radiomics increasingly proposed for use in research and clinical contexts, new techniques are necessary for standardizing and replicating radiomics findings across software implementations. We have developed a software toolkit for the creation of 3D digital reference objects with customizable size, shape, intensity, texture, and margin sharpness values. Using user-supplied input parameters, these objects are defined mathematically as continuous functions, discretized, and then saved as DICOM objects. Here, we present the definition of these objects, parameterized derivations of a subset of their radiomics values, computer code for object generation, example use cases, and a user-downloadable sample collection used for the examples cited in this paper.

Standardization in Quantitative Imaging: A Multicenter Comparison of Radiomic Features from Different Software Packages on Digital Reference Objects and Patient Data Sets.

Radiomic features are being increasingly studied for clinical applications. We aimed to assess the agreement among radiomic features when computed by several groups by using different software packages under very tightly controlled conditions, which included standardized feature definitions and common image data sets. Ten sites (9 from the NCI's Quantitative Imaging Network] positron emission tomography-computed tomography working group plus one site from outside that group) participated in this project. Nine common quantitative imaging features were selected for comparison including features that describe morphology, intensity, shape, and texture. The common image data sets were: three 3D digital reference objects (DROs) and 10 patient image scans from the Lung Image Database Consortium data set using a specific lesion in each scan. Each object (DRO or lesion) was accompanied by an already-defined volume of interest, from which the features were calculated. Feature values for each object (DRO or lesion) were reported. The coefficient of variation (CV), expressed as a percentage, was calculated across software packages for each feature on each object. Thirteen sets of results were obtained for the DROs and patient data sets. Five of the 9 features showed excellent agreement with CV < 1%; 1 feature had moderate agreement (CV < 10%), and 3 features had larger variations (CV ≥ 10%) even after attempts at harmonization of feature calculations. This work highlights the value of feature definition standardization as well as the need to further clarify definitions for some features.

IPEM code of practice for high-energy photon therapy dosimetry based on the NPL absorbed dose calibration service.

The 1990 code of practice (COP), produced by the IPSM (now the Institute of Physics and Engineering in Medicine, IPEM) and the UK National Physical Laboratory (NPL), gave instructions for determining absorbed dose to water for megavoltage photon (MV) radiotherapy beams (Lillicrap et al 1990). The simplicity and clarity of the 1990 COP led to widespread uptake and high levels of consistency in external dosimetry audits. An addendum was published in 2014 to include the non-conventional conditions in Tomotherapy units. However, the 1990 COP lacked detailed recommendations for calibration conditions, and the corresponding nomenclature, to account for modern treatment units with different reference fields, including small fields as described in IAEA TRS483 (International Atomic Energy Agency (IAEA) 2017, Vienna). This updated COP recommends the irradiation geometries, the choice of ionisation chambers, appropriate correction factors and the derivation of absorbed dose to water calibration coefficients, for carrying out reference dosimetry measurements on MV external beam radiotherapy machines. It also includes worked examples of application to different conditions. The strengths of the 1990 COP are retained: recommending the NPL2611 chamber type as secondary standard; the use of tissue phantom ratio (TPR) as the beam quality specifier; and NPL-provided direct calibration coefficients for the user's chamber in a range of beam qualities similar to those in clinical use. In addition, the formalism is now extended to units that cannot achieve the standard reference field size of 10 cm × 10 cm, and recommendations are given for measuring dose in non-reference conditions. This COP is designed around the service that NPL provides and thus it does not require the range of different options presented in TRS483, such as generic correction factors for beam quality. This approach results in a significantly simpler, more concise and easier to follow protocol.

Determination of consensus k Q values for megavoltage photon beams for the update of IAEA TRS-398.

The IAEA is currently coordinating a multi-year project to update the TRS-398 Code of Practice for the dosimetry of external beam radiotherapy based on standards of absorbed dose to water. One major aspect of the project is the determination of new beam quality correction factors, k Q , for megavoltage photon beams consistent with developments in radiotherapy dosimetry and technology since the publication of TRS-398 in 2000. Specifically, all values must be based on, or consistent with, the key data of ICRU Report 90. Data sets obtained from Monte Carlo (MC) calculations by advanced users and measurements at primary standards laboratories have been compiled for 23 cylindrical ionization chamber types, consisting of 725 MC-calculated and 179 experimental data points. These have been used to derive consensus k Q values as a function of the beam quality index TPR20,10 with a combined standard uncertainty of 0.6%. Mean values of MC-derived chamber-specific [Formula: see text] factors for cylindrical and plane-parallel chamber types in 60Co beams have also been obtained with an estimated uncertainty of 0.4%.

Switch-conversional ratiometric fluorescence biosensor for miRNA detection.

MicroRNAs play a crucial role in regulating gene expression and cellular function. Reliable detection of miRNA is highly demanded in clinical diagnosis and therapy. Herein, we designed a structure-convertible DNA switch and constructed a novel switch-conversional ratiometric fluorescence biosensor (SCRF biosensor) for highly sensitive miRNA detection by the use of amplicon fragments to convert the structure of the switch. The DNA switch was a sophisticated designed single-strand DNA with a stem-loop structure and modified with two fluorophores (Cy3 and Cy5) and one quencher at specific sites of the switch. Amplicon fragments (c*) were produced by an exponential amplification reaction. When the c* hybridized to the loop of a DNA switch, the structure of the switch would convert, and fluorescence resonance energy transfer occurred between Cy5 and Cy3. Then two fluorescence signals with different trends would be observed. As a result, by the ratio of the two signals, we can quantitatively and quickly detect the target miRNA with the concentration range from 100 fM to 100 nM and the excellent detection limit down to 70.9 fM, providing this new SCRF biosensor broad application prospects.

A Mail Audit Independent Peer Review System for Dosimetry Verification of a Small Animal Irradiator.

Dedicated precision orthovoltage small animal irradiators have become widely available in the past decade and are commonly used for radiation biology research. However, there is a lack of dosimetric standardization among these irradiators, which affects the reproducibility of radiation-based animal studies. The purpose of this study was to develop a mail-based, independent peer review system to verify dose delivery among institutions using X-RAD 225Cx irradiators (Precision X-Ray, North Branford, CT). A robust, user-friendly mouse phantom was constructed from high-impact polystyrene and designed with dimensions similar to those of a typical laboratory mouse. The phantom accommodates three thermoluminescent dosimeters (TLDs) to measure dose. The mouse peer review system was commissioned in a small animal irradiator using anterior-posterior and posterior-anterior beams of 225 kVp and then mailed to three institutions to test the feasibility of the audit service. The energy correction factor for TLDs in the mouse phantom was derived to validate the delivered dose using this particular animal irradiation system. This feasibility study indicated that three institutions were able to deliver a radiation dose to the mouse phantom within ±10% of the target dose. The developed mail audit independent peer review system for the verification of mouse dosimetry can be expanded to characterize other commercially available orthovoltage irradiators, thereby enhancing the reproducibility of studies employing these irradiators.

The influence of lack of reference conditions on dosimetry in pre-clinical radiotherapy with medium energy x-ray beams.

Despite well-established dosimetry in clinical radiotherapy, dose measurements in pre-clinical and radiobiology studies are frequently inadequate, thus undermining the reliability and reproducibility of published findings. The lack of suitable dosimetry protocols, coupled with the increasing complexity of pre-clinical irradiation platforms, undermines confidence in preclinical studies and represents a serious obstacle in the translation to clinical practice. To accurately measure output of a pre-clinical radiotherapy unit, appropriate Codes of Practice (CoP) for medium energy x-rays needs to be employed. However, determination of absorbed dose to water (Dw) relies on application of backscatter factor (Bw) employing in-air method or carrying out in-phantom measurement at the reference depth of 2 cm in a full backscatter (i.e. 30 × 30 × 30 cm3) condition. Both of these methods require thickness of at least 30 cm of underlying material, which are never fulfilled in typical pre-clinical irradiations. This work is focused on evaluation the effects of the lack of recommended reference conditions in dosimetry measurements for pre-clinical settings and is aimed at extending the recommendations of the current CoP to practical experimental conditions and highlighting the potential impact of the lack of correct backscatter considerations on radiobiological studies.

50 Years of the IAEA/WHO postal dose audit programme for radiotherapy: what can we learn from 13756 results?

Background: The IAEA/WHO postal dose audit programme has been operating since 1969 with the aim of improving the accuracy and consistency of dosimetry in radiotherapy in low-income and middle-income countries world-wide. This study summarises the 50 years' experience of audits and explores the quality of reference dosimetry in participating radiotherapy centres throughout the years.Material and methods: During the IAEA/WHO postal audits the dose determined from the mailed dosimeter is compared with that stated by the participant. Agreement to within ±5% is regarded acceptable whilst deviations outside ±5% limits trigger follow-up actions. Of particular interest in this study was the dependence of clinical dosimetry quality on factors related to the centre infrastructure and expertise in dosimetry of its staff.Results: The IAEA/WHO dose audit programme noted great increase in the overall percentage of acceptable results from about 50% in its early years to 99% at present, although there is some variability of results amongst participating countries. Whereas results for younger radiotherapy machines show the agreement rate between the measured and the stated doses well above 90%, for those over 20 years old the rate dropped to <80%. Linac dosimetry was always better than 60Co dosimetry and multi-machine centres generally performed better than single machine centres equipped with cobalt alone. Second and subsequent participation in audits showed higher quality dosimetry than the first participation. The implementation of modern dosimetry protocols resulted in more accurate dosimetry than the use of the older protocols.Conclusions: Over the 50 years that the IAEA has accumulated dosimetry audit data, practices in radiotherapy centres have significantly improved. Higher quality dosimetry confirmed in audits is generally associated with better infrastructure and adequate dosimetry expertise of medical physicists in participating centres.