Towards liquid EPR dosimetry using nitroxides in aqueous solution.

Objective. Water-equivalent dosimeters are desirable for dosimetry in radiotherapy. The present work investigates basic characteristics of novel aqueous detector materials and presents a signal loss approach for electron paramagnetic resonance (EPR) dosimetry.Approach. The proposed principle is based on the radiation dose dependent annihilation of EPR active nitroxides (NO·) in aqueous solutions. Stable nitroxide radicals (3-Maleimido-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (MmP), 3-Carbamoyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (CmP)) in aqueous solutions containing dimethyl sulfoxide (DMSO) as an additive were filled in glass capillaries for irradiation and EPR readout. Radiation doses ranging from 1 to 64 Gy were applied with a clinical 6 MV flattening filter free photon beam. EPR readout was then performed with a X-band benchtop spectrometer. The dose response, temporal stability and reproducibility of the samples' EPR signal amplitudes as well as the influence of the nitroxide concentration between 10 and 160µM on the absolute signal loss were investigated using MmP. CmP was used to examine the dependence of the dose response on DMSO concentration between 0 and 10 vol%. An indirect effect model was fitted to the experimental data assuming irradiation induced radical reactions as the underlying mechanism.Main results. For an initial MmP concentration of 20µM, absolute EPR signal loss is linear up to a dose of 16 Gy with a yield G(-NO·) of approximately 0.4µmol J-1. Within five weeks upon sample irradiation to doses between 0 and 32 Gy relative EPR signal fluctuations were on average (126 readouts) below 1% (1σ). For c(MmP) ≥ 20µM, absolute signal loss is only weakly dependent on c(MmP), whereas it increases strongly with increasing c(DMSO) in the range 0-5 vol%. An indirect effect model is applicable to describe the reaction mechanism resulting in the observed dose response curve.Significance. Liquids consisting of nitroxides in aqueous solution and small amounts of DMSO (2 vol%) show promising basic characteristics for application as water-equivalent EPR dosimeter materials in radiotherapy. The EPR signal loss is based on an indirect effect mediated by diffusing radicals originating from the radiolysis of the water/DMSO mixture.

Adapting a practical EPR dosimetry protocol to measure output factors in small fields with alanine.

PURPOSE: Modern radiotherapy techniques often deliver small radiation fields. In this work, a practical Electron Paramagnetic Resonance (EPR) dosimetry protocol is adapted and applied to measure output factors (OF) in small fields of a 6 MV radiotherapy system. Correction factors and uncertainties are presented and OFs are compared to the values obtained by following TRS-483 using an ionization chamber (IC). METHODS: Irradiations were performed at 10 cm depth inside a water phantom positioned at 90 cm source to surface distance with a 6 MV flattening filter free photon beam of a Halcyon radiotherapy system. OFs for different nominal field sizes (1 × 1, 2 × 2, 3 × 3, 4 × 4, normalized to 10 × 10 cm2 ) were determined with a PinPoint 3D (PTW 31022) IC following TRS-483 as well as with alanine pellets with a diameter of 4 mm and a height of 2.4 mm. EPR readout was performed with a benchtop X-band spectrometer. Correction factors due to volume averaging and due to positional uncertainties were derived from 2D film measurements. RESULTS: OFs obtained from both dosimeter types agreed within 0.7% after applying corrections for the volume averaging effect. For the used alanine pellets, volume averaging correction factors of 1.030(2) for the 1 × 1 cm2 field and <1.002 for the larger field sizes were determined. The correction factor for positional uncertainties of 1 mm was in the order of 1.018 for the 1 × 1 cm2 field. Combined relative standard uncertainties uc for the OFs resulting from alanine measurements were estimated to be below 1.5% for all field sizes. For IC measurements, uc was estimated to be below 1.0%. CONCLUSIONS: A practical EPR dosimetry protocol is adaptable for precisely measuring OFs in small fields down to 1 × 1 cm2 . It is recommended to consider the effect of positional uncertainties for field sizes <2 × 2 cm2 .

Prospective superficial EPR in-vivo dosimetry study during hypofractionated radiotherapy of breast cancer patients treated with helical tomotherapy.

BACKGROUND: In-vivo dosimetry (IVD) is a patient specific measure of quality control and safety during radiotherapy. With regard to current reporting thresholds for significant occurrences in radiotherapy defined by German regulatory authorities, the present study examines the clinical feasibility of superficial electron paramagnetic resonance (EPR) IVD of cumulative total doses applied to breast cancer patients treated with helical intensity-modulated radiotherapy (tomotherapy). METHODS: In total, 10 female patients with left- or right-sided breast cancer were enrolled in this prospective IVD study. Each patient received a hypofractionated whole breast irradiation. A total median dose of 42.4 Gy in 16 fractions (5 fractions per week) was prescribed to the planning target volume. The treatments were completely delivered using helical tomotherapy and daily image guidance via megavoltage CT (MVCT). For each patient, three EPR dosimeters were prepared and placed at distinct locations on the patient's skin during the delivery of all fractions. Two dosimeters were placed next to the ipsilateral and contralateral mammilla and one dosimeter was placed ventrally to the thyroid (out-of-primary-beam). The total doses delivered to the dosimeters were readout after all fractions had been administered. The measured total dose values were compared to the planned dose values derived from the treatment planning system (TPS). Daily positional variations (displacement vectors) of the ipsilateral mammilla and of the respective dosimeter were analyzed with respect to the planned positions using the daily registered MVCT image. RESULTS: Averaged over all patients, the mean absolute dose differences between measured and planned total dose values (± standard deviation (SD)) were: 0.49 ± 0.85 Gy for the ipsilateral dosimeter, 0.17 ± 0.49 Gy for the contralateral dosimeter and -0.12 ± 0.30 Gy for the thyroid dosimeter. The mean lengths of the ipsilateral displacement vectors (± SD) averaged over all patients and fractions were: 10 ± 7 mm for the dosimeter and 8 ± 4 mm for the mammilla. CONCLUSION: Superficial EPR IVD is suitable as additional safeguard for dose delivery during helical tomotherapy of breast cancer. Despite positional uncertainties in clinical routine, the observed dose deviations at the ipsilateral breast were on average small compared to national reporting thresholds for total dose deviations (i.e. 10%/4 Gy). EPR IVD may allow for the detection of critical dose errors during whole breast irradiations.

Suitability of superficial electron paramagnetic resonance dosimetry for in vivo measurement and verification of cumulative total doses during IMRT: A proof of principle.

PURPOSE: The present study investigates superficial in vivo dosimetry (IVD) by means of a previously proposed electron paramagnetic resonance (EPR) dosimetry system aiming at measuring and verifying total doses delivered by complex radiotherapy treatments. In view of novel regulatory requirements in Germany, differences between measured and planned total doses to the EPR dosimeters are analyzed and compared to reporting thresholds for significant occurrences. METHODS: EPR dosimeters, each consisting of one lithium formate monohydrate (LFM) and one polycrystalline l-alanine (ALA) pellet, were attached to the surface of an anthropomorphic head phantom. Three head and neck treatments with total target doses ranging from 30 to 64Gy were fully delivered to the phantom by helical tomotherapy. During each treatment, eight EPR dosimeters were placed at distinct spots: (i) within or next to the planning target volume (PTV), (ii) near to organs at risk including the parotids and the lenses, (iii) at the thyroid lying out-of-field. EPR read out was always performed after all fractions were delivered. EPR results were compared to thermoluminescence dosimeter (TLD) measurements and to the planned total doses derived from the treatment planning system (TPS). Planned total doses to the EPR dosimeters ranged from about 2 to 64Gy. RESULTS: By taking uncertainties into account, the measured and planned doses were in good agreement. Exceptions occurred mainly at the thyroid (out-of-field) and lenses (extreme sparing). The maximum total dose difference between EPR results and corresponding planned doses was 1.3Gy occurring at the lenses. Remarkably, each LFM and ALA pellet placed within or next to the PTV provided dose values that were within ±4% of the planned dose. Dose deviations from planned dose values were comparable for EPR and TLD measurements. CONCLUSION: The results of this proof of principle study suggests that superficial EPR-IVD is applicable in a wide dose range and in various irradiation conditions - being a valuable tool for monitoring cumulative total doses delivered by complex IMRT treatments. EPR-IVD in combination with helical tomotherapy is suitable to reliably detect local dose deviations at superficial dosimeter spots in the order of current national reporting thresholds for significant occurrences (i.e. 10%/4Gy).

A practical EPR dosimetry system for routine use in radiotherapy: uncertainty analysis of lithium formate dosimeters at the therapeutic dose level.

In electron paramagnetic resonance (EPR) dosimetry, solid dosimeter materials such as alanine (AL) or, more recently, lithium formate monohydrate (LFM) are typically used. These materials offer high potential for applications in radiotherapy based on their favorable dosimetric properties. Nevertheless, EPR dosimetry is not widespread in the clinics. This work presents an uncertainty analysis of EPR dosimetry in the dose range from 1 to 70 Gy using a compact spectrometer and applying a practical procedure being suitable for routine use in radiotherapy. The performances of self-pressed LFM pellets and commercial AL pellets are compared side by side. All pellets had a diameter of 4 mm and a height of 2 mm (AL) or 4 mm (LFM). The mean pellet mass was 35.81 mg and 73.81 mg for AL and LFM, respectively. Before irradiation, the pellets were stored for at least 8 weeks at 34 ± 2% relative humidity. For irradiation, the pellets were put inside an airtight capsule. In total, 25 pellets per material were examined. The pellets were irradiated at a temperature of 25 ± 2.5 (2σ) °C to doses of either 1, 5, 20, 50 or 70 Gy (five pellets per dose value and material) by a clinical 6 MV photon beam. Measurement uncertainties were obtained from five independent readouts per pellet within five weeks following irradiation using a benchtop EPR spectrometer. The measurement time of a single readout was restricted to 10 min per pellet. Dose values were derived from EPR signal amplitudes using a specifically developed spectral fitting procedure. Signal fading characteristics were analyzed and taken into account during evaluation. The relative dose uncertainties (1σ) for a single readout at doses ≥ 5 Gy are below 2.8% (AL) and 1.1% (LFM) but increase to 12.3% (AL) and 2.6% (LFM) at 1 Gy. By averaging five independent readouts, the uncertainties at 1 Gy decrease to 2.6% (AL) and 0.8% (LFM). In terms of dose uncertainty, the LFM pellets are superior to the commercial AL pellets owing to their narrower EPR spectrum and approximately doubled mass resulting in higher EPR signal intensities. In case of the LFM pellets, the EPR dosimetry system shows a high level of precision (< 3%) down to 1 Gy being preferable for applications in radiotherapy. The uncertainties can be further decreased by averaging multiple dose values from independent readouts.

EPR imaging of magnetic field effects on radiation dose distributions around millimeter-size air cavities.

New hybrid radiotherapy treatment systems combining an MRI scanner with a source of ionizing radiation are being introduced in the clinic. The strong magnetic fields of MRI considerably affect radiation dose distributions, especially at tissue-air interfaces due to the electron return effect (ERE). Experimental investigation of the ERE within a sub-millimeter thick surface layer is still highly challenging. In the present work, we examine and quantify the magnetic field induced perturbations of dose distributions within a 0.5 mm layer surrounding millimeter-size air cavities by applying electron paramagnetic resonance imaging (EPRI). Air-filled fused quartz tubes (inner diameter 3 or 4 mm) mimic small air cavities and serve as model systems. The tubes were irradiated inside a PMMA phantom by a 6 MV photon beam. The irradiations were performed in the presence or absence of a transverse, magnetic field providing a magnetic field strength of 1.0 Tesla. The spatial distributions of radiation induced paramagnetic defects in the quartz tubes were subsequently determined by applying field-swept echo-detected EPRI and were then converted to relative dose distributions. The transverse magnetic field leads to considerable local dose enhancements and reductions (up to 35%) with respect to the mean dose within the quartz tubes. The experimentally determined dose distributions are in good quantitative agreement with Monte Carlo radiation transport simulations. The results of this work demonstrate the feasibility of field-swept echo-detected EPRI to measure magnetic field induced perturbations of dose distributions within a sub-millimeter thick surface layer at the dosimeter-air interface.

Dosimetric effects of swelling or shrinking tissue during helical tomotherapy breast irradiation. A phantom study.

During radiation therapy of the female breast, the actual target volume compared to the planning target volume may change due to swelling or shrinking of the tissue. Under- or overdosage is to be expected, especially when performing IMRT or tomotherapy techniques. The objective of this study is to develop a model-based quantification of these dose effects, with a particular focus on the changes in the surface dose. A cylindrical phantom was used as an artificial surrogate of the human torso. By adding and removing Superflab layers of various thicknesses, both radial breast swelling and shrinking could be simulated. The effects on dose distribution were evaluated using film dosimetry. The results were compared to dose calculations. To estimate the true surface doses, we subtracted the influence of the film material on air measurements. During a swelling of 5, 10, and 15 mm, the planning target volume was consistently underdosed by 2%, 5%, and 7% of the prescribed dose, respectively. Swelling led to reduced dose values of up to 72%, 55%, and 50% at the outer edge of the actual target volume. The measured surface dose decreased successively from 31% to 23%. During shrinking, the dose in the planning target volume increased successively from 100% to 106%. The measured surface doses increased from 29% to 36%. The calculated dose values agreed with the measured values within error limits. During radiotherapy of the female breast, new planning appears to be essential for radial tissue swelling of 5 mm or more because of severe underdosing. Shrinking leads to moderate overdosing and an increased surface dose. In addition, caution is advised when removing bolus material with respect to the planned situation.