Development of a validation imaging dataset for Molecular Radiotherapy dosimetry multicenter intercomparison exercises based on anthropomorphic phantoms.

Validation of a Molecular Radiotherapy (MRT) dosimetry system requires imaging data for which an accompanying "ground truth" pharmacokinetic model and absorbed dose calculation are known. METHODS: We present a methodology for production of a validation dataset for image based 177Lu dotatate dosimetry calculations. A pharmacokinetic model is presented with activity concentrations corresponding to common imaging timepoints. Anthropomorphic 3D printed phantoms, corresponding to the organs at risk, have been developed to provide SPECT/CT and Whole Body imaging with known organ activities corresponding to common clinical timepoints. RESULTS: Results for the accuracy of phantom filling reproduce the activity concentrations from the pharmacokinetic model for all timepoints and organs within measurement uncertainties, with a mean deviation of 0.6(8)%. The imaging dataset, ancillary data and phantoms designs are provided as a source of well characterized input data for the validation of clinical MRT dosimetry systems. CONCLUSIONS: The combination of pharmacokinetic modelling with the use of anthropomorphic 3D printed phantoms are a promising procedure to provide data for the validation of Molecular Radiotherapy Dosimetry systems, allowing multicentre comparisons.

Triple modality image reconstruction of PET data using SPECT, PET, CT information increases lesion uptake in images of patients treated with radioembolization with [Formula: see text] micro-spheres.

PURPOSE: Nuclear medicine imaging modalities like computed tomography (CT), single photon emission CT (SPECT) and positron emission tomography (PET) are employed in the field of theranostics to estimate and plan the dose delivered to tumors and the surrounding tissues and to monitor the effect of the therapy. However, therapeutic radionuclides often provide poor images, which translate to inaccurate treatment planning and inadequate monitoring images. Multimodality information can be exploited in the reconstruction to enhance image quality. Triple modality PET/SPECT/CT scanners are particularly useful in this context due to the easier registration process between images. In this study, we propose to include PET, SPECT and CT information in the reconstruction of PET data. The method is applied to Yttrium-90 ([Formula: see text]Y) data. METHODS: Data from a NEMA phantom filled with [Formula: see text]Y were used for validation. PET, SPECT and CT data from 10 patients treated with Selective Internal Radiation Therapy (SIRT) were used. Different combinations of prior images using the Hybrid kernelized expectation maximization were investigated in terms of VOI activity and noise suppression. RESULTS: Our results show that triple modality PET reconstruction provides significantly higher uptake when compared to the method used as standard in the hospital and OSEM. In particular, using CT-guided SPECT images, as guiding information in the PET reconstruction significantly increases uptake quantification on tumoral lesions. CONCLUSION: This work proposes the first triple modality reconstruction method and demonstrates up to 69% lesion uptake increase over standard methods with SIRT [Formula: see text]Y patient data. Promising results are expected for other radionuclide combination used in theranostic applications using PET and SPECT.

Quantitative validation of Monte Carlo SPECT simulation: application to a Mediso AnyScan GATE simulation.

BACKGROUND: Monte Carlo (MC) simulations are used in nuclear medicine imaging as they provide unparalleled insight into processes that are not directly experimentally measurable, such as scatter and attenuation in an acquisition. Whilst MC is often used to provide a 'ground-truth', this is only the case if the simulation is fully validated against experimental data. This work presents a quantitative validation for a MC simulation of a single-photon emission computed tomography (SPECT) system. METHODS: An MC simulation model of the Mediso AnyScan SCP SPECT system installed at the UK National Physical Laboratory was developed in the GATE (Geant4 Application for Tomographic Emission) toolkit. Components of the detector head and two collimator configurations were modelled according to technical specifications and physical measurements. Experimental detection efficiency measurements were collected for a range of energies, permitting an energy-dependent intrinsic camera efficiency correction function to be determined and applied to the simulation on an event-by-event basis. Experimental data were collected in a range of geometries with [Formula: see text]Tc for comparison to simulation. The procedure was then repeated with [Formula: see text]Lu to determine how the validation extended to another isotope and set of collimators. RESULTS: The simulation's spatial resolution, sensitivity, energy spectra and the projection images were compared with experimental measurements. The simulation and experimental uncertainties were determined and propagated to all calculations, permitting the quantitative agreement between simulated and experimental SPECT acquisitions to be determined. Statistical agreement was seen in sinograms and projection images of both [Formula: see text]Tc and [Formula: see text]Lu data. Average simulated and experimental sensitivity ratios of ([Formula: see text]) were seen for emission and scatter windows of [Formula: see text]Tc, and ([Formula: see text]) and ([Formula: see text]) for the 113 and 208 keV emissions of [Formula: see text]Lu, respectively. CONCLUSIONS: MC simulations will always be an approximation of a physical system and the level of agreement should be assessed. A validation method is presented to quantify the level of agreement between a simulation model and a physical SPECT system.

On the use of solid 133Ba sources as surrogate for liquid 131I in SPECT/CT calibration: a European multi-centre evaluation.

INTRODUCTION: Commissioning, calibration, and quality control procedures for nuclear medicine imaging systems are typically performed using hollow containers filled with radionuclide solutions. This leads to multiple sources of uncertainty, many of which can be overcome by using traceable, sealed, long-lived surrogate sources containing a radionuclide of comparable energies and emission probabilities. This study presents the results of a quantitative SPECT/CT imaging comparison exercise performed within the MRTDosimetry consortium to assess the feasibility of using 133Ba as a surrogate for 131I imaging. MATERIALS AND METHODS: Two sets of four traceable 133Ba sources were produced at two National Metrology Institutes and encapsulated in 3D-printed cylinders (volume range 1.68-107.4 mL). Corresponding hollow cylinders to be filled with liquid 131I and a mounting baseplate for repeatable positioning within a Jaszczak phantom were also produced. A quantitative SPECT/CT imaging comparison exercise was conducted between seven members of the consortium (eight SPECT/CT systems from two major vendors) based on a standardised protocol. Each site had to perform three measurements with the two sets of 133Ba sources and liquid 131I. RESULTS: As anticipated, the 131I pseudo-image calibration factors (cps/MBq) were higher than those for 133Ba for all reconstructions and systems. A site-specific cross-calibration reduced the performance differences between both radionuclides with respect to a cross-calibration based on the ratio of emission probabilities from a median of 12-1.5%. The site-specific cross-calibration method also showed agreement between 133Ba and 131I for all cylinder volumes, which highlights the potential use of 133Ba sources to calculate recovery coefficients for partial volume correction. CONCLUSION: This comparison exercise demonstrated that traceable solid 133Ba sources can be used as surrogate for liquid 131I imaging. The use of solid surrogate sources could solve the radiation protection problem inherent in the preparation of phantoms with 131I liquid activity solutions as well as reduce the measurement uncertainties in the activity. This is particularly relevant for stability measurements, which have to be carried out at regular intervals.

Hybrid kernelised expectation maximisation for Bremsstrahlung SPECT reconstruction in SIRT with 90Y micro-spheres.

BACKGROUND: Selective internal radiation therapy with Yttrium-90 microspheres is an effective therapy for liver cancer and liver metastases. Yttrium-90 is mainly a high-energy beta particle emitter. These beta particles emit Bremsstrahlung radiation during their interaction with tissue making post-therapy imaging of the radioactivity distribution feasible. Nevertheless, image quality and quantification is difficult due to the continuous energy spectrum which makes resolution modelling, attenuation and scatter estimation challenging and therefore the dosimetry quantification is inaccurate. As a consequence a reconstruction algorithm able to improve resolution could be beneficial. METHODS: In this study, the hybrid kernelised expectation maximisation (HKEM) is used to improve resolution and contrast and reduce noise, in addition a modified HKEM called frozen HKEM (FHKEM) is investigated to further reduce noise. The iterative part of the FHKEM kernel was frozen at the 72nd sub-iteration. When using ordered subsets algorithms the data is divided in smaller subsets and the smallest algorithm iterative step is called sub-iteration. A NEMA phantom with spherical inserts was used for the optimisation and validation of the algorithm, and data from 5 patients treated with Selective internal radiation therapy were used as proof of clinical relevance of the method. RESULTS: The results suggest a maximum improvement of 56% for region of interest mean recovery coefficient at fixed coefficient of variation and better identification of the hot volumes in the NEMA phantom. Similar improvements were achieved with patient data, showing 47% mean value improvement over the gold standard used in hospitals. CONCLUSIONS: Such quantitative improvements could facilitate improved dosimetry calculations with SPECT when treating patients with Selective internal radiation therapy, as well as provide a more visible position of the cancerous lesions in the liver.

A multicentre and multi-national evaluation of the accuracy of quantitative Lu-177 SPECT/CT imaging performed within the MRTDosimetry project.

PURPOSE: Patient-specific dosimetry is required to ensure the safety of molecular radiotherapy and to predict response. Dosimetry involves several steps, the first of which is the determination of the activity of the radiopharmaceutical taken up by an organ/lesion over time. As uncertainties propagate along each of the subsequent steps (integration of the time-activity curve, absorbed dose calculation), establishing a reliable activity quantification is essential. The MRTDosimetry project was a European initiative to bring together expertise in metrology and nuclear medicine research, with one main goal of standardizing quantitative 177Lu SPECT/CT imaging based on a calibration protocol developed and tested in a multicentre inter-comparison. This study presents the setup and results of this comparison exercise. METHODS: The inter-comparison included nine SPECT/CT systems. Each site performed a set of three measurements with the same setup (system, acquisition and reconstruction): (1) Determination of an image calibration for conversion from counts to activity concentration (large cylinder phantom), (2) determination of recovery coefficients for partial volume correction (IEC NEMA PET body phantom with sphere inserts), (3) validation of the established quantitative imaging setup using a 3D printed two-organ phantom (ICRP110-based kidney and spleen). In contrast to previous efforts, traceability of the activity measurement was required for each participant, and all participants were asked to calculate uncertainties for their SPECT-based activities. RESULTS: Similar combinations of imaging system and reconstruction lead to similar image calibration factors. The activity ratio results of the anthropomorphic phantom validation demonstrate significant harmonization of quantitative imaging performance between the sites with all sites falling within one standard deviation of the mean values for all inserts. Activity recovery was underestimated for total kidney, spleen, and kidney cortex, while it was overestimated for the medulla. CONCLUSION: This international comparison exercise demonstrates that harmonization of quantitative SPECT/CT is feasible when following very specific instructions of a dedicated calibration protocol, as developed within the MRTDosimetry project. While quantitative imaging performance demonstrates significant harmonization, an over- and underestimation of the activity recovery highlights the limitations of any partial volume correction in the presence of spill-in and spill-out between two adjacent volumes of interests.

Absolute standardisation and determination of the half-life and gamma emission intensities of 89Zr.

An absolute standardisation of 89Zr was performed alongside determination of gamma emission intensities and half-life. The collected data were evaluated alongside complementary works from previous publications and new recommended nuclear data values are presented including a new evaluated T1/2 = 78.361(25) h and new absolute intensities for gamma transitions resulting from its decay to 89Y. Dial settings for commercially available radionuclide calibrators are also presented and show a relative difference of approximately 3% compared to previously published values.

123I intercomparison exercises: Assessment of measurement capabilities in UK hospitals.

Three comparison exercises have been performed in 1996, 1999 and 2015 with 123I to assess the UK hospitals measurement capabilities using radionuclide calibrators for this particular radionuclide. The exercise performed in 1996 showed that only 62% of the participants could measure the solution to within 10% of the standardised value and only 28% could measure within 5% of the certificated value. The intercomparison exercise performed in 1999 showed no improvement in the measurement capability, with only 66% of the participants measuring to within 10% of the standardised value. The exercise performed in 2015 showed great improvement in the hospitals measurement capability, 94% of participants reported results within 10% of the certificated activity and 85% of the participants reported results within the 5% of the reported activity. The intercomparison exercises are an important way to identify possible measurement problems within the medical community. Additionally, the intercomparison exercises provide hospitals with traceability to national primary standards and improve measurement capability within the Nuclear Medicine community.

Standardisation of (90)Y and determination of calibration factors for (90)Y microspheres (resin) for the NPL secondary ionisation chamber and a Capintec CRC-25R.

The use of (90)Y resin microspheres (SIR-Spheres® microspheres) in Nuclear Medicine has dramatically increased in recent years due to its favourable outcome in the treatment of liver cancer and liver metastases (Rajekar et al., 2011). The measurement of administered activity before and residual activity after treatment in radionuclide calibrators is required to determine total activity delivered to the patient. In comparison with External Beam Radiotherapy (EBRT) where administered doses are often know to within ±5%, the actual administered activity in nuclear medicine procedures may only be known to within ±20% and subsequent dose calculations can result in even larger uncertainties (Fenwick et al., 2009). It is a well-recognised issue that ion chambers are instruments that are sensitive to the measurement geometry and matrix of a source, in particular for pure beta or low energy (<100keV) x-ray emitters (Gadd et al., 2006). This paper presents new calibration factors for NPL secondary standard ionisation chamber system (Vinten 671) and a Capintec CRC-25R radionuclide calibrator along with a discussion of the measurement problems associated with this radionuclide and matrix. Calibration of the NPL secondary standard system for this measurement matrix will enable NPL to provide standards for the Nuclear Medicine community and consequently increase the measurement capability.