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.

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.

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.

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.

Single scan SeHCAT studies: a model for the prediction of the 3-h counts.

OBJECTIVES: As part of the 75-Selenium homocholic acid taurine (SeHCAT) study, counts are acquired as a baseline to allow the calculation of the retention at 7 days. In this work, we evaluated whether it was possible to replace the baseline image with a predictive model based on the patient's height and weight. METHOD: Height and weight data from 723 patients scanned at three hospitals using seven gamma cameras were compiled. A number of different models were trialled, with fitting parameters determined by regression. A predictive model based on height and logarithm of weight was found to have the best correlation with the measured counts in the 3-h study. RESULTS: There was a strong correlation (R2 = 0.91) between the measured counts and the predicted counts using a model based on height and logarithm of weight. Treating the standard SeHCAT test result as the gold standard, the test result when predicted baseline counts were used had a sensitivity and specificity of 97.5 and 98.0%, respectively, at a threshold of 15%. In total 694/723 (96.0%) of patients had no change to their severity grading when using the predicted baseline counts. CONCLUSION: This work presents a model that was able to predict the counts in the 3 h SeHCAT study for patients on seven gamma cameras. This can enable a single scan study, giving significant savings to patient and staff time and imaging resources.

Standardised quantitative radioiodine SPECT/CT Imaging for multicentre dosimetry trials in molecular radiotherapy.

The SEL-I-METRY trial (EudraCT No 2015-002269-47) is the first multicentre trial to investigate the role of 123I and 131I SPECT/CT-based tumour dosimetry to predict response to radioiodine therapy. Standardised dosimetry methodology is essential to provide a robust evidence-base for absorbed dose-response thresholds for molecular radiotherapy (MRT). In this paper a practical standardised protocol is used to establish the first network of centres with consistent methods of radioiodine activity quantification. Nine SPECT/CT systems at eight centres were set-up for quantitative radioiodine imaging. The dead-time of the systems was characterised for up to 2.8 GBq 131I. Volume dependent calibration factors were measured on centrally reconstructed images of 123I and 131I in six (0.8-196 ml) cylinders. Validation of image quantification using these calibration factors was performed on three systems, by imaging a 3D-printed phantom mimicking a patient's activity distribution. The percentage differences between the activities measured in the SPECT/CT image and those measured by the radionuclide calibrator were calculated. Additionally uncertainties on the SPECT/CT-based activities were calculated to indicate the limit on the quantitative accuracy of this method. For systems set-up to image high 131I count rates, the count rate versus activity did not peak below 2.8 GBq and fit a non-paralysable model. The dead-times and volume-dependent calibration factors were comparable between systems of the same model and crystal thickness. Therefore a global calibration curve could be fitted to each. The errors on the validation phantom activities' were comparable to the measurement uncertainties derived from uncertainty analysis, at 10% and 16% on average for 123I and 131I respectively in a 5 cm sphere. In conclusion, the dead-time and calibration factors varied between centres, with different models of system. However, global calibration factors may be applied to the same system model with the same crystal thickness, to simplify set-up of future multi-centre MRT studies.

Inter-comparison of quantitative imaging of lutetium-177 (177Lu) in European hospitals.

BACKGROUND: This inter-comparison exercise was performed to demonstrate the variability of quantitative SPECT/CT imaging for lutetium-177 (177Lu) in current clinical practice. Our aim was to assess the feasibility of using international inter-comparison exercises as a means to ensure consistency between clinical sites whilst enabling the sites to use their own choice of quantitative imaging protocols, specific to their systems. Dual-compartment concentric spherical sources of accurately known activity concentrations were prepared and sent to seven European clinical sites. The site staff were not aware of the true volumes or activity within the sources-they performed SPECT/CT imaging of the source, positioned within a water-filled phantom, using their own choice of parameters and reported their estimate of the activities within the source. RESULTS: The volumes reported by the participants for the inner section of the source were all within 29% of the true value and within 60% of the true value for the outer section. The activities reported by the participants for the inner section of the source were all within 20% of the true value, whilst those reported for the outer section were up to 83% different to the true value. CONCLUSIONS: A variety of calibration and segmentation methods were used by the participants for this exercise which demonstrated the variability of quantitative imaging across clinical sites. This paper presents a method to assess consistency between sites using different calibration and segmentation methods.

Septal penetration correction in I-131 imaging following thyroid cancer treatment.

Whole body gamma camera images acquired after I-131 treatment for thyroid cancer can suffer from collimator septal penetration artefacts because of the high energy of the gamma photons. This results in the appearance of 'spoke' artefacts, emanating from regions of high activity concentration, caused by the non-isotropic attenuation of the collimator. Deconvolution has the potential to reduce such artefacts, by taking into account the non-Gaussian point-spread-function (PSF) of the system. A Richardson-Lucy deconvolution algorithm, with and without prior scatter-correction was tested as a method of reducing septal penetration in planar gamma camera images. Phantom images (hot spheres within a warm background) were acquired and deconvolution using a measured PSF was applied. The results were evaluated through region-of-interest and line profile analysis to determine the success of artefact reduction and the optimal number of deconvolution iterations and damping parameter (λ). Without scatter-correction, the optimal results were obtained with 15 iterations and λ = 0.01, with the counts in the spokes reduced to 20% of the original value, indicating a substantial decrease in their prominence. When a triple-energy-window scatter-correction was applied prior to deconvolution, the optimal results were obtained with six iterations and λ = 0.02, which reduced the spoke counts to 3% of the original value. The prior application of scatter-correction therefore produced the best results, with a marked change in the appearance of the images. The optimal settings were then applied to six patient datasets, to demonstrate its utility in the clinical setting. In all datasets, spoke artefacts were substantially reduced after the application of scatter-correction and deconvolution, with the mean spoke count being reduced to 10% of the original value. This indicates that deconvolution is a promising technique for septal penetration artefact reduction that could potentially improve the diagnostic accuracy of I-131 imaging. Novelty and significance This work has demonstrated that scatter correction combined with deconvolution can be used to substantially reduce the appearance of septal penetration artefacts in I-131 phantom and patient gamma camera planar images, enable improved visualisation of the I-131 distribution. Deconvolution with symmetric PSF has previously been used to reduce artefacts in gamma camera images however this work details the novel use of an asymmetric PSF to remove the angularly dependent septal penetration artefacts.

Clinical applications of textural analysis in non-small cell lung cancer.

Lung cancer is the leading cause of cancer mortality worldwide. Treatment pathways include regular cross-sectional imaging, generating large data sets which present intriguing possibilities for exploitation beyond standard visual interpretation. This additional data mining has been termed "radiomics" and includes semantic and agnostic approaches. Textural analysis (TA) is an example of the latter, and uses a range of mathematically derived features to describe an image or region of an image. Often TA is used to describe a suspected or known tumour. TA is an attractive tool as large existing image sets can be submitted to diverse techniques for data processing, presentation, interpretation and hypothesis testing with annotated clinical outcomes. There is a growing anthology of published data using different TA techniques to differentiate between benign and malignant lung nodules, differentiate tissue subtypes of lung cancer, prognosticate and predict outcome and treatment response, as well as predict treatment side effects and potentially aid radiotherapy planning. The aim of this systematic review is to summarize the current published data and understand the potential future role of TA in managing lung cancer.

Factors influencing the robustness of P-value measurements in CT texture prognosis studies.

Several studies have recently reported on the value of CT texture analysis in predicting survival, although the topic remains controversial, with further validation needed in order to consolidate the evidence base. The aim of this study was to investigate the effect of varying the input parameters in the Kaplan-Meier analysis, to determine whether the resulting P-value can be considered to be a robust indicator of the parameter's prognostic potential. A retrospective analysis of the CT-based normalised entropy of 51 patients with lung cancer was performed and overall survival data for these patients were collected. A normalised entropy cut-off was chosen to split the patient cohort into two groups and log-rank testing was performed to assess the survival difference of the two groups. This was repeated for varying normalised entropy cut-offs and varying follow-up periods. Our findings were also compared with previously published results to assess robustness of this parameter in a multi-centre patient cohort. The P-value was found to be highly sensitive to the choice of cut-off value, with small changes in cut-off producing substantial changes in P. The P-value was also sensitive to follow-up period, with particularly noisy results at short follow-up periods. Using matched conditions to previously published results, a P-value of 0.162 was obtained. Survival analysis results can be highly sensitive to the choice in texture cut-off value in dichotomising patients, which should be taken into account when performing such studies to avoid reporting false positive results. Short follow-up periods also produce unstable results and should therefore be avoided to ensure the results produced are reproducible. Previously published findings that indicated the prognostic value of normalised entropy were not replicated here, but further studies with larger patient numbers would be required to determine the cause of the different outcomes.

Three dosimetry models of lipoma arborescens treated by 90Y synovectomy.

PURPOSE: Lipoma arborescens (LA) is a benign intra-articular lipomatous proliferation of the synovial membrane. This extremely rare condition has previously been treated by intra-articular (90)Y radiosynoviorthesis but dosimetry literature on this form of radionuclide therapy is nonexistent. The authors detail methodology for successful treatment of LA and provide for the first time estimates of radiation dosimetry. The authors also analyze the biodistribution of the radiopharmaceutical over the course of the patient's treatment through sequential imaging. METHODS: A patient with bilateral LA underwent intracavity injection of (90)Y citrate colloid to the right and left knee joint spaces (181 and 198 MBq, respectively). SPECT/CT datasets were acquired over 9 days to quantify the biodistribution and kinetics of the radiopharmaceutical. Radiation dosimetry was performed using the MIRD schema (through OLINDA software), a custom voxel-based method, and a direct Monte Carlo calculation (OEDIPE). RESULTS: Follow-up MRI showed marked reduction in LA size in both knees. Mean absorbed doses to the LA were 21.2 ± 0.8 and 42.9 ± 2.3 Gy using OLINDA, 8.1 ± 0.3 and 16.7 ± 0.5 Gy using voxel based methodology, and 8.2 ± 0.3 and 15.7 ± 0.5 Gy for OEDIPE in the right and left LA, respectively. Distribution of the radiopharmaceutical within the joint space alters over the imaging period, with less than 1% of the remaining activity having moved posteriorly in the knee cavity. No uptake was detected outside of the joint space after assessment with whole-body scintigraphy. CONCLUSIONS: An activity of approximately 185 MBq successfully relieved clinical symptoms of LA. There was good correlation between direct Monte Carlo and voxel based techniques, but OLINDA was shown to overestimate the absorbed dose to the tumor. Accurate dosimetry may help select an activity more tailored to the specific size and location of the LA.

Lipoma arborescens successfully treated with (90)Y synovectomy.

Lipoma arborescens (LA) in the knee is a benign intra-articular lipomatous proliferation of the synovial membrane, and data on treatment of LA by radionuclide therapy is sparse. We present a rare case of bilateral LA in the knees successfully treated with injection of Y-citrate colloid. We assessed the biodistribution of the radiopharmaceutical through the use of SPECT/CT imaging. Our images show slight redistribution of the radiocolloid in the knee joint, whereas most of the radioactivity remains localized around the LA. MRI scans confirmed the efficacy of this treatment, with a significant reduction in LA volume after 6 months.

The importance of scatter correction for the assessment of lung shunting prior to yttrium-90 radioembolization therapy.

BACKGROUND: Treatment of inoperable hepatocellular carcinoma or secondary metastases by radioembolization using yttrium-90 (90Y) microspheres is a promising method for the treatment of unresectable liver metastases. A pretreatment scintigraphy planar scan using 99mTc-labelled macroaggregated albumin (99mTc-MAA) injected directly into the hepatic artery is carried out to assess the degree of portal shunting of blood between the liver and the lungs. The quantitative results of this scan are used to modulate the activity of therapeutic 90Y microspheres injected into the patient to limit the radiation dose received by the lungs. The presence of scattered events in the MAA lung shunt scan leads to an overestimation of the true shunting ratio, which in turn leads to the administered therapeutic activity being lowered unnecessarily to comply with the protocols of radiation protection. Overall, this may impact the efficacy of treatment. MATERIALS AND METHODS: This study analyses the impact of a window-based analytical scatter-correction method on lung shunt analysis using an anthropomorphic torso phantom, and retrospectively analysed three patient case studies. RESULTS: Our results of scatter in the phantom show a marked decrease in the lung shunt percentage. Clinical analysis of patient data shows that the lung shunt percentage can be overestimated by up to 50% in clinical cases, and depending on the lung shunt percentage, the efficacy of treatment by therapeutic dose reduction may be compromised. CONCLUSION: Our results indicate that scatter correction should be used on 90Y pretreatment 99mTc-MAA scans in order to more accurately assess the lung shunting percentage before therapy.