David Minarik

Evaluation of quantitative (90)Y SPECT based on experimental phantom studies.

In SPECT imaging of pure beta emitters, such as (90)Y, the acquired spectrum is very complex, which increases the demands on the imaging protocol and the reconstruction. In this work, we have evaluated the quantitative accuracy of bremsstrahlung SPECT with focus on the reconstruction algorithm including model-based attenuation, scatter and collimator-detector response (CDR) compensations. The scatter and CDR compensation methods require pre-calculated point-spread functions, which were generated with the SIMIND MC program. The SIMIND program is dedicated for simulation of scintillation camera imaging and only handles photons. The aim of this work was therefore twofold. The first aim was to implement simulation of bremsstrahlung imaging into the SIMIND code and to validate simulations against experimental measurements. The second was to investigate the quality of bremsstrahlung SPECT imaging and to evaluate the possibility of quantifying the activity in differently shaped sources. In addition, a feasibility test was performed on a patient that underwent treatment with (90)Y-Ibritumomab tiuxetan (Zevalin). The MCNPX MC program was used to generate bremsstrahlung photon spectra which were used as source input in the SIMIND program. The obtained bremsstrahlung spectra were separately validated by experimental measurement using a HPGe detector. Validation of the SIMIND generated images was done by a comparison to gamma camera measurements of a syringe containing (90)Y. Results showed a slight deviation between simulations and measurements in image regions outside the source, but the agreement was sufficient for the purpose of generating scatter and CDR kernels. For the bremsstrahlung SPECT experiment, the RSD torso phantom with (90)Y in the liver insert was measured with and without background activities. Projection data were obtained using a GE VH/Hawkeye system. Image reconstruction was performed by using the OSEM algorithm with and without different combinations of model-based attenuation, scatter and CDR compensations. The reconstructed images were then evaluated in terms of the accuracy of the total activity estimate in the liver insert. It was found that the activity in a large source such as the liver was estimated with a bias of around -70%, when no compensations were included in the reconstruction, whereas when compensations were included the bias obtained was between -10 and 16%. It is concluded that although the (90)Y bremsstrahlung spectrum is continuous with no pronounced peak and the count rate is low, it is possible to achieve reasonably accurate activity estimates from bremsstrahlung SPECT images if proper compensations are applied in the reconstruction. This conclusion was also confirmed by the patient study.

EANM procedural guidelines for radionuclide myocardial perfusion imaging with SPECT and SPECT/CT : 2015 revision

Since the publication of the European Association of Nuclear Medicine (EANM) procedural guidelines for radionuclide myocardial perfusion imaging (MPI) in 2005, many small and some larger steps of progress have been made, improving MPI procedures. In this paper, the major changes from the updated 2015 procedural guidelines are highlighted, focusing on the important changes related to new instrumentation with improved image information and the possibility to reduce radiation exposure, which is further discussed in relation to the recent developments of new International Commission on Radiological Protection (ICRP) models. Introduction of the selective coronary vasodilator regadenoson and the use of coronary CT-contrast agents for hybrid imaging with SPECT/CT angiography are other important areas for nuclear cardiology that were not included in the previous guidelines. A large number of minor changes have been described in more detail in the fully revised version available at the EANM home page: http://eanm.org/publications/guidelines/2015_07_EANM_FINAL_myocardial_perfusion_guideline.pdf.

90Y Bremsstrahlung Imaging for Absorbed-Dose Assessment in High-Dose Radioimmunotherapy

This feasibility study demonstrates 90Y quantitative bremsstrahlung imaging of patients undergoing high-dose myeloablative 90Y-ibritumomab treatment. Methods: The study includes pretherapy 111In SPECT/CT and planar whole-body (WB) imaging at 7 d and therapy 90Y SPECT/CT at 6 d and 90Y WB imaging at 1 d. Time–activity curves and organ-absorbed doses derived from 90Y SPECT images were compared with pretherapy 111In estimates. Organ activities derived from 90Y WB images at the first day were compared with corresponding pretherapy estimates. Results: Pretherapy 111In images from 3 patients were similar to the 90Y images. Differences between absorbed-dose estimates from pretherapy 111In and 90Y therapy were within 25%, except for the lungs. Corresponding activity differences derived from WB images were within 25%. Differences were ascribed to incomplete compensation methods and real differences in pharmacokinetics between pretherapy and therapy. Conclusion: Quantitative bremsstrahlung imaging to estimate organ activities and absorbed doses is feasible.

Evaluation of quantitative planar (90)Y bremsstrahlung whole-body imaging.

With high-dose administration of (90)Y labeled antibodies, it is possible to image (90)Y without an admixture of (111)In. We have earlier shown that it is possible to perform quantitative (90)Y bremsstrahlung SPECT for dosimetry purposes with reasonable accuracy. However, whole-body (WB) activity quantification with the conjugate view method is not as time consuming as SPECT and has been the method of choice for dosimetry. We have investigated the possibility of using a conjugate view method where scatter-, backscatter- and septal-penetration compensations are performed by inverse filtering and attenuation correction is performed with a WB x-ray image, for total-body and organ activity quantification of (90)Y. The method was evaluated using both Monte Carlo simulated scintillation camera images using realistic source distributions, and by an experimental phantom study. The method was evaluated in terms of image quality and accuracy of the activity quantification. The experimental phantom study was performed using the RSD torso phantom with (90)Y activity uniformly distributed in the liver insert. A GE Discovery VH/Hawkeye system was used to acquire the image. The simulation study was performed for a realistic activity distribution in the NCAT anthropomorphic phantom where (90)Y bremsstrahlung images were generated using the SIMIND MC program. Two different phantom configurations and two activity distributions were simulated. To mimic the RSD phantom experiment one simulation study was also made with (90)Y activity located only in the liver. The SIMIND program was configured to resemble a GE Discovery VH/Hawkeye system. An x-ray projector program was used to generate whole-body x-ray images from the NCAT phantom for attenuation correction in the conjugate view method. Organ activities were calculated from ROIs that exactly covered the organs. Corrections for background activity, overlapping activity and source extension in the depth direction were applied on the ROI data. The total-body activities for the simulated images were generally overestimated by around 10%, which is reasonable since the correction for source extension was not applied on the total-body values. The accuracy of the organ activities was mostly within 15% for both the simulation study and the experimental study. The results suggest that it is possible to quantify (90)Y activity in ROIs with reasonable accuracy using this method.

Effective dose to adult patients from 338 radiopharmaceuticals estimated using ICRP biokinetic data, ICRP/ICRU computational reference phantoms and ICRP 2007 tissue weighting factors

BackgroundEffective dose represents the potential risk to a population of stochastic effects of ionizing radiation (mainly lethal cancer). In recent years, there have been a number of revisions and updates influencing the way to estimate the effective dose. The aim of this work was to recalculate the effective dose values for the 338 different radiopharmaceuticals previously published by the International Commission on Radiological Protection (ICRP).MethodThe new estimations are based on information on the cumulated activities per unit administered activity in various organs and tissues and for the various radiopharmaceuticals obtained from the ICRP publications 53, 80 and 106. The effective dose for adults was calculated using the new ICRP/International Commission on Radiation Units (ICRU) reference voxel phantoms and decay data from the ICRP publication 107. The ICRP human alimentary tract model has also been applied at the recalculations. The effective dose was calculated using the new tissue weighting factors from ICRP publications 103 and the prior factors from ICRP publication 60. The results of the new calculations were compared with the effective dose values published by the ICRP, which were generated with the Medical Internal Radiation Dose (MIRD) adult phantom and the tissue weighting factors from ICRP publication 60.ResultsFor 79% of the radiopharmaceuticals, the new calculations gave a lower effective dose per unit administered activity than earlier estimated. As a mean for all radiopharmaceuticals, the effective dose was 25% lower. The use of the new adult computational voxel phantoms has a larger impact on the change of effective doses than the change to new tissue weighting factors.ConclusionThe use of the new computational voxel phantoms and the new weighting factors has generated new effective dose estimations. These are supposed to result in more realistic estimations of the radiation risk to a population undergoing nuclear medicine investigations than hitherto available values.

Analytical Validation of the Automated Bone Scan Index as an Imaging Biomarker to Standardize the Quantitative Changes in Bone Scans of Patients with Metastatic Prostate Cancer.

A reproducible and quantitative imaging biomarker is needed to standardize the evaluation of changes in bone scans of prostate cancer patients with skeletal metastasis. We performed a series of analytic validation studies to evaluate the performance of the automated bone scan index (BSI) as an imaging biomarker in patients with metastatic prostate cancer. Methods: Three separate analytic studies were performed to evaluate the accuracy, precision, and reproducibility of the automated BSI. Simulation study: bone scan simulations with predefined tumor burdens were created to assess accuracy and precision. Fifty bone scans were simulated with a tumor burden ranging from low to high disease confluence (0.10–13.0 BSI). A second group of 50 scans was divided into 5 subgroups, each containing 10 simulated bone scans, corresponding to BSI values of 0.5, 1.0, 3.0, 5.0, and 10.0. Repeat bone scan study: to assess the reproducibility in a routine clinical setting, 2 repeat bone scans were obtained from metastatic prostate cancer patients after a single 600-MBq 99mTc-methylene diphosphonate injection. Follow-up bone scan study: 2 follow-up bone scans of metastatic prostate cancer patients were analyzed to determine the interobserver variability between the automated BSIs and the visual interpretations in assessing changes. The automated BSI was generated using the upgraded EXINI boneBSI software (version 2). The results were evaluated using linear regression, Pearson correlation, Cohen κ measurement, coefficient of variation, and SD. Results: Linearity of the automated BSI interpretations in the range of 0.10–13.0 was confirmed, and Pearson correlation was observed at 0.995 (n = 50; 95% confidence interval, 0.99–0.99; P < 0.0001). The mean coefficient of variation was less than 20%. The mean BSI difference between the 2 repeat bone scans of 35 patients was 0.05 (SD = 0.15), with an upper confidence limit of 0.30. The interobserver agreement in the automated BSI interpretations was more consistent (κ = 0.96, P < 0.0001) than the qualitative visual assessment of the changes (κ = 0.70, P < 0.0001) was in the bone scans of 173 patients. Conclusion: The automated BSI provides a consistent imaging biomarker capable of standardizing quantitative changes in the bone scans of patients with metastatic prostate cancer.

Automated Bone Scan Index as a quantitative imaging biomarker in metastatic castration-resistant prostate cancer patients being treated with enzalutamide.

BackgroundHaving performed analytical validation studies, we are now assessing the clinical utility of the upgraded automated Bone Scan Index (BSI) in metastatic castration-resistant prostate cancer (mCRPC). In the present study, we retrospectively evaluated the discriminatory strength of the automated BSI in predicting overall survival (OS) in mCRPC patients being treated with enzalutamide.MethodsRetrospectively, we included patients who received enzalutamide as a clinically approved therapy for mCRPC and had undergone bone scan prior to starting therapy. Automated BSI, prostate-specific antigen (PSA), hemoglobin (HgB), and alkaline phosphatase (ALP) were obtained at baseline. Change in automated BSI and PSA were obtained from patients who have had bone scan at week 12 of treatment follow-up. Automated BSI was obtained using the analytically validated EXINI BoneBSI version 2. Kendall’s tau (τ) was used to assess the correlation of BSI with other blood-based biomarkers. Concordance index (C-index) was used to evaluate the discriminating strength of automated BSI in predicting OS.ResultsEighty mCRPC patients with baseline bone scans were included in the study. There was a weak correlation of automated BSI with PSA (τ = 0.30), with HgB (τ = −0.17), and with ALP (τ = 0.56). At baseline, the automated BSI was observed to be predictive of OS (C-index 0.72, standard error (SE) 0.03). Adding automated BSI to the blood-based model significantly improved the C-index from 0.67 to 0.72, p = 0.017. Treatment follow-up bone scans were available from 62 patients. Both change in BSI and percent change in PSA were predictive of OS. However, the combined predictive model of percent PSA change and change in automated BSI (C-index 0.77) was significantly higher than that of percent PSA change alone (C-index 0.73), p = 0.041.ConclusionsThe upgraded and analytically validated automated BSI was found to be a strong predictor of OS in mCRPC patients. Additionally, the change in automated BSI demonstrated an additive clinical value to the change in PSA in mCRPC patients being treated with enzalutamide.

Prompt gamma tomography during BNCT – a feasibility study

The success of clinical boron neutron capture therapy (BNCT) lies in the ability to manage the radiobiological effect on the tumour and healthy tissue, and thus, accurate dosimetry measurements is pertinent for each individual patient. In the present work we investigate the possibility of performing online prompt gamma tomography (PGT) during BNCT. A prototype detector system was constructed, which is in principle a pin-hole collimator with a HPGe crystal to be mounted on a C-bow device, with shielding of lithium-plastic and lead. The detector system was used to measure on a phantom placed in an epithermal neutron beam and on a 137Cs-source. The possibility of tomographic reconstruction using the detector system was tested on a phantom filled with a 131I-solution with a smaller sphere inserted containing a higher specific activity (ratio 10:1). The detector system was possible to operate up to about 6 × 108 cm-2 s-1 thermal neutron fluence at the peak in the phantom, at which time it was saturated. A 478 keV boron-peak was visible in the measured spectra but the signal-to-noise-ratio was rather low. No post-irradiation damage or neutron activation was detectable. A tomographic reconstruction of the phantom filled with 131I-solutions was performed using an algorithm developed in house and based on the MLEM method. The image quality is fairly good and the results provide a clear indication that the detector system can be used to obtain data that enables tomographic reconstruction. A spatial resolution of the detector system of about 2 cm was obtained from both the measurement on the 137Cs-source and the 131I-phantom. In conclusion, the presented feasibility study on a prototype PGT system is encouraging further studies specifically directed at improving the signal-to-noise-ratio in measurements in epithermal neutron beams. (Less)

A Preanalytic Validation Study of Automated Bone Scan Index: Effect on Accuracy and Reproducibility Due to the Procedural Variabilities in Bone Scan Image Acquisition

The effect of the procedural variability in image acquisition on the quantitative assessment of bone scan is unknown. Here, we have developed and performed preanalytical studies to assess the impact of the variability in scanning speed and in vendor-specific γ-camera on reproducibility and accuracy of the automated bone scan index (BSI). Methods: Two separate preanalytical studies were performed: a patient study and a simulation study. In the patient study, to evaluate the effect on BSI reproducibility, repeated bone scans were prospectively obtained from metastatic prostate cancer patients enrolled in 3 groups (Grp). In Grp1, the repeated scan speed and the γ-camera vendor were the same as that of the original scan. In Grp2, the repeated scan was twice the speed of the original scan. In Grp3, the repeated scan used a different γ-camera vendor than that used in the original scan. In the simulation study, to evaluate the effect on BSI accuracy, bone scans of a virtual phantom with predefined skeletal tumor burden (phantom-BSI) were simulated against the range of image counts (0.2, 0.5, 1.0, and 1.5 million) and separately against the resolution settings of the γ-cameras. The automated BSI was measured with a computer-automated platform. Reproducibility was measured as the absolute difference between the repeated BSI values, and accuracy was measured as the absolute difference between the observed BSI and the phantom-BSI values. Descriptive statistics were used to compare the generated data. Results: In the patient study, 75 patients, 25 in each group, were enrolled. The reproducibility of Grp2 (mean ± SD, 0.35 ± 0.59) was observed to be significantly lower than that of Grp1 (mean ± SD, 0.10 ± 0.13; P < 0.0001) and that of Grp3 (mean ± SD, 0.09 ± 0.10; P < 0.0001). However, no significant difference was observed between the reproducibility of Grp3 and Grp1 (P = 0.388). In the simulation study, the accuracy at 0.5 million counts (mean ± SD, 0.57 ± 0.38) and at 0.2 million counts (mean ± SD, 4.67 ± 0.85) was significantly lower than that observed at 1.5 million counts (mean ± SD, 0.20 ± 0.26; P < 0.0001). No significant difference was observed in the accuracy data of the simulation study with vendor-specific γ-cameras (P = 0.266). Conclusion: In this study, we observed that the automated BSI accuracy and reproducibility were dependent on scanning speed but not on the vendor-specific γ-cameras. Prospective BSI studies should standardize scanning speed of bone scans to obtain image counts at or above 1.5 million.

An internal radiation dosimetry computer program, IDAC 2.0, for estimation of patient doses from radiopharmaceuticals.

The internal dosimetry computer program internal dose assessment by computer (IDAC) for calculations of absorbed doses to organs and tissues as well as effective doses to patients from examinations with radiopharmaceuticals has been developed. The new version, IDAC2.0, incorporates the International Commission on Radiation Protection (ICRP)/ICRU computational adult male and female voxel phantoms and decay data from the ICRP publication 107. Instead of only 25 source and target regions, calculation can now be made with 63 source regions to 73 target regions. The major advantage of having the new phantom is that the calculations of the effective doses can be made with the latest tissue weighting factors of ICRP publication 103. IDAC2.0 uses the ICRP human alimentary tract (HAT) model for orally administrated activity and for excretion through the gastrointestinal tract and effective doses have been recalculated for radiopharmaceuticals that are orally administered. The results of the program are consistent with published data using the same specific absorption fractions and also compared with published data from the same computational phantoms but with segmentation of organs leading to another set of specific absorption fractions. The effective dose is recalculated for all the 34 radiopharmaceuticals that are administered orally and has been published by the ICRP. Using the new HAT model, new tissue weighting factors and the new adult computational voxel phantoms lead to an average effective dose of half of its earlier estimated value. The reduction mainly depends on electron transport simulations to walled organs and the transition from the stylised phantom with unrealistic interorgan distances to more realistic voxel phantoms.