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1.	Andersson, Martin, et al. (författare) Effective dose to adult patients from 338 radiopharmaceuticals estimated using ICRP biokinetic data, ICRP/ICRU computational reference phantoms and ICRP 2007 tissue weighting factors 2014 Ingår i: EJNMMI Physics. - : Springer. - 2197-7364. ; 1:1 Tidskriftsartikel (refereegranskat)abstract Background: Effective 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).Method: The 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.Results: For 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.Conclusion: The 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.
2.	Merida, Ines, et al. (författare) Pseudo-CT generation in brain MR-PET attenuation correction: comparison of several multi-atlas methods. 2015 Ingår i: EJNMMI physics. Proceedings of the 4th PSMR Conference on PET/MR and SPECT/MR. - : Springer. - 2197-7364. Konferensbidrag (refereegranskat)
3.	Yang, CT, et al. (författare) Biocompatible branched copolymer nanoparticles prepared by RAFT polymerization as MRI/PET bimodal tracers 2015 Ingår i: EJNMMI physics. - 2197-7364. ; 2:Suppl 1, s. A90- Tidskriftsartikel (refereegranskat)
4.	Bebbington, Natalie A., et al. (författare) A Nordic survey of CT doses in hybrid PET/CT and SPECT/CT examinations 2019 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 6:1 Tidskriftsartikel (refereegranskat)abstract Background: Computed tomography (CT) scans are routinely performed in positron emission tomography (PET) and single photon emission computed tomography (SPECT) examinations globally, yet few surveys have been conducted to gather national diagnostic reference level (NDRL) data for CT radiation doses in positron emission tomography/computed tomography (PET/CT) and single photon emission computed tomography/computed tomography (SPECT/CT). In this first Nordic-wide study of CT doses in hybrid imaging, Nordic NDRL CT doses are suggested for PET/CT and SPECT/CT examinations specific to the clinical purpose of CT, and the scope for optimisation is evaluated. Data on hybrid imaging CT exposures and clinical purpose of CT were gathered for 5 PET/CT and 8 SPECT/CT examinations via designed booklet. For each included dataset for a given facility and scanner type, the computed tomography dose index by volume (CTDIvol) and dose length product (DLP) was interpolated for a 75-kg person (referred to as CTDIvol,75kg and DLP75kg). Suggested NDRL (75th percentile) and achievable doses (50th percentile) were determined for CTDIvol,75kg and DLP75kg according to clinical purpose of CT. Differences in maximum and minimum doses (derived for a 75-kg patient) between facilities were also calculated for each examination and clinical purpose. Results: Data were processed from 83 scanners from 43 facilities. Data were sufficient to suggest Nordic NDRL CT doses for the following: PET/CT oncology (localisation/characterisation, 15 systems); infection/inflammation (localisation/characterisation, 13 systems); brain (attenuation correction (AC) only, 11 systems); cardiac PET/CT and SPECT/CT (AC only, 30 systems); SPECT/CT lung (localisation/characterisation, 12 systems); bone (localisation/characterisation, 30 systems); and parathyroid (localisation/characterisation, 13 systems). Great variations in dose were seen for all aforementioned examinations. Greatest differences in DLP75kg for each examination, specific to clinical purpose, were as follows: SPECT/CT lung AC only (27.4); PET/CT and SPECT/CT cardiac AC only (19.6); infection/inflammation AC only (18.1); PET/CT brain localisation/characterisation (16.8); SPECT/CT bone localisation/characterisation (10.0); PET/CT oncology AC only (9.0); and SPECT/CT parathyroid localisation/characterisation (7.8). Conclusions: Suggested Nordic NDRL CT doses are presented according to clinical purpose of CT for PET/CT oncology, infection/inflammation, brain, PET/CT and SPECT/CT cardiac, and SPECT/CT lung, bone, and parathyroid. The large variation in doses suggests great scope for optimisation in all 8 examinations.
5.	Bjöersdorff, Mimmi, et al. (författare) Impact of penalizing factor in a block-sequential regularized expectation maximization reconstruction algorithm for 18 F-fluorocholine PET-CT regarding image quality and interpretation 2019 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 6:1 Tidskriftsartikel (refereegranskat)abstract Background: Recently, the block-sequential regularized expectation maximization (BSREM) reconstruction algorithm was commercially introduced (Q.Clear, GE Healthcare, Milwaukee, WI, USA). However, the combination of noise-penalizing factor (β), acquisition time, and administered activity for optimal image quality has not been established for 18 F-fluorocholine (FCH). The aim was to compare image quality and diagnostic performance of different reconstruction protocols for patients with prostate cancer being examined with 18 F-FCH on a silicon photomultiplier-based PET-CT. Thirteen patients were included, injected with 4 MBq/kg, and images were acquired after 1 h. Images were reconstructed with frame durations of 1.0, 1.5, and 2.0 min using β of 150, 200, 300, 400, 500, and 550. An ordered subset expectation maximization (OSEM) reconstruction with a frame duration of 2.0 min was used for comparison. Images were quantitatively analyzed regarding standardized uptake values (SUV) in metastatic lymph nodes, local background, and muscle to obtain contrast-to-noise ratios (CNR) as well as the noise level in muscle. Images were analyzed regarding image quality and number of metastatic lymph nodes by two nuclear medicine physicians. Results: The highest median CNR was found for BSREM with a β of 300 and a frame duration of 2.0 min. The OSEM reconstruction had the lowest median CNR. Both the noise level and lesion SUV max decreased with increasing β. For a frame duration of 1.5 min, the median quality score was highest for β 400-500, and for a frame duration of 2.0 min the score was highest for β 300-500. There was no statistically significant difference in the number of suspected lymph node metastases between the different image series for one of the physicians, and for the other physician the number of lymph nodes differed only for one combination of image series. Conclusions: To achieve acceptable image quality at 4 MBq/kg 18 F-FCH, we propose using a β of 400-550 with a frame duration of 1.5 min. The lower β should be used if a high CNR is desired and the higher if a low noise level is important.
6.	Borrelli, P., et al. (författare) AI-based detection of lung lesions in F-18 FDG PET-CT from lung cancer patients 2021 Ingår i: Ejnmmi Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 8:1 Tidskriftsartikel (refereegranskat)abstract Background[F-18]-fluorodeoxyglucose (FDG) positron emission tomography with computed tomography (PET-CT) is a well-established modality in the work-up of patients with suspected or confirmed diagnosis of lung cancer. Recent research efforts have focused on extracting theragnostic and textural information from manually indicated lung lesions. Both semi-automatic and fully automatic use of artificial intelligence (AI) to localise and classify FDG-avid foci has been demonstrated. To fully harness AI's usefulness, we have developed a method which both automatically detects abnormal lung lesions and calculates the total lesion glycolysis (TLG) on FDG PET-CT.MethodsOne hundred twelve patients (59 females and 53 males) who underwent FDG PET-CT due to suspected or for the management of known lung cancer were studied retrospectively. These patients were divided into a training group (59%; n = 66), a validation group (20.5%; n = 23) and a test group (20.5%; n = 23). A nuclear medicine physician manually segmented abnormal lung lesions with increased FDG-uptake in all PET-CT studies. The AI-based method was trained to segment the lesions based on the manual segmentations. TLG was then calculated from manual and AI-based measurements, respectively and analysed with Bland-Altman plots.ResultsThe AI-tool's performance in detecting lesions had a sensitivity of 90%. One small lesion was missed in two patients, respectively, where both had a larger lesion which was correctly detected. The positive and negative predictive values were 88% and 100%, respectively. The correlation between manual and AI TLG measurements was strong (R-2 = 0.74). Bias was 42 g and 95% limits of agreement ranged from -736 to 819 g. Agreement was particularly high in smaller lesions.ConclusionsThe AI-based method is suitable for the detection of lung lesions and automatic calculation of TLG in small- to medium-sized tumours. In a clinical setting, it will have an added value due to its capability to sort out negative examinations resulting in prioritised and focused care on patients with potentially malignant lesions.
7.	Borrelli, P., et al. (författare) Freely available convolutional neural network-based quantification of PET/CT lesions is associated with survival in patients with lung cancer 2022 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 9:1 Tidskriftsartikel (refereegranskat)abstract Background: Metabolic positron emission tomography/computed tomography (PET/CT) parameters describing tumour activity contain valuable prognostic information, but to perform the measurements manually leads to both intra- and inter-reader variability and is too time-consuming in clinical practice. The use of modern artificial intelligence-based methods offers new possibilities for automated and objective image analysis of PET/CT data. Purpose: We aimed to train a convolutional neural network (CNN) to segment and quantify tumour burden in [18F]-fluorodeoxyglucose (FDG) PET/CT images and to evaluate the association between CNN-based measurements and overall survival (OS) in patients with lung cancer. A secondary aim was to make the method available to other researchers. Methods: A total of 320 consecutive patients referred for FDG PET/CT due to suspected lung cancer were retrospectively selected for this study. Two nuclear medicine specialists manually segmented abnormal FDG uptake in all of the PET/CT studies. One-third of the patients were assigned to a test group. Survival data were collected for this group. The CNN was trained to segment lung tumours and thoracic lymph nodes. Total lesion glycolysis (TLG) was calculated from the CNN-based and manual segmentations. Associations between TLG and OS were investigated using a univariate Cox proportional hazards regression model. Results: The test group comprised 106 patients (median age, 76years (IQR 61–79); n = 59 female). Both CNN-based TLG (hazard ratio 1.64, 95% confidence interval 1.21–2.21; p = 0.001) and manual TLG (hazard ratio 1.54, 95% confidence interval 1.14–2.07; p = 0.004) estimations were significantly associated with OS. Conclusion: Fully automated CNN-based TLG measurements of PET/CT data showed were significantly associated with OS in patients with lung cancer. This type of measurement may be of value for the management of future patients with lung cancer. The CNN is publicly available for research purposes. © 2022, The Author(s).
8.	Chiesa, C., et al. (författare) EANM dosimetry committee series on standard operational procedures: a unified methodology for Tc-99m-MAA pre- and Y-90 peri-therapy dosimetry in liver radioembolization with Y-90 microspheres 2021 Ingår i: Ejnmmi Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 8:1 Tidskriftsartikel (refereegranskat)abstract The aim of this standard operational procedure is to standardize the methodology employed for the evaluation of pre- and post-treatment absorbed dose calculations in Y-90 microsphere liver radioembolization. Basic assumptions include the permanent trapping of microspheres, the local energy deposition method for voxel dosimetry, and the patient-relative calibration method for activity quantification.The identity of Tc-99m albumin macro-aggregates (MAA) and Y-90 microsphere biodistribution is also assumed. The large observed discrepancies in some patients between Tc-99m-MAA predictions and actual Y-90 microsphere distributions for lesions is discussed. Absorbed dose predictions to whole non-tumoural liver are considered more reliable and the basic predictors of toxicity. Treatment planning based on mean absorbed dose delivered to the whole non-tumoural liver is advised, except in super-selective treatments. Given the potential mismatch between MAA simulation and actual therapy, absorbed doses should be calculated both pre- and post-therapy. Distinct evaluation between target tumours and non-tumoural tissue, including lungs in cases of lung shunt, are vital for proper optimization of therapy. Dosimetry should be performed first according to a mean absorbed dose approach, with an optional, but important, voxel level evaluation. Fully corrected Tc-99m-MAA Single Photon Emission Computed Tomography (SPECT)/computed tomography (CT) and Y-90 TOF PET/CT are regarded as optimal acquisition methodologies, but, for institutes where SPECT/CT is not available, non-attenuation corrected Tc-99m-MAA SPECT may be used. This offers better planning quality than non dosimetric methods such as Body Surface Area (BSA) or mono-compartmental dosimetry. Quantitative Y-90 bremsstrahlung SPECT can be used if dedicated correction methods are available. The proposed methodology is feasible with standard camera software and a spreadsheet. Available commercial or free software can help facilitate the process and improve calculation time.
9.	Conti, Maurizio, et al. (författare) Physics of pure and non-pure positron emitters for PET : a review and a discussion 2016 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 3:1 Forskningsöversikt (refereegranskat)abstract With the increased interest in new PET tracers, gene-targeted therapy, immunoPET, and theranostics, other radioisotopes will be increasingly used in clinical PET scanners, in addition to F-18. Some of the most interesting radioisotopes with prospective use in the new fields are not pure short-range beta(+) emitters but can be associated with gamma emissions in coincidence with the annihilation radiation (prompt gamma), gamma-gamma cascades, intense Bremsstrahlung radiation, high-energy positrons that may escape out of the patient skin, and high-energy gamma rays that result in some e(+)/e(-) pair production. The high level of sophistication in data correction and excellent quantitative accuracy that has been reached for F-18 in recent years can be questioned by these effects. In this work, we review the physics and the scientific literature and evaluate the effect of these additional phenomena on the PET data for each of a series of radioisotopes: C-11, N-13, O-15, F-18, Cu-64, Ga-68, Br-76, Rb-82, Y-86, Zr-89, Y-90, and I-124. In particular, we discuss the present complications arising from the prompt gammas, and we review the scientific literature on prompt gamma correction. For some of the radioisotopes considered in this work, prompt gamma correction is definitely needed to assure acceptable image quality, and several approaches have been proposed in recent years. Bremsstrahlung photons and Lu-176 background were also evaluated.
10.	Freedman, Nanette, et al. (författare) Personalized radiation dosimetry for PRRT : how many scans are really required? 2020 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 7:1 Tidskriftsartikel (refereegranskat)abstract PurposeOver recent years, peptide receptor radiotherapy (PRRT) has been recognized as an effective treatment for patients with metastatic neuroendocrine tumors (NETs). Personalized dosimetry can contribute to improve the outcome of peptide receptor radiotherapy (PRRT) in patients with metastatic NETs. Dosimetry can aid treatment planning, ensuring that absorbed dose to vulnerable normal organs (kidneys and bone marrow) does not exceed safe limits over serial treatments, and that absorbed dose to tumor is sufficient. Absorbed dose is estimated from a series of post-treatment SPECT/CT images. Total self-dose is proportional to the integral under the time activity concentration curve (TACC). Method dependence of image-based absorbed dose calculations has been previously investigated, and we set out here to extend previous work by examining implications of number of data points in the TACC and the numerical integration methods used in estimating absorbed dose.MethodsIn this retrospective study, absorbed dose estimates and effective half-lives were calculated by fitting curves to TACCs for normal organs and tumors in 30 consecutive patients who underwent a series of 4 post-treatment SPECT/CT scans at 4 h, 24 h, 4–5 days, and 1 week following 177Lu-DOTATATE PRRT. We examined the effects of including only 2 or 3 rather than all 4 data points in the TACC, and the effect of numerical integration method (mono-exponential alone or in combination with trapezoidal rule) on the absorbed dose and half-life estimates. Our current method is the combination of trapezoidal rule over the first 24 h, with mono-exponential fit thereafter extrapolated to infinity. The other methods were compared to this current method.ResultsDifferences in absorbed dose and effective half-life between the current method and estimates based only on the second, third, and fourth scans were very small (mean differences < 2.5%), whereas differences between the current method and 4-point mono-exponential fit were higher (mean differences < 5%) with a larger range. It appears that in a 4-point mono-exponential fit the early (4 h) time point may skew results, causing some large errors. Differences between the current method and values based on only 2 time points were relatively small (mean differences < 3.5%) when the 24 h and 1 week scans were used, but when the 24 h and 4–5 days scans, or the 4–5 days and 1 week scans were used, differences were greater.ConclusionThis study indicates that for 177Lu-DOTATATE PRRT, accurate estimates of absorbed dose for organs and tumors may be estimated from scans at 24 h, 72 h, and 1 week post-treatment without an earlier scan. It may even be possible to cut out the 72 h scan, though the uncertainty increases. However, further work on more patients is required to validate this.
11.	Grafström, J, et al. (författare) A method for comparing intra-tumoural radioactivity uptake heterogeneity in preclinical positron emission tomography studies 2015 Ingår i: EJNMMI physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 2:1, s. 19- Tidskriftsartikel (refereegranskat)
12.	Gustafsson, Agneta, et al. (författare) A multicentre simulation study of planar whole-body bone scintigraphy in Sweden 2022 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 9:1 Tidskriftsartikel (refereegranskat)abstract Background: Whole-body bone scintigraphy is a clinically useful non-invasive and highly sensitive imaging method enabling detection of metabolic changes at an early stage of disease, often earlier than with conventional radiologic procedures. Bone scintigraphy is one of the most common nuclear medicine methods used worldwide. Therefore, it is important that the examination is implemented and performed in an optimal manner giving the patient added value in the subsequent care process. The aim of this national multicentre survey was to investigate Swedish nuclear medicine departments compliance with European practice guidelines for bone scintigraphy. In addition, the effect of image acquisition parameters on the ability to detect metabolic lesions was investigated. Methods: Twenty-five hospital sites participated in the study. The SIMIND Monte Carlo (MC) simulation and the XCAT phantom were used to simulate ten fictive patient cases with increased metabolic activity distributed at ten different locations in the skeleton. The intensity of the metabolic activity was set into six different levels. Individual simulations were performed for each site, corresponding to their specific camera system and acquisition parameters. Simulated image data sets were then sent to each site and were visually evaluated in terms of if there was one or several locations with increased metabolic activity relative to normal activity. Result: There is a high compliance in Sweden with the EANM guidelines regarding image acquisition parameters for whole-body bone scintigraphy. However, up to 40% of the participating sites acquire lower count density in the images than recommended. Despite this, the image quality was adequate to maintain a stable detection level. None of the hospital sites or individual responders deviated according to the statistical analysis. There is a need for at least 2.5 times metabolic activity compared to normal for a lesion to be detected. Conclusion: The imaging process is well harmonized throughout the country and there is a high compliance with the EANM guidelines. There is a need for at least 2.5 times the normal metabolic activity for a lesion to be detected as abnormal.
13.	Harms, Hendrik Johannes, et al. (författare) Automatic extraction of forward stroke volume using dynamic PET/CT : a dual-tracer and dual-scanner validation in patients with heart valve disease. 2015 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 2:1 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The aim of this study was to develop and validate an automated method for extracting forward stroke volume (FSV) using indicator dilution theory directly from dynamic positron emission tomography (PET) studies for two different tracers and scanners.METHODS: 35 subjects underwent a dynamic (11)C-acetate PET scan on a Siemens Biograph TruePoint-64 PET/CT (scanner I). In addition, 10 subjects underwent both dynamic (15)O-water PET and (11)C-acetate PET scans on a GE Discovery-ST PET/CT (scanner II). The left ventricular (LV)-aortic time-activity curve (TAC) was extracted automatically from PET data using cluster analysis. The first-pass peak was isolated by automatic extrapolation of the downslope of the TAC. FSV was calculated as the injected dose divided by the product of heart rate and the area under the curve of the first-pass peak. Gold standard FSV was measured using phase-contrast cardiovascular magnetic resonance (CMR).RESULTS: FSVPET correlated highly with FSVCMR (r = 0.87, slope = 0.90 for scanner I, r = 0.87, slope = 1.65, and r = 0.85, slope = 1.69 for scanner II for (15)O-water and (11)C-acetate, respectively) although a systematic bias was observed for both scanners (p < 0.001 for all). FSV based on (11)C-acetate and (15)O-water correlated highly (r = 0.99, slope = 1.03) with no significant difference between FSV estimates (p = 0.14).CONCLUSIONS: FSV can be obtained automatically using dynamic PET/CT and cluster analysis. Results are almost identical for (11)C-acetate and (15)O-water. A scanner-dependent bias was observed, and a scanner calibration factor is required for multi-scanner studies. Generalization of the method to other tracers and scanners requires further validation.
14.	Hemmingsson, Jens, 1986, et al. (författare) Active bone marrow S-values for the low-energy electron emitter terbium-161 compared to S-values for lutetium-177 and yttrium-90. 2022 Ingår i: EJNMMI physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 9:1 Tidskriftsartikel (refereegranskat)abstract Based on theoretical and preclinical results, terbium-161 may be a valid alternative to lutetium-177 and yttrium-90 in radionuclide therapies. The large low-energy electron emission from terbium-161 is a favorable feature in the treatment of disseminated disease, but its impact on the radiosensitive bone marrow needs to be evaluated. Using voxel-based skeletal dosimetry models in which active bone marrow is defined as regions containing stem cells and progenitor cells of the hematopoietic lineage, we generated S-values (absorbed dose per decay) for terbium-161 and evaluated its distribution-dependence in bone marrow cavities.S-values in the active bone marrow were calculated for terbium-161, lutetium-177, and yttrium-90 irradiation using two (male/female) image-based bone marrow dosimetry models. The radionuclides were distributed to one of the three structures that define the spongiosa bone region in the skeletal models: (i) active bone marrow, (ii) inactive bone marrow, or (iii) surface or whole volume of the trabecular bone. Decay data from ICRP 107 were combined with specific absorbed fractions to calculate S-values for 13 skeletal sites. To increase the utility, the skeletal site-specific S-values were averaged to produce whole-body average S-values and spongiosa average S-values.For yttrium-90, the high-energy β particles irradiate the active marrow regardless of the source compartment, consistently generating the highest S-values (65-90% higher). Between terbium-161 and lutetium-177, the largest differences in S-values were with an active marrow source (50%), such as self-irradiation, due to the contribution of the short-ranged conversion and Auger electrons from terbium-161. Their influence decreased as the source moved to inactive marrow or the surface or volume of the trabecular bone, reducing the S-values and the differences between terbium-161 and lutetium-177 (15-35%).The S-values of terbium-161 for active bone marrow and, consequently, the bone marrow toxicity profile were more dependent on the radionuclide distribution within the bone marrow cavity than the S-values of lutetium-177 and yttrium-90. This effect was attributed to the considerable low-energy electron emission of terbium-161. Therefore, it will be critical to investigate the bone marrow distribution of a particular radiopharmaceutical for accurate estimation of the active bone marrow dose.
15.	Högberg, Jonas, et al. (författare) Comparison of Otsu and an adapted Chan-Vese method to determine thyroid active volume using Monte Carlo generated SPECT images 2024 Ingår i: EJNMMI Physics. - : Springer Nature. - 2197-7364. ; 11:1 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The Otsu method and the Chan-Vese model are two methods proven to perform well in determining volumes of different organs and specific tissue fractions. This study aimed to compare the performance of the two methods regarding segmentation of active thyroid gland volumes, reflecting different clinical settings by varying the parameters: gland size, gland activity concentration, background activity concentration and gland activity concentration heterogeneity.METHODS: A computed tomography was performed on three playdough thyroid phantoms with volumes 20, 35 and 50 ml. The image data were separated into playdough and water based on Hounsfield values. Sixty single photon emission computed tomography (SPECT) projections were simulated by Monte Carlo method with isotope Technetium-99 m ([Formula: see text]Tc). Linear combinations of SPECT images were made, generating 12 different combinations of volume and background: each with both homogeneous thyroid activity concentration and three hotspots of different relative activity concentrations (48 SPECT images in total). The relative background levels chosen were 5 %, 10 %, 15 % and 20 % of the phantom activity concentration and the hotspot activities were 100 % (homogeneous case) 150 %, 200 % and 250 %. Poisson noise, (coefficient of variation of 0.8 at a 20 % background level, scattering excluded), was added before reconstruction was done with the Monte Carlo-based SPECT reconstruction algorithm Sahlgrenska Academy reconstruction code (SARec). Two different segmentation algorithms were applied: Otsu's threshold selection method and an adaptation of the Chan-Vese model for active contours without edges; the results were evaluated concerning relative volume, mean absolute error and standard deviation per thyroid volume, as well as dice similarity coefficient.RESULTS: Both methods segment the images well and deviate similarly from the true volumes. They seem to slightly overestimate small volumes and underestimate large ones. Different background levels affect the two methods similarly as well. However, the Chan-Vese model deviates less and paired t-testing showed significant difference between distributions of dice similarity coefficients (p-value [Formula: see text]).CONCLUSIONS: The investigations indicate that the Chan-Vese model performs better and is slightly more robust, while being more challenging to implement and use clinically. There is a trade-off between performance and user-friendliness.
16.	Högberg, Jonas, 1976, et al. (författare) Increased absorbed liver dose in Selective Internal Radiation Therapy (SIRT) correlates with increased sphere-cluster frequency and absorbed dose inhomogeneity 2015 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 2:1 Tidskriftsartikel (refereegranskat)abstract Background The higher tolerated mean absorbed dose for selective internal radiation therapy (SIRT) with intra-arterially infused 90Y microspheres compared to external beam therapy is speculated to be caused by absorbed dose inhomogeneity, which allows for liver regeneration. However, the complex liver microanatomy and rheology makes modelling less valuable if the tolerance doses are not based on the actual microsphere distribution. The present study demonstrates the sphere distribution and small-scale absorbed dose inhomogeneity and its correlation with the mean absorbed dose in liver tissue resected after SIRT. Methods A patient with marginally resectable cholangiocarcinoma underwent SIRT 9 days prior to resection including adjacent normal liver tissue. The resected specimen was formalin-fixed and sliced into 1 to 2-mm sections. Forty-one normal liver biopsies 6-8 mm in diameter were punched from these sections and the radioactivity measured. Sixteen biopsies were further processed for detailed analyses by consecutive serial sectioning of 15 30-μm sections per biopsy, mounted and stained with haematoxylin-eosin. All sections were scrutinised for isolated or conglomerate spheres. Small-scale dose distributions were obtained by applying a 90Y-dose point kernel to the microsphere distributions. Results A total of 3888 spheres were found in the 240 sections. Clusters were frequently found as strings in the arterioles and as conglomerates in small arteries, with the largest cluster comprising 453 spheres. An increased mean absorbed dose in the punch biopsies correlated with large clusters and a greater coefficient of variation. In simulations the absorbed dose was 5–1240 Gy; 90% were 10-97 Gy and 45% were <30 Gy, the assumed tolerance in external beam therapy. Conclusions Sphere clusters were located in both arterioles and small arteries and increased in size with increasing sphere concentration, resulting in increased absorbed dose inhomogeneity, which contradicts earlier modelling studies.
17.	Jessen, Lovisa, et al. (författare) 3D printed non-uniform anthropomorphic phantoms for quantitative SPECT 2024 Ingår i: EJNMMI Physics. - 2197-7364. ; 11:1 Tidskriftsartikel (refereegranskat)abstract Background: A 3D printing grid-based method was developed to construct anthropomorphic phantoms with non-uniform activity distributions, to be used for evaluation of quantitative SPECT images. The aims were to characterize the grid-based method and to evaluate its capability to provide realistically shaped phantoms with non-uniform activity distributions. Methods: Characterization of the grid structures was performed by printing grid-filled spheres. Evaluation was performed by micro-CT imaging to investigate the printing accuracy and by studying the modulation contrast (CM) in SPECT images for 177Lu and 99mTc as a function of the grid fillable-volume fraction (FVF) determined from weighing. The grid-based technique was applied for the construction of two kidney phantoms and two thyroid phantoms, designed using templates from the XCAT digital phantoms. The kidneys were constructed with a hollow outer container shaped as cortex, an inner grid-based structure representing medulla and a solid section representing pelvis. The thyroids consisted of two lobes printed as grid-based structures, with void hot spots within the lobes. The phantoms were filled with solutions of 177Lu (kidneys) or 99mTc (thyroids) and imaged with SPECT. For verification, Monte Carlo simulations of SPECT imaging were performed for activity distributions corresponding to those of the printed phantoms. Measured and simulated SPECT images were compared qualitatively and quantitatively. Results: Micro-CT images showed that printing inaccuracies were mainly uniform across the grid. The relationships between the FVF from weighing and CM were found to be linear (r = 0.9995 and r = 0.9993 for 177Lu and 99mTc, respectively). The FVF-deviations from the design were up to 15% for thyroids and 4% for kidneys, mainly related to possibilities of cleaning after printing. Measured and simulated SPECT images of kidneys and thyroids exhibited similar activity distributions and quantitative comparisons agreed well, thus verifying the grid-based method. Conclusions: We find the grid-based technique useful for the provision of 3D printed, realistically shaped, phantoms with non-uniform activity distributions, which can be used for evaluation of different quantitative methods in SPECT imaging.
18.	Jönsson, L., et al. (författare) Quantitative analysis of phantom studies of 111In and 68Ga imaging of neuroendocrine tumours 2018 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 5:1 Tidskriftsartikel (refereegranskat)abstract Background: Nuclear medicine imaging of neuroendocrine tumours is performed either by SPECT/CT imaging, using 111In-octreotide or by PET/CT imaging using 68Ga-radiolabelled somatostatin analogs. These imaging techniques will give different image quality and different detection thresholds for tumours, depending on size and activity uptake. The aim was to evaluate the image quality for 111In-SPECT and 68Ga-PET imaging, i.e. the smallest volume possible to visualize for different source-to-background activity ratios. The accuracy of quantification of lesion volume and activity was also investigated to develop an objective evaluation for radionuclide therapy eligibility. The phantom study was performed using the NEMA IEC Body Phantom with six hot spheres having inner diameters of 10, 13, 17, 22, 28, and 37 mm, filled with either 68Ga or 111In with sphere-to-background ratios (SBRs) of no background activity, 5:1, 2.5:1, and 1.25:1. Activity ratios of 1.25:1 and 2.5:1 are clinically found for lesions close to the liver and spleen. Clinical acquisition and reconstruction protocols were applied. Line profiles were drawn to evaluate the smallest detectable volume within a given SBR. Recovery curves based on threshold-based VOIs, threshold-based VOIs adapted to the background and CT-based ROIs were obtained for all SBRs and sphere diameters, allowing for quantification. Results: The 10-mm sphere was not possible to detect in SPECT images. It was detectable in PET images for SBRs of 2.5:1 and higher. In a background corresponding to the activity uptake in the liver, spheres larger than 22–37 mm were detectable in the 111In-SPECT images and spheres larger than 13–22 mm were detectable in the 68Ga-PET images. The maximum activity concentration was accurately quantified for spheres larger than 22 mm in the PET images; however, the quantification was impaired by sphere size and background activity. Conclusions: It was not possible to detect the 10-mm sphere in any of the SPECT images. In a background corresponding to the activity uptake in the liver, spheres larger than approximately 30 mm were visible in the 111In-SPECT images and spheres larger than approximately 17 mm were visible in the 68Ga-PET images. Sphere diameter and background activity strongly affect the possibility of a correct quantification.
19.	Kamp, A., et al. (författare) A revised compartmental model for biokinetics and dosimetry of 2- F-18 FDG 2023 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 10:1 Tidskriftsartikel (refereegranskat)abstract BackgroundThe aim was to review available biokinetic data, collect own experimental data, and propose an updated compartmental model for 2-[F-18]FDG in the frame of the revision of the ICRP report on dose coefficients for radiopharmaceuticals used in diagnostic nuclear medicine.MethodsThe compartmental model was developed based on published biokinetic data for 2-[F-18]FDG. Additional data on urinary excretion in 23 patients (11 males, 12 females) undergoing whole-body PET/CT examinations were obtained within this study. The unknown biokinetic model parameters were derived using the software SAAM II and verified with a modified version of IDAC-Iodide. Dose coefficients for reference adults were calculated with the programme IDAC-Dose 2.1. A dynamic bladder model was employed for urinary bladder dosimetry.ResultsThe proposed model consists of following compartments: blood, heart wall, brain, liver, lungs, pancreas, spleen, kidneys, urinary bladder content and a generic pool compartment "Other". The latter was introduced to account for 2-[F-18]FDG in body organ and tissues besides the explicitly modelled ones. The model predictions showed a good agreement with experimental data. Urinary bladder wall received the highest absorbed dose coefficient of 7.5E-02 mGy/MBq under the assumption of initial urine volume of 100 ml, first voiding at 45 min p.i. and 3.75 h voiding intervals thereafter. The effective dose coefficient calculated according to the current dosimetry framework of ICRP amounted to 1.7E-02 mSv/MBq, compared to 1.9E-02 mSv/MBq in ICRP Publication 128.ConclusionA compartmental model for 2-[F-18]FDG was proposed and will be used to replace the descriptive biokinetic model of ICRP Publication 128. The revised model and the provided dose coefficients are expected to improve reference dosimetry for patients administered with 2-[F-18]FDG.
20.	Kero, Tanja, et al. (författare) Quantitative myocardial blood flow imaging with integrated time-of-flight PET-MR 2017 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 4:1 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The use of integrated PET-MR offers new opportunities for comprehensive assessment of cardiac morphology and function. However, little is known on the quantitative accuracy of cardiac PET imaging with integrated time-of-flight PET-MR. The aim of the present work was to validate the GE Signa PET-MR scanner for quantitative cardiac PET perfusion imaging. Eleven patients (nine male; mean age 59 years; range 46-74 years) with known or suspected coronary artery disease underwent (15)O-water PET scans at rest and during adenosine-induced hyperaemia on a GE Discovery ST PET-CT and a GE Signa PET-MR scanner. PET-MR images were reconstructed using settings recommended by the manufacturer, including time-of-flight (TOF). Data were analysed semi-automatically using Cardiac VUer software, resulting in both parametric myocardial blood flow (MBF) images and segment-based MBF values. Correlation and agreement between PET-CT-based and PET-MR-based MBF values for all three coronary artery territories were assessed using regression analysis and intra-class correlation coefficients (ICC). In addition to the cardiac PET-MR reconstruction protocol as recommended by the manufacturer, comparisons were made using a PET-CT resolution-matched reconstruction protocol both without and with TOF to assess the effect of time-of-flight and reconstruction parameters on quantitative MBF values.RESULTS: Stress MBF data from one patient was excluded due to movement during the PET-CT scanning. Mean MBF values at rest and stress were (0.92 ± 0.12) and (2.74 ± 1.37) mL/g/min for PET-CT and (0.90 ± 0.23) and (2.65 ± 1.15) mL/g/min for PET-MR (p = 0.33 and p = 0.74). ICC between PET-CT-based and PET-MR-based regional MBF was 0.98. Image quality was improved with PET-MR as compared to PET-CT. ICC between PET-MR-based regional MBF with and without TOF and using different filter and reconstruction settings was 1.00.CONCLUSIONS: PET-MR-based MBF values correlated well with PET-CT-based MBF values and the parametric PET-MR images were excellent. TOF and reconstruction settings had little impact on MBF values.
21.	Leube, Julian, et al. (författare) Analysis of a deep learning-based method for generation of SPECT projections based on a large Monte Carlo simulated dataset 2022 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 9:1 Tidskriftsartikel (refereegranskat)abstract Background: In recent years, a lot of effort has been put in the enhancement of medical imaging using artificial intelligence. However, limited patient data in combination with the unavailability of a ground truth often pose a challenge to a systematic validation of such methodologies. The goal of this work was to investigate a recently proposed method for an artificial intelligence-based generation of synthetic SPECT projections, for acceleration of the image acquisition process based on a large dataset of realistic SPECT simulations. Methods: A database of 10,000 SPECT projection datasets of heterogeneous activity distributions of randomly placed random shapes was simulated for a clinical SPECT/CT system using the SIMIND Monte Carlo program. Synthetic projections at fixed angular increments from a set of input projections at evenly distributed angles were generated by different u-shaped convolutional neural networks (u-nets). These u-nets differed in noise realization used for the training data, number of input projections, projection angle increment, and number of training/validation datasets. Synthetic projections were generated for 500 test projection datasets for each u-net, and a quantitative analysis was performed using statistical hypothesis tests based on structural similarity index measure and normalized root-mean-squared error. Additional simulations with varying detector orbits were performed on a subset of the dataset to study the effect of the detector orbit on the performance of the methodology. For verification of the results, the u-nets were applied to Jaszczak and NEMA physical phantom data obtained on a clinical SPECT/CT system. Results: No statistically significant differences were observed between u-nets trained with different noise realizations. In contrast, a statistically significant deterioration was found for training with a small subset (400 datasets) of the 10,000 simulated projection datasets in comparison with using a large subset (9500 datasets) for training. A good agreement between synthetic (i.e., u-net generated) and simulated projections before adding noise demonstrates a denoising effect. Finally, the physical phantom measurements show that our findings also apply for projections measured on a clinical SPECT/CT system. Conclusion: Our study shows the large potential of u-nets for accelerating SPECT/CT imaging. In addition, our analysis numerically reveals a denoising effect when generating synthetic projections with a u-net. Clinically interesting, the methodology has proven robust against camera orbit deviations in a clinically realistic range. Lastly, we found that a small number of training samples (e.g., ~ 400 datasets) may not be sufficient for reliable generalization of the u-net.
22.	Lindström, Elin, et al. (författare) Evaluation of block-sequential regularized expectation maximization reconstruction of 68Ga-DOTATOC, 18F-fluoride, and 11C-acetate whole-body examinations acquired on a digital time-of-flight PET/CT scanner 2020 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 7:1 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Block-sequential regularized expectation maximization (BSREM) is a fully convergent iterative image reconstruction algorithm. We hypothesize that tracers with different distribution patterns will result in different optimal settings for the BSREM algorithm. The aim of this study was to evaluate the image quality with variations in the applied β-value and acquisition time for three positron emission tomography (PET) tracers. NEMA image quality phantom measurements and clinical whole-body digital time-of-flight (TOF) PET/computed tomography (CT) examinations with 68Ga-DOTATOC (n = 13), 18F-fluoride (n = 10), and 11C-acetate (n = 13) were included. Each scan was reconstructed using BSREM with β-values of 133, 267, 400, and 533, and ordered subsets expectation maximization (OSEM; 3 iterations, 16 subsets, and 5-mm Gaussian post-processing filter). Both reconstruction methods included TOF and point spread function (PSF) recovery. Quantitative measures of noise, signal-to-noise ratio (SNR), and signal-to-background ratio (SBR) were analysed for various acquisition times per bed position (bp).RESULTS: The highest β-value resulted in the lowest level of noise, which in turn resulted in the highest SNR and lowest SBR. Noise levels equal to or lower than those of OSEM were found with β-values equal to or higher than 400, 533, and 267 for 68Ga-DOTATOC, 18F-fluoride, and 11C-acetate, respectively. The specified β-ranges resulted in increased SNR at a minimum of 25% (P < 0.0001) and SBR at a maximum of 23% (P < 0.0001) as compared to OSEM. At a reduced acquisition time by 25% for 68Ga-DOTATOC and 18F-fluoride, and 67% for 11C-acetate, BSREM with β-values equal to or higher than 533 resulted in noise equal to or lower than that of OSEM at full acquisition duration (2 min/bp for 68Ga-DOTATOC and 18F-fluoride, 3 min/bp for 11C-acetate). The reduced acquisition time with β 533 resulted in increased SNR (16-26%, P < 0.003) and SBR (6-18%, P < 0.0001 (P = 0.07 for 11C-acetate)) compared to the full acquisition OSEM.CONCLUSIONS: Within tracer-specific ranges of β-values, BSREM reconstruction resulted in increased SNR and SBR with respect to conventional OSEM reconstruction. Similar SNR, SBR, and noise levels could be attained with BSREM at relatively shorter acquisition times or, alternatively, lower administered dosages, compared to those attained with OSEM.
23.	Magnander, Tobias, et al. (författare) A novel statistical analysis method to improve the detection of hepatic foci of (111)In-octreotide in SPECT/CT imaging. 2016 Ingår i: EJNMMI physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 3:1 Tidskriftsartikel (refereegranskat)abstract Low uptake ratios, high noise, poor resolution, and low contrast all combine to make the detection of neuroendocrine liver tumours by (111)In-octreotide single photon emission tomography (SPECT) imaging a challenge. The aim of this study was to develop a segmentation analysis method that could improve the accuracy of hepatic neuroendocrine tumour detection.
24.	Marin, Ida, et al. (författare) Establishment of a clinical SPECT/CT protocol for imaging of(161)Tb 2020 Ingår i: Ejnmmi Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 7:1 Tidskriftsartikel (refereegranskat)abstract Background It has been proposed, and preclinically demonstrated, that(161)Tb is a better alternative to(177)Lu for the treatment of small prostate cancer lesions due to its high emission of low-energy electrons.Tb-161 also emits photons suitable for single-photon emission computed tomography (SPECT) imaging. This study aims to establish a SPECT protocol for(161)Tb imaging in the clinic. Materials and methods Optimal settings using various gamma-camera collimators and energy windows were explored by imaging a Jaszczak phantom, including hollow-sphere inserts, filled with(161)Tb. The collimators examined were extended low-energy general purpose (ELEGP), medium-energy general purpose (MEGP), and low-energy high resolution (LEHR), respectively. In addition, three ordered subset expectation maximization (OSEM) algorithms were investigated: attenuation-corrected OSEM (A-OSEM); attenuation and dual- or triple-energy window scatter-corrected OSEM (AS-OSEM); and attenuation, scatter, and collimator-detector response-corrected OSEM (ASC-OSEM), where the latter utilized Monte Carlo-based reconstruction. Uniformity corrections, using intrinsic and extrinsic correction maps, were also investigated. Image quality was assessed by estimated recovery coefficients (RC), noise, and signal-to-noise ratio (SNR). Sensitivity was determined using a circular flat phantom. Results The best RC and SNR were obtained at an energy window between 67.1 and 82.1 keV. Ring artifacts, caused by non-uniformity, were removed with extrinsic uniformity correction for the energy window between 67.1 and 82.1 keV, but not with intrinsic correction. Analyzing the lower energy window between 48.9 and 62.9 keV, the ring artifacts remained after uniformity corrections. The recovery was similar for the different collimators when using a specific OSEM reconstruction. Recovery and SNR were highest for ASC-OSEM, followed by AS-OSEM and A-OSEM. When using the optimized parameter setting, the resolution of(161)Tb was higher than for(177)Lu (8.4 +/- 0.7 vs. 10.4 +/- 0.6 mm, respectively). The sensitivities for(161)Tb and(177)Lu were 7.41 and 8.46 cps/MBq, respectively. Conclusion SPECT with high resolution is feasible with(161)Tb; however, extrinsic uniformity correction is recommended to avoid ring artifacts. The LEHR collimator was the best choice of the three tested to obtain a high-resolution image. Due to the complex emission spectrum of low-energy photons, window-based scatter correction had a minor impact on the image quality compared to using attenuation correction only. On the other hand, performing attenuation, scatter, and collimator-detector correction clearly improved image quality. Based on these data, SPECT-based dosimetry for(161)Tb-labeled radiopharmaceuticals is feasible.
25.	Matheson, GJ, et al. (författare) Parametric and non-parametric Poisson regression for modelling of the arterial input function in positron emission tomography 2023 Ingår i: EJNMMI physics. - 2197-7364. ; 10:1, s. 72- Tidskriftsartikel (refereegranskat)
26.	Mellhammar, Emma, et al. (författare) Small-scale dosimetry for alpha particle 241Am source cell irradiation and estimation of γ-H2AX foci distribution in prostate cancer cell line PC3 2022 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 9:1 Tidskriftsartikel (refereegranskat)abstract Background: The development of new targeted alpha therapies motivates improving alpha particle dosimetry. For alpha particles, microscopic targets must be considered to estimate dosimetric quantities that can predict the biological response. As double-strand breaks (DSB) on DNA are the main cause of cell death by ionizing radiation, cell nuclei are relevant volumes necessary to consider as targets. Since a large variance is expected of alpha particle hits in individual cell nuclei irradiated by an uncollimated alpha-emitting source, the damage induced should have a similar distribution. The induction of DSB can be measured by immunofluorescent γ-H2AX staining. The cell γ-H2AX foci distribution and alpha particle hits distribution should be comparable and thereby verify the necessity to consider the relevant dosimetric volumes. Methods: A Monte Carlo simulation model of an 241Am source alpha particle irradiation setup was combined with two versions of realistic cell nuclei phantoms. These were generated from DAPI-stained PC3 cells imaged with fluorescent microscopy, one consisting of elliptical cylinders and the other of segmented mesh volumes. PC3 cells were irradiated with the 241Am source for 4, 8 and 12 min, and after 30 min fixated and stained with immunofluorescent γ-H2AX marker. The detected radiation-induced foci (RIF) were compared to simulated RIF. Results: The mesh volume phantom detected a higher mean of alpha particle hits and energy imparted (MeV) per cell nuclei than the elliptical cylinder phantom, but the mean specific energy (Gy) was very similar. The mesh volume phantom detected a slightly larger variance between individual cells, stemming from the more extreme and less continuous distribution of cell nuclei sizes represented in this phantom. The simulated RIF distribution from both phantoms was in good agreement with the detected RIF, although the detected distribution had a zero-inflated shape not seen in the simulated distributions. An estimate of undetected foci was used to correct the detected RIF distribution and improved the agreement with the simulations. Conclusion: Two methods to generate cell nuclei phantoms for Monte Carlo dosimetry simulations were tested and generated similar results. The simulated and detected RIF distributions from alpha particle-irradiated PC3 cells were in good agreement, proposing the necessity to consider microscopic targets in alpha particle dosimetry.
27.	Morphis, Michaella, et al. (författare) Evaluation of Iodine-123 and Iodine-131 SPECT activity quantification : a Monte Carlo study 2021 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 8:1 Tidskriftsartikel (refereegranskat)abstract Purpose: The quantitative accuracy of Nuclear Medicine images, acquired for both planar and SPECT studies, is influenced by the isotope-collimator combination as well as image corrections incorporated in the iterative reconstruction process. These factors can be investigated and optimised using Monte Carlo simulations. This study aimed to evaluate SPECT quantification accuracy for 123I with both the low-energy high resolution (LEHR) and medium-energy (ME) collimators and 131I with the high-energy (HE) collimator. Methods: Simulated SPECT projection images were reconstructed using the OS-EM iterative algorithm, which was optimised for the number of updates, with appropriate corrections for scatter, attenuation and collimator detector response (CDR), including septal scatter and penetration compensation. An appropriate calibration factor (CF) was determined from four different source geometries (activity-filled: water-filled cylindrical phantom, sphere in water-filled (cold) cylindrical phantom, sphere in air and point-like source), investigated with different volume of interest (VOI) diameters. Recovery curves were constructed from recovery coefficients to correct for partial volume effects (PVEs). The quantitative method was evaluated for spheres in voxel-based digital cylindrical and patient phantoms. Results: The optimal number of OS-EM updates was 60 for all isotope-collimator combinations. The CFpoint with a VOI diameter equal to the physical size plus a 3.0-cm margin was selected, for all isotope-collimator geometries. The spheres’ quantification errors in the voxel-based digital cylindrical and patient phantoms were less than 3.2% and 5.4%, respectively, for all isotope-collimator combinations. Conclusion: The study showed that quantification errors of less than 6.0% could be attained, for all isotope-collimator combinations, if corrections for; scatter, attenuation, CDR (including septal scatter and penetration) and PVEs are performed. 123I LEHR and 123I ME quantification accuracies compared well when appropriate corrections for septal scatter and penetration were applied. This can be useful in departments that perform 123I studies and may not have access to ME collimators.
28.	Nordström, Jonny, et al. (författare) Calculation of left ventricular volumes and ejection fraction from dynamic cardiac-gated 15O-water PET/CT : 5D-PET 2017 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 4:1, s. 26- Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Quantitative measurement of myocardial blood flow (MBF) is of increasing interest in the clinical assessment of patients with suspected coronary artery disease (CAD). (15)O-water positron emission tomography (PET) is considered the gold standard for non-invasive MBF measurements. However, calculation of left ventricular (LV) volumes and ejection fraction (EF) is not possible from standard (15)O-water uptake images. The purpose of the present work was to investigate the possibility of calculating LV volumes and LVEF from cardiac-gated parametric blood volume (V B) (15)O-water images and from first pass (FP) images. Sixteen patients with mitral or aortic regurgitation underwent an eight-gate dynamic cardiac-gated (15)O-water PET/CT scan and cardiac MRI. V B and FP images were generated for each gate. Calculations of end-systolic volume (ESV), end-diastolic volume (EDV), stroke volume (SV) and LVEF were performed with automatic segmentation of V B and FP images, using commercially available software. LV volumes and LVEF were calculated with surface-, count-, and volume-based methods, and the results were compared with gold standard MRI.RESULTS: Using V B images, high correlations between PET and MRI ESV (r = 0.89, p < 0.001), EDV (r = 0.85, p < 0.001), SV (r = 0.74, p = 0.006) and LVEF (r = 0.72, p = 0.008) were found for the volume-based method. Correlations for FP images were slightly, but not significantly, lower than those for V B images when compared to MRI. Surface- and count-based methods showed no significant difference compared with the volume-based correlations with MRI. The volume-based method showed the best agreement with MRI with no significant difference on average for EDV and LVEF but with an overestimation of values for ESV (14%, p = 0.005) and SV (18%, p = 0.004) when using V B images. Using FP images, none of the parameters showed a significant difference from MRI. Inter-operator repeatability was excellent for all parameters (ICC > 0.86, p < 0.001).CONCLUSION: Calculation of LV volumes and LVEF from dynamic (15)O-water PET is feasible and shows good correlation with MRI. However, the analysis method is laborious, and future work is needed for more automation to make the method more easily applicable in a clinical setting.
29.	Oddstig, Jenny, et al. (författare) Head-to-head comparison of a Si-photomultiplier-based and a conventional photomultiplier-based PET-CT system 2021 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 8:1 Tidskriftsartikel (refereegranskat)abstract Background: A novel generation of PET scanners based on silicon (Si)-photomultiplier (PM) technology has recently been introduced. Concurrently, there has been development of new reconstruction methods aimed at increasing the detectability of small lesions without increasing image noise. The combination of new detector technologies and new reconstruction algorithms has been found to increase image quality. However, it is unknown to what extent the demonstrated improvement of image quality is due to scanner hardware development or improved reconstruction algorithms. To isolate the contribution of the hardware, this study aimed to compare the ability to detect small hotspots in phantoms using the latest generation SiPM-based PET/CT scanner (GE Discovery MI) relative to conventional PM-based PET/CT scanner (GE Discovery 690), using identical reconstruction protocols. Materials and methods: Two different phantoms (NEMA body and Jasczcak) with fillable spheres (31 μl to 26.5 ml) and varying sphere-to-background-ratios (SBR) were scanned in one bed position for 15–600 s on both scanners. The data were reconstructed using identical reconstruction parameters on both scanners. The recovery-coefficient (RC), noise level, contrast (spherepeak/backgroundpeak-value), and detectability of each sphere were calculated and compared between the scanners at each acquisition time. Results: The RC-curves for the NEMA phantom were near-identical for both scanners at SBR 10:1. For smaller spheres in the Jaszczak phantom, the contrast was 1.22 higher for the DMI scanner at SBR 15:1. The ratio decreased for lower SBR, with a ratio of 1.03 at SBR 3.85:1. Regarding the detectability of spheres, the sensitivity was 98% and 88% for the DMI and D690, respectively, for SBR 15:1. For SBR 7.5, the sensitivity was 75% and 83% for the DMI and D690, respectively. For SBR 3.85:1, the sensitivity was 43% and 30% for the DMI and D690, respectively. Conclusion: Marginally higher contrast in small spheres was seen for the SiPM-based scanner but there was no significant difference in detectability between the scanners. It was difficult to detect differences between the scanners, suggesting that the SiPM-based detectors are not the primary reason for improved image quality.
30.	Peterson, Mikael, et al. (författare) Monte Carlo-based quantitative pinhole SPECT reconstruction using a ray-tracing back-projector 2017 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 4:1 Tidskriftsartikel (refereegranskat)abstract Background: Monte Carlo simulations provide accurate models of nuclear medicine imaging systems as they can properly account for the full physics of photon transport. The accuracy of the model included in the maximum-likelihood–expectation-maximization (ML-EM) reconstruction limits the overall accuracy of the reconstruction results. In this paper, we present a Monte Carlo-based ML-EM reconstruction method for pinhole single-photon emission computed tomography (SPECT) that has been incorporated into the SIMIND Monte Carlo program. The Monte Carlo-based model, which accounts for all of the physical and geometrical characteristics of the camera system, is used in the forward-projection step of the reconstruction, while a simpler model based on ray-tracing is used for back-projection. The aim of this work was to investigate the quantitative accuracy of this combination of forward- and back-projectors in the clinical pinhole camera GE Discovery NM 530c. Results: The total activity was estimated in 99mTc-filled spheres with volumes between 0.5 and 16 mL. The total sphere activity was generally overestimated but remained within 10% of the reference activity defined by the phantom preparation. The recovered activity converged towards the reference activity as the number of iterations increased. Furthermore, the recovery of the activity concentrations within the physical boundaries of the spheres increased with increasing sphere volume. Additionally, the Monte Carlo-based reconstruction enabled recovery of the true activity concentration in the myocardium of a cardiac phantom mounted in a torso phantom regardless of whether the torso was empty or water-filled. A qualitative comparison to data reconstructed using the clinical reconstruction algorithm showed that the two methods performed similarly, although the images reconstructed using the clinical software were more uniform due to the incorporation of noise regularization and post-filtration in that reconstruction technique. Conclusions: We developed a Monte Carlo-based reconstruction method for pinhole SPECT and evaluated it using phantom measurements. The combination of a Monte Carlo-based forward-projector and a simplified analytical ray-tracing back-projector produced quantitative images of acceptable image quality. No explicit calibration is necessary in this method since the forward-projector model maintains a relationship between the number of counts and activity.
31.	Roth, Daniel, et al. (författare) Characterisation of a hand-held CZT-based gamma camera for 177Lu imaging 2020 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 7:1 Tidskriftsartikel (refereegranskat)abstract Background: Currently, hand-held gamma cameras are being developed for 99mTc imaging, mainly for sentinel lymph node detection. These cameras offer advantages, such as mobility and ease of access, and may be useful also for other applications such as biokinetic studies in animals or for imaging of small, superficial structures in patients. In this work, the suitability of a CZT-based hand-held camera for 177Lu imaging is investigated. The energy response of CZT-based detectors combined with the multiple photon emissions of 177Lu poses new challenges compared to 99mTc imaging, and a thorough camera characterisation is thus warranted. Methods: Three collimators (LEHR, LEHS, and MEGP) and three energy windows (55 keV, 113 keV, and 208 keV) are investigated. Characterised camera properties include the system spatial resolution, energy resolution, sensitivity, image uniformity, septal penetration, and temperature dependence. Characterisations are made starting from NEMA guidelines when applicable, with adjustments made when required. The applicability of the camera is demonstrated by imaging of a superficially located tumour in a patient undergoing [177 Lu]Lu-DOTA-TATE therapy. Results: Overall, the results are encouraging. Compared to a conventional gamma camera, the hand-held camera generally has a higher sensitivity for a given collimator. For source-collimator distances below 3 cm, the spatial resolution FWHM is within 6 mm for the LEHR and MEGP collimators. Before uniformity correction, the central field-of-view integral uniformity shows best results for the 113-keV window, with values obtained between 11 and 14%. The corresponding values after uniformity correction are within 3%. Effects of septal penetration are observed but are manageable with a proper combination of collimator and energy window setting. Septal penetration and collimator scatter not only affect the 208-keV window but also contribute with counts in lower windows due to energy-tailing effects. The patient study revealed non-uniform uptake patterns in a region that appeared uniform in a conventional gamma camera image. Conclusions: The results show that the hand-held camera can be used for 177Lu imaging. A 113-keV energy window combined with LEHR or MEGP collimators provides the best image system characteristics.
32.	Roth, Daniel, et al. (författare) Feasibility of 177Lu activity quantification using a small portable CZT-based gamma-camera 2024 Ingår i: EJNMMI Physics. - 2197-7364. ; 11:1 Tidskriftsartikel (refereegranskat)abstract Background: In image processing for activity quantification, the end goal is to produce a metric that is independent of the measurement geometry. Photon attenuation needs to be accounted for and can be accomplished utilizing spectral information, avoiding the need of additional image acquisitions. The aim of this work is to investigate the feasibility of 177Lu activity quantification with a small CZT-based hand-held gamma-camera, using such an attenuation correction method. Methods: A previously presented dual photopeak method, based on the differential attenuation for two photon energies, is adapted for the three photopeaks at 55 keV, 113 keV, and 208 keV for 177Lu. The measurement model describes the count rates in each energy window as a function of source depth and activity, accounting for distance-dependent system sensitivity, attenuation, and build-up. Parameter values are estimated from characterizing measurements, and the source depth and activity are obtained by minimizing the difference between measured and modelled count rates. The method is applied and evaluated in phantom measurements, in a clinical setting for superficial lesions in two patients, and in a pre-clinical setting for one human tumour xenograft. Evaluation is made for a LEHR and an MEGP collimator. Results: For phantom measurements at clinically relevant depths, the average (and standard deviation) in activity errors are 17% ± 9.6% (LEHR) and 2.9% ± 3.6% (MEGP). For patient measurements, deviations from activity estimates from planar images from a full-sized gamma-camera are 0% ± 21% (LEHR) and 16% ± 18% (MEGP). For mouse measurements, average deviations of − 16% (LEHR) and − 6% (MEGP) are obtained when compared to a small-animal SPECT/CT system. The MEGP collimator appears to be better suited for activity quantification, yielding a smaller variability in activity estimates, whereas the LEHR results are more severely affected by septal penetration. Conclusions: Activity quantification for 177Lu using the hand-held camera is found to be feasible. The readily available nature of the hand-held camera may enable more frequent activity quantification in e.g., superficial structures in patients or in the pre-clinical setting.
33.	Roth, Daniel, et al. (författare) Monte Carlo modelling of a compact CZT-based gamma camera with application to 177Lu imaging 2022 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 9:1 Tidskriftsartikel (refereegranskat)abstract Background: Semiconductor gamma-camera systems based on cadmium zinc telluride (CZT) detectors present new challenges due to an energy-response that includes effects of low-energy tailing. In particular, such energy tails produce effects that need to be considered when imaging radionuclides with multiple emissions such as 177Lu. Monte Carlo simulation can be used to investigate the behaviour of such systems and optimise their use, provided that the detector model closely reflects the real physical detector. The aim of this work is to develop a CZT model applicable for simulation of CZT-based gamma cameras. Methods: The equations describing the charge transport and signal induction are considered in three dimensions and are solved numerically, and the CZT model is then realised by coupling the detector-response to the photon-transport handled by the SIMIND Monte Carlo program. The CZT model is tuned to reproduce experimentally measured energy spectra of a hand-held gamma camera system for multiple radionuclides (99 mTc , 123I and 177Lu ) and parallel-hole collimators (MEGP, LEHR) as well as an uncollimated system. Results: Overall, the model results agree well with measurements across the range of experimental conditions. The applicability of the model is demonstrated by separating energy spectra into components to investigate the interference of high-energy photons on lower energy-windows, where pronounced effects of low-energy tailing for 177Lu are observed. Conclusions: The developed model provides understanding of the specifics of the camera response and is expected to be helpful for future optimisation of gamma camera applications.
34.	Rydén, Tobias, et al. (författare) Fast GPU-based Monte Carlo code for SPECT/CT reconstructions generates improved Lu-177 images 2018 Ingår i: Ejnmmi Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 5:1 Tidskriftsartikel (refereegranskat)abstract Background: Full Monte Carlo (MC)-based SPECT reconstructions have a strong potential for correcting for image degrading factors, but the reconstruction times are long. The objective of this study was to develop a highly parallel Monte Carlo code for fast, ordered subset expectation maximum (OSEM) reconstructions of SPECT/CT images. The MC code was written in the Compute Unified Device Architecture language for a computer with four graphics processing units (GPUs) (GeForce GTX Titan X, Nvidia, USA). This enabled simulations of parallel photon emissions from the voxels matrix (1283 or 2563). Each computed tomography (CT) number was converted to attenuation coefficients for photo absorption, coherent scattering, and incoherent scattering. For photon scattering, the deflection angle was determined by the differential scattering cross sections. An angular response function was developed and used to model the accepted angles for photon interaction with the crystal, and a detector scattering kernel was used for modeling the photon scattering in the detector. Predefined energy and spatial resolution kernels for the crystal were used. The MC code was implemented in the OSEM reconstruction of clinical and phantom Lu-177 SPECT/CT images. The Jaszczak image quality phantom was used to evaluate the performance of the MC reconstruction in comparison with attenuated corrected (AC) OSEM reconstructions and attenuated corrected OSEM reconstructions with resolution recovery corrections (RRC). Result: The performance of the MC code was 3200 million photons/s. The required number of photons emitted per voxel to obtain a sufficiently low noise level in the simulated image was 200 for a 1283 voxel matrix. With this number of emitted photons/ voxel, the MC-based OSEM reconstruction with ten subsets was performed within 20 s/iteration. The images converged after around six iterations. Therefore, the reconstruction time was around 3 min. The activity recovery for the spheres in the Jaszczak phantom was clearly improved with MC-based OSEM reconstruction, e.g., the activity recovery was 88% for the largest sphere, while it was 66% for AC-OSEM and 79% for RRC-OSEM. Conclusion: The GPU-based MC code generated an MC-based SPECT/CT reconstruction within a few minutes, and reconstructed patient images of Lu-177-DOTATATE treatments revealed clearly improved resolution and contrast.
35.	Sandblom, Viktor, 1987, et al. (författare) Evaluation of two intraoperative gamma detectors for assessment of 177Lu activity concentration in vivo 2017 Ingår i: European Journal of Nuclear Medicine and Molecular Imaging Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 4:1 Tidskriftsartikel (refereegranskat)abstract Background Patients with somatostatin receptor-expressing neuroendocrine tumours can be treated with intravenously administered 177Lu-octreotate. Few patients are cured with the present protocol due to the current dose limitation of normal organs at risk, such as the kidneys. By locally administering 177Lu-octreotate to the liver for the purpose of treating liver metastases, a substantially reduced absorbed dose to organs at risk could be achieved. The development of such a technique requires the capability of measuring the 177Lu activity concentration in tissues in vivo. The aim of this study was to evaluate different performance parameters of two commercially available intraoperative gamma detectors in order to investigate whether intraoperative gamma detector measurements could be used to determine 177Lu activity concentration in vivo. Results Measurements were made using different sources containing 177Lu. Response linearity, sensitivity, spatial resolution and its depth dependence, organ thickness dependence of the measured count rate and tumour detectability were assessed for two intraoperative gamma detectors. The two detectors (a scintillation and a semiconductor detector) showed differences in technical performance. For example, the sensitivity was higher for the scintillation detector, while the spatial resolution was better for the semiconductor detector. Regarding organ thickness dependence and tumour detectability, similar results were obtained for both detectors, and even relatively small simulated tumours of low tumour-to-background activity concentration ratios could be detected. Conclusions Acceptable results were obtained for both detectors, although the semiconductor detector proved more advantageous for our purpose. The measurements demonstrated factors that must be corrected for, such as organ thickness or dead-time effects. Altogether, intraoperative gamma detector measurements could be used to determine 177Lu activity concentration in vivo.
36.	Sandgren, Kristina, et al. (författare) Radiation dosimetry of [Ga-68]PSMA-11 in low-risk prostate cancer patients 2019 Ingår i: EJNMMI Physics. - : Springer. - 2197-7364. ; 6 Tidskriftsartikel (refereegranskat)abstract Background: 68Ga-labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC ([68Ga]PSMA-11) has been increasingly used to image prostate cancer using positron emission tomography (PET)/computed tomography (CT) both during diagnosis and treatment planning. It has been shown to be of clinical value for patients both in the primary and secondary stages of prostate cancer. The aim of this study was to determine the effective dose and organ doses from injection of [68Ga]PSMA-11 in a cohort of low-risk prostate cancer patients.Methods: Six low-risk prostate cancer patients were injected with 133–178 MBq [68Ga]PSMA-11 and examined with four PET/CT acquisitions from injection to 255 min post-injection. Urine was collected up to 4 h post-injection, and venous blood samples were drawn at 45 min, 85 min, 175 min, and 245 min post-injection. Kidneys, liver, lungs, spleen, salivary and lacrimal glands, and total body where delineated, and cumulated activities and absorbed organ doses calculated. The software IDAC-Dose 2.1 was used to calculate absorbed organ doses according to the International Commission on Radiological Protection (ICRP) publication 107 using specific absorbed fractions published in ICRP 133 and effective dose according to ICRP Publication 103. We also estimated the absorbed dose to the eye lenses using Monte Carlo methods.Results: [68Ga]PSMA-11 was rapidly cleared from the blood and accumulated preferentially in the kidneys and the liver. The substance has a biological half-life in blood of 6.5 min (91%) and 4.4 h (9%). The effective dose was calculated to 0.022 mSv/MBq. The kidneys received approximately 40 mGy after an injection with 160 MBq [68Ga]PSMA-11 while the lacrimal glands obtained an absorbed dose of 0.12 mGy per administered MBq. Regarding the eye lenses, the absorbed dose was low (0.0051 mGy/MBq).Conclusion: The effective dose for [68Ga]PSMA-11 is 0.022 mSv/MBq, where the kidneys and lacrimal glands receiving the highest organ dose.
37.	Sandström, Mattias, et al. (författare) Kidney dosimetry in 777 patients during 177Lu-DOTATATE therapy : aspects on extrapolations and measurement time points 2020 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 7:1 Tidskriftsartikel (refereegranskat)abstract PurposeFractionated peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE is increasingly applied as an effective treatment for patients with disseminated neuroendocrine tumors. In parallel to dose planning before external beam radiation therapy, dosimetry is also needed to optimize PRRT to the individual patient. Accordingly, absorbed doses to organs at risk need to be calculated during PRRT, based on serial measurements of radioactivity distribution utilizing SPECT/CT. The dosimetry should be based on as few measurements as possible, while still retaining reliable results. The main aim of the present work was to calculate the fractional contribution of the extrapolations of the curve fits for the absorbed dose calculations to the kidneys. The secondary aim was to study agreement between absorbed dose (AD) and the effective half-life (teff) for the kidneys, estimated by means of measurements at one or two time points, in comparison to our current method employing three time points.MethodsIn 777 patients with disseminated neuroendocrine tumors undergoing PRRT, SPECT/CT over the abdomen was acquired at 1, 4, and 7 days after 177Lu-DOTATATE infusion. The absorbed dose to the kidneys was calculated from SPECT/CT radioactivity distribution data, and the teff and fractional contributions of the extrapolations were estimated, utilizing data from one, two, and three time points, respectively.ResultsThe fractional contributions from extrapolations before day 1 measurement and after day 7 measurement were approximately 26% and 11%, respectively. The mean differences in absorbed dose, based on one, two, and three time points were small, but with high method dependence for individual patients. The differences in estimated teff were small when it was based on measurements at days 1 and 7, but high for days 1 and 4 time points.ConclusionWhen assessing simplifications of methods for calculation of the absorbed dose to the kidneys, it was of the uttermost importance to incorporate the fractional contribution for the extrapolations included in the reference method. Measurements at an early and a late time point were found most important. An intermediate measurement contributes with an idea of the goodness of the fit.
38.	Sandström, Mattias, et al. (författare) Method dependence, observer variability and kidney volumes in radiation dosimetry of (177)Lu-DOTATATE therapy in patients with neuroendocrine tumours. 2015 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 2:1 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Radionuclide therapy can be individualized by performing dosimetry. To determine absorbed organ doses in (177)Lu-DOTATATE therapy, three methods based on activity concentrations are currently in use: the small volume of interest (sVOI) method, and two methods based on large VOIs either on anatomical CT (aVOI) or on thresholds on functional images (tVOI). The main aim of the present work was to validate the sVOI in comparison to the other two methods regarding agreement and time efficiency. Secondary aims were to investigate inter-observer variability for the sVOI and the change of functional organ volumes following therapy.METHODS: Thirty patients diagnosed with neuroendocrine tumours undergoing therapy with (177)Lu-DOTATATE were included. Each patient underwent three SPECT/CT scans at 1, 4 and 7 days after the treatment. Three independent observers calculated absorbed doses to the right and left kidney and the spleen using sVOI and one observer used aVOI. For tVOI, the absorbed doses were calculated based on automatically drawn isocontours around the organs at different thresholds (42, 50, 60 and 70 %). The inter-observer difference between the calculated absorbed doses for sVOI was calculated, and the differences between the three methods were computed. Ratios of organ volumes acquired at days 1, 4 and 7 versus the volume at day 1 were calculated for the tVOI method.RESULTS: The differences in results of the absorbed dose calculations using all the sVOI and tVOI were small (<5 %). Absorbed dose calculations using aVOI differed slightly more from these results but were still below 10 %. The differences between the three dose calculation methods varied between <5 and 10 %. The organ volumes derived from the tVOI were independent of time for the spleen while they decreased with time for the kidneys. The fastest analysis was performed with the sVOI method.CONCLUSIONS: All three dose calculation methods rendered comparable results with small inter-observer differences for sVOI. Unlike the spleen, the functional volume of the kidneys decreased over time during therapy, which suggests that the absorbed dose calculation for the kidneys on activity concentrations should be performed for each time point. The sVOI is the preferred method for calculating absorbed doses in solid organs.
39.	Shekari, M, et al. (författare) Harmonization of brain PET images in multi-center PET studies using Hoffman phantom scan 2023 Ingår i: EJNMMI physics. - 2197-7364. ; 10:1, s. 68- Tidskriftsartikel (refereegranskat)
40.	Siebinga, Hinke, et al. (författare) Predicting [177Lu]Lu-HA-DOTATATE kidney and tumor accumulation based on [68Ga]Ga-HA-DOTATATE diagnostic imaging using semi-physiological population pharmacokinetic modeling 2023 Ingår i: EJNMMI Physics. - : Springer. - 2197-7364. ; 10:1 Tidskriftsartikel (refereegranskat)abstract BackgroundPrediction of [177Lu]Lu-HA-DOTATATE kidney and tumor uptake based on diagnostic [68Ga]Ga-HA-DOTATATE imaging would be a crucial step for precision dosing of [177Lu]Lu-HA-DOTATATE. In this study, the population pharmacokinetic (PK) differences between [177Lu]Lu-HA-DOTATATE and [68Ga]Ga-HA-DOTATATE were assessed and subsequently [177Lu]Lu-HA-DOTATATE was predicted based on [68Ga]Ga-HA-DOTATATE imaging.MethodsA semi-physiological nonlinear mixed-effects model was developed for [68Ga]Ga-HA-DOTATATE and [177Lu]Lu-HA-DOTATATE, including six compartments (representing blood, spleen, kidney, tumor lesions, other somatostatin receptor expressing organs and a lumped rest compartment). Model parameters were fixed based on a previously developed physiologically based pharmacokinetic model for [68Ga]Ga-HA-DOTATATE. For [177Lu]Lu-HA-DOTATATE, PK parameters were based on literature values or estimated based on scan data (four time points post-injection) from nine patients. Finally, individual [177Lu]Lu-HA-DOTATATE uptake into tumors and kidneys was predicted based on individual [68Ga]Ga-HA-DOTATATE scan data using Bayesian estimates. Predictions were evaluated compared to observed data using a relative prediction error (RPE) for both area under the curve (AUC) and absorbed dose. Lastly, to assess the predictive value of diagnostic imaging to predict therapeutic exposure, individual prediction RPEs (using Bayesian estimation) were compared to those from population predictions (using the population model).ResultsPopulation uptake rate parameters for spleen, kidney and tumors differed by a 0.29-fold (15% relative standard error (RSE)), 0.49-fold (15% RSE) and 1.43-fold (14% RSE), respectively, for [177Lu]Lu-HA-DOTATATE compared to [68Ga]Ga-HA-DOTATATE. Model predictions adequately described observed data in kidney and tumors for both peptides (based on visual inspection of goodness-of-fit plots). Individual predictions of tumor uptake were better (RPE AUC –40 to 28%) compared to kidney predictions (RPE AUC –53 to 41%). Absorbed dose predictions were less predictive for both tumor and kidneys (RPE tumor and kidney –51 to 44% and –58 to 82%, respectively). For most patients, [177Lu]Lu-HA-DOTATATE tumor accumulation predictions based on individual PK parameters estimated from diagnostic imaging outperformed predictions based on population parameters.ConclusionOur semi-physiological PK model indicated clear differences in PK parameters for [68Ga]Ga-HA-DOTATATE and [177Lu]Lu-HA-DOTATATE. Diagnostic images provided additional information to individually predict [177Lu]Lu-HA-DOTATATE tumor uptake compared to using a population approach. In addition, individual predictions indicated that many aspects, apart from PK differences, play a part in predicting [177Lu]Lu-HA-DOTATATE distribution.
41.	Sjögreen Gleisner, Katarina, et al. (författare) Variations in the practice of molecular radiotherapy and implementation of dosimetry : results from a European survey 2017 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 4:1 Tidskriftsartikel (refereegranskat)abstract Background: Currently, the implementation of dosimetry in molecular radiotherapy (MRT) is not well investigated, and in view of the Council Directive (2013/59/Euratom), there is a need to understand the current availability of dosimetry-based MRT in clinical practice and research studies. The aim of this study was to assess the current practice of MRT and dosimetry across European countries. Methods: An electronic questionnaire was distributed to European countries. This addressed 18 explicitly considered therapies, and for each therapy, a similar set of questions were included. Questions covered the number of patients and treatments during 2015, involvement of medical specialties and medical physicists, implementation of absorbed dose planning, post-therapy imaging and dosimetry, and the basis of therapy prescription. Results: Responses were obtained from 26 countries and 208 hospitals, administering in total 42,853 treatments. The most common therapies were 131I-NaI for benign thyroid diseases and thyroid ablation of adults. The involvement of a medical physicist (mean over all 18 therapies) was reported to be either minority or never by 32% of the responders. The percentage of responders that reported that dosimetry was included on an always/majority basis differed between the therapies and showed a median value of 36%. The highest percentages were obtained for 177Lu-PSMA therapy (100%), 90Y microspheres of glass (84%) and resin (82%), 131I-mIBG for neuroblastoma (59%), and 131I-NaI for benign thyroid diseases (54%). The majority of therapies were prescribed based on fixed-activity protocols. The highest number of absorbed-dose based prescriptions were reported for 90Y microsphere treatments in the liver (64% and 96% of responses for resin and glass, respectively), 131I-NaI treatment of benign thyroid diseases (38% of responses), and for 131I-mIBG treatment of neuroblastoma (18% of responses). Conclusions: There is a wide variation in MRT practice across Europe and for different therapies, including the extent of medical-physicist involvement and the implementation of dosimetry-guided treatments.
42.	Sousa, João M., et al. (författare) Accuracy and precision of zero-echo-time, single- and multi-atlas attenuation correction for dynamic [11C]PE2I PET-MR brain imaging 2020 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 7:1 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: A valid photon attenuation correction (AC) method is instrumental for obtaining quantitatively correct PET images. Integrated PET/MR systems provide no direct information on attenuation, and novel methods for MR-based AC (MRAC) are still under investigation. Evaluations of various AC methods have mainly focused on static brain PET acquisitions. In this study, we determined the validity of three MRAC methods in a dynamic PET/MR study of the brain.METHODS: Nine participants underwent dynamic brain PET/MR scanning using the dopamine transporter radioligand [11C]PE2I. Three MRAC methods were evaluated: single-atlas (Atlas), multi-atlas (MaxProb) and zero-echo-time (ZTE). The 68Ge-transmission data from a previous stand-alone PET scan was used as reference method. Parametric relative delivery (R1) images and binding potential (BPND) maps were generated using cerebellar grey matter as reference region. Evaluation was based on bias in MRAC maps, accuracy and precision of [11C]PE2I BPND and R1 estimates, and [11C]PE2I time-activity curves. BPND was examined for striatal regions and R1 in clusters of regions across the brain.RESULTS: For BPND, ZTE-MRAC showed the highest accuracy (bias < 2%) in striatal regions. Atlas-MRAC exhibited a significant bias in caudate nucleus (- 12%) while MaxProb-MRAC revealed a substantial, non-significant bias in the putamen (9%). R1 estimates had a marginal bias for all MRAC methods (- 1.0-3.2%). MaxProb-MRAC showed the largest intersubject variability for both R1 and BPND. Standardized uptake values (SUV) of striatal regions displayed the strongest average bias for ZTE-MRAC (~ 10%), although constant over time and with the smallest intersubject variability. Atlas-MRAC had highest variation in bias over time (+10 to - 10%), followed by MaxProb-MRAC (+5 to - 5%), but MaxProb showed the lowest mean bias. For the cerebellum, MaxProb-MRAC showed the highest variability while bias was constant over time for Atlas- and ZTE-MRAC.CONCLUSIONS: Both Maxprob- and ZTE-MRAC performed better than Atlas-MRAC when using a 68Ge transmission scan as reference method. Overall, ZTE-MRAC showed the highest precision and accuracy in outcome parameters of dynamic [11C]PE2I PET analysis with use of kinetic modelling.
43.	Sousa, João M., et al. (författare) Evaluation of zero-echo-time attenuation correction for integrated PET/MR brain imaging-comparison to head atlas and 68Ge-transmission-based attenuation correction 2018 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 5:20 Tidskriftsartikel (refereegranskat)abstract Background: MRI does not offer a direct method to obtain attenuation correction maps as its predecessors (stand-alone PET and PET/CT), and bone visualisation is particularly challenging. Recently, zero-echo-time (ZTE) was suggested for MR-based attenuation correction (AC). The aim of this work was to evaluate ZTE- and atlas-AC by comparison to 68Ge-transmission scan-based AC.Nine patients underwent brain PET/MR and stand-alone PET scanning using the dopamine transporter ligand 11C-PE2I. For each of them, two AC maps were obtained from the MR images: an atlas-based, obtained from T1-weighted LAVA-FLEX imaging with cortical bone inserted using a CT-based atlas, and an AC map generated from proton-density-weighted ZTE images. Stand-alone PET 68Ge-transmission AC map was used as gold standard. PET images were reconstructed using the three AC methods and standardised uptake value (SUV) values for the striatal, limbic and cortical regions, as well as the cerebellum (VOIs) were compared. SUV ratio (SUVR) values normalised for the cerebellum were also assessed. Bias, precision and agreement were calculated; statistical significance was evaluated using Wilcoxon matched-pairs signed-rank test.Results: Both ZTE- and atlas-AC showed a similar bias of 6–8% in SUV values across the regions. Correlation coefficients with 68Ge-AC were consistently high for ZTE-AC (r 0.99 for all regions), whereas they were lower for atlas-AC, varying from 0.99 in the striatum to 0.88 in the posterior cortical regions. SUVR showed an overall bias of 2.9 and 0.5% for atlas-AC and ZTE-AC, respectively. Correlations with 68Ge-AC were higher for ZTE-AC, varying from 0.99 in the striatum to 0.96 in the limbic regions, compared to atlas-AC (0.99 striatum to 0.77 posterior cortex).Conclusions: Absolute SUV values showed less variability for ZTE-AC than for atlas-AC when compared to 68Ge-AC, but bias was similar for both methods. This bias is largely caused by higher linear attenuation coefficients in atlas- and ZTE-AC image compared to 68Ge-images. For SUVR, bias was lower when using ZTE-AC than for atlas-AC. ZTE-AC shows to be a more robust technique than atlas-AC in terms of both intra- and inter-patient variability.
44.	Stokke, Caroline, et al. (författare) Dosimetry-based treatment planning for molecular radiotherapy : A summary of the 2017 report from the Internal Dosimetry Task Force 2017 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 4:1 Forskningsöversikt (refereegranskat)abstract Background: The European directive on basic safety standards (Council directive 2013/ 59 Euratom) mandates dosimetry-based treatment planning for radiopharmaceutical therapies. The directive comes into operation February 2018, and the aim of a report produced by the Internal Dosimetry Task Force of the European Association of Nuclear Medicine is to address this aspect of the directive. A summary of the report is presented. Results: A brief review of five of the most common therapy procedures is included in the current text, focused on the potential to perform patient-specific dosimetry. In the full report, 11 different therapeutic procedures are included, allowing additional considerations of effectiveness, references to specific literature on quantitative imaging and dosimetry, and existing evidence for absorbed dose-effect correlations for each treatment. Individualized treatment planning with tracer diagnostics and verification of the absorbed doses delivered following therapy is found to be scientifically feasible for almost all procedures investigated, using quantitative imaging and/or external monitoring. Translation of this directive into clinical practice will have significant implications for resource requirements. Conclusions: Molecular radiotherapy is undergoing a significant expansion, and the groundwork for dosimetry-based treatment planning is already in place. The mandated individualization is likely to improve the effectiveness of the treatments, although must be adequately resourced.
45.	Sundlöv, Anna, et al. (författare) Feasibility of simplifying renal dosimetry in Lu-177 peptide receptor radionuclide therapy 2018 Ingår i: Ejnmmi Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 5:1 Tidskriftsartikel (refereegranskat)abstract Background: Recently, Lu-177-dotatate therapy for neuroendocrine tumours has received regulatory approval. Dosimetry can be used to optimize treatment on an individual basis, but there is no international consensus as to how it should be done. The aim of this study is to determine a feasible and accurate dosimetry method to guide individualized peptide receptor radionuclide therapy (PRRT) for patients with neuroendocrine tumours. As part of a clinical trial on Lu-177-dotatate therapy, renal dosimetry was performed for all patients in each treatment cycle, using a hybrid planar-SPECT/CT method. In the present study, we use the image data acquired from 22 patients and 119 cycles and define a set of alternative treatment planning strategies, each representing a simplification in terms of image acquisition and dosimetric calculations. The results from the simplified strategies are compared to the results from the protocol-prescribed hybrid planar-SPECT/CT-based method by analysing differences both in per-cycle and total cumulative absorbed dose (AD) analyses. Results: In general, the SPECT-based methods gave results that were largely consistent with the protocol-specified hybrid method, both in the per-cycle and cumulative AD analyses. Notably, performing one SPECT/CT per cycle at 96 h yielded ADs that were very similar to the protocol method. The methods using planar dosimetry resulted in larger variations, as expected, while giving 4 cycles to all patients resulted in the largest inter-individual differences in cumulative AD. Conclusions: Performing one SPECT/CT at 96 h in every treatment cycle gives sufficiently reliable dosimetric results to base individualized treatment planning on, with a reasonable demand on resources.
46.	Svensson, Johanna, et al. (författare) A novel planar image-based method for bone marrow dosimetry in (177)Lu-DOTATATE treatment correlates with haematological toxicity. 2016 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 3:1 Tidskriftsartikel (refereegranskat)abstract (177)Lu-DOTATATE is a valuable treatment option for patients with advanced neuroendocrine tumours overexpressing somatostatin receptors. Though well tolerated in general, bone marrow toxicity can, besides renal exposure, become dose limiting and affect the ability to sustain future therapies. The aim of this study was to develop a novel planar image-based method for bone marrow dosimetry and evaluate its correlation with haematological toxicity during (177)Lu-DOTATATE treatment. In this study, 46 patients with advanced neuroendocrine tumours were treated with 7.2GBq (3.5-8.3GBq) of (177)Lu-DOTATATE on two to five occasions. Planar gamma camera images were acquired at 2, 24, 48 and 168h post-injection. Whole-body regions of interest were created in the images, and a threshold-based segmentation algorithm was applied to separate the uptake of (177)Lu-DOTATATE into high and low uptake compartments. The conjugate view method was used to quantify the activity, the accumulated activity was calculated and the absorbed dose to the bone marrow was estimated according to the MIRD scheme. Patients were monitored for haematological toxicity based on haemoglobin (Hb), white blood cell (WBC) and platelet (PLT) counts every other week during the treatment period.The mean absorbed dose to the bone marrow was estimated to 0.20Gy (0.11-0.37Gy) per 7.4GBq of (177)Lu-DOTATATE, and the mean dose per fraction correlated with a decrease in Hb (p=0.01), WBC (p<0.01) and PLT (p<0.01) counts. The total mean absorbed dose to the bone marrow was 0.64Gy (0.30-1.5Gy) per 24GBq (8.2-37GBq) of (177)Lu-DOTATATE and also correlated with a decrease in Hb (p<0.01), WBC (p=0.01) and PLT (p<0.01) counts.The planar image-based method developed in this study resulted in similar absorbed doses to the bone marrow as reported in earlier studies with blood-based bone marrow dosimetry. The results correlated with haematological toxicity, making it a promising method for estimating bone marrow doses in (177)Lu-DOTATATE treatment without the need for blood and urine sampling.
47.	Svensson, Johanna, et al. (författare) Radiation exposure of the spleen during Lu-177-DOTATATE treatment and its correlation with haematological toxicity and spleen volume 2016 Ingår i: Ejnmmi Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 3:1 Tidskriftsartikel (refereegranskat)abstract Background: Somatostatin analogue-based radionuclide therapy with Lu-177-DOTATATE is an important treatment option for patients with advanced neuroendocrine tumours overexpressing somatostatin receptors. In addition to the kidneys, the bone marrow is a major dose-limiting organ. The correlation between developed haematological toxicity and absorbed dose to the bone marrow is poor, which indicates that other factors affect haematological response. The spleen has an important role in the haematopoetic system, including being a reservoir for blood cells. It is also the organ that receives the highest mean absorbed dose during Lu-177-DOTATATE treatment. The aim of this study was to analyse mean absorbed dose to the spleen and its correlation with haematological toxicity, and to explore changes in splenic volume. The study included 41 patients treated with 7.2 GBq (3.5-8.3 GBq) of Lu-177-DOTATATE on two to five occasions. Following each fraction, planar whole-body scans were acquired at 2, 24, 48, and 168 h, and a SPECT/CT at 24 h post-injection. Mean absorbed spleen dose was calculated utilising planar images for time-activity data and SPECT to adjust activity amounts. Splenic volume information was collected from diagnostic CT scans at baseline and follow-up. Results: Median and total absorbed spleen doses were estimated to 4.5 and 15 Gy, respectively. Total absorbed spleen dose correlated with decrease in Hb (p = 0.02), but not WBC (p = 0.31) or PLT (p = 0.65) counts. For patients without bone metastases, mean absorbed spleen dose correlated with decrease in PLT (p = 0.04) but not Hb (p = 0.16) or WBC (p = 0.42) counts. The spleen volume was reduced to 75 % (p < 0.001) of original values (200 vs. 260 ml) at a mean followup of 36 months. Conclusions: Haematological toxicity according to Hb counts was moderately but significantly correlated with total absorbed spleen dose. This supports the possibility that radiation exposure of the spleen affects overall haematological response during Lu-177-DOTATATE treatment.
48.	Tossici-Bolt, L, et al. (författare) [123I]FP-CIT ENC-DAT normal database: the impact of the reconstruction and quantification methods 2017 Ingår i: EJNMMI physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 4:1, s. 8- Tidskriftsartikel (refereegranskat)
49.	Tran-Gia, Johannes, et al. (författare) A multicentre and multi-national evaluation of the accuracy of quantitative Lu-177 SPECT/CT imaging performed within the MRTDosimetry project 2021 Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 8:1 Tidskriftsartikel (refereegranskat)abstract 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.
50.	Tran-Gia, Johannes, et al. (författare) On the use of solid 133Ba sources as surrogate for liquid 131I in SPECT/CT calibration : a European multi-centre evaluation 2023 Ingår i: EJNMMI Physics. - 2197-7364. ; 10:1 Tidskriftsartikel (refereegranskat)abstract 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.

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