| 1. |
- Hsu, David Fc, et al.
(författare)
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Studies of a Next Generation Silicon-Photomultiplier-Based Time-of-Flight PET/CT System
- 2017
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine and Molecular Imaging. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 58:9, s. 1511-1518
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Tidskriftsartikel (refereegranskat)abstract
- This article presents system performance studies of the Discovery MI PET/CT system, a new time-of-flight (TOF) system based on silicon photomultipliers. System performance and clinical imaging comparisons were made between this next-generation system and other commercially available PET/CT and PET/MR systems, as well as between different reconstruction algorithms. Methods: Spatial resolution, sensitivity, NECR, scatter fraction, count rate accuracy, and image quality were characterized with the NEMA NU-2 2012 standards. Energy and coincidence time resolution were measured. Tests were conducted independently and results were averaged on two Discovery MI scanners installed at Stanford and Uppsala University Hospitals. Back-to-back patient scans were also performed between the Discovery MI PET/CT, Discovery 690 PET/CT, and SIGNA PET/MR systems. Clinical images were reconstructed with both ordered-subset expectation maximization (OSEM) and the "Q.Clear" reconstruction algorithms, and examined qualitatively. Results: The averaged full-width half max (FWHM) of the radial/tangential/axial spatial resolution reconstructed with FBP at 1, 10, and 20 cm from the system center are, respectively, 4.10/4.19/4.48 mm, 5.47/4.49/6.01 mm, and 7.53/4.90/6.10 mm. The averaged sensitivity is 13.7 cps/kBq at the center of the FOV. Averaged peak noise equivalent count rate is 193.4 kcps at 21.9 kBq/mL with a scatter fraction of 40.6%. The averaged contrast recovery coefficients for the image quality phantom are 53.7/64.0/73.1/82.7/86.8/90.7 for the 10/13/17/22/28/37 mm diameter spheres. The average photopeak energy resolution is 9.40% FWHM and the average coincidence time resolution is 375.4 ps FWHM. Clinical image comparisons between the PET/CT systems demonstrate the high quality of the Discovery MI system. Comparisons between the Discovery MI and SIGNA systems show similar spatial resolution and overall imaging performance. Lastly, results indicate significant image quality and contrast-to-noise performance enhancement for the "Q.Clear" reconstruction algorithm when compared to OSEM. Conclusion: Excellent performance was achieved with the new Discovery MI system, including 375 ps FWHM coincidence time resolution and sensitivity of 14 cps/kBq. Comparisons between different image reconstruction algorithms and other multimodal SiPM and non-SiPM-based PET detector system designs indicate substantial performance enhancements are possible with this next-generation system.
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| 2. |
- Hsu, David, et al.
(författare)
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Studies of a Next Generation Silicon-Photomultiplier-Based Time-of-Flight PET/CT System
- 2017
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Ingår i: Journal of Nuclear Medicine. - 0161-5505 .- 1535-5667. ; 58:S1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: This article presents studies performed with the Discovery MI PET/CT system, a new time-of-flight (TOF) system based on silicon photomultipliers. System performance was characterized according to the NEMA NU-2 2012 standards. Comparisons of performance and clinical images were also made between this next-generation system and other commercially available PET/CT and PET/MR systems, as well as between different image reconstruction algorithms.Methods: Spatial resolution, sensitivity, NECR, scatter fraction, count rate accuracy, and image quality were characterized according to the NEMA NU-2 2012 standards. In addition, energy and coincidence time resolution were measured using a line source at the center of the field-of-view (CFOV). Tests were conducted independently on two Discovery MI scanners installed at Stanford University Hospital and Uppsala University Hospital, and results were averaged between the two systems. In addition, back-to-back patient scans were performed between the Discovery MI PET/CT, Discovery 690 PET/CT, and SIGNA PET/MR systems. Clinical images were reconstructed with both ordered-subset expectation maximization (OSEM) reconstruction algorithms and the block-sequential regularized expectation maximization (BSREM) "Q.Clear" reconstruction algorithm, and examined qualitatively.Results: The averaged FWHM of the radial, tangential, and axial spatial resolution reconstructed with filtered backprojection (FBP) at 1/10/20 cm from the system center are, respectively, 4.10/4.19/4.48 mm, 5.47/4.49/6.01 mm, and 7.53/4.90/6.10 mm. The averaged sensitivity is 13.7 cps/kBq at the center and 13.4 cps/kBq at 10 cm radial offset from the center. Averaged peak noise equivalent count rate (NECR) is 193.4 kcps at 21.9 kBq/mL with a scatter fraction (SF) of 40.6%. The averaged contrast recovery (CR) coefficients for the image quality (IQ) phantom are 53.7/64.0/73.1/82.7/86.8/90.7 for the 10/13/17/22/28/37 mm diameter spheres over 3 separate acquisitions. The average photopeak energy resolution is 9.40% FWHM and the average coincidence time resolution is 375.4 ps FWHM. Clinical image comparisons between the PET/CT systems demonstrate the very high quality of the Discovery MI system. Comparisons between the Discovery MI PET/CT and SIGNA PET/MR systems, which contain identical detector architectures but with different detector diameters, show similar spatial resolution and overall imaging performance. Lastly, results indicate significant image quality and contrast-to-noise performance enhancement for the "Q.Clear" reconstruction algorithm when compared to OSEM.Conclusion: Excellent performance was achieved with the new Discovery MI system, including 375 ps FWHM coincidence time resolution and sensitivity of 14 cps/kBq. Comparisons between different image reconstruction algorithms and other multimodal SiPM and non-SiPM-based PET detector system designs indicate substantial performance enhancements are possible with this next-generation system. Research Support: None
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| 3. |
- Ilan, Ezgi, et al.
(författare)
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Comparison of 68Ga-DOTATATE and 177Lu-DOTATATE kinetics in neuroendocrine tumors
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Tidskriftsartikel (refereegranskat)abstract
- Absorbed dose planning prior peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE would allow maximization of the absorbed dose to tumor tissue whilst minimizing the risk for side-effects in healthy organs. Unfortunately, dosimetry during 177Lu-DOTATATE is only possible post therapy and using 68Ga-DOTATATE to act as surrogate for 177Lu-DOTATATE could potentially enable prediction of absorbed doses prior PRRT with 177Lu-DOTATATE. The aim of this study was to compare uptake and kinetics of 68Ga-DOTATATE and 177Lu-DOTATATE in tumors by performing dynamic or serial scans with both radiopharmaceuticals in the same patients. Methods Six NET patients underwent a 45-min dynamic PET scan after injection of 124 ±38 MBq 68Ga-DOTATATE and serial SPECT scans after a bolus injection of 500 ± 0 MBq 177Lu-DOTATATE assuring similar peptide content in the radiopharmaceuticals. Tumor and whole-blood SUV, tumor-to-blood-ratio (TBR), and net influx rate (Ki) were determined for 68Ga-DOTATATE and 177Lu-DOTATATE. Ki was determined by non-linear regression of an irreversible two-tissue compartment model with a loss parameter and by the Patlak method. Results In majority of tumors, tumor SUV was higher in 68Ga-DOTATATE than in 177Lu-DOTATATE and whole-blood SUV was lower in 68Ga-DOTATATE than in 177Lu-DOTATATE, resulting in a lower TBR for 68Ga-DOTATATE than for 177Lu-DOTATATE. For Ki, Spearman correlation was 0.55 between 68Ga- DOTATATE and 177Lu-DOTATATE with a Demining regression slope of 0.93. For Patlak based Ki (with correction for partial volume effect based on data <100 min p.i. for 177Lu-DOTATATE), the Spearman correlation was 0.90 and with a Deming regression slope close to 1 (0.83). Using a later time interval (with correction for partial volume effect based on data >100 min p.i) for the Patlak analysis also resulted in high correlation (0.87) but the Deming regression slope was 0.18. Conclusion Linear relation with good agreement was found between the SUVs of 68Ga-DOTATATE and 177Lu-DOTATATE. Similar Ki was observed for 68Ga-DOTATATE and 177Lu-DOTATATE during early time interval (<100 min p.i of 177Lu-DOTATATE) however not during late time interval (>100 min p.i.). Hence, late kinetics of 177Lu-DOTATATE cannot be predicted using 68Ga-DOTATATE PET.
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| 4. |
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| 5. |
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| 6. |
- Ilan, Ezgi, et al.
(författare)
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Dose Response of Pancreatic Neuroendocrine Tumors Treated with Peptide Receptor Radionuclide Therapy Using 177Lu-DOTATATE
- 2015
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 56:2, s. 177-182
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Tidskriftsartikel (refereegranskat)abstract
- UNLABELLED: Peptide receptor radionuclide therapy (PRRT) is a promising treatment for patients with neuroendocrine tumors, giving rise to improved survival. Dosimetric calculations in relation to PRRT have been concentrated to normal organ dosimetry in order to limit side effects. However, the relation between the absorbed dose to the tumor and treatment response has so far not been established. Better knowledge in this respect may improve the understanding of treatment effects, allow for improved selection of those patients who are expected to benefit from PRRT, and avoid unnecessary treatments. The aim of the present work was to evaluate the dose-response relationship for pancreatic neuroendocrine tumors treated with PRRT using (177)Lu-DOTATATE.METHODS: Tumor-absorbed dose calculations were performed for 24 lesions in 24 patients with metastasized pancreatic neuroendocrine tumors treated with repeated cycles of (177)Lu-DOTATATE at 8-wk intervals. The absorbed dose calculations relied on sequential SPECT/CT imaging at 24, 96, and 168 h after infusion of (177)Lu-DOTATATE. The unit density sphere model from OLINDA was used for absorbed dose calculations. The absorbed doses were corrected for partial-volume effect based on phantom measurements. On the basis of these results, only tumors larger than 2.2 cm in diameter at any time during the treatment were included for analysis. To further decrease the effect of partial-volume effect, a subgroup of tumors (>4.0 cm) was analyzed separately. Tumor response was evaluated by CT using Response Evaluation Criteria In Solid Tumors.RESULTS: Tumor-absorbed doses until best response ranged approximately from 10 to 340 Gy. A 2-parameter sigmoid fit was fitted to the data, and a significant correlation between the absorbed dose and tumor reduction was found, with a Pearson correlation coefficient (R(2)) of 0.64 for tumors larger than 2.2 cm and 0.91 for the subgroup of tumors larger than 4.0 cm. The largest tumor reduction was 57% after a total absorbed dose of 170 Gy.CONCLUSION: The results imply a significant correlation between absorbed dose and tumor reduction. However, further studies are necessary to address the large variations in response for similar absorbed doses.
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| 7. |
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| 8. |
- Ilan, Ezgi, et al.
(författare)
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Parametric Net Influx Rate Images of 68Ga-DOTATOC and 68Ga-DOTATATE : Quantitative Accuracy and Improved Image Contrast
- 2017
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 58:5, s. 744-749
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Tidskriftsartikel (refereegranskat)abstract
- (68)Ga-DOTATOC and (68)Ga-DOTATATE are radiolabelled somatostatin analogs used for diagnosis of somatostatin receptor expressing neuroendocrine tumors (NETs) and SUV -measurements are suggested for treatment monitoring. However, changes in net-influx rate (Ki) may better reflect treatment effects than those of the SUV, and accordingly there is a need to compute parametric images showing Ki at the voxel level. The aim of this study was to evaluate parametric methods for computation of parametric Ki images by comparison to volume of interest based methods and to assess image contrast in terms of tumor-to-liver ratio.METHODS: Ten patients with metastatic NETs underwent a 45-min dynamic PET examination followed by whole-body PET/CT at 1 h post injection of (68)Ga-DOTATOC and (68)Ga-DOTATATE on consecutive days. Parametric Ki images were computed using a basis function method (BFM) implementation of the two tissue irreversible compartment model and the Patlak method using a descending aorta image-derived input function, and mean tumor Ki values were determined for 50% isocontour VOIs and compared to Ki values based on non-linear regression (NLR) of the whole-VOI time-activity curve. A subsample of healthy liver was delineated in the whole-body and Ki images and tumor-to-liver ratios were calculated in order to evaluate image contrast. Correlation and agreement between VOI-based and parametric Ki values were assessed using regression and Bland-Altman analysis.RESULTS: Correlation (R2) between NLR-based and parametric image-based (BFM) tumor Ki values was 0.98 (slope 0.81) and 0.97 (slope 0.88) for (68)Ga-DOTATOC and (68)Ga DOTATATE, respectively. For Patlak analysis, correlation between NLR-based and parametric based (Patlak) tumor Ki were 0.95 (slope 0.71) and 0.92 (slope 0.74) for (68)Ga-DOTATOC and (68)Ga-DOTATATE, respectively. There was no bias between NLR and parametric based Ki-values. Tumor-to-liver contrast was 1.6 and 2.0 times higher in the parametric BFM-Ki images, and 2.3 and 3.0 times in the Patlak images, than in the whole-body images for (68)Ga-DOTATOC and (68)Ga-DOTATATE, respectively.CONCLUSION: A high correlation and agreement between NLR- and parametric based Ki values was found, showing that parametric net influx rate images are quantitatively accurate. In addition, tumor-to-liver contrast was superior in the parametric Ki images compared to whole-body images both for (68)Ga-DOTATOC and (68)Ga DOTATATE.
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| 9. |
- Ilan, Ezgi, et al.
(författare)
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Performance comparison of three commercially available PET systems : SIGNA PET/MR, Discovery IQ and Discovery MI
- 2017
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Ingår i: Journal of Nuclear Medicine. - 0161-5505 .- 1535-5667. ; 58:S1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: The NEMA performance measurement standard (NEMA NU 2-2012) for PET scanners provides guidelines on how to assess the performance of Positron Emission Tomography (PET). Three different state of the art PET systems were installed at Uppsala University Hospital between years 2014-2016 and independent NEMA standard tests were performed. The aim of this study was to compare system performance of the three scanners.Methods: Three commercially available scanners from GE-healthcare (SIGNA PET/MR; Discovery IQ PET/CT; Discovery MI PET/CT) were evaluated. The SIGNA and MI systems are based on LYSO crystals and digital SiPMs, whereas the IQ uses BGO crystals and regular PMTs. Spatial resolution, sensitivity, count rate statistics, count rate accuracy and image quality were assessed according to the NEMA NU 2-2012 standards. In addition to the NEMA standard test, recovery was assessed for different reconstructions using the NEMA image quality phantom at a contrast of 4:1 in all spheres, and a triple line insert phantom. These tests were performed on all three scanners in a single session, avoiding differences due to variability in phantom preparation.Results: Full width of half maximum (FWHM) of the spatial resolution (radial/tangential/axial) reconstructed with filtered back projection (FBP) at 1,10 and 20 cm from the centre of FOV is illustrated in figure 1A for each system. The average sensitivity, Peak NECR, scatter fraction and count rate accuracy of each system is presented in table 1. The average image contrast recovery coefficients of SIGNA, IQ and MI varied between 45, 40 and 56 % (10 mm sphere) to 74, 72 and 84 % (22 mm sphere) respectively. The average image contrast recovery coefficients is presented in figure 1B. The lung error for SIGNA, IQ and MI were 2.7, 18 and 5.2 % respectively. Using reconstruction settings recommended for clinical use (Signa: TOF-OSEM, 2 iterations/28 subsets, 5 mm post-filter; IQ: OSEM, 4/12, 4 mm; MI: TOF-OSEM, 3/16, 5 mm, all with resolution recovery) recovery based on a volume of interest over whole spheres varied between 50, 38 and 51 % (10 mm sphere) to 86, 83 and 87 % (22 mm sphere), respectively. In addition to the recommended settings for clinical use, Q.Clear (Block-sequential regularized expectation maximization (BSREM) with PSF modeling) reconstructions with beta values ranging from 100 to 500 with step of 200 were reconstructed. The volume recovery of each system for varying reconstructions is presented in Figure 1C. The mean radial/tangential/central spatial resolution of SIGNA, IQ and MI using the triple line insert phantom when using the recommended standard reconstructions and Q.Clear reconstruction is presented in Figure 1D.Conclusion: As expected, the two ToF systems based on LYSO crystals coupled to digital SiPMs (SIGNA and MI), resulted in an overall better resolution, image quality, NECR and volume recovery than the non-TOF BGO coupled to non-digital detector system (IQ). The image quality and spatial resolution improved when Q.Clear reconstruction was used. The sensitivity was higher in SIGNA than in MI and IQ due to a 25 cm axial FOV in SIGNA, compared to 20 cm for MI and IQ. In conclusion, the new SiPM-based PET detector systems provide a considerable enhancement in system performance.
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| 10. |
- Ilan, Ezgi
(författare)
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Theranostics in Neuroendocrine Tumors : Somatostatin Receptor Imaging and Therapy
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neuroendocrine tumors (NETs) are characterized by cellular overexpression of somatostatin receptors (SSTR), which allows for the use of radiolabeled somatostatin analogs (SSA) for both imaging and therapy. Because NETs often are diagnosed at a metastatic stage, curative surgery is not possible. Monthly long-acting SSA preparation constitutes first-line therapy for low-grade small-intestinal NETs and pancreatic NETs. Peptide receptor radionuclide therapy (PRRT), with radiolabeled SSAs such as 177Lu-DOTATATE, has been shown to be an effective therapeutic alternative for NETs, improving symptoms and quality of life. The gold-standard method for SSTR imaging and diagnosis of NETs is positron emission tomography (PET) using Gallium-68 (68Ga)-labeled SSAs, such as 68Ga-DOTATOC and 68Ga-DOTATATE. The tumor standardized uptake value (SUV) has been proposed both as a marker of SSTR tumor density and a tool for evaluating therapy response. Changes of tumor SUV on 68Ga-DOTATOC- and DOTATATE-PET have, however, not been shown to correlate with the patient outcome.This thesis is based on five original papers, evaluating the relation between tumor-absorbed dose and tumor shrinkage and developing novel theranostic methods in which quantitative PET imaging with 68Ga-DOTATATE and 68Ga-DOTATOC is used to optimize PRRT with 177Lu-DOTATATE in NET patients.A high and significant positive correlation was found between tumor-absorbed dose and tumor shrinkage in pancreatic NETs treated with 177Lu-DOTATATE. Furthermore, it was found that tumor SUV in 68Ga-DOTATATE and 68Ga-DOTATOC failed to correlate linearly with the net influx rate (Ki), assumed to reflect the SSTR density, due to low tracer availability in blood for high Ki values. SUV blood was significantly higher in tumors with high Ki (>0.2) than in tumors with low Ki, and it was found that the tumor-to-blood ratio (TBR) correlates linearly with Ki. Thus, both Ki and TBR may be used as tools to monitor NET therapy response rather than SUV. It was also found that parametric Ki images, illustrating Ki at the voxel level, provide higher tumor-to-liver contrast than static whole-body PET images. Further, it was found that administration of a single dose of cold peptide pre-PRRT with 177Lu-DOTATATE gave rise to faster recycling of SSTRs in tumors than in normal organs. A linear relation was found for tumor SUV and early Ki, between 68Ga-DOTATATE-PET and 177Lu-DOTATE-SPECT; however, the kinetics for 68Ga-DOTATAE could not be used for predicting that of 177Lu-DOTATATE because of tumor clearance of 177Lu-DOTATATE at late time interval.In conclusion, quantitative PET imaging with 68Ga-DOTATATE and 68Ga-DOTATOC shows great potential for both evaluating therapy response and optimizing PRRT with 177Lu-DOTATATE.
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