PET imaging and quantification of small animals using a clinical SiPM-based camera.

BACKGROUND: Small-animal PET imaging is an important tool in preclinical oncology. This study evaluated the ability of a clinical SiPM-PET camera to image several rats simultaneously and to perform quantification data analysis. METHODS: Intrinsic spatial resolution was measured using 18F line sources, and image quality was assessed using a NEMA NU 4-2018 phantom. Quantification was evaluated using a fillable micro-hollow sphere phantom containing 4 spheres of different sizes (ranging from 3.95 to 7.86 mm). Recovery coefficients were computed for the maximum (Amax) and the mean (A50) pixel values measured on a 50% isocontour drawn on each sphere. Measurements were performed first with the phantom placed in the centre of the field of view and then in the off-centre position with the presence of three scattering sources to simulate the acquisition of four animals simultaneously. Quantification accuracy was finally validated using four 3D-printed phantoms mimicking rats with four subcutaneous tumours each. All experiments were performed for both 18F and 68Ga radionuclides. RESULTS: Radial spatial resolutions measured using the PSF reconstruction algorithm were 1.80 mm and 1.78 mm for centred and off-centred acquisitions, respectively. Spill-overs in air and water and uniformity computed with the NEMA phantom centred in the FOV were 0.05, 0.1 and 5.55% for 18F and 0.08, 0.12 and 2.81% for 68Ga, respectively. Recovery coefficients calculated with the 18F-filled micro-hollow sphere phantom for each sphere varied from 0.51 to 1.43 for Amax and from 0.40 to 1.01 for A50. These values decreased from 0.28 to 0.92 for Amax and from 0.22 to 0.66 for A50 for 68 Ga acquisition. The results were not significantly different when imaging phantoms in the off-centre position with 3 scattering sources. Measurements performed with the four 3D-printed phantoms showed a good correlation between theoretical and measured activity in simulated tumours, with r2 values of 0.99 and 0.97 obtained for 18F and 68Ga, respectively. CONCLUSION: We found that the clinical SiPM-based PET system was close to that obtained with a dedicated small-animal PET device. This study showed the ability of such a system to image four rats simultaneously and to perform quantification analysis for radionuclides commonly used in oncology.

Safety and Therapeutic Optimization of Lutetium-177 Based Radiopharmaceuticals.

Peptide receptor radionuclide therapy (PRRT) using Lutetium-177 (177Lu) based radiopharmaceuticals has emerged as a therapeutic area in the field of nuclear medicine and oncology, allowing for personalized medicine. Since the first market authorization in 2018 of [¹77Lu]Lu-DOTATATE (Lutathera®) targeting somatostatin receptor type 2 in the treatment of gastroenteropancreatic neuroendocrine tumors, intensive research has led to transfer innovative 177Lu containing pharmaceuticals to the clinic. Recently, a second market authorization in the field was obtained for [¹77Lu]Lu-PSMA-617 (Pluvicto®) in the treatment of prostate cancer. The efficacy of 177Lu radiopharmaceuticals are now quite well-reported and data on the safety and management of patients are needed. This review will focus on several clinically tested and reported tailored approaches to enhance the risk-benefit trade-off of radioligand therapy. The aim is to help clinicians and nuclear medicine staff set up safe and optimized procedures using the approved 177Lu based radiopharmaceuticals.

Impact of disposable syringes type choice on myocardial perfusion imaging procedures with [99mTc]Tc-tetrofosmin.

BACKGROUND: Residual activity in dispensing syringes is a problem that has been sporadically reported with various radiopharmaceuticals. Studies with [99mTc]Tc-tetrofosmin are non-consistent so far. The aim was to quantify the residual activity of [99mTc]Tc-tetrofosmin in different syringes in a clinical setting and to assess its impact on the clinical imaging procedure. METHODS: The residual activity of [99mTc]Tc-tetrofosmin was measured in 3 types of syringes: 3-part lubricated and non-lubricated syringes and 2-part syringe (n ≥ 30 for each syringe). The residual activity was located and quantified using a CzT SPECT camera and radio-counting then was correlated with different clinical parameters and processed by multiple linear regression analysis. RESULTS: Residual activity was different in all syringe types but lubricated syringes showed significantly higher levels with a mean ± SD of 26.12 ± 10.21% (P < .001). For these syringes, the residual activity was mainly located on the lubricated body. They also have a positive and significant impact on the standardized counting duration of patients' acquisitions. CONCLUSION: Lubricated syringes with high residual activity should be avoided as they increase the risk of prolonging patient acquisition time and potentially increasing the risk of poor image quality.

Feasibility of Imaging Small Animals on a 360° Whole-Body Cadmium Zinc Telluride SPECT Camera: a Phantom Study.

PURPOSE: Single-photon emission computed tomography has found an important place in preclinical cancer research. Nevertheless, the cameras dedicated to small animals are not widely available. The present study aimed to assess the feasibility of imaging small animals by a newly released 360° cadmium zinc telluride camera (VERITON, Spectrum Dynamics, Israel) dedicated to human patients. PROCEDURES: A cylindrical phantom containing hot spheres was used to evaluate the intrinsic performance of the camera first without the presence of background activity and then with two contrasts between background and hot spheres (1/4 and 1/10). Acquisitions were repeated with different scan durations (10 and 20 min), two tested radioisotopes (Tc-99 m and I-123), and a set of reconstruction parameters (10 iterations [i] 8 subsets [s], 10i16s, 10i32s). A 3D-printed phantom mimicking a rat with four subcutaneous tumours was then used to test the camera under preclinical conditions. RESULTS: The results obtained from the micro-hollow sphere phantom showed that it was possible to visualize spheres with an inner diameter of 3.95 mm without background activity. Moreover, spheres with diameters of 4.95 mm can be seen in the condition of high contrast between background and spheres (1/10) and 7.86 mm with lower contrast (1/4). The rat-sized phantom acquisitions showed that 10- and 8-mm subcutaneous tumours were visible with a good contrast obtained for the two radioisotopes tested in this study. Both Tc-99 m and I-123 measurements demonstrated that a 10-min acquisition reconstructed with an ordered subset expectation maximization algorithm applying 10i32s was optimal to obtain sufficient image quality in terms of noise, resolution, and contrast. CONCLUSION: Phantom results showed the ability of the system to detect sub-centimetre lesions for various radioisotopes. It seemed feasible to image small animals using a 360° cadmium zinc telluride gamma camera for preclinical cancer research purposes.

Advances in PET/CT Technology: An Update.

This article reviews the current evolution and future directions in PET/CT technology focusing on three areas: time of flight, image reconstruction, and data-driven gating. Image reconstruction is considered with advances in point spread function modelling, Bayesian penalised likelihood reconstruction, and artificial intelligence approaches. Data-driven gating is examined with reference to respiratory motion, cardiac motion, and head motion. For each of these technological advancements, theory will be briefly discussed, benefits of their use in routine practice will be detailed and potential future developments will be discussed. Representative clinical cases will be presented, demonstrating the huge opportunities given to the PET community by hardware and software advances in PET technology when it comes to lesion detection, disease characterization, accurate quantitation and quicker scans. Through this review, hospitals are encouraged to embrace, evaluate and appropriately implement the wide range of new PET technologies that are available now or in the near future, for the improvement of patient care.

Management and evaluation of sodium [131I] iodide contamination after oral administration.

Radioiodine therapy using oral administration of Iodine-131 (I) is a widespread employed strategy for the treatment of hyperthyroidism and thyroid cancer. Such a therapy requires well-trained staff, equipment and procedures regarding radiation safety. The aims of this work are to report an incidental experience of radioprotection with a 370 MBq sodium [I] iodide capsule, which arose following vomiting one minute after the oral administration in a nuclear medicine department and assessment of capsule leakage in a stomach like environment by in vitro experiment. Measurements of the radiation dose rate at the different steps of the decontamination procedure were performed and management of the situation described. Dose rate in vomit was 113 µSv/h [directional dose equivalent H'(0.07)] after capsule withdrawal and was decreased by 10 times after the first decontamination attempt. To evaluate the I release following administration to the patient, an in vitro experiment was designed to recap capsules degradation in a stomach like environment including acidic solution (pH 1) and temperature at 35-37°c. A significant release of I (<6%) was observed in the first 2 min of the in vitro experiment. Sodium [I] iodide capsules disruption occurred at 150 s for capsule 1 and 133 s for capsule 2. Incidental contamination with I in the clinics is of important concern in nuclear medicine and precautions that allow optimization and pertinent management of the situation should be known by the nuclear medicine and radioprotection community.

Evaluation of a new multipurpose whole-body CzT-based camera: comparison with a dual-head Anger camera and first clinical images.

BACKGROUND: Evaluate the physical performance of the VERITON CzT camera (Spectrum Dynamics, Caesarea, Israel) that benefits from new detection architecture enabling whole-body imaging compared to that of a conventional dual-head Anger camera. METHODS: Different line sources and phantom measurements were performed on each system to evaluate spatial resolution, sensitivity, energy resolution and image quality with acquisition and reconstruction parameters similar to those used in clinical routine. Extrinsic resolution was assessed using 99mTc capillary sources placed successively in air, in a head and in a body phantom filled with background activity. Spectral acquisitions for various radioelements used in nuclear medicine (99mTc, 123I, 201Tl, 111In) were performed to evaluate energy resolution by computing the FWHM of the measured photoelectric peak. Tomographic sensitivity was calculated by recording the total number of counts detected during tomographic acquisition for a set of source geometries representative of different clinical situations. Sensitivity was also evaluated in focus mode for the CzT camera, which consisted of forcing detectors to collect data in a reduced field-of-view. Image quality was assessed with a Jaszczak phantom filled with 350 MBq of 99mTc and scanned on each system with 30-,20-,10- and 5-min acquisition times. RESULTS: Extrinsic and tomographic resolution in the brain and body phantoms at the centre of the FOV was estimated at 3.55, 7.72 and 6.66 mm for the CzT system and 2.47, 7.75 and 7.72 mm for the conventional system, respectively. The energy resolution measured at 140 keV was 5.46% versus 9.21% for the Anger camera and was higher in a same manner for all energy peaks tested. Tomographic sensitivity for a point source in air was estimated at 236 counts·s-1·MBq-1 and increased to 1159 counts·s-1·MBq-1 using focus mode, which was 1.6 times and 8 times greater than the sensitivity measured on the scintillation camera (144 counts·s-1·MBq-1). Head and body measurements also showed higher sensitivity for the CzT camera in particular with focus mode. The Jaszczak phantom showed high image contrast uniformity and a high signal-to-noise ratio on the CzT system, even when decreasing acquisition time by 6-fold. Representative clinical cases are shown to illustrate these results. CONCLUSION: The CzT camera has a superior sensitivity, higher energy resolution and better image contrast than the conventional SPECT camera, whereas spatial resolution remains similar. Introduction of this new technology may change current practices in nuclear medicine such as decreasing acquisition time and activity injected to patient.

Why harmonization is needed when using FDG PET/CT as a prognosticator: demonstration with EARL-compliant SUV as an independent prognostic factor in lung cancer.

BACKGROUND: To determine EARL-compliant prognostic SUV thresholds in a mature cohort of patients with locally advanced NSCLC, and to demonstrate how detrimental it is to use a threshold determined on an older-generation PET system with a newer PET/CT machine, and vice versa, or to use such a threshold with non-harmonized multicentre pooled data. MATERIALS AND METHODS: This was a single-centre retrospective study including 139 consecutive stage IIIA-IIIB patients. PET data were acquired as per the EANM guidelines and reconstructed with unfiltered point spread function (PSF) reconstruction. Subsequently, a 6.3 mm Gaussian filter was applied using the EQ.PET (Siemens Healthineers) methodology to meet the EANM/EARL harmonizing standards (PSFEARL). A multicentre study including non-EARL-compliant systems was simulated by randomly creating four groups of patients whose images were reconstructed with unfiltered PSF and PSF with Gaussian post-filtering of 3, 5, and 10 mm. Identification of optimal SUV thresholds was based on a two-fold cross-validation process that partitioned the overall sample into learning and validation subsamples. Proportional Cox hazards models were used to estimate age-adjusted and multivariable-adjusted hazard ratios (HRs) and their 95% confidence intervals. Kaplan-Meier curves were compared using the log rank test. RESULTS: Median follow-up was 28 months (1-104 months). For the whole population, the estimated overall survival rate at 36 months was 0.39 [0.31-0.47]. The optimal SUVmax cutoff value was 25.43 (95% CI: 23.41-26.31) and 8.47 (95% CI: 7.23-9.31) for the PSF and for the EARL-compliant dataset respectively. These SUVmax cutoff values were both significantly and independently associated with lung cancer mortality; HRs were 1.73 (1.05-2.84) and 1.92 (1.16-3.19) for the PSF and the EARL-compliant dataset respectively. When (i) applying the optimal PSF SUVmax cutoff on an EARL-compliant dataset and the optimal EARL SUVmax cutoff on a PSF dataset or (ii) applying the optimal EARL compliant SUVmax cutoff to a simulated multicentre dataset, the tumour SUVmax was no longer significantly associated with lung cancer mortality. CONCLUSION: The present study provides the PET community with an EARL-compliant SUVmax as an independent prognosticator for advanced NSCLC that should be confirmed in a larger cohort, ideally at other EARL accredited centres, and highlights the need to harmonize PET quantitative metrics when using them for risk stratification of patients.

Correction to: Why harmonization is needed when using FDG PET/CT as a prognosticator: demonstration with EARL-compliant SUV as an independent prognostic factor in lung cancer.

An error occurred in the labelling of Fig. 3, where math symbols for SUV thresholds were inverted in panel b when the EARL threshold was applied to the PSF dataset and vice versa. This figure should read as follows: Fig. 3: Prognostic value of tumour SUVmax.

Optimization of a dedicated protocol using a small-voxel PSF reconstruction for head-and-neck 18FDG PET/CT imaging in differentiated thyroid cancer.

BACKGROUND: 18FDG PET/CT is crucial before neck surgery for nodal recurrence localization in iodine-refractory differentiated or poorly differentiated thyroid cancer (DTC/PDTC). A dedicated head-and-neck (HN) acquisition performed with a thin matrix and point-spread-function (PSF) modelling in addition to the whole-body PET study has been shown to improve the detection of small cancer deposits. Different protocols have been reported with various acquisition times of HN PET/CT. We aimed to compare two reconstruction algorithms for disease detection and to determine the optimal acquisition time per bed position using the Siemens Biograph6 with extended field-of-view. METHODS: Twenty-one consecutive and unselected patients with DTC/PDTC underwent HN PET/CT acquisition using list-mode. PET data were reconstructed, mimicking five different acquisition times per bed position from 2 to 10 min. Each PET data set was reconstructed using 3D-ordered subset expectation maximisation (3D-OSEM) or iterative reconstruction with PSF modelling with no post filtering (PSFallpass). These reconstructions resulted in 210 anonymized datasets that were randomly reviewed to assess 18FDG uptake in cervical lymph nodes or in the thyroid bed using a 5-point scale. Noise level, maximal standard uptake values (SUVmax), tumour/background ratios (TBRs) and dimensions of the corresponding lesion on the CT scan were recorded. In surgical patients, the largest tumoral size of each lymph node metastasis was measured by a pathologist. RESULTS: The 120 HN PET studies of the 12 patients with at least 1 18FDG focus scored malignant formed the study group. Noise level significantly decreased between 2 and 4 min for both 3D-OSEM and PSFallpass reconstructions (p < 0.01). TBRs were similar for all the acquisition times for both 3D-OSEM and PSFallpass reconstructions (p = 0.25 and 0.44, respectively). The detection rate of malignant foci significantly improved from 2 to 10 min for PSFallpass reconstruction (20/26 to 26/26; p = 0.01) but not for 3D-OSEM (15/26 to 19/26; p = 0.26). For each of the five acquisition times, PSFallpass detected more malignant foci than 3D-OSEM (p < 0.01). In the seven surgical patients, PSFallpass evidenced smaller malignant lymph nodes than 3D-OSEM at 8 and 10 min. At 10 min, the mean size of the lymph node metastases neither detected with PSFallpass nor 3D-OSEM was 3 ± 0.6 mm vs 5.8 ± 1.1 mm for those detected with PSFallpass only and 10.9 ± 3.3 for those detected with both reconstructions (p < 0.001). CONCLUSIONS: PSFallpass HN PET improves lesion detectability as compared with 3D-OSEM HN PET. PSFallpass with an acquisition time between 8 and 10 min provides the best performance for tumour detection.

Diagnostic value of quantitative assessment of cardiac 18F-fluoro-2-deoxyglucose uptake in suspected cardiac sarcoidosis.

OBJECTIVE: The identification of cardiac sarcoidosis is challenging as there is no gold standard consensually admitted for its diagnosis. The aim of this study was to evaluate the diagnostic value of the assessment of cardiac dynamic 18F-fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET/CT) and net influx constant (Ki) in patients suspected of cardiac sarcoidosis. METHODS: Data obtained from 30 biopsy-proven sarcoidosis patients suspected of cardiac sarcoidosis who underwent a 50-min list-mode cardiac dynamic 18F-FDG PET/CT after a 24 h high-fat and low-carbohydrate diet were analyzed. A normalized coefficient of variation of quantitative glucose influx constant, calculated as the ratio: standard deviation of the segmental Ki (min-1)/global Ki (min-1) was determined using a validated software (Carimas® 2.4, Turku PET Centre). Cardiac sarcoidosis was diagnosed according to the Japanese Ministry of Health and Welfare criteria. Receiving operating curve analysis was performed to determine sensitivity and specificity of cardiac dynamic 18F-FDG PET/CT analysis to diagnose cardiac sarcoidosis. RESULTS: Six out of 30 patients (20%) were diagnosed as having cardiac sarcoidosis. Myocardial glucose metabolism was significantly heterogeneous in patients with cardiac sarcoidosis who showed significantly higher normalized coefficient of variation values compared to patients without cardiac sarcoidosis (0.513 ± 0.175 vs. 0.205 ± 0.081; p = 0.0007). Using ROC curve analysis, we found a cut-off value of 0.38 for the diagnosis of cardiac sarcoidosis with a sensitivity of 100% and a specificity of 91%. CONCLUSIONS: Our results suggest that quantitative analysis of cardiac dynamic 18F-FDG PET/CT could be a useful tool for the diagnosis of cardiac sarcoidosis.

EORTC PET response criteria are more influenced by reconstruction inconsistencies than PERCIST but both benefit from the EARL harmonization program.

BACKGROUND: This study evaluates the consistency of PET evaluation response criteria in solid tumours (PERCIST) and European Organisation for Research and Treatment of Cancer (EORTC) classification across different reconstruction algorithms and whether aligning standardized uptake values (SUVs) to the European Association of Nuclear Medicine acquisition (EANM)/EARL standards provides more consistent response classification. MATERIALS AND METHODS: Baseline (PET1) and response assessment (PET2) scans in 61 patients with non-small cell lung cancer were acquired in protocols compliant with the EANM guidelines and were reconstructed with point-spread function (PSF) or PSF + time-of-flight (TOF) reconstruction for optimal tumour detection and with a standardized ordered subset expectation maximization (OSEM) reconstruction known to fulfil EANM harmonizing standards. Patients were recruited in three centres. Following reconstruction, EQ.PET, a proprietary software solution was applied to the PSF ± TOF data (PSF ± TOF.EQ) to harmonize SUVs to the EANM standards. The impact of differing reconstructions on PERCIST and EORTC classification was evaluated using standardized uptake values corrected for lean body mass (SUL). RESULTS: Using OSEMPET1/OSEMPET2 (standard scenario), responders displayed a reduction of -57.5% ± 23.4 and -63.9% ± 22.4 for SULmax and SULpeak, respectively, while progressing tumours had an increase of +63.4% ± 26.5 and +60.7% ± 19.6 for SULmax and SULpeak respectively. The use of PSF ± TOF reconstruction impacted the classification of tumour response. For example, taking the OSEMPET1/PSF ± TOFPET2 scenario reduced the apparent reduction in SUL in responding tumours (-39.7% ± 31.3 and -55.5% ± 26.3 for SULmax and SULpeak, respectively) but increased the apparent increase in SUL in progressing tumours (+130.0% ± 50.7 and +91.1% ± 39.6 for SULmax and SULpeak, respectively). Consequently, variation in reconstruction methodology (PSF ± TOFPET1/OSEMPET2 or OSEM PET1/PSF ± TOFPET2) led, respectively, to 11/61 (18.0%) and 10/61 (16.4%) PERCIST classification discordances and to 17/61 (28.9%) and 19/61 (31.1%) EORTC classification discordances. An agreement was better for these scenarios with application of the propriety filter, with kappa values of 1.00 and 0.95 compared to 0.75 and 0.77 for PERCIST and kappa values of 0.93 and 0.95 compared to 0.61 and 0.55 for EORTC, respectively. CONCLUSION: PERCIST classification is less sensitive to reconstruction algorithm-dependent variability than EORTC classification but harmonizing SULs within the EARL program is equally effective with either.

Generating harmonized SUV within the EANM EARL accreditation program: software approach versus EARL-compliant reconstruction.

BACKGROUND: Evolutions in hardware and software PET technology, such as point spread function (PSF) reconstruction, have been shown to improve diagnostic performance, but can also lead to important device-dependent and reconstruction-dependent variations in standardized uptake values (SUVs). This may preclude the multicentre use of SUVs as a prognostic or diagnostic tool or as a biomarker of the early response to antineoplastic treatments. This study compared two SUV harmonization strategies using a newer reconstruction algorithm that improves lesion detection while maintaining comparability with older systems: (1) the use of a second reconstruction compliant with harmonization standards and (2) the use of a proprietary software tool (EQ.PET). METHODS: PET data from 50 consecutive non-small cell lung cancer patients were reconstructed with PSF reconstruction for optimal tumor detection and an ordered subset expectation maximization (OSEM3D) reconstruction to mimic a former generation PET. An additional PSF reconstruction was performed with a 7 mm Gaussian filter (PSF7, first method), and, post-reconstruction, the EQ filter (same Gaussian filter) was applied to the PSF data (PSFEQ, second method) for harmonization purposes. The 7 mm kernel filter was chosen to comply with the European Association of Nuclear Medicine (EANM) standards. SUVs for all reconstructions were compared with regression analyses and/or Bland-Altman plots. RESULTS: Overall, 171 lesions were analyzed: 55 lung lesions (32.2%), 87 lymph nodes (50.9%), and 29 metastases (16.9%). In these lesions, the mean PSF7/OSEM3D ratios for SUVmax and SUVpeak were 1.02 (95% CI: 0.93-1.11) and 1.04 (95% CI: 0.95-1.14), respectively. The mean PSFEQ/OSEM3D ratios for SUVmax and SUVpeak were 1.01 (95% CI: 0.91-1.11) and 1.04 (95% CI: 0.94-1.14), respectively. When comparing PSF7 and PSFEQ, Bland-Altman analysis showed that the mean PSF7/PSFEQ ratios for SUVmax and SUVpeak were 1.01 (95% CI: 0.96-1.06) and 1.01 (95% CI: 0.97-1.04), respectively. CONCLUSION: The issue of reconstruction dependency in SUV values that hampers the comparison of data between different PET systems can be overcome using two reconstructions for harmonized quantification and optimal diagnosis or using the EQ.PET technology. Both technologies produce similar results, EQ.PET sparing reconstruction and interpretation time. Other manufacturers are encouraged to either emulate this solution or to produce a vendor-neutral approach.

Does PET SUV Harmonization Affect PERCIST Response Classification?

Pre- and posttreatment PET comparative scans should ideally be obtained with identical acquisition and processing, but this is often impractical. The degree to which differing protocols affect PERCIST classification is unclear. This study evaluates the consistency of PERCIST classification across different reconstruction algorithms and whether a proprietary software tool can harmonize SUV estimation sufficiently to provide consistent response classification. METHODS: Eighty-six patients with non-small cell lung cancer, colorectal liver metastases, or metastatic melanoma who were scanned for therapy monitoring purposes were prospectively recruited in this multicenter trial. Pre- and posttreatment PET scans were acquired in protocols compliant with the Society of Nuclear Medicine and Molecular Imaging and the European Association of Nuclear Medicine (EANM) acquisition guidelines and were reconstructed with a point spread function (PSF) or PSF + time-of-flight (TOF) for optimal tumor detection and also with standardized ordered-subset expectation maximization (OSEM) known to fulfill EANM harmonizing standards. After reconstruction, a proprietary software solution was applied to the PSF ± TOF data (PSF ± TOF.EQ) to harmonize SUVs with the OSEM values. The impact of differing reconstructions on PERCIST classification was evaluated. RESULTS: For the OSEMPET1/OSEMPET2 (OSEM reconstruction for pre- and posttherapeutic PET, respectively) scenario, which was taken as the reference standard, the change in SUL was -41% ± 25 and +56% ± 62 in the groups of tumors showing a decrease and an increase in 18F-FDG uptake, respectively. The use of PSF reconstruction affected classification of tumor response. For example, taking the PSF ± TOFPET1/OSEMPET2 scenario increased the apparent reduction in SUL in responding tumors (-48% ± 22) but reduced the apparent increase in SUL in progressing tumors (+37% ± 43), as compared with the OSEMPET1/OSEMPET2 scenario. As a result, variation in reconstruction methodology (PSF ± TOFPET1/OSEMPET2 or OSEM PET1/PSF ± TOFPET2) led to 13 of 86 (15%) and 17 of 86 (20%) PERCIST classification discordances, respectively. Agreement was better for these scenarios with application of the propriety filter, with κ values of 1 and 0.95 compared with 0.79 and 0.72, respectively. CONCLUSION: Reconstruction algorithm-dependent variability in PERCIST classification is a significant issue but can be overcome by harmonizing SULs using a proprietary software tool.

First determination of the heart-to-mediastinum ratio using cardiac dual isotope (¹²³I-MIBG/99mTc-tetrofosmin) CZT imaging in patients with heart failure: the ADRECARD study.

PURPOSE: Cardiac innervation is assessed using the heart-to-mediastinum ratio (HMR) of metaiodobenzylguanidine (MIBG) on planar imaging using Anger single photon emission computed tomography (A-SPECT). The aim of the study was to determine the HMR of MIBG obtained using a CZT-based camera (D-SPECT; Spectrum Dynamics, Israel) in comparison with that obtained using conventional planar imaging. METHODS: The ADRECARD study prospectively evaluated 44 patients with heart failure. They underwent planar acquisition using the A-SPECT camera 4 h after (123)I-MIBG injection (236.4 ± 39.7 MBq). To localize the heart using D-SPECT, (99m)Tc-tetrofosmin (753 ± 133 MBq) was administered and dual isotope acquisition was performed using the D-SPECT system. HMR was calculated using both planar A-SPECT imaging and front view D-SPECT cine data. In a phantom study, we estimated a model fitting the A-SPECT and the D-SPECT data that was further applied to correct for differences between the cameras. RESULTS: A total of 44 patients (39 men and 5 women, aged 60 ± 11 years) with ischaemic (31 patients) and nonischaemic (13 patients) cardiomyopathy completed the study. Most patients (28 of 44) were NYHA class II, and the mean left ventricular ejection fraction was 33 ± 7 %. The mean HMR values were 1.34 ± 0.15 and 1.45 ± 0.27 from A-SPECT and D-SPECT, respectively (p < 0.0001). After correction, Lin's concordance correlation showed an almost perfect concordance between corrected D-SPECT HMR and A-SPECT HMR, and Bland-Altman analysis demonstrated a high agreement between the two measurements. CONCLUSION: The ADRECARD study demonstrated that determination of late HMR during cardiac MIBG imaging using dual isotope ((123)I and (99m)Tc) acquisition on a CZT camera (D-SPECT) is feasible in patients with heart failure. A linear correction based on the phantom study yielded a high agreement between (123)I MIBG HMR obtained using a CZT camera and that from conventional planar imaging.

Harmonizing FDG PET quantification while maintaining optimal lesion detection: prospective multicentre validation in 517 oncology patients.

PURPOSE: Point-spread function (PSF) or PSF + time-of-flight (TOF) reconstruction may improve lesion detection in oncologic PET, but can alter quantitation resulting in variable standardized uptake values (SUVs) between different PET systems. This study aims to validate a proprietary software tool (EQ.PET) to harmonize SUVs across different PET systems independent of the reconstruction algorithm used. METHODS: NEMA NU2 phantom data were used to calculate the appropriate filter for each PSF or PSF+TOF reconstruction from three different PET systems, in order to obtain EANM compliant recovery coefficients. PET data from 517 oncology patients were reconstructed with a PSF or PSF+TOF reconstruction for optimal tumour detection and an ordered subset expectation maximization (OSEM3D) reconstruction known to fulfil EANM guidelines. Post-reconstruction, the proprietary filter was applied to the PSF or PSF+TOF data (PSFEQ or PSF+TOFEQ). SUVs for PSF or PSF+TOF and PSFEQ or PSF+TOFEQ were compared to SUVs for the OSEM3D reconstruction. The impact of potential confounders on the EQ.PET methodology including lesion and patient characteristics was studied, as was the adherence to imaging guidelines. RESULTS: For the 1380 tumour lesions studied, Bland-Altman analysis showed a mean ratio between PSF or PSF+TOF and OSEM3D of 1.46 (95%CI: 0.86-2.06) and 1.23 (95%CI: 0.95-1.51) for SUVmax and SUVpeak, respectively. Application of the proprietary filter improved these ratios to 1.02 (95%CI: 0.88-1.16) and 1.04 (95%CI: 0.92-1.17) for SUVmax and SUVpeak, respectively. The influence of the different confounding factors studied (lesion size, location, radial offset and patient's BMI) was less than 5%. Adherence to the European Association of Nuclear Medicine (EANM) guidelines for tumour imaging was good. CONCLUSION: These data indicate that it is not necessary to sacrifice the superior lesion detection and image quality achieved by newer reconstruction techniques in the quest for harmonizing quantitative comparability between PET systems.

Staging the axilla in breast cancer patients with ¹8F-FDG PET: how small are the metastases that we can detect with new generation clinical PET systems?

PURPOSE: Point spread function (PSF) reconstruction improves spatial resolution throughout the entire field of view of a PET system and can detect smaller metastatic deposits than conventional algorithms such as OSEM. We assessed the impact of PSF reconstruction on quantitative values and diagnostic accuracy for axillary staging of breast cancer patients, compared with an OSEM reconstruction, with emphasis on the size of nodal metastases. METHODS: This was a prospective study in a single referral centre in which 50 patients underwent an (18)F-FDG PET examination before axillary lymph node dissection. PET data were reconstructed with an OSEM algorithm and PSF reconstruction, analysed blindly and validated by a pathologist who measured the largest nodal metastasis per axilla. This size was used to evaluate PET diagnostic performance. RESULTS: On pathology, 34 patients (68%) had nodal involvement. Overall, the median size of the largest nodal metastasis per axilla was 7 mm (range 0.5 - 40 mm). PSF reconstruction detected more involved nodes than OSEM reconstruction (p = 0.003). The mean PSF to OSEM SUVmax ratio was 1.66 (95 % CI 1.01 - 2.32). The sensitivities of PSF and OSEM reconstructions were, respectively, 96% and 92% in patients with a largest nodal metastasis of >7 mm, 60% and 40% in patients with a largest nodal metastasis of ≤7 mm, and 92% and 69% in patients with a primary tumour ≤30 mm. Biggerstaff graphical comparison showed that globally PSF reconstruction was superior to OSEM reconstruction. The median sizes of the largest nodal metastasis in patients with nodal involvement not detected by either PSF or OSEM reconstruction, detected by PSF but not by OSEM reconstruction and detected by both reconstructions were 3, 6 and 16 mm (p = 0.0064) respectively. In patients with nodal involvement detected by PSF reconstruction but not by OSEM reconstruction, the smallest detectable metastasis was 1.8 mm. CONCLUSION: As a result of better activity recovery, PET with PSF reconstruction performed better than PET with OSEM reconstruction in detecting nodal metastases ≤7 mm. However, its sensitivity is still insufficient for it to replace surgical approaches for axillary staging. PET with PSF reconstruction could be used to perform sentinel node biopsy more safely in patients with a primary tumour ≤30 mm and with unremarkable PET results in the axilla.

Harmonizing SUVs in multicentre trials when using different generation PET systems: prospective validation in non-small cell lung cancer patients.

PURPOSE: We prospectively evaluated whether a strategy using point spread function (PSF) reconstruction for both diagnostic and quantitative analysis in non-small cell lung cancer (NSCLC) patients meets the European Association of Nuclear Medicine (EANM) guidelines for harmonization of quantitative values. METHODS: The NEMA NU-2 phantom was used to determine the optimal filter to apply to PSF-reconstructed images in order to obtain recovery coefficients (RCs) fulfilling the EANM guidelines for tumour positron emission tomography (PET) imaging (PSF(EANM)). PET data of 52 consecutive NSCLC patients were reconstructed with unfiltered PSF reconstruction (PSF(allpass)), PSF(EANM) and with a conventional ordered subset expectation maximization (OSEM) algorithm known to meet EANM guidelines. To mimic a situation in which a patient would undergo pre- and post-therapy PET scans on different generation PET systems, standardized uptake values (SUVs) for OSEM reconstruction were compared to SUVs for PSF(EANM) and PSF(allpass) reconstruction. RESULTS: Overall, in 195 lesions, Bland-Altman analysis demonstrated that the mean ratio between PSF(EANM) and OSEM data was 1.03 [95% confidence interval (CI) 0.94-1.12] and 1.02 (95% CI 0.90-1.14) for SUV(max) and SUV(mean), respectively. No difference was noticed when analysing lesions based on their size and location or on patient body habitus and image noise. Ten patients (84 lesions) underwent two PET scans for response monitoring. Using the European Organization for Research and Treatment of Cancer (EORTC) criteria, there was an almost perfect agreement between OSEM(PET1)/OSEM(PET2) (current standard) and OSEM(PET1)/PSF(EANM-PET2) or PSF(EANM-PET1)/OSEM(PET2) with kappa values of 0.95 (95% CI 0.91-1.00) and 0.99 (95% CI 0.96-1.00), respectively. The use of PSF(allpass) either for pre- or post-treatment (i.e. OSEM(PET1)/PSF(allpass-PET2) or PSF(allpass-PET1)/OSEM(PET2)) showed considerably less agreement with kappa values of 0.75 (95% CI 0.67-0.83) and 0.86 (95% CI 0.78-0.94), respectively. CONCLUSION: Protocol-optimized images and compliance with EANM guidelines allowed for a reliable pre- and post-therapy evaluation when using different generation PET systems. These data obtained in NSCLC patients could be extrapolated to other solid tumours.

High-throughput small animal PET imaging in cancer research: evaluation of the capability of the Inveon scanner to image four mice simultaneously.

The aim of this study was to assess the capability of small animal PET (SA-PET) devices to image four mice simultaneously to improve the throughput of SA-PET experiments in cancer research. A customized bed was designed to image up to four mice simultaneously. This bed can easily replace the bed provided by the manufacturer and is connected to an anaesthesia device. A mouse-sized phantom was imaged, mimicking simultaneous imaging of four mice with computation of recovery coefficients and spillover ratios (SORs). In addition, eight mice bearing subcutaneous tumours (human embryonal carcinoma, n=22 tumours) were simultaneously imaged in groups of four on an Inveon SA-PET scanner after injection of F-fluoro-D-glucose. Tumour activity (Bq/ml), as determined by the SA-PET, was compared with ex-vivo counting. For a 5-mm rod, recovery coefficients were 1.15 and 1.05 for a phantom imaged at the central field of view or off-centred on the customized bed, respectively. SORair and SORwater were 0.05 and 0.04 for a phantom imaged alone and 0.15 and 0.06 for a phantom imaged with three additional scatter sources, respectively. Correlation between SA-PET and ex-vivo quantification was good (r=0.91, P<0.0001). The mean ratio of PET quantitative data and ex-vivo counting was equal to 0.9 (95% confidence interval: 0.70-1.09). New generation SA-PET may be suitable for simultaneously imaging four tumour-bearing mice, although improvement in scatter correction efficiency appears necessary. The type of customized bed developed in this study could be easily adapted to other large-bore SA-PET scanners.

High throughput static and dynamic small animal imaging using clinical PET/CT: potential preclinical applications.

PURPOSE: The objective of the study was to evaluate state-of-the-art clinical PET/CT technology in performing static and dynamic imaging of several mice simultaneously. METHODS: A mouse-sized phantom was imaged mimicking simultaneous imaging of three mice with computation of recovery coefficients (RCs) and spillover ratios (SORs). Fifteen mice harbouring abdominal or subcutaneous tumours were imaged on clinical PET/CT with point spread function (PSF) reconstruction after injection of [18F]fluorodeoxyglucose or [18F]fluorothymidine. Three of these mice were imaged alone and simultaneously at radial positions -5, 0 and 5 cm. The remaining 12 tumour-bearing mice were imaged in groups of 3 to establish the quantitative accuracy of PET data using ex vivo gamma counting as the reference. Finally, a dynamic scan was performed in three mice simultaneously after the injection of (68)Ga-ethylenediaminetetraacetic acid (EDTA). RESULTS: For typical lesion sizes of 7-8 mm phantom experiments indicated RCs of 0.42 and 0.76 for ordered subsets expectation maximization (OSEM) and PSF reconstruction, respectively. For PSF reconstruction, SOR(air) and SOR(water) were 5.3 and 7.5%, respectively. A strong correlation (r (2) = 0.97, p < 0.0001) between quantitative data obtained in mice imaged alone and simultaneously in a group of three was found following PSF reconstruction. The correlation between ex vivo counting and PET/CT data was better with PSF reconstruction (r (2) = 0.98; slope = 0.89, p < 0.0001) than without (r (2) = 0.96; slope = 0.62, p < 0.001). Valid time-activity curves of the blood pool, kidneys and bladder could be derived from (68)Ga-EDTA dynamic acquisition. CONCLUSION: New generation clinical PET/CT can be used for simultaneous imaging of multiple small animals in experiments requiring high throughput and where a dedicated small animal PET system is not available.