EANM practice guideline for quantitative SPECT-CT.

PURPOSE: Quantitative SPECT-CT is a modality of growing importance with initial developments in post radionuclide therapy dosimetry, and more recent expansion into bone, cardiac and brain imaging together with the concept of theranostics more generally. The aim of this document is to provide guidelines for nuclear medicine departments setting up and developing their quantitative SPECT-CT service with guidance on protocols, harmonisation and clinical use cases. METHODS: These practice guidelines were written by members of the European Association of Nuclear Medicine Physics, Dosimetry, Oncology and Bone committees representing the current major stakeholders in Quantitative SPECT-CT. The guidelines have also been reviewed and approved by all EANM committees and have been endorsed by the European Association of Nuclear Medicine. CONCLUSION: The present practice guidelines will help practitioners, scientists and researchers perform high-quality quantitative SPECT-CT and will provide a framework for the continuing development of quantitative SPECT-CT as an established modality.

The prevalence of image degradation due to motion in rest-stress rubidium-82 imaging on a SiPM PET-CT system.

BACKGROUND: Motion of the heart is known to affect image quality in cardiac PET. The prevalence of motion blurring in routine cardiac PET is not fully appreciated due to challenges identifying subtle motion artefacts. This study utilizes a recent prototype Data-Driven Motion Correction (DDMC) algorithm to generate corrected images that are compared with non-corrected images to identify visual differences in relative rubidium-82 perfusion images due to motion. METHODS: 300 stress and 300 rest static images were reconstructed with DDMC and without correction (NMC). The 600 DDMC/NMC image pairs were assigned Visual Difference Score (VDS). The number of non-diagnostic images were noted. A "Dwell Fraction" (DF) was derived from the data to quantify motion and predict image degradation. RESULTS: Motion degradation (VDS = 1 or 2) was evident in 58% of stress images and 33% of rest images. Seven NMC images were non-diagnostic-these originated from six studies giving a 2% rate of non-diagnostic studies due to motion. The DF metric was able to effectively predict image degradation. The DDMC heart identification and tracking was successful in all images. CONCLUSION: Motion degradation is present in almost half of all relative perfusion images. The DDMC algorithm is a robust tool for predicting, assessing and correcting image degradation.

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.

A preliminary evaluation of a high temporal resolution data-driven motion correction algorithm for rubidium-82 on a SiPM PET-CT system.

BACKGROUND: In myocardial perfusion PET, images are acquired during vasodilator stress, increasing the likelihood of intra-frame motion blurring of the heart in reconstructed static images to assess relative perfusion. This work evaluated a prototype data-driven motion correction (DDMC) algorithm designed specifically for cardiac PET. METHODS: A cardiac torso phantom, with a solid defect, was scanned stationary and being manually pulled to-and-fro in the axial direction with a random motion. Non-motion-corrected (NMC) and DDMC images were reconstructed. Total perfusion deficit was measured in the defect and profiles through the cardiac insert were defined. In addition, 46 static perfusion images from 36 rubidium-82 MPI patients were selected based upon a perception of motion blurring in the images. NMC and DDMC images were reconstructed, blinded, and scored on image quality and perceived motion. RESULTS: Phantom data demonstrated near-perfect recovery of myocardial wall visualization and defect quantification with DDMC compared with the stationary phantom. Quality of clinical images was NMC: 10 non-diagnostic, 31 adequate, and 5 good; DDMC images: 0 non-diagnostic, 6 adequate, and 40 good. CONCLUSION: The DDMC algorithm shows great promise in rubidium MPI PET with substantial improvements in image quality and the potential to salvage images considered non-diagnostic due to significant motion blurring.

Assessment of motion correction in dynamic rubidium-82 cardiac PET with and without frame-by-frame adjustment of attenuation maps for calculation of myocardial blood flow.

BACKGROUND: Patient motion during pharmacological stressing can have substantial impact on myocardial blood flow (MBF) estimated from dynamic PET. This work evaluated a motion correction algorithm with and without adjustment of the PET attenuation map. METHODS: Frame-by-frame motion correction was performed by three users on 30 rubidium-82 studies. Data were divided equally into three groups of motion severity [mild (M1), moderate (M2) and severe (M3)]. MBF data were compared for non-motion corrected (NC), motion-corrected-only (MC) and with adjustment of the attenuation map (MCAC). Percentage differences of MBF were calculated in the coronary territories and 17-segment polar plots. Polar plots of spill-over were also generated from the data. RESULTS: Median differences of 23% were seen in the RCA and 18% for the LAD in the M3 category for MC vs NC images. Differences for MCAC vs MC images were considerably smaller and typically < 10%. Spill-over plots for MC and MCAC were notably more uniform compared with NC images. CONCLUSION: Motion correction for dynamic rubidium data is desirable for future MBF software updates. Adjustment of the PET attenuation map results in only marginal differences and therefore is unlikely to be an essential requirement. Assessing the uniformity of spill-over plots is a useful visual aid for verifying motion correction techniques.

Spatial dependence of activity concentration recovery for a conjugate gradient (Siemens xSPECT) algorithm using manufacturer-defined reconstruction presets.

Siemens absolute quantitative reconstruction, xSPECT, is available with manufacturer-defined reconstruction presets to assist with optimization. This phantom study evaluates the impact of these presets on the spatial dependence of activity concentration recovery (ACR). Single-photon emission computed tomography/computed tomography scans of a 5 : 1 and 10 : 1 (sphere : background) contrast NEMA phantom were performed on a Siemens Intevo 6. Three sphere position configurations, achieved by rotating the sphere mount through 0°, 120° and 240°, were used and three replicate images of each configuration were acquired. xSPECT reconstruction was performed using 'Fast', 'Standard' and 'Best' presets. Maximum voxel and A50 threshold ACR were measured in each sphere. The average ACR per sphere was calculated across replicates. Percentage variation of ACR, about this average, for each sphere within a given configuration across replicates and also alternative configurations was calculated. Within a given sphere configuration, percentage variation for maximum voxel ACR in like-for-like spheres across replicates was within 11% for all three presets across all sphere sizes, and within 3% for 10 : 1 and 9% for 5 : 1 contrast in the three largest spheres. Substantial variation of ACR was observed when comparing like-for-like spheres in different configurations. In the three largest spheres, variation in maximum ACR of up to 35 and 32% was measured for 10 : 1 and 5 : 1 contrast, respectively. Variation in activity concentration may be substantially greater than perceived from using a single phantom configuration. The spatial dependence observed using the manufacturer presets highlights the need for evaluation of user-defined reconstruction parameters.

Assessing time-of-flight signal-to-noise ratio gains within the myocardium and subsequent reductions in administered activity in cardiac PET studies.

BACKGROUND: Time-of-flight (TOF) is known to increase signal-to-noise ratio (SNR) and facilitate reductions in administered activity. Established measures of SNR gain are derived from areas of uniform uptake, which is not applicable to the heterogeneous uptake in cardiac PET images using fluoro-deoxyglucose (FDG). This study aimed to develop a technique to quantify SNR gains within the myocardium due to TOF. METHODS: Reference TOF SNR gains were measured in 88 FDG oncology patients. Phantom data were used to translate reference SNR gains and validate a method of quantifying SNR gains within the myocardium from parametric images produced from multiple replicate images. This technique was applied to 13 FDG cardiac viability patients. RESULTS: Reference TOF SNR gains of +23% ± 8.5% were measured in oncology patients. Measurements of SNR gain from the phantom data were in agreement and showed the parametric image technique to be sufficiently robust. SNR gains within the myocardium in the viability patients were +21% ± 2.8%. CONCLUSION: A method to quantify SNR gains from TOF within the myocardium has been developed and evaluated. SNR gains within the myocardium are comparable to those observed by established methods. This allows guidance for protocol optimization for TOF systems in cardiac PET.

The impact of prompt gamma compensation on myocardial blood flow measurements with rubidium-82 dynamic PET.

BACKGROUND: Rubidium-82 myocardial perfusion imaging is a well-established technique for assessing myocardial ischemia. With continuing interest on myocardial blood flow (MBF) and myocardial flow reserve (MFR) measurements, there is a requirement to fully appreciate the impact of technical aspects of the process. One such factor for rubidium-82 is prompt gamma compensation (PGC). This study aims to assess the impact of PGC on MBF and MFR calculated from dynamic Rb-82 data. METHODS: Dynamic rest and stress images were acquired on a Siemens Biograph mCT and reconstructed with and without PGC in 50 patients (29 male). MBF and MFR were measured in the three main coronary territories as well as globally. RESULTS: With PGC, statistically significant reductions in MBF were observed in LAD (-6.9%), LCx (-4.8%), and globally (-6.5%) but only in obese patients. Significant increases in MBF were observed in RCA (+6.4%) in only nonobese patients. In very obese patients, differences of up to 40% in MBF were observed between PGC and non-PGC images. In nearly all cases, similar PGC differences were observed at stress and rest so there were no significant differences in MFR; however, in a small number of very obese patients, differences in excess of 20% were observed. CONCLUSION: PGC results in statistically significant changes in MBF, with the greatest reductions observed in the LAD and LCx territories of obese patients. In most cases, the impact on stress and rest data is of similar relative magnitudes and changes to MFR are small.

Harmonizing standardized uptake value recovery between two PET/CT systems from different manufacturers when using resolution modelling and time-of-flight.

PET iterative reconstruction algorithms with resolution modelling (RM) can be used to improve spatial resolution in the images. However, RM has a significant impact on quantification, which raises issues for harmonization across multicentre networks or collaborations. This investigation compared quantification from two modern time-of-flight (TOF) PET/CT systems from different manufacturers with RM with the intention to harmonize recovery. Images of a National Electrical Manufacturers Association image quality phantom with a sphere-to-background concentration ratio of 4 : 1 were acquired on a GE Discovery 710 and a Siemens Biograph mCT and reconstructed with RM and TOF. Voxel dimensions and image noise (background coefficient of variation) were matched. One to five iterations were used with 2 and 4 mm Gaussian filters. Mean and maximum contrast recovery (CR) were measured for the 10, 13, 17 and 22 mm hot phantom spheres. Notable differences in CR for images reconstructed with matched reconstruction parameters were observed between the scanners. A set of parameters was found that reduced differences in CR between scanners. Using these parameters, relative differences for the Biograph compared with the Discovery were -8.1, -3.7, +7 and +0.7% for mean CR and -23.1, -6.9, +9.1 and +0.9% for maximum CR in the 10, 13, 17 and 22 mm spheres, respectively. This study has used a technique of harmonizing standardized uptake value recovery on PET/CT systems from different vendors with advanced reconstructions including TOF and RM using phantom data. Considerable quantitative differences may occur in images, which highlights the need to apply methods such as those used in this work for multicentre studies.

Evaluation of general-purpose collimators against high-resolution collimators with resolution recovery with a view to reducing radiation dose in myocardial perfusion SPECT: A preliminary phantom study.

BACKGROUND: There is a growing focus on reducing radiation dose to patients undergoing myocardial perfusion imaging. This preliminary phantom study aims to evaluate the use of general-purpose collimators with resolution recovery (RR) to allow a reduction in patient radiation dose. METHODS: Images of a cardiac torso phantom with inferior and anterior wall defects were acquired on a GE Infinia and Siemens Symbia T6 using both high-resolution and general-purpose collimators. Imaging time, a surrogate for administered activity, was reduced between 35% and 40% with general-purpose collimators to match the counts acquired with high-resolution collimators. Images were reconstructed with RR with and without attenuation correction. Two pixel sizes were also investigated. Defect contrast was measured. RESULTS: Defect contrast on general-purpose images was superior or comparable to the high-resolution collimators on both systems despite the reduced imaging time. Infinia general-purpose images required a smaller pixel size to be used to maintain defect contrast, while Symbia T6 general-purpose images did not require a change in pixel size to that used for standard myocardial perfusion SPECT. CONCLUSION: This study suggests that general-purpose collimators with RR offer a potential for substantial dose reductions while providing similar or better image quality to images acquired using high-resolution collimators.

Activity concentration measurements using a conjugate gradient (Siemens xSPECT) reconstruction algorithm in SPECT/CT.

The interest in quantitative single photon emission computer tomography (SPECT) shows potential in a number of clinical applications and now several vendors are providing software and hardware solutions to allow 'SUV-SPECT' to mirror metrics used in PET imaging. This brief technical report assesses the accuracy of activity concentration measurements using a new algorithm 'xSPECT' from Siemens Healthcare. SPECT/CT data were acquired from a uniform cylinder with 5, 10, 15 and 20 s/projection and NEMA image quality phantom with 25 s/projection. The NEMA phantom had hot spheres filled with an 8 : 1 activity concentration relative to the background compartment. Reconstructions were performed using parameters defined by manufacturer presets available with the algorithm. The accuracy of activity concentration measurements was assessed. A dose calibrator-camera cross-calibration factor (CCF) was derived from the uniform phantom data. In uniform phantom images, a positive bias was observed, ranging from ∼6% in the lower count images to ∼4% in the higher-count images. On the basis of the higher-count data, a CCF of 0.96 was derived. As expected, considerable negative bias was measured in the NEMA spheres using region mean values whereas positive bias was measured in the four largest NEMA spheres. Nonmonotonically increasing recovery curves for the hot spheres suggested the presence of Gibbs edge enhancement from resolution modelling. Sufficiently accurate activity concentration measurements can easily be measured on images reconstructed with the xSPECT algorithm without a CCF. However, the use of a CCF is likely to improve accuracy further. A manual conversion of voxel values into SUV should be possible, provided that the patient weight, injected activity and time between injection and imaging are all known accurately.

The performance of quantitation methods in the evaluation of cardiac implantable electronic device (CIED) infection: A technical review.

BACKGROUND: Quantitative assessment of [18F]-FDG PET/CT images has been shown to be useful in the diagnosis of cardiac implantable electronic device (CIED) infection. This study aimed to compare the accuracy of various quantitative methods, using the same patient cohort and to assess the utility of dual time point imaging. METHODS: The study comprised a retrospective review of 80 [18F]-FDG PET/CT studies. Of these, 41 were oncological patients with an asymptomatic CIED in situ (Group 1), and 39 were studies performed in patients with symptomatic devices. Of these, 14 were subsequently deemed on follow-up to be non-infected (Group 2), and 25 confirmed as infected post-device extraction (Group 3). Ratios of maximal uptake around the CIED in both the attenuation corrected and non-attenuation corrected images were calculated to regions of normal physiological uptake, along with the maximal standardized uptake value (SUVmax) alone. Receiver operating characteristic analysis was performed for all methods at both time points. Measurement reliability was assessed using the intraclass correlation coefficient (ICC). RESULTS: Using Group 1 as a reference, all methods gave an area under the curve (AUC) greater than 0.93. Using Group 2 as reference, the accuracy varied greatly, with AUC values ranging from 0.71 to 0.97. The hepatic blood pool (HBP) ratio gave the highest AUC values. The calculated ICC values for each method showed the SUVmax and HBP measurement to have the greatest reliability, with values of 1.0 and 0.97, respectively. CONCLUSIONS: Quantitation of [18F] FDG uptake was found to have a high degree of accuracy in confirming the diagnosis of CIED infection. Normalization to HBP uptake was found to give the greatest AUC and demonstrated excellent reliability. Inconsistencies from published data indicate that individual imaging centers should only use published data for guidance.

The assessment of time-of-flight on image quality and quantification with reduced administered activity and scan times in 18F-FDG PET.

OBJECTIVES: The last decade has seen considerable technological innovations in PET detectors with the availability, among other advances, of time-of-flight (TOF). TOF has been shown to increase the signal-to-noise ratio (SNR), which should allow for a reduction in acquired counts while maintaining image quality. METHODS: Fifty-eight patients referred for routine F-flurodeoxyglucose ((18)F-FDG) oncology PET studies were included in this study. Patients with weight below or above 100 kg were prescribed 350 or 400 MBq of (18)F-FDG, respectively. Listmode data were acquired for 2.5 min per bed position and reconstructed with ordered-subset expectation maximization (OSEM) reconstruction. TOF reconstruction was performed on reduced-count data, with two levels of reduction (-20 and -40% for patients <100 kg and -16 and -30% for patients >100 kg) achieved by clipping the listmode data. Liver SNR, mediastinum mean standardized uptake value (SUV(mean)), and lesion maximum standardized uptake value (SUV(max)) were measured in all images. All images were visually assessed as adequate or suboptimal. RESULTS: No significant difference was seen in mediastinum SUV(mean) or lesion SUV(max) when comparing reduced-count TOF with full-count OSEM images. Compared with the original OSEM images, liver SNR was higher for TOF images using the more conservative -20% reduction of counts (P < 0.001, Wilcoxon's signed-rank test), whereas no significant statistical difference was seen with -40% reductions. CONCLUSION: Incorporation of TOF allows for a reduction in acquired counts; this method has been implemented at our institution, with administered activity reduced for all patients to 280 MBq and a reduction in scan times for all but the largest patients. This has significantly reduced the patient radiation dose and improved scanner flexibility and throughput.

Impact of point spread function modeling and time-of-flight on myocardial blood flow and myocardial flow reserve measurements for rubidium-82 cardiac PET.

BACKGROUND: Myocardial flow reserve (MFR) obtained from dynamic cardiac positron emission tomography (PET) with rubidium-82 (Rb-82) has been shown to be a useful measurement in assessing coronary artery disease. Advanced PET reconstructions with point spread function modeling and time-of-flight have been shown to improve image quality but also have an impact on kinetic analysis of dynamic data. This study aims to determine the impact of these algorithms on MFR data. METHODS: Dynamic Rb-82 cardiac PET images from 37 patients were reconstructed with standard and advanced reconstructions. Area under curve (AUC) of the blood input function (BIF), myocardial blood flow (MBF) and MFR were compared with each reconstruction. RESULTS: No significant differences were seen in MFR for the two reconstructions. A relatively small mean difference in MBF data of +11.9% was observed with advanced reconstruction compared with the standard reconstruction but there was considerable variability in the degree of change (95% confidence intervals of -16.2% to +40.0%). Small systematic relative differences were seen for AUC BIF (mean difference of -6.3%; 95% CI -17.5% to +5.4%). CONCLUSION: MFR results from Rb-82 dynamic PET appear to be robust when generated by standard or advanced PET reconstructions. Considerable increases in MBF values may occur with advanced reconstructions, and further work is required to fully understand this.

Impact of point spread function modelling and time of flight on FDG uptake measurements in lung lesions using alternative filtering strategies.

BACKGROUND: The use of maximum standardised uptake value (SUVmax) is commonplace in oncology positron emission tomography (PET). Point spread function (PSF) modelling and time-of-flight (TOF) reconstructions have a significant impact on SUVmax, presenting a challenge for centres with defined protocols for lesion classification based on SUVmax thresholds. This has perhaps led to the slow adoption of these reconstructions. This work evaluated the impact of PSF and/or TOF reconstructions on SUVmax, SUVpeak and total lesion glycolysis (TLG) under two different schemes of post-filtering. METHODS: Post-filters to match voxel variance or SUVmax were determined using a NEMA NU-2 phantom. Images from 68 consecutive lung cancer patients were reconstructed with the standard iterative algorithm along with TOF; PSF modelling - Siemens HD·PET (HD); and combined PSF modelling and TOF - Siemens ultraHD·PET (UHD) with the two post-filter sets. SUVmax, SUVpeak, TLG and signal-to-noise ratio of tumour relative to liver (SNR(T-L)) were measured in 74 lesions for each reconstruction. Relative differences in uptake measures were calculated, and the clinical impact of any changes was assessed using published guidelines and local practice. RESULTS: When matching voxel variance, SUVmax increased substantially (mean increase +32% and +49% for HD and UHD, respectively), potentially impacting outcome in the majority of patients. Increases in SUVpeak were less notable (mean increase +17% and +23% for HD and UHD, respectively). Increases with TOF alone were far less for both measures. Mean changes to TLG were <10% for all algorithms for either set of post-filters. SNR(T-L) were greater than ordered subset expectation maximisation (OSEM) in all reconstructions using both post-filtering sets. CONCLUSIONS: Matching image voxel variance with PSF and/or TOF reconstructions, particularly with PSF modelling and in small lesions, resulted in considerable increases in SUVmax, inhibiting the use of defined protocols for lesion classification based on SUVmax. However, reduced partial volume effects may increase lesion detectability. Matching SUVmax in phantoms translated well to patient studies for PSF reconstruction but less well with TOF, where a small positive bias was observed in patient images. Matching SUVmax significantly reduced voxel variance and potential variability of uptake measures. Finally, TLG may be less sensitive to reconstruction methods compared with either SUVmax or SUVpeak.

Multicomponent synthesis of 1-aryl 1,2,4-triazoles.

A multicomponent (single reactor) process for the synthesis of 1-aryl 1,2,4-triazoles was explored and developed. This transformation prepared the 1,2,4-triazole directly from anilines, amino pyridines, and pyrimidines. The reaction scope was explored with 21 different substrates, and the position of the nitrogen atoms in the newly formed ring was established by (15)N labeling and NMR spectroscopy.