Quantitative evaluation of a deep learning-based framework to generate whole-body attenuation maps using LSO background radiation in long axial FOV PET scanners.

PURPOSE: Attenuation correction is a critically important step in data correction in positron emission tomography (PET) image formation. The current standard method involves conversion of Hounsfield units from a computed tomography (CT) image to construct attenuation maps (µ-maps) at 511 keV. In this work, the increased sensitivity of long axial field-of-view (LAFOV) PET scanners was exploited to develop and evaluate a deep learning (DL) and joint reconstruction-based method to generate µ-maps utilizing background radiation from lutetium-based (LSO) scintillators. METHODS: Data from 18 subjects were used to train convolutional neural networks to enhance initial µ-maps generated using joint activity and attenuation reconstruction algorithm (MLACF) with transmission data from LSO background radiation acquired before and after the administration of 18F-fluorodeoxyglucose (18F-FDG) (µ-mapMLACF-PRE and µ-mapMLACF-POST respectively). The deep learning-enhanced µ-maps (µ-mapDL-MLACF-PRE and µ-mapDL-MLACF-POST) were compared against MLACF-derived and CT-based maps (µ-mapCT). The performance of the method was also evaluated by assessing PET images reconstructed using each µ-map and computing volume-of-interest based standard uptake value measurements and percentage relative mean error (rME) and relative mean absolute error (rMAE) relative to CT-based method. RESULTS: No statistically significant difference was observed in rME values for µ-mapDL-MLACF-PRE and µ-mapDL-MLACF-POST both in fat-based and water-based soft tissue as well as bones, suggesting that presence of the radiopharmaceutical activity in the body had negligible effects on the resulting µ-maps. The rMAE values µ-mapDL-MLACF-POST were reduced by a factor of 3.3 in average compared to the rMAE of µ-mapMLACF-POST. Similarly, the average rMAE values of PET images reconstructed using µ-mapDL-MLACF-POST (PETDL-MLACF-POST) were 2.6 times smaller than the average rMAE values of PET images reconstructed using µ-mapMLACF-POST. The mean absolute errors in SUV values of PETDL-MLACF-POST compared to PETCT were less than 5% in healthy organs, less than 7% in brain grey matter and 4.3% for all tumours combined. CONCLUSION: We describe a deep learning-based method to accurately generate µ-maps from PET emission data and LSO background radiation, enabling CT-free attenuation and scatter correction in LAFOV PET scanners.

First results on kinetic modelling and parametric imaging of dynamic 18F-FDG datasets from a long axial FOV PET scanner in oncological patients.

PURPOSE: To investigate the kinetics of 18F-fluorodeoxyglucose (18F-FDG) by positron emission tomography (PET) in multiple organs and test the feasibility of total-body parametric imaging using an image-derived input function (IDIF). METHODS: Twenty-four oncological patients underwent dynamic 18F-FDG scans lasting 65 min using a long  axial FOV (LAFOV) PET/CT system. Time activity curves (TAC) were extracted from semi-automated segmentations of multiple organs, cerebral grey and white matter, and from vascular structures. The tissue and tumor lesion TACs were fitted using an irreversible two-tissue compartment (2TC) and a Patlak model. Parametric images were also generated using direct and indirect Patlak methods and their performances were evaluated. RESULTS: We report estimates of kinetic parameters and metabolic rate of glucose consumption (MRFDG) for different organs and tumor lesions. In some organs, there were significant differences between MRFDG values estimated using 2TC and Patlak models. No statistically significant difference was seen between MRFDG values estimated using 2TC and Patlak methods in tumor lesions (paired t-test, P = 0.65). Parametric imaging showed that net influx (Ki) images generated using direct and indirect Patlak methods had superior tumor-to-background ratio (TBR) to standard uptake value (SUV) images (3.1- and 3.0-fold mean increases in TBRmean, respectively). Influx images generated using the direct Patlak method had twofold higher contrast-to-noise ratio in tumor lesions compared to images generated using the indirect Patlak method. CONCLUSION: We performed pharmacokinetic modelling of multiple organs using linear and non-linear models using dynamic total-body 18F-FDG images. Although parametric images did not reveal more tumors than SUV images, the results confirmed that parametric imaging furnishes improved tumor contrast. We thus demonstrate the feasibility of total-body kinetic modelling and parametric imaging in basic research and oncological studies. LAFOV PET can enhance dynamic imaging capabilities by providing high sensitivity parametric images and allowing total-body pharmacokinetic analysis.

A CT-less approach to quantitative PET imaging using the LSO intrinsic radiation for long-axial FOV PET scanners.

PURPOSE: Long-axial field-of-view (FOV) positron emission tomography (PET) scanners have gained a lot of interest in the recent years. Such scanners provide increased sensitivity and enable unique imaging opportunities that were not previously feasible. Benefiting from the high sensitivity of a long-axial FOV PET scanner, we studied a computed tomography (CT)-less reconstruction algorithm for the Siemens Biograph Vision Quadra with an axial FOV of 106 cm. METHODS: In this work, the background radiation from radioisotope lutetium-176 in the scintillators was used to create an initial estimate of the attenuation maps. Then, joint activity and attenuation reconstruction algorithms were used to create an improved attenuation map of the object. The final attenuation maps were then used to reconstruct quantitative PET images, which were compared against CT-based PET images. The proposed method was evaluated on data from three patients who underwent a flurodeoxyglucouse PET scan. RESULTS: Segmentation of the PET images of the three studied patients showed an average quantitative error of 6.5%-8.3% across all studied organs when using attenuation maps from maximum likelihood estimation of attenuation and activity and 5.3%-6.6% when using attenuation maps from maximum likelihood estimation of activity and attenuation correction coefficients. CONCLUSIONS: Benefiting from the background radiation of lutetium-based scintillators, a quantitative CT-less PET imaging technique was evaluated in this work.

Respiratory Motion Compensation for PET/CT with Motion Information Derived from Matched Attenuation-Corrected Gated PET Data.

Respiratory motion degrades the detection and quantification capabilities of PET/CT imaging. Moreover, mismatch between a fast helical CT image and a time-averaged PET image due to respiratory motion results in additional attenuation correction artifacts and inaccurate localization. Current motion compensation approaches typically have 3 limitations: the mismatch among respiration-gated PET images and the CT attenuation correction (CTAC) map can introduce artifacts in the gated PET reconstructions that can subsequently affect the accuracy of the motion estimation; sinogram-based correction approaches do not correct for intragate motion due to intracycle and intercycle breathing variations; and the mismatch between the PET motion compensation reference gate and the CT image can cause an additional CT-mismatch artifact. In this study, we established a motion correction framework to address these limitations. Methods: In the proposed framework, the combined emission-transmission reconstruction algorithm was used for phase-matched gated PET reconstructions to facilitate the motion model building. An event-by-event nonrigid respiratory motion compensation method with correlations between internal organ motion and external respiratory signals was used to correct both intracycle and intercycle breathing variations. The PET reference gate was automatically determined by a newly proposed CT-matching algorithm. We applied the new framework to 13 human datasets with 3 different radiotracers and 323 lesions and compared its performance with CTAC and non-attenuation correction (NAC) approaches. Validation using 4-dimensional CT was performed for one lung cancer dataset. Results: For the 10 18F-FDG studies, the proposed method outperformed (P < 0.006) both the CTAC and the NAC methods in terms of region-of-interest-based SUVmean, SUVmax, and SUV ratio improvements over no motion correction (SUVmean: 19.9% vs. 14.0% vs. 13.2%; SUVmax: 15.5% vs. 10.8% vs. 10.6%; SUV ratio: 24.1% vs. 17.6% vs. 16.2%, for the proposed, CTAC, and NAC methods, respectively). The proposed method increased SUV ratios over no motion correction for 94.4% of lesions, compared with 84.8% and 86.4% using the CTAC and NAC methods, respectively. For the 2 18F-fluoropropyl-(+)-dihydrotetrabenazine studies, the proposed method reduced the CT-mismatch artifacts in the lower lung where the CTAC approach failed and maintained the quantification accuracy of bone marrow where the NAC approach failed. For the 18F-FMISO study, the proposed method outperformed both the CTAC and the NAC methods in terms of motion estimation accuracy at 2 lung lesion locations. Conclusion: The proposed PET/CT respiratory event-by-event motion-correction framework with motion information derived from matched attenuation-corrected PET data provides image quality superior to that of the CTAC and NAC methods for multiple tracers.

Metal Artifact Reduction of CT Scans to Improve PET/CT.

In recent years, different metal artifact reduction methods have been developed for CT. These methods have only recently been introduced for PET/CT even though they could be beneficial for interpretation, segmentation, and quantification of the PET/CT images. In this study, phantom and patient scans were analyzed visually and quantitatively to measure the effect on PET images of iterative metal artifact reduction (iMAR) of CT data. Methods: The phantom consisted of 2 types of hip prostheses in a solution of 18F-FDG and water. 18F-FDG PET/CT scans of 14 patients with metal implants (either dental implants, hip prostheses, shoulder prostheses, or pedicle screws) and 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA) PET/CT scans of 7 patients with hip prostheses were scored by 2 experienced nuclear medicine physicians to analyze clinical relevance. For all patients, a lesion was located in the field of view of the metal implant. Phantom and patients were scanned in a PET/CT scanner. The standard low-dose CT scans were processed with the iMAR algorithm. The PET data were reconstructed using attenuation correction provided by both standard CT and iMAR-processed CT. Results: For the phantom scans, cold artifacts were visible on the PET image. There was a 30% deficit in 18F-FDG concentration, which was restored by iMAR processing, indicating that metal artifacts on CT images induce quantification errors in PET data. The iMAR algorithm was useful for most patients. When iMAR was used, the confidence in interpretation increased or stayed the same, with an average improvement of 28% ± 20% (scored on a scale of 0%-100% confidence). The SUV increase or decrease depended on the type of metal artifact. The mean difference in absolute values of SUVmean of the lesions was 3.5% ± 3.3%. Conclusion: The iMAR algorithm increases the confidence of the interpretation of the PET/CT scan and influences the SUV. The added value of iMAR depends on the indication for the PET/CT scan, location and size/type of the prosthesis, and location and extent of the disease.

LSO background radiation as a transmission source using time of flight.

LSO scintillators (Lu2Sio5:Ce) have a background radiation which originates from the isotope Lu-176 that is present in natural occurring lutetium. The decay that occurs in this isotope is a beta decay that is in coincidence with cascade gamma emissions with energies of 307,202 and 88 keV. The coincidental nature of the beta decay with the gamma emissions allow for separation of emission data originating from a positron annihilation event from transmission type data from the Lu-176 beta decay. By using the time of flight information, and information of the chord length between two LSO pixels in coincidence as a result of a beta emission and emitted gamma, a second time window can be set to observe transmission events simultaneously to emission events. Using the time when the PET scanner is not actively acquiring positron emission data, a continuous blank can be acquired and used to reconstruct a transmission image. With this blank and the measured transmission data, a transmission image can be reconstructed. This reconstructed transmission image can be used to perform emission data corrections such as attenuation correction and scatter corrections or starting images for algorithms that estimate emission and attenuation simultaneously. It is observed that the flux of the background activity is high enough to create useful transmission images with an acquisition time of 10 min.

An assessment of the impact of incorporating time-of-flight information into clinical PET/CT imaging.

The introduction of fast scintillators with good stopping power for 511-keV photons has renewed interest in time-of-flight (TOF) PET. The ability to measure the difference between the arrival times of a pair of photons originating from positron annihilation improves the image signal-to-noise ratio (SNR). The level of improvement depends upon the extent and distribution of the positron activity and the time resolution of the PET scanner. While specific estimates can be made for phantom imaging, the impact of TOF PET is more difficult to quantify in clinical situations. The results presented here quantify the benefit of TOF in a challenging phantom experiment and then assess both qualitatively and quantitatively the impact of incorporating TOF information into the reconstruction of clinical studies. A clear correlation between patient body mass index and gain in SNR was observed in this study involving 100 oncology patient studies, with a gain due to TOF ranging from 1.1 to 1.8, which is consistent with the 590-ps time resolution of the TOF PET scanner. The visual comparison of TOF and non-TOF images performed by two nuclear medicine physicians confirmed the advantages of incorporating TOF into the reconstruction, advantages that include better definition of small lesions and image details, improved uniformity, and noise reduction.

Experimental comparison of lesion detectability for four fully-3D PET reconstruction schemes.

The objective of this work was to evaluate the lesion detection performance of four fully-3D positron emission tomography (PET) reconstruction schemes using experimentally acquired data. A multi-compartment anthropomorphic phantom was set up to mimic whole-body (18)F-fluorodeoxyglucose (FDG) cancer imaging and scanned 12 times in 3D mode, obtaining count levels typical of noisy clinical scans. Eight of the scans had 26 (68)Ge "shell-less" lesions (6, 8-, 10-, 12-, 16-mm diameter) placed throughout the phantom with various target:background ratios. This provided lesion-present and lesion-absent datasets with known truth appropriate for evaluating lesion detectability by localization receiver operating characteristic (LROC) methods. Four reconstruction schemes were studied: 1) Fourier rebinning (FORE) followed by 2D attenuation-weighted ordered-subsets expectation-maximization, 2) fully-3D AW-OSEM, 3) fully-3D ordinary-Poisson line-of-response (LOR-)OSEM; and 4) fully-3D LOR-OSEM with an accurate point-spread function (PSF) model. Two forms of LROC analysis were performed. First, a channelized nonprewhitened (CNPW) observer was used to optimize processing parameters (number of iterations, post-reconstruction filter) for the human observer study. Human observers then rated each image and selected the most-likely lesion location. The area under the LROC curve ( A(LROC)) and the probability of correct localization were used as figures-of-merit. The results of the human observer study found no statistically significant difference between FORE and AW-OSEM3D ( A(LROC)=0.41 and 0.36, respectively), an increase in lesion detection performance for LOR-OSEM3D ( A(LROC)=0.45, p=0.076), and additional improvement with the use of the PSF model ( A(LROC)=0.55, p=0.024). The numerical CNPW observer provided the same rankings among algorithms, but obtained different values of A(LROC). These results show improved lesion detection performance for the reconstruction algorithms with more sophisticated statistical and imaging models as compared to the previous-generation algorithms.