90Y post-radioembolization clinical assessment with whole-body Biograph Vision Quadra PET/CT: image quality, tumor, liver and lung dosimetry.

PURPOSE: Evaluation of 90Y liver radioembolization post-treatment clinical data using a whole-body Biograph Vision Quadra PET/CT to investigate the potential of protocol optimization in terms of scan time and dosimetry. METHODS: 17 patients with hepatocellular carcinoma with median (IQR) injected activity 2393 (1348-3298) MBq were included. Pre-treatment dosimetry plan was based on 99mTc-MAA SPECT/CT with Simplicit90Y™ and post-treatment validation with Quadra using Simplicit90Y™ and HERMIA independently. Regarding the image analysis, mean and peak SNR, the coefficient of variation (COV) and lesion-to-background ratio (LBR) were evaluated. For the post-treatment dosimetry validation, the mean tumor, whole liver and lung absorbed dose evaluation was performed using Simplicit90Y and HERMES. Images were reconstructed with 20-, 15-, 10-, 5- and 1- min sinograms with 2, 4, 6 and 8 iterations. Wilcoxon signed rank test was used to show statistical significance (p < 0.05). RESULTS: There was no difference of statistical significance between 20- and 5- min reconstructed times for the peak SNR, COV and LBR. In addition, there was no difference of statistical significance between 20- and 1- min reconstructed times for all dosimetry metrics. Lung dosimetry showed consistently lower values than the expected. Tumor absorbed dose based on Simplicit90Y™ was similar to the expected while HERMES consistently underestimated significantly the measured tumor absorbed dose. Finally, there was no difference of statistical significance between expected and measured tumor, whole liver and lung dose for all reconstruction times. CONCLUSION: In this study we evaluated, in terms of image quality and dosimetry, whole-body PET clinical images of patients after having been treated with 90Y microspheres radioembolization for liver cancer. Compared to the 20-min standard scan, the simulated 5-min reconstructed images provided equal image peak SNR and noise behavior, while performing also similarly for post-treatment dosimetry of tumor, whole liver and lung absorbed doses.

FDG imaging with long-axial field-of-view PET/CT in patients with high blood glucose-a matched pair analysis.

PURPOSE: High blood glucose (hBG) in patients undergoing [18F]FDG PET/CT scans often results in rescheduling the examination, which may lead to clinical delay for the patient and decrease productivity for the department. The aim of this study was to evaluate whether long-axial field-of-view (LAFOV) PET/CT can minimize the effect of altered bio-distribution in hBG patients and is able to provide diagnostic image quality in hBG situations. MATERIALS AND METHODS: Oncologic patients with elevated blood glucose (≥ 8.0 mmol/l) and normal blood glucose (< 8.0 mmol/l, nBG) levels were matched for tumor entity, gender, age, and BMI. hBG patients were further subdivided into two groups (BG 8-11 mmol/l and BG > 11 mmol/l). Tracer uptake in the liver, muscle, and tumor was evaluated. Furthermore, image quality was compared between long acquisitions (ultra-high sensitivity mode, 360 s) on a LAFOV PET/CT and routine acquisitions equivalent to a short-axial field-of-view scanner (simulated (sSAFOV), obtained with high sensitivity mode, 120 s). Tumor-to-background ratio (TBR) and contrast-to-noise ratio (CNR) were used as the main image quality criteria. RESULTS: Thirty-one hBG patients met the inclusion criteria and were matched with 31 nBG patients. Overall, liver uptake was significantly higher in hBG patients (SUVmean, 3.07 ± 0.41 vs. 2.37 ± 0.33; p = 0.03), and brain uptake was significantly lower (SUVmax, 7.58 ± 0.74 vs. 13.38 ± 3.94; p < 0.001), whereas muscle (shoulder/gluteal) uptake showed no statistically significant difference. Tumor uptake was lower in hBG patients, resulting in a significantly lower TBR in the hBG cohort (3.48 ± 0.74 vs. 5.29 ± 1.48, p < 0.001). CNR was higher in nBG compared to hBG patients (12.17 ± 4.86 vs. 23.31 ± 12.22, p < 0.001). However, subgroup analysis of nBG 8-11 mmol/l on sSAFOV PET/CT compared to hBG (> 11 mmol/l) patients examined with LAFOV PET/CT showed no statistical significant difference in CNR (19.84 ± 8.40 vs. 17.79 ± 9.3, p = 0.08). CONCLUSION: While elevated blood glucose (> 11 mmol) negatively affected TBR and CNR in our cohort, the images from a LAFOV PET-scanner had comparable CNR to PET-images acquired from nBG patients using sSAFOV PET/CT. Therefore, we argue that oncologic patients with increased blood sugar levels might be imaged safely with LAFOV PET/CT when rescheduling is not feasible.

The clinical acceptability of short versus long duration acquisitions for head and neck cancer using long-axial field-of-view PET/CT: a retrospective evaluation.

PURPOSE: To evaluate the utility of long duration (10 min) acquisitions compared to standard 4 min scans in the evaluation of head and neck cancer (HNC) using a long-axial field-of-view (LAFOV) system in 2-[18F]FDG PET/CT. METHODS: HNC patients undergoing LAFOV PET/CT were included retrospectively according to a predefined sample size calculation. For each acquisition, FDG avid lymph nodes (LN) which were highly probable or equivocal for malignancy were identified by two board certified nuclear medicine physicians in consensus. The aim of this study was to establish the clinical acceptability of short-duration (4 min, C40%) acquisitions compared to full-count (10 min, C100%) in terms of the detection of LN metastases in HNC. Secondary endpoints were the positive predictive value for LN status (PPV) and comparison of SUVmax at C40% and C100%. Histology reports or confirmatory imaging were the reference standard. RESULTS: A total of 1218 records were screened and target recruitment was met with n = 64 HNC patients undergoing LAFOV. Median age was 65 years (IQR: 59-73). At C40%, a total of 387 lesions were detected (highly probable LN n = 274 and equivocal n = 113. The total number of lesions detected at C100% acquisition was 439, of them 291 (66%) highly probable LN and 148 (34%) equivocal. Detection rate between the two acquisitions did not demonstrate any significant differences (Pearson's Chi-Square test, p = 0.792). Sensitivity, specificity, PPV, NPV and accuracy for C40% were 83%, 44%, 55%, 76% and 36%, whilst for C100% were 85%, 56%, 55%, 85% and 43%, respectively. The improved accuracy reached borderline significance (p = 0.057). At the ROC analysis, lower SUVmax was identified for C100% (3.5) compared to C40% (4.5). CONCLUSION: In terms of LN detection, C40% acquisitions showed no significant difference compared to the C100% acquisitions. There was some improvement for lesions detection at C100%, with a small increment in accuracy reaching borderline significance, suggestive that the higher sensitivity afforded by LAFOV might translate to improved clinical performance in some patients.

Internal dosimetry study of [82Rb]Cl using a long axial field-of-view PET/CT.

PURPOSE: Long axial field-of-view (LAFOV) positron emission tomography (PET) systems allow to image all major organs with one bed position, which is particularly useful for acquiring whole-body dynamic data using short-lived radioisotopes like 82Rb. METHODS: We determined the absorbed dose in target organs of three subjects (29, 40, and 57 years old) using two different methods, i.e., MIRD and voxel dosimetry. The subjects were injected with 407.0 to 419.61 MBq of [82Rb]Cl and were scanned dynamically for 7 min with a LAFOV PET/CT scanner. RESULTS: Using the MIRD formalism and voxel dosimetry, the absorbed dose ranged from 1.84 to 2.78 µGy/MBq (1.57 to 3.92 µGy/MBq for voxel dosimetry) for the heart wall, 2.76 to 5.73 µGy/MBq (3.22 to 5.37 µGy/MBq for voxel dosimetry) for the kidneys, and 0.94 to 1.88 µGy/MBq (0.98 to 1.92 µGy/MBq for voxel dosimetry) for the lungs. The total body effective dose lied between 0.50 and 0.76 µSv/MBq. CONCLUSION: Our study suggests that the radiation dose associated with [82Rb]Cl PET/CT can be assessed by means of dynamic LAFOV PET and that it is lower compared to literature values.

Long-axial field-of-view PET/CT for the assessment of inflammation in calcified coronary artery plaques with [68 Ga]Ga-DOTA-TOC.

PURPOSE: Inflamed, prone-to-rupture coronary plaques are an important cause of myocardial infarction and their early identification is crucial. Atherosclerotic plaques are characterized by overexpression of the type-2 somatostatin receptor (SST2) in activated macrophages. SST2 ligand imaging (e.g. with [68 Ga]Ga-DOTA-TOC) has shown promise in detecting and quantifying the inflammatory activity within atherosclerotic plaques. However, the sensitivity of standard axial field of view (SAFOV) PET scanners may be suboptimal for imaging coronary arteries. Long-axial field of view (LAFOV) PET/CT scanners may help overcome this limitation. We aim to assess the ability of [68 Ga]Ga-DOTA-TOC LAFOV-PET/CT in detecting calcified, SST2 overexpressing coronary artery plaques. METHODS: In this retrospective study, 108 oncological patients underwent [68 Ga]Ga-DOTA-TOC PET/CT on a LAFOV system. [68 Ga]Ga-DOTA-TOC uptake and calcifications in the coronary arteries were evaluated visually and semi-quantitatively. Data on patients' cardiac risk factors and coronary artery calcium score were also collected. Patients were followed up for 21.5 ± 3.4 months. RESULTS: A total of 66 patients (61.1%) presented with calcified coronary artery plaques. Of these, 32 patients had increased [68 Ga]Ga-DOTA-TOC uptake in at least one coronary vessel (TBR: 1.65 ± 0.53). Patients with single-vessel calcifications showed statistically significantly lower uptake (SUVmax 1.10 ± 0.28) compared to patients with two- (SUVmax 1.31 ± 0.29, p < 0.01) or three-vessel calcifications (SUVmax 1.24 ± 0.33, p < 0.01). There was a correlation between coronary artery calcium score (CACS) and [68 Ga]Ga-DOTA-TOC uptake, especially in the LAD (p = 0.02). Stroke and all-cause death occurred more frequently in patients with increased [68 Ga]Ga-DOTA-TOC uptake (15.63% vs. 0%; p:0.001 and 21.88% vs. 6.58%; p: 0.04, respectively) during the follow-up period. CONCLUSION: [68 Ga]Ga-DOTA-TOC as a marker for the macrophage activity can reveal unknown cases of inflamed calcified coronary artery plaques using a LAFOV PET system. [68 Ga]Ga-DOTA-TOC uptake increased with the degree of calcification and correlated with higher risk of stroke and all-cause death. [68 Ga]Ga-DOTA-TOC LAFOV PET/CT may be useful to assess patients' cardiovascular risk.

Long-axial field-of-view PET/CT improves radiomics feature reliability.

PURPOSE: To assess the influence of long-axial field-of-view (LAFOV) PET/CT systems on radiomics feature reliability, to assess the suitability for short-duration or low-activity acquisitions for textural feature analysis and to investigate the influence of acceptance angle. METHODS: 34 patients were analysed: twelve patients underwent oncological 2-[18F]-FDG PET/CT, fourteen [18F]PSMA-1007 and eight [68Ga]Ga-DOTATOC. Data were obtained using a 106 cm LAFOV system for 10 min. Sinograms were generated from list-mode data corresponding to scan durations of 2, 5, 10, 20, 30, 60, 120, 240, 360 and 600s using both standard (minimum ring difference MRD 85 crystals) and maximum acceptance angles (MRD 322). Target lesions were segmented and radiomics features were calculated. To assess feature correlation, Pearson's product-moment correlation coefficient (PPMCC) was calculated with respect to the full duration acquisition for MRD 85 and 322 respectively. The number of features with excellent (r > 0.9), moderate (r > 0.7 and < 0.9) and poor (r ≤ 0.7) correlation was compared as a measure of feature stability. Intra-class heterogeneity was assessed by means of the quartile coefficient of dispersion. RESULTS: As expected, PPMCC improved with acquisition time for all features. By 240s almost all features showed at least moderate agreement with the full count (C100%) data, and by 360s almost all showed excellent agreement. Compared to standard-axial field of view (SAFOV) equivalent scans, fewer features showed moderate or poor agreement, and this was most pronounced for [68Ga]Ga-DOTATOC. Data obtained at C100% at MRD 322 were better able to capture between-patient heterogeneities. CONCLUSION: The improved feature reliability at longer acquisition times and higher MRD demonstrate the advantages of high sensitivity LAFOV systems for reproducible and low-noise data. High fidelity between MRD 85 and MRD 322 was seen at all scan durations > 2s. When contrasted with data comparable to a simulated SAFOV acquisition, full-count and full-MRD data were better able to capture underlying feature heterogeneities.

Whole-Body Multiparametric PET in Clinical Oncology: Current Status, Challenges, and Opportunities.

The interpretation of clinical oncologic PET studies has historically used static reconstructions based on SUVs. SUVs and SUV-based images have important limitations, including dependence on uptake times and reduced conspicuity of tracer-avid lesions in organs with high background uptake. The acquisition of dynamic PET images enables additional PET reconstructions via Patlak modeling, which assumes that a tracer is irreversibly trapped by tissues of interest. The resulting multiparametric PET images capture a tracer's net trapping rate (Ki) and apparent volume of distribution (VD), separating the contributions of bound and free tracer fractions to the PET signal captured in the SUV. Potential benefits of multiparametric PET include higher quantitative stability, superior lesion conspicuity, and greater accuracy for differentiating malignant and benign lesions. However, the imaging protocols necessary for multiparametric PET are inherently more complex and time-intensive, despite the recent introduction of automated or semiautomated scanner-based reconstruction packages. In this Review, we examine the current state of multiparametric PET in whole-body oncologic imaging. We summarize the Patlak methodology and relevant tracer kinetics, discuss clinical workflows and protocol considerations, and highlight clinical challenges and opportunities. We aim to help oncologic imagers make informed decisions about whether to implement multiparametric PET in their clinical practices.

Combined [68 Ga]Ga-PSMA-11 and low-dose 2-[18F]FDG PET/CT using a long-axial field of view scanner for patients referred for [177Lu]-PSMA-radioligand therapy.

PURPOSE: Performing 2-[18F]FDG PET/CT in addition to a PSMA-ligand PET/CT can assist in the detection of lesions with low PSMA expression and may help in prognostication and identification of patients who likely benefit from PSMA-radioligand therapy (PSMA-RLT). However, the cost and time needed for a separate PET/CT examination might hinder its routine implementation. In this communication, we present our initial experiences with additional low-dose 2-[18F]FDG PET/CT as part of a dual-tracer and same-day imaging protocol which exploits the higher sensitivity exhibited by long-axial field-of-view (LAFOV) and total-body PET/CT systems and demonstrates its feasibility. METHODS: Fourteen patients referred for evaluation for PSMA-RLT received [68 Ga]Ga-PSMA-11 PET/CT at 1 h p.i. with a standard activity of 150 MBq and an additional low-dose 2-[18F]FDG PET/CT with 40 MBq 1 h thereafter using a long-axial field-of-view PET/CT system in a single sitting and as per institutional protocol. Scans were scrutinized by two experienced nuclear medicine physicians for mismatch findings. RESULTS: The combined protocol identified additional lesions with low or absent PSMA-expression but high FDG-avidity in 1/14 (7%) patients. The protocol was easily implemented and well tolerated by all patients. CONCLUSION: Additional low-dose 2-[18F]FDG-PET/CT is feasible as part of a same-day imaging protocol and can help reveal lesions of low PSMA avidity as part of therapy assessment for [177Lu]-PSMA radioligand therapy and demonstrates higher sensitivity compared to [68 Ga]Ga-PSMA-11 PET/CT alone in some patients.

Phantom-based evaluation of yttrium-90 datasets using biograph vision quadra.

PURPOSE: The image quality characteristics of two NEMA phantoms with yttrium-90 (90Y) were evaluated on a long axial field-of-view (AFOV) PET/CT. The purpose was to identify the optimized reconstruction setup for the imaging of patients with hepatocellular carcinoma after 90Y radioembolization. METHODS: Two NEMA phantoms were used, where one had a 1:10 sphere to background activity concentration ratio and the second had cold background. Reconstruction parameters used are as follows: iterations 2 to 8, Gaussian filter 2- to 6-mm full-width-at-half-maximum, reconstruction matrices 440 × 440 and 220 × 220, high sensitivity (HS), and ultra-high sensitivity (UHS) modes. 50-, 40-, 30-, 20-, 10-, and 5-min acquisitions were reconstructed. The measurements included recovery coefficients (RC), signal-to-noise ratio (SNR), background variability, and lung error which measures the residual error in the corrections. Patient data were reconstructed with 20-, 10-, 5-, and 1-min time frames and evaluated in terms of SNR. RESULTS: The RC for the hot phantom was 0.36, 0.45, 0.53, 0.63, 0.68, and 0.84 for the spheres with diameters of 10, 13, 17, 22, 28, and 37 mm, respectively, for UHS 2 iterations, a 220 × 220 matrix, and 50-min acquisition. The RC values did not differ with acquisition times down to 20 min. The SNR was the highest for 2 iterations, measured 11.7, 16.6, 17.6, 19.4, 21.9, and 27.7 while the background variability was the lowest (27.59, 27.08, 27.36, 26.44, 30.11, and 33.51%). The lung error was 18%. For the patient dataset, the SNR was 19%, 20%, 24%, and 31% higher for 2 iterations compared to 4 iterations for 20-, 10-, 5-, and 1-min time frames, respectively. CONCLUSIONS: This study evaluates the NEMA image quality of a long AFOV PET/CT scanner with 90Y. It provides high RC for the smallest sphere compared to other standard AFOV scanners at shorter scan times. The maximum patient SNR was for 2 iterations, 20 min, while 5 min delivers images with acceptable SNR.

Feasibility of using abbreviated scan protocols with population-based input functions for accurate kinetic modeling of [18F]-FDG datasets from a long axial FOV PET scanner.

BACKGROUND: Accurate kinetic modeling of 18F-fluorodeoxyglucose ([18F]-FDG) positron emission tomography (PET) data requires accurate knowledge of the available tracer concentration in the plasma during the scan time, known as the arterial input function (AIF). The gold standard method to derive the AIF requires collection of serial arterial blood samples, but the introduction of long axial field of view (LAFOV) PET systems enables the use of non-invasive image-derived input functions (IDIFs) from large blood pools such as the aorta without any need for bed movement. However, such protocols require a prolonged dynamic PET acquisition, which is impractical in a busy clinical setting. Population-based input functions (PBIFs) have previously shown potential in accurate Patlak analysis of [18F]-FDG datasets and can enable the use of shortened dynamic imaging protocols. Here, we exploit the high sensitivity and temporal resolution of a LAFOV PET system and explore the use of PBIF with abbreviated protocols in [18F]-FDG total body kinetic modeling. METHODS: Dynamic PET data were acquired in 24 oncological subjects for 65 min following the administration of [18F]-FDG. IDIFs were extracted from the descending thoracic aorta, and a PBIF was generated from 16 datasets. Five different scaled PBIFs (sPBIFs) were generated by scaling the PBIF with the AUC of IDIF curve tails using various portions of image data (35-65, 40-65, 45-65, 50-65, and 55-65 min post-injection). The sPBIFs were compared with the IDIFs using the AUCs and Patlak Ki estimates in tumor lesions and cerebral gray matter. Patlak plot start time (t*) was also varied to evaluate the performance of shorter acquisitions on the accuracy of Patlak Ki estimates. Patlak Ki estimates with IDIF and t* = 35 min were used as reference, and mean bias and precision (standard deviation of bias) were calculated to assess the relative performance of different sPBIFs. A comparison of parametric images generated using IDIF and sPBIFs was also performed. RESULTS: There was no statistically significant difference between AUCs of the IDIF and sPBIFs (Wilcoxon test: P > 0.05). Excellent agreement was shown between Patlak Ki estimates obtained using sPBIF and IDIF. Using the sPBIF55-65 with the Patlak model, 20 min of PET data (i.e., 45 to 65 min post-injection) achieved < 15% precision error in Ki estimates in tumor lesions compared to the estimates with the IDIF. Parametric images reconstructed using the IDIF and sPBIFs with and without an abbreviated protocol were visually comparable. Using Patlak Ki generated with an IDIF and 30 min of PET data as reference, Patlak Ki images generated using sPBIF55-65 with 20 min of PET data (t* = 45 min) provided excellent image quality with structural similarity index measure > 0.99 and peak signal-to-noise ratio > 55 dB. CONCLUSION: We demonstrate the feasibility of performing accurate [18F]-FDG Patlak analysis using sPBIFs with only 20 min of PET data from a LAFOV PET scanner.

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.

An encoder-decoder network for direct image reconstruction on sinograms of a long axial field of view PET.

PURPOSE: Deep learning is an emerging reconstruction method for positron emission tomography (PET), which can tackle complex PET corrections in an integrated procedure. This paper optimizes the direct PET reconstruction from sinogram on a long axial field of view (LAFOV) PET. METHODS: This paper proposes a novel deep learning architecture to reduce the biases during direct reconstruction from sinograms to images. This architecture is based on an encoder-decoder network, where the perceptual loss is used with pre-trained convolutional layers. It is trained and tested on data of 80 patients acquired from recent Siemens Biograph Vision Quadra long axial FOV (LAFOV) PET/CT. The patients are randomly split into a training dataset of 60 patients, a validation dataset of 10 patients, and a test dataset of 10 patients. The 3D sinograms are converted into 2D sinogram slices and used as input to the network. In addition, the vendor reconstructed images are considered as ground truths. Finally, the proposed method is compared with DeepPET, a benchmark deep learning method for PET reconstruction. RESULTS: Compared with DeepPET, the proposed network significantly reduces the root-mean-squared error (NRMSE) from 0.63 to 0.6 (p < 0.01) and increases the structural similarity index (SSIM) and peak signal-to-noise ratio (PSNR) from 0.93 to 0.95 (p < 0.01) and from 82.02 to 82.36 (p < 0.01), respectively. The reconstruction time is approximately 10 s per patient, which is shortened by 23 times compared with the conventional method. The errors of mean standardized uptake values (SUVmean) for lesions between ground truth and the predicted result are reduced from 33.5 to 18.7% (p = 0.03). In addition, the error of max SUV is reduced from 32.7 to 21.8% (p = 0.02). CONCLUSION: The results demonstrate the feasibility of using deep learning to reconstruct images with acceptable image quality and short reconstruction time. It is shown that the proposed method can improve the quality of deep learning-based reconstructed images without additional CT images for attenuation and scattering corrections. This study demonstrated the feasibility of deep learning to rapidly reconstruct images without additional CT images for complex corrections from actual clinical measurements on LAFOV PET. Despite improving the current development, AI-based reconstruction does not work appropriately for untrained scenarios due to limited extrapolation capability and cannot completely replace conventional reconstruction currently.

Abbreviated scan protocols to capture 18F-FDG kinetics for long axial FOV PET scanners.

PURPOSE: Kinetic parameters from dynamic 18F-fluorodeoxyglucose (FDG) imaging offer complementary insights to the study of disease compared to static clinical imaging. However, dynamic imaging protocols are cumbersome due to the long acquisition time. Long axial field-of-view (LAFOV) PET scanners (> 70 cm) have two advantages for dynamic imaging over clinical PET scanners with a standard axial field-of-view (SAFOV; 16-30 cm). The large axial coverage enables multi-organ dynamic imaging in a single bed position, and the high sensitivity may enable clinically routine abbreviated dynamic imaging protocols. METHODS: In this work, we studied two abbreviated protocols using data from a 65-min dynamic 18F-FDG scan: (A) dynamic imaging immediately post-injection (p.i.) for variable durations, and (B) dynamic imaging immediately p.i. for variable durations plus a 1-h p.i. (5-min-long) datapoint. Nine cancer patients were imaged on the Biograph Vision Quadra (Siemens Healthineers). Time-activity curves over the lesions (N = 39) were fitted using the Patlak graphical analysis and a 2-tissue-compartment (2C, k4 = 0) model for variable scan durations (5-60 min). Kinetic parameters from the complete dataset served as the reference. Lesions from all cancers were grouped into low, medium, and high flux groups, and bias and precision of Ki (Patlak) and Ki, K1, k2, and k3 (2C) were calculated for each group. RESULTS: Using only early dynamic data with the 2C (or Patlak) model, accurate quantification of Ki required at least 50 (or 55) min of dynamic data for low flux lesions, at least 30 (or 40) min for medium flux lesions, and at least 15 (or 20) min for high flux lesions to achieve both 10% bias and precision. The addition of the final (5-min) datapoint allowed for accurate quantification of Ki with a bias and precision of 10% using only 10-15 min of early dynamic data for either model. CONCLUSION: Dynamic imaging for 10-15 min immediately p.i. followed by a 5-min scan at 1-h p.i can accurately and precisely quantify 18F-FDG on a long axial FOV scanner, potentially allowing for more widespread use of dynamic 18F-FDG imaging.

Microglial activation and blood-brain barrier permeability in cerebral small vessel disease.

Cerebral small vessel disease (SVD) is a major cause of stroke and dementia. The underlying pathogenesis is poorly understood, but both neuroinflammation and increased blood-brain barrier permeability have been hypothesized to play a role, and preclinical studies suggest the two processes may be linked. We used PET magnetic resonance to simultaneously measure microglial activation using the translocator protein radioligand 11C-PK11195, and blood-brain barrier permeability using dynamic contrast enhanced MRI. A case control design was used with two disease groups with sporadic SVD (n = 20), monogenic SVD (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, CADASIL), and normal controls (n = 20) were studied. Hotspots of increased glial activation and blood-brain barrier permeability were identified as values greater than the 95th percentile of the distribution in controls. In sporadic SVD there was an increase in the volume of hotspots of both 11C-PK11195 binding (P = 0.003) and blood-brain barrier permeability (P = 0.007) in the normal appearing white matter, in addition to increased mean blood-brain barrier permeability (P < 0.001). In CADASIL no increase in blood-brain barrier permeability was detected; there was a non-significant trend to increased 11C-PK11195 binding (P = 0.073). Hotspots of 11C-PK11195 binding and blood-brain barrier permeability were not spatially related. A panel of 93 blood biomarkers relating to cardiovascular disease, inflammation and endothelial activation were measured in each participant; principal component analysis was performed and the first component related to blood-brain barrier permeability and microglial activation. Within the sporadic SVD group both hotspot and mean volume blood-brain barrier permeability values in the normal appearing white matter were associated with dimension 1 (ß = 0.829, P = 0.017, and ß = 0.976, P = 0.003, respectively). There was no association with 11C-PK11195 binding. No associations with blood markers were found in the CADASIL group. In conclusion, in sporadic SVD both microglial activation and increased blood-brain barrier permeability occur, but these are spatially distinct processes. No evidence of increased blood-brain barrier permeability was found in CADASIL.

PRESERVE: Randomized Trial of Intensive Versus Standard Blood Pressure Control in Small Vessel Disease.

[Figure: see text].

Validation of a combined image derived input function and venous sampling approach for the quantification of [18F]GE-179 PET binding in the brain.

Blood-based kinetic analysis of PET data relies on an accurate estimate of the arterial plasma input function (PIF). An alternative to invasive measurements from arterial sampling is an image-derived input function (IDIF). However, an IDIF provides the whole blood radioactivity concentration, rather than the required free tracer radioactivity concentration in plasma. To estimate the tracer PIF, we corrected an IDIF from the carotid artery with estimates of plasma parent fraction (PF) and plasma-to-whole blood (PWB) ratio obtained from five venous samples. We compared the combined IDIF+venous approach to gold standard data from arterial sampling in 10 healthy volunteers undergoing [18F]GE-179 brain PET imaging of the NMDA receptor. Arterial and venous PF and PWB ratio estimates determined from 7 patients with traumatic brain injury (TBI) were also compared to assess the potential effect of medication. There was high agreement between areas under the curves of the estimates of PF (r = 0.99, p<0.001), PWB ratio (r = 0.93, p<0.001), and the PIF (r = 0.92, p<0.001) as well as total distribution volume (VT) in 11 regions across the brain (r = 0.95, p<0.001). IDIF+venous VT had a mean bias of -1.7% and a comparable regional coefficient of variation (arterial: 21.3 ± 2.5%, IDIF+venous: 21.5 ± 2.0%). Simplification of the IDIF+venous method to use only one venous sample provided less accurate VT estimates (mean bias 9.9%; r = 0.71, p<0.001). A version of the method that avoids the need for blood sampling by combining the IDIF with population-based PF and PWB ratio estimates systematically underestimated VT (mean bias -20.9%), and produced VT estimates with a poor correlation to those obtained using arterial data (r = 0.45, p<0.001). Arterial and venous blood data from 7 TBI patients showed high correlations for PF (r = 0.92, p = 0.003) and PWB ratio (r = 0.93, p = 0.003). In conclusion, the IDIF+venous method with five venous samples provides a viable alternative to arterial sampling for quantification of [18F]GE-179 VT.

Feasibility of late acquisition [68Ga]Ga-PSMA-11 PET/CT using a long axial field-of-view PET/CT scanner for the diagnosis of recurrent prostate cancer-first clinical experiences.

PURPOSE: While acquisition of images in [68 Ga]Ga-PSMA-11 following longer uptake times can improve lesion uptake and contrast, resultant imaging quality and count statistics are limited by the isotope's half-life (68 min). Here, we present a series of cases demonstrating that when performed using a long axial field-of-view (LAFOV) PET/CT system, late imaging is feasible and can even provide improved image quality compared to regular acquisitions. METHODS: In this retrospective case series, we report our initial experiences with 10 patients who underwent standard imaging at 1 h p.i. following administration of 192 ± 36 MBq [68 Ga]Ga-PSMA-11 with additional late imaging performed at 4 h p.i. Images were acquired in a single bed position for 6 min at 1 h p.i. and 16 min p.i. at 4 h p.i. using a LAFOV scanner (106 cm axial FOV). Two experienced nuclear medicine physicians reviewed all scans in consensus and evaluated overall image quality (5-point Likert scale), lesion uptake in terms of standardised uptake values (SUV), tumour to background ratio (TBR) and target-lesion signal to background noise (SNR). RESULTS: Subjective image quality as rated on a 5-point Likert scale was only modestly lower for late acquisitions (4.2/5 at 4 h p.i.; 5/5 1 h p.i.), TBR was significantly improved (4 h: 3.41 vs 1 h: 1.93, p < 0.001) and SNR was improved with borderline significance (4 h: 33.02 vs 1 h: 24.80, p = 0.062) at later imaging. Images were obtained with total acquisition times comparable to routine examinations on standard axial FOV scanners. CONCLUSION: Late acquisition in tandem with a LAFOV PET/CT resulted in improvements in TBR and SNR and was associated with only modest impairment in subjective visual imaging quality. These data show that later acquisition times for [68 Ga]Ga-PSMA-11 may be preferable when performed on LAFOV systems.

Clinical performance of long axial field of view PET/CT: a head-to-head intra-individual comparison of the Biograph Vision Quadra with the Biograph Vision PET/CT.

PURPOSE: To investigate the performance of the new long axial field-of-view (LAFOV) Biograph Vision Quadra PET/CT and a standard axial field-of-view (SAFOV) Biograph Vision 600 PET/CT (both: Siemens Healthineers) system using an intra-patient comparison. METHODS: Forty-four patients undergoing routine oncological PET/CT were prospectively included and underwent a same-day dual-scanning protocol following a single administration of either 18F-FDG (n = 20), 18F-PSMA-1007 (n = 16) or 68Ga-DOTA-TOC (n = 8). Half the patients first received a clinically routine examination on the SAFOV (FOVaxial 26.3 cm) in continuous bed motion and then immediately afterwards on the LAFOV system (10-min acquisition in list mode, FOVaxial 106 cm); the second half underwent scanning in the reverse order. Comparisons between the LAFOV at different emulated scan times (by rebinning list mode data) and the SAFOV were made for target lesion integral activity, signal to noise (SNR), target lesion to background ratio (TBR) and visual image quality. RESULTS: Equivalent target lesion integral activity to the SAFOV acquisitions (16-min duration for a 106 cm FOV) were obtained on the LAFOV in 1.63 ± 0.19 min (mean ± standard error). Equivalent SNR was obtained by 1.82 ± 1.00 min LAFOV acquisitions. No statistically significant differences (p > 0.05) in TBR were observed even for 0.5 min LAFOV examinations. Subjective image quality rated by two physicians confirmed the 10 min LAFOV to be of the highest quality, with equivalence between the LAFOV and the SAFOV at 1.8 ± 0.85 min. By analogy, if the LAFOV scans were maintained at 10 min, proportional reductions in applied radiopharmaceutical could obtain equivalent lesion integral activity for activities under 40 MBq and equivalent doses for the PET component of <1 mSv. CONCLUSION: Improved image quality, lesion quantification and SNR resulting from higher sensitivity were demonstrated for an LAFOV system in a head-to-head comparison under clinical conditions. The LAFOV system could deliver images of comparable quality and lesion quantification in under 2 min, compared to routine SAFOV acquisition (16 min for equivalent FOV coverage). Alternatively, the LAFOV system could allow for low-dose examination protocols. Shorter LAFOV acquisitions (0.5 min), while of lower visual quality and SNR, were of adequate quality with respect to target lesion identification, suggesting that ultra-fast or low-dose acquisitions can be acceptable in selected settings.

OCT Angiography: Measurement of Retinal Macular Microvasculature with Spectralis II OCT Angiography - Reliability and Reproducibility.

AIM: The aim of the present study was to investigate the reliability of macular microvasculature measurements in normal subjects by Heidelberg Spectralis II optical coherence tomography angiography (OCT-A) in combination with a newly made software. SUBJECTS AND METHODS: This prospective study included 23 eyes of 23 persons from the Erlangen Glaucoma Registry (ISSN 2191-5008, CS-2011; NTC00494923). The subjects underwent a complete clinical, standardized ophthalmologic examination to rule out any eye disease. En face OCT-A imaging was done using Heidelberg Spectralis II OCT (Heidelberg, Germany). Images were recorded with a 15 × 15° angle and a lateral resolution of 5.7 µm/pixel, resulting in a retinal section of 2.9 × 2.9 mm. The Erlangen-Angio-Tool (EA-Tool) OCT-A application performed multiple segmentations, allowing analysis of the vessel density in 12 segments. The software was coded in MATLAB. Macular data on the superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) were exported into the application and analyzed separately. The EA-Tool calculated the percentage of "white area" in the "total area" of the region of interest, called vessel density. Foveolar avascular zones (FAZs) of the SVP, ICP, and DCP were calculated manually. To investigate the reproducibility of the new software, individual scans (SVP, ICP, and DCP) were analyzed twice with the EA-Tool and intraclass coefficients (ICCs) of the vessel density values were calculated. Statistical analysis was performed with SPSS version 21.0. RESULTS: The mean vessel density of the SVP ranged between 30.4 and 33.5, that of the ICP between 20.9 and 24.7, and that of the DCP between 23.5 and 27.6. Bland-Altman plots showed a good reliability of two consecutive scans of each sector (S1-S12) in the SVP, ICP, and DCP. Testing reproducibility, no statistically significantly different sectorial coefficients of variation of the SVP, ICP, and DCP were observed (p > 0.05). The mean FAZ area of the SVP was 0.43 ± 0.16 mm2, that of the ICP 0.28 ± 0.1 mm2, and that of the DCP 0.44 ± 0.12 mm2. CONCLUSIONS: Spectralis OCT II, in combination with the semiautomated vessel density software EA-Tool, showed good or even excellent ICCs in 75% of all segments of the SVP, ICP, and DCP. The ICCs for the FAZ area in the SVP, ICP, and DCP were excellent.