Dynamic total-body PET/CT imaging with reduced acquisition time shows acceptable performance in quantification of [18F]FDG tumor kinetic metrics.

PURPOSE: To investigate the feasibility of reducing the acquisition time for continuous dynamic positron emission tomography (PET) while retaining acceptable performance in quantifying kinetic metrics of 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) in tumors. METHODS: In total, 78 oncological patients underwent total-body dynamic PET imaging for ≥ 60 min, with 8, 20, and 50 patients receiving full activity (3.7 MBq/kg), half activity (1.85 MBq/kg), and ultra-low activity (0.37 MBq/kg) of [18F]FDG, respectively. The dynamic data were divided into 21-, 30-, 45- and ≥ 60-min groups. The kinetic analysis involved model fitting to derive constant rates (VB, K1 to k3, and Ki) for both tumors and normal tissues, using both reversible and irreversible two-tissue-compartment models. One-way ANOVA with repeated measures or the Freidman test compared the kinetic metrics among groups, while the Deming regression assessed the correlation of kinetic metrics among groups. RESULTS: All kinetic metrics in the 30-min and 45-min groups were statistically comparable to those in the ≥ 60-min group. The relative differences between the 30-min and ≥ 60-min groups ranged from 12.3% ± 15.1% for K1 to 29.8% ± 30.0% for VB, and those between the 45-min and ≥ 60-min groups ranged from 7.5% ± 8.7% for Ki to 24.0% ± 24.3% for VB. However, this comparability was not observed between the 21-min and ≥ 60-min groups. The significance trend of these comparisons remained consistent across different models (reversible or irreversible), administrated activity levels, and partial volume corrections for lesions. Significant correlations in tumor kinetic metrics were identified between the 30-/45-min and ≥ 60-min groups, with Deming regression slopes > 0.813. In addition, the comparability of kinetic metrics between the 30-min and ≥ 60-min groups were established for normal tissues. CONCLUSION: The acquisition time for dynamic PET imaging can be reduced to 30 min without compromising the ability to reveal tumor kinetic metrics of [18F]FDG, using the total-body PET/CT system.

VgrG Spike Dictates PAAR Requirement for the Assembly of the Type VI Secretion System.

Widely employed by Gram-negative pathogens for competition and pathogenesis, the type six protein secretion system (T6SS) can inject toxic effectors into neighboring cells through the penetration of a spear-like structure comprising a long Hcp tube and a VgrG-PAAR spike complex. The cone-shaped PAAR is believed to sharpen the T6SS spear for penetration but it remains unclear why PAAR is required for T6SS functions in some bacteria but dispensable in others. Here, we report the conditional requirement of PAAR for T6SS functions in Aeromonas dhakensis, an emerging human pathogen that may cause severe bacteremia. By deleting the two PAAR paralogs, we show that PAAR is not required for T6SS secretion, bacterial killing, or specific effector delivery in A. dhakensis. By constructing combinatorial PAAR and vgrG deletions, we demonstrate that deletion of individual PAAR moderately reduced T6SS functions but double or triple deletions of PAAR in the vgrG deletion mutants severely impaired T6SS functions. Notably, the auxiliary-cluster-encoded PAAR2 and VgrG3 are less critical than the main-cluster-encoded PAAR1 and VgrG1&2 proteins to T6SS functions. In addition, PAAR1 but not PAAR2 contributes to antieukaryotic virulence in amoeba. Our data suggest that, for a multi-PAAR T6SS, the variable role of PAAR paralogs correlates with the VgrG-spike composition that collectively dictates T6SS assembly. IMPORTANCE Gram-negative bacteria often encode multiple paralogs of the cone-shaped PAAR that sits atop the VgrG-spike and is thought to sharpen the spear-like T6SS puncturing device. However, it is unclear why PAAR is required for the assembly of some but not all T6SSs and why there are multiple PAARs if they are not required. Our data delineate a VgrG-mediated conditional requirement for PAAR and suggest a core-auxiliary relationship among different PAAR-VgrG modules that may have been acquired sequentially by the T6SS during evolution.

An exploration of the feasibility and clinical value of half-dose 5-h total-body 18F-FDG PET/CT scan in patients with Takayasu arteritis.

PURPOSE: To explore the feasibility and clinical value of 5-h delayed 18F-fluorodeoxyglucose (18F-FDG) total-body (TB) positron emission tomography/computed tomography (PET/CT) in patients with Takayasu arteritis (TA). METHODS: This study included nine healthy volunteers who underwent 1-, 2.5-, and 5-h triple-time TB PET/CT scans and 55 patients with TA who underwent 2- and 5-h dual-time TB PET/CT scans with 1.85 MBq/kg 18F-FDG. The liver, blood pool, and gluteus maximus muscle signal-to-noise ratios (SNRs) were calculated by dividing the SUVmean by its standard deviation to evaluate imaging quality. TA lesions' 18F-FDG uptake was graded on a three-point scale (I, II, III), with grades II and III considered positive lesions. Lesion-to-blood maximum standardised uptake value (SUVmax) ratio (LBR) was calculated by dividing the lesion SUVmax by the blood pool SUVmax. RESULTS: The liver, blood pool, and muscle SNR of the healthy volunteers at 2.5- and 5-h were similar (0.117 and 0.115, respectively, p = 0.095). We detected 415 TA lesions in 39 patients with active TA. The average 2- and 5-h scan LBRs were 3.67 and 7.59, respectively (p < 0.001). Similar TA lesion detection rates were noted in the 2-h (92.0%; 382/415) and 5-h (94.2%; 391/415) scans (p = 0.140). We detected 143 TA lesions in 19 patients with inactive TA. The 2- and 5-h scan LBRs were 2.99 and 5.71, respectively (p < 0.001). Similar positive detection rates in inactive TA were noted in the 2-h (97.9%; 140/143) and 5-h (98.6%; 141/143) scans (p = 0.500). CONCLUSION: The 2- and 5-h 18F-FDG TB PET/CT scans had similar positive detection rates, but both combined could better detect inflammatory lesions in patients with TA.

An artificial intelligence-driven image quality assessment system for whole-body [18F]FDG PET/CT.

PURPOSE: Image quality control is a prerequisite for applying PET/CT. This study aimed to develop an artificial intelligence-driven real-time and accurate whole-body [18F]FDG PET/CT image quality assessment system. METHODS: This study included 173 patients (age, 59 ± 12 years; 66.3% males) with whole-body [18F]FDG PET/CT imaging. Images of ten patients were used as an educational set. Images of the rest 163 patients were reconstructed to 952 images by simulating several scanning times and randomly split into training (60%, 98 patients, 578 images), validation (20%, 33 patients, 192 images), and test (20%, 32 patients,182 images) sets. Two experienced physicians (R1 and R2) independently assessed the image quality of thorax, abdomen, and pelvis region twice (R1a and b; R2a and b), 1 month apart, using a 5-point Likert scale. Objective image quality metrics were extracted from the mediastinal blood pool, three liver levels, and the bilateral gluteus maximus. The developed convolutional neural networks for image quality assessment (IQA-CNNs) generated the subjective quality scores and objective image metrics. The IQA-CNNs and physicians' performances were compared for localization accuracy, score agreement, and process time. RESULTS: The physicians demonstrated good inter- and intra-rater subjective assessment agreement, with kappa coefficients (R1a vs. R2a, R1a vs. R1b, R2a vs. R2b, and R1a vs. R2b) of 0.78, 0.77, 0.76, and 0.80. The IQA-CNNs and R1 or R2 agreed in the subjective assessments, with kappa coefficients of 0.79 and 0.78. IQA-CNNs and R1 or R2 also agreed in their objective image quality assessment (ICC > 0.60). The IQA-CNNs evaluation speed was 200 times faster than the manual assessment. CONCLUSION: An automated system for rapid assessment of [18F]FDG PET/CT image quality was developed, showing comparable performance to senior physicians. The system generates a comprehensive and detailed image quality assessment report, including subjective visual scores and objective image metrics for various anatomical regions.

Caged Luciferase Inhibitor-Based Bioluminescence Switching Strategy Enables Efficient Detection of Serum APN Activity and the Identification of Its Roles in Metastasis of Non-Small Cell Lung Cancer.

Bioluminogenic probes emerged as powerful tools for imaging and analysis of various bioanalyses, but traditional approaches would be limited to the low sensitivity during determine the low activity of protease in clinical specimens. Herein, we proposed a caged luciferase inhibitor-based bioluminescence-switching strategy (CLIBS) by using a cleavable luciferase inhibitor to modulate the activity of luciferase reporter to amplify the detective signals, which led to the enhancement of detection sensitivity, and enabled the determination of circulating Aminopeptidase N (APN) activity in thousands of times diluted serum. By applying the CLIBS to serum samples in non-small cell lung cancer (NSCLC) patients from two clinical cohorts, we revealed that, for the first time, higher circulating APN activities but not its concentration, were associated with more NSCLC metastasis or higher metastasis stages by subsequent clinical analysis, and can serve as an independent factor for forecasting NSCLC patients' risk of metastasis.

Expert consensus on oncological [18F]FDG total-body PET/CT imaging (version 1).

BACKGROUND: [18F]FDG imaging on total-body PET/CT (TB PET/CT) scanners, with improved sensitivity, offers new potentials for cancer diagnosis, staging, and radiation treatment planning. This consensus provides the protocols for clinical practices with a goal of paving the way for future studies with the total-body scanners in oncological [18F]FDG TB PET/CT imaging. METHODS: The consensus was summarized based on the published guidelines and peer-reviewed articles of TB PET/CT in the literature, along with the opinions of the experts from major research institutions with a total of 40,000 cases performed on the TB PET/CT scanners. RESULTS: This consensus describes the protocols for routine and dynamic [18F]FDG TB PET/CT scanning focusing on the reduction of imaging acquisition time and FDG injected activity, which may serve as a reference for research and clinic oncological PET/CT studies. CONCLUSION: This expert consensus focuses on the reduction of acquisition time and FDG injected activity with a TB PET/CT scanner, which may improve the patient throughput or reduce the radiation exposure in daily clinical oncologic imaging. KEY POINTS: • [18F]FDG-imaging protocols for oncological total-body PET/CT with reduced acquisition time or with different FDG activity levels have been summarized from multicenter studies. • Total-body PET/CT provides better image quality and improved diagnostic insights. • Clinical workflow and patient management have been improved.

Noninvasive Evaluation of EGFR Expression of Digestive Tumors Using 99mTc-MAG3-Cet-F(ab')2-Based SPECT/CT Imaging.

Purpose: This study is aimed at investigating the feasibility of cetuximab (Cet) F(ab')2 fragment- (Cet-F(ab')2-) based single photon emission tomography/computed tomography (SPECT/CT) for assessing the epidermal growth factor receptor (EGFR) expression in digestive tumor mouse models. Methods: Cet-F(ab')2 was synthesized using immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS) protease and purified with protein A beads. The product and its in vitro stability in normal saline and 1% bovine serum albumin were analyzed with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The EGFR expression in the human colon tumor cell line HT29 and the human stomach tumor cell line MGC803 were verified using western blotting and immunocytochemistry. Cet-F(ab')2 was conjugated with 5(6)-carboxytetramethylrhodamine succinimidyl ester to demonstrate its binding ability to the MGC803 and HT29 cells. Cet-F(ab')2 was conjugated with NHS-MAG3 for 99mTc radiolabeling. The best imaging time was determined using a biodistribution assay at 1, 4, 16, and 24 h after injection of the 99mTc-MAG3-Cet-F(ab')2 tracer. Furthermore, 99mTc-MAG3-Cet-F(ab')2 SPECT/CT was performed on MGC803 and HT29 tumor-bearing nude mice. Results: HT29 cells had low EGFR expression while MGC803 cell exhibited the high EGFR expression. Cet-F(ab')2 and intact cetuximab showed similar high binding ability to MGC803 cells but not to HT29 cells. Cet-F(ab')2 and 99mTc-MAG3-Cet-F(ab')2 showed excellent in vitro stability. The biodistribution assay showed that the target to nontarget ratio was the highest at 16 h (17.29 ± 5.72, n = 4) after tracer injection. The 99mTc-MAG3-Cet-F(ab')2-based SPECT/CT imaging revealed rapid and sustained tracer uptake in MGC803 tumors rather than in HT29 tumors with high image contrast, which was consistent with the results in vitro. Conclusion: SPECT/CT imaging using 99mTc-MAG3-Cet-F(ab')2 enables the evaluation of the EGFR expression in murine EGFR-positive tumors, indicating the potential utility for noninvasive evaluation of the EGFR expression in tumors.

Ultrafast 30-s total-body PET/CT scan: a preliminary study.

PURPOSE: The aim of this study is to explore the diagnostic value of the images obtained in ultrafast 30-s acquisition time by the total-body PET/CT (18F-FDG injection dose of about 3.7 MBq/kg), and to evaluate whether they can meet the requirements of clinical diagnosis or not. METHODS: This retrospective study explored the clinical value of ultrafast 30-s 18F-FDG total-body PET/CT in 88 oncology patients, using the post-surgical pathological diagnosis as the reference standard. The data were acquired over 300 s and reconstructed using all 300-s data (G300) and only the initial 30 s (G30). Two readers independently assessed all images qualitatively and quantitatively. The diagnostic performance was compared between G300 and G30. RESULTS: The G300 average qualitative score was higher than G30 (P < 0.001). G300 and G30 also differed quantitatively in the liver and mediastinum SUVmax, SD, and SNR (all P < 0.001), but had similar sensitivities (89.09% vs. 86.36%, P = 0.250). The G300 group had higher accuracy (79.73%) and a larger area under the curve (0.709) than G30 (77.70% and 0.695, respectively; all P > 0.05). CONCLUSION: The 30-s total-body PET/CT could meet clinical diagnostic requirements for malignant tumors in patients intolerant to prolonged horizontal positioning.

Short-time total-body dynamic PET imaging performance in quantifying the kinetic metrics of 18F-FDG in healthy volunteers.

PURPOSE: To investigate the performance of short-time dynamic imaging in quantifying kinetic metrics of 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG). METHODS: Dynamic total-body positron emission tomography (PET) imaging was performed in 11 healthy volunteers for 75 min. The data were divided into 30-, 45- and 75-min groups. Nonlinear regression (NLR) generated constant rates (k1 to k3) and NLR-based Ki in various organs. The Patlak method calculated parametric Ki images to generate Patlak-based Ki values. Paired samples t-test or the Wilcoxon signed-rank test compared the kinetic metrics between the groups, depending on data normality. Deming regression and Bland-Altman analysis assessed the correlation and agreement between NLR- and Patlak-based Ki. A two-sided P < 0.05 was considered statistically significant. RESULTS: The 45- and 75-min groups were similar in NLR-based kinetic metrics. The relative difference ranges were as follows: k1, from 3.4% (P = 0.627) in the spleen to 57.9% (P = 0.130) in the white matter; k2, from 6.0% (P = 0.904) in the spleen to 60.7% (P = 0.235) in the left ventricle (LV) myocardium; k3, from 45.6% (P = 0.302) in the LV myocardium to 96.3% (P = 0.478) in the liver; Ki, from 14.0% (P = 0.488) in the liver to 77.8% (P = 0.067) in the kidney. Patlak-based Ki values were also similar between these groups in all organs, except the grey matter (9.6%, P = 0.029) and cerebellum (14.4%, P = 0.002). However, significant differences in kinetic metrics were found between the 30-min and 75-min groups in most organs both in NLR- and Patlak-based analyses. The NLR- and Patlak-based Ki values significantly correlated, with no bias in any of the organs. CONCLUSION: Dynamic imaging using a high-sensitivity total-body PET scanner for a shorter time of 45 min could achieve relevant kinetic metrics of 18F-FDG as done by long-time imaging.

Investigating ultra-low-dose total-body [18F]-FDG PET/CT in colorectal cancer: initial experience.

PURPOSE: This study was to evaluate the effects of an ultra-low dose of [18F]-FDG on the image quality of total-body PET/CT and its lesion detectability in colorectal cancer (CRC). METHODS: Sixty-two CRC patients who underwent total-body PET/CT (uEXPLORER, United Imaging Healthcare, Shanghai, China) with an ultra-low dose (0.37 MBq/kg) of [18F]-FDG were enrolled in this retrospective study. The PET images were reconstructed with the entire 15-min dataset first and then split into 13-, 8-, 5-, 4-, 3-, 2-, and 1-min duration groups to simulate fast scanning images. For simplicity, the images reconstructed with the data from 15 to 1 min were referred to as G15, G13, and so on until G1. Subjective image quality was assessed with 5-point Likert scales. The objective image quality parameters included the SUVmax, SUVmean, and signal-to-noise ratio (SNR) of the liver and blood pool and the SUVmax and tumor-to-background ratio (TBR) of the lesions. G15 served as the control to evaluate lesion detectability. RESULTS: A total of 62 patients (43 men, 19 women; age 41-88, mean ± SD 64.0 ± 10.9 years) with 64 CRC primary tumor lesions and 10 low-grade intraepithelial neoplasia (LGIN) lesions were enrolled in this study. The subjective scores were highest for G15 (4.5 ± 0.5) and then decreased from G13 (4.3 ± 0.4) to G8 (3.7 ± 0.5). The liver SNR increased with the extension of acquisition time from G8 (17.2 ± 2.8) to G13 (20.6 ± 3.4) and G15 (21.9 ± 3.4). The liver SNR of G8 was not significantly different from that of G13 (p = 0.15) and was significantly different from that of G15 (p = 0.001). All 64 CRC lesions could be identified in all image groups, even on G1. One of ten LGINs was missed on G1, G2, and G3, and one LGIN was missed on G1, G2, G3, and G4. G15 served as the control, and 100% (48/48) lymph nodes could be found on G13 and G8 compared to 93.8% (45/48) lymph nodes on G5 and G4, 85.4% (41/48) lymph nodes on G3, 81.3% (39/48) lymph nodes on G2, and 77.1% (37/48) lymph nodes on G1. For liver metastases, there were no missed liver lesions on G13 and G8 and 3, 4, 6, 7, and 9 missed liver lesions on G5, G4, G3, G2, and G1, respectively. For other areas of metastasis, including the lung, peritoneum, and ovaries, there were no missed lesions in any group. CONCLUSIONS: Total-body PET/CT with an ultra-low dose of [18F]-FDG can maintain satisfactory image quality and lesion detectability in CRC.

Correlation among maximum standardized 18F-FDG uptake and pathological differentiation, tumor size, and Ki67 in patients with moderately and poorly differentiated intrahepatic cholangiocarcinoma.

OBJECTIVE: To investigate the correlation among the maximum standardized uptake value (SUVmax) on fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) and tumor differentiation, size, and Ki67 in patients with moderately and poorly differentiate dintrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: The 18F-FDG PET/CT imaging data of 116 patients with single ICC lesions confirmed by pathology were retrospectively evaluated. Pathological characteristics of the tumor such as the largest tumor diameter, differentiation, Ki67 expression, SUVmax of the primary tumor, and the tumor to normal background ratio (TNR) were recorded. RESULTS: Among the 116 lesions, 45, 51, and 20 lesions were classified into the moderately differentiated, moderately-poorly, and poorly differentiated groups, respectively. There were significant differences in the SUVmax (P=0.033) and TNR (P=0.044) among the three groups. Maximum SUV was significantly correlated with differentiation (r=0.244, P=0.008). When the cases were categorized according to the tumor size (group 1, ≤3cm, n=14; group 2, >3 and ≤5 cm, n=37; group 3, >5 and ≤10 cm, n=52; group 4, >10 cm, n=13), there were significant differences in the SUVmax (P<0.001) and TNR (P<0.001) among the four groups. Maximum SUV was significantly correlated with tumor size (r=0.481, P<0.001). Among the 116 lesions, 38 lesions and 78 lesions were classified into the low Ki67 and high Ki67 expression groups, respectively. There were significant differences in the SUVmax (P=0.028) and TNR (P=0.007) between the two groups. Maximum SUV was significantly correlated with Ki67 expression (r=0.242, P=0.009). CONCLUSION: In moderately and poorly differentiated ICC, the SUVmax and TNR are significantly associated with tumor differentiation, size, and Ki67 expression.

Kinetic metrics of 18F-FDG in normal human organs identified by systematic dynamic total-body positron emission tomography.

PURPOSE: To investigate the kinetic metrics of 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) in normal organs by using dynamic total-body (TB) positron emission tomography (PET). METHODS: Dynamic TB-PET was performed for nine healthy volunteers. Time-to-activity curves (TACs) were obtained by drawing regions of interest in the organs. A two-tissue compartment model was fitted for each tissue TAC. Constant rates, including k1, k2, and k3, and the metabolic rate of FDG (MRFDG) were obtained. The parameter statistics, including the average, standard deviation, coefficient of variance, and inter-site and inter-individual variances, were compared. RESULTS: Constant rates and MRFDG varied significantly among organs and subjects, but not among sides or sub-regions within an organ. The mean k1 and k2 ranged from 0.0158 min-1 in the right lower lung to 1.1883 min-1 in the anterior wall of the left ventricle (LV) myocardium and from 0.1116 min-1 in the left parietal white matter to 4.6272 min-1 in the left thyroid, respectively. The k3 was lowest in the right upper area of the liver and highest in the septal wall of the LV myocardium. Mean MRFDG ranged from 23.1696 µmol/100 g/min in the parietal cortex to 0.5945 µmol/100 g/min in the lung. Four groups of organs with similar kinetic characteristics were identified: (1) the cerebral white matter, lung, liver, muscle, bone, and bone marrow; (2) cerebral and cerebellar cortex; (3) LV myocardium and thyroid; and (4) pancreas, spleen, and kidney. CONCLUSION: The kinetic rates and MRFDG significantly differed among organs. The kinetic metrics of FDG parameters in normal organs can serve as a reference for future dynamic PET imaging and research.

Ultra-low-activity total-body dynamic PET imaging allows equal performance to full-activity PET imaging for investigating kinetic metrics of 18F-FDG in healthy volunteers.

PURPOSE: To investigate the feasibility of ultra-low-activity total-body positron emission tomography (PET) dynamic imaging for quantifying kinetic metrics of 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) in normal organs and to verify its clinical relevance with full-activity imaging. METHODS: Dynamic total-body PET imaging was performed in 20 healthy volunteers, with eight using full activity (3.7 MBq/kg) of 18F-FDG and 12 using 10× activity reduction (0.37 MBq/kg). Image contrast, in terms of liver-to-muscle ratio (LMR), liver-to-blood ratio (LBR), and blood-to-muscle ratio (BMR) of radioactivity concentrations were assessed. A two-tissue compartment model was fitted to the time-to-activity curves in organs based on regions of interest (ROIs) delineation using PMOD, and constant rates (k1, k2, and k3) were generated. Kinetic constants, corresponding coefficients of variance (CoVs), image contrast, radiation dose, prompt counts, and data size were compared between full- and low-activity groups. RESULTS: All constant rates, corresponding CoVs, and image contrast in different organs were comparable with none significant differences between full- and ultra-low-activity groups. PET images in the ultra-low-activity group generated significantly lower effective radiation dose (median, 0.419 vs. 4.886 mSv, P < 0.001), reduced prompt counts (median, 2.79 vs. 55.68 billion, P < 0.001), and smaller data size (median, 71.11 vs. 723.18 GB, P < 0.001). CONCLUSION: Total-body dynamic PET imaging using 10× reduction of injected activity could achieve relevant kinetic metrics of 18F-FDG and comparable image contrast with full-activity imaging. Activity reduction results in significant decrease of radiation dose and data size, rendering it more acceptable and easier for data reconstruction, transmission, and storage for clinical practice.

Total-body 18F-FDG PET/CT scan in oncology patients: how fast could it be?

PURPOSE: The aim of the study was to determine a faster PET acquisition protocol for a total-body PET/CT scanner by assessing the image quality that is equivalent to a conventional digital PET/CT scanner from both a phantom and a clinical perspective. METHODS: A phantom study using a NEMA/IEC NU-2 body phantom was first performed in both a total-body PET/CT (uEXPLORER) and a routine digital PET/CT (uMI 780), with a hot sphere to background activity concentration ratio of 4:1. The contrast recovery coefficient (CRC), background variability (BV), and recovery coefficient (RC: RCmax and RCmean) were assessed in the uEXPLORER with different scanning durations and reconstruction protocols, which were compared to those acquired from the uMI 780 with clinical acquisition settings. The coefficient of variation (COV) of the uMI 780 with clinical settings was calculated and used as a threshold reference to determine the optimized scanning duration and reconstruction protocol for the uEXPLORER. The obtained protocol from the phantom study was subsequently tested and validated in 30 oncology patients. Images acquired from the uMI 780 with 2-3 min per bed position were referred as G780 and served as the reference for comparison. All PET raw data from the uEXPLORER were reconstructed using the data-cutting technique to simulate a 30-s, 45-s, or 60-s acquisition duration, respectively. The iterations were 2 and 3 for the uEXPLORER, referred as G30s_3i, G45s_2i, G45s_3i, G60s_2i, and G60s_3i, respectively. A 5-point Likert scale was used in the qualitative analysis to assess the image quality. The image quality was also evaluated by the liver COV, the lesion target-to-background ratio (TBR), and the lesion signal-to-noise ratio (SNR). RESULTS: In the phantom study, CRC, BV, RCmax, and RCmean in the uEXPLORER with different scanning durations and reconstruction iterations were compared with those in the uMI 780 with clinical settings. A minor fluctuation was found among different scanning durations. COV of the uMI 780 with clinical settings was 11.6%, and a protocol with a 30-45-s scanning duration and 2 or 3 iterations for the uEXPLORER was found to provide an equivalent image quality as the uMI 780. An almost perfect agreement was shown with a kappa value of 0.875. The qualitative score of the G30s_3i in the uEXPLORER was inferior to the G780 reference (p = 0.001); however, the scores of other groups in the uEXPLORER with a 45-s and above acquisition time were higher than the G780 in the uMI 780. In quantitative analysis, the delay time between the two scans in the two orders was not significantly different. There was no significant difference of the liver COV between the G780 and G30s_3i (p = 0.162). A total of 33 lesions were analyzed in the clinical patient study. There was no significant difference in lesion TBR between the reference G780 and the G45s_2i obtained from the uEXPLORER (p = 0.072), while the latter showed a higher lesion SNR value compared to that in uMI 780 with clinical settings (p < 0.001). CONCLUSIONS: This study showed that a fast PET protocol with a 30-45-s acquisition time in the total-body uEXPLORER PET/CT can provide an equivalent image quality as the conventional digital uMI 780 PET/CT with longer clinical acquisition settings.

Can the BMI-based dose regimen be used to reduce injection activity and to obtain a constant image quality in oncological patients by 18F-FDG total-body PET/CT imaging?

PURPOSE: PET image quality is influenced by the patient size according to the current guideline. The study aimed to propose an optimized dose regimen to yield a constant image quality independent of patient habitus to meet the clinical needs. METHODS: A first patient cohort of 78 consecutive oncological patients (59.7 ± 13.7 years) who underwent a total-body PET/CT scan were retrospectively enrolled to develop the regimen. The patients were randomly distributed in four body mass index (BMI) groups according to the World Health Organization (WHO) criteria. The liver SNR (signal-to-noise ratio, SNRL) was obtained by manually drawing regions of interest (ROIs) and normalized (SNRnorm) by the product of injected activity and acquisition time. Fits of SNRnorm against different patient-dependent parameters were performed to determine the best correlating parameter and fit method. A qualitative assessment on image quality was performed using a 5-point Likert scale to determine the acceptable threshold of SNRL. Thus, an optimized regimen was proposed and validated by a second patient cohort consisted of prospectively enrolled 38 oncological patients. RESULTS: The linear fit showed SNRnorm had the strongest correlation (R2 = 0.69) with the BMI than other patient-dependent parameters and fit method. The qualitative assessment indicated a SNRL value of 14.0 as an acceptable threshold to achieve sufficient image quality. The optimized dose regimen was determined as a quadratic relation with BMI: injected activity (MBq) = 39.2 (MBq)/(- 0.03*BMI + 1.49)2. In the validation study, the SNRL no longer decreased with the increase of BMI. There was no significant difference of the image quality regarding the value of SNRL between different BMI groups (p > 0.05). In addition, the injected activity was reduced by 75.6 ± 2.9%, 72.1 ± 4.0%, 67.1 ± 4.4%, and 64.8 ± 3.5% compared with the first cohort for the four BMI groups, respectively. CONCLUSION: The study proposed a quadratic relation between the 18F-FDG injected activity and the patient's BMI for total-body 18F-FDG PET imaging. In this regimen, the image quality can maintain in a constant level independent of patient habitus and meet the clinical requirement with a reduced injected activity.

Clinical efficacy and safety of a focused-radiofrequency device on middle and lower face rejuvenation: a retrospective clinical study.

The aim of the present study was to evaluate the efficacy and safety of a unipolar focused-RF device used to rejuvenate the middle and lower face and to create an assessment system. This retrospective study comprised 52 patients with mild-to-moderate skin laxity and wrinkles who received 1-3 treatments 1 month apart and were followed up for 1-7 months. At baseline and post-treatment, three blinded observers measured facial contour and lines, analyzed VISIA scores, and assessed the results using Alexiades Comprehensive Grading Scale (ACGS) and Global Aesthetic Improvement Scale (GAIS). Significant improvements were observed (P < .05) in facial width (left 5.95%, right 5.66%), nasolabial folds (left 18.98%, right 20.56%), marionette lines (left 18.88%, right 25.80%), and cheek lines (left 3.35%, right 3.05%) and in the scores of wrinkles (15.37%), texture (13.67%), pores (6.48%), and red areas (6.57%) using VISIA. There was an obvious reduction in wrinkles, laxity, erythema/telangiectasia based on ACGS, and 75% improved and 5.8% much improved using GAIS. There was no severe side effect. We suggest that the unipolar focused-RF device is an effective and safe technique for middle and lower face rejuvenation and provides a series of comprehensive assessment methods based on standardized photos using VISIA.

The image quality, lesion detectability, and acquisition time of 18F-FDG total-body PET/CT in oncological patients.

PURPOSE: The purpose was to investigate the effects of short acquisition time on the image quality and the lesion detectability of oncological 18F-FDG total-body PET/CT. METHODS: Nineteen oncological patients (6/13 women/men, age 65.6 ± 9.4 years) underwent total-body PET/CT on uEXPLORER scanner using 3D list mode. The administration of 18F-FDG was weight-based (4.4 MBq/kg). The acquisition time was 900 s, and PET data were reconstructed into 900-, 180-, 120-, 60-, 30-, and 18-s duration groups. The subjective PET image quality was scored using a 5-point scale (5, excellent; 1, poor) in 3 perspectives: overall quality, noise, and lesion conspicuity. The objective image quality was evaluated by SUVmax and standard deviation (SD) of the liver, SUVmax of the tumor, and tumor-to-background ratio (TBR). The lesion detectability was the percentage of identifiable lesions in the groups of 180 to 18 s using the group 900 s as reference. RESULTS: Our results showed that sufficient and acceptable subjective image quality could be achieved with 60- and 30-s groups, and good image quality scores were given to 180- and 120-s groups without significant difference. For shortened acquisition time, SD was increased, while SUVmax of tumor and TBR remained unchanged. The lesion detectability was decreased with shorter acquisition time, but the detection performance could be maintained until the 60-s group compared with the 900-s group, although the image quality degraded. CONCLUSION: The total-body PET/CT can significantly shorten the acquisition time with maintained lesion detectability and image quality.

Total-Body PET/CT: Current Applications and Future Perspectives.

OBJECTIVE. The purpose of this article is to describe the clinical applications of a total-body PET scanner and discuss future expectations. CONCLUSION. PET has been widely used in the fields of oncology, neurology, and cardiology. However, current PET scanners have limitations, including long scanning time, low signal-to-noise ratio, and high dose of ionizing radiation. Total-body PET with a long scan range provides solutions to these problems, markedly increasing the sensitivity of the system.

Plastid-expressed Bacillus thuringiensis (Bt) cry3Bb confers high mortality to a leaf eating beetle in poplar.

KEY MESSAGE: The Bacillus thuringiensis (Bt) cry3Bb gene was successfully introduced into poplar plastid genome, leading to transplastomic poplar with high mortality to Plagiodera versicolora. Poplar (Populus L.) is one of the main resource of woody industry, but being damaged by insect pests. The feasibility and efficiency of plastid transformation technology for controlling two lepidopteran caterpillars have been demonstrated previously. Here, we introduced B. thuringiensis (Bt) cry3Bb into poplar plastid genome by biolistic bombardment for controlling P. versicolora, a widely distributed forest pest. Chimeric cry3Bb gene is controlled by the tobacco plastid rRNA operon promoter combined with the 5'UTR from gene10 of bacteriophage T7 (NtPrrn:T7g10) and the 3'UTR from the E. coli ribosomal RNA operon rrnB (TrrnB). The integration of transgene and homoplasmy of transplastomic poplar plants was confirmed by Southern blot analysis. Northern blot analysis indicated that cry3Bb was transcribed to both read through and shorter length transcripts in plastid. The transplastomic poplar expressing Cry3Bb insecticidal protein showed the highest accumulation level in young leaves, which reach up to 16.8 µg/g fresh weight, and comparatively low levels in mature and old leaves. Feeding the young leaves from Bt-Cry3Bb plastid lines to P. versicolora caused 100% mortality in the first-instar larvae after only 1 day, in the second-instar larvae after 2 days, and in the third-instar larvae for 3 days. Thus, we report a successful extension of plastid engineering poplar against the chrysomelid beetle.

Advancing single-cell proteomics and metabolomics with microfluidic technologies.

Recent advances in single-cell analysis have unraveled substantial heterogeneity among seemingly identical cells at genomic and transcriptomic levels. These discoveries have urged scientists to develop new tools that are capable of investigating single cells from a broader set of "omics". Proteomics and metabolomics, for instance, are of particular interest as they are closely correlated with a dynamic picture of cellular behaviors and phenotypic identities. The development of such tools requires highly efficient isolation and processing of a large number of individual cells, where techniques such as microfluidics are extremely useful. Here, we review the recent advances in single-cell proteomics and metabolomics, with a focus on microfluidics-based platforms. We highlight a vast array of emerging microfluidic formats for single-cell isolation and manipulation, and how the state-of-the-art analytical tools are coupled with such platforms for proteomic and metabolomic profiling.