99mTc-3PRGD2 SPECT/CT Imaging for Diagnosing Lymph Node Metastasis of Primary Malignant Lung Tumors.

OBJECTIVE: To evaluate 99mtechnetium-three polyethylene glycol spacers-arginine-glycine-aspartic acid (99mTc-3PRGD2) single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging for diagnosing lymph node metastasis of primary malignant lung neoplasms. MATERIALS AND METHODS: We prospectively enrolled 26 patients with primary malignant lung tumors who underwent 99mTc-3PRGD2 SPECT/CT and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT imaging. Both imaging methods were analyzed in qualitative (visual dichotomous and 5-point grades for lymph nodes and lung tumors, respectively) and semi-quantitative (maximum tissue-to-background radioactive count) manners for the lymph nodes and lung tumors. The performance of the differentiation of lymph nodes with and without metastasis was determined at the per-lymph node station and per-patient levels using histopathological results as the reference standard. RESULTS: Total 42 stations had metastatic lymph nodes and 136 stations had benign lymph nodes. The differences between metastatic and benign lymph nodes in the visual qualitative and semiquantitative analyses of 99mTc-3PRGD2 SPECT/CT and 18F-FDG PET/CT were statistically significant (all P < 0.001). The area under the receiver operating characteristic curve (AUC) in the semi-quantitative analysis of 99mTc-3PRGD2 SPECT/CT was 0.908 (95% confidence interval [CI], 0.851-0.966), and the sensitivity, specificity, positive predictive value, and negative predictive value were 0.86 (36/42), 0.88 (120/136), 0.69 (36/52), and 0.95 (120/126), respectively. Among the 26 patients (including two patients each with two lung tumors), 15 had pathologically confirmed lymph node metastasis. The difference between primary lung lesions in patients with and without lymph node metastasis was statistically significant only in the semi-quantitative analysis of 99mTc-3PRGD2 SPECT/CT (P = 0.007), with an AUC of 0.807 (95% CI, 0.641-0.974). CONCLUSION: 99mTc-3PRGD2 SPECT/CT imaging may notably perform in the direct diagnosis of lymph node metastasis of primary malignant lung tumors and indirectly predict the presence of lymph node metastasis through uptake in the primary lesions.

On-chip single-mode thin-film lithium niobate Fabry-Perot resonator laser based on Sagnac loop reflectors.

We demonstrate an on-chip single-mode Er3+-doped thin-film lithium niobate (Er:TFLN) laser which consists of a Fabry-Perot (FP) resonator based on Sagnac loop reflectors (SLRs). The fabricated Er:TFLN laser has a footprint of 6.5 mm × 1.5 mm with a loaded quality (Q) factor of 1.6 × 105 and a free spectral range (FSR) of 63 pm. We generate the single-mode laser at 1544 nm wavelength with a maximum output power of 44.7 µW and a slope efficiency of 0.18%.

Diagnostic value of dynamic 18F-FDG PET/CT imaging in non-small cell lung cancer and FDG hypermetabolic lymph nodes.

Background: We aimed to investigate the diagnostic value of dynamic 2-deoxy-2-[18F]-fluoro-D-glucose positron emission tomography-computed tomography in non-small cell lung cancer and fluoro-D-glucose hypermetabolic lymph nodes. Methods: Patients who made an active appointment for positron emission tomography-computed tomography were randomly enrolled by referring to previous imaging data and clinical information. Finally, 34 histopathologically confirmed non-small cell lung cancers (18 adenocarcinoma and 16 squamous cell carcinoma cases) were prospectively studied using dynamic and static 2-deoxy-2-[18F]-fluoro-D-glucose positron emission tomography-computed tomography imaging (the diagnostic study has not yet been registered on a clinical trial platform). In dynamic positron emission tomography images, a volume of interest, defined by the thoracic aorta, was selected for estimating the arterial input function. Patlak and irreversible two-tissue compartment model analyses were performed based on the pixel points to obtain first-order characteristic kinetic parameters for each lesion and hypermetabolic lymph node. The first-order characteristic kinetic parameters were obtained based on the basic data of dynamic positron emission tomography images in the corresponding model and the lesion delineation of region-of-interest based on computed tomography images, such as V_Median (the median gray intensity of V), k3_Entropy, VB_Entropy, K1_Uniformity, and ki_Uniformity. The first-order characteristic kinetic parameters were also modeled by logistic regression for the differential diagnosis of non-small cell lung cancer and hypermetabolic lymph nodes. Maximum and mean standard uptake values (SUVmax and SUVmean, respectively) were obtained from static positron emission tomography images. The diagnostic efficacy of the parameters was evaluated using the receiver operating characteristic curve and the DeLong test. Results: There was a significant difference in the V_Median values of adenocarcinoma and squamous cell carcinoma. The regression models for K1, k3, and V provided good predictions of adenocarcinoma and squamous cell carcinoma typology. Significant differences were observed in k3_Entropy, VB_Entropy, K1_Uniformity, and ki_Uniformity between benign and malignant lymph nodes. The regression model of Ki, VB, and k3 could make a good prediction for identifying benign and malignant lymph nodes. Conclusions: Dynamic 2-deoxy-2-[18F]-fluoro-D-glucose positron emission tomography-computed tomography imaging showed high diagnostic value in the staging of non-small cell lung cancer and fluoro-D-glucose hypermetabolic lymph nodes, and can be of great use in non-small cell lung cancer lymph node staging and surgical decision-making.

Background-free single-beam coherent Raman spectroscopy assisted by air lasing.

We develop a background-free single-beam coherent Raman scattering technique enabling the high-sensitivity detection of greenhouse gases. In this scheme, Raman coherence prepared by a femtosecond laser is interrogated by self-generated narrowband air lasing, thus allowing single-beam measurements without complex pulse shaping. The unique temporal and spectral characteristics of air lasing are beneficial for improving the signal-to-noise ratio and spectral resolution of Raman signals. With this method, SF6 gas present at a concentration of 0.38% was detected in an SF6-air mixture. This technique provides a simple and promising route for remote detection due to the low divergence of Raman signals and the availability of high-energy pump lasers, which may broaden the potential applications of air lasing.

Photon retention in coherently excited nitrogen ions.

Quantum coherence in quantum optics is an essential part of optical information processing and light manipulation. Alkali metal vapors, despite the numerous shortcomings, are traditionally used in quantum optics as a working medium due to convenient near-infrared excitation, strong dipole transitions and long-lived coherence. Here, we proposed and experimentally demonstrated photon retention and subsequent re-emittance with the quantum coherence in a system of coherently excited molecular nitrogen ions (N2+) which are produced using a strong 800 nm femtosecond laser pulse. Such photon retention, facilitated by quantum coherence, keeps releasing directly-unmeasurable coherent photons for tens of picoseconds, but is able to be read out by a time-delayed femtosecond pulse centered at 1580 nm via two-photon resonant absorption, resulting in a strong radiation at 329.3 nm. We reveal a pivotal role of the excited-state population to transmit such extremely weak re-emitted photons in this system. This new finding unveils the nature of the coherent quantum control in N2+ for the potential platform for optical information storage in the remote atmosphere, and facilitates further exploration of fundamental interactions in the quantum optical platform with strong-field ionized molecules..

Development of a generalized model for kidney depth estimation in the Chinese population: A multi-center study.

PURPOSE: To establish an accurate and reliable equation for kidney depth estimation in adult patients from different Chinese geographical regions. METHOD: This multicenter study enrolled Eastern Asian Chinese patients with abdominal PET/CT scans at 26 imaging centers from six macro-regions across China in 3 years. Age, gender, height, weight, primary disease and its extent on PET scans of the participants were collected as potential predictive factors. Kidney depth on CT, defined as the average of the vertical distances from the posterior skin to the farthest anterior and closest posterior surfaces of each kidney, was measured as the standard reference. The new kidney depth model was constructed using a multiple regression model, and its performance was compared to those of three established models by computing the absolute value of estimation errors in comparison with CT-measured kidney depth. RESULTS: A total of 2502 patients were enrolled and classified into training (n=1653) and testing (n = 849) subsets. In the training subset, two kidney depth models were constructed: Left (cm): 0.013×age+0.117×gender-0.044×height+0.087×weight+7.951, Right (cm): 0.005×age+0.013×gender-0.035×height+0.082×weight+7.266 (weight: kg, height: cm, gender = 0 if female, 1 if male). In the testing subset, one-way analysis of variance showed that the estimation errors of the new models did not significantly differ among the 6 regions. Bland-Altman analysis determined that new equations had lower estimated biases (left: 0.039 cm, right: 0.018 cm) compared with other existing models. CONCLUSION: The new equations were highly accurate for kidney depth estimation in adults from all over China, with lower estimation errors compared to other established models.

99mTc-3PRGD2 scintigraphy to stage liver fibrosis and evaluate reversal after fibrotic stimulus withdrawn.

OBJECTIVE: Scintigraphy using 99mTc-3PRGD2 targeting integrin αvß3 could assess activation of hepatic stellate cells (HSCs). Liver fibrogenesis is intimately associated with activation of HSCs, and the fibrolytic process is accompanied by the reduction of the activated HSCs. In this study, we aimed to evaluate the feasibility of this method to assess the severity of liver fibrosis and the reversal after the fibrotic stimulus withdrawal. METHODS: Liver fibrosis of different stages was induced by thioacetamide (TAA) injection for 2, 4 and 6 weeks (n = 6 for each time point). Another 6 rats with 8-week TAA administration (the 8-week group) and 6 rats which were injected with TAA for 6 weeks, and then withdrawn of TAA for 2 weeks (spontaneous recovery rats, SRR) were designed. The ratios of radioactivity detected in the liver vs. the heart at 30 min post-injection of 99mTc-3PRGD2 (L/H30min), the collagen proportionate area (CPA), the protein and mRNA levels of integrin αv, integrin ß3 were analyzed and compared among groups. RESULTS: The Ishak stage scores of the livers in the control and 2, 4, 6-week groups increased when the TAA administration period was extended. L/H30min increased with the upgrading of liver fibrosis and the differences between each pair of groups were statistically significant (p 30 min in the 8-week group was similar to that in the 6-week group (p > 0.05), but was significantly higher than that in the SRR group (p = 0.005). CONCLUSIONS: Scintigraphy using 99mTc-3PRGD2 may provide a non-invasive method for grading liver fibrosis and assessing liver fibrosis reversal.

Effect of different segmentation algorithms on metabolic tumor volume measured on 18F-FDG PET/CT of cervical primary squamous cell carcinoma.

BACKGROUND AND PURPOSE: It is known that fluorine-18 fluorodeoxyglucose PET/computed tomography (CT) segmentation algorithms have an impact on the metabolic tumor volume (MTV). This leads to some uncertainties in PET/CT guidance of tumor radiotherapy. The aim of this study was to investigate the effect of segmentation algorithms on the PET/CT-based MTV and their correlations with the gross tumor volumes (GTVs) of cervical primary squamous cell carcinoma. MATERIALS AND METHODS: Fifty-five patients with International Federation of Gynecology and Obstetrics stage Ia∼IIb and histologically proven cervical squamous cell carcinoma were enrolled. A fluorine-18 fluorodeoxyglucose PET/CT scan was performed before definitive surgery. GTV was measured on surgical specimens. MTVs were estimated on PET/CT scans using different segmentation algorithms, including a fixed percentage of the maximum standardized uptake value (20∼60% SUVmax) threshold and iterative adaptive algorithm. We divided all patients into four different groups according to the SUVmax within target volume. The comparisons of absolute values and percentage differences between MTVs by segmentation and GTV were performed in different SUVmax subgroups. The optimal threshold percentage was determined from MTV20%∼MTV60%, and was correlated with SUVmax. The correlation of MTViterative adaptive with GTV was also investigated. RESULTS: MTV50% and MTV60% were similar to GTV in the SUVmax up to 5 (P>0.05). MTV30%∼MTV60% were similar to GTV (P>0.05) in the 50.05) in the 100.05) in the SUVmax of at least 15 group. MTViterative adaptive was similar to GTV in both total and different SUVmax groups (P>0.05). Significant differences were observed among the fixed percentage method and the optimal threshold percentage was inversely correlated with SUVmax. The iterative adaptive segmentation algorithm led to the highest accuracy (6.66±50.83%). A significantly positive correlation was also observed between MTViterative adaptive and GTV (Pearson's correlation r=0.87, P<0.0001). CONCLUSION: MTViterative adaptive is independent of SUVmax, more accurate, and correlated with GTV. Iterative adaptive algorithm segmentation may be more suitable than the fixed percentage threshold method to estimate the tumor volume of cervical primary squamous cell carcinoma.

Relationship of 18F-FDG PET/CT metabolic, clinical and pathological characteristics of primary squamous cell carcinoma of the cervix.

The objectives of this retrospective study were to use preoperative 18fluoro-d-glucose (18FDG) PET/CT in patients with primary cervical squamous cell carcinoma to explore the relationship between clinical, pathological and metabolic characteristics. Eighty consecutive patients with squamous cell carcinoma of cervix received 18FDG PET/CT scan before treatment. Metabolic tumor volume (MTV), total lesion glycolysis (TLG) and the peak standardized uptake value (SUVpeak) of the cervical tumors were calculated by an iterative adaptive algorithm. The association of these metabolic markers with serum squamous cell carcinoma antigen (SCC-ag), International Federation of Gynecology and Obstetrics (FIGO) stage, maximum tumor size and depth of cervical stromal invasion of the tumor was determined by the multivariate analysis. MTV and TLG were significantly higher in subjects with serum SCC-ag levels ≥3.95, with FIGO stage 1b2 and with a maximum tumor size of ≥4 cm (p≤0.009). Higher SUVpeak levels were associated with a maximum tumor size of ≥4 cm and with a cervical stromal invasion depth of ≥1/2 (p≤0.003). Multivariate analysis indicated that MTV was independently associated with FIGO stage Ib2 (p=0.041) and depth of cervical stromal invasion (p=0.020). TLG and SUVpeak were independently associated with maximum tumor size (p≤0.004) and depth of cervical stromal invasion (p≤0.013). Significant linear correlation was found between SUVpeak and tumor size; the Pearson correlation coefficient was 0.34 (p=0.002). Metabolic parameters such as MTV, TLG and SUVpeak are able to predict clinical and pathological status in preoperative cervical cancer.

18F-FLT and 18F-FDG PET-CT imaging in the evaluation of early therapeutic effects of chemotherapy on Walker 256 tumor-bearing rats.

The present study aimed to evaluate the early therapeutic effects of chemotherapy on Walker 256 tumor-bearing Wistar rats via F-18-fluoro-3'-deoxy-3'-L-fluorothymidine (18F-FLT) and F-18-fluoro-deoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) imaging. Walker 256 tumor-bearing Wistar rats were subjected to 18F-FLT and 18F-FDG PET-CT imaging prior to and 24 and 48 h after epirubicin chemotherapy. 18F-FLT and 18F-FDG uptake [tumor/muscle (T/M)], the percentage of injected dose per gram (% ID/g), and the Ki-67 labeling index (LI-Ki-67) were quantitatively determined for each rat prior to and following epirubicin chemotherapy. The correlation between % ID/g and tumor LI-Ki-67 was analyzed. Both 18F-FLT and 18F-FDG tumor uptake decreased significantly at 24 and 48 h after chemotherapy (P<0.01 and P<0.05, respectively). LI-Ki-67 also significantly reduced 24 and 48 h after chemotherapy (P<0.001). Furthermore, 18F-FLT and 18F-FDG T/M tumor uptake correlated positively with LI-Ki-67 before and after chemotherapy (r=0.842 and 0.813, respectively). During the early post-chemotherapy stage, 18F-FLT and 18F-FDG uptake in Walker 256 tumors reduced significantly, which correlated positively with the tumor cell proliferative activity.

Assessing activation of hepatic stellate cells by (99m)Tc-3PRGD2 scintigraphy targeting integrin αvß3: a feasibility study.

OBJECTIVE: Hepatic stellate cell (HSC) activation, which is accompanied by increased expression of integrin αvß3, is an important factor in liver fibrogenesis. Molecular imaging targeting the integrin αvß3 could provide a non-invasive method for evaluating the expression and the function of the integrin αvß3 on the activated HSCs (aHSCs) in the injured liver, and then provide important prognostic information. (99m)Tc-3PRGD2 is such a radiotracer specific for integrin αvß3. In this study, we aimed to compare the differences in liver uptake and retention of the (99m)Tc-3PRGD2 between normal liver and injured liver to evaluate the feasibility of (99m)Tc-3PRGD2 scintigraphy for this purpose. METHODS: We used planar scintigraphy to assess changes in integrin αvß3 binding of intravenously-administered (99m)Tc-3PRGD2 in the livers of rats with thioacetamide (TAA)-induced liver fibrosis compared with the controls. We co-injected cold c(RGDyK) with (99m)Tc-3PRGD2 to assess the specific binding of the radiotracer. We performed Sirius red staining to assess liver fibrosis, immunofluorescent colocalization to identify the location of integrin αvß3 expressed in the fibrotic liver, and we measured protein and messenger RNA expression of integrin αvß3 and alpha smooth muscle actin (α-SMA) in the control and fibrotic livers. RESULTS: The fibrotic livers showed enhanced (99m)Tc-3PRGD2 uptake and retention. The radiotracer was demonstrated to bind specifically with the integrin αvß3 mainly expressed on the aHSCs. The liver-to-heart ratio at 30 min post-injection was higher in the fibrotic livers than in the control livers (TAA, 1.98±0.08 vs. control, 1.50±0.12, p<0.01). The liver t1/2 was longer than in the controls (TAA, 27.07±10.69 min vs. control, 12.67±4.10 min, p<0.01). The difference of heart t1/2 between the two groups was not statistically significant (TAA, 3.13±0.63 min vs. control, 3.41±0.77 min, p=0.94). CONCLUSIONS: (99m)Tc-3PRGD2 molecular imaging can provide a non-invasive method for assessing activation of HSCs.

Value of ¹8F-FDG PET/CT in the diagnosis of primary gastric cancer via stomach distension.

OBJECTIVE: To clarify the usefulness of (18)F-FDG PET/CT for detecting primary gastric cancer via gastric distention using a mixture of milk and Diatrizoate Meglumine. MATERIALS AND METHODS: A total of 68 patients (male: 47, female: 21; age: 41-87 years) suspected of gastric carcinoma underwent (18)F-FDG PET/CT imaging. After whole-body PET/CT imaging in a fasting state, the patients drank a measured amount of milk with Diatrizoate Meglumine. Local gastric district PET/CT imaging was performed 30 min later. The imaging was analyzed by semi-quantitative analysis, standardized uptake value (SUV) of the primary tumor was measured in a region of interest. The diagnosis results were confirmed by gastroscopy, pathology, and follow-up results. RESULTS: Of the 68 patients, 56 malignant gastric neoplasm patients (male: 37, female: 19) were conformed. The sensitivity, specificity, positive predictive value and negative predictive value of fasting whole-body PET/CT imaging for a primary malignant tumor were 92.9%, 75.0%, 94.5%, and 69.0%, respectively. The values for distension with a mixture of milk and Diatrizoate Meglumine were 91.1%, 91.7%, 98.1%, and 68.8%, respectively. The area under the curve was 0.919 ± 0.033 and 0.883 ± 0.066 for the diagnosis of gastric cancer with SUVmax in a fasting state and after intake of mixture respectively, the differences were not statistically significant (P=0.359). Using gastric distension with a mixture of milk and Diatrizoate Meglumine, the mean ratio of the lesion's SUVmax to the adjacent gastric wall SUVmax increased significantly from 3.30 ± 3.05 to 13.50 ± 15.05, which was statistically significant (P<0.001). CONCLUSIONS: (18)F-FDG PET/CT imaging is highly accurate for the diagnosis of primary gastric carcinoma. Gastric distention can display the lesions more clearly, however, it cannot significantly improve diagnostic accuracy.

Sphincter of Oddi manometry by choledochoscope in patients with duodenobiliary reflux.

BACKGROUND AND AIM: Previous research has confirmed that duodenobiliary reflux exists in patients with choledocholithiasis. The objective of this study was to investigate whether the motor activity of the sphincter of Oddi (SO) has an effect on duodenobiliary reflux. METHODS: A total of 51 patients orally ingested 1mL water containing technetium-99m diethylenetriaminepentaacetatic acid, and a 2-h bile collection was obtained from the T tube. Technetium counts in the collected bile were performed using an RM905 radioactivity meter. The patients were divided into two groups: reflux group (duodenobiliary reflux positive) and control group (duodenobiliary reflux negative). Next, 33 cases were randomly selected and double blinded to receive SO manometry by choledochoscope. RESULTS: Of the 51 total cases, 16 bile samples exhibited radioactivity. The average SO basal pressure and contraction pressure values were 7.2±3.9mmHg and 53.5±24.5mmHg, respectively, in the reflux group, and 14.7±11.0mmHg and 117.2±65.6mmHg, respectively, in the control group. The choledochus pressure values were 5.1±1.6mmHg and 11.5±7.4mmHg in the reflux group and the control group, respectively. The differences between the groups were statistically significant; however, the SO contraction frequency, SO contraction duration, and duodenum pressure values were not significantly different between the groups. CONCLUSION: The decreases in the SO basal pressure and SO contraction pressure, and the decrease in choledochus pressure, might play a role in duodenobiliary reflux.