Texture Features of 18F-Fluorodeoxyglucose Positron Emission Tomography for Predicting Programmed Death-Ligand-1 Levels in Non-Small Cell Lung Cancer.

Background: Identifying programmed death-ligand-1 (PD-L1) expression is crucial for optimizing treatment strategies involving immune checkpoint inhibitors. However, the role of intratumoral metabolic heterogeneity specifically derived from 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) images in predicting PD-L1 expression in patients with newly diagnosed non-small cell lung cancer (NSCLC) remains unexplored. Here, we investigated the association between FDG PET texture features and PD-L1 expression by retrospectively analyzing the data of patients newly diagnosed with NSCLC who underwent FDG PET/CT scans and PD-L1 immunohistochemical staining before treatment. Methods: Patients were categorized based on their tumor proportion scores (TPSs) into negative-, low-, and high-PD-L1 expression groups. We computed the maximum standardized uptake value and 31 texture features for the primary tumor from PET images and compared differences in parameters among the groups. Results: Of the 83 patients, 12, 45, and 26 were assigned to the negative-, low-, and high-PD-L1 expression groups, respectively. Six specific texture features (low gray-level run emphasis, short-run low gray-level emphasis, long-run high gray-level emphasis, low gray-level zone emphasis, high gray-level zone emphasis, and short-zone low gray-level emphasis) helped distinguish among all possible combinations. Conclusions: Our findings revealed that FDG PET texture features are potential imaging biomarkers for predicting PD-L1 expression in patients newly diagnosed with NSCLC.

Feasibility of PiB positron emission tomography/computed tomography for treatment monitoring with Tafamidis in a patient with transthyretin cardiac amyloidosis.

We present a 77-year-old woman with wild-type ATTR cardiac amyloidosis (ATTR-CA) who presented with dyspnea, arrhythmia, and elevated NT-pro BNP. Initial imaging including cardiac MRI, PYP scintigraphy, PiB PET/CT and NaF PET/CT revealed cardiac abnormalities. Tafamidis treatment was initiated. After 14 months, symptomatic improvement and reduced NT-pro BNP were observed. Cardiac MRI and PYP scintigraphy showed no significant change and increased NaF accumulation, while PiB PET/CT showed decreased amyloid deposition, suggesting that it may be superior to NaF PET/CT in assessing the therapeutic effect of tafamidis in ATTR-CA.

Predictive value of local control by 4'-[methyl-11C]-thiotymidine PET volume parameters in p16-negative oropharyngeal, hypopharyngeal, and supraglottic squamous cell carcinoma.

PURPOSE: We investigated the potential of baseline 4'-[methyl- 11 C]-thiothymidine ([ 11 C]4DST) PET for predicting loco-regional control of head and neck squamous cell carcinoma (HNSCC). METHODS: A retrospective analysis was performed using volumetric parameters, such as SUVmax, proliferative tumor volume (PTV), and total lesion proliferation (TLP), of pretreatment [ 11 C]4DST PET for 91 patients with HNSCC with primary lesions in the oral cavity, hypopharynx, supraglottis, and oropharynx, which included p16-negative patients. PTV and TLP were calculated for primary lesions and metastatic lymph nodes combined. We examined the association among the parameters and relapse-free survival and whether case selection focused on biological characteristics improved the accuracy of prognosis prediction. RESULTS: The area under the curves (AUCs) using PTV and TLP were high for the oropharyngeal/hypopharyngeal/supraglottis groups (0.91 and 0.87, respectively), whereas that of SUVmax was 0.66 ( P  < 0.01). On the other hand, the oral group had lower AUCs for PTV and TLP (0.72 and 0.77, respectively). When all cases were examined, the AUCs using PTV and TLP were 0.84 and 0.83, respectively. CONCLUSION: Baseline [ 11 C]4DST PET/CT volume-based parameters can provide important prognostic information with p16-negative oropharyngeal, hypopharyngeal, and supraglottic cancer patients.

Feasibility of 11C-Pittsburgh compound B positron emission tomography/computed tomography for treatment monitoring with Tafamidis in a patient with transthyretin cardiac amyloidosis.

We present a 77-year-old woman with wild-type ATTR cardiac amyloidosis (ATTR-CA) who presented with dyspnea, arrhythmia, and elevated NT-pro BNP. Initial imaging including cardiac MRI, PYP scintigraphy, PiB PET/CT and NaF PET/CT revealed cardiac abnormalities. Tafamidis treatment was initiated. After 14 months, symptomatic improvement and reduced NT-pro BNP were observed. Cardiac MRI and PYP scintigraphy showed no significant change and increased NaF accumulation, while PiB PET/CT showed decreased amyloid deposition, suggesting that it may be superior to NaF PET/CT in assessing the therapeutic effect of tafamidis in ATTR-CA.

Physiological myocardial 18F-FDG uptake pattern in oncologic PET/CT: comparison with findings in cardiac sarcoidosis.

Objectives: Physiological myocardial 18F-fluorodeoxyglucose (18F-FDG) uptake in oncologic positron emission tomography (PET)/computed tomography (CT) is commonly observed with multiple variations under clinical fasting conditions. The purpose of the present study was to evaluate physiological myocardial 18F-FDG uptake pattern by comparing with the results in cardiac sarcoidosis. Methods: A total of 174 examinations in 174 patients without cardiac disease and 27 examinations in 17 patients with cardiac sarcoidosis were performed. The polar map images generated from 18F-FDG PET/CT data were visually assessed as "basal-ring," "focal," and "focal on diffuse" patterns. Semi-quantitative analysis was also performed using the regional relative 18F-FDG uptake (% uptake). Results: On visual analysis, the "focal on diffuse" pattern was the most common in both examinations (43% and 59%, respectively). The physiological % uptake in the lateral and basal septal walls tended to be higher. Subgroup analysis showed significantly higher uptake in the mid-wall and left circumflex territory. In cardiac sarcoidosis patients, there was a significant difference only between segments 2 and 15 (p=0.04). No significant differences were observed between the base-mid-apical territory and coronary artery branch territory. Conclusion: High 18F-FDG uptake in the basal septal walls is likely to be observed as both physiological uptake in patients without cardiac disease and pathological uptake in patients with cardiac sarcoidosis.

Comparative evaluation of 11C-methionine and 18F-fluorodeoxyglucose positron emission tomography for distinguishing between primary central nervous system lymphoma and isocitrate dehydrogenase-wildtype glioblastoma.

PURPOSE: Distinguishing between primary central nervous system lymphoma (PCNSL) and isocitrate dehydrogenase (IDH)-wildtype glioblastoma is important for therapeutic decision-making. This study aimed to compare the performance of 11C-methionine (MET) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for distinguishing between these two major malignant brain tumors. METHODS: We retrospectively conducted qualitative and semiquantitative analyses of pre-treatment MET and FDG PET/computed tomography (CT) images of 22 patients with PCNSL and 64 patients with IDH-wildtype glioblastoma. For semiquantitative analysis, we calculated the tumor-to-normal tissue (T/N) ratio by dividing the maximum standardized uptake value (SUV) for the tumor (T) by the average SUV for the normal tissue (N). For performance evaluation, we employed receiver operating characteristic curve analysis and calculated the areas under the curve (AUC) values. RESULTS: In the qualitative analysis, all PCNSLs and IDH-wildtype glioblastomas were MET-positive, while 95% and 84% of PCNSLs and IDH-wildtype glioblastomas, respectively, were FDG-positive. Eleven patients were excluded from the FDG PET/CT semiquantitative analysis because of hyperglycemia. There was no difference in MET T/N ratio between PCNSL and IDH-wildtype glioblastoma (p = 0.37). FDG T/N ratio was significantly higher in PCNSL than in IDH-wildtype glioblastoma (p < 0.001). The AUC value for distinguishing PCNSL from IDH-wildtype glioblastoma was significantly higher for the FDG T/N ratio (0.871) than for the MET T/N ratio (0.565) (p = 0.0027). CONCLUSION: MET PET could detect both PCNSL and IDH-wildtype glioblastoma, but unlike FDG PET, it could not distinguish between these two major malignant brain tumors.

Stimulatory and inhibitory effect of antipsychotic agents including dopaminergic neuro-depressants on dopamine formation from p-tyramine mediated by cytochrome P450 2D6.

BACKGROUND AND OBJECTIVES: The effects of antipsychotic agents, including dopamine D2 receptor blocking agents such as haloperidol, chlorpromazine, and sulpiride, and related compounds such as mirtazapine and sertraline, on dopamine formation from p-tyramine catalyzed by cytochrome P450 (CYP) 2D6.2 (Arg296Cys;Ser486Thr), CYP2D6.10 (Pro34Ser;Ser486Thr), and CYP2D6.39 (Ser486Thr) were compared with those of CYP2D6.1. METHODS: Dopamine was determined by high-performance liquid chromatography, and Michaelis constants (Km), maximal velocity (kcat) values for dopamine formation, and inhibition constants (Ki) of psychotropic agents were estimated. RESULTS: Km values for all CYP2D6 variants decreased at lower concentrations, and kcat values for CYP2D6 variants except for CYP2D6.10 gradually increased with increasing haloperidol concentrations up to 5 or 10 µM. The kcat/Km values for all CYP2D6 variants increased at under 2.5 µM concentrations. Lower sertraline concentrations decreased Km values for CYP2D6.10. Chlorpromazine at concentrations under 10 µM competitively inhibited the activities catalyzed by all variants; however, the activities for only CYP2D6.10 were increased by chlorpromazine at concentrations over 250 µM. Mirtazapine and sertraline similarly decreased dopamine formation among all variants except for CYP2D6.10. However, CYP2D6.10 inhibition by mirtazapine was weaker than that of the other variants, and sertraline decreased Km values for CYP2D6.10. CONCLUSION: Haloperidol and sertraline, but not sulpiride, decreased the Km and/or increased kcat values for CYP2D6. The present findings suggest that Dopamine D2 receptor-blocking agents and related compounds may polymorphically affect dopamine formation catalyzed by CYP2D6 in the brain.

Buccal Abscess Caused by Toothbrush Trauma: A Case Report of a Two-Year-Old.

Children often experience impalement trauma when they fall while holding objects in their mouths. While most cases heal without complications, here we report a case of buccal abscess formation after toothbrush trauma. A two-year-old boy fell while running with a toothbrush in his mouth, which punctured his right buccal mucosa. The following day, he presented to a pediatrician with a fever and buccal swelling and was treated with oral antibiotics. However, the buccal swelling did not improve, and the patient was referred to our department. Four days after the visit, the buccal swelling and fever worsened, requiring hospitalization, intravenous antibiotics, and drainage. The inflammation quickly disappeared following treatment, with no recurrence. Prophylactic antibiotic administration for oral impalement trauma is controversial. Our results suggest that prophylactic antibiotics covering both anaerobic and aerobic bacteria are necessary in cases of toothbrush-related oral trauma, where multiple bacterial infections may occur.

A missense variant at the RAC1-PAK1 binding site of RAC1 inactivates downstream signaling in VACTERL association.

RAC1 at 7p22.1 encodes a RAC family small GTPase that regulates actin cytoskeleton organization and intracellular signaling pathways. Pathogenic RAC1 variants result in developmental delay and multiple anomalies. Here, exome sequencing identified a rare de novo RAC1 variant [NM_018890.4:c.118T > C p.(Tyr40His)] in a male patient. Fetal ultrasonography indicated the patient to have multiple anomalies, including persistent left superior vena cava, total anomalous pulmonary venous return, esophageal atresia, scoliosis, and right-hand polydactyly. After birth, craniofacial dysmorphism and esophagobronchial fistula were confirmed and VACTERL association was suspected. One day after birth, the patient died of respiratory failure caused by tracheal aplasia type III. The molecular mechanisms of pathogenic RAC1 variants remain largely unclear; therefore, we biochemically examined the pathophysiological significance of RAC1-p.Tyr40His by focusing on the best characterized downstream effector of RAC1, PAK1, which activates Hedgehog signaling. RAC1-p.Tyr40His interacted minimally with PAK1, and did not enable PAK1 activation. Variants in the RAC1 Switch II region consistently activate downstream signals, whereas the p.Tyr40His variant at the RAC1-PAK1 binding site and adjacent to the Switch I region may deactivate the signals. It is important to accumulate data from individuals with different RAC1 variants to gain a full understanding of their varied clinical presentations.

Normative change with gestation in fetal intraventricular pressure difference with color M-mode Doppler echocardiography.

AIM: The intraventricular pressure difference (IVPD) is the pressure difference in early diastole from the base to the apex of the ventricle. It is a useful marker for evaluating diastolic function because of its role as a suction force. This study investigated the changes in total and segmental IVPDs in normal fetuses throughout gestation to obtain normative data equations. METHODS: One hundred thirty-seven healthy pregnant women at 12-40 weeks of gestation were prospectively enrolled to evaluate IVPD. The color M mode was performed, and the image was evaluated using our own code to calculate the IVPD. Segmental IVPD was divided into mid to apex and base. Pearson's correlation coefficient was used to evaluate this relationship. RESULTS: There was a significant, positive relationship between IVPD and gestational age in both ventricles (right ventricle [RV]: r = 0.800, left ventricle [LV]: r = 0.818). As for segmental IVPD, basal and mid-apical IVPD also increased with gestation in both ventricles (RV: basal, r = 0.627; mid-apical, r = 0.705; LV: basal r = 0.758; mid-apical, r = 0.756). IVPG, which was calculated as IVPD/ventricular length, also showed a weak, positive relationship with gestation in both ventricles (RV r = 0.351, p < 0.001; LV r = 0.373, p < 0.001). CONCLUSION: The total and segmental IVPDs significantly increased linearly through time.

FDG PET texture indices as imaging biomarkers for epidermal growth factor receptor mutation status in lung adenocarcinoma.

Identifying the epidermal growth factor receptor (EGFR) mutation status is important for the optimal treatment of patients with EGFR mutations. We investigated the relationship between 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) texture indices and EGFR mutation status in patients with newly diagnosed lung adenocarcinoma. We retrospectively analyzed data of patients with newly diagnosed lung adenocarcinoma who underwent pretreatment FDG PET/computed tomography and EGFR mutation testing between August 2014 and November 2020. Patients were divided into mutated EGFR and wild-type EGFR groups. The maximum standardized uptake value (SUVmax) and 31 texture indices for the primary tumor were calculated from PET images and compared between the two groups. Of the 66 patients included, 22 had mutated EGFR and 44 had wild-type EGFR. The SUVmax did not significantly differ between the two groups. Among the 31 evaluated texture indices, the following five showed a statistically significant difference between the groups: correlation (P = 0.003), gray-level nonuniformity for run (P = 0.042), run length nonuniformity (P = 0.02), coarseness (P = 0.006), and gray-level nonuniformity for zone (P = 0.04). Based on the preliminary results of this study in a small patient population, FDG PET texture indices may be potential imaging biomarkers for the EGFR mutation status in patients with newly diagnosed lung adenocarcinoma.

An analysis of the left top pulmonary vein and comparison with the right top pulmonary vein for lung resection by three-dimensional CT angiography and thin-section images.

PURPOSE: The right top pulmonary vein (RTPV) is defined as an anomalous branch of the right superior PV (SPV) draining into the PV or left atrium (LA). Several previous reports have described the RTPV, but only a few have mentioned the left top PV (LTPV). The present study aimed to evaluate the branching patterns of the RTPV and LTPV using thin-section CT images and three-dimensional CT angiography (3D-CTA). MATERIALS AND METHODS: This study included 1437 consecutive patients for evaluation of the right side and 1454 consecutive patients for the left side who were suspected of lung cancer and underwent CTA. We assessed the presence of each RTPV and LTPV and their branching patterns on the CTA images. When the RTPV or LTPV was identified, the maximum short-axis diameter was measured. RESULTS: RTPV was found in 9.1% (131/1437), whereas LTPV was found in 2.9% (42/1454) of the patients. RTPV was also observed in 17.1% (7/41) of LTPV cases, except for one case in which the right side could not be evaluated. The most common RTPV inflow site was the right inferior PV (IPV) in 64.9% (85/131) of the patients, whereas that of the LTPV was the left IPV in 100.0% (42/42) of the patients. The mean diameter of the RTPV and LTPV was 3.3 mm (range, 1.3-7.5 mm) and 2.4 mm (range, 0.9-6.3 mm), respectively (P < 0.01). CONCLUSION: The top PV branching pattern variations can be evaluated using thin-section CT and 3D-CTA images. RTPV is not a rare finding, and LTPV should also be identified in lung cancer cases scheduled for resection.

S-Palmitoylation of the serotonin transporter promotes its cell surface expression and serotonin uptake.

The neurotransmitter serotonin (5-HT) is transported back into serotonergic neurons by the serotonin transporter (SERT). SERT is a main target of antidepressants, and much effort has therefore focused on finding relationships between SERT and depression. However, it is not fully understood how SERT is regulated at the cellular level. Here, we report post-translational regulation of SERT by S-palmitoylation, in which palmitate is covalently attached to cysteine residues of proteins. Using AD293 cells (a human embryonic kidney 293-derived cell line with improved cell adherence) transiently transfected with FLAG-tagged human SERT, we observed S-palmitoylation of immature SERT containing high-mannose type N-glycans or no N-glycan, which is presumed to be localized in the early secretory pathway, such as the endoplasmic reticulum. Mutational analysis by alanine substitutions shows that S-palmitoylation of immature SERT occurs at least at Cys-147 and Cys-155, juxtamembrane cysteine residues within the first intracellular loop. Furthermore, mutation of Cys-147 reduced cellular uptake of a fluorescent SERT substrate that mimics 5-HT without decreasing SERT on the cell surface. On the other hand, combined mutation of Cys-147 and Cys-155 inhibited SERT surface expression and reduced the uptake of the 5-HT mimic. Thus, S-palmitoylation of Cys-147 and Cys-155 is important for both the cell surface expression and 5-HT uptake capacity of SERT. Given the importance of S-palmitoylation in brain homeostasis, further investigation of SERT S-palmitoylation could provide new insights into the treatment of depression.

Characterization of aroma profiles of kokuto-shochu prepared from three different cultivars of sugarcane.

Kokuto-shochu is a traditional Japanese spirit prepared from kokuto, obtained by evaporating water from sugarcane (Saccharum officinarum L.) juice. To clarify the effects of sugarcane cultivars on the sensory quality of kokuto-shochu, we investigated the flavor characteristics and composition of volatiles in kokuto-shochu prepared from kokuto using three different sugarcane cultivars, NiF8, Ni15, and RK97-14. Furthermore, experiments were conducted by using the cultivars collected between 2018 and 2020 to observe annual variations in their properties. The amino acid content of the three kokuto varieties did not differ significantly, but the amino acid content of NiF8 was two to five times higher than that of RK97-14, which was the same for all samples collected in the selected years. The browning degrees of kokuto were also higher in NiF8, and they were positively correlated to the amino acid contents of kokuto. The kokuto-like aroma of shochu made from Ni15 was stronger than that of shochu made from RK97-14. The concentration of ethyl lactate in shochu made from Ni15 was higher, however, the concentration of guaiacol was the lowest in the three cultivars' products. Shochu made from NiF8 had the highest levels of Maillard reaction products (MRPs; pyrazines and furans), ß-damascenone, and guaiacol amounts. In contrast, shochu made from RK97-14 tended to have a fruity flavor, and lower MRP levels than those made from NiF8. Thus, it was shown that sugarcane cultivars affect the sensory characteristics and volatiles in kokuto-shochu.

Feasibility of whole-body 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography angiography using continuous bed motion in patients with vascular disease: a pilot study.

OBJECTIVE: Positron emission tomography (PET) angiography is a promising PET imaging method for vessel evaluation. With advances in PET technologies, PET angiography of the whole body is now possible using continuous bed motion (CBM) mode. This study aimed to evaluate the image quality for depicting the aorta and main branches and the diagnostic performance of whole-body PET angiography in patients with vascular disease. METHODS: We retrospectively identified 12 consecutive patients who underwent whole-body 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET angiography in CBM mode. Whole-body PET angiography was performed between 20 and 45 s after administering [18F]FDG using CBM from the neck to the pelvis. The visibility of whole-body PET angiography was assessed for the 24 segments in three regions per patient using a 4-point grading scale (1, unacceptable; 2, poor; 3, good; 4, excellent), and grades 3 and 4 were considered diagnostic. The diagnostic accuracy of whole-body PET angiography for detecting vascular abnormalities was calculated using contrast-enhanced CT as a reference standard. RESULTS: We evaluated 285 segments from 12 patients, and overall, 170/285 segments (60%) were considered diagnostic throughout the whole body, including 96/117 (82%), 22/72 (31%), and 52/96 (54%) segments in the neck-to-chest region, abdominal region, and pelvic region, respectively. The sensitivity, specificity, and accuracy of whole-body PET angiography for detecting vascular abnormalities were 75.9%, 98.8%, and 96.5%, respectively. CONCLUSIONS: Whole-body PET angiography showed a better image quality for the neck-to-chest and pelvic regions in this setting, although it provided limited information on the vessels in the abdominal region.

[18F] FDG uptake in patients with spondyloarthritis: correlation with serum inflammatory biomarker levels.

BACKGROUND: We aimed to evaluate the correlation between 2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake and disease activity assessed by serum inflammatory biomarker levels in patients with spondyloarthritis (SpA). METHODS: A total of 36 SpA patients (24 untreated and 12 treated) were examined using FDG positron emission tomography (PET)/computed tomography and classified into axial SpA (axSpA) and peripheral SpA (pSpA). FDG uptake was evaluated in 23 regions of the body and scored as follows: 0 = less than liver uptake; 1 = more than or equal to liver uptake; and 2 = more than or equal to twice liver uptake. A score of 1 or 2 was considered positive. The number of positive regions and the total score were counted in each patient. The maximum standardized uptake value (SUVmax) was calculated for each region, and maximum SUVmax (MaxSUVmax) was used as a representative value. Correlation of PET findings with serum inflammatory biomarker levels, including C-reactive protein (CRP), erythrocyte sedimentation rate, and matrix metalloproteinase 3 (MMP-3), was analyzed. RESULTS: All but two patients had at least one positive lesion. PET indices correlated significantly with most of the serum inflammatory biomarker levels in untreated SpA, but not in treated SpA. Further, MaxSUVmax, number of positive regions, and total score correlated significantly with CRP (all P values < 0.001), and the number of positive regions (P = 0.012) and total score (P = 0.007) correlated significantly with MMP-3 in untreated pSpA. PET indices did not correlate with any serum inflammatory biomarker level in untreated axSpA. CONCLUSION: FDG uptake in untreated pSpA correlated significantly with serum inflammatory biomarker levels.