Assessing the diagnostic value of left ventricular synchrony indices derived from phase analysis by D-SPECT in identifying obstructive coronary artery disease.

This study aimed to assess the diagnostic efficacy of left ventricular synchrony (LVS) for detecting coronary artery disease (CAD). We explored whether the LVS index derived from phase analysis of D-SPECT provides superior diagnostic value compared to conventional perfusion analysis in identifying obstructive CAD. Patients with suspected or confirmed CAD underwent drug-stress/rest gated D-SPECT myocardial perfusion imaging (MPI) and coronary angiography (CAG). A 50% stenosis was set as the threshold for obstructive CAD. 110 participants were enrolled in this analysis. There were significant differences in phase standard deviation (PSD), phase histogram bandwidth (PHB) and entropy among the four groups. Patients without cardiac disease and those with mild-moderate stenosis exhibited no noticeable contraction asynchrony. However, LVS indices demonstrated a gradual increase with the progression of coronary stenosis when compared to NC (P < 0.001). Obstructive CAD was identified in 43 out of 110 participants (39%). Optimal cutoff values for diagnosing obstructive CAD during stress were determined as 7.6° for PSD, 24° for PHB, and 37% for entropy, respectively. Notably, PSD, PHB, and entropy indices exhibited higher sensitivity compared to MPI. The integration of the stress-induced LVS indices into routine MPI analysis resulted in a significantly greater area under the curve (AUC), leading to improved diagnostic performance and enhanced differential capacity. Stress-induced LVS indices increase with the severity of coronary artery stenosis by D-SPECT phase analysis. Further, the indices-derived phase analysis exhibits superior sensitivity and discriminatory ability compared to MPI in detecting obstructive CAD.

18F-FDG PET/CT characterization and response evaluation in a case of lymphomatoid granulomatosis involving the main pulmonary artery.

Main pulmonary artery (MPA) involvement of lymphomatoid granulomatosis (LYG) is extremely rare. We described fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) findings in a case with LYG originated from the MPA. Fluorine-18-FDG PET/CT demonstrated nodular hypermetabolic foci in the MPA, corresponding well to the intraluminal filling defects on CT pulmonary angiography, and the secondary right heart dysfunction was observed. Final diagnosis was made after transcatheter MPA biopsies and multi-disciplinary consultation. The patient recovered completely following the steroid therapy and MPA stenting, which was illustrated on the second 18F-FDG PET/CT.

SOX10 deficiency-mediated LAMB3 upregulation determines the invasiveness of MAPKi-resistant melanoma.

Melanoma that develops adaptive resistance to MAPK inhibitors (MAPKi) through transcriptional reprograming-mediated phenotype switching is associated with enhanced metastatic potential, yet the underlying mechanism of this improved invasiveness has not been fully elucidated. In this study, we show that MAPKi-resistant melanoma cells are more motile and invasive than the parental cells. We further show that LAMB3, a ß subunit of the extracellular matrix protein laminin-332 is upregulated in MAPKi-resistant melanoma cells and that the LAMB3-Integrin α3/α6 signaling mediates the motile and invasive phenotype of resistant cells. In addition, we demonstrate that SOX10 deficiency in MAPKi-resistant melanoma cells drives LAMB3 upregulation through TGF-ß signaling. Transcriptome profiling and functional studies further reveal a FAK/MMPs axis mediates the pro-invasiveness effect of LAMB3. Using a mouse lung metastasis model, we demonstrate LAMB3 depletion inhibits the metastatic potential of MAPKi-resistant cells in vivo. In summary, this study identifies a SOX10low/TGF-ß/LAMB3/FAK/MMPs signaling pathway that determines the migration and invasion properties of MAPKi-resistant melanoma cells and provide rationales for co-targeting LAMB3 to curb the metastasis of melanoma cells in targeted therapy.

Correlation study on 18F-FDG PET/CT metabolic characteristics of primary lesion with clinical stage in lung cancer.

BACKGROUND: 18F-FDG PET/CT metabolic characteristics provide the crucial biologic and molecular information for tumors. To explore the relationships between 18F-FDG PET/CT derived parameters such as maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG) of primary tumor and clinical stage in different histopathologic subtypes of lung cancer. METHODS: A total of 97 newly diagnosed lung cancer patients (69 males, 28 females; average age 65.1 years) with pathologically proven were retrospectively analyzed, who had undergone 18F-FDG PET/CT scan before treatment from September 2016 to November 2017. SUVmax, MTV and TLG of primary tumor were measured. Clinical stage was mainly determined by 18F-FDG PET/CT, in conjunction with conventional imaging and endoscopic biopsy. Mann-Whitney U test, χ2 test, Spearman correlation test and ROC curve analysis were used for statistical analysis. RESULTS: There were 53 adenocarcinomas (AC), 28 squamous carcinomas (SCC), 13 small cell carcinomas (SCLC), one adenosquamous carcinoma, one mucoepidermoid carcinoma, and one sarcomatoid carcinoma in 97 patients. Both AC and SCLC revealed more cases in stage IV than in stage I-III (P<0.01). There was no significant difference in four stages of SCC (P>0.05). Metabolic parameters of SCC were higher than AC including SUVmax, MTV and TLG (P<0.01). SCLC showed a higher value than AC in TLG (P<0.05). No significant differences were found between AC and SCLC in SUVmax and MTV, also between SCC and SCLC in SUVmax, MTV and TLG (P>0.05). MTV and TLG except SUVmax were positively correlated with stage in AC (P≤0.001). Only MTV showed a positive correlation with stage in SCC (P<0.05). Whereas there were no definitive relationships between metabolic parameters and stage in SCLC (P>0.05). AC with a higher MTV (MTV≥5.965 cm3) indicated a significantly higher rate of distant metastasis than those with a lower MTV (77.5% (31/40) vs. 30.8% (4/13), χ2=9.553, P<0.01), as well as AC with a higher TLG (TLG≥46.922) than those with a lower TLG (88.5% (23/26) vs. 44.4% (12/27), χ2=11.422, P<0.01). CONCLUSIONS: Histopathologic subtypes have a significant influence on the relationships between MTV/TLG not SUVmax of primary foci and stage in lung cancer. Primary MTV/TLG is related to clinical stage closely in AC, and a higher MTV/TLG results in a higher risk of distant metastasis.

18F-FDG PET/CT delayed images with forced diuresis for revaluating abdominopelvic malignancies.

PURPOSE: The aim of this retrospective study was to evaluate the role of delayed images after forced diuresis coupled with oral hydration in abdominopelvic 18F-FDG PET/CT. MATERIALS AND METHODS: Forty-six patients consisting of 17 urological diseases, 9 gynecological tumors, 18 colorectal malignancies, and 2 cancers of unknown primary site were retrospectively analyzed. All patients who presented with indeterminate or equivocal abdominopelvic foci on standard 18F-FDG PET/CT underwent a delayed abdominopelvic imaging after administration of 20 mg furosemide intravenously and extra water intake of 500 mL. PET/CT images before and after furosemide were compared with each other and their findings correlated with pathology or clinical follow-up (>6 months). RESULTS: On initial PET/CT, the glucose metabolism characters of lesions were disguised by radioactive urine, or some undetermined 18F-FDG accumulating foci near the urinary tract appeared. While postdiuretic PET/CT demonstrated an excellent urinary tracer washout, and hypermetabolic lesions could be clearly detected and precisely localized in all cases. On the other hand, the suspected active foci caused by potential stagnation of excreted 18F-FDG in urinary tract were eliminated. The sensitivity, specificity, and accuracy were 94.4% (34/36), 8/10, 91.3% (42/46), respectively. Furthermore, the additional lesions with surrounding invasion or locoregional metastasis were discovered in 8 of 46 (17.4%) patients only by the delayed images, including 2 gynecological and 6 rectal malignancies. CONCLUSION: Detection of abdominopelvic malignancies can be improved using delayed 18F-FDG PET/CT images after a diuretic and oral hydration.

Uterine Intravenous Leiomyomatosis with Intracardiac Extension and Pulmonary Benign Metastases on FDG PET/CT: A Case Report.

A 48-year-old woman presented with a 50-day history of irregular vaginal bleeding and lower abdominal pain. Ultrasound indicated an extremely large occupying lesion in the pelvic cavity that was highly suggestive of malignancy. Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) was performed to further assess the nature of pelvic abnormality. PET/CT images demonstrated a diffusely lobulated mass ranging from cervix up to the inferior pole of kidneys with mild FDG uptake. Simultaneously, multiple nodules in bilateral lungs and a hypodense lesion in the right ventricle were shown without FDG-avidity. Based on the imaging results, the presumptive diagnosis was uterine intravenous leiomyomatosis with intracardiac extension and pulmonary benign metastases, which was subsequently confirmed by MRI and the lesion biopsy.

Tumor necrosis factor α knockout increases fertility of mice.

Tumor necrosis factor α (TNFα) acts through two receptors, TNFα receptor| (TNFR|) and TNFα‖ (TNFR‖). Tumor necrosis factor α receptor| knockout mice had early senescence and poor fertility, whereas TNFR‖ knockout mice had reproductive performance not different from wild type (WT) mice. In the present study, TNFα knockout mice were used to study the roles of TNFα in female reproduction. The TNFα-/- mice had similar vaginal opening time (PD 27.6 ± 1.8 vs PD 27.7 ± 1.9, respectively, P > 0.05) and exogenous gonadotropin primed TNFα-/- mice shed more ova (28.9 ± 3.75 vs 9.8 ± 0.51, respectively, P = 0.001) compared with WT controls. At 2 mo of age, in 21 d, TNFα-/- mice had more estrous cycles than WT counterparts (6.0 ± 0.25 vs 4.0 ± 0.28, respectively, P < 0.05). Tumor necrosis factor α mutation also influenced ovarian follicular development; TNFα-/- mice had approximately a two-fold larger follicle pool in the early neonatal period (6087 ± 508.15 vs 3440 ± 261.91, respectively, P = 0.004), whereas TNFα knockout affected growth of primordial follicles to the antral stage as well. Moreover, TNFα-/- mice gave birth to 21% more pups than control mice during a 12 mo breeding period (37.38 ± 3.69 vs 22.38 ± 3.53, respectively, P = 0.03). At 1 y of age, the follicular reserve in TNFα-/- mice was more than that in WT mice. These physiological differences in TNFα-/- mice were associated with increased proliferation of granulosa cells and decreased apoptosis of oocytes. This was apparently the first demonstration that in the TNFα-/- mouse model, multiple parameters of ovarian function were altered, and that lack of TNFα increased fertility in mice.