Spectral Analysis Based on Hemodynamic Habitat Imaging Predicts Isocitrate Dehydrogenase Status and Prognosis in High-Grade Glioma.

BACKGROUND: The intratumoral heterogeneity of high-grade gliomas (HGGs) is associated with isocitrate dehydrogenase (IDH) status and prognosis, which can be established by quantitative radioanalysis of spatial tumor habitats. Therefore, we designed a framework for tackling tumors based on spatial metabolism using the hemodynamic tissue signature (HTS), focusing on metabolic changes in tumor habitat to predict IDH status and assess prognosis in patients with HGG. METHODS: Preoperative data for 121 patients with HGG with subsequent histologic confirmation of HGG were prospectively collected (January 2016 to December 2020). The HTS was mapped from the image data, chemical shift imaging voxels were selected from the HTS habitat as the region of interest, and the metabolic ratio of the HTS was calculated using weighted least square method fitting. The metabolic rate of the tumor enhancement area was used as a control to analyze the efficacy of each HTS metabolic rate in predicting the IDH status and prognosis of HGG. RESULTS: Total choline (Cho)/total creatine and Cho/N-acetyl-aspartate showed significant differences between IDH-wildtype and IDH-mutant in high- and low-angiogenic enhanced tumor sites (P < 0.05); Cho/total creatine was an independent risk factor for prognosis of HGG patients in high-angiogenic enhanced tumor habitats, with significant differences in survival time between groups (P < 0.05). The metabolic ratio in the tumor enhanced area could not predict IDH status or evaluate prognosis. CONCLUSIONS: Spectral analysis based on hemodynamic habitat imaging can clearly distinguish IDH mutations and the prognosis assessment is more accurate, rendering it superior to traditional spectral analysis in tumor enhancement areas.

LncRNA GAL promotes colorectal cancer liver metastasis through stabilizing GLUT1.

Colorectal cancer liver metastasis (CRLM) is the leading cause of colorectal cancer-related deaths and remains a clinical challenge. Enhancement of glucose uptake is involved in CRLM; however, whether long noncoding RNAs (lncRNAs) participate in these molecular events remains largely unclear. Here, we report an lncRNA, GAL (glucose transporter 1 (GLUT1) associated lncRNA), that was upregulated in CRLM tissues compared with primary colorectal cancer (CRC) tissues or matched normal tissues and was associated with the overall survival rates of CRLM patients. Functionally, GAL served as an oncogene because it promoted CRC cell migration and invasion in vitro and enhanced the ability of CRC cells to metastasize from the intestine to the liver in vivo. Mechanistically, GAL interacted with the GLUT1 protein to increase GLUT1 SUMOylation, inhibiting the effect of the ubiquitin-proteasome system on the GLUT1 protein. GLUT1-knockout (-/+) repressed the GAL-mediated increase in CRC cell uptake of glucose, migrate, and invade in vitro, as well as metastasis from the intestine to the liver in vivo, and enforced expression of GLUT1 rescued GAL knockout-induced biological functions in CRC cells. Taken together, our findings demonstrated that GAL promotes CRLM by stabilizing GLUT1, suggesting that the GAL-GLUT1 complex may act as a potential therapeutic target for CRLM.

Vessel Size Imaging is Associated with IDH Mutation and Patient Survival in Diffuse Lower-Grade Glioma.

BACKGROUND: Patients with isocitrate dehydrogenase (IDH) mutant gliomas have better survival and appear to be more sensitive to chemotherapy than their IDH wild-type counterparts. We attempted to assess the correlations of vessel size imaging (VSI) values with IDH mutation status and patient survival in diffuse lower-grade glioma (LGG). METHODS: We enrolled 60 patients with diffuse LGGs, among which 43 had IDH-mutant tumors. All patients underwent VSI examination and VSI values for active tumors were calculated. Receiver operating characteristic (ROC) curves were established to evaluate the detection efficiency. Logistic regression was employed to determine the ability of variables to discriminate IDH mutational status. Kaplan-Meier survival analysis and Cox proportional hazards models were utilized to estimate the correlations of VSI values and other risk factors with patient survival. RESULTS: We observed that VSI values were lower in IDH-mutant LGGs than IDH wild-type LGGs. The VSImax and VSImean values had AUC values of 0.7305 and 0.7401, respectively, in distinguishing IDH-mutant LGGs from IDH wild-type LGGs. Logistic regression showed that VSImean values, age and tumor location were associated with IDH-mutant status, and the formula integrating the three factors had an AUC value of 0.7798 when distinguishing IDH-mutant LGGs from IDH wild-type LGGs. Moreover, LGG patients with high VSI values exhibited worse survival rates than those with low VSI values for both progression-free survival (PFS) and overall survival (OS). Multivariate Cox proportional hazards regression analysis suggested that IDH mutation status, VSImean values and multiple lesions or lobes were risk factors for PFS of LGG patients. CONCLUSION: VSI value is associated with IDH genotype and maybe an independent predictor of the survival of patients with LGGs.

Carcinoma of unknown primary detected by whole-body diffusion-weighted imaging: A case report and review of the literature.

Carcinoma of unknown primary accounts for 2%-5% of all head and neck tumors. Identification of the primary site is challenging. We present a case report of a 43-year-old man with metastatic cervical lymphadenopathy for 3 year, and the primary tumor was unknown after routine examinations, including positron emission tomography/computed tomography. Whole-body diffusion-weighted imaging was performed to detect small lesions in the nasopharynx, and a biopsy confirmed the lesions as squamous cell carcinoma. Therefore, the primary tumor site was found in a patient with carcinoma of unknown primary, suggesting that whole-body diffusion-weighted imaging can be very helpful in detecting small occult cancer.

Microvascular characteristics of lower-grade diffuse gliomas: investigating vessel size imaging for differentiating grades and subtypes.

OBJECTIVES: Vessel size imaging (VSI) could reveal average microvessel diameter. The aim was to investigate microvascular characteristics and the efficacy of VSI in lower-grade glioma (LGG) grading and subtype differentiation based on 2016 classification of central nervous system tumours. METHODS: Fifty-seven LGG (grade II/III, 36/21) patients who received VSI examination before surgery were retrospectively analysed. The average (Rmean) and maximum (Rmax) vessel size indexes were obtained. The long (VDmax) and short (VDmin) vascular diameter, microvascular area (MVA) and density (MVD) were obtained using paraffin specimens. The patients were divided into grades II and III, and histological and molecular subtypes. The differences among microvascular parameters of different subtypes and grades were compared. Two-sample t-test, analysis of variance test, Mann-Whitney test, the Kruskal-Wallis test and Pearson correlation analysis were used for statistics. RESULTS: Rmean, Rmax, VDmin, VDmax, and MVA were higher in grade-III than in grade-II LGGs (p < 0.05) in each type except the isocitrate dehydrogenase (IDH) mutant with 1p/19q-intact type. For grade II, the IDH mutant with 1p/19q co-deleted and IDH wildtype possessed more dominant angiogenesis than IDH mutant with 1p/19q-intact type, revealed by lower Rmean, Rmax and VDmin while higher MVD for the former (p < 0.05), the same as oligodendroglioma versus astrocytoma. Rmean and Rmax correlated with VDmin (r = 0.804, 0.815, p < 0.05), VDmax (r = 0.766, 0.774, p < 0.05) and MVA (r = 0.755, 0.759, p < 0.05), respectively, while they had no correlation with MVD (r = -0.085, -0.080, p > 0.05). CONCLUSIONS: VSI holds great potential for non-invasively revealing microvascular characteristics of LGGs pre-surgery and differentiating their grades and molecular subtypes. KEY POINTS: • VSI can assist in differentiating grade-II and -III gliomas. • The IDH gene and 1p/19q chromosome may influence the angiogenesis in grade-II gliomas. • VSI is valuable for differentiating the molecular subtypes of grade-II gliomas.

Dynamic MR imaging for functional vascularization depends on tissue factor signaling in glioblastoma.

Glomeruloid vascular proliferation (GVP) is a diagnostic hallmark and links to aggressive behavior, therapy resistance and poor prognosis in glioblastoma (GBM). It lacks clinical approaches to predict and monitor its formation and dynamic change. Yet the mechanism of GVPs also remains largely unknown. Using an in situ GBM xenograft mouse model, combined clinical MRI images of pre-surgery tumor and pathological investigation, we demonstrated that the inhibition of tissue factor (TF) decreased GVPs in Mouse GBM xenograft model. TF shRNA reduced microvascular area and diameter, other than bevacizumab. TF dominantly functions via PAR2/HB-EGF-dependent activation under hypoxia in endothelial cells (ECs), resulting in a reduction of GVPs and cancer cells invasion. TF expression strongly correlated to GVPs and microvascular area (MVA) in GBM specimens from 56 patients, which could be quantitatively evaluated in an advanced MRI images system in 33 GBM patients. This study presented an approach to assess GVPs that could be served as a MRI imaging biomarker in GBM and uncovered a molecular mechanism of GVPs.

Textural features of dynamic contrast-enhanced MRI derived model-free and model-based parameter maps in glioma grading.

BACKGROUND: Presurgical glioma grading by dynamic contrast-enhanced MRI (DCE-MRI) has unresolved issues. PURPOSE: The aim of this study was to investigate the ability of textural features derived from pharmacokinetic model-based or model-free parameter maps of DCE-MRI in discriminating between different grades of gliomas, and their correlation with pathological index. STUDY TYPE: Retrospective. SUBJECTS: Forty-two adults with brain gliomas. FIELD STRENGTH/SEQUENCE: 3.0T, including conventional anatomic sequences and DCE-MRI sequences (variable flip angle T1-weighted imaging and three-dimensional gradient echo volumetric imaging). ASSESSMENT: Regions of interest on the cross-sectional images with maximal tumor lesion. Five commonly used textural features, including Energy, Entropy, Inertia, Correlation, and Inverse Difference Moment (IDM), were generated. RESULTS: All textural features of model-free parameters (initial area under curve [IAUC], maximal signal intensity [Max SI], maximal up-slope [Max Slope]) could effectively differentiate between grade II (n = 15), grade III (n = 13), and grade IV (n = 14) gliomas (P < 0.05). Two textural features, Entropy and IDM, of four DCE-MRI parameters, including Max SI, Max Slope (model-free parameters), vp (Extended Tofts), and vp (Patlak) could differentiate grade III and IV gliomas (P < 0.01) in four measurements. Both Entropy and IDM of Patlak-based Ktrans and vp could differentiate grade II (n = 15) from III (n = 13) gliomas (P < 0.01) in four measurements. No textural features of any DCE-MRI parameter maps could discriminate between subtypes of grade II and III gliomas (P < 0.05). Both Entropy and IDM of Extended Tofts- and Patlak-based vp showed highest area under curve in discriminating between grade III and IV gliomas. However, intraclass correlation coefficient (ICC) of these features revealed relatively lower inter-observer agreement. No significant correlation was found between microvascular density and textural features, compared with a moderate correlation found between cellular proliferation index and those features. DATA CONCLUSION: Textural features of DCE-MRI parameter maps displayed a good ability in glioma grading. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1099-1111.

Quantitative in vivo imaging of tissue factor expression in glioma using dynamic contrast-enhanced MRI derived parameters.

OBJECTIVE: Tissue Factor (TF) has been well established in angiogenesis, invasion, metastasis, and prognosis in glioma. A noninvasive assessment of TF expression status in glioma is therefore of obvious clinical relevance. Dynamic contrast-enhanced (DCE) MRI parameters have been used to evaluate microvascular characteristics and predict molecular expression status in tumors. Our aim is to investigate whether quantitative DCE-MRI parameters could assess TF expression in glioma. MATERIALS AND METHODS: Thirty-two patients with histopathologically diagnosed supratentorial glioma who underwent DCE-MRI were retrospectively recruited. Extended Tofts linear model was used for DCE-MRI post-processing. Hot-spot, whole tumor cross-sectional approaches, and histogram were used for analysis of model based parameters. Four serial paraffin sections of each case were stained with TF, CD105, CD34 and α-Sooth Muscle Actin, respectively for evaluating the association of TF and microvascular properties. Pearson correlation was performed between percentage of TF expression area and DCE-MRI parameters, multiple microvascular indexes. RESULTS: Volume transfer constant (Ktrans) hot-spot value best correlated with TF (r=0.886, p<0.001), followed by 90th percentile Ktrans value (r=0.801, p<0.001). Moreover, histogram analysis of Ktrans value demonstrated that weak TF expression was associated with less heterogeneous and positively skewed distribution. Finally, pathology analysis revealed TF was associated with glioma grade and significantly correlated with these two dynamic angiogenic indexes which could be used to explain the strong correlation between Ktrans and TF expression. CONCLUSION: Our results indicate that Ktrans may serve as a potential clinical imaging biomarker to predict TF expression status preoperatively in gliomas.

Glioma grading by microvascular permeability parameters derived from dynamic contrast-enhanced MRI and intratumoral susceptibility signal on susceptibility weighted imaging.

BACKGROUND: Dynamic contrast-enhanced MRI (DCE-MRI) estimates vascular permeability of brain tumors, and susceptibility-weighted imaging (SWI) may demonstrate tumor vascularity by intratumoral susceptibility signals (ITSS). This study assessed volume transfer constant (Ktrans) accuracy, the volume of extravascular extracellular space (EES) per unit volume of tissue (Ve) derived from DCE-MRI, and the degree of ITSS in glioma grading. METHODS: Thirty-two patients with different glioma grades were enrolled in this retrospective study. Patients underwent DCE-MRI and non-contrast enhanced SWI by three-tesla scanning. Ktrans values, Ve, and the degree of ITSS in glioma were compared. Receiver operating characteristic (ROC) curve analysis determined diagnostic performances of Ktrans and Ve in glioma grading, and Spearman's correlation analysis determined the associations between Ktrans, Ve, ITSS, and tumor grade. RESULTS: Ktrans and Ve values were significantly different between low grade gliomas (LGGs) and both high grade gliomas (HGGs) and grade II, III and IV gliomas (P<0.01). The degree of ITSS of LGGs was lower than HGGs (P<0.01), and the ITSS of grade II gliomas was lower than grade III or IV gliomas. Ktrans and Ve were correlated with glioma grade (P<0.01), while ITSS was moderately correlated (P<0.01). Ktrans values were moderately correlated with ITSS in the same segments (P<0.01). CONCLUSION: Ktrans and Ve values, and ITSS helped distinguish the differences between LGGs and HGGs and between grade II, III and IV gliomas. There was a moderate correlation between Ktrans and ITSS in the same tumor segments.

Stereotactic body radiotherapy with concurrent chemotherapy extends survival of patients with limited stage small cell lung cancer: a single-center prospective phase II study.

We carried out a prospective phase II study of patients with limited stage small cell lung cancer (LS-SCLC) assigned to receive stereotactic body radiotherapy (SBRT) concurrently with cisplatin-based chemotherapeutic regimen with OS and PFS as the primary study endpoints. Patients with pathologically proven LS-SCLC received 4-6 cycles of cisplatin 75 mg/(m(2)/day) given intravenously on day 1 and etoposide 80 mg/(m(2)/day) given intravenously on days 1-5, both at 3 weekly intervals. SBRT at a dose of 4,000-4,500 cGy in ten fractions was given concurrently with chemotherapy starting on day 1. The Kaplan-Meier curve and life tables were used to describe survival data. Adverse events were evaluated according to the common terminology criteria for adverse events version of the radiation therapy oncology group (RTOG). Twenty-nine patients were included and followed up for a median duration of 19 (range 10-85) months. The median OS was 27 (95% CI 20.2-33.8) months. The median PFS was 12 (95% CI 4.2-19.8) months. No grade 4 adverse events were observed. Grade 3 adverse events occurred in only 5 (13.8%, 5/29) patients. Neutropenia of any grade was observed in 6 (15%, 6/29) patients, with grade 3 neutropenia only seen in one (3.4%, 1/29) patient. The combination of chemotherapy and early concurrent SBRT could be a safe and effective treatment for LS-SCLC patients. Our study confirmed that SBRT with concurrent chemotherapy is another new treatment option for LS-SCLC patients.

Left coronary artery-to-right atrium fistula: an evaluation of MSCT angiography before and after transcatheter closure with a PDA occluder.

The MSCT manifestations of a left coronary artery-to-right atrium fistula before and after the transcatheter closure were reported. Before treatment, MSCT showed a dilated left coronary sinus and the dilated left main trunk, which coursed along the coronary sulcus to form the left circumflex artery, draining directly into the right atrium in the left middle part. The fistula was occluded with a PDA occluder. Four days after the occlusion, MSCT showed that the fistula was completely occluded and there was massive thrombosis in the central part and around the occluder. The thrombus was found even in the segment near to the start point of the oblique marginal artery.