Prediction of high-grade patterns of stage IA lung invasive adenocarcinoma based on high-resolution CT features: a bicentric study.

OBJECTIVES: This study aims to predict the high-grade pattern (HGP) of stage IA lung invasive adenocarcinoma (IAC) based on the high-resolution CT (HRCT) features. METHODS: The clinical, pathological, and HRCT imaging data of 457 patients (from bicentric) with pathologically confirmed stage IA IAC (459 lesions in total) were retrospectively analyzed. The 459 lesions were classified into high-grade pattern (HGP) (n = 101) and non-high-grade pattern (n-HGP) (n = 358) groups depending on the presence of HGP (micropapillary and solid) in pathological results. The clinical and pathological data contained age, gender, smoking history, tumor stage, pathological type, and presence or absence of tumor spread through air spaces (STAS). CT features consisted of lesion location, size, density, shape, spiculation, lobulation, vacuole, air bronchogram, and pleural indentation. The independent predictors for HGP were screened by univariable and multivariable logistic regression analyses. The clinical, CT, and clinical-CT models were constructed according to the multivariable analysis results. RESULTS: The multivariate analysis suggested the independent predictors of HGP, encompassing tumor size (p = 0.001; OR = 1.090, 95% CI 1.035-1.148), density (p < 0.001; OR = 9.454, 95% CI 4.911-18.199), and lobulation (p = 0.002; OR = 2.722, 95% CI 1.438-5.154). The AUC values of clinical, CT, and clinical-CT models for predicting HGP were 0.641 (95% CI 0.583-0.699) (sensitivity = 69.3%, specificity = 79.2%), 0.851 (95% CI 0.806-0.896) (sensitivity = 79.2%, specificity = 79.6%), and 0.852 (95% CI 0.808-0.896) (sensitivity = 74.3%, specificity = 85.8%). CONCLUSION: The logistic regression model based on HRCT features has a good diagnostic performance for the high-grade pattern of stage IA IAC. KEY POINTS: • The AUC values of clinical, CT, and clinical-CT models for predicting high-grade patterns were 0.641 (95% CI 0.583-0.699), 0.851 (95% CI 0.806-0.896), and 0.852 (95% CI 0.808-0.896). • Tumor size, density, and lobulation were independent predictive markers for high-grade patterns. • The logistic regression model based on HRCT features has a good diagnostic performance for the high-grade patterns of invasive adenocarcinoma.

Imaging the Transformation of Ipsilateral Internal Capsule Following Focal Cerebral Ischemia in Rat by Diffusion Kurtosis Imaging.

BACKGROUND: The purpose of our study is to explore the relationship between recovery of neural function and transformation of the internal capsule (IC) after transient middle cerebral artery occlusion (MCAO) by using diffusion kurtosis imaging (DKI). METHODS: Six male adult Sprague-Dawley rats implemented with transient MCAO were used in this study. Sensorimotor function was assessed according to repetitive behavioral testing on day 1, 3, 7, 14, and 28 after cerebral ischemia. Metrics of DKI were acquired, and the time course of the region-to-normal ratio was evaluated in IC. RESULTS: After cerebral ischemia, relative fractional anisotropy in IC decreased on day 3 (P < .01). Relative mean diffusivity (rMD) increased on day 28 (P < .05). Relative mean diffusional kurtosis (rMK) increased on day 3 (P < .01) and decreased on day 7 (P < .05). Relative axial diffusional kurtosis (rKa) increased on day 3 (P < .01) and declined on day 7 (P < .05). Relative radial diffusional kurtosis (rKr) was reduced on day 7 (P < .05). Changes in rMK were larger than changes in rMD on day 3 (P < .05). The factor of rKa and rKr revealed marked difference on day 7 (P < .05) and day 14 (P < .05). Neurological function score showed that rats exhibited functional recovery from day 7 (P < .01) post stroke. CONCLUSIONS: This longitudinal multiparametric magnetic resonance imaging study suggested that K metrics offers information complimentary to conventional diffusion metrics and revealed the procedure during the structural modification in the ipsilateral IC following focal cerebral ischemia. After transient MCAO, the neural transformation occurred in a time-dependent procedure.

Combining systemic and stereotactic MEMRI to detect the correlation between gliosis and neuronal connective pathway at the chronic stage after stroke.

BACKGROUND: The early dysfunction and subsequent recovery after stroke, characterized by the destruction and remodeling of connective pathways between cortex and subcortical regions, is associated with neuroinflammation. As major components of the inflammatory process, reactive astrocytes have double-edged effects on pathological progression. The temporal patterns of astrocyte and neuronal pathway activity can be revealed by systemic and stereotactic manganese-enhanced magnetic resonance imaging (MEMRI), respectively. In the present study, we aimed to detect an association between astrocyte activity and recovery of neuronal connective pathways by combining systemic with stereotactic MEMRI. METHODS: Fifty adult rats, divided into two groups, underwent a 60-min occlusion of the middle cerebral artery. The groups were given either a systemic administration or stereotactic injection of MnCl2 at 1, 3, 7, and 14 days after stroke and underwent MRI 4 and 2 days later, respectively. Immunofluorescence (IF) of group 1 was conducted to corroborate the results. Repetitive behavioral testing was also performed with all rats at 1, 3, 7, and 14 days to obtain a functional score. RESULTS: Ring- or crescent-shaped enhancements formed in the striatal peri-infarct regions (STR) at 11 and 18 days. This was concurrent with the activity of glial fibrillary acidic protein (GFAP)-positive astrocytes, which mainly localized at the peri-infarct region and significantly increased in number at 11 and 18 days after stroke. Microglia/macrophages, detected by IF, mainly localized in the lesion core, rather than in the region of enhancement. The ipsilateral substantia nigra (SN) revealed Mn-related signal enhancement reduction and subsequent signs of the recovery process at 3 to 5 days and 9 to 16 days, respectively. Behavioral testing showed that sensorimotor functions were initially disturbed, but subsequently recovered at 7 and 14 days. CONCLUSIONS: We found a positive temporal correlation between astrogliosis and the recovery of neuronal connective pathways at the chronic stage by using the in vivo method of MEMRI. Our results highlighted the potential contribution of astrocytes to the neuronal recovery of these connective pathways.

Normalization of T2 relaxation time and apparent diffusion coefficient in relation to the inflammatory changes in the substantia nigra of rats with focal cerebral ischemia.

BACKGROUND: Focal cerebral ischemia results in delayed neurodegeneration in remote brain regions, such as the substantia nigra. To date, a reasonable explanation is still lacking regarding the correlation of magnetic resonance (MR) signal pseudo-normalization following a transient abnormal change and subsequent progressive pathological damage. PURPOSE: To characterize the substantia nigra following middle cerebral artery occlusion and to evaluate the potential pathophysiological changes associated with the pseudo-normalization of MR signals in the substantia nigra at the subacute stage after stroke onset. MATERIAL AND METHODS: Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion. During the occlusion of single middle cerebral artery, computed tomography (CT) perfusion was acquired to observe the blood flow perfusion in the primary ischemic striatum and ipsilateral substantia nigra. Next, the MR T2 relaxation time and apparent diffusion coefficient changes within the substantia nigra were determined on days 1, 3, 7, and 14 after stroke onset, and compared with immunohistochemistry for microglia activation and astrogliosis. RESULTS: Twenty-four rats with strong hypoperfusion in the primary ischemic territory and no alterations of the perfusion in the ipsilateral substantia nigra detected both visually and measurably during the middle cerebral artery occlusion were further studied. All animals showed MR pseudo-normalization with T2 relaxation time and apparent diffusion coefficient recovered in the ipsilateral substantia nigra at the subacute phase following focal cerebral ischemia. Normalization of the MR signals corresponded well with the spatio-temporal occurrence of microglia activation and astrogliosis. CONCLUSION: The pseudo-normalization of T2 relaxation time and apparent diffusion coefficient reflects the neuroinflammatory changes that accompany activation of microglia and astrocytes in the ipsilateral substantia nigra following middle cerebral artery occlusion.

Comparison of USPIO-enhanced MRI and Gd-DTPA enhancement during the subacute stage of focal cerebral ischemia in rats.

BACKGROUND: Being one class of magnetic resonance imaging (MRI) contrast agents, ultrasmall superparamagnetic particles of iron oxides (USPIO) bear the potential to study neuroinflammation following stroke, but there is still debate over whether the iron oxides particles may enter the brain tissue passively over a damaged blood-brain barrier (BBB). PURPOSE: To compare the enhancement patterns of USPIO and gadopentate dimeglumine (Gd-DTPA) during the subacute stage of focal cerebral ischemia, to examine the relationship between USPIO enhancement and BBB disturbance, as well as with neuroinflammatory cell response. MATERIAL AND METHODS: Multiple MR sequences were obtained on days 3 and 6 after transient middle cerebral artery occlusion induced in rats with and without the application of USPIO and Gd-DTPA. The enhancement patterns of the two contrast agents were compared and correlated to histology, including IgG for BBB permeability, Prussian Blue staining for iron particle detection, and CD68 immunohistochemistry staining to identify macrophage/microglia. RESULTS: Gd-DTPA enhancement depicted BBB breakdown being in line with IgG leakage. The USPIO enhanced images demonstrated both diffuse and focal signal alteration in ischemic lesions. The diffuse enhanced pattern had a similar spatial and temporal profile as with Gd-DTPA enhancement. In addition, focal enhanced signal loss was visible on T1-, T2-, and T2*-weighted images, with a peak tendency of MR signal loss, macrophage/microglia concentration and iron particle accumulation at a later phase of the study. CONCLUSION: After focal cerebral ischemia, Gd-DTPA-enhanced MRI showed a higher sensitivity in detecting BBB alterations than did USPIO enhancement. USPIO provided complementary information regarding inflammatory cell activity in neuroinflammatory to cerebral ischemia that had not been visualized using conventional Gd-DTPA. The assessment using multiple MR parameters may identify intracellular and extracellular USPIO in vivo.

In vivo USPIO-enhanced MR signal characteristics of secondary degeneration in the ipsilateral substantia nigra after middle cerebral artery occlusion at 3T.

BACKGROUND AND PURPOSE: Ultrasmall superparamagnetic iron oxide (USPIO) particles to enhance MRI have been used to study neuroinflammation in vivo. Our purpose was to observe the USPIO-enhanced MR signal alterations in the primary ischemic lesion and ipsilateral substantia nigra after middle cerebral artery occlusion (MCAO) to verify the subsequent sequelae of neuroinflammation seen in the primary ischemic focus and secondary degeneration region. MATERIALS AND METHODS: Sprague-Dawley rats were subjected to transient MCAO. In addition to conventional T2-, T1-weighted imaging, USPIO-enhanced MRI was performed in USPIO-injected stroke rats, while Gd-enhanced imaging was acquired in control stroke rats, on days 3, 6 using a 3-T MR scanner. The MR signal characteristics in the primary ischemic striatum, ipsilateral substantia nigra were noted, compared on histopathological H&E, Prussian blue (PB) staining. RESULTS: After MCAO, USPIO-induced T2 hypointensity changes were observed in the primary ischemic region with BBB impairment at both time points. In the substantia nigra ipsilateral to the primary ischemic lesion, there was no evidence of USPIO accumulation detected by MRI and PB staining, and no BBB leakage reflected by Gd-enhanced imaging on days 3 and 6. CONCLUSION: USPIO-enhanced MR signals have variable characteristics in both primary and remote sites after focal cerebral ischemia. This suggests that the neuroinflammatory response to brain ischemia in the primary ischemic focus and secondary degeneration region have different temporal patterns and pathophysiological mechanisms.

Contrast-enhanced CT longitudinal tail sign as a marker of positive resection margins in adenoid cystic carcinoma of the central airway.

BACKGROUND: Due to submucosal infiltration's biological nature along the airway, adenoid cystic carcinoma (ACC) frequently leaves positive surgical margins. This study evaluated the clinicopathologic, and computed tomography (CT) features for predicting surgical margin status in central airway ACC. METHODS: We retrospectively analyzed the files of 71 patients with ACC of the central airway proven by histopathology and surgery who had presented between January 2010 and December 2018. All patients were classified into positive and negative surgical margin groups according to margin status. Univariate analysis and multivariable logistic regression models were then performed to compare demography, histopathology, and CT characteristics between ACC patients with positive and negative margins. RESULTS: After surgical resection, 59 (83.1%) patients had positive margins, and 12 (16.9%) had negative margins. The contrast-enhanced CT (CECT) longitudinal tail sign (LTS) was identified in 55 of 59 (93.2%) patients with positive margins and was the only feature that had a significant association with positive margins (odds ratio 41.250, 95% CI: 7.886-215.767; P<0.001). Moreover, positive margins in upper or/and lower directions were associated with the LTS in corresponding directions (P<0.001). CONCLUSIONS: Most central airway ACC patients exhibited positive margins following surgery. The appearance of the LTS on CECT was significantly associated with positive margins and could help preoperatively predict the submucosal invasion of ACC.

CT diagnosis and prognosis prediction of tracheal adenoid cystic carcinoma.

PURPOSE: To evaluate computed tomography (CT) features and establish a predictive model for the clinical diagnosis and prognosis of tracheal adenoid cystic carcinoma (ACC). METHOD: From January 2010 to December 2018, 82 patients with tracheal tumors, including 46 patients with ACC confirmed by surgery and histopathology, were enrolled in this study. These patients' clinicopathologic information, CT features and survival outcomes were recorded and analyzed. Independent predictors of diagnosis and prognosis of tracheal ACC were determined by both univariate and multivariate analyses. RESULTS: Compared with tracheal non-ACC patients, univariate analysis showed that ACC patients were more likely to have extensive longitudinal length (p < 0.001) and to appear as annular wall thickening (p = 0.001), transmural growth (p = 0.036), poorly defined border (p = 0.003) and mild enhancement (p = 0.001). Multivariate logistic analysis showed that longitudinal length and enhancement degree were independent predictors of tracheal ACC. The 3-year and 5-year disease-free survival (DFS) were 75.7 % and 64.5 %, respectively. Longitudinal length (≥ 34 mm), transverse length (≥ 20 mm) and transmural growth were associated with poor DFS in univariate analysis. After multivariate adjustment, only transverse length (≥ 20 mm) was an adverse prognostic factor for DFS (hazard ratio = 4.594, 95 % confidence interval = 1.240-17.017; p = 0.022). CONCLUSIONS: CT longitudinal length and enhancement degree of tumors showed satisfactory discrimination for tracheal ACC. Excessive CT transverse length might be an unfavorable indicator for ACC recurrence and could be helpful for predicting the survival outcomes of ACC at the initial diagnosis.

A computational study on the influence of aortic valve disease on hemodynamics in dilated aorta.

A computational hemodynamics method was employed to investigate how the morphotype and functional state of aortic valve would affect the characteristics of blood flow in aortas with pathological dilation, especially the intensity and distribution of flow turbulence. Two patient-specific aortas diagnosed to have pathological dilation of the ascending segment while differential aortic valve conditions (i.e., one with a stenotic and regurgitant RL bicuspid aortic valve (RL-BAV), whereas the other with a quasi-normal tricuspid aortic valve (TAV)) were studied. When building the computational models, in addition to in vivo data-based reconstruction of geometrical model and boundary condition setting, the large eddy simulation method was adopted to quantify potential flow turbulence in the aortas. Obtained results revealed the presence of complex flow patterns (denoted by time-varying changes in vortex structure), flow turbulence (indicated by high turbulent eddy viscosity (TEV)), and regional high wall shear stress (WSS) in the ascending segment of both aortas. Such hemodynamic characteristics were significantly augmented in the aorta with RL-BAV. For instance, the space-averaged TEV in late systole and the wall area exposed to high time-averaged WSS (judged by WSS> two times of the mean WSS in the entire aorta) in the ascending aortic segment were increased by 176% and 465%, respectively. Relatively, flow patterns in the descending aortic segment were less influenced by the aortic valve disease. These results indicate that aortic valve disease has profound impacts on flow characteristics in the ascending aorta, especially the distribution and degree of high WSS and flow turbulence.

Abnormal Gray Matter Structural Networks in Idiopathic Normal Pressure Hydrocephalus.

Purpose: Idiopathic normal pressure hydrocephalus (iNPH) is known as a treatable form of dementia. Network analysis is emerging as a useful method to study neurological disorder diseases. No study has examined changes of structural brain networks of iNPH patients. We aimed to investigate alterations in the gray matter (GM) structural network of iNPH patients compared with normal elderly volunteers. Materials and Methods: Structural networks were reconstructed using covariance between regional GM volumes extracted from three-dimensional T1-weighted images of 29 possible iNPH patients and 30 demographically similar normal-control (NC) participants and compared with each other. Results: Global network modularity was significantly larger in the iNPH network (P < 0.05). Global network measures were not significantly different between the two networks (P > 0.05). Regional network analysis demonstrated eight nodes with significantly decreased betweenness located in the bilateral frontal, right temporal, right insula and right posterior cingulate regions, whereas only the left anterior cingulate was detected with significantly larger betweenness. The hubs of the iNPH network were mostly located in temporal areas and the limbic lobe, those of the NC network were mainly located in frontal areas. Conclusions: Network analysis was a promising method to study iNPH. Increased network modularity of the iNPH group was detected here, and modularity analysis should be paid much attention to explore the biomarker to select shunting-responsive patients.

Inhibition of Notch1 Signaling at the Subacute Stage of Stroke Promotes Endogenous Neurogenesis and Motor Recovery After Stroke.

Background and Purpose: It is still not clear whether Notch1 signaling inhibition can promote functional outcomes after stroke, given that it plays time-dependent roles in the sequential process of endogenous neurogenesis. The purpose of this study was to identify the appropriate time frame for Notch1 signaling inhibition according to the temporal evolution of Notch1 signaling activation and the responses of neural stem cells (NSCs), in order to target it for therapeutic intervention and stimulate neurorestorative strategies after stroke. Methods: Sprague-Dawley (SD) rats were subjected to 90-min of middle cerebral artery occlusion (MCAO). Rats were sacrificed before, and at day 1, day 2, day 3, day 4, and day 7 after ischemia for immunohistochemical analysis of the Notch intracellular domain (NICD), Nestin and doublecortin (Dcx). Next, MCAO rats were treated with the γ-secretase inhibitor N-[N-(3,5-di uorophenacetyl)-1-alanyl]-S-phenylglycine t-butylester (DAPT) or with saline at day 4 after ischemia, and subsequently evaluated with behavioral test analysis and magnetic resonance imaging (MRI). The rat brains were then harvested for immunohistochemical analysis of Dcx, NeuN and myelin basic protein (MBP) at 2, 3, 4, and 8 weeks. Results: Notch1 signaling was maximally activated at day 3 after ischemia in parallel with the temporal evolution of NSCs. Inhibiting Notch1 signaling at day 4 after reperfusion with DAPT further promoted recovery of MRI parameters of the corticospinal tract (CST) and the functional outcomes, concomitantly with an increase in neuroblasts, their migration to the ischemic boundary, and potential differentiation to mature neurons, as well as the amelioration of axonal bundle integrity. Conclusion: Inhibition of Notch1 signaling at the subacute stage of stroke could maximally promote endogenous neurogenesis and axonal reorganization.

Dynamic Evaluation of Notch Signaling-Mediated Angiogenesis in Ischemic Rats Using Magnetic Resonance Imaging.

OBJECTIVE: The Notch signaling pathway is involved in angiogenesis induced by brain ischemia and can be efficiently inhibited by the γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester (DAPT). The aim of the present study was to noninvasively investigate the effect of DAPT treatment on angiogenesis in brain repair after stroke using magnetic resonance imaging (MRI). METHODS: Sprague-Dawley rats (n = 40) were subjected to 90 minutes of transient middle cerebral artery (MCA) occlusion and treated with PBS (n = 20) or DAPT (n = 20) at 72 hours after the onset of ischemia. MRI measurements including T2-weighted imaging (T2WI), susceptibility-weighted imaging (SWI), and cerebral blood flow (CBF) were performed at 24 hours after reperfusion and weekly up to 4 weeks using a 3-Tesla system. Histological measurements were obtained at each time point after MRI scans. RESULTS: SWI showed that DAPT treatment significantly enhanced angiogenesis in the ischemic boundary zone (IBZ) with respect to the control group, with local CBF in the angiogenic area elevated, along with increases in vascular density confirmed by histology. CONCLUSION: Treatment of ischemic stroke with DAPT significantly augments angiogenesis, which promotes poststroke brain remodeling by elevating CBF level, and these processes can be dynamically monitored and evaluated by MRI.

MRI detects protective effects of DAPT treatment with modulation of microglia/macrophages at subacute and chronic stages following cerebral ischemia.

Notch homolog 1 (Notch 1) signaling is regarded as a potential therapeutic target for modulating the inflammatory response and exhibiting neuroprotective effects in cerebral injury following stroke. N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t­butylester (DAPT) efficiently inhibits activation of the Notch 1 signaling pathway in microglia and may protect brain tissue from ischemic damage. However, the temporal proliferation and morphological alterations of microglia/macrophages throughout progression of the disease, as well as the comprehensive alterations of the whole brain following DAPT treatment, remain to be elucidated. The present study evaluated the temporal proliferation and the morphological alterations of microglia/macrophages over the period of the subacute and chronic stages, in addition to dynamic alterations of brain tissue, using the magnetic resonance imaging (MRI) method, following DAPT treatment. Sprague­Dawley rats (n=40) were subjected to 90 min of middle cerebral artery occlusion and were treated with DAPT (n=20) or acted as controls with no treatment (n=20). The two groups of rats underwent MRI scans prior to the induction of stroke symptoms and at 24 h, 7, 14, 21 and 28 days following the stroke. A total of five rats from each group were sacrificed at 7, 14, 21 and 28 days following induction of stroke. Compared with control rats, the MRI data of the ipsilateral striatum in treated rats revealed ameliorated brain edema at the subacute stage and recovered brain tissue at the chronic stage. In addition to this, treatment attenuated the round­shape and promoted a ramified­shape of microglia/macrophages. The present study confirmed the protective effect of DAPT treatment by dynamically monitoring the cerebral alterations and indicated the possibility of DAPT treatment to alter microglial characteristics to induce a protective effect, via inhibition of the Notch signaling pathway.