Morphometric similarity network alterations in COVID-19 survivors correlate with behavioral features and transcriptional signatures.

OBJECTIVES: To explore the differences in the cortical morphometric similarity network (MSN) between COVID-19 survivors and healthy controls, and the correlation between these differences and behavioralfeatures and transcriptional signatures. MATERIALS & METHODS: 39 COVID-19 survivors and 39 age-, sex- and education years-matched healthy controls (HCs) were included. All participants underwent MRI and behavioral assessments (PCL-17, GAD-7, PHQ-9). MSN analysis was used to compute COVID-19 survivors vs. HCs differences across brain regions. Correlation analysis was used to determine the associations between regional MSN differences and behavioral assessments, and determine the spatial similarities between regional MSN differences and risk genes transcriptional activity. RESULTS: COVID-19 survivors exhibited decreased regional MSN in insula, precuneus, transverse temporal, entorhinal, para-hippocampal, rostral middle frontal and supramarginal cortices, and increased regional MSN in pars triangularis, lateral orbitofrontal, superior frontal, superior parietal, postcentral, and inferior temporal cortices. Regional MSN value of lateral orbitofrontal cortex was positively associated with GAD-7 and PHQ-9 scores, and rostral middle frontal was negatively related to PHQ-9 scores. The analysis of spatial similarities showed that seven risk genes (MFGE8, MOB2, NUP62, PMPCA, SDSL, TMEM178B, and ZBTB11) were related to regional MSN values. CONCLUSION: The MSN differences were associated with behavioral and transcriptional signatures, early psychological counseling or intervention may be required to COVID-19 survivors. Our study provided a new insight into understanding the altered coordination of structure in COVID-19 and may offer a new endophenotype to further investigate the brain substrate.

An all-in-one biomimetic iron-small interfering RNA nanoplatform induces ferroptosis for cancer therapy.

Iron-dependent ferroptosis is a promising therapeutic strategy for cancers. However, the sustained overexpression of the antioxidant glutathione (GSH) in cancer cells substantially limits its therapeutic effect. Seeking efficient approaches that can perform high GSH depletion efficiency remains a significant task. Herein, we construct an all-in-one nanoplatform with functions of tumor targeting, monitoring and treatment for cancer ferroptosis therapy by constructing a homotypic cancer cell membrane-camouflaged iron-small interfering RNA nanohybrid (CM-Fe-siR). The SLC7A11-targeted siRNA in the nanohybrid inhibits the biosynthesis of GSH by cutting off the supply of intracellular cystine, an essential ingredient in GSH synthesis, which subsequently results in the accumulation of reactive oxygen species (ROS) that are generated from Fenton reaction induced by iron. Meanwhile, the intracellular deficiency of GSH inactivates glutathione peroxidase 4 (GPX4, a lipid repair enzyme), which further increases the accretion of lipid peroxides to enhance iron-induced ferroptosis. This biomimetic nanohybrid shows a remarkable anti-cancer effect by triggering sustainable and efficient ferroptosis via these multiple synergistic actions. Besides, the nanohybrids enable in vivo magnetic resonance imaging (MRI) monitoring of therapy. The biomimetic CM-Fe-siR all-in-one nanoplatform may provide an efficient means of ferroptosis therapy for cancers. STATEMENT OF SIGNIFICANCE: Ferroptosis therapy based on the Fenton reaction of iron nanomaterials has aroused much attention in cancer treatment; however, the therapeutic efficacy is greatly inhibited by the sustained overexpression of the antioxidant GSH in cancer cells. It is of great importance to exploit more reagents or techniques performing high GSH depletion efficiency. Here, we facilely construct an all-in-one cancer cell membrane-camouflaged iron-siRNA nanoplatform, which possesses good biosafety, tumor-targeting, and noninvasive MRI monitoring capabilities. It effectively inhibits the GSH synthesis, and further simultaneously promotes the ROS accumulation and GPX4 inactivation, leading to enhanced cancer ferroptosis. This work highlights that the biomimetic iron-siRNA nanohybrids have a high potential in clinical application for imaging-guided cancer ferroptosis therapy.

MRI-Based Radiomics Nomogram: Prediction of Axillary Non-Sentinel Lymph Node Metastasis in Patients With Sentinel Lymph Node-Positive Breast Cancer.

Background: Overtreatment of axillary lymph node dissection (ALND) may occur in patients with axillary positive sentinel lymph node (SLN) but negative non-SLN (NSLN). Developing a magnetic resonance imaging (MRI)-based radiomics nomogram to predict axillary NSLN metastasis in patients with SLN-positive breast cancer could effectively decrease the probability of overtreatment and optimize a personalized axillary surgical strategy. Methods: This retrospective study included 285 patients with positive SLN breast cancer. Fifty five of them had metastatic NSLNs and 230 had non-metastatic NSLNs. MRI-based radiomic features of primary tumors were extracted and MRI morphologic findings of the primary tumor and axillary lymph nodes were assessed. Four models, namely, a radiomics signature, an MRI-clinical nomogram, and two MRI-clinical-radiomics nomograms were established based on MRI morphologic findings, clinicopathologic characteristics, and MRI-based radiomic features to predict the NSLN status. The optimal predictors in each model were selected using the 5-fold cross-validation (CV) method. Their predictive performances were determined by the receiver operating characteristic (ROC) curves analysis. The area under the curves (AUCs) of different models was compared by the Delong test. Their discrimination capability, calibration curve, and clinical usefulness were also assessed. Results: The 5-fold CV analysis showed that the AUCs ranged from 0.770 to 0.847 for the radiomics signature, from 0.720 to 0.824 for the MRI-clinical nomogram, from 0.843 to 0.932 for the MRI-clinical-radiomics nomogram. The optimal predictive factors in the radiomics signature, MRI-clinical nomogram, and MRI-clinical-radiomics nomogram were one texture feature of diffusion-weighted imaging (DWI), two clinicopathologic features together with one MRI morphologic finding, and the DWI-based texture feature together with the two clinicopathologic features plus the one MRI morphologic finding, respectively. The MRI-clinical-radiomics nomogram with CA 15-3 included achieved the highest AUC compared with the radiomics signature (0.868 vs. 0.806, P <0.001) and MRI-clinical nomogram (0.868 vs. 0.761; P <0.001). In addition, the MRI-clinical-radiomics nomogram without CA 15-3 showed a higher performance than that of the radiomics signature (AUC, 0.852 vs. 0.806, P = 0.016) and the MRI-clinical nomogram (AUC, 0.852 vs. 0.761, P = 0.007). The MRI-clinical-radiomics nomograms showed good discrimination and good calibration. Decision curve analysis demonstrated that the MRI-clinical-radiomics nomograms were clinically useful. Conclusion: The MRI-clinical-radiomics nomograms developed in our study showed high predictive performance, which can be used to predict the axillary NSLN status in SLN-positive breast cancer patients before surgery.

Radiomics Nomograms Based on Non-enhanced MRI and Clinical Risk Factors for the Differentiation of Chondrosarcoma from Enchondroma.

BACKGROUND: Differentiating chondrosarcoma from enchondroma using conventional MRI remains challenging. An effective method for accurate preoperative diagnosis could affect the management and prognosis of patients. PURPOSE: To validate and evaluate radiomics nomograms based on non-enhanced MRI and clinical risk factors for the differentiation of chondrosarcoma from enchondroma. STUDY TYPE: Retrospective. POPULATION: A total of 103 patients with pathologically confirmed chondrosarcoma (n = 53) and enchondroma (n = 50) were randomly divided into training (n = 68) and validation (n = 35) groups. FIELD STRENGTH/SEQUENCE: Axial non-contrast-enhanced T1-weighted images (T1WI) and fat-suppressed T2-weighted images (T2WI-FS) were acquired at 3.0 T. ASSESSMENT: Clinical risk factors (sex, age, and tumor location) and diagnosis assessment based on morphologic MRI by three radiologists were recorded. Three radiomics signatures were established based on the T1WI, T2WI-FS, and T1WI + T2WI-FS sequences. Three clinical radiomics nomograms were developed based on the clinical risk factors and three radiomics signatures. STATISTICAL TESTS: The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of radiomics signatures and clinical radiomics nomograms. RESULTS: Tumor location was an important clinical risk factor (P < 0.05). The radiomics signature based on T1WI and T1WI + T2WI-FS features performed better than that based on T2WI-FS in the validation group (AUC in the validation group: 0.961, 0.938, and 0.833, respectively; P < 0.05). In the validation group, the three clinical radiomics nomograms (T1WI, T2WI-FS, and T1WI + T2WI-FS) achieved AUCs of 0.938, 0.935, and 0.954, respectively. In all patients, the clinical radiomics nomogram based on T2WI-FS (AUC = 0.967) performed better than that based on T2WI-FS (AUC = 0.901, P < 0.05). DATA CONCLUSION: The proposed clinical radiomics nomogram showed promising performance in differentiating chondrosarcoma from enchondroma. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

Nanomedicine Directs Neuronal Differentiation of Neural Stem Cells via Silencing Long Noncoding RNA for Stroke Therapy.

Transplantation of neural stem cells (NSCs) is a promising treatment paradigm to replace lost neurons and reconstruct the damaged neural circuit after ischemic stroke. However, most transplanted NSCs often differentiate into astrocytes rather than functional neurons, and the poor neuronal differentiation adversely affects the therapeutic outcome of NSCs and limits their clinical translation for stroke therapy. Herein, a theranostic nanomedicine is developed to codeliver superparamagnetic iron oxide nanoparticles (SPIO) and small interfering RNA/antisense oligonucleotides (siRNA/ASO) against Pnky long noncoding RNA (lncRNA) into NSCs. This nanomedicine not only directs neuronal differentiation of NSCs through silencing the Pnky lncRNA but also allows an in vivo tracking of NSCs with magnetic resonance imaging. The enhanced neuronal differentiation of NSCs significantly improved the structural and functional recovery of the damaged brain after a stroke. The results demonstrate the great potential of the multifunctional nanomedicine targeting lncRNA to enhance stem cell-based therapies for a stroke.

Mean Apparent Propagator MRI Is Better Than Conventional Diffusion Tensor Imaging for the Evaluation of Parkinson's Disease: A Prospective Pilot Study.

BACKGROUND AND PURPOSE: Mean apparent propagator (MAP) MRI is a novel diffusion imaging method to map tissue microstructure. The purpose of this study was to evaluate the diagnostic value of the MAP MRI in Parkinson's disease (PD) in comparison with conventional diffusion tensor imaging (DTI). METHODS: 23 PD patients and 22 age- and gender-matched healthy controls were included. MAP MRI and DTI were performed on a 3T MR scanner with a 20-channel head coil. The MAP metrics including mean square displacement (MSD), return to the origin probability (RTOP), return to the axis probability (RTAP), and return to the plane probability (RTPP), and DTI metrics including fractional anisotropy (FA), and mean diffusivity (MD), were measured in subcortical gray matter and compared between the two groups. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic performance of all the metrics. The association between the diffusion metrics and disease severity was assessed by Pearson correlation analysis. RESULTS: For MAP MRI, the mean values of MSD in the bilateral caudate, pallidum, putamen, thalamus and substantia nigra (SN) were higher in PD patients than in healthy controls (p FDR ≤ 0.001); the mean values of the zero displacement probabilities (RTOP, RTAP, and RTPP) in the bilateral caudate, pallidum, putamen and thalamus were lower in PD patients (p FDR < 0.001). For DTI, only FA in the bilateral SN was significantly higher in PD patients than those in the controls (p FDR < 0.001). ROC analysis showed that the areas under the curves of MAP MRI metrics (MSD, RTOP, RTAP, and RTPP) in the bilateral caudate, pallidum, putamen and thalamus (range, 0.85-0.94) were greater than those of FA and MD of DTI (range, 0.55-0.69) in discriminating between PD patients and healthy controls. RTAP in the ipsilateral pallidum (r = -0.56, p FDR = 0.027), RTOP in the bilateral and contralateral putamen (r = -0.58, p FDR = 0.019; r = -0.57, p FDR = 0.024) were negatively correlated with UPDRS III motor scores. CONCLUSION: MAP MRI outperformed the conventional DTI in the diagnosis of PD and evaluation of the disease severity.

Clinicoradiologic characteristics of endolymphatic sac tumors.

PURPOSE: Endolymphatic sac tumor (ELST) is a rare, slow-growing, and low-grade malignant tumor arising from the endolymphatic sac in the posterior petrous bone. The purpose of this study is to describe the clinical and radiologic features, and investigate the clinicoradiologic correlation of ELST. METHODS: We retrospectively reviewed the clinical, computed tomography (CT), magnetic resonance imaging (MRI), and pathologic findings of 14 patients with 15 ELSTs. RESULTS: Patients comprised of eight women and six men with a mean age of 42.3 years at the time of diagnosis and 35.2 years at the time of initial symptoms. The mean interval between initial symptoms and diagnosis was 84.7 months. The most frequent cochleovestibular symptom was hearing loss in 14 patients (100%); other cochleovestibular symptoms were tinnitus in eight patients (57.1%), vertigo in three patients (21.4%), and aural fullness in three patients (21.4%). Ten patients (71.4%) presented with facial paralyses and five patients (14.3%) presented lower cranial nerve deficits. CT findings revealed spiculated, stippled, or reticular high density within the tumors. The lesions involved mastoid cells, vertical facial nerve canal, semicircular canal, cochlea, tympanum, jugular foramen, internal auditory canal, or petrous apex. On the available MRI, all the eight lesions showed patchy and/or speckled hyperintensity on unenhanced T1WI. Five lesions showed flow voids on T2WI and T1WI. Three lesions had blood fluid levels within cysts. CONCLUSION: CT and MRI findings of ELSTs are associated with clinical features. Imaging tests should be performed to identify ELSTs early and ensure greater potential for hearing preservation in patients with cochleovestibular symptoms.

Neural Activity During Mental Rotation in Deaf Signers: The Influence of Long-Term Sign Language Experience.

OBJECTIVES: Mental rotation is the brain's visuospatial understanding of what objects are and where they belong. Previous research indicated that deaf signers showed behavioral enhancement for nonlinguistic visual tasks, including mental rotation. In this study, we investigated the neural difference of mental rotation processing between deaf signers and hearing nonsigners using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). DESIGN: The participants performed a block-designed experiment, consisting of alternating blocks of comparison and rotation periods, separated by a baseline or fixation period. Mental rotation tasks were performed using three-dimensional figures. fMRI images were acquired during the entire experiment, and the fMRI data were analyzed with Analysis of Functional NeuroImages. A factorial design analysis of variance was designed for fMRI analyses. The differences of activation were analyzed for the main effects of group and task, as well as for the interaction of group by task. RESULTS: The study showed differences in activated areas between deaf signers and hearing nonsigners on the mental rotation of three-dimensional figures. Subtracting activations of fixation from activations of rotation, both groups showed consistent activation in bilateral occipital lobe, bilateral parietal lobe, and bilateral posterior temporal lobe. There were different main effects of task (rotation versus comparison) with significant activation clusters in the bilateral precuneus, the right middle frontal gyrus, the bilateral medial frontal gyrus, the right interior frontal gyrus, the right superior frontal gyrus, the right anterior cingulate, and the bilateral posterior cingulate. There were significant interaction effects of group by task in the bilateral anterior cingulate, the right inferior frontal gyrus, the left superior frontal gyrus, the left posterior cingulate, the left middle temporal gyrus, and the right inferior parietal lobe. In simple effects of deaf and hearing groups with rotation minus comparison, deaf signers mainly showed activity in the right hemisphere, while hearing nonsigners showed bilateral activity. In the simple effects of rotation task, decreased activities were shown for deaf signers compared with hearing nonsigners throughout several regions, including the bilateral parahippocampal gyrus, the left posterior cingulate cortex, the right anterior cingulate cortex, and the right inferior parietal lobe. CONCLUSION: Decreased activations in several brain regions of deaf signers when compared to hearing nonsigners reflected increased neural efficiency and a precise functional circuitry, which was generated through long-term experience with sign language processing. In addition, we inferred tentatively that there may be a lateralization pattern to the right hemisphere for deaf signers when performing mental rotation tasks.

Decision-making in primary onset middle-age type 2 diabetes mellitus: a BOLD-fMRI study.

Although type 2 diabetes mellitus (T2DM) is a well-recognized risk factor for dementia, the neural mechanisms that underlying cognitive impairment in T2DM remain unclear. We used functional magnetic resonance imaging (fMRI) during a computerized version of the Iowa Gambling Task to investigate the neural basis of decision making at the initial onset stage of T2DM. Eighteen newly diagnosed middle-aged T2DM patients, with no previous diabetic treatment history, and 18 matched controls were recruited. Results indicated that T2DM patients made more disadvantageous decisions than controls. Compared to healthy subjects, T2DM patients showed decreased activation in the ventral medial prefrontal cortex (VMPFC), orbitofrontal cortex (OFC) and anterior cingulate cortex, and increased activity in the dorsolateral prefrontal cortex, posterior cingulate cortex, insula and occipital lobes. IGT performance positively correlated with changes in brain activation in the VMPFC and OFC in both groups. Moreover, poor glycemic control was associated with decision-making function both in behavioral and brain activity in the VMPFC and OFC in patients. Conclusively, T2DM patients may suffer from weaknesses in their prefrontal cortex functions that lead to poorer decision-making under ambiguity, at least as assessed by the IGT.

Spatial Working Memory Impairment in Patients with Non-neuropsychiatric Systemic Lupus Erythematosus: A Blood-oxygen-level Dependent Functional Magnetic Resonance Imaging Study.

OBJECTIVE: Using ethology and functional magnetic resonance imaging (fMRI) to explore mild cognitive dysfunction and spatial working memory (WM) impairment in patients with systemic lupus erythematosus (SLE) without overt neuropsychiatric symptoms (non-NPSLE) and to study whether any clinical biomarkers could serve as predictors of brain dysfunction in this disease. METHODS: Eighteen non-NPSLE patients and 18 matched subjects were all tested using the Montreal cognitive assessment scale test and scanned using blood-oxygen-level dependent fMRI while performing the n-back task to investigate the activation intensity of some cognition-related areas. RESULTS: Ethology results showed that non-NPSLE patients had mild cognitive dysfunction and memory dysfunction (p < 0.05). The fMRI scan confirmed a neural network consisting of bilateral dorsolateral prefrontal cortex (DLPFC), premotor area, parietal lobe, and supplementary motor area (SMA)/anterior cingulate cortex (ACC) that was activated during the n-back task, with right hemisphere dominance. However, only the right SMA/ACC showed a load effect in the non-NPSLE group; the activation intensity of most WM-related brain areas for the non-NPSLE group was lower than for the control group under 3 memory loads. Further, we found that the activation intensity of some cognition-related areas, including the bilateral caudate nucleus/insula and hippocampus/parahippocampal gyrus were lower than the control group under the memory loads. An inverse correlation existed between individual activation intensity and disease duration. CONCLUSION: Non-NPSLE-related brain damage with right DLPFC-posterior parietal lobe and parahippocampal gyrus default network causes impairment of spatial WM and mild cognitive dysfunction. Patients with longer disease duration would be expected to exhibit increased central nervous system damage.

Spatial working memory impairment in primary onset middle-age type 2 diabetes mellitus: An ethology and BOLD-fMRI study.

PURPOSE: To explore mild cognitive dysfunction and/or spatial working memory impairment in patients with primary onset middle-age type 2 diabetes mellitus (T2DM] using ethology (behavior tests) and blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI). MATERIALS AND METHODS: Eighteen primary onset T2DM patients and 18 matched subjects with normal blood glucose levels were all tested using the Montreal cognitive assessment scale test, the Wechsler Memory Scale Chinese-revised test, and scanned using BOLD-fMRI (1.5T, EPI sequence) while performing the n-back task to find the activation intensity of some cognition-related areas. RESULTS: The ethology results showed that T2DM patients had a mild cognitive impairment and memory dysfunction (P < 0.05). The fMRI scan identified a neural network consisting of bilateral dorsolateral prefrontal cortex (DLPFC), bilateral premotor area (PreMA), bilateral parietal lobe (PA), and anterior cingulate cortex (ACC) / supplementary motor area (SMA) that was activated during the n-back task, with right hemisphere dominance. However, only the right PA and ACC/SMA showed a load effect via quantitative analysis in the T2DM group; the activation intensity of most working memory-related brain areas for the T2DM group were lower than for the control group under three memory loads. Furthermore, we found that the activation intensity of some cognition-related areas, including the right insular lobe, left caudate nucleus, and bilateral hippocampus/parahippocampal gyrus were lower than the control group under the memory loads. CONCLUSION: Diabetes-related brain damage of primary onset middle-age T2DM patients with right DLPFC-posterior parietal lobe and parahippocampal gyrus default network causes impairment of spatial working memory and mild cognitive dysfunction.

Spatial working memory impairment in subclinical hypothyroidism: an FMRI study.

OBJECTIVE: Using a block-designed BOLD-fMRI to explore the neural basis of spatial working memory impairment in patients with subclinical hypothyroidism (SCH) performing an n-back task. METHODS: Sixteen patients with SCH before and after being treated with levothyroxine (LT4) for 6 months and 16 matched euthyroid subjects were scanned by fMRI under the n-back task. RESULTS: The fMRI scan found that a neural network consisting of bilateral dorsolateral prefrontal cortex (DLPFC), bilateral premotor area (PreMA), supplementary motor area/anterior cingulate cortex, bilateral parietal lobe (PA) and right caudate nucleus/thalamus was activated, with right hemisphere dominance. In euthyroid subjects, all these regions of interest (ROIs) showed load effect; however, only left DLPFC, left PA, bilateral PreMA and right caudate nucleus/thalamus showed the same effect in Pre-SCH patients. Furthermore, activation intensities of most ROIs (especially DLPFC and right PA) for Pre-SCH patients were lower than those in the euthyroid subjects (F <3.046, p > 0.062). Importantly, after a 6-month treatment with LT4, the load effect in SCH patients appeared the same as in the euthyroid subjects in all the ROIs (F >13.176, p < 0.0001). CONCLUSION: Our previous study shows that verbal working memory of SCH patients is impaired with abnormal activity in bilateral frontal areas. In this study, the results indicated that SCH patients may also have spatial working memory impairments, and the altered activities of right DLPFC and right posterior parietal lobe may be one of the underlying neural mechanisms. Most importantly, this study shows that LT4 replacement therapy can improve the memory impairment and reverse the altered neural activity network.

Functional magnetic resonance imaging of methamphetamine craving.

The study aimed to explore the abnormal activation of special brain areas associated with methamphetamine craving using functional magnetic resonance imaging (fMRI) and to reveal the neurobiological basis of addiction. Twenty-six methamphetamine addicts and 26 healthy subjects were scanned by brain fMRI while watching pictures of happy, sad, or methamphetamine to acquire resource data. SPM5 was used to analyze fMRI data to get related brain activation map, and it was found that methamphetamine addicts had high brain activation in cingulate and low activation in frontal lobe when watching methamphetamine-cue pictures. This study demonstrated that methamphetamine addicts had emotion-related brain activation abnormalities.

Spatial working memory dysfunction in minimal hepatic encephalopathy: an ethology and BOLD-fMRI study.

The term "minimal hepatic encephalopathy" (MHE) refers to a population of individuals who have no recognizable clinical symptoms but perform abnormally on neuropsychological and neurophysiological tests. Research shows that MHE patients have impairments in cognition affecting their daily lives that should be treated. This study explored the neural basis of spatial working memory impairment in MHE patients using behavioral test and BOLD-fMRI. Twelve normal controls, twelve cirrhosis patients without MHE and twelve MHE patients took part. The memory quotient of the MHE group (Wechsler Memory Scale-Chinese revised: WMS-CR) was lower than the normal control group and the cirrhosis-without-MHE group, and primarily concerned short-term memory and transient memory. Performance accuracy was lower for the MHE group than the control group and the cirrhosis-without-MHE group, and mean reaction time was prolonged. The fMRI data highlighted a neural network consisting of: bilateral prefrontal cortex (PFC), bilateral premotor area (PreMA), supplementary motor area (SMA) and bilateral parietal areas (PA), which was activated in the n-back task. The load effect of BOLD-fMRI response appeared in all regions of interest (ROI) for the normal control group, but only appeared in PreMA and PA, and did not vary with n-back load in PFC or SMA for the MHE group. Activation intensities for all ROIs were higher for the normal control group than the MHE group, especially in 2-back load. In conclusion, these results demonstrate that MHE patients have debilitated spatial working memory, and that impairments of bilateral PFC, PMA, SMA, and PA commonly lead to spatial working memory dysfunction. Furthermore, PFC impairment may form the neural basis of spatial working memory impairment.

Peripheral pulmonary nodules: relationship between multi-slice spiral CT perfusion imaging and tumor angiogenesis and VEGF expression.

BACKGROUND: The aim of this study is to investigate the relationship between 16-slice spiral CT perfusion imaging and tumor angiogenesis and VEGF (vascular endothelial growth factor) expression in patients with benign and malignant pulmonary nodules, and differential diagnosis between benign and malignant pulmonary nodules. METHODS: Sixty-four patients with benign and malignant pulmonary nodules underwent 16-slice spiral CT perfusion imaging. The CT perfusion imaging was analyzed for TDC (time density curve), perfusion parametric maps, and the respective perfusion parameters. Immunohistochemical findings of MVD (microvessel density) measurement and VEGF expression was evaluated. RESULTS: The shape of the TDC of peripheral lung cancer was similar to those of inflammatory nodule. PH (peak height), PHpm/PHa (peak height ratio of pulmonary nodule to aorta), BF (blood flow), BV (blood volume) value of peripheral lung cancer and inflammatory nodule were not statistically significant (all P > 0.05). Both showed significantly higher PH, PHpm/PHa, BF, BV value than those of benign nodule (all P < 0.05). Peripheral lung cancer showed significantly higher PS (permeability surface) value than that of inflammatory nodule and benign nodule (all P < 0.05). BV, BF, PS, MTT, PH, PHpm/PHa, and MVD among three groups of peripheral lung cancers were not significantly (all P > 0.05). In the case of adenocarcinoma, BV, BF, PS, PHpm/PHa, and MVD between poorly and well differentiation and between poorly and moderately differentiation were statistically significant (all P < 0.05). The peripheral lung cancers with VEGF positive expression showed significantly higher PH, PHpm/PHa, BF, BV, PS, and MVD value than those of the peripheral lung cancer with VEGF negative expression, and than those of benign nodule with VEGF positive expression (all P < 0.05). When investigating VEGF negative expression, it is found that PH, PHpm/PHa, and MVD of inflammatory nodule were significantly higher than those of peripheral lung cancer, PS of inflammatory nodule were significantly lower than that of peripheral lung cancer (all P < 0.05). PH, PHpm/PHa, BF, and BV of benign nodule were significantly lower than those of inflammatory nodule (all P < 0.05), rather than PS and MTT (mean transit time) (all P > 0.05). PH, PHpm/PHa, BV, and PS of benign nodule were significantly lower than those of peripheral lung cancer (all P < 0.05). In the case of VEGF positive expression, MVD was positively correlated with PH, PHpm/PHa, BF, BV, and PS of peripheral lung cancer and PS of benign nodule (all P < 0.05). CONCLUSION: Multi-slice spiral CT perfusion imaging closely correlated with tumor angiogenesis and reflected MVD measurement and VEGF expression. It provided not only a non-invasive method of quantitative assessment for blood flow patterns of peripheral pulmonary nodules but also an applicable diagnostic method for peripheral pulmonary nodules.