MicroRNA-377-3p exacerbates chronic obstructive pulmonary disease through suppressing ZFP36L1 expression and inducing lung fibroblast senescence.

Chronic obstructive pulmonary disease (COPD) is a leading aging related cause of global mortality. Small airway narrowing is recognized as an early and significant factor for COPD development. Senescent fibroblasts were observed to accumulate in lung of COPD patients and promote COPD progression through aberrant extracellular matrix (ECM) deposition and senescence-associated secretory phenotype (SASP). On the basis of our previous study, we further investigated the the causes for the increased levels of miR-377-3p in the blood of COPD patients, as well as its regulatory function in the pathological progression of COPD. We found that the majority of up-regulated miR-377-3p was localized in lung fibroblasts. Inhibition of miR-377-3p improved chronic smoking-induced COPD in mice. Mechanistically, miR-377-3p promoted senescence of lung fibroblasts, while knockdown of miR-377-3p attenuated bleomycin-induced senescence in lung fibroblasts. We also identified ZFP36L1 as a direct target for miR-377-3p that likely mediated its pro senescence activity in lung fibroblasts. Our data reveal that miR-377-3p is crucial for COPD pathogenesis, and may serve as a potential target for COPD therapy.

TAF1B depletion leads to apoptotic cell death by inducing nucleolar stress and activating p53-miR-101 circuit in hepatocellular carcinoma.

Background: TAF1B (TATA Box Binding Protein (TBP)-Associated Factor) is an RNA polymerase regulating rDNA activity, stress response, and cell cycle. However, the function of TAF1B in the progression of hepatocellular carcinoma (HCC) is unknown. Objective: In this study, we intended to characterize the crucial role and molecular mechanisms of TAF1B in modulating nucleolar stress in HCC. Methods: We analyzed the differential expression and prognostic value of TAF1B in hepatocellular carcinoma based on The Cancer Genome Atlas (TCGA) database, tumor and paraneoplastic tissue samples from clinical hepatocellular carcinoma patients, and typical hepatocellular carcinoma. We detected cell proliferation and apoptosis by lentiviral knockdown of TAF1B expression levels in HepG2 and SMMC-7721 cells using clone formation, apoptosis, and Western blotting (WB) detection of apoptosis marker proteins. Simultaneously, we investigated the influence of TAF1B knockdown on the function of the pre-initiation complex (PIC) by WB, and co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP) assays verified the interaction between the complexes and the effect on rDNA activity. Immunofluorescence assays measured the expression of marker proteins of nucleolus stress, fluorescence in situ hybridization (FISH) assays checked the rDNA activity, and qRT-PCR assays tested the pre-rRNA levels. Regarding molecular mechanisms, we investigated the role of p53 and miR-101 in modulating nucleolar stress and apoptosis. Finally, the impact of TAF1B knockdown on tumor growth, apoptosis, and p53 expression was observed in xenograft tumors. Result: We identified that TAF1B was highly expressed in hepatocellular carcinoma and associated with poor prognosis in HCC patients. TAF1B depletion modulated nucleolar stress and apoptosis in hepatocellular carcinoma cells through positive and negative feedback from p53-miR-101. RNA polymerase I transcription repression triggered post-transcriptional activation of miR-101 in a p53-dependent manner. In turn, miR-101 negatively feeds back through direct inhibition of the p53-mediated PARP pathway. Conclusion: These findings broaden our comprehension of the function of TAF1B-mediated nucleolar stress in hepatocellular carcinoma and may offer new biomarkers for exploring prospective therapeutic targets in HCC.

Evaluation of the Effects of Anti-PD-1 Therapy on Triple-Negative Breast Cancer in Mice by Diffusion Kurtosis Imaging and Dynamic Contrast-Enhanced Imaging.

BACKGROUND: The monitoring of immunotherapies is still based on changes in the tumor size in imaging, with a long evaluation period and low sensitivity. PURPOSE: To investigate the effectiveness of diffusion kurtosis imaging (DKI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the therapeutic efficacy of anti-programmed death-1 (PD-1) therapy in a mouse triple negative breast cancer (TNBC) model. STUDY TYPE: Prospective. ANIMAL MODEL: A total of 54 BALB/c mouse subcutaneous 4 T1 transplantation models of TNBC. FIELD STRENGTH/SEQUENCE: A 3.0-T; turbo spin echo (TSE) T2-weighted imaging, DKI with seven b values (0, 500, 1000, 1500, 2000, 2500, and 3000 sec/mm2 ) and T1-twist DCE acquisition series. ASSESSMENT: DKI and DCE-MRI parameters were evaluated by two radiologists independently. Regions of interest (ROIs) were drawn manually on the maximum cross-sectional area of the lesion; care was taken to avoid necrotic areas. The tumor cell density, the CD45 and CD31 levels were analyzed by two pathologists. STATISTICAL TESTS: The two-tailed unpaired t-test, Mann-Whitney U test, Fisher's exact test and Pearson correlation coefficient were performed. A P < 0.05 was considered statistically significant. RESULTS: The apparent diffusion coefficient (ADC), mean diffusivity (MD), Ktrans and Kep values were significantly different between the two groups at each time point after treatment. There were significant differences in the mean kurtosis (MK) and Ve values between the two groups at 5 and 10 days after treatment but no significant differences at 15 days (P = 0.317 and 0.183, respectively). The ADC and MD values were significantly correlated with tumor cell density (ADC, r = -0.833; MD, r = 0.890) and the CD45 level (ADC, r = 0.720; MD, r = 0.718). The Ktrans and Kep values were significantly correlated with the CD31 level (Ktrans , r = 0.820; Kep , r = 0.683). DATA CONCLUSION: DKI and DCE-MRI could reflect the changes in tumor microstructure and tumor tissue vasculature after anti-PD-1 therapy, respectively. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 4.

Performance of radiomics models for tumour-infiltrating lymphocyte (TIL) prediction in breast cancer: the role of the dynamic contrast-enhanced (DCE) MRI phase.

OBJECTIVE: To systematically investigate the effect of imaging features at different DCE-MRI phases to optimise a radiomics model based on DCE-MRI for the prediction of tumour-infiltrating lymphocyte (TIL) levels in breast cancer. MATERIALS AND METHODS: This study retrospectively collected 133 patients with pathologically proven breast cancer, including 73 patients with low TIL levels and 60 patients with high TIL levels. The volumes of breast cancer lesions were manually delineated on T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and each phase of DCE-MRI, followed by 6250 quantitative feature extractions. The least absolute shrinkage and selection operator (LASSO) method was used to select predictive feature sets for the classifiers. Four models were developed for predicting TILs: (1) single enhanced phase radiomics models; (2) fusion enhanced multi-phase radiomics models; (3) fusion multi-sequence radiomics models; and (4) a combined radiomics-based clinical model. RESULTS: Image features extracted from the delayed phase MRI, especially DCE_Phase 6 (DCE_P6), demonstrated dominant predictive performances over features from other phases. The fusion multi-sequence radiomics model and combined radiomics-based clinical model achieved the highest predictive performances with areas under the curve (AUCs) of 0.934 and 0.950, respectively; however, the differences were not statistically significant. CONCLUSION: The DCE-MRI radiomics model, especially image features extracted from the delayed phases, can help improve the performance in predicting TILs. The radiomics nomogram is effective in predicting TILs in breast cancer. KEY POINTS: • Radiomics features extracted from DCE-MRI, especially delayed phase images, help predict TIL levels in breast cancer. • We developed a nomogram based on MRI to predict TILs in breast cancer that achieved the highest AUC of 0.950.

Whole Volume Apparent Diffusion Coefficient (ADC) Histogram as a Quantitative Imaging Biomarker to Differentiate Breast Lesions: Correlation with the Ki-67 Proliferation Index.

OBJECTIVES: To evaluate the value of the whole volume apparent diffusion coefficient (ADC) histogram in distinguishing between benign and malignant breast lesions and differentiating different molecular subtypes of breast cancers and to assess the correlation between ADC histogram parameters and Ki-67 expression in breast cancers. METHODS: The institutional review board approved this retrospective study. Between September 2016 and February 2019, 189 patients with 84 benign lesions and 105 breast cancers underwent magnetic resonance imaging (MRI). Volumetric ADC histograms were created by placing regions of interest (ROIs) on the whole lesion. The relationships between the ADC parameters and Ki-67 were analysed using Spearman's correlation analysis. RESULTS: Of the 189 breast lesions included, there were significant differences in patient age (P < 0.001) and lesion size (P = 0.006) between the benign and malignant lesions. The results also demonstrated significant differences in all ADC histogram parameters between benign and malignant lesions (all P < 0.001). The median and mean ADC histogram parameters performed better than the other ADC histogram parameters (AUCs were 0.943 and 0.930, respectively). The receiver operating characteristic (ROC) analysis revealed that the 10th percentile ADC value and entropy could determine the human epidermal growth factor receptor 2 (HER-2) status (both P = 0.001) and estrogen receptor (ER)/progesterone receptor (PR) status (P = 0.020 and P = 0.041, respectively). Among all breast cancer lesions, 35 tumours in the low-proliferation group (Ki - 67 < 14%) and 70 tumours in the high-proliferation group (Ki - 67 ≥ 14) were analysed with ROC curves and correlation analyses. The ROC analysis revealed that entropy and skewness could determine the Ki-67 status (P = 0.007 and P < 0.001, respectively), and there were weak correlations between ADC entropy (r = 0.383) and skewness (r = 0.209) and the Ki-67 index. CONCLUSION: The volumetric ADC histogram could serve as an imaging marker to determine breast lesion characteristics and may be a supplemental method in predicting tumour proliferation in breast cancer.

Magnetic Resonance Imaging (MRI) Phenotypes May Provide Additional Information for Risk Stratification for Encapsulated Papillary Carcinoma of the Breast.

BACKGROUND: Encapsulated papillary carcinoma (EPC) of the breast is a rare entity. EPC can be underappreciated on percutaneous biopsy, which may require additional procedures if invasion is not recognized preoperatively. We aimed to investigate the magnetic resonance imaging (MRI) phenotypes correlated with preoperative pathological risk stratification for clinical guidance. MATERIALS AND METHODS: The preoperative MRI scans of 30 patients diagnosed with 36 EPCs in multiple centers between August 2015 and February 2020 were reviewed by two breast radiologists. According to the WHO classification published in 2019, EPCs were classified into two pathological subtypes: encapsulated papillary carcinoma and encapsulated papillary carcinoma with invasion. Clinicopathological analysis of the two subtypes and MR feature analysis were performed. RESULTS: Evaluation of the MRI phenotypes and pathological subtype information revealed that not circumscribed (P=0.04) was more common in EPCs with invasion than in EPCs. There was a significant difference in the age of patients (P=0.05), and the risk increased with age. The maximum diameter of the tumor increased with tumor risk, but there was no significant difference (P=0.36). Nearly half of the EPC with invasion patients showed hyperintensity on T1WI (P=0.19). A total of 63.6% of the EPC with invasion group showed non-mass enhancement surrounding (P=0.85). In addition, 29 patients (96.7%) had no axillary lymph node metastasis, and only one patient with EPC with invasion had axillary lymph node metastasis. Further pathological information analysis of EPCs showed that higher Ki-67 levels were more common in patients with EPCs with invasion (P=0.04). A total of 29 patients (96.7%) had the luminal phenotype, and one patient with EPC with invasion had the Her-2-positive phenotype. CONCLUSION: The margin, age and Ki-67 level were the key features for EPC risk stratification. In addition, these MRI signs, including a larger tumor, non-mass enhancement surrounding and axillary lymph node metastasis, may be suggestive of a high-risk stratification. Therefore, MRI phenotypes may provide additional information for the risk stratification of EPCs.

Size-Switchable Nanoparticles with Self-Destructive and Tumor Penetration Characteristics for Site-Specific Phototherapy of Cancer.

The normoxic and hypoxic microenvironments in solid tumors cause cancer cells to show different sensitivities to various treatments. Therefore, it is essential to develop different therapeutic modalities based on the tumor microenvironment. In this study, we designed size-switchable nanoparticles with self-destruction and tumor penetration characteristics for site-specific phototherapy of cancer. This was achieved by photodynamic therapy in the perivascular normoxic microenvironment due to high local oxygen concentrations and photothermal therapy (PTT) in the hypoxic microenvironment, which are not in proximity to blood vessels due to a lack of effective approaches for heat transfer. In brief, a poly(amidoamine) dendrimer with photothermal agent indocyanine green (PAMAM-ICG) was conjugated to the amphiphilic polymer through a singlet oxygen-responsive thioketal linker and then loaded with photosensitizer chlorin e6 (Ce6) to construct a nanotherapy platform (denoted as SNPICG/Ce6). After intravenous injection, SNPICG/Ce6 was accumulated at the perivascular sites of the tumor. The singlet oxygen produced by Ce6 can ablate the tumor cells in the normoxic microenvironment and simultaneously cleave the thioketal linker, allowing the release of small PAMAM-ICGs with improved tumor penetration for PTT in the hypoxic microenvironment. This tailored site-specific phototherapy in normoxic and hypoxic microenvironments provides an effective strategy for cancer therapy.

Whole-Lesion Histogram Analysis of the Apparent Diffusion Coefficient as a Quantitative Imaging Biomarker for Assessing the Level of Tumor-Infiltrating Lymphocytes: Value in Molecular Subtypes of Breast Cancer.

PURPOSE: To assess whether apparent diffusion coefficient (ADC) metrics can be used to assess tumor-infiltrating lymphocyte (TIL) levels in breast cancer, particularly in the molecular subtypes of breast cancer. METHODS: In total, 114 patients with breast cancer met the inclusion criteria (mean age: 52 years; range: 29-85 years) and underwent multi-parametric breast magnetic resonance imaging (MRI). The patients were imaged by diffusion-weighted (DW)-MRI (1.5 T) using a single-shot spin-echo echo-planar imaging sequence. Two readers independently drew a region of interest (ROI) on the ADC maps of the whole tumor. The mean ADC and histogram parameters (10th, 25th, 50th, 75th, and 90th percentiles of ADC, skewness, entropy, and kurtosis) were used as features to analyze associations with the TIL levels in breast cancer. Additionally, the correlation between the ADC values and Ki-67 expression were analyzed. Continuous variables were compared with Student's t-test or Mann-Whitney U test if the variables were not normally distributed. Categorical variables were compared using Pearson's chi-square test or Fisher's exact test. Associations between TIL levels and imaging features were evaluated by the Mann-Whitney U and Kruskal-Wallis tests. RESULTS: A statistically significant difference existed in the 10th and 25th percentile ADC values between the low and high TIL groups in breast cancer (P=0.012 and 0.027). For the luminal subtype of breast cancer, the 10th percentile ADC value was significantly lower in the low TIL group (P=0.041); for the non-luminal subtype of breast cancer, the kurtosis was significantly lower in the low TIL group (P=0.023). The Ki-67 index showed statistical significance for evaluating the TIL levels in breast cancer (P=0.007). Additionally, the skewness was significantly higher for samples with high Ki-67 levels in breast cancer (P=0.029). CONCLUSIONS: Our findings suggest that whole-lesion ADC histogram parameters can be used as surrogate biomarkers to evaluate TIL levels in molecular subtypes of breast cancer.

Negative Schizotypy and Altered Functional Connectivity During Facial Emotion Processing.

Background: Impairment in facial emotion perception is an important domain of social cognition deficits in schizophrenia. Although impaired facial emotion perception has been found in individuals with negative schizotypy (NS), little is known about the corresponding change in brain functional connectivity. Methods: Sixty-four participants were classified into a high NS group (n = 34) and a low NS group (n = 30) based on their total scores on the Chapman scales for physical and social anhedonia. All participants undertook a facial emotion discrimination functional imaging task that consisted of four emotional valences (angry, fear, happy, and neutral). For univariate analysis, the signal change at the bilateral amygdala was compared for each emotional contrast using SPSS (P < .05). For the functional connectivity analysis, we calculated the beta-series functional connectivity of the bilateral amygdala with the medial prefrontal cortex (mPFC) and compared the group differences in SPM12 (P < .05, small volume family-wise error correction). Results: No significant differences were found between the high and low NS groups in accuracy and reaction time in the facial emotion discrimination task. The high NS group showed reduced brain activations at the amygdala under fearful and neutral conditions. Reduced functional connectivity between the amygdala and the mPFC/dorsal anterior cingulate cortex under the happy and fearful conditions in the high NS group was also found. Conclusions: Our findings suggest that the individuals with high NS showed altered brain activity and functional connectivity at the amygdala during facial emotion processing and provide new evidence for understanding social cognition deficits in at-risk individuals.

Hyaluronan-modified superparamagnetic iron oxide nanoparticles for bimodal breast cancer imaging and photothermal therapy.

Theranostic nanoparticles with both imaging and therapeutic abilities are highly promising in successful diagnosis and treatment of the most devastating cancers. In this study, the dual-modal imaging and photothermal effect of hyaluronan (HA)-modified superparamagnetic iron oxide nanoparticles (HA-SPIONs), which was developed in a previous study, were investigated for CD44 HA receptor-overexpressing breast cancer in both in vitro and in vivo experiments. Heat is found to be rapidly generated by near-infrared laser range irradiation of HA-SPIONs. When incubated with CD44 HA receptor-overexpressing MDA-MB-231 cells in vitro, HA-SPIONs exhibited significant specific cellular uptake and specific accumulation confirmed by Prussian blue staining. The in vitro and in vivo results of magnetic resonance imaging and photothermal ablation demonstrated that HA-SPIONs exhibited significant negative contrast enhancement on T2-weighted magnetic resonance imaging and photothermal effect targeted CD44 HA receptor-overexpressing breast cancer. All these results indicated that HA-SPIONs have great potential for effective diagnosis and treatment of cancer.

The neural basis of olfactory function and its relationship with anhedonia in individuals with schizotypy: An exploratory study.

Previous studies have established a linkage between olfactory deficits and negative symptoms in schizophrenia. However, it is not known whether olfactory function is associated with hedonic traits in individuals with schizotypy. Seventeen individuals with schizotypy and 18 age- and sex-matched controls participated in this study. Hedonic traits were assessed with the Chapman Scales for Physical and Social Anhedonia (CSAS and CPAS). Olfactory function was assessed with the Sniffin' Stick Test (olfactory threshold, odour discrimination and odour identification). All participants undertook a structural imaging scan for grey matter volume measurements. Individuals with schizotypy had significantly higher CSAS and CPAS scores than healthy controls. They had normal olfactory function. Their odour identification ability was inversely correlated with physical and social anhedonia. The volume of the right parahippocampal gyrus was positively associated with odour identification ability, and negatively associated with physical and social anhedonia. Furthermore, mediation analysis suggested that odour identification ability influences anhedonia through its effect on the right parahippocampal gyrus. No such relationship was found in controls. These findings suggest that there is a relationship between odour identification and anhedonia in individuals with schizotypy, and the association may be mediated by parahippocampal gyrus volume.

Dimensional schizotypy and social cognition: an fMRI imaging study.

Impairment in empathy has been demonstrated in patients with schizophrenia and individuals with psychosis proneness. In the present study, we examined the neural correlates underlying theory of mind (ToM) and empathy and the relationships between these two social cognitive abilities with schizotypy. Fifty-six first-year college students (31 males, 25 females) between 17 and 21 years of age (M = 19.3, SD = 0.9) from a medical university in China participated. All participants undertook a comic strips functional imaging task that specifically examined both empathy and ToM. In addition, they completed two self-report scales: the Chapman Psychosis Proneness scale and the Interpersonal Responsivity Index (IRI). Results showed that both empathy and ToM conditions of the task were associated with brain activity in the middle temporal gyrus, the temporo-parietal junction (TPJ), the precuneus and the posterior cingulate gyrus. In addition, we found positive correlations between negative schizotypy and brain activity in regions involved in social cognition, namely, the middle temporal gyrus, the TPJ, as well as the medial prefrontal gyrus. These findings highlight that different dimensions of schizotypy may show different associations with brain regions involved in social cognitive abilities. More importantly, the positive correlation between brain activity and anhedonia suggests the presence of compensatory mechanisms in high-risk populations.

Increased interhemispheric functional connectivity in college students with non-clinical depressive symptoms in resting state.

The underlying neural basis of non-clinical depressive symptoms (nCDSs) remains unclear. Interhemispheric functional connectivity has been suggested as one of the most robust characteristics of brain's intrinsic functional architecture. Here, we investigated the functional connectivity between homotopic points in the brain using the voxel-mirrored homotopic connectivity (VMHC) approach. We performed VMHC analysis on resting-state functional magnetic resonance imaging (rs-fMRI) data from 17 individuals with nCDSs and 20 healthy controls (HCs) who were enrolled from a sample of 1105 college students. We found increased VMHCs in the bilateral posterior cerebellum and fusiform gyrus in nCDSs subjects compared with HCs. Furthermore, receiver operating characteristic (ROC) curves indicated that VMHC values in the posterior cerebellum lobes could use to differente nCDSs from HCs [area under the curve (AUC), 0.756; p<0.01]. We suggest increased VMHCs indicate a possible compensatory mechanism involved in the pathophysiology of nCDSs. VMHC values of the posterior cerebellum lobes might serve as a reliable biomarker for identifying nCDSs.

Glycosaminoglycan-targeted iron oxide nanoparticles for magnetic resonance imaging of liver carcinoma.

To develop an efficient probe for targeted magnetic resonance (MR) imaging of liver carcinoma, the surface modification of superparamagnetic iron oxide nanoparticles (SPIONs) was carried out by conjugating a naturally-occurring glycosaminoglycan with specific biological recognition to human hepatocellular liver carcinoma (HepG2) cells. These modified SPIOs have good water dispersibility, superparamagnetic property, cytocompatibility and high magnetic relaxivity for MR imaging. When incubated with HepG2 cells, they demonstrated significant cellular uptake and specific accumulation, as confirmed by Prussian blue staining and confocal microscopy. The in vitro MR imaging of HepG2 cells and in vivo MR imaging of HepG2 tumors confirmed their effectiveness for targeted MR imaging of liver carcinoma.

Distinct structural neural patterns of trait physical and social anhedonia: evidence from cortical thickness, subcortical volumes and inter-regional correlations.

Anhedonia is an enduring trait accounting for the reduced capacity to experience pleasure. Few studies have investigated the brain structural features associated with trait anhedonia. In this study, the relationships between cortical thickness, volume of subcortical structures and scores on the Chapman physical and social anhedonia scales were examined in a non-clinical sample (n=72, 35 males). FreeSurfer was used to examine the cortical thickness and the volume of six identified subcortical structures related to trait anhedonia. We found that the cortical thickness of the superior frontal gyrus and the volume of the pallidum in the left hemisphere were correlated with anhedonia scores in both physical and social aspects. Specifically, positive correlations were found between levels of social anhedonia and the thickness of the postcentral and the inferior parietal gyri. Cortico-subcortical inter-correlations between these clusters were also observed. Our findings revealed distinct correlation patterns of neural substrates with trait physical and social anhedonia in a non-clinical sample. These findings contribute to the understanding of the pathologies underlying the anhedonia phenotype in schizophrenia and other psychiatric disorders.

In vivo assessment of the vascular disrupting effect of M410 by DCE-MRI biomarker in a rabbit model of liver tumor.

The present study aimed to prospectively monitor the vascular disrupting effect of M410 by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in rabbits with VX2 liver tumors. Twenty-eight rabbits bearing VX2 tumors in the left lobe of the liver were established and randomly divided into treatment and control groups, intravenously injected with 25 mg/kg M410 or sterile saline, respectively. Conventional and DCE-MRI data were acquired on a 3.0-T MR unit at pretreatment, 4 h, 1, 4, 7 and 14 days post-treatment. Histopathological examinations [hematoxylin and eosin (H&E) and CD34 immunohistochemisty staining] were performed at each time point. The dynamic changes in tumor volume, kinetic DCE-MRI parameter [volume transfer constant (Ktrans)] and histological data were evaluated. Tumors grew slower in the M410 group 4-14 days following treatment, compared with rapidly growing tumors in the control group (P<0.05). At 4 h, 1 and 4 days, Ktrans significantly decreased in the M410 group compared with that in the control group (P<0.05). However, Ktrans values were similar in the two groups for the other time points studied. The changes in DCE-MRI parameters were consistent with the results obtained from H&E and CD34 staining of the tumor tissues. DCE-MRI parameter Ktrans may be used as a non-invasive imaging biomarker to monitor the dynamic histological changes in tumors following treatment with the vascular targeting agent M410.

Differentiation of central lung cancer from atelectasis: comparison of diffusion-weighted MRI with PET/CT.

OBJECTIVE: Prospectively assess the performance of diffusion-weighted magnetic resonance imaging (DW-MRI) for differentiation of central lung cancer from atelectasis. MATERIALS AND METHODS: 38 consecutive lung cancer patients (26 males, 12 females; age range: 28-71 years; mean age: 49 years) who were referred for thoracic MR imaging examinations were enrolled. MR examinations were performed using a 1.5-T clinical scanner and scanning sequences of T1WI, T2WI, and DWI. Cancers and atelectasis were measured by mapping of the apparent diffusion coefficients (ADCs) obtained with a b-value of 500 s/mm(2). RESULTS: PET/CT and DW-MR allowed differentiation of tumor and atelectasis in all 38 cases, but T2WI did not allow differentiation in 9 cases. Comparison of conventional T2WI and DW-MRI indicated a higher contrast noise ratio of the central lung carcinoma than the atelectasis by DW-MRI. ADC maps indicated significantly lower mean ADC in the central lung carcinoma than in the atelectasis (1.83±0.58 vs. 2.90±0.26 mm(2)/s, p<0.0001). ADC values of small cell lung carcinoma were significantly greater than those from squamous cell carcinoma and adenocarcinoma (p<0.0001 for both). CONCLUSIONS: DW-MR imaging provides valuable information not obtained by conventional MR and may be useful for differentiation of central lung carcinoma from atelectasis. Future developments may allow DW-MR imaging to be used as an alternative to PET-CT in imaging of patients with lung cancer.

[Hepatic metastasis of human colon carcinoma: establishment of a nude mouse model and its magnetic resonance imaging].

OBJECTIVE: To establish a nude mouse model mimicking hepatic metastasis of human colon carcinoma and study its magnetic resonance imaging (MRI) features and the quality of diffusion-weighted images (DWI). METHODS: Human colon carcinoma SW480 cells were inoculated subcutaneously ((1x10(7)/ml, 0.5 ml) in the costal regions of 2 nude mice, and after successful tumor formation, the generated tumors were harvested and cut into tissue blocks of 1 mm(3). The tissue blocks were subsequently implanted into the liver of 36 nude mice, from which TSE-T1WI, T2WI and EPI-DWI were obtained after tumor growth. RESULTS: The success rate of intrahepatic tumor implantation was 100% (36/36), and the tumors grown in the liver measured 0.7 to 2 cm in diameter 2 to 6 weeks after implantation. All the tumors were clearly visualized on T1WI and T2WI images, with isointensity on T1WI and hyperintensity on T2WI. Compared with the T2WI, DWI showed conspicuous geometry deformation in 4 mice to cause difficult detection, moderate to slight geometric deformation in 14 mice which remained detectable, and no geometric deformation in 18 mice. CONCLUSION: The nude mouse model of hepatic metastasis of SW480 colon cancer cell line, with ideal implantation and tumor growth rate, allows convenient tumor observation on MR T1WI, T2WI and DWI, and the MRI findings of the tumor are well consistent with those by pathological examination, suggesting the validity of this model for molecular imaging research of human colon cancer.

[Relationship between early enhanced helical CT and tumor angiogenesis in bladder cancer].

OBJECTIVE: To study the relationship between enhanced degree in the cancer lesion and angiogenesis in the tumor through early manifestations in enhanced helical CT in patients with bladder cancer. METHODS: Fifty-three patients with bladder carcinoma were examined by pelvic plain CT and helical CT scan at peak enhancement of cancer lesion. Histologic grade, vascular endothelial growth factor (VEGF) and micro-vascular density (MVD) were analyzed for each resected cancer lesion. Pearson and Spearman correlation tests were used to assess the relationship between CT enhancement and histologic grade, VEGF or MVD. RESULTS: In early enhancing phase of helical CT, different degrees of enhancement were observed in 73 bladder cancer lesions. The difference between average CT attenuation and MVD in different histologic grade cancer lesions was statistically significant (P < 0.001). A positive correlation was found between the CT enhancement and MVD (gamma = 0.936, P < 0.001), histologic grade (gamma = 0.75, P < 0.001), but VEGF of bladder cancer did not correlate with the CT enhancement or MVD. CONCLUSION: The early enhancement of helical CT enhancement of bladder cancer, showing a positive relation to MVD and histologic grade, can reflect the tumor angiogenesis and blood supply.