Whole-Organ CT Perfusion of the Pancreas: Impact of Iterative Reconstruction on Image Quality,Perfusion Parameters and Radiation Dose in 256-Slice CT-Preliminary Findings

Background

This study was performed to assess whether iterative reconstruction can reduce radiation dose while maintaining acceptable image quality, and to investigate whether perfusion parameters vary from conventional filtered back projection (FBP) at the low-tube-voltage (80-kVp) during whole-pancreas perfusion examination using a 256-slice CT.

Methods

76 patients with known or suspected pancreatic mass underwent whole-pancreas perfusion by a 256-slice CT. High- and low-tube-voltage CT images were acquired. 120-kVp image data (protocol A) and 80-kVp image data (protocol B) were reconstructed with conventional FBP, and 80-kVp image data were reconstructed with iDose⁴ (protocol C) iterative reconstruction. The image noise; contrast-to-noise ratio (CNR) relative to muscle for the pancreas, liver, and aorta; and radiation dose of each protocol were assessed quantitatively. Overall image quality was assessed qualitatively. Among 76 patients, 23 were eventually proven to have a normal pancreas. Perfusion parameters of normal pancreas in each protocol including blood volume, blood flow, and permeability-surface area product were measured.

Results

In the quantitative study, protocol C reduced image noise by 36.8% compared to protocol B (P<0.001). Protocol C yielded significantly higher CNR relative to muscle for the aorta, pancreas and liver compared to protocol B (P<0.001), and offered no significant difference compared to protocol A. In the qualitative study, protocols C and A gained similar scores and protocol B gained the lowest score for overall image quality (P<0.001). Mean effective doses were 23.37 mSv for protocol A and 10.81 mSv for protocols B and C. There were no significant differences in the normal pancreas perfusion values among three different protocols.

Conclusion

Low-tube-voltage and iDose⁴ iterative reconstruction can dramatically decrease the radiation dose with acceptable image quality during whole-pancreas CT perfusion and have no significant impact on the perfusion parameters of normal pancreas compared to the conventional FBP reconstruction using a 256-slice CT scanner.     

Reproducibility of Volumetric Computed Tomography of Stable Small Pulmonary Nodules with Implications on Estimated Growth Rate and Optimal Scan Interval

Purpose

To use clinically measured reproducibility of volumetric CT (vCT) of lung nodules to estimate error in nodule growth rate in order to determine optimal scan interval for patient follow-up.

Methods

We performed quantitative vCT on 89 stable non-calcified nodules and 49 calcified nodules measuring 3–13 mm diameter in 71 patients who underwent 3–9 repeat vCT studies for clinical evaluation of pulmonary nodules. Calculated volume standard deviation as a function of mean nodule volume was used to compute error in estimated growth rate. This error was then used to determine the optimal patient follow-up scan interval while fixing the false positive rate at 5%.

Results

Linear regression of nodule volume standard deviation versus the mean nodule volume for stable non-calcified nodules yielded a slope of 0.057±0.002 (r² = 0.79, p<0.001). For calcified stable nodules, the regression slope was 0.052±0.005 (r² = 0.65, p = 0.03). Using this with the error propagation formula, the optimal patient follow-up scan interval was calculated to be 81 days, independent of initial nodule volume.

Conclusions

Reproducibility of vCT is excellent, and the standard error is proportional to the mean calculated nodule volume for the range of nodules examined. This relationship constrains statistical certainty of vCT calculated doubling times and results in an optimal scan interval that is independent of the initial nodule volume.     

Prognosis of Thyroid Nodules in Individuals Living in the Zhitomir Region of Ukraine

Objective

After the accident at the Chernobyl Nuclear Power Plant (CNPP), the incidence of thyroid cancer increased among children. Recently, a strong relationship between solid thyroid nodules and the incidence of thyroid cancer was shown in atomic bomb survivors. To assess the prognosis of benign thyroid nodules in individuals living in the Zhitomir region of Ukraine, around the CNPP, we conducted a follow-up investigation of screening data from 1991 to 2000 in the Ukraine.

Patients and Methods

Participants of this study were 160 inhabitants with thyroid nodules (nodule group) and 160 inhabitants without thyroid nodules (normal control group) intially identified by ultrasonography from 1991 to 2000. All participants were aged 0 to 10 years old and lived in the same area at the time of the accident. We performed follow-up screening of participants and assessed thyroid nodules by fine needle aspiration biopsy.

Results

Among the nodule group participants, the number and size of nodules were significantly increased at the follow-up screening compared with the initial screening. No thyroid nodules were observed among the normal control group participants. The prevalence of thyroid abnormality, especially nodules that could be cancerous (malignant or suspicious by fine needle aspiration biopsy), was 7.5% in the nodule group and 0% in the normal control group (P<0.001).

Conclusions

Our study indicated that a thyroid nodule in childhood is a prognostic factor associated with an increase in the number and size of nodules in individuals living in the Zhitomir region of Ukraine.     

Computed tomography imaging of primary lung cancer in mice using a liposomal-iodinated contrast agent

Purpose

To investigate the utility of a liposomal-iodinated nanoparticle contrast agent and computed tomography (CT) imaging for characterization of primary nodules in genetically engineered mouse models of non-small cell lung cancer.

Methods

Primary lung cancers with mutations in K-ras alone (Kras^LA1) or in combination with p53 (LSL-Kras^G12D;p53^FL/FL) were generated. A liposomal-iodine contrast agent containing 120 mg Iodine/mL was administered systemically at a dose of 16 µl/gm body weight. Longitudinal micro-CT imaging with cardio-respiratory gating was performed pre-contrast and at 0 hr, day 3, and day 7 post-contrast administration. CT-derived nodule sizes were used to assess tumor growth. Signal attenuation was measured in individual nodules to study dynamic enhancement of lung nodules.

Results

A good correlation was seen between volume and diameter-based assessment of nodules (R²>0.8) for both lung cancer models. The LSL-Kras^G12D;p53^FL/FL model showed rapid growth as demonstrated by systemically higher volume changes compared to the lung nodules in Kras^LA1 mice (p<0.05). Early phase imaging using the nanoparticle contrast agent enabled visualization of nodule blood supply. Delayed-phase imaging demonstrated significant differential signal enhancement in the lung nodules of LSL-Kras^G12D;p53^FL/FL mice compared to nodules in Kras^LA1 mice (p<0.05) indicating higher uptake and accumulation of the nanoparticle contrast agent in rapidly growing nodules.

Conclusions

The nanoparticle iodinated contrast agent enabled visualization of blood supply to the nodules during the early-phase imaging. Delayed-phase imaging enabled characterization of slow growing and rapidly growing nodules based on signal enhancement. The use of this agent could facilitate early detection and diagnosis of pulmonary lesions as well as have implications on treatment response and monitoring.     

Pulmonary Nodule Detection in Patients with a Primary Malignancy Using Hybrid PET/MRI: Is There Value in Adding Contrast-Enhanced MR Imaging?

Purpose

To investigate the added value of post-contrast VIBE (volumetric-interpolated breath-hold examination) to PET/MR imaging for pulmonary nodule detection in patients with primary malignancies.

Materials and Methods

This retrospective institutional review board–approved study, with waiver of informed consent, included 51 consecutive patients who underwent ¹⁸F-fluorodeoxyglucose (FDG) PET/MR followed by PET/CT for cancer staging. In all patients, the thorax was examined with pre-and post-contrast VIBE MR with simultaneous PET acquisition. Two readers blinded to the patients’ data independently recorded their level of suspicion for pulmonary nodules based on PET, pre-contrast VIBE, and fused PET/MR images (first session), and reassessed them 4-weeks later after addition of post-contrast VIBE (second session). Jackknife alternative free-response receiver-operating-characteristic (JAFROC) analysis was performed, with PET/CT as the reference standard.

Results

A total of 151 pulmonary nodules (44 FDG-avid, 107 non-FDG-avid nodules) were detected on PET/CT, including 62 nodules≥5mm in diameter and 89 nodules<5mm. In the first session, the average nodule detection rate was 53.3% for all nodules, 97.7% for FDG-avid, 35.0% for non-FDG-avid nodules, 87.9% for nodules≥5mm and 29.2% for nodules<5mm. In the second session, the average detection rate was 53.3% for all nodules, 97.7% for FDG-avid, 35.0% for non-FDG-avid nodules, 85.5% for nodules≥5mm and 30.9% for nodules<5mm. The average JAFROC figure-of-merit was 0.837 in the first session and 0.848 in the second session. There were no significant differences in detection performance between sessions (P=0.48).

Conclusion

The addition of post-contrast VIBE to hybrid PET/MR imaging provided no additional value in the detection of pulmonary nodules.     

Chest Computed Tomography Findings in HIV-Infected Individuals in the Era of Antiretroviral Therapy

Background

Chest radiographic abnormalities were common in HIV-infected individuals in the pre-combination antiretroviral therapy era, but findings may differ now due to a changing spectrum of pulmonary complications.

Methods

Cross-sectional study of radiographic abnormalities in an HIV-infected outpatient population during the antiretroviral therapy era. Demographics, chest computed tomography, and pulmonary function tests were obtained in HIV-infected volunteers without acute respiratory illness from the University of Pittsburgh HIV/AIDS clinic. Overall prevalence of radiographic abnormalities and potential risk factors for having any abnormality, nodules, or emphysema were evaluated using univariate and multivariable analyses.

Results

A majority of the 121 participants (55.4%) had a radiographic abnormality with the most common being emphysema (26.4%), nodules (17.4%), and bronchiectasis (10.7%). In multivariate models, age (odds ratio [OR] per year  = 1.07, 95% confidence interval [CI] 1.04–1.14, p<0.001), pneumonia history (OR  = 3.60, 95% CI  = 1.27–10.20, p = 0.016), and having ever smoked (OR  = 3.66, p = 0.013, 95% CI  = 1.31–10.12) were significant predictors of having any radiographic abnormality. Use of antiretroviral therapy, CD4 cell count, and HIV viral load were not associated with presence of abnormalities. Individuals with radiographic emphysema were more likely to have airway obstruction on pulmonary function tests. Only 85.8% participants with nodules had follow-up imaging resulting in 52.4% having stable nodules, 23.8% resolution of their nodules, 4.8% development of a new nodule, and 4.8% primary lung cancer.

Conclusions

Radiographic abnormalities remain common in HIV-infected individuals with emphysema, nodules, and bronchiectasis being the most common. Age, smoking, and pneumonia were associated with radiographic abnormalities, but HIV-associated factors did not seem to predict risk.     

Semi-Automatic Quantification of Subsolid Pulmonary Nodules: Comparison with Manual Measurements

Rationale

Accurate measurement of subsolid pulmonary nodules (SSN) is becoming increasingly important in the management of these nodules. SSNs were previously quantified with time-consuming manual measurements. The aim of the present study is to test the feasibility of semi-automatic SSNs measurements and to compare the results to the manual measurements.

Methods

In 33 lung cancer screening participants with 33 SSNs, the nodules were previously quantified by two observers manually. In the present study two observers quantified these nodules by using semi-automated nodule volumetry software. Nodules were quantified for effective diameter, volume and mass. The manual and semi-automatic measurements were compared using Bland-Altman plots and paired T tests. Observer agreement was calculated as an intraclass correlation coefficient. Data are presented as mean (SD).

Results

Semi-automated measurements were feasible in all 33 nodules. Nodule diameter, volume and mass were 11.2 (3.3) mm, 935 (691) ml and 379 (311) milligrams for observer 1 and 11.1 (3.7) mm, 986 (797) ml and 399 (344) milligrams for observer 2, respectively. Agreement between observers and within observer 1 for the semi-automatic measurements was good with an intraclass correlation coefficient >0.89. For observer 1 and observer 2, measured diameter was 8.8% and 10.3% larger (p<0.001), measured volume was 24.3% and 26.5% larger (p<0.001) and measured mass was 10.6% and 12.0% larger (p<0.001) with the semi-automatic program compared to the manual measurements.

Conclusion

Semi-automated measurement of the diameter, volume and mass of SSNs is feasible with good observer agreement. Semi-automated measurement makes quantification of mass and volume feasible in daily practice.     

The Association of Thyroid Nodule with Non-Iodized Salt among Chinese Children

Objective

The controversy that iodized salt may increase the risk of thyroid disorders has been aroused in China during the past decade. Most of studies focused on adult rather than children. We aimed to explore whether iodized salt was associated with an increased risk of thyroid nodule in Chinese children.

Methods

The cross-sectional study was conducted in Hangzhou, China, in 2010. Iodized salt intake, urine iodine concentration (UIC) and thyroid nodule (by ultrasonography) were measured in 3026 children. The associations of iodized salt with thyroid nodule were evaluated using multiple logistic regression models.

Results

The prevalence of thyroid nodule was 10.59% among Chinese children. Girls (11.89%) had higher prevalence of thyroid nodule than boys (9.26%). No significant association was observed between type of salt and thyroid nodule in pooled samples, boys and girls, respectively. Similar associations were observed between UIC and thyroid nodule. There was no significant association between milk consumption and thyroid nodule as well.

Conclusion

The present study indicated that non-iodized salt may not increase the risk of thyroid nodules among Chinese children. Similar associations were observed between milk consumption, UIC and thyroid nodules.     

A Tri-Modality Image Fusion Method for Target Delineation of Brain Tumors in Radiotherapy

Purpose

To develop a tri-modality image fusion method for better target delineation in image-guided radiotherapy for patients with brain tumors.

Methods

A new method of tri-modality image fusion was developed, which can fuse and display all image sets in one panel and one operation. And a feasibility study in gross tumor volume (GTV) delineation using data from three patients with brain tumors was conducted, which included images of simulation CT, MRI, and ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) examinations before radiotherapy. Tri-modality image fusion was implemented after image registrations of CT+PET and CT+MRI, and the transparency weight of each modality could be adjusted and set by users. Three radiation oncologists delineated GTVs for all patients using dual-modality (MRI/CT) and tri-modality (MRI/CT/PET) image fusion respectively. Inter-observer variation was assessed by the coefficient of variation (COV), the average distance between surface and centroid (ADSC), and the local standard deviation (SD_local). Analysis of COV was also performed to evaluate intra-observer volume variation.

Results

The inter-observer variation analysis showed that, the mean COV was 0.14(±0.09) and 0.07(±0.01) for dual-modality and tri-modality respectively; the standard deviation of ADSC was significantly reduced (p<0.05) with tri-modality; SD_local averaged over median GTV surface was reduced in patient 2 (from 0.57 cm to 0.39 cm) and patient 3 (from 0.42 cm to 0.36 cm) with the new method. The intra-observer volume variation was also significantly reduced (p = 0.00) with the tri-modality method as compared with using the dual-modality method.

Conclusion

With the new tri-modality image fusion method smaller inter- and intra-observer variation in GTV definition for the brain tumors can be achieved, which improves the consistency and accuracy for target delineation in individualized radiotherapy.     

Identifying abnormalities in symbiotic development between Trifolium spp. and Rhizobium leguminosarum bv. trifolii leading to sub-optimal and ineffective nodule phenotypes

Background and Aims

Legumes overcome nitrogen limitations by entering into a mutualistic symbiosis with N₂-fixing bacteria (rhizobia). Fully compatible associations (effective) between Trifolium spp. and Rhizobium leguminosarum bv. trifolii result from successful recognition of symbiotic partners in the rhizosphere, root hair infection and the formation of nodules where N₂-fixing bacteroids reside. Poorly compatible associations can result in root nodule formation with minimal (sub-optimal) or no (ineffective) N₂-fixation. Despite the abundance and persistence of strains in agricultural soils which are poorly compatible with the commercially grown clover species, little is known of how and why they fail symbiotically. The aims of this research were to determine the morphological aberrations occurring in sub-optimal and ineffective clover nodules and to determine whether reduced bacteroid numbers or reduced N₂-fixing activity is the main cause for the Sub-optimal phenotype.

Methods

Symbiotic effectiveness of four Trifolium hosts with each of four R. leguminosarum bv. trifolii strains was assessed by analysis of plant yields and nitrogen content; nodule yields, abundance, morphology and internal structure; and bacteroid cytology, quantity and activity.

Key Results

Effective nodules (Nodule Function 83–100 %) contained four developmental zones and N₂-fixing bacteroids. In contrast, Sub-optimal nodules of the same age (Nodule Function 24–57 %) carried prematurely senescing bacteroids and a small bacteroid pool resulting in reduced shoot N. Ineffective-differentiated nodules carried bacteroids aborted at stage 2 or 3 in differentiation. In contrast, bacteroids were not observed in Ineffective-vegetative nodules despite the presence of bacteria within infection threads.

Conclusions

Three major responses to N₂-fixation incompatibility between Trifolium spp. and R. l. trifolii strains were found: failed bacterial endocytosis from infection threads into plant cortical cells, bacteroid differentiation aborted prematurely, and a reduced pool of functional bacteroids which underwent premature senescence. We discuss possible underlying genetic causes of these developmental abnormalities and consider impacts on N₂-fixation of clovers.     

Activation of c-Src tyrosine kinase mediated the degradation of occludin in ventilator-induced lung injury

Background

Ventilator-induced lung injury (VILI) is characterized by increased alveolar permeability, pulmonary edema. The tyrosine kinase, c-Src, is involved in VILI but its role has not been fully elucidated. This study examined the relationship between c-Src activation and occludin levels in VILI both in vitro and in vivo.

Methods

For the in vivo study, Wistar rats were randomly divided into five groups: control (group C); normal tidal volume (group M); normal tidal volume + c-Src inhibitor (PP2) (group M + P); high tidal volume (group H); and high tidal volume + c-Src inhibitor (PP2) (group H + P). Rats in all groups but group C underwent mechanical ventilation for 4 h. For the in vitro study, MLE-12 cells pretreated with PP2 and siRNA underwent cyclic stretching at 8% or 20% for 0, 1, 2 and 4 h. The expressions of occludin, c-Src, and p-c-Src were analyzed by western blotting, hematoxylin and eosin (HE) staining, and immunofluorescence.

Results

For the in vivo study, rats in group H showed decreased occludin expression and activated c-Src compared with group C. HE staining and lung injury score showed more severe lung injury and alveolar edema in group H compared with group M and group C. Group H + P had less pulmonary edema induced by the high tidal volume ventilation. For the in vitro study, occludin expression decreased and c-Src activation increased as indicated by the phosphorylation of c-Src over time. Consistently, PP2 could restore occludin levels.

Conclusions

Mechanical ventilation can activate c-Src by phosphorylation and increase the degradation of occludin. c-Src inhibitor can ameliorate barrier function and lung injury by up-regulating occludin.     

Novel and Convenient Method to Evaluate the Character of Solitary Pulmonary Nodule-Comparison of Three Mathematical Prediction Models and Further Stratification of Risk Factors

Objective

To study risk factors that affect the evaluation of malignancy in patients with solitary pulmonary nodules (SPN) and verify different predictive models for malignant probability of SPN.

Methods

Retrospectively analyzed 107 cases of SPN with definite post-operative histological diagnosis whom underwent surgical procedures in China-Japan Friendship Hospital from November of 2010 to February of 2013. Age, gender, smoking history, malignancy history of patients, imaging features of the nodule including maximum diameter, position, spiculation, lobulation, calcification and serum level of CEA and Cyfra21-1 were assessed as potential risk factors. Univariate analysis model was used to establish statistical correlation between risk factors and post-operative histological diagnosis. Receiver operating characteristic (ROC) curves were drawn using different predictive models for malignant probability of SPN to get areas under the curves (AUC values), sensitivity, specificity, positive predictive values, negative predictive values for each model, respectively. The predictive effectiveness of each model was statistically assessed subsequently.

Results

In 107 patients, 78 cases were malignant (72.9%), 29 cases were benign (27.1%). Statistical significant difference was found between benign and malignant group in age, maximum diameter, serum level of Cyfra21-1, spiculation, lobulation and calcification of the nodules. The AUC values were 0.786±0.053 (Mayo model), 0.682±0.060 (VA model) and 0.810±0.051 (Peking University People’s Hospital model), respectively.

Conclusions

Serum level of Cyfra21-1, patient’s age, maximum diameter of the nodule, spiculation, lobulation and calcification of the nodule are independent risk factors associated with the malignant probability of SPN. Peking University People’s Hospital model is of high accuracy and clinical value for patients with SPN. Adding serum index (e.g. Cyfra21-1) into the prediction models as a new risk factor and adjusting the weight of age in the models might improve the accuracy of prediction for SPN.     

A Model to Discriminate Malignant from Benign Thyroid Nodules Using Artificial Neural Network

Objective

This study aimed to construct a model for using in differentiating benign and malignant nodules with the artificial neural network and to increase the objective diagnostic accuracy of US.

Materials and methods

618 consecutive patients (528 women, 161 men) with 689 thyroid nodules (425 malignant and 264 benign nodules) were enrolled in the present study. The presence and absence of each sonographic feature was assessed for each nodule - shape, margin, echogenicity, internal composition, presence of calcifications, peripheral halo and vascularity on color Doppler. The variables meet the following criteria: important sonographic features and statistically significant difference were selected as the input layer to build the ANN for predicting the malignancy of nodules.

Results

Six sonographic features including shape (Taller than wide, p<0.001), margin (Not Well-circumscribed, p<0.001), echogenicity (Hypoechogenicity, p<0.001), internal composition (Solid, p<0.001), presence of calcifications (Microcalcification, p<0.001) and peripheral halo (Absent, p<0.001) were significantly associated with malignant nodules. A three-layer 6-8-1 feed-forward ANN model was built. In the training cohort, the accuracy of the ANN in predicting malignancy of thyroid nodules was 82.3% (AUROC = 0.818), the sensitivity and specificity was 84.5% and 79.1%, respectively. In the validation cohort, the accuracy, sensitivity and specificity was 83.1%, 83.8% and 81.8%, respectively. The AUROC was 0.828.

Conclusion

ANN constructed by sonographic features can discriminate benign and malignant thyroid nodules with high diagnostic accuracy.     

Reduced Radiation Exposure for Face Transplant Surgical Planning Computed Tomography Angiography

Objective

To test the hypothesis that wide area detector face transplant surgical planning CT angiograms with simulated lower radiation dose and iterative reconstruction (AIDR3D) are comparable in image quality to those with standard tube current and filtered back projection (FBP) reconstruction.

Materials and Methods

The sinograms from 320-detector row CT angiography of four clinical candidates for face transplantation were processed utilizing standard FBP, FBP with simulated 75, 62, and 50% tube current, and AIDR3D with corresponding dose reduction. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured at muscle, fat, artery, and vein. Image quality for each reconstruction strategy was assessed by two independent readers using a 4-point scale.

Results

Compared to FBP, the median SNR and CNR for AIDR3D images were higher at all sites for all 4 different tube currents. The AIDR3D with simulated 50% tube current achieved comparable SNR and CNR to FBP with standard dose (median muscle SNR: 5.77 vs. 6.23; fat SNR: 6.40 vs. 5.75; artery SNR: 43.8 vs. 45.0; vein SNR: 54.9 vs. 55.7; artery CNR: 38.1 vs. 38.6; vein CNR: 49.0 vs. 48.7; all p-values >0.19). The interobserver agreement in the image quality score was good (weighted κ = 0.7). The overall score and the scores for smaller arteries were significantly lower when FBP with 50% dose reduction was used. The AIDR3D reconstruction images with 4 different simulated doses achieved a mean score ranging from 3.68 to 3.82 that were comparable to the scores from images reconstructed using FBP with original dose (3.68–3.77).

Conclusions

Simulated radiation dose reduction applied to clinical CT angiography for face transplant planning suggests that AIDR3D allows for a 50% reduction in radiation dose, as compared to FBP, while preserving image quality.     

Can Spectral CT Imaging Improve the Differentiation between Malignant and Benign Solitary Pulmonary Nodules?

Purpose

To quantitatively assess the value of dual-energy CT (DECT) in differentiating malignancy and benignity of solitary pulmonary nodules.

Materials and Methods

Sixty-three patients with solitary pulmonary nodules detected by CT plain scan underwent contrast enhanced CT scans in arterial phase (AP) and venous phase (VP) with spectral imaging mode for tumor type differentiation. The Gemstone Spectral Imaging (GSI) viewer was used for image display and data analysis. Region of interest was placed on the relatively homogeneous area of the nodule to measure iodine concentration (IC) on iodine-based material decomposition images and CT numbers on monochromatic image sets to generate spectral HU curve. Normalized IC (NIC), slope of the spectral HU curve (λ_HU) and net CT number enhancement on 70keV images were calculated. The two-sample t-test was used to compare quantitative parameters. Receiver operating characteristic curves were generated to calculate sensitivity and specificity.

Results

There were 63 nodules, with 37 malignant nodules (59%) and 26 benign nodules (41%). NIC, λ_HU and net CT number enhancement on 70keV images for malignant nodules were all greater than those of benign nodules. NIC and λ_HU had intermediate to high performances to differentiate malignant nodules from benign ones with the areas under curve of 0.89 and 0.86 respectively in AP, 0.96 and 0.89 respectively in VP. Using 0.30 as a threshold value for NIC in VP, one could obtain sensitivity of 93.8% and specificity of 85.7% for differentiating malignant from benign solitary pulmonary nodules. These values were statistically higher than the corresponding values of 74.2% and 53.8% obtained with the conventional CT number enhancement.

Conclusions

DECT imaging with GSI mode provides more promising value in quantitative way for distinguishing malignant nodules from benign ones than CT enhancement numbers.     

Anergic Pulmonary Tuberculosis Is Associated with Contraction of the Vd2+T Cell Population,Apoptosis and Enhanced Inhibitory Cytokine Production

Objective

To study the association of anergic pulmonary tuberculosis with Vδ2⁺ T cells and related cytokine levels.

Methods

82 pulmonary tuberculosis patients were divided into two groups according to their purified protein derivative tuberculin skin test (TST) results: 39 with TST-negative anergic pulmonary tuberculosis and 43 with TST-positive pulmonary tuberculosis, while 40 healthy volunteers were used as control. Based on chest X-ray results, the tuberculosis lesions were scored according to their severity, with a score of ≤ 2.5 ranking as mild, 2.5-6 as moderate and ≥ 6 as severe. The Vδ2⁺ T cell percentage and their expression levels of the apoptosis-related membrane surface molecule FasL in peripheral blood and bronchoalveolar lavage fluids (BALF) were analyzed by flow cytometry, while IL-2, IL-4, IL-6 and IL-10 cytokine and γ-interferon (γ-IFN) concentrations in peripheral blood were determined by ELISA.

Results

Most of the patients with chest X-ray lesion scores higher than 6 belonged to the anergic tuberculosis group (P<0.05). Anergic pulmonary tuberculosis patients displayed reduced peripheral blood Vδ2⁺ T cell counts (P<0.05) and higher FasL expression in peripheral blood Vδ2 ⁺ T cells (P <0.05). The Vδ2⁺ T cell percentages in the BALF of all tuberculosis patients were lower than in their peripheral blood (P <0.05), and IL-4 and IL-10 concentrations in peripheral blood of anergic tuberculosis patients were higher than in TST-positive tuberculosis patients and healthy controls (P <0.05).

Conclusion

Anergic pulmonary tuberculosis is accompanied by reduced Vδ2⁺ T cell percentage, and elevated Vδ2⁺ T cell FasL expression as well as enhanced IL-4 and IL-10 levels in peripheral blood.     

Quantitative CT Analysis of Pulmonary Ground-Glass Opacity Nodules for the Distinction of Invasive Adenocarcinoma from Pre-Invasive or Minimally Invasive Adenocarcinoma

Objectives

We aimed to analyze the CT findings of ground-glass opacity nodules diagnosed pathologically as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma in order to investigate whether quantitative CT parameters enable distinction of invasive adenocarcinoma from pre-invasive or minimally invasive adenocarcinoma.

Methods

We reviewed CT images and pathologic specimens from 191 resected ground-glass opacity nodules with little or no solid component at CT. Nodule size, volume, density, mass, skewness/kurtosis, and CT attenuation values at the 2.5^th–97.5^th percentiles on histogram, and texture parameters (uniformity and entropy) were assessed from CT datasets.

Results

Of 191 tumors, 38 were AISs (20%), 61 were MIAs (32%), and 92 (48%) were invasive adenocarcinomas. Multivariate logistic regression analysis helped identify the 75^th percentile CT attenuation value (P = 0.04) and entropy (P<0.01) as independent predictors for invasive adenocarcinoma, with an area under the receiver operating characteristic curve of 0.780.

Conclusion

Quantitative analysis of preoperative CT imaging metrics can help distinguish invasive adenocarcinoma from pre-invasive or minimally invasive adenocarcinoma.     

Pathological Changes in Pulmonary Circulation in Carbon Tetrachloride (ccl4)-Induced Cirrhotic Mice

Rationale

Lack of an experimental model of portopulmonary hypertension (POPH) has been a major obstacle in understanding of pathophysiological mechanisms underlying the disease.

Objective

We investigated the effects of CCl₄-mediated cirrhosis on the pulmonary vasculature, as an initial step towards an improved understanding of POPH.

Methods And Results

Male C57BL/6 mice received intraperitoneal injection of either sterile olive oil or CCl₄ 3 times/week for 12 weeks. Cirrhosis and portal hypertension were confirmed by evidence of bridging fibrosis and nodule formation in CCl₄-treated liver determined by trichrome/picrosirius red staining and an increase in spleen weight/body weight ratio, respectively. Staining for the oxidative stress marker, 4-hydroxynonenal (4-HNE), was strong in the liver but was absent in the lung, suggesting that CCl₄ did not directly induce oxidative injury in the lung. Pulmonary acceleration time (PAT) and the ratio of PAT/pulmonary ejection time (PET) measured by echocardiography were significantly decreased in cirrhotic mice. Increase in right ventricle (RV) weight/body weight as well as in the weight ratio of RV/(left ventricle + septum) further demonstrated the presence of pathological changes in the pulmonary circulation in these mice. Histological examination revealed that lungs of cirrhotic mice have excessive accumulation of perivascular collagen and thickening of the media of the pulmonary artery.

Conclusion

Collectively, our data demonstrate that chronic CCl₄ treatment induces pathological changes in pulmonary circulation in cirrhotic mice. We propose that this murine cirrhotic model provides an exceptional tool for future studies of the molecular mechanisms mediating pulmonary vascular diseases associated with cirrhosis and for evaluation of novel therapeutic interventions.     

Detection of Time-Varying Structures by Large Deformation Diffeomorphic Metric Mapping to Aid Reading of High-Resolution CT Images of the Lung

Objectives

To evaluate the accuracy of advanced non-linear registration of serial lung Computed Tomography (CT) images using Large Deformation Diffeomorphic Metric Mapping (LDDMM).

Methods

Fifteen cases of lung cancer with serial lung CT images (interval: 62.2±26.9 days) were used. After affine transformation, three dimensional, non-linear volume registration was conducted using LDDMM with or without cascading elasticity control. Registration accuracy was evaluated by measuring the displacement of landmarks placed on vessel bifurcations for each lung segment. Subtraction images and Jacobian color maps, calculated from the transformation matrix derived from image warping, were generated, which were used to evaluate time-course changes of the tumors.

Results

The average displacement of landmarks was 0.02±0.16 mm and 0.12±0.60 mm for proximal and distal landmarks after LDDMM transformation with cascading elasticity control, which was significantly smaller than 3.11±2.47 mm and 3.99±3.05 mm, respectively, after affine transformation. Emerged or vanished nodules were visualized on subtraction images, and enlarging or shrinking nodules were displayed on Jacobian maps enabled by highly accurate registration of the nodules using LDDMM. However, some residual misalignments were observed, even with non-linear transformation when substantial changes existed between the image pairs.

Conclusions

LDDMM provides accurate registration of serial lung CT images, and temporal subtraction images with Jacobian maps help radiologists to find changes in pulmonary nodules.     

Chronic Hypoxia Increases TRPC6 Expression and Basal Intracellular Ca2+ Concentration in Rat Distal Pulmonary Venous Smooth Muscle

Background

Hypoxia causes remodeling and contractile responses in both pulmonary artery (PA) and pulmonary vein (PV). Here we explore the effect of hypoxia on PV and pulmonary venous smooth muscle cells (PVSMCs).

Methods

Chronic hypoxic pulmonary hypertension (CHPH) model was established by exposing rats to 10% O₂ for 21 days. Rat distal PVSMCs were isolated and cultured for in vitro experiments. The fura-2 based fluorescence calcium imaging was used to measure the basal intracellular Ca²⁺ concentration ([Ca²⁺]_i) and store-operated Ca²⁺ entry (SOCE). Quantitative RT-PCR and western blotting were performed to measure the expression of mRNA and levels of canonical transient receptor potential (TRPC) protein respectively.

Results

Hypoxia increased the basal [Ca²⁺]_i and SOCE in both freshly dissociated and serum cultured distal PVSMCs. Moreover, hypoxia increased TRPC6 expression at mRNA and protein levels in both cultured PVSMCs exposed to prolonged hypoxia (4% O₂, 60 h) and distal PV isolated from CHPH rats. Hypoxia also enhanced proliferation and migration of rat distal PVSMCs.

Conclusions

Hypoxia induces elevation of SOCE in distal PVSMCs, leading to enhancement of basal [Ca²⁺]_i in PVSMCs. This enhancement is potentially correlated with the increased expression of TRPC6. Hypoxia triggered intracellular calcium contributes to promoted proliferation and migration of PVSMCs.