Clinical application of computed tomographic volumetric imaging in postoperative lung function assessment in patients with lung cancer.

BACKGROUND: To evaluate the effectiveness of the computed tomographic (CT) volumetric analysis in postoperative lung function assessment and the predicting value for postoperative complications in patients who had segmentectomy for lung cancer. METHODS: CT scanning and pulmonary function examination were performed for 100 patients with lung cancer. CT volumetric analyses were performed by specific software, for the volume of the inspiratory phase (Vin), the mean inspiratory lung density (MLDin), the volume of expiratory phase (Vex), and the mean lung density at expiratory phase (MLDex). Pulmonary function examination results and CT volumetric analysis results were used to predict postoperative lung function. The concordance and correlations of these values were assessed by Bland-Altman analysis and Pearson correlation analysis, respectively. Multivariate binomial logistic regression analysis was executed to assess the associations of CT data with complication occurrence. RESULTS: Correlations between CT scanning data and pulmonary function examination results were significant in both pre- and post-operation (0.8083 ≤ r ≤ 0.9390). Forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and the ratio of FVC and FEV1 estimated by CT volumetric analyses showed high concordance with those detected by pulmonary function examination. Preoperative (Vin-Vex) and (MLDex- MLDin) values were identified as predictors for post-surgery complications, with hazard ratios of 5.378 and 6.524, respectively. CONCLUSIONS: CT volumetric imaging analysis has the potential to determine the pre- and post-operative lung function, as well as to predict post-surgery complication occurrence in lung cancer patients with pulmonary lobectomy.

Histomorphometric lung density evaluation of Immulina treatment using a murine influenza pneumonia model.

Histomorphometric lung density measurements were used to evaluate the effects of Immulina on mouse pneumonia. Mice were intra-nasally exposed to H1N1 influenza virus at a dose of 5 × 104 PFU/50 µL/mouse. Lung density was measured using the NIH ImageJ software program. Density values were compared to semiquantitative pneumonia severity scores. Lung photomicrographs were evaluated at 25-×, 40-× and 400-× magnification. The study included viral inoculated controls (IC) and non-inoculated controls (NC) and mice either treated or not treated with Immulina. Three doses of Immulina were included (25, 50 or 100 mg/kg) and administered using 3 protocols: prophylactic treatment (P), prodromal treatment (PD) and therapeutic treatment (TH) (note that in most of the evaluations of the data for the three treatment protocols were combined). Groups of mice were evaluated on days 3, 5, 7, 10 and 15 following exposure. The occurrence of "digital pneumonia" (DP) was defined as a density measurement above the 95% confidence limit of the corresponding NC values. A significant reduction in the occurrence of DP with Immulina treatment at the higher doses compared to IC was seen as early as day 3 and persisted up to day 15. There were also statistically significant dose-variable reductions in lung density in response to Immulina. The study suggests early administration of Immulina (P or PD protocols) may enhance resistance against influenza-induced viral pneumonia. A moderate correlation between pneumonia severity scores and lung density was observed for the 25-× and 40-× images (R = 0.56 and 0.53 respectively), and a strong correlation (R = 0.68) for 400-× images.

Obesity in women with asthma: Baseline disadvantage plus greater small-airway responsiveness.

BACKGROUND: Obesity is known to diminish lung volumes and worsen asthma. However, mechanistic understanding is lacking, especially as concerns small-airway responsiveness. The objective of this study was therefore to compare small-airway responsiveness, as represented by the change in expiratory:inspiratory mean lung density ratios (MLDe/i , as determined by computed tomography [CT]) throughout methacholine testing in obese versus non-obese women with asthma. METHODS: Thoracic CT was performed during methacholine bronchoconstriction challenges to produce standardized response curves (SRC: response parameter versus ln[1 + % PD20], where PD20 is the cumulative methacholine dose) for 31 asthma patients (n = 18 non-obese and n = 13 obese patients). Mixed models evaluated obesity effects and interactions on SRCs while adjusting for age and bronchial morphology. Small airway responsiveness as represented by SRC slope was calculated for each third of the MLDe/i response and compared between groups. RESULTS: Obesity-associated effects observed during experimental bronchoconstriction included: (i) a significant baseline effect for forced expiratory volume in 1 second with lower values for the obese (73.11 ± 13.44) versus non-obese (82.19 ± 8.78; p = 0.002) groups prior to methacholine testing and (ii) significantly higher responsiveness in small airways as estimated via differences in MLDe/i slopes (group×ln(1 + % PD20 interaction; p = 0.023). The latter were pinpointed to higher slopes in the obese group at the beginning 2/3 of SRCs (p = 0.004 and p = 0.021). Significant obesity effects (p = 0.035 and p = 0.008) indicating lower forced vital capacity and greater % change in MLDe/I (respectively) throughout methacholine testing, were also observed. CONCLUSION: In addition to baseline differences, small-airway responsiveness (as represented by the change in MLDe/i ) during methacholine challenge is greater in obese women with asthma as compared to the non-obese.

Free-breathing MR elastography of the lungs: An in vivo study.

PURPOSE: Lung stiffness alters with many diseases; therefore, several MR elastography (MRE) studies were performed earlier to investigate the stiffness of the right lung during breathhold at residual volume and total lung capacity. The aims of this study were 1) to estimate shear stiffness of the lungs using MRE under free breathing and demonstrate the measurements' repeatability and reproducibility, and 2) to compare lung stiffness under free breathing to breathhold and as a function of age and gender. METHODS: Twenty-five healthy volunteers were scanned on a 1.5 Tesla MRI scanner. Spin-echo dual-density spiral and a spin-echo EPI MRE sequences were used to measure shear stiffness of the lungs during free breathing and breathhold at midpoint of tidal volume, respectively. Concordance correlation coefficient and Bland-Altman analyses were performed to determine the repeatability and reproducibility of the spin-echo dual-density spiral-derived shear stiffness. Repeated measures analyses of variances were used to investigate differences in shear stiffness between spin-echo dual-density spiral and spin-echo EPI, right and left lungs, males and females, and different age groups. RESULTS: Free-breathing MRE sequence was highly repeatable and reproducible (concordance correlation coefficient > 0.86 for both lungs). Lung stiffness was significantly lower in breathhold than in free breathing (P < .001), which can be attributed to potential stress relaxation of lung parenchyma or breathhold inconsistencies. However, there was no significant difference between different age groups (P = .08). The left lung showed slightly higher stiffness values than the right lung (P = .14). There is no significant difference in lung stiffness between genders. CONCLUSION: This study demonstrated the feasibility of free-breathing lung MRE with excellent repeatability and reproducibility. Stiffness changes with age and during the respiratory cycle. However, gender does not influence lungs stiffness.

Tiny golden angle ultrashort echo-time lung imaging in mice.

Imaging the lung parenchyma with MRI is particularly difficult in small animals due to the high respiratory and heart rates, and ultrashort T2* at high magnetic field strength caused by the high susceptibilities induced by the air-tissue interfaces. In this study, a 2D ultrashort echo-time (UTE) technique was combined with tiny golden angle (tyGA) ordering. Data were acquired continuously at 11.7 T and retrospective center-of-k-space gating was applied to reconstruct respiratory multistage images. Lung (proton) density (fP ), T2*, signal-to-noise ratio (SNR), fractional ventilation (FV) and perfusion (f) were quantified, and the application to dynamic contrast agent (CA)-enhanced (DCE) qualitative perfusion assessment tested. The interobserver and intraobserver and interstudy reproducibility of the quantitative parameters were investigated. High-quality images of the lung parenchyma could be acquired in all animals. Over all lung regions a mean T2* of 0.20 ± 0.05 ms was observed. FV resulted as 0.31 ± 0.13, and a trend towards lower SNR values during inspiration (EX: SNR = 12.48 ± 6.68, IN: SNR = 11.79 ± 5.86) and a significant (P < 0.001) decrease in lung density (EX: fP  = 0.69 ± 0.13, IN: fP  = 0.62 ± 0.13) were observed. Quantitative perfusion results as 34.63 ± 9.05 mL/cm3 /min (systole) and 32.77 ± 8.55 mL/cm3 /min (diastole) on average. The CA dynamics could be assessed and, because of the continuous nature of the data acquisition, reconstructed at different temporal resolutions. Where a good to excellent interobserver reproducibility and an excellent intraobserver reproducibility resulted, the interstudy reproducibility was only fair to good. In conclusion, the combination of tiny golden angles with UTE (2D tyGA UTE) resulted in a reliable imaging technique for lung morphology and function in mice, providing uniform k-space coverage and thus low-artefact images of the lung parenchyma after gating.

Three-dimensional magnetic resonance imaging ultrashort echo-time cones for assessing lung density in pediatric patients.

BACKGROUND: MRI of lung parenchyma is challenging because of the rapid decay of signal by susceptibility effects of aerated lung on routine fast spin-echo sequences. OBJECTIVE: To assess lung signal intensity in children on ultrashort echo-time sequences in comparison to a fast spin-echo technique. MATERIALS AND METHODS: We conducted a retrospective study of lung MRI obtained in 30 patients (median age 5 years, range 2 months to 18 years) including 15 with normal lungs and 15 with cystic fibrosis. On a fast spin-echo sequence with radial readout and an ultrashort echo-time sequence, both lungs were segmented and signal intensities were extracted. We compared lung-to-background signal ratios and histogram analysis between the two patient cohorts using non-parametric tests and correlation analysis. RESULTS: On ultrashort echo-time the lung-to-background ratio was age-dependent, ranging from 3.15 to 1.33 with high negative correlation (Rs = -0.86). Signal in posterior dependent portions of the lung was 18% and 11% higher than that of the anterior lung for age groups 0-2 and 2-18 years, respectively. The fast spin-echo sequence showed no variation of signal ratios by age or location, with a median of 0.99 (0.98-1.02). Histograms of ultrashort echo-time slices between controls and children with aggravated cystic fibrosis with mucus plugging and wall thickening exhibited significant discrepancies that differentiated between normal and pathological lungs. CONCLUSION: Signal intensity of lung on ultrashort echo-time is higher than that on fast spin-echo sequences, is age-dependent and shows a gravity-dependent anterior to posterior gradient. This signal variation appears similar to lung density described on CT.

Lung density analysis using quantitative computed tomography in children with pectus excavatum.

PURPOSE: To evaluate the mean lung density in children with pectus excavatum (PE) and to assess the correlation between the cardiac rotation angle, Haller index, pulmonary function test, and lung density. MATERIAL AND METHODS: This retrospective study included 33 children with PE and 31 healthy controls. The densities of lung parenchyma were evaluated by quantitative computed tomography (CT). Three lung levels were determined: T4 vertebra level, T10 vertebra level, and the level of the measurement of the cardiac rotation angle. The cardiac rotation angle and the Haller index were calculated. All measurements were done by 2 radiologists, independently. Student's t-test or the Mann-Whitney U test, intraclass correlation coefficients, Pearson or Spearman's rank correlation coefficient, and Kruskal-Wallis test were used for statistical analysis. A p-value less than 0.05 was considered as statistically significant. RESULTS: All the lung levels in the PE group had lower mean densities than healthy children, with statistical significance in the right lung at the T10 vertebra level (-818.60 ± 33.49 HU, -798.45 ± 40.24 HU; p = 0.028). There was a correlation between the cardiac rotation angle and the Haller index (r = 0.593; p < 0.001). There were no correlations between mean lung density and cardiac rotation angle, Haller index, and pulmonary function tests. CONCLUSIONS: The lower mean lung densities were found in PE, especially in the right lower lobe. The parenchymal aeration should be considered independently from the severity of PE.

Lung density measurement in postmortem computed tomography: a new tool to assess immediate neonatal breath in suspected neonaticides.

INTRO: Evidence of breath after birth is one of the main forensic issues in suspected neonaticide. Hydrostatic test (HT) and pathological examination are currently used to assess it, but they are not entirely reliable or immediately available. OBJECTIVE: To determine the performance of postmortem computed tomography (PMCT) to assess neonatal breath in suspected neonaticide, by comparing lung CT attenuation values between live birth and stillbirth cases, in correlation with HT and pathology. METHOD: Cases of suspected neonaticides who underwent a PMCT and complete forensic autopsy with an HT were retrospectively selected from the databases of four French Forensic Medicine Departments. The diagnosis of vitality (i.e., stillbirth or live birth) was based on the pathological examination and/or a combination of arguments, including HT result. Lung density on CT was measured in Hounsfield units (HU) by ROIs drawn in both pulmonary parenchymas. RESULTS: Eleven patients were included, six live birth and five stillbirth cases. The result of HT was concordant with pathological examination when available (seven cases). Mean lung densities in live birth cases (- 173 HU [- 255; - 91 CI 95%]) were significantly lower than in stillbirth cases (40 HU [28; 52 CI 95%]) (p < 0.05), with a very high degree of interobserver reproducibility (ICC = 0.998 (CI 95% 0.991-0.999; p < 0.001). CONCLUSION: PMCT and especially lung CT attenuation measurement is a reliable and easy-to-use method for assessing neonatal breath in suspected neonaticides.

[Method for Spectral Analysis of the Respiratory Cycle Based on Dynamic Pulmonary Computed Tomography].

Dynamic pulmonary computed tomography (CT) enables morphological analyses of tumor adhesion and infiltration and functional analyses of the lungs based on four-dimensional data. However, the functional analysis requires visualization of the respiratory cycle. The aim of the present study was to investigate the utility of spectral analysis as part of the functional analysis of the lungs based on dynamic pulmonary CT. In this study, the reference curves for the respiratory cycle were obtained using measurements of all phases of respiration based on the movement of the diaphragm. The reference curves and fields of the unaffected lung were divided into three sections: upper, middle, and lower. The central position within each lung field in the axial section was used as the fixed location, and the lung field concentrations (CT values within each lung field) were measured. Using the maximum entropy (ME) method, the spectral analysis was performed for the lung field concentration curves obtained in this manner. The investigated items were the peak frequency in the power spectrum based on the ME analysis of the reference curve and the time difference from this peak frequency in the upper, middle, and lower lung field concentration curves. The time differences (median±standard deviation) from the reference values were 0.18±0.20, 0.34±0.33, and 0.34±0.35 s in the upper, middle, and lower lung fields, respectively, indicating the smallest time difference in the upper lung field. Performing spectral analysis using the ME method on lung field concentration curves enables assessment of the respiratory cycle based on dynamic pulmonary CT, and this approach is consistent with the visual assessment of the respiratory cycle.

Computer-aided identification of interstitial lung disease based on computed tomography.

OBJECTIVE: Identification of interstitial lung disease (ILD) may be difficult in certain cases using pulmonary function tests (PFTs) or subjective radiological analysis. We evaluated the efficacy of quantitative computed tomography (CT) with 3-dimensional (3D) reconstruction for distinguishing ILD patients from healthy controls. MATERIALS AND METHODS: We retrospectively collected chest CT images of 102 ILD patients and 102 healthy matched controls, and measured the following parameters: lung parenchymal volume, emphysema indices low attenuation area LAA910 volume, LAA950 volume, LAA910%, and LAA950%, and mean lung density (MLD) for whole lung, left lung, right lung, and each lobe, respectively. The Mann-Whitney U test was used to compare quantitative CT parameters between groups. Receiver operating characteristic (ROC) curves, Bayesian stepwise discriminant analysis, and deep neural network analysis were used to test the discriminative performance of quantitative CT parameters. Binary logistic regression was performed to identify ILD markers. RESULTS: Total lung volume was lower in ILD patients than controls, while emphysema and MLD values were higher (P < 0.001) except LAA910 volume in right middle lobe. LAA910 volume, LAA950 volume, LAA910%, LAA950%, and MLD accurately distinguished ILD patients from healthy controls (AUC >0.5, P < 0.05), and high MLD was a significant marker for ILD (OR = 1.047, P < 0.05). CONCLUSIONS: This quantitative CT analysis can effectively identify ILD patients, providing an alternative to subjective image analysis and PFTs.

Signs of Gas Trapping in Normal Lung Density Regions in Smokers.

RATIONALE: A substantial proportion of subjects without overt airflow obstruction have significant respiratory morbidity and structural abnormalities as visualized by computed tomography. Whether regions of the lung that appear normal using traditional computed tomography criteria have mild disease is not known. OBJECTIVES: To identify subthreshold structural disease in normal-appearing lung regions in smokers. METHODS: We analyzed 8,034 subjects with complete inspiratory and expiratory computed tomographic data participating in the COPDGene Study, including 103 lifetime nonsmokers. The ratio of the mean lung density at end expiration (E) to end inspiration (I) was calculated in lung regions with normal density (ND) by traditional thresholds for mild emphysema (-910 Hounsfield units) and gas trapping (-856 Hounsfield units) to derive the ND-E/I ratio. Multivariable regression analysis was used to measure the associations between ND-E/I, lung function, and respiratory morbidity. MEASUREMENTS AND MAIN RESULTS: The ND-E/I ratio was greater in smokers than in nonsmokers, and it progressively increased from mild to severe chronic obstructive pulmonary disease severity. A proportion of 26.3% of smokers without airflow obstruction had ND-E/I greater than the 90th percentile of normal. ND-E/I was independently associated with FEV1 (adjusted ß = -0.020; 95% confidence interval [CI], -0.032 to -0.007; P = 0.001), St. George's Respiratory Questionnaire scores (adjusted ß = 0.952; 95% CI, 0.529 to 1.374; P < 0.001), 6-minute-walk distance (adjusted ß = -10.412; 95% CI, -12.267 to -8.556; P < 0.001), and body mass index, airflow obstruction, dyspnea, and exercise capacity index (adjusted ß = 0.169; 95% CI, 0.148 to 0.190; P < 0.001), and also with FEV1 change at follow-up (adjusted ß = -3.013; 95% CI, -4.478 to -1.548; P = 0.001). CONCLUSIONS: Subthreshold gas trapping representing mild small airway disease is prevalent in normal-appearing lung regions in smokers without airflow obstruction, and it is associated with respiratory morbidity. Clinical trial registered with www.clinicaltrials.gov (NCT00608764).

[Development of Audio Indicator System for Respiratory Dynamic CT Imaging].

We created the device, which can conduct a radiological technologist's voice to a subject during CT scanning. For 149 lung cancer, dynamic respiratory CT were performed. 92 cases were performed using this device, the others were without this device. The respiratory cycle and respiratory amplitude were analyzed from the lung density. A stable respirating cycle was obtained by using the audio indicator system. The audio indicator system is useful for respiratory dynamic CT.

Chronic Hypoxia Accentuates Dysanaptic Lung Growth.

RATIONALE: Adults born and raised at high altitudes have larger lung volumes and greater pulmonary diffusion capacity compared with adults at low altitude; however, it remains unclear whether the air and tissue volumes have comparable increases and whether there is a difference in airway size. OBJECTIVES: To assess the effect of chronic hypoxia on lung growth using in vivo high-resolution computed tomography measurements. METHODS: Healthy adults born and raised at moderate altitude (2,000 m above sea level; n = 19) and at low altitude (400 m above sea level; n = 23) underwent high-resolution computed tomography. Differences in total lung, air, and tissue volume, mean lung density, as well as airway lumen and wall areas in anatomically matched airways were compared between groups. MEASUREMENTS AND MAIN RESULTS: No significant differences for age, sex, weight, or height were found between the two groups (P > 0.05). In a multivariate regression model, altitude was a significant contributor for total lung volume (P = 0.02), air volume (P = 0.03), and tissue volume (P = 0.03), whereby the volumes were greater for the moderate- versus the low-altitude group. However, altitude was not a significant contributor for mean lung density (P = 0.35) or lumen and wall areas in anatomically matched segmental, subsegmental, and subsubsegmental airways. CONCLUSIONS: Our findings suggest that the adult lung did not increase lung volume later in life by expansion of an existing number of alveoli, but rather from increased alveolarization early in life. In addition, chronic hypoxia accentuates dysanaptic lung growth by increasing the lung parenchyma but not the airways.

Alpha-1-Antitrypsin Deficiency: Disease Management and Learning from Studies.

Alpha-1-antitrypsin deficiency (AATD) is one of the most frequent genetic causes of liver and lung diseases. Despite its known association with chronic obstructive pulmonary disease (COPD), AATD is largely unrecognised and underdiagnosed. Cases of AATD exist within every COPD or spirometry population but must be actively investigated. AATD is a laboratory diagnosis that must be confirmed by a blood test. A number of clinical 'clues' can raise suspicion of AATD, potentially facilitating earlier diagnosis and initiation of appropriate treatment. Alpha-1-antitrypsin augmentation therapy has a clear role in patients with severe AATD and a FEV1 ≤65% predicted. Emerging evidence suggests that attenuating the decline in lung density may prolong the time to respiratory failure.

Assessing the efficacy of Alpha1-Proteinase inhibitor (human) augmentation therapy for Alpha1-Antitrypsin deficiency - Related emphysema: Challenges and opportunities.

Clinical benefit of Alpha1-Proteinase Inhibitor (Human) (A1-PI) products for Alpha1-antitrypsin deficiency (AATD) is uncertain, based on a systematic review of observational studies and randomized controlled trials (RCTs) in AATD of Alpha1-Proteinase Inhibitor (Human) (A1-PI) products. At the recommended dose, A1-PI products raise its serum concentration but do not normalize levels. Observational studies suggest A1-PI might modestly slow progression of airflow limitation in patients with intermediate airflow obstruction, a finding not confirmed by three placebo-controlled RCTs of limited power, which showed non-significant rates of forced expiratory volume in 1 s (FEV1) change favoring placebo. These RCTs found trends favoring A1-PI in loss of high-resolution computerized tomographic (HRCT) lung density. While two meta-analyses of HRCT lung density change in RCTs achieved significance favoring A1-PI arms, clinical benefit remains uncertain. HRCT lung density measurements don't distinguish changes in measured density due to fluid shifts into and out of the lungs and changes in lung inflammation from those due to progressive loss of alveolar mass. A meta-analysis of RCTs found exacerbations significantly increased in A1-PI groups compared to placebo. No RCTs have shown favorable effects of A1-PI on mortality, FEV1, 6-min walking distance, quality of life, change in diffusion capacity of carbon monoxide (DLCO), or exacerbation frequency. A fourth RCT comparing two dose regimens of A1-PI is underway. RCTs have not provided evidence of clinical benefit in terms of how patients feel, function, or survive. Results have implications for the design of future clinical trials of A1-PI and potentially other products targeting AATD-associated emphysema.

Utility of block-matching and 3D filter for reproducibility of lung density and denoising in low-dose chest CT: A pilot study.

PURPOSE: This study aimed to acquire an image quality consistent with that of full-dose chest computed tomography (CT) when obtaining low-dose chest CT images and to analyze the effects of block-matching and 3D (BM3D) filters on lung density measurements and noise reduction in lung parenchyma. METHODS: Using full-dose chest CT images, we evaluated lung density measurements and noise reduction in lung parenchyma images for low-dose chest CT. Three filters (median, Wiener, and the proposed BM3D) were applied to low-dose chest CT images for comparison and analysis with images from full-dose chest CT. To evaluate lung density measurements, we measured CT attenuation at the 15th percentile of the lung CT histogram. The coefficient of variation (COV) and contrast-to-noise ratio (CNR) were used to evaluate the noise level. RESULTS: The 15th percentile of the lung CT histogram showed the smallest difference between full- and low-dose CT when applying the BM3D filter, and the highest difference between full- and low-dose CT without filters (full-dose =  - 926.28 ± 0.32, BM3D =  - 926.65 ± 0.32, and low-dose =  - 959.43 ± 0.95) (p < 0.05). The COV was smallest when applying the BM3D filter, whereas the CNR was the highest (p < 0.05). CONCLUSIONS: The results of the study prove that the BM3D filter can reduce image noise while increasing the reproducibility of the lung density, even for low-dose chest CT.

X-ray dose delivered during a longitudinal micro-CT study has no adverse effect on cardiac and pulmonary tissue in C57BL/6 mice.

BACKGROUND: Micro-computed tomography (micro-CT) offers numerous advantages for small animal imaging, including the ability to monitor the same animals throughout a longitudinal study. However, concerns are often raised regarding the effects of X-ray dose accumulated over the course of the experiment. PURPOSE: To scan C57BL/6 mice multiple times per week for 6 weeks, in order to determine the effect of the cumulative dose on pulmonary and cardiac tissue at the end of the study. MATERIAL AND METHODS: C57BL/6 male mice were split into two groups (irradiated group = 10, control group = 10). The irradiated group was scanned (80 kVp/50 mA) three times weekly for 6 weeks, resulting in a weekly dose of 0.84 Gy, and a total study dose of 5.04 Gy. The control group was scanned on the final week. Scans from week 6 were reconstructed and the lungs and heart were analyzed. RESULTS: Overall, there was no significant difference in lung volume or lung density or in left ventricular volume or ejection fraction between the control group and the irradiated group. Histological samples taken from excised lung and myocardial tissue also showed no evidence of inflammation or fibrosis in the irradiated group. CONCLUSION: This study demonstrated that a 5 Gy X-ray dose accumulated over 6 weeks during a longitudinal micro-CT study had no significant effects on the pulmonary and myocardial tissue of C57BL/6 mice. As a result, the many advantages of micro-CT imaging, including rapid acquisition of high-resolution, isotropic images in free-breathing mice, can be taken advantage of in longitudinal studies without concern for negative dose-related effects.

Quantitative analysis of pulmonary perfusion with dual-energy CT angiography: comparison of two quantification methods in patients with pulmonary embolism.

The study aimed to evaluate a quantification method of pulmonary perfusion with Dual-Energy CT Angiography (DE-CTA) normalized by lung density in the prediction of outcome in acute pulmonary embolism (PE). In this prospective study with CTA scans acquired with different breathing protocols, two perfusion parameters were calculated: %PBV (relative value of PBV, expressed per unit volume) and PBVm (PBV normalized by lung density, expressed per unit mass). DE-CTA parameters were correlated with simplified pulmonary embolism severity index (sPESI) and with outcome groups, alone and in combinationwith tomographic right-to-left ventricular ratios (RV/LV). PBVm showed significant correlation with sPESI. PBVm presented higher accuracy than %PBV In the prediction of ICU admission or death in patients with PE, with the best performance when combined with RV/LV volumetric ratio.

Association of Respiratory Functional Indices and Smoking with Pleural Movement and Mean Lung Density Assessed Using Four-Dimensional Dynamic-Ventilation Computed Tomography in Smokers and Patients with COPD.

Purpose: To correlate the ratio of the non-dependent to dependent aspects of the maximal pleural movement vector (MPMVND/D) and gravity-oriented collapse ratio (GCRND/D), and the mean lung field density (MLD) obtained using four-dimensional (4D) dynamic-ventilation computed tomography (DVCT) with airflow limitation parameters and the Brinkman index. Materials and Methods: Forty-seven patients, including 22 patients with COPD, 13 non-COPD smokers, and 12 non-smokers, with no/slight pleural adhesion confirmed using a thoracoscope, underwent 4D-DVCT with 16 cm coverage. Coordinates for the lung field center, as well as ventral and dorsal pleural points, set on the central trans-axial levels in the median and para-median sagittal planes at end-inspiration, were automatically measured (13-17 frame images, 0.35 seconds/frame). MPMVND/D and GCRND/D were calculated based on MPMV and GCR values for all the included points and the lung field center. MLD was automatically measured in each of the time frames, and the maximal change ratio of MLD (MLDCR) was calculated. These measured values were compared among COPD patients, non-COPD smokers, and non-smokers, and were correlated with the Brinkman index, FEV1/FVC, FEV1 predicted, RV/TLC, and FEF25-75% using Spearman's rank coefficients. Results: MPMVND/D was highest in non-smokers (0.819±0.464), followed by non-COPD smokers (0.405±0.131) and patients with COPD (-0.219±0.900). GCRND/D in non-smokers (1.003±1.384) was higher than that in patients with COPD (-0.164±1.199). MLDCR in non-COPD smokers (0.105±0.028) was higher than that in patients with COPD (0.078±0.027). MPMVND/D showed positive correlations with FEV1 predicted (r=0.397, p=0.006), FEV1/FVC (r=0.501, p<0.001), and FEF25-75% (r=0.368, p=0.012). GCRND/D also demonstrated positive correlations with FEV1 (r=0.397, p=0.006), FEV1/FVC (r=0.445, p=0.002), and FEF25-75% (r=0.371, p=0.011). MPMVND/D showed a negative correlation with the Brinkman index (r=-0.398, p=0.006). Conclusion: We demonstrated that reduced MPMVND/D and GCRND/D were associated with respiratory functional indices, in addition to a negative association of MPMVND/D with the Brinkman index, which should be recognized when assessing local pleural adhesion on DVCT, especially for ventral pleural aspects.

Diagnosis and augmentation therapy for alpha-1 antitrypsin deficiency: current knowledge and future potential.

The underdiagnosis of alpha-1 antitrypsin (AAT) deficiency (AATD) has been recognized for many years, yet little progress has been made in treatment of the disease. In this review, we summarize the AATD disease process as well as its diagnosis and treatment by AAT augmentation therapy. AATD is a rare autosomal disease that primarily affects the lungs and liver. AATD is associated with an increased susceptibility to developing pulmonary emphysema. The specific pharmacological treatment for AATD is intravenous administration of exogenous AAT. Augmentation therapy with AAT increases serum and pulmonary epithelial AAT levels, restores anti-elastase capacity, and decreases inflammatory mediators in the lung. Augmentation therapy reduces the loss of lung density over time, thus slowing progression of the disease. The effects of augmentation therapy on outcomes, such as frequency/duration of flare-ups, quality of life, lung function decline and mortality, are assessed. Wider testing for AATD, potentially through primary care physicians, could result in earlier treatment and better outcomes for individuals with AATD-induced lung respiratory disease.