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The aim – investigate the effect of whole-body vibration with high-frequency on the mineral density of the tibia of rats treated with glucocorticoids.Material and methods. 54 adult male Wistar rats were randomized to three groups: control, experimental group I - rats treated with methylprednisolone and experimental group II - methylprednisolone with whole-body vibration. Rats of the two experimental groups received methylprednisolone at a dose of 3 mg/kg every other day for 24 weeks. Group II was subjected to a total vertical vibration (50 Hz, with a vibration acceleration of 0.3g) for 30 min per day, 5 days per week throughout the experiment. Mineral density was assessed by CT densitometry at 8-16-24 weeks of the study.Results. The most significant bone loss was observed in experimental group I at the 16th and 24th week of the experiment, which decreased by 18.6% and 20.8%, respectively, compared with the control group. In experimental group II, the bone density index did not statistically decrease at the 8th week of our study, but at the 16th week decreased by -16.3%; and on the 24th week by -23.5% according to the control group. The density of the cortical layer of bone tissue did not change statistically in the experimental groups in relation to the control group.Conclusions. Our study demonstrated that high-frequency mechanical oscillations could partially suppress the harmful effects of methylprednisolone on bone mineral density in rats. Because glucocorticoids are an important cause of secondary osteoporosis in humans, mechanical stimulation in the form of exercise and training can prevent bone loss and stimulate bone formation.

Objective: to assess the accuracy of CT densitometry as a method for measuring the X-ray density of an object, as well as factors affecting the measurement results.Material and methods. X-ray density indicators were measured in various zones of phantoms containing drinking water with a volume of 0.5, 1.0, 1.5, and 2.0 l, as well as 5 identical vials with a capacity of 0.25 l with iopromide solutions with a concentration of 0, 5.2, 7.6, 10 and 20 ml/l. For each phantom, from 5 to 10 scans were made, followed by measuring the X-ray density of the contents in the central zone closest to the CT system center of rotation, and two zones located to the periphery from the center of rotation.Results. As a result of analyzing the values of measuring X-ray density in various parts of water-containing phantoms, an increase in the values of X-ray density near the center of rotation of the system and in the upper sections of the phantom with an increase in the volume of phantom was revealed. In the lower peripheral zone in 1.5 and 2.0 liter phantoms, the X-ray density was unchanged. The overestimation of the X-ray density values of the CT images of phantoms with small and large concentrations of iopromide during co-scanning compared with separate scanning was determined.Conclusion. CT densitometry is a highly sensitive method for measuring the X-ray density of image elements, however, the X-ray density of neighboring structures and the location of this zone relative to the center of rotation of the CT system affect the CT densitometry results. During jointly scanning phantoms of various densities, their mutual influence and the appearance of specific artifacts in the form of dark stripes on the lines of continuation of horizontal levels and “pulling up” the edges of these horizontal contrast levels to the center of rotation of the system were noted.

Rationale: Although small airway disease (SAD) is a feature of asthma, the association between SAD and relevant asthma outcomes remains unclear. The Assessment of Small Airways Involvement in Asthma (ATLANTIS) study was designed to identify the combination of physiological and imaging variables that best measure the presence and extent of SAD in asthma cross-sectionally and longitudinally. In this longitudinal analysis, we determined which small airway parameters studied were most strongly associated with asthma control, exacerbations, and quality of life. Methods: Total 773 participants with mild, moderate, or severe stable asthma were followed up for one year with a six-month clinic follow-up. Physiological tests included spirometry, lung volumes, impulse oscillometry (IOS), multiple breath nitrogen washout (MBNW), and percentage fall in forced vital capacity during methacholine challenge. Computed tomography was performed to determine CT densitometry of small airways disease. We examined the associations between these measurements and asthma exacerbations, control, and quality of life using univariate and multivariate analyses. Findings: Univariate analyses revealed that components of IOS, lung volumes, MBNW, and FEF25-75 were significantly correlated with asthma control and exacerbations (Spearman correlations: 0·20–0·25, p < 0·0001 Bonferroni correction). As a composite of IOS s, the ordinal score independently predicted asthma control and exacerbation in a multivariate analysis with known exacerbation predictors. CT parameters were not significantly correlated with asthma control, exacerbation, or quality of life. Interpretation: The results confirm that SAD, as measured by physiological tests, is longitudinally associated with clinically important asthma outcomes, such as asthma control and exacerbations. Funding: Chiesi Farmaceutici Declaration of Interest: MK reports grants paid to their institution for their research from National Institutes of Health, American Lung Association, Chiesi Farmaceutici (for support of this study), AstraZeneca and Sanofi-Regeneron; reports personal fees for consultancies from Chiesi Farmaceutici, Genentech (Roche), GSK, Sanofi Regeneron, and Astra-Zeneca, Speaker fees from Chiesi Farmaceutici; personal fees from participation in a data safety and monitoring board for Astra-Zeneca and ALung and leadership in the American Thoracic Society; MR has nothing to report; BH has nothing to report; DB has nothing to report; MVB receives grants paid to their institution from Chiesi Farmaceutici (for this study), Sanofi, Genentech, GSK and Roche; LMF reported personal fees for consultancies from Chiesi Farmaceutici; Speaker fees from participation in advisory boards for Chiesi Farmaceutici, Astra-Zeneca, GSK, Alfasigma, Novartis and Verona Pharma; Travel expense reimbursement from Chiesi Farmaceutici, Novartis and Menarini; personal fees from participation in a data safety and monitoring board for Novartis; GN reports being employed by Chiesi Farmaceutici; AP reports funding by Chiesi Farmaceutici (for this and other studies), AstraZeneca, GSK, Boehringer Ingelheim, Pfizer, Teva and Sanofi paid to their institution; reports personal fees for consulting from Chiesi Farmaceutici, AstraZeneca, GSK, Novartis, Sanofi, Iqvia, Avillion, Elpen Pharmaceutic, ALS; reports personal fees for lectures and presentations from Chiesi Farmaceutici, AstraZeneca, GSK, Boehringer Ingelheim, Menarini, Novartis, Zambon, Mundipharma, Teva, Sanofi, Edmond Pharma, Iqvia, MSD, Avillion, Elpen Pharmaceutic, ALS. KFR reported support from Chiesi Farmaceutici paid to their institution for this study; reports speaker fees from Astra-Zeneca, Boehringer Ingelheim, Chiesi Farmaceutici, Novartis, Sanofi & Regeneron, GlaxoSmithKline, Berlin Chemie and Roche Pharma; personal fees from participation in a data safety and monitoring board for Astra- Zeneca, Boehringer Ingelheim and Sanofi & Regeneron; reports leadership or fiduciary role for German Center for Lung Research, German Chest Society and American Thoracic Society; DS reports personal fees for consulting from Aerogen, Astra-Zeneca, Boehringer Ingelheim, Chiesi Farmaceutici, Cipla, CSL Behring, Epiendo, Genentech, GlaxoSmithKline, Glenmark, Gossamerbio, Kinaset, Menarini, Novartis, Pulmatrix, Sanofi, Teva, Theravance, Verona; CB reports paid to their institution from Chiesi Farmaceutici for this study, NIHR Biomedical Research Centre, grants paid to their institution GSK, AZ, BI, Novartis, Chiesi Farmaceutici, Sanofi, Genetech, Merck, Mologic, 4DPharma, Gossamer, personal fees for consulting from GSK, AZ, BI, Novartis, Chiesi Farmaceutici, Sanofi, Genentech, Merck, Mologic, 4DPharma, Gossamer, TEVA, Regeneron, Roche, CSL Behring; SS reports funding paid to their institution from Chiesi Farmaceutici for support of this study, personal fees from GSK, Novartis, ERT Medical, Astra Zeneca, Knopp Biotech, Owlstone Medical, Mundipharma, CSL Behring, Boehringer Ingelheim; reports personal fees for lectures from Chiesi Farmaceutici. Ethical Approval: The Medical Ethics Committee of each centre approved the protocol.

Rationale and Objectives This study aimed to determine the diagnostic aid of computed tomography (CT) features for the differentiation of active alveolitis and fibrosis using a CT texture analysis (CTTA) prototype and CT densitometry in patients with systemic sclerosis (SSc) using ancillary high-resolution computed tomography (HRCT) features and their longitudinal course as standard of reference. Materials and Methods We retrospectively analyzed thin-slice noncontrast chest CT image data of 43 patients with SSc (18 men, mean age 51.55 ± 15.52 years; range 23–71 years). All of them had repeated noncontrast enhanced HRCT of the lung. Classification into active alveolitis or fibrosis was done on HRCT based on classical HRCT findings (active alveolitis [19; 44.2%] and fibrosis [24; 55.8%]) and their course at midterm. Results were compared to pulmonary functional tests and were followed up by CT. Ground glass opacity was considered suggestive of alveolitis, whereas coarse reticulation with parenchymal distortion, traction bronchiectasis, and honeycombing were assigned to fibrosis. Results Statistically significant differences in CTTA were found for first-order textural features (mean intensity, average, deviation, skewness) and second-order statistics (entropy of co-occurrence matrix, mean number of nonuniformity (NGLDM), entropy of NGLDM, entropy of heterogeneity, intensity, and average). Cut-off value for the prediction of fibrosis at baseline was significant for entropy of intensity ( P value P value P value P value At pulmonary functional tests, forced expiratory volume in 1 second and single-breath diffusion capacity for carbon monoxide were significantly lower in fibrosis than in alveolitis 2.03 ± 0.78 vs. 2.61 ± 0.83, P P Conclusions CTTA parameters are significantly different in active alveolitis vs. fibrosis in patients with SSc and may be helpful for differentiation of these two entities.

BACKGROUND The lesion size is a risk factor for keloid recurrence after postoperative radiotherapy. However, it remains unclear whether the major axis diameter is the most appropriate parameter to evaluate lesion size, because keloids are often irregular in shape. Additionally, no previous study has investigated computed tomography (CT) densitometry parameters of keloids as potential predictors for recurrence after postoperative radiotherapy. MATERIALS AND METHODS The size and CT densitometry parameters were measured for 74 lesions with CT images of sufficient quality for evaluation. The association between recurrence and size or CT densitometry parameters was analyzed for 64 lesions that could be followed up for 6 months or more. RESULTS The major axis diameter × minor axis diameter × thickness showed the strongest correlation with volume (ρ = 0.96, P

COPD is diagnosed and evaluated by pulmonary function testing (PFT). Chest computed tomography (CT) primarily serves a descriptive role for diagnosis and severity evaluation. CT densitometry-based emphysema quantification and lobar fissure integrity assessment are most commonly used, mainly for lung volume reduction purposes and scientific efforts.A shift towards a more quantitative role for CT to assess pulmonary function is a logical next step, since more, currently underutilised, information is present in CT images. For instance, lung volumes such as residual volume and total lung capacity can be extracted from CT; these are strongly correlated to lung volumes measured by PFT.This review assesses the current evidence for use of quantitative CT as a proxy for PFT in COPD and discusses challenges in the movement towards CT as a more quantitative modality in COPD diagnosis and evaluation. To better understand the relevance of the traditional PFT measurements and the role CT might play in the replacement of these parameters, COPD pathology and traditional PFT measurements are discussed.

Diana Crossley,1 Mary Renton,1 Muhammad Khan,1 Emma V Low,1 Alice M Turner2 1Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK; 2Institute of Applied Health Sciences, University of Birmingham, Birmingham, UK Background: The aim of the study was to assess the relationship between computed tomography (CT) densitometry and routine clinical markers in patients with chronic obstructive pulmonary disease (COPD) and alpha-1 anti-trypsin deficiency (AATD).Methods: Multiple databases were searched using a combination of pertinent terms and those articles relating quantitatively measured CT densitometry to clinical outcomes. Studies that used visual scoring only were excluded, as were those measured in expiration only. A thorough review of abstracts and full manuscripts was conducted by 2 reviewers; data extraction and assessment of bias was conducted by 1 reviewer and the 4 reviewers independently assessed for quality. Pooled correlation coefficients were calculated, and heterogeneity was explored.Results: A total of 112 studies were identified, 82 being suitable for meta-analysis. The most commonly used density threshold was −950 HU, and a significant association between CT density and all included clinical parameters was demonstrated. There was marked heterogeneity between studies secondary to large variety of disease severity within commonly included cohorts and differences in CT acquisition parameters.Conclusion: CT density shows a good relationship to clinically relevant parameters; however, study heterogeneity and lack of longitudinal data mean that it is difficult to compare studies or derive a minimal clinically important difference. We recommend that international consensus is reached to standardize CT conduct and analysis in future COPD and AATD studies. Keywords: computed tomography, CT, densitometry, emphysema, chronic obstructive pulmonary disease, alpha-1 anti-trypsin deficiency

Introduction: The SGRQ is used to determine subjective evidence of benefit and has an established minimal clinically important difference (MCID). New therapies which have detectable short term effects on lung function become noticed by patients with COPD, reducing symptoms and improving exercise. However in chronic diseases the influence of age related deterioration in health and the impact of disease progression is slow and less readily detectable in patients in the absence of an acute intervening event. This is important for the design and interpretation of trials of disease modifying therapies. Aims and Objectives: To determine the relationship and decline of SGRQ in patients with AATD not receiving augmentation therapy Methods: We studied the relationship of SGRQ to pulmonary physiology and disease progression in 517 patients with AATD. All subjects were assessed annually over at least 3 years to obtain 4 data points enabling annual decline to be determined. Results: The SGRQ (total score) was statistically related to baseline FEV1 (r2 =0.377;p Conclusions: These unique data have important implications for trial design. Studies of augmentation therapy in AATD have shown efficacy determined by preservation of lung tissue determined by CT densitometry (Chapman, K. et al. Lancet 2015;386:360–368). However such studies have not demonstrated an effect on lung function decline or health status. The current data suggest that if augmentation were to prevent decline in SGRQ, a study of 8 years would be required to attain the MCID for this health status measure.

Introduction: The study of rare diseases presents major practical problems including access to national centres particularly for the most severely affected patients. For this reason the National Institute for Health Research established a Rare Diseases Translational Research Collaboration. Methods: The Alpha-1-Antitrypsin Rare Diseases Translational Research Collaboration established a hub and spoke academic network to study 100 patients with mild to moderate COPD and 100 with severe and very severe disease using an anonymised comprehensive database paired with uniform biological sample collection for biomarker studies. Results: The network of academic centres is shown in the figure. To date 98 patients have been recruited and demographic data, CT scans and biological samples have been collated at the lead Birmingham site for analysis. Aα-Val 360 (a specific footprint of neutrophil elastase activity in vivo) showed a positive correlation with the degree of emphysema as assessed by the % low attenuation voxels ( th percentile point (r = 0.275 and 0.22 respectively, p Conclusion: The NIHR AATD network provides an effective resource to study the whole of the disease spectrum for clinical and biomarker studies. Aα-Val 360 remains the best validated specific marker of the degree of emphysema in AATD.

Introduction Quantitatively measuring the severity of emphysema in patients with COPD and AATD by CT densitometry is rapidly being recognised as an accurate and sensitive measure of disease stage and progression. We aim to elucidate the utility and interpretation of densitometry objectively through a new systematic review, and to establish the minimally clinically important difference (MCID) in density decline. An MCID for FEV1 and SGRQ in COPD is already well established, but in AATD specifically, this MCID should indicate those patient with significant net tissue loss and therefore consideration of further therapies. Methods We conducted an extensive and robust systematic review adhering to the Cochrane guidelines, with care to include all relevant studies, to eliminate bias and to meta-analyse appropriate results Results Due to wide variable outcome measures reported in both the measure of density i.e. differing %LAA (low attenuation areas) or the 15 th percentile point, a narrative meta-analysis was conducted where necessary. We propose an MCID incorporating important clinical variables such as lung function, and quality of life measures. Conclusion. The MCID of CT quantified density change will provide a useful additional tool in assessing patients with emphysema, and to potentially identify earlier those patients who are rapid decliners.

CT densitometry is the most accurate, specific and sensitive measure of the severity of emphysema in patients with COPD and α1-antitrypsin deficiency (AATD). Health status is increasingly documented using subjective measurement tools such as SGRQ (St Georges Respiratory Questionnaire) and the CAT (COPD Assessment Test) score which relates (though poorly) to the degree of physiological impairment (Ghobadi et al., 2012). The relationship of these health status tools to objective measures of the degree of emphysema determined by CT scanning parameters is unknown. The relationship between SGRQ and CAT scores with CT scan densitometry was explored in the first 84 patients with PiZZ AATD analysed as part of the NIHR Rare Diseases Translational Research Collaboration. CT density was measured as the percent of low attenuation voxels (LAA) at -950 HU, and the 15th percentile point using semi-automated software programme, Pulmo-CMS (Medis Medical Imaging, Leiden, Netherlands) and questionnaires were completed as part of broad clinical assessment. The patients were aged 31-65 and had an FEV1(% predicted) that ranged from 15-125. As expected the health status also showed a wide range from 6-88 for the SGRQ and 1-39 for the CAT. There was a significant negative correlation between SGRQ and both the %LAA value at -950HU and perc15 (r=-0.390, p These results demonstrate that the degree of emphysema in AATD, as quantified by CT density measurements, is related to conventional measures of health status.

The aim of this study is to evaluate the usefulness of high-resolution computed tomography (HRCT) densitometry in the diagnosis of otosclerosis and to investigate the relationship between CT densitometry and audiometry.HRCT findings and audiometry were compared among 34 patients (34 ears, the otosclerosis group) with surgically confirmed otosclerosis between January 2007 and December 2007 and 33 patients (33 opposite normal ears, the control group) with facial paralysis diagnosed at the same period of time. Seven regions of interest (ROI) were set manually around the otic capsule on the axial slice of 0.75-mm-thick CT image. The mean CT values of these seven regions were measured. In each ROI, the mean CT value of the otosclerosis group and that of the control group were compared. Based on the CT findings, the ears with otosclerosis were classified into two groups: Group A showed no pathological CT findings; Group B showed low density around the cochlea. In the otosclerosis group, the relationship between the findings of CT and the results of audiometry was analyzed.The mean CT values in the area posterior to the oval window and anterior to the oval window were significantly lower for the otosclerosis group compared with the control group (the former t=-2.030, p=0.046; the latter Z=-4.979, p0.01). Group A consisted of 30 patients, 7 of which (23.33%) exhibited conductive hearing loss, and 23 of which (76.67%) exhibited mixed hearing loss; Group B had 4 patients, all with mixed hearing loss. For the otosclerosis group, the mean CT value in the area posterior to the oval window was positively correlated with the mean air conduction threshold (r=0.4273, p=0.0117) and with the mean air-bone gap (r=0.3995, p=0.0192).Quantitative evaluation of CT with slices less than 1mm in thickness may provide important information for the diagnosis and assessment of otosclerosis which are unattainable through other methods.

UNLABELLED Lung volume reduction (LVR) is an effective therapy for end-stage emphysema. Preliminary and postprocedure imaging is usually limited to CT for anatomic delineation of the location and severity of the most acutely affected lung zones. The purpose of this study was to investigate the potential of using a new quantitative gas trapping index (GTI) derived from a (133)Xe ventilation scan to assess the severity of emphysema. METHODS Using the equilibration and washout phases of a (133)Xe ventilation study, a GTI was compared with visual National Emphysema Treatment Trial (NETT) CT scoring, semiautomated CT densitometry, and (99m)Tc perfusion scintigraphy in 28 patients being evaluated for LVR. The GTI was calculated as the percentage of (133)Xe gas retention in a 3-min washout image compared with the peak equilibrium image for 6 lung zones. RESULTS The GTI correlated best with the percentage of perfusion (-0.39, P

Computed tomography examinations have been made in 12 patients with posttraumatic algodystrophy. Significant differences of sides were found to be a measure of demineralisation by CT densitometry. 7 patients could be repeatedly examined during up to 60 weeks after the trauma. CT-integrated densitometry enables to quantify the process of de- and remineralisation and to objectify the disease according to the spongiosa bone. It seems to be possible to value the process of mineralisation by this method.

The aim of this study was to assess the feasibility of three-dimensional (3D) reconstructions and quantitative analysis of the volume of each component of the lung with cystic fibrosis (CF).Twenty-two patients with CF (mean age 17+/-8 years) were included in the study. The patients underwent an unenhanced single-slice spiral computed tomography (CT) chest scan with the following parameters: collimation 3 mm, table feed 6 mm x rot(-1), reconstruction interval 1 mm, soft tissue reconstruction kernel. Four image data sets were obtained: native axial slices, cine-mode display, virtual bronchographic volume-rendered images with algorithm for tissue transition display and virtual endoluminal views. The lungs were segmented manually from the hilum to the visceral pleura on the axial images, and the entire lung volume was calculated. A histogram was generated representing the fractional volume of tissues, the density of which was within a preset range. A curve was then obtained from the histogram.Native axial images and cine-mode display allowed complete evaluation of lung volumes. Virtual bronchography allowed a better assessment of the distribution of bronchiectasis. Virtual bronchoscopy was limited by the fact that it visualised only the surface, without differentiating mucus from the bronchial wall. Manual segmentation and generation of density-volume curves required 41+/-7 min for each lung. Three curve patterns were identified depending on disease severity.Volume-density analysis of lungs with CF is feasible. Its main advantage is that image analysis is not analogical, as the assessment is not performed using scoring systems or similar ordinal scales. This technique cannot differentiate acute from chronic findings, and the predictive value of the curve should be assessed.

Testing the hypothesis that CT densitometry indexes could be influenced by total lung capacity (TLC), gender and height in normal individuals.In this ethics committee-approved prospective study, 100 healthy non-smoking volunteers who provided written informed consent were included. From a helical scan of the chest, the relative area (RA) of the lung with attenuation coefficients lower than -960 HU and the 1st and 15th percentiles of the distribution of attenuation coefficients were calculated. Regression lines were drawn between each CT index and volunteers' height and total TLC at CT.In males, there was no statistically significant correlation between any CT index and height. In females, there was a statistically significant correlation between the RA of the lung with attenuation coefficients lower than -960 HU and the 1st percentile and height but not with the 15th percentile. For both genders, there were significant correlations between all CT indexes and TLC. The relationships between CT indexes and TLC were different in males and females.CT indexes are correlated with TLC and height but more closely with TLC than with height, and differently in males and females.CT indexes are influenced by TLC, gender and height in normal individuals and are more closely correlated with TLC than with height. The relationships between CT indexes and TLC or height are different in males and females. CT indexes used to quantify emphysema should thus be adjusted according to TLC and gender.

Introduction: Spirometry, the standard method to diagnose COPD, has poor sensitivity for early emphysema. This may delay diagnosis and lead to a poorer prognosis. Nanoparticles are deposited in the lungs by diffusion only, which makes their deposition depend on time and diffusion distance in distal airspaces. Aim: To determine whether emphysema can be identified and graded according to nanoparticle deposition after a single inhalation. Emphysema patients are expected to have reduced deposition relative to controls, due to a larger diffusion distance in enlarged distal airspaces. Further, we expect a correlation between disease severity and nanoparticle deposition. Methods: 22 patients with COPD and 15 normal subjects underwent Airspace Dimension Test (ADT) and spirometry after bronchodilation. ADT is performed as a single, maximal inhalation of nanoaerosol. Particle concentration is measured in the inhaled aerosol and an alveolar sample exhaled after a standardised breath-hold. The difference in particle concentration reflects deposition. CT was performed in the patient group. The images were reconstructed and processed with syngo.via Pulmo3D software to perform CT densitometric analysis. Low attenuation regions were quantified as the 15th percentile point (PD15). Results: All COPD patients fulfilled the GOLD criteria, while all healthy subjects had normal spirometry. There was highly significant difference in deposition of nanoparticles between the two groups (p Conclusion: The ADT can identify emphysema in patients with COPD. The results show a correlation to the extent of emphysema as measured by CT densitometry.

Introduction: CT can provide tissue density information from the lungs, whilst hyperpolarised 3He diffusion MRI (dMRI) enables estimation of mean alveolar dimensions. In order to reconcile the micro-structural information available from these two imaging modalities, a quantitative regional comparison is needed. Objective: To develop a framework to compare measures of lung microstructure in lobar regions using CT densitometry and 3He dMRI in a cohort of asthma patients. Methods: Inspiratory CT and 3He dMRI images were obtained in a study of 23 asthmatics. Lung lobar regions were automatically segmented from CT images and manually segmented from 3He dMRI. Coronal CT slices were reconstructed and matched to the same slices as the MRI, and mean tissue density was calculated for each lobe. Estimates of mean alveolar dimension were derived in the same lobar regions using quantitative models from 3He dMRI [Parra-Robles et al., Proc. ISMRM 2014, 3529]. Results: Statistically significant linear correlations (p-values

Alpha-1-antitrypsin (AAT) deficiency is a genetic risk factor for pulmonary emphysema. In 1972-74 all 200,000 Swedish new-born infants were screened for AAT deficiency. The aim of the present study was to investigate whether the PiZZ and PiSZ individuals identified by this screening have signs of emphysema and the role of smoking in this, compared with a random sample of control subjects at 35 years of age. The study participants underwent complete pulmonary function tests (PFT) and CT densitometry. The fifteenth percentile density (PD15) and the relative area below -910 HU (RA-910) were analyzed. Fifty-four PiZZ, 21 PiSZ and 66 PiMM control subjects participated in the study. No significant differences were found in lung function between the never-smoking AAT-deficient and control subjects. The 16 PiZZ ever-smokers had significantly lower carbon monoxide transfer coefficient (KCO) than the 20 PiSZ never-smokers (p = 0.014) and the 44 PiMM never-smokers (p = 0.005). After correction for the CT derived lung volume, the PiZZ ever-smokers had significantly lower PD15 (p = 0.046) than the ever-smoking controls. We conclude that 35-year-old PiZZ and PiSZ never-smokers have normal lung function when compared with never-smoking control subjects. The differences in KCO and CT densitometric parameters between the PiZZ ever-smokers and the control subjects may indicate early signs of emphysema.

The solitary pulmonary nodule will be found increasingly by the use of newer imaging techniques, including computed tomography (CT) screening. The aim must be to have an approach that avoids unnecessary surgery or biopsy with their attendant risks. Plain films characterisation, CT assessment, including densitometry and enhancement, and growth patterns are discussed and evaluated. The use of Bayes theorem to guide these assessment strategies is also described.

Factors accelerating cerebral degenerative changes represent potentially modifiable risks for cognitive decline. Putative risk factors accelerating mild cognitive decline and dementia were correlated with repeated measures of cerebral atrophy, CT densitometry, perfusions and cognitive testing among neurologically and cognitively normative volunteers. TIAs, hypertension, smoking and male gender accelerate cerebral degenerative changes, mild cognitive decline and dementia. Intervention by control of risk factors and cholinesterase inhibitors should prevent cerebral atropho-degenerative changes so that optimal cognitive performance is maintained.

To compare subjective visual grading of pulmonary emphysema with macroscopic morphometry and computed tomographic (CT) densitometry.In 62 consecutive patients who underwent thinsection CT before surgical lung resection, emphysema was objectively quantified with computer-assisted macroscopic morphometry and CT densitometry. The percentage of lung macroscopically occupied by emphysema was compared with the percentage occupied on CT scans by pixels with attenuation values lower than a predefined threshold (CT densitometry). Three readers with varying degrees of expertise subjectively graded emphysema with visual assessment at two reading sessions. Data from objective quantification and subjective grading were analyzed with correlation coefficients, and interobserver and intraobserver agreement were calculated.Subjective grading of emphysema showed less agreement with the macroscopic reference standard results (r = 0.439-0.505; P.05) than with objective CT densitometric results (r = 0.555-0.623; P.001). The 95% CIs for the intercepts of the linear regression lines were suggestive of systematic subjective overestimation of emphysema by all three readers. Interobserver agreement was moderate (kappa = 0.431-0.589). Intraobserver agreement was good to excellent (kappa = 0.738-0.936). The expertise of individual readers did not substantially influence results.Systematic overestimation and moderate interobserver agreement may compromise subjective visual grading of emphysema, which suggests that subjective visual grading should be supplemented with objective methods to achieve precise, reader-independent quantification of emphysema.

Rationale and Objectives To investigate the ability of variogram analysis of octree-decomposed computed tomography (CT) images and volume change maps to detect radiation-induced damage in rat lungs. Materials and Methods The lungs of female Sprague-Dawley rats were exposed to one of five absorbed doses (0, 6, 9, 12, or 15 Gy) of gamma radiation from a Co-60 source. At 6 months postexposure, pulmonary function tests were performed and four-dimensional (4D) CT images were acquired using a respiratory-gated microCT scanner. Volume change maps were then calculated from the 4DCT images. Octree decomposition was performed on CT images and volume change maps, and variogram analysis was applied to the decomposed images. Correlations of measured parameters with dose were evaluated. Results The effects of irradiation were not detectable from measured parameters, indicating only mild lung damage. Additionally, there were no significant correlations of pulmonary function results or CT densitometry with radiation dose. However, the variogram analysis did detect a significant correlation with dose in both the CT images (r = −0.57, P = .003) and the volume change maps (r = −0.53, P = .008). Conclusion This is the first study to use variogram analysis of lung images to assess pulmonary damage in a model of radiation injury. Results show that this approach is more sensitive to detecting radiation damage than conventional measures such as pulmonary function tests or CT densitometry.

Purpose: Preoperative pulmonary assessment is undertaken in patients with resectable lung cancer to identify those at increased risk of perioperative complications. Guidelines from the American College of Chest Physicians indicate that if the FEV1 and DLCO are � 60% of predicted, patients are suitable for resection without further evaluation. The aim of our study is to determine if quantitative measures of lung volume and density obtained from pre-operative CT scans correlate with pulmonary function tests. This may allow us to predict pulmonary function in patients with lung cancer and identify patients who would tolerate surgical resection. Materials and Methods: Patients were identified retrospectively from the lung cancer database of a tertiary hospital. Image segmentation software was utilized to estimate total lung volume, normal lung volume (values -500 HU to -910 HU), emphysematous volume (values less than -910 HU), and mean lung density from pre-operative CT studies for each patient and these values were compared to contemporaneous pulmonary function tests. Results: A total of 77 patients were enrolled. FEV1 was found to correlate significantly with the mean lung density (r=.762, p

PURPOSE We aimed to compare the inspiratory and expiratory quantitative computed tomography (CT) densitometric data of healthy volunteers, individuals with chronic obstructive pulmonary disease (COPD) risk, and COPD patients to aid in the early diagnosis of COPD. MATERIALS AND METHODS Of the study patients, 14 were healthy volunteers (Group I), 12 were patients at risk for COPD (Group II), and 13 were COPD patients (Group III). The high-resolution CT was performed at three levels (the upper, middle, and lower parts of the lungs). All images were evaluated with a specific program for the segmentation of pulmonary parenchyma. The mean lung density (MLD) was measured, and the emphysema index (EI) was calculated using this program. RESULTS Both MLD values and calculated EI ratios showed significant differences between Groups I and III, and Groups II and III in both expiratory and inspiratory phases (P < 0.05). However, in the comparison of healthy volunteers and patients at risk for COPD (Group I and II), only expiratory-phase MLD values showed statistically significant difference (P < 0.001). CONCLUSION In patients at risk for COPD, expiratory-phase MLD measurements can be used as an early diagnostic method.

Lung densitometry is an effective method to assess overall progression of emphysema, but generally the location of the progression is not estimated. We hypothesized that progression of emphysema is the result of extension from affected areas toward less affected areas in the lung. To test this hypothesis, a method was developed to assess emphysema severity at different levels in the lungs in order to estimate regional changes.Fifty subjects with emphysema due to alpha(1)-antitrypsin deficiency (AATD) [AATD deficiency of phenotype PiZZ (PiZ) group] and 16 subjects with general emphysema (general emphysema without phenotype PiZZ [non-PiZ] group) were scanned with CT at baseline and after 30 months. Densitometry was performed in 12 axial partitions of equal volumes. To indicate predominant location, craniocaudal locality was defined as the slope in the plot of densities against partitions. Regional progression of emphysema was calculated after volume correction, and its slope identifies the area of predominant progression. The hypothesis was tested by investigating the correlation between predominant location and predominant progression.As expected, the PiZ patients showed more basal emphysema than the non-PiZ group (craniocaudal locality, - 40.0 g/L vs - 6.2 g/L). Overall progression rate in PiZ patients was lower than in non-PiZ subjects. A significant correlation was found between craniocaudal locality and progression slope in PiZ subjects (R = 0.566, p0.001). In the non-PiZ group, no correlation was found.In the PiZ group, the more emphysema is distributed basally, the more progression was found in the basal area. This finding suggests that emphysema due to AATD spreads out from affected areas.

Emphysema is a condition of the lung, characterized by the abnormal increase in the size of the airspace distal to the terminal bronchioles. Currently, emphysema is the fourth leading cause of death in the USA, affecting 14 million people. The present article describes the principal tools in the imaging diagnosis of emphysema, from the early days until the present. We describe traditional techniques, such as chest X-ray, together with the evolution of computed tomography (CT) to more advanced forms, such as high resolution CT, as well as three-dimensional CT densitometry and volumetric assessment.

Summary form only given. The authors present the results of an experiment designed to reduce the noise in computed tomography density images. Noise was examined from a statistical point of view, and the minimal area required for reliable density measurement was determined. It was established that density measurement of slices 5- and 10-mm thick is reliable and repeatable with an error less than +or-5 HU in an area greater than 40 mm/sup 2/, independently of scanning parameters. >

As an author of a previously published clinical investigation on the CT densitometric diagnosis of otosclerosis (1), I always keep an eye on more recent publications in that field. I was surprised that our paper was not mentioned in the study above, since it not only was one of the first investigations in the field but also presented a new measurement parameter, in addition to previous ones. Since the conclusion of the study above is also not in agreement with our results, I would like to write you a brief letter about our paper.

Introduction Alpha-1 antitrypsin deficiency (AATD) is a hereditary disorder affecting about 1 in 3000 people in the UK commonly associated with early-onset emphysema. There are two common deficiency alleles - PiS and PiZ. PiZZ patients have severe AATD, with levels of 10–15% normal. PiSZ patients have less severe deficiency (≈ 40% normal) and are generally thought to have a minimal risk. We hypothesised that if PiSZ patients were at lower risk of COPD than PiZZ, and their lung disease would be more characteristic of usual COPD than that of PiZZ patients. Method 104 PiSZ patients and 638 PiZZ patients from the UK AATD registry (ADAPT) were compared for their demographics, lung function, risk factors for COPD (e.g. smoking, occupation), co-morbidities associated with COPD, index status (i.e. if diagnosed due to lung disease or family screening) and CT densitometry (where available). Outcome in terms of lung function decline and mortality was also assessed. Univariate statistics were used to guide subsequent regression analyses. Results Emphysema was more likely in PiZZ than PiSZ patients (OR 11.0 (5.7–21.3); p Conclusion PiSZ patients have a milder form of AATD associated with better lung function. The data suggests the pattern of emphysema is closer to usual COPD than classical AATD. Further analyses comparing PiSZ to PiMM are now ongoing.

Adrenal masses are a relatively common finding on computed tomography (CT) and magnetic resonance imaging (MRI). Until recently, adrenal biopsy, resection, or clinical follow-up were the only methods of distinguishing benign adenomas from malignancies. On the basis of their higher lipid content, adenomas have characteristic appearances on CT and MRI that can be used to separate them from non-lipid-containing lesions such as metastases. CT densitometry with or without contrast media and chemical shift MRI (CSI) are two examples of techniques with adequate sensitivity (50–90%) and excellent specificity (>95%) for adrenal adenomas. While the need for invasive tissue sampling is reduced because of these techniques, it is eliminated because lesions not meeting the criteria for adenomas are not always malignant. However, CT densitometry and CSI are likely to reduce significantly the need for histology sampling of incidentally discovered adrenal masses due to the high specificity of these new techniques.

Bilateral sensorineural hearing loss can be caused by a variety of temporal bone abnormalities including primary cochlear otoscierosis, local and systemic bony diseases and some metabolic conditions. These may be identified using computerized tomography (CT), with attenuation recordings taken across the cochlear capsule (CT densitometry). Eighty patients with bilateral sensorineural hearing loss were screened over a period of six and a half years using this technique, and only three cases (3.8 per cent) of treatable disease were detected. Positive yields may be increased by screening selected cases with other clinical or biochemical stigmata of temporal bone disease.

PURPOSE: To quantify inter- and intrascanner conformity in computed tomographic (CT) densitometry of the lungs. MATERIALS AND METHODS: With six scanners from four manufacturers, a lung densitometry protocol with several variations was applied for performance comparison. Phantoms included water, air, and a humanoid thorax phantom equipped with a dog lung and exchangeable pseudolungs of polyethylene foam. RESULTS: All scanners produced acceptable CT numbers (Hounsfield units) for water, but some not for air. An incorrect calibration of air density affected all CT numbers at lung densities, but the error was easily correctable. Some systems were more sensitive to object size than others were. Sensitivity of CT numbers to section thickness, reconstruction filter, zoom factor, and table height was small, except for two scanners in relation to section thickness. CONCLUSION: After correction for poor air calibration, scanner conformity was acceptable when the reproducibility of lung densitometry in clinical prac...

Lung density measurements using computed tomography have been made in mice, rats, and pure-bred beagles and mongrel dogs. Density was found to be dependent on a number of factors including the location of the area scanned, and the age and species of the animal. Lung density was found to decrease by approximately 40% from initial values in a group of rats scanned at intervals between 30 and 800 days old. Age-related density changes were not seen for the lungs of mice or dogs; however measurements were not made over a prolonged period. A gradient of increasing density from the base to apex of the lung was seen for 30 and 175-day-old rats (scanned in the prone position) while an apex to base density gradient was seen for both types of dog studied (scanned in the supine position). In none of the species studied was there a systematic difference in density of the right and left lungs. Differences in average lung density between the mice, rats and dogs reported here are consistent with the relationship between lung morphology, metabolic rate and body size which obtains for a range of mammalian species.

Purpose: To evaluate the effect of reconstruction algorithms on the CT measurement of mean lung mass density and normal thoracic structures. Materials and Methods: Forty-six patients with a 2 -9 cm-sized lung mass underwent thoracic CT examinations with intravenous contrast enhancement and using a CT HiSpeed Advantage scanner (GE Medical Systems). In each examination, the axial image of the lung mass was reconstructed using soft, standard, detail, and bone algorithms. The mean value and standard deviation of mass density in Hounsfield Units (HU) were measured using ROIs of three different sizes (50 mm2, 200 mm2, and 350 mm2or more), and the same method was used to measure the density of normal lung, muscle, bone, and vessels. In 21 patients, mass density was also measured on unenhanced and delayed enhanced images and the degree of enhancement was calculated. Results: The average maximum difference in mean mass density in the images of the four different algorithms was less than 1 (range, 0.1 -1.9) HU (ROI size, 350 mm 2 or more), 0 -4.2 HU (200 mm 2), and 0.1 -3.6 HU (50mm2). The average maximum difference in the degree of lung mass enhancement was 0.5 -1.2 (range, 0 -1.6 )HU (ROI size, 350 mm2or more). The mean density of the four normal thoracic structures was highest in images reconstructed with the bone algorithm, though there was no significant difference between the four different algorithms (p = 1.000). Conclusion: The measured mean CT density of a lung mass larger than 2 cm does not significantly change ac-cording to the reconstruction algorithm used. When using a small ROI, however, the density difference may increase.

Hypothesis: Partial liquid ventilation uses flurocarbons (PFC) which have a great capacity for O2 and CO2 but also present a major diffusion barrier. Therefore, effective gas exchange requires a maximum surface area at the gas/liquid interface.

The current level of computed tomography (CT) scanner resolution is such that CT is possibly the best radiographic procedure available for viewing gross pulmonary anatomy and pathology. CT densitometry, in contrast, is of limited value in assessing diffuse lung disease because of partial volume errors created by the wide range of intrathoracic tissue densities. Anteroposterior density gradients and total mean lung density can be used advantageously in a select group of patients with suspected high-density disease. The morphologic patterns of diffuse high-density lung disease as viewed on conventional roentgenograms correlate closely with those depicted on CT images. Density measurements in normal and abnormal patients suggest that the medulla of the lung may be a reservoir zone that accommodates increased blood flow via distention and recruitment of vessels under appropriate conditions. Pulmonary diseases that cause oligemia can be identified and distinguished by their combined CT densitometric and morphologic characteristics. Combined high- and low-density disease may need total integration of plain radiographs, isotopic scans, and CT scans for proper interpretation.

In CT densitometry the precision, sensitivity and accuracy of the procedure are limited by photon noise, the degree of tissue differentiation and artefacts caused by the finite size of the x-ray beam, hardening of the x-rays and scattered radiation. These artefacts are highly dependent on the CT settings, such as x-ray spectrum and effective energy, intensity of photon flux and collimation of the beam. To monitor the progression of a disease or the efficacy of a therapy, longitudinal studies are necessary; thus the radiation dose per examination should be kept at a minimum. For bone evaluation of the peripheral skeleton it is shown that there is a narrow optimal energy range of 30-40 keV where a dose below 150 mu Sv is sufficient to detect a change of 1% in trabecular bone density at the 0.1 confidence level. Concomitantly accuracy might be better than 1% if adequate beam collimation is applied.

The influence of (1) calcium concentration, (2) exposure technique, (3) reconstruction algorithm, (4) nodule size, and (5) nodule location on the CT attenuation values (CT density) of pulmonary nodules was examined in a frozen human thorax. Nodules with calcium concentrations of 0-310 mg/ml and diameters of either 0.95 or 1.59 cm were inserted into a frozen, unembalmed human thorax. The nodules were placed either at the lung apex or 4 cm below the tracheal carina. Each nodule was scanned on a GE CT 9800 scanner; five different exposure techniques were used. The slice thickness was uniformly 1.5 mm. As expected, increasing the kilovoltage caused a significant decrease in CT nodule density in all nodules with calcium concentrations greater than 80 mg/ml. The inverse relationship between kilovoltage and nodule density was exaggerated with increasing calcium concentration. A high-resolution (bone) algorithm gave a significantly higher CT number than did a smoothed (standard) algorithm, regardless of nodule size and location, but this difference could be attributed almost entirely to the edge-enhancement effect of the bone algorithm. The CT density of the larger nodules was significantly higher than that of the smaller nodules at calcium concentrations greater than 65 mg/ml for both standard and bone algorithms. Densities were significantly higher in the mid lung than in the apex with a standard algorithm, but this was not the case with a bone algorithm. The GE CT 9800 scanner had a linear response between CT density and increasing calcium concentration within the confines of a human thorax. A high-resolution (bone) reconstruction algorithm has higher spatial resolution but does show an edge-enhancing effect not found with the smoothed algorithm. Two major variables in CT densitometry for pulmonary nodules are the kilo electron voltage of the X-ray beam and the reconstruction algorithm used; these two parameters should be standardized, with a high kilovoltage and high-resolution algorithm favored on the GE CT 9800 scanner.