OBJECTIVE This study evaluates the relationships between quantitative CT (QCT) and spirometric measurements of disease severity in cigarette smokers with and without chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS Inspiratory and expiratory CT scans of 4062 subjects in the Genetic Epidemiology of COPD (COPDGene) Study were evaluated. Measures examined included emphysema, defined as the percentage of low-attenuation areas ≤ −950 HU on inspiratory CT, which we refer to as “LAA-950I”; air trapping, defined as the percentage of low-attenuation areas ≤ −856 HU on expiratory CT, which we refer to as “LAA-856E”; and the inner diameter, inner and outer areas, wall area, airway wall thickness, and square root of the wall area of a hypothetical airway of 10-mm internal perimeter of segmental and subsegmental airways. Correlations were determined between spirometry and several QCT measures using statistics software (SAS, version 9.2). RESULTS QCT measurements of low-attenuation areas correlate strongly and significantly (p < 0.0001) with spirometry. The correlation between LAA-856E and forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) (r = −0.77 and −0.84, respectively) is stronger than the correlation between LAA-950I and FEV1 and FEV1/FVC (r = −0.67 and r = −0.76). Inspiratory and expiratory volume changes decreased with increasing disease severity, as measured by the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) staging system (p < 0.0001). When airway variables were included with low-attenuation area measures in a multiple regression model, the model accounted for a statistically greater proportion of variation in FEV1 and FEV1/FVC (R2 = 0.72 and 0.77, respectively). Airway measurements alone are less correlated with spirometric measures of FEV1 (r = 0.15 to −0.44) and FEV1/FVC (r = 0.19 to −0.34). CONCLUSION QCT measurements are strongly associated with spirometric results showing impairment in smokers. LAA-856E strongly correlates with physiologic measurements of airway obstruction. Airway measurements can be used concurrently with QCT measures of low-attenuation areas to accurately predict lung function.

Objectives The purposes of this study are to evaluate the normal range of quantitative CT (QCT) measures of lung attenuation and airway parameters measurements in healthy non-smoking adults and to identify sources of variation in those measures and possible means to adjust for them. Materials and Methods Within the COPDGene® study, 92 healthy non-Hispanic White non-smokers [29 male, 63 female, mean age 62.7 (SD 9.0), BMI 28.1 (SD 5.1)] underwent volumetric CT at full inspiration and at the end of a normal expiration. On QCT analysis (Pulmonary Workstation 2, VIDA Diagnostics), inspiratory low attenuation areas were defined as lung tissue with attenuation values ≤ −950 Hounsfield Units (HU) on inspiratory CT (LAAI-950). Expiratory low attenuation areas were defined as lung tissue ≤ −856 HU on expiratory CT (LAAE-856). We used simple linear regression to determine the impact of age and gender on QCT parameters and multiple regression to assess the additional impact of total lung capacity and functional residual capacity measured by CT (TLCCT and FRCCT), scanner type, and mean tracheal air attenuation. Airways were evaluated using measures of airway wall thickness (AWT), inner luminal area (ILA), wall area percent (WA%) and standardized thickness of an airway with inner perimeter of 10mm (Pi10). Results Mean %LAAI-950 was 2.0 (SD 2.7), and mean %LAAE-856 was 9.2 (SD 6.8). Mean %LAAI-950 was 3.6 (SD 3.2) % in men, compared with 1.3 (SD 2.0) in women (P<0.001). The %LAAI-950 did not change significantly with age (P=0.08) or BMI (P=0.52). %LAAE-856 did not show any independent relationship with age (P=0.33), gender (P=0.70), or BMI (P=0.32). On multivariate analysis, %LAAI-950 showed a direct relationship to TLCCT (P=0.002) and an inverse relationship to mean tracheal air attenuation (P=0.003), and %LAAE-856 was related to age (P=0.001), FRCCT (P=0.007) and scanner type (P<0.001). Multivariate analysis of segmental airways showed that ILA and WA% were significantly related to TLCCT (P<0.001) and age (0.006). WA% was also associated with gender (P=0.05), axial pixel size (P=0.03) and slice interval (P=0.04). Lastly, AWT is strongly influenced by axial pixel size (P<0.001). Conclusions Although the attenuation characteristics of normal lung differ by age and gender, these differences do not persist on multivariate analysis. Potential sources of variation in measurement of attenuation-based quantitative CT parameters include depth of inspiration/expiration, and scanner type. Tracheal air attenuation may partially correct variation due to scanner type. Sources of variation in QCT airway measurements may include age, gender, BMI, depth of inspiration, and spatial resolution.

Cognitive functions show many alternative outcomes and great individual variation during normal aging. We examined learning over the adult life span in CBA mice, along with morphological and electrophysiological substrates. Our aim was to compare cerebellum-dependent delay eyeblink classical conditioning and hippocampus-dependent contextual fear conditioning in the same animals using the same conditioned and unconditioned stimuli for eyeblink and fear conditioning. In a subset of the behaviorally tested mice, we used unbiased stereology to estimate the total number of Purkinje neurons in cerebellar cortex and pyramidal neurons in the hippocampus. Several forms of synaptic plasticity were assessed at different ages in CBA mice: long-term depression (LTD) in both cerebellum and hippocampus and NMDA-mediated long-term potentiation (LTP) and voltage-dependent calcium channel LTP in hippocampus. Forty-four CBA mice tested at one of five ages (4,8,12,18, or 24 months) demonstrated statistically significant age differences in cerebellum-dependent delay eyeblink conditioning, with 24-month mice showing impairment in comparison with younger mice. These same CBA mice showed no significant differences in contextual or cued fear conditioning. Stereology indicated significant loss of Purkinje neurons in the 18-and 24-month groups, whereas pyramidal neuron numbers were stable across age. Slice electrophysiology recorded from an additional 48 CBA mice indicated significant deficits in LTD appearing in cerebellum between 4 and 8 months, whereas 4-to 12-month mice demonstrated similar hippocampal LTD and LTP values. Our results demonstrate that processes of aging impact brain structures and associated behaviors differentially, with cerebellum showing earlier senescence than hippocampus.aging | cerebellum | hippocampus | behavior | synaptic plasticity P rocesses of normal aging do not affect the CNS uniformly.There is stability in neuron number in most brain regions, including most regions of the hippocampus (reviewed in refs. 1 and 2), whereas significant loss of Purkinje neurons occurs in the cerebellum (3, 4). Stereological assessments of hippocampal pyramidal and granule neurons and cerebellar granule and Purkinje neurons in the same mice aged 12 or 28 months revealed stability in hippocampal neurons and cerebellar granule neurons and significant loss of Purkinje neurons (5). Learning and memory show many alternative outcomes and great individual variation during normal aging. Cerebellum-dependent learning is associated with Purkinje neuron number and is impaired by age-related decrements in morphology and function. Hippocampus-dependent learning is associated with reduced capacity for new learning in pyramidal neurons in the perforant pathway in normal aging (6). Data over the adult life span in human (7) and nonhuman mammals (8) suggest that cerebellum-essential tasks show age-related deficits at earlier ages than do hippocampus-essential tasks.Traditionally, cerebellar and hippocampal substrates of learning, memory, and ag...

The aim of this study was to compare the clinical, radiological and histological findings in a large population of subjects enrolled during a multicentre study of idiopathic pulmonary fibrosis, with a focus on discordance between imaging and histologic diagnoses of usual interstitial pneumonia (UIP).Two independent radiologists retrospectively reviewed 241 subjects who underwent high-resolution computed tomography (HRCT) and surgical lung biopsies. HRCT findings were classified as UIP, possible UIP and inconsistent with UIP. Histological findings were classified as definite, probable, possible and not UIP.Of the 241 cases, 102 (42.3%) had HRCT findings of UIP, 64 (26.6%) had possible UIP and 75 (31.1%) were inconsistent with UIP. Among those with UIP on HRCT, 99 (97.1%) had histologically definite or probable UIP (concordant group), and 71 (94.7%) of those with "inconsistent" HRCT features had histologically definite or probable UIP (discordant group). Discordant subjects were slightly younger and less likely to be smokers than concordant subjects, but no survival differences were identified.In this population of patients enrolled with a diagnosis of idiopathic pulmonary fibrosis, 94.7% of those with HRCT findings "inconsistent with UIP" demonstrated histological UIP. This suggests that the term "inconsistent with UIP" is misleading.

Purpose To correlate currently available quantitative CT measurements for airway disease with physiological indices and the body-mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index in patients with chronic obstructive pulmonary disease (COPD). Materials and methods This study was approved by our institutional review board (IRB number 2778). Written informed consent was obtained from all subjects. The subjects included 188 current and former cigarette smokers from the COPDGene cohort who underwent inspiratory and expiratory CT and also had physiological measurements for the evaluation of airflow limitation, including FEF25–75%, airway resistance (Raw), and specific airway conductance (sGaw). The BODE index was used as the index of clinical symptoms. Quantitative CT measures included % low attenuation areas [% voxels ≤ 950 Hounsfield unit (HU) on inspiratory CT, %LAA−950ins], percent gas trapping (% voxels ≤ −856 HU on expiratory CT, %LAA−856exp), relative inspiratory to expiratory volume change of voxels with attenuation values from −856 to −950 HU [Relative Volume Change (RVC)−856 to −950], expiratory to inspiratory ratio of mean lung density (E/I-ratio MLD), Pi10, and airway wall thickness (WT), luminal diameter (LD) and airway wall area percent (WA%) in the segmental, subsegmental and subsubsegmental bronchi on inspiratory CT. Correlation coefficients were calculated between the QCT measurements and physiological measurements in all subjects and in the subjects with mild emphysema (%LAA−950ins <10%). Univariate and multiple variable analysis for the BODE index were also performed. Adjustments were made for age, gender, smoking pack years, FEF25–75%, Raw, and sGaw. Results Quantitative CT measurements had significant correlations with physiological indices. Among them, E/I-ratio MLD had the strongest correlations with FEF25–75% (r = −0.648, <0.001) and sGaw (r = −0.624, <0.001) while in the subjects with mild emphysema subsegmental WA% and segmental WA% had the strongest correlation with FEF25–75% (r = −0.669, <0.001) and sGaw (r = −0.638, <0.001), respectively. The multiple variable analyses showed that RVC−856 to −950 was an independent predictor of the BODE index showing the highest R2 (0.468) as an independent variable among the QCT measurements. Conclusion Quantitative CT measurements of gas trapping such as E/I-ratioMLD, correlate better with physiological indices for airway disease than those of airway such as WA% or LD. In mild emphysema, however, quantitative CT measurements of airway correlate better with the physiological indices. RVC−856 to −950 is a predictor of the BODE index.