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[Exercise tolerance in relation to ventilatory drive and respiratory muscle function in COPD].

OBJECTIVE: To assess the relationships between exercise tolerance and respiratory drive and respiratory muscle function in COPD. METHODS: 28 patients with COPD and 26 normal subjects were involved in the study. Routine pulmonary function, pulmonary diffusing capacity, P0.1, PImax were measured at rest. Oxygen consumption (VO2), carbon dioxide production (VCO2), minute ventilation (VE) etc were measured during exercise testing. Borg Scale was recorded simultaneously. Arterial blood gases were measured before and after exercise. RESULTS: (1) PImax in COPD group (40 +/- 15 mm Hg) was significantly lower than that in the normal group [(53 +/- 19) mm Hg, P < 0.05]. P0.1 in COPD group [(2.8 +/- 0.9) mm Hg] was significantly higher than that in the normal group [(2.0 +/- 0.7) mm Hg, P < 0.05]. Inspiratory drive efficacy (VT/P0.1) in COPD group [(0.21 +/- 0.04) L/mm Hg] was significantly lower than that in the normal group [(0.28 +/- 0.07) L/mm Hg, P < 0.05]. P0.1/PImax in COPD group was (0.069 +/- 0.021), significantly higher than that in the normal group [(0.037 +/- 0.009), P < 0.01]. (2) VO2max was correlated with P0.1/Pimax and Borg Scale in COPD patients (r = 0.66, P < 0.01, and r = 0.53, P < 0.05 respectively). Borg Scale was also positively correlated with P0.1/PImax in COPD group (r = 0.49, P < 0.05). CONCLUSION: In addition to airway obstruction and the damaged gas exchange, exercise intolerance in COPD may also be related to the increased respiratory drive and dysfunction of respiratory muscle.

Adult↗

Interstitial lung disease in systemic sclerosis: comparison of BALF lymphocyte phenotype and DLCO impairment.

Patients with scleroderma (systemic sclerosis-SSc) frequently develop an interstitial lung disease. The role of lymphocytes in fibrosing alveolitis preceding lung fibrosis has been established. The purpose of this work was to evaluate cell profiles and lymphocyte phenotypes in the bronchoalveolar lavage (BAL) fluid and to correlate them with depression in lung function tests detected by depletion of diffusing capacity (DLCO). BAL was carried out in 25 untreated, non-smoking patients suffering from diffuse scleroderma and in 12 healthy non-smoking volunteers. For the analysis of lymphocyte sub-sets flow cytometry and monoclonal antibodies were used. The following cell sub-types were counted: T lymphocytes, B lymphocytes, helper lymphocytes, suppressor/cytotoxic lymphocytes, natural killer cells, cytotoxic T lymphocytes and activated T lymphocytes. The total cell count was higher in the group of patients with mild and moderate impairment in DLCO. The percentage of lymphocytes was greater in patients with DLCO lower than 65% of the predicted value since neutrophilia was found in patients with severe DLCO depletion, i.e. significant when compared with healthy subjects. The proportions of suppressor/cytotoxic lymphocytes and of activated T lymphocytes were higher in patients than in controls. The statistical analysis revealed significant differences between patients with moderate and mild changes in DLCO and the healthy volunteers. A decreased helper/suppressor ratio was noticed in these patients. We concluded that the BALF lymphocyte phenotype analysis may reflect the features of alveolitis in patients with SSc.

Adult↗

Lung volume is a determinant of aerosol bolus dispersion.

The technique of inhaling a small volume element labeled with particles ("aerosol bolus") can be used to assess convective gas mixing in the lung. While a bolus undergoes mixing in the lung, particles are dispersed in an increasing volume of the respired air. However, determining factors of bolus dispersion are not yet completely understood. The present study tested the hypothesis that bolus dispersion is related, among others, to the total volume in which the bolus is allowed to mix--i.e., to the individual lung size. Bolus dispersion was measured in 32 anesthetized, mechanically ventilated dogs with total lung capacities (TLCs) of 1.1-2.5 L. Six-milliliter aerosol boluses were introduced at various preselected time-points during inspiration to probe different volumetric lung depths. Dispersion (SD) was determined by moment analysis of particle concentrations in the expired air. We found linear correlations between SD at a given lung depth and the individual end-inspiratory lung volume (V(L)). The relationship was tightest for boluses inhaled deepest into the lungs: SD(40) = 0.068 V(L) - 1.77, r(2) = 0.59. Normalizing SD to V(L) abolished this dependency and resulted in a considerable reduction of inter-individual variability as compared to the uncorrected measurements. These data indicate that lung size influences measurements of bolus dispersion. It therefore appears reasonable to apply a normalization procedure before interpreting the data. Apart from a reduction in measurement variability, this should help to separate the effects on bolus dispersion of altered lung volumes and altered mixing processes in diseased lungs.

Administration, Inhalation↗

Pulmonary gas exchange and educational level: a community study.

Socio-economic status (SES) is related to increased risk of airway disease in terms of forced expiratory volume in one second (FEV1) and forced vital capacity. No data are available as to what extent SES predicts alveolar function in a general population. In this cross-sectional study, 1,275 subjects aged 18-73 yrs underwent pulmonary testing, including the single-breath carbon monoxide transfer capacity of the lungs (TL,CO). Educational level was used as an index for SES. Mean +/- SD TL,CO % predicted was 97% among those with primary school education, 99% among those with secondary school education and 104% among those with a university degree. In a multiple linear regression analysis, adjusting for age, height, haemoglobin, carboxyhaemoglobin, smoking habits, occupational exposure, FEV1 and body mass index, TL,CO was significantly related to educational level in males but not in females. Occupational exposure was not significant. In this study, socio-economic status was found to be an independent determinant of TL,CO. Even in an affluent country such as Norway, socio-environmental risk factors may differ based on individuals' SES. Such risk factors may, for instance, be higher exposure to airborne pollutants, poorer housing conditions, or lower consumption of fruit and vegetables. Further exploration is called for.

Adolescent↗

Effect of pattern and severity of respiratory muscle weakness on carbon monoxide gas transfer and lung volumes.

In clinical practice, an elevated carbon monoxide (CO) transfer coefficient (KCO) and restrictive ventilatory defect are taken as features of respiratory muscle weakness (RMW). However, the authors hypothesised that both pattern and severity of RMW effect gas transfer and lung volumes. Measurements of CO transfer and lung volumes were performed in patients with isolated diaphragm weakness (n=10), inspiratory muscle weakness (n=12), combined inspiratory and expiratory muscle weakness (n=5) and healthy controls (n=6). Patients with diaphragm weakness and inspiratory muscle weakness had reduced total lung capacity (TLC) (83.6% predicted and 68.9% pred, respectively), functional residual capacity (FRC) (83.9% pred and 83.6% pred) and transfer factor of the lung for CO (TL,CO) (86.2% pred and 66.2% pred) with increased KCO (114.1% pred and 130.2% pred). Patients with combined inspiratory and expiratory muscle weakness had reduced TLC (80.9% pred) but increased FRC (109.9% pred) and RV (157.4% pred) with decreased TL,CO (58.0% pred) and KCO (85.5% pred). In patients with diaphragm weakness, the increase in carbon monoxide transfer coefficient was similar to that of normal subjects when alveolar volume was reduced. However, the increase in carbon monoxide transfer coefficient in inspiratory muscle weakness was often less than expected, while in combined inspiratory and expiratory muscle weakness, the carbon monoxide transfer coefficient was normal/reduced despite further reductions in alveolar volume, which may indicate subtle abnormalities of the lung parenchyma or pulmonary vasculature. Thus, this study demonstrates the limitations of using carbon monoxide transfer coefficient in the diagnosis of respiratory muscle weakness, particularly if no account is taken of the alveolar volume at which the carbon monoxide transfer coefficient is made.

Adult↗

Long-term effects of nasal intermittent positive-pressure ventilation on pulmonary function and sleep architecture in patients with neuromuscular diseases.

STUDY OBJECTIVE: This article evaluates the long-term clinical and physiologic effects of nocturnal nasal intermittent positive-pressure ventilation (NIPPV) in patients with neuromuscular disease. METHODS: Before and after 18 +/- 2 months of NIPPV, we measured during the daytime arterial blood gases, lung mechanics, and respiratory muscle strength in 8 patients (51 +/- 5 years; mean +/- SEM). Sleep parameters were also evaluated at 10 +/- 2 months. RESULTS: All patients tolerated NIPPV and none required hospitalization during follow-up. After NIPPV, daytime arterial PO2 increased (71 +/- 4 to 81 +/- 2 mm Hg; p < 0.05) and arterial PCO2 decreased (46 +/- 3 to 41 +/- 1 mm Hg; p < 0.05). The change of PaO2 after NIPPV was related to its baseline value (r2 = 0.78, p < 0.05). Vital capacity (50 +/- 6% predicted), total lung capacity (63 +/- 4% predicted), alveolar-arterial oxygen gradient (20 +/- 3 mm Hg), and maximal inspiratory (39 +/- 9% predicted) or expiratory (32 +/- 5% predicted) pressures did not change after NIPPV. The apnea-hypopnea index fell from 22 +/- 6 to 1 +/- 1 (p < 0.05), and both sleep architecture and sleep efficiency (from 59 +/- 8% to 83 +/- 5%; p < 0.05) were enhanced. The time spent with an arterial oxygen saturation (SaO2) value below 90% decreased from 160 +/- 53 min to 8 +/- 4 min (p < 0.05). Mean (88 +/- 3 to 95 +/- 1%; p < 0.05) and minimal nocturnal SaO2 (67 +/- 5 to 89 +/- 1%; p < 0.001) improved after NIPPV. CONCLUSIONS: In patients with neuromuscular disease, long-term NIPPV is well tolerated and easy to implement clinically. In these patients, long-term NIPPV improves daytime arterial blood gas values and sleep-disordered breathing. However, it does not modify lung mechanics or respiratory muscle strength.

Adult↗

Fibroblast chemotactic response elicited by native bronchoalveolar lavage fluid from patients with fibrosing alveolitis.

BACKGROUND: In fibrosing alveolitis activation of lung fibroblasts is the decisive event in the pathogenetic sequence leading to pulmonary fibrosis. Fibroblast stimulating activity was measured in bronchoalveolar lavage (BAL) fluid to assess its relationship to the activity of fibrosing alveolitis. METHODS: Nine control subjects and 40 patients with fibrosing alveolitis caused by idiopathic pulmonary fibrosis (n = 22) or pulmonary involvement in systemic sclerosis (n = 18) were studied. All patients were followed up by lung function testing for a minimum of six months (mean (SE) 13.3 (1.4) months). Twenty five patients received immunosuppressive therapy and 15 refused. At the beginning of follow up BAL was performed and, as a possible indicator of fibroblast stimulating mediators within the lungs, chemotactic migration of cultured human fibroblasts elicited by native BAL fluid was measured in Boyden-type chambers and expressed as a percentage of the chemoattractant effect of 25 ng/ml platelet derived growth factor. The procollagen III peptide level in BAL fluid served as a marker for collagen synthesis. RESULTS: Chemoattractant activity was elevated in the patients with idiopathic pulmonary fibrosis and systemic sclerosis compared with the control group, (mean (SE) 56.4% (8.5%)) and 72.3% (16.3%) v 12.6% (4.0%). Chemoattractant activity was inversely correlated with total lung capacity (TLC) (r = -0.45) and with vital capacity (VC) (r = -0.33). Procollagen III peptide concentrations in BAL fluid and chemoattractant activity were not significantly correlated. For further evaluation chemoattractant activity of 36% (mean value of controls +2 SD) was used to separate normal (< 36%) from elevated (> or = 36%) activity. At the end of follow up, untreated patients with high chemoattractant activity (> or = 36%) showed a significant reduction of VC, TLC, and exercise arterial oxygen tension (PaO2) and a small decrease in carbon monoxide transfer factor (TLCO), whereas a significant improvement in VC, TLC, and TLCO and a small increase of exercise PaO2 occurred in treated patients with high chemoattractant activity. Patients with low chemoattractant activity (< 36%) showed no consistent change in lung function measurements, irrespective of treatment. In contrast, lung function results and differential cell counts in BAL fluid failed to identify progressive disease. CONCLUSIONS: In patients with fibrosing alveolitis the chemoattractant activity of BAL fluid seems to be an independent indicator of lung fibroblast stimulating activity providing relevant information about disease activity, and may help to improve the clinical management of these patients.

Adult↗

Pulmonary function in men after repeated sessions of oxygen breathing at 0.25 MPa for 90 min.

HYPOTHESIS: We wanted to evaluate the pulmonary effects of discontinuous oxygen breathing (15 min O2, 2 min air breaks, 15:2), at 0.25 MPa once a day for 90 min O2 (6 sequences) over 10 d. This sequence, which has never been evaluated, is currently used in our hyperbaric therapy center. METHODS: Clinical and functional pulmonary status (questionnaire, spirometry, flow/volume loop, pulmonary diffusing capacity for carbon monoxide) was assessed in 10 non-smoking healthy volunteers after one exposure at 0.25 MPa consisting of 90 min of discontinuous oxygen breathing (15:2) and in 10 non-smoking patients who received a hyperbaric treatment consisting of 90 min of the same discontinuous O2 breathing (15:2) once a day over 10 d. The patients received daily intravenous methylprednisolone (1 mg x kg(-1)) and nicergoline (60 mg). RESULTS: There were no respiratory symptoms in either group. As expected, for a single exposure of that duration, lung function did not change in volunteers; however, a significant decrease in maximal expiratory flows (MEF) at 50 (-15%) and 25% (-33%) of forced vital capacity (p < 0.05) without change in forced vital capacity (FVC) appeared in patients treated over 10 d. CONCLUSION: Repetition of the 15:2 oxygen breathing sequence for 90 min once a day over 10 d led to greater flow limitation in peripheral airways than reported after continuous oxygen breathing of 210 min at 0.3 MPa which showed a 7% decrement in MEF50 and a 12% decrement in MEF25. No studies reporting these indexes were found in the 0.2-0.25 MPa range. Similar decrements in MEF50 and MEF25 with steady FVC have been reported after 14 d of daily hyperbaric therapy (0.24 MPa) with 30:5 sequence (-9% and -13%, respectively), 80% of the patients were symptom free. Similarily, our patients were all symptom free and remained so 1 yr after the study, hence, this toxicity is of weak clinical significance in subjects free of inflammatory lung diseases. HBO therapy, though safe, is not totally without effect on the lung.

Adult↗

Determinants of response to immunosuppressive therapy in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) response to corticosteroids and cytotoxic medications appears to be the most important determinant of survival. The purpose of this retrospective study was to analyse the determinants of response to immunosuppressive therapy with prednisone alone, or prednisone and cyclophosphamide, in IPF. Twenty five consecutive patients were studied. Initial evaluation in untreated patients included clinical, biological and functional parameters. Sequential evaluation by pulmonary function tests (forced vital capacity (FVC) and transfer factor of the lungs for carbon monoxide (TLCO)) was performed at a 3 month interval. Response to therapy was defined as an improvement in FVC and/or TLCO of more than 10% after 12 months, with maintenance of this improvement for at least another 12 months. Twelve of the 25 patients were classified as responders. A symptomatic disease of less than 12 months duration before onset of therapy related to response. FVC was more impaired in the group of responders when the comparison was limited to patients with an FVC of less than 90%. Bronchoalveolar lavage cell counts were not significantly different between responders and non-responders. Assessment of pulmonary function after 3 months of treatment was predictive of maintenance of the response or of even further improvement. Patients with improved FVC after 3 months of therapy had a significantly shorter symptomatic disease before onset of treatment (7.6 +/- 7.1 vs 20.2 +/- 18.6 months). A beneficial effect of addition of cyclophosphamide was observed only in patients who demonstrated an early but short-lived improvement to steroids. Adverse reactions of immunosuppressive therapy were noticed in 10 patients, and required discontinuation of treatment in six of them.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchoalveolar Lavage Fluid↗

The effect of right ventricular hypertrophy on left ventricular ejection fraction in pulmonary emphysema.

STUDY OBJECTIVE: The development of right ventricular (RV) hypertrophy in emphysema is accompanied by involvement of the left ventricle (LV) and its systolic function. Our objective was to study the relation between RV hypertrophy and LV ejection fraction in emphysema by means of MRI. PATIENTS: Ten emphysematous patients (FEV1, 0.99+/-0.32 L; FEV1/vital capacity (VC), 0.32+/-0.11 [mean+/-SD]) and 10 age-matched control subjects were included. Exclusion criteria were any history of systemic hypertension, ischemic or valvular heart disease, or episodes of right- and/or left-sided cardiac failure. MEASUREMENTS AND RESULTS: Rapid scout imaging was used to measure RV and LV wall mass, wall thickness, and end-diastolic volume. Stroke volume was derived from the main pulmonary artery flow. RV wall volume, RV wall thickness, and the ratio of RV to LV wall thickness were significantly larger in the patient group than in the control group (p<0.01). Furthermore, patients had significantly lower values of LV ejection fraction (p<0.01) than the control subjects. A flattening or leftward displacement of the ventricular septum during systole was observed. In addition, our study showed an increase of LV ejection fraction proportional with the RV wall thickness (r=0.78, p<0.01) in severely emphysematous patients. CONCLUSION: These data are in support of the hypothesis that flattening of the interventricular septum explains the relatively normal LV ejection fraction in emphysematous patients with severe RV hypertrophy.

Aged↗

Small airways in idiopathic pulmonary fibrosis. Comparison of morphologic and physiologic observations.

18 patients with idiopathic pulmonary fibrosis were studied to determine if they had morphologic evidence of small airways disease and if physiologic testing could predict morphologic findings. In the presence of normal airway function by standard physiologic studies (forced expiratory volume in 1 s/forced vital capacity and airway resistance by plethysmography), dynamic compliance, maximum expiratory flow-volume curves, and maximum flowstatic recoil curves were measured to detect physiologic alterations consistent with small airways abnormalities. These physiologic data were then compared with estimates of small airways diameter made in lung biopsy specimens.94% (17 of 18) of the patients had peribronchiolar fibrosis or peribronchiolar inflammation or bronchiolitis. 67% (12 of 18) had an overall estimate of small airways diameter of "narrowed," whereas 33% (6 of 18) had airways that overall were "not narrowed." 59% (10 of 17) had frequency-dependent dynamic compliance, 50% (9 of 18) had abnormal maximum expiratory flow-volume curves, and 39% (7 of 18) had abnormal maximum flow-static recoil curves. Comparisons between morphologic and physiologic data revealed a significant correlation between the results of dynamic compliance and the overall estimate of small airways diameter (P = 0.001), and the results of maximum flow-volume curves and the overall estimate of small airways diameter (P = 0.009); there was no significant correlation between the results of maximum flow-static recoil curves and the overall estimate of small airways diameter (P = 0.1). THE RESULTS OF THIS STUDY SUGGEST THAT: (a) idiopathic pulmonary fibrosis is a disease of small airways as well as alveoli; (b) dynamic compliance and the maximum expiratory flow-volume curve can predict the overall status of small airways diameter in idiopathic pulmonary fibrosis; and (c) whereas the maximum flowstatic recoil curve predicts the overall estimate of small airways diameter in most patients with this disease, it is the least sensitive of these three monitors of small airways.

Adult↗

Asbestos exposure-cigarette smoking interactions among shipyard workers.

We studied the roentgenograms, pulmonary function tests, and physical findings of 294 shipyard workers to evaluate asbestos exposure-cigarette smoking interactions. Roentgenographic parenchymal opacities, decreased pulmonary diffusing capacity for carbon monoxide, decreased flow at low lung volume, rales, and clubbing were each significantly related to the number of years elapsed since first exposure to asbestos and cigarette smoking status when analyzed by logistic regression. A dose-dependent cigarette smoking response that was consistent with synergism was present only for parenchymal opacities and decreased flow at low lung volume. These findings suggest that decreased flow at low lung volume, possibly reflecting peribronchiolar fibrosis, may be a functional corollary to smoking-associated parenchymal roentgenographic opacities among some asbestos-exposed individuals.

Asbestos↗

Experimental evaluation of the effect of filtration of diesel exhaust by biologic exposure indicators.

The airway resistance, compliance of the respiratory system, transfer factor, and alveolar volume of 33 healthy rabbits were studied before and after exposure to diluted diesel exhaust generated in an experimental motor. Three diesel fuels and two particle traps were tested. Subsequent to the post-exposure lung function measurements, the animals were sacrificed and the lungs were processed for morphologic examination. The concentrations of particles, nitrogen dioxide, and formaldehyde were measured. The inflammatory airway changes were most pronounced in animals exposed to exhaust from standard fuel. Small changes were identified in animals exposed to exhaust filtered through the catalytic trap as well or exposed to unfiltered exhaust from fuels intended for densely built-up areas. Increase in compliance of the respiratory system was associated with the concentration of soot particles and formaldehyde. Compliance decreased significantly in animals exposed to exhaust from standard fuel filtered through the particle traps and increased almost significantly in animals exposed to unfiltered exhaust from the same fuel.

Air Pollutants↗

Evolution of primary Raynaud's phenomenon (Raynaud's disease) to connective tissue disease.

Eighty-seven patients diagnosed as having primary Raynaud's phenomenon (Raynaud's disease) were reexamined after this symptom had been present for a mean of 8.8 years (range 2.0-34.5). One or more additional clinical feature(s) suggesting an underlying connective tissue disease were found in 12 patients (14%) at first evaluation, and in 23 (26%) by the last evaluation. The most frequent findings were puffy fingers (10 patients), digital tip pitting scars (8 patients), and digital tip ulcerations (6 patients). Distal esophageal hypomotility and/or decreased pulmonary diffusing capacity for carbon monoxide were found in 12 patients. Only 4 individuals (5%) developed clear evidence of a connective tissue disease, and in all cases, the diagnosis was the CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias) syndrome variant of systemic sclerosis. This condition became obvious 8-17 years after the onset of Raynaud's phenomenon. One or more serologic test values were initially abnormal in 2 of these CREST syndrome patients, as well as in 12 patients who continued to have primary Raynaud's phenomenon at the last evaluation. The combination of puffy fingers, digital pitting scars, and serum anticentromere antibody, all consistent with CREST syndrome, occurred in a small group of patients. None of the 78 patients whose serologic tests were repeated during followup had a change in the serologic profile. These results suggest that only a small proportion of patients with primary Raynaud's phenomenon develop one of the connective tissue diseases during the first decade after onset. When such a disorder does appear, systemic sclerosis with the CREST syndrome variant is the most likely eventual diagnosis.

Adolescent↗

MR tagging of human lungs using hyperpolarized 3He gas.

PURPOSE: To evaluate the use of spin-tagging in conjunction with hyperpolarized gas imaging for monitoring lung ventilation and gas diffusion. METHODS AND MATERIALS: Images were taken at 0.15 T using single shot RARE, with hyperpolarized (3)He gas prepared by the metastability exchange technique. Sinusoidal modulation of the longitudinal magnetization (tag) was produced by two 90-degree rf pulses separated by a gradient pulse. The diffusion of (3)He gas in the lungs was measured by monitoring the decay of the tags. This study was conducted on a 25-year-old, male, healthy volunteer. RESULTS: Clear tags in hyperpolarized (3)He gas both in vivo and in vitro were generated. The relative movement of the lung compared to a static, partial breath-hold was measured following inspiration or expiration. The diffusion coefficient of (3)He in the lungs was found to be 0.02 +/- 0.005 cm(2)seconds(-1). CONCLUSION: The spin-tagging of hyperpolarized (3)He in the lungs is possible, and allows regional lung movements to be measured following inspiration and expiration. It also allows quantification of the diffusion of the (3)He gas.

Adult↗

Exploring lung function with hyperpolarized (129)Xe nuclear magnetic resonance.

With the use of polarization-transfer pulse sequences and hyperpolarized (129)Xe NMR, gas exchange in the lung can be measured quantitatively. However, harnessing the inherently high sensitivity of this technique as a tool for exploring lung function requires a fundamental understanding of the xenon gas-exchange and diffusion processes in the lung, and how these may differ between healthy and pathological conditions. Toward this goal, we employed NMR spectroscopy and imaging techniques in animal models to investigate the dependence of the relative xenon gas exchange rate on the inflation level of the lung and the tissue density. The spectroscopic results indicate that gas exchange occurs on a time scale of milliseconds, with an average effective diffusion constant of about 3.3 x 10(-6)cm(2)/s in the lung parenchyma. Polarization-transfer imaging pulse sequences, which were optimized based on the spectroscopic results, detected regionally increased gas-exchange rates in the lung, indicative of increased tissue density secondary to gravitational compression. By exploiting the gas-exchange process in the lung to encode physiologic parameters, these methods may be extended to noninvasive regional assessments of lung-tissue density and the alveolar surface-to-volume ratio, and allow lung pathology to be detected at an earlier stage than is currently possible.

Algorithms↗

19F MR imaging of ventilation and diffusion in excised lungs.

Perfluorinated gases, particularly C2F6, are potentially suitable alternatives to hyperpolarized noble gases for pulmonary airspace spin density and diffusion MRI. This work focuses mainly on 19F imaging of C2F6 gas in healthy and emphysematous explanted lungs, avoiding regulatory issues of human in vivo measurements. Three-dimensional gradient echo and spin echo spin density images of human lungs can be made in 10 s with adequate signal-to-noise, demonstrating the feasibility for breathing dynamics to be captured during a succession of short breath holds. As expected, the spin echo images have much smaller susceptibility artifacts than the gradient echo images. 19F and 3He images of the same lungs are compared. The apparent diffusion coefficient (ADC) of C2F6 is sensitive to restrictions imposed by the lung microstructure: the average ADC is measured to be 0.018 cm2/s in healthy lungs versus 0.031 cm2/s in emphysematous lungs at a diffusion time Delta=2.2 ms. The low free diffusivity of pure C2F6 (D0=0.033 cm2/s) places it in a regime where the ADC measurement allows the surface-to-volume ratio to be determined in each voxel, a potentially valuable quantitative characterization of regional lung tissue destruction in emphysema.

Animals↗