Quantitative and O2 Enhanced MRI of the Pathologic Lung: Findings in Emphysema, Fibrosis, and Cystic Fibrosis

Purpose: beyond the pure morphological visual representation, MR imaging offers the possibility to quantify parameters in the healthy, as well as, in pathologic lung parenchyma. Gas exchange is the primary function of the lung and the transport of oxygen plays a key role in pulmonary physiology and pathophysiology. The purpose of this review is to present a short overview of the relaxation mechanisms of the lung and the current technical concepts of T1 mapping and methods of oxygen enhanced MR imaging. Material and Methods: molecular oxygen has weak paramagnetic properties so that an increase in oxygen concentration results in shortening of the T1 relaxation time and thus to an increase of the signal intensity in T1 weighted images. A possible way to gain deeper insights into the relaxation mechanisms of the lung is the calculation of parameter Maps. T1 Maps based on a snapshot FLASH sequence obtained during the inhalation of various oxygen concentrations provide data for the creation of the so-called oxygen transfer function (OTF), assigning a measurement for local oxygen transfer. T1 weighted single shot TSE sequences also permit expression of the signal changing effects associated with the inhalation of pure oxygen. Results: the average of the mean T1 values over the entire lung in inspiration amounts to 1199 +/− 117 milliseconds, the average of the mean T1 values in expiration was 1333 +/− 167 milliseconds. T1 Maps of patients with emphysema and lung fibrosis show fundamentally different behavior patterns. Oxygen enhanced MRT is able to demonstrate reduced diffusion capacity and diminished oxygen transport in patients with emphysema and cystic fibrosis. Discussion: results published in literature indicate that T1 mapping and oxygen enhanced MR imaging are promising new methods in functional imaging of the lung and when evaluated in conjunction with the pure morphological images can provide additional valuable information

T1 mapping of the entire lung parenchyma: Influence of respiratory phase and correlation to lung function test results in patients with diffuse lung disease

The T1 values of lung parenchyma of 25 patients with fibrosis and emphysema were measured in the entire lung, and the effect of inspiration and expiration was investigated. T1 map acquisition was based on a snapshot-fast low-angle shot (FLASH) sequence. Lung function and blood gas tests were measured. The study documents reverse respiratory phase dependence of T1 measurements of the entire lung parenchyma in patients with emphysema and fibrosis. Furthermore, expiratory measurements showed higher and reverse differences between patient groups compared to inspiratory measurements. For the emphysema group, the average T1 value in inspiration was 1033 ± 74 ms. The average of the mean T1 values in expiration was 982 ± 56 ms. For the patients with fibrosis, the average T 1 value in inspiration was 996 ± 103 ms. Compared to that, the average T1 value in expiration was 1282 ± 170 ms. Linear regression of T1 vs. lung function parameters showed the highest regression coefficients for total lung capacity (TLC) and residual volume (RV) in expiration, the values were inversely proportionally dependent on the pooled expiratory T1 values. These findings underline the strong but nonuniform influence of the inspirational status during T1 measurements of the lung. T1 maps in both emphysema and fibrosis should preferably be acquired at expiration if reliable data are to be obtained

British Journal of Clinical Pharmacology / Dissociation between systemic and pulmonary anti-inflammatory effects of dexamethasone in humans

AIMS The local pulmonary inflammatory response has a different temporal and qualitative profile compared with the systemic inflammatory response. Although glucocorticoids substantially downregulate the systemic release of acute-phase mediators, it is not clear whether they have comparable inhibitory effects in the human lung compartment. Therefore, we compared the anti-inflammatory effects of a pure glucocorticoid agonist, dexamethasone, on bronchoalveolar lavage and blood cytokine concentrations in response to bronchially instilled endotoxin. METHODS In this randomized, double-blind and placebo-controlled trial, 24 volunteers received dexamethasone or placebo and had endotoxin instilled into a lung segment and saline instilled into a contralateral segment, followed by bronchoalveolar lavage. RESULTS Bronchially instilled endotoxin induced a local and systemic inflammatory response. Dexamethasone strongly blunted the systemic interleukin (IL) 6 and C-reactive protein release. In sharp contrast, dexamethasone left the local release of acute-phase mediators in the lungs virtually unchanged: bronchoalveolar lavage levels of IL-6 were only 18% lower and levels of IL-8 were even higher with dexamethasone compared with placebo, although the differences between treatments were not statistically significant (P = 0.07 and P = 0.08, respectively). However, dexamethasone had inhibitory effects on pulmonary protein extravasation and neutrophil migration. CONCLUSIONS The present study demonstrated a remarkable dissociation between the systemic anti-inflammatory effects of glucocorticoids and its protective effects on capillary leak on the one hand and surprisingly low anti-inflammatory effects in the lungs on the other.F 5404-B21(VLID)310833

Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension

Primary pulmonary hypertension is a fatal disease causing progressive right heart failure within 3 years after diagnosis. We describe a new concept for treatment of the disease using vasoactive intestinal peptide, a neuropeptide primarily functioning as a neurotransmitter that acts as a potent systemic and pulmonary vasodilator. Our rationale is based on the finding of a deficiency of the peptide in serum and lung tissue of patients with primary pulmonary hypertension, as evidenced by radioimmunoassay and immunohistochemistry. The relevance of this finding is underlined by an upregulation of corresponding receptor sites as shown by Northern blot analysis, Western blot analysis, and immunological techniques. Consequently, the substitution with the hormone results in substantial improvement of hemodynamic and prognostic parameters of the disease without side effects. It decreased the mean pulmonary artery pressure in our eight study patients, increased cardiac output, and mixed venous oxygen saturation. Our data provide enough proof for further investigation of vasoactive intestinal peptide and its role in primary pulmonary hypertension