The association of the N-terminal pro-brain-type natriuretic peptide response to exercise with disease severity in therapy-naive pulmonary arterial hypertension: a cohort study.

BACKGROUND: While the N-terminal pro-brain-type natriuretic peptide (NT-proBNP) at rest is known to be associated with prognosis in pulmonary arterial hypertension (PAH), it is unclear if the NT-proBNP response to exercise (ΔNT-proBNP) can contribute to a better assessment of disease severity. METHODS: We investigated the association of NT-proBNP values at rest and during peak exercise with hemodynamics and cardiopulmonary exercise testing parameters in 63 therapy-naive PAH patients. RESULTS: The median NT-proBNP increases from 1414 at rest to 1500 pg/ml at peak exercise. The ΔNT-proBNP is baseline-dependent in PAH. Both, NT-proBNP at rest and NT-proBNP at peak exercise, are significantly correlated with hemodynamics and functional capacity. However, neither NT-proBNP at peak exercise nor ΔNT-proBNP correlated better with surrogate markers of disease severity than NT-proBNP at rest. CONCLUSION: The ΔNT-proBNP does not contribute to a better assessment of disease severity in PAH.

The association of N-terminal pro-brain-type natriuretic peptide with hemodynamics and functional capacity in therapy-naive precapillary pulmonary hypertension: results from a cohort study.

BACKGROUND: N-terminal pro-brain-type natriuretic peptide (NT-proBNP) is currently used as a surrogate marker for disease severity in pulmonary hypertension (PH). However, NT-proBNP tends to have a high variability and may insufficiently correlate with hemodynamics and exercise capacity. METHODS: To investigate the association of NT-proBNP with hemodynamics and cardio-pulmonary exercise testing (CPET) in 84 therapy-naive patients with precapillary PH. RESULTS: NT-proBNP levels were significantly correlated with hemodynamics and CPET parameters except for cardiac index, diffusion capacity, PaO2 at peak exercise, and peak minute ventilation. NT-proBNP correlated best with hemodynamics and CPET in women and patients >65 years. NT-proBNP correlated better with CPET in pulmonary arterial hypertension compared to chronic thromboembolic PH (CTEPH). CONCLUSION: NT-proBNP is associated with disease severity in precapillary PH. The association might be age- and gender-dependent. NT-proBNP may insufficiently correlate with disease severity in CTEPH, possibly due to comorbidity.

[Risk stratification and follow-up assessment of patients with pulmonary arterial hypertension: Recommendations of the Cologne Consensus Conference 2016]. / Risikostratifizierung und Verlaufskontrollen bei PAH-Patienten: Empfehlungen der Kölner Konsensus-Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed information about the diagnosis of pulmonary hypertension, and furthermore provide novel recommendations for risk stratification and follow-up assessments. However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to risk stratification and follow-up assessment of patients with PAH. This manuscript summarizes the results and recommendations of this working group.

Obstructive sleep apnea might trigger acute pulmonary embolism: results from a cohort study.

BACKGROUND: Obstructive sleep apnea (OSA) might be an independent risk factor for acute pulmonary embolism (APE). AIM OF THE STUDY: A prospective cohort study was conducted to investigate if APE is sleep-related in untreated OSA syndrome or not. METHODS: 206 APE patients were evaluated by portable monitoring and polysomnography. APE symptoms which caused an arousal from sleep or occurred within the first hour after wake-up were considered to be sleep-related. RESULTS: APE manifestation is significantly more often sleep-related in patients with moderate or severe OSA compared to subjects with an apnea-hypopnea index ≤15/h (p < 0.001). The relative risk of sleep-related APE increases with the severity of OSA. CONCLUSIONS: OSA might trigger APE, possibly reflecting a pathophysiological relationship between these two conditions.

The N-terminal pro-brain-type natriuretic peptide based short-term prognosis in patients with acute pulmonary embolism according to renal function.

N-terminal pro-brain-type natriuretic peptide (NT-proBNP) is currently used for risk stratification in acute pulmonary embolism (PE). We aimed to clarify the impact of renal function on the validity of the NT-proBNP based prognosis, assuming that the biomarker is accumulated in renal insufficiency. The NT-proBNP based prediction of PE related in-hospital death was investigated according to renal function in 329 patients with acute PE. The normalized NT-proBNP ratios (NT-proBNP level divided by the age-adjusted normal upper range) were inversely correlated (r = -0.414, P < 0.001) to the estimated glomerular filtration rates (eGFR). A cut-off point of ≥ 2.5 for the normalized NT-proBNP ratio was found to be best for the prediction of mortality (AUC 0.716, 95% CI 0.626-0.805, P < 0.001) and was a significant predictor for death in univariate and multivariate analysis. A normalized NT-proBNP ratio ≥ 2.5 was a significant predictor for PE-mortality only in patients with an eGFR ≥ 60 ml/min/1.73 m². Renal insufficiency significantly predicted mortality in univariate but not in multivariate analysis. High-risk PE and cerebrovascular diseases were significantly more frequent in renal dysfunction and significantly predicted death in univariate and multivariate analysis. The validity of the NT-proBNP based short-term prognosis might be limited in renal dysfunction not only by accumulation, but also because renal insufficiency itself and concurrent conditions are contributing to PE related mortality.

The impact of age on the delay in diagnosis in patients with acute pulmonary embolism.

It has been speculated that the atypical clinical presentation of acute pulmonary embolism (PE) in older patients leads to a late diagnosis and therefore contributes to a worse prognosis. Therefore, we prospectively evaluated the delay in diagnosis and its relation to the in-hospital mortality in 202 patients with acute PE. Patients >65 years presented more often with hypoxia (P = .017) and with a history of syncope (P = .046). Delay in diagnosis was not statistically different in both age groups. Older age was significantly associated with an increased risk for in-hospital mortality (OR 4.36, 95% CI 0.93-20.37, P = .043), whereas the delay in diagnosis was not associated with an increase of in-hospital mortality. We therefore conclude that the clinical presentation of acute PE in older patients cannot be considered as a risk factor for late diagnosis and is not responsible for their higher in-hospital death rate.

Time between first symptoms and diagnosis in patients with acute pulmonary embolism: are patients with recurrent episodes diagnosed earlier?

BACKGROUND: Early diagnosis can be life-saving in acute pulmonary embolism (PE). It is unknown, whether patients with recurrent PE are diagnosed earlier than those with their first episode. METHODS: Admission data of patients with symptomatic acute PE were reviewed over a period of 47 months. Delay in diagnosis, demographics, body mass index, comorbidity, mortality, risk factors for venous thromboembolism and socio-economic status were recorded. RESULTS: 56 out of 248 patients had recurrent PE, 192 patients were hospitalized because of their first episode. Delay in diagnosis after symptom onset was significantly greater in patients with recurrent than in patients with their first PE (3.4 ± 2.3 vs. 2.2 ± 1.7 days, p = 0.006). Recurrent PE was significantly more often unprovoked (p < 0.001); by contrast, preceding trauma or surgery were significantly (p = 0.007) more frequent in first PE. CONCLUSIONS: Missing predisposing factors in unprovoked PE might explain the greater delay in diagnosis in recurrent PE. Physicians should focus more on informing patients about the possibility of PE recurrence and associated symptoms and thereby enable earlier diagnosis in recurrent PE.

[Non-invasive diagnosis of pulmonary hypertension: ESC/ERS Guidelines with commentary of the Cologne Consensus Conference 2010]. / Nicht-invasive Diagnostik der pulmonalen Hypertonie: ESC/ERS-Leitlinien mit Kommentierung der Kölner Konsensus-Konferenz 2010.

The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension have been adopted for Germany. The guidelines contain detailed recommendations for the diagnosis of pulmonary hypertension. However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update y appears necessary. In June 2010, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to non-invasive diagnosis of PH. This commentary summarizes the results and recommendations of the working group on treatment of PAH.

Effectiveness of thrombolysis in patients with intermediate-risk pulmonary embolism: influence on length of hospital stay.

INTRODUCTION: The effects of thrombolysis on the clinical outcome of patients with intermediate-risk pulmonary embolism (PE) are still under debate. The effect of thrombolysis on the length of stay (LOS) in hospital is unknown. The aim of this study was to identify factors associated with LOS and to investigate whether LOS is suitable to assess effectiveness of thrombolysis in patients with intermediate-risk PE. METHODS: Data were reviewed from December 2005 until October 2009. The LOS in the intensive care unit (ICU) was expressed in hours, and total LOS was recorded in days. Total LOS was not noted in case of preterm withdrawal of therapy or death. RESULTS: Of a total of 202 patients, 84 received alteplase plus heparin and 118 patients were treated with anticoagulants alone. Total median LOS was significantly shorter (10 vs. 12 days) in the alteplase group (P=0.005), while there was no difference in the LOS in the ICU. Age above 65 years (P=0.036) and comorbidity (P<0.001) were independent predictors for a prolonged hospital stay, whereas thrombolysis independently predicted a shorter total LOS in multivariate analysis (P=0.001). Thrombolysis has shown to be able to independently predict home discharge (P=0.029). CONCLUSION: LOS is influenced by patient-related factors such as age and comorbidity. Thrombolysis may lead to a reduction of total median LOS for patients with intermediate-risk PE, possibly indicating that it is more effective than anticoagulant therapy alone in this group of patients.

Central thromboembolism is a possible predictor of right heart dysfunction in normotensive patients with acute pulmonary embolism.

BACKGROUND: Right heart dysfunction is a crucial factor in risk stratification of normotensive patients with pulmonary embolism. Apart from biomarkers, determinants of right heart dysfunction in this group of patients are not yet well established. AIM AND METHOD: In order to identify such determinants, we analysed data of 252 patients with acute pulmonary embolism admitted to our hospital in 2008. RESULTS: 69 out of 140 patients showed right heart dysfunction by echocardiography within 24 hours after diagnosis, 71 did not. Right ventricular dysfunction was significantly more frequent in patients with central clots on computed tomography (p=0.004), a history of syncope (p<0.001) and among women on oral contraceptives (p=0.003). In multiple regression analysis, only central thromboembolism (p<0.001) was identified as individual predictor of right ventricular dysfunction. Age, gender, body mass index, idiopathic or recurrent thromboembolism, duration of symptoms, preceding surgery, room air oxygen saturation, carcinoma, hypertension, diabetes, renal disease, congestive left heart failure and concomitant lung disease were equally distributed. In comparison with NT-pro brain natriuretic peptide (PPV 67%, NPV 75%, p=0.782) and troponin I (PPV 76%, NPV 62%, p=0.336), central thromboembolism has shown to have a greater statistical power in predicting right heart dysfunction in normotensive patients with pulmonary embolism (PPV 78%, NPV 88%, p<0.001). CONCLUSION: Among normotensive patients with acute pulmonary embolism, those with central clots seem to be at greater risk for echocardiographically evaluated right ventricular dysfunction.

[Lipoid pneumonia - an underestimated syndrome]. / Lipidpneumonie - ein unterschätztes Krankheitsbild?

Lipoid pneumonia, first described by Laughlen 1925 may be classified as endogenous or exogenous. The endogenous form is seen when fat is deposited into the lung tissue. It is usually associated with proximal obstructive lesions, necrotic tissue after radio- or chemotherapy, with lipid storage disease or hyperlipidemia . Exogenous lipoid pneumonia results from inhaling or aspirating animal, vegetable or mineral oil. There are usually some underlying neurological defects or esophageal abnormalities. Patients may present with cough, sputum, hemoptysis and chest pain or may be asymptomatic. There is no classic chest film appearance: it may appear as diffuse airspace infiltration or localized consolidation simulating tumour. Computed tomography is diagnostically helpful and shows hypodense areas measuring from -100 to - 30 Hounsfield units. Bronchoscopic biopsies are mandatory for histological confirmation of the diagnosis. Treatment of exogenous lipoid pneumonia has always been conservative by discontinuing the use of oil, correction of underlying defects that may favor aspiration and treatment of intercurrent pneumonia. Other measures, for example corticosteroid therapy, are of uncertain benefit. Complications of lipoid pneumonia that worsen prognosis are recurrent bacterial pneumonias including nontuberculous mycobacteria or aspergillus, or lung cancer that has developed in areas of pre-existing exogenous lipoid pneumonia.

Human herpesvirus 6 in bronchalveolar lavage fluid after lung transplantation: a risk factor for bronchiolitis obliterans syndrome?

Bronchiolitis obliterans syndrome (BOS) is the limiting factor to long-term survival after lung transplantation. Previous studies suggested respiratory viral tract infections are associated with the development of BOS. To identify the impact of virus detection in bronchoalveolar lavage (BAL) fluid, we analyzed BAL samples from 87 consecutive lung transplant recipients for human herpesvirus (HHV)-6, Epstein-Barr virus, Herpes simplex virus 1/2, Cytomegalovirus, respiratory syncytical virus and adenovirus by PCR. Acute rejection, BOS and death were recorded for a mean follow-up time of 3.27 +/- 0.47 years. Results of PCR analysis and other potential risk factors were entered into a Cox regression analysis of BOS predictors and death. Only acute rejection was a distinct risk factor for BOS of all stages, death and death from BOS. HHV-6 was detected in 20 patients. Univariate and multivariate analysis revealed that HHV-6 was associated with an increased risk to develop BOS > orb = stage 1 and death, separate from the risk attributable to acute rejection. Identification of HHV-6 DNA in BAL fluid is a potential risk factor for BOS. Our results warrant further studies to elucidate a possible causal link between HHV-6 and BOS.

Bronchial epithelial cell B7-1 and B7-2 mRNA expression after lung transplantation: a role in allograft rejection?

Obliterative bronchiolitis is commonly interpreted as chronic rejection and involves the bronchial and bronchiolar epithelium. Upregulation of major histocompatibility complex (MHC) II on bronchial epithelial cells (BEC) had been hypothesised to be an important trigger of a bronchus directed rejection response. More recently, the additional expression of the costimulatory molecules B7-1 (CD80) and B7-2 (CD86) on antigen presenting cells were found to play an important role in the activation of T-lymphocytes in transplant rejection. The role of the expression of these molecules by BEC is unclear. BEC obtained by bronchial brushing and bronchoalveolar lavage fluid (BALF) cells from lung transplant recipients were studied and evaluated for messenger ribonucleic acid (mRNA) expression of B7-1 and B7-2 by semi-quantitative reverse transcriptase-polymerase chain reaction. Significantly elevated B7-1/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA ratios were found in BEC from patients examined during the first 3 months after lung transplantation. Interestingly, in a small group of patients with bronchiolitis obliterans syndrome the B7-1/GAPDH and B7-2/GAPDH ratios were significantly elevated for BEC, whereas no differences were found for the BALF cells. In summary, B7 messenger ribonucleic acid expression by bronchial epithelial cells may play a role in (chronic) lung allograft rejection.

Role of brain natriuretic peptide in risk stratification of patients with congestive heart failure.

OBJECTIVES: Using a prospective study design, we assessed the value of brain natriuretic peptide (BNP) to identify patients with heart failure who have an increased risk of deterioration of their functional status. Furthermore, we examined the relationship between BNP and various clinical characteristics incorporated into an established survival model used for risk stratification. BACKGROUND: Prediction of the clinical course is a crucial part of the decision-making process about the adequate treatment strategy for patients with advanced congestive heart failure (CHF). Although laborious, multivariable indexes have been established for risk stratification, simple plasma BNP measurements may be as useful as prognostic indicators. METHODS: In 78 patients referred to our heart failure clinic, plasma BNP levels were compared with the results of a multivariable prognostic model. To assess the prognostic power of BNP, the clinical course of this cohort was monitored for a median follow-up period of 398 days. RESULTS: At study entry, plasma BNP and the heart failure survival score (HFSS) showed a significant correlation (r = -0.706). During follow-up, Kaplan-Meier estimates of freedom from clinical events differed significantly for patients above and below the 75th percentile concentrations of plasma BNP (p < 0.0001). Changes in plasma BNP were significantly related to changes in limitations of physical activity, as demonstrated by logistic regression analysis (chi-square statistic = 24.9, p < 0.0001). Proportional hazards analysis confirmed BNP as a powerful predictor of functional status deterioration (p < 0.0001). This prognostic information was as powerful as that derived from the multivariable HFSS. CONCLUSIONS: Measurement of plasma BNP concentrations might provide a useful and cost-effective screening tool that helps reduce the need and frequency for more expensive cardiac tests.

Pressure-guided nonsurgical myocardial reduction induced by small septal infarctions in hypertrophic obstructive cardiomyopathy.

OBJECTIVES: We sought to assess the safety and efficacy of pressure-guided nonsurgical myocardial reduction (NSMR) with the induction of small septal infarctions in patients with hypertrophic obstructive cardiomyopathy (HOCM). BACKGROUND: Nonsurgical myocardial reduction has been shown to decrease left ventricular outflow tract (LVOT) obstruction and to improve symptoms in patients with HOCM. Infarct sizes differ considerably among studies published so far. METHODS: In 50 patients, the LVOT gradient was invasively determined at the time of the intervention, four to six months (n = 49) and 12 to 18 months (n = 25) after NSMR. New York Heart Association functional class and quality of life were assessed by using a standard questionnaire. Exercise capacity was tested by spiro-ergometry. Left ventricular (LV) mass was determined by electron beam computed tomography. RESULTS: Small septal infarctions (mean creatine kinase value 413 +/- 193 U/l) resulted in a sustained decrease in LVOT gradients, from 80 +/- 33 to 18 +/- 17 mm Hg after four to six months (p < 0.001, n = 49) and to 17 +/- 15 mm Hg (p < 0.001, n = 25) after 12 to 18 months. Nonsurgical myocardial reduction was followed by a decrease in LV hypertrophy, which was associated with a sustained increase in exercise capacity, as well as improvement in quality of life. CONCLUSIONS: Pressure-guided NSMR inducing small septal infarctions was sufficient to result in a sustained decrease in LVOT obstruction and to improve symptoms. The incidence of complications, such as complete heart block with necessary permanent pacemaker implantation (<10%), seems to be diminished by minimizing the infarct size.

Cellular chimerism of the lung after transplantation. An interphase cytogenetic study.

The present study evaluated the origin of endothelial and epithelial cells, as well as of lymphocytes and macrophages, after lung transplantation. Biopsy specimens from patients who underwent lung and heart-lung transplantation and received organs of sex-mismatched donors were studied by means of nonisotopic in situ hybridization with DNA probes of the X and Y chromosome. By means of monoclonal antibodies against leukocytes, T and B lymphocytes, and macrophages, the various infiltrating cell types were analyzed. In all allografted lungs, the endothelial cells and bronchial and alveolar epithelium retained the donor sex type. The lymphocytes of the donor were almost completely replaced by recipient cells 1 month after transplantation. Low numbers of alveolar macrophages of the donor were present during the entire period under study. Low numbers of donor lymphocytes and high numbers of donor alveolar macrophages in the allografted lung seem to be correlated with a worse clinical course.

Elevated levels of interleukin-8 and transforming growth factor-beta in bronchoalveolar lavage fluid from patients with bronchiolitis obliterans syndrome: proinflammatory role of bronchial epithelial cells. Munich Lung Transplant Group.

BACKGROUND: Obliterative bronchiolitis (OB), the most important long-term complication after lung transplantation, is thought to be a manifestation of chronic rejection within the airways, with the hallmarks inflammation and fibroproliferation. METHODS: To characterize the inflammatory process in the context of OB we quantified tumor necrosis factor-alpha, interleukin (IL)-8, IL-10, and transforming growth factor (TGF)-beta on the protein and mRNA level in bronchoalveolar lavage fluid samples obtained from patients with bronchiolitis obliterans syndrome (BOS) and without BOS. In addition, bronchial cells sampled by bronchial brushing were analyzed for mRNA expression. RESULTS: In respiratory epithelial lining fluid (ELF) from BOS patients the protein levels of IL-8 (52.4+/-22.2 vs. 4.4+/-0.9 pg/ml ELF, P<0.005) and TGF-beta (5.6+/-1.9 vs. 0.9+/-0.2 ng/ml ELF, P<0.005) were significantly elevated. In addition, bronchoalveolar lavage fluid cells of BOS patients showed increased expression of TGF-beta (1.13+/-0.44 vs. 0.45+/-0.16, optical density [O.D.]/O.D. glyceraldehyde-3-phosphate dehydrogenase [GAPDH], P=0.11) and IL-8 (0.25+/-0.13 vs. 0.09+/-0.03 O.D/O.D. GAPDH, P=0.53) without the differences reaching statistical significance. In contrast, IL-8 mRNA expression of bronchial cells was significantly higher in the BOS group (0.85+/-0.40 vs. 0.22+/-0.10 O.D./O.D. GAPDH, P<0.05). CONCLUSIONS: We assume that IL-8 and TGF-beta may act as key mediators for airway inflammation and fibroproliferation in the pathogenesis of OB, with bronchial epithelial cells serving as a relevant source of IL-8.

Evidence for oxidative stress in bronchiolitis obliterans syndrome after lung and heart-lung transplantation. The Munich Lung Transplant Group.

Bronchiolitis obliterans syndrome (BOS) is the most serious long-term sequel of lung or heart-lung transplantation (H/LTX). Neutrophilia in the lower respiratory tract is a prominent feature of BOS. Because polymorphonuclear leukocytes (PMN) are capable of releasing large quantities of reactive oxygen species, we measured indicators of oxidative stress and glutathione levels representing antioxidant defense in H/LTX patients (HLTX, n=6; double-LTX, n=7; single-LTX, n=9). We analyzed 19 bronchoalveolar lavage (BAL) samples from 13 non-BOS patients (nine female, four male: age 39+/-4 years) and 17 BAL samples from nine BOS patients (five female, four male: age 33+/-2 years). PMN were the predominant BAL cell population in BOS (61.7+/-7.8% vs. 12.3+/-3.4%, P<0.001). Myeloperoxidase activity in the epithelial lining fluid and oxidized methionine residues in BAL-derived proteins were elevated in BOS (8.6+/-1.6 U/ml vs. 2.2+/-0.6 U/ml, P<0.01; and 12.6+/-1.1% vs. 7.7+/-0.8%, P<0.001, respectively). In addition, the concentration of reduced glutathione in epithelial lining fluid was decreased in BOS (162.6+/-20.1 microM vs. 345.8+/-57.1 microM, P<0.01), whereas the proportion of oxidized glutathione was increased (13.9+/-2.0O% vs. 6.7+/-1.2%, P<0.001). PMN, myeloperoxidase, and oxidized methionine residues were inversely correlated, whereas reduced glutathione was positively correlated with forced expiratory volume in 1 sec (P<0.05 to P<0.001). We conclude that excessive oxidative stress and a lack of glutathione are associated with BOS after H/LTX and may play relevant roles in the development of this disorder.

Optimization and evaluation of the signal intensity change in multisection oxygen-enhanced MR lung imaging.

The behavior of the signal intensity in MRI of human lungs was investigated during inhalation of pure oxygen. Nine volunteers were examined, five using a breath-hold and four using a non-breath-hold technique. Four coronal slices were acquired in each volunteer using an inversion recovery turbo spin-echo sequence. The inversion time of the sequence was optimized for maximum contrast. Breathing of pure oxygen and room air was alternated in the volunteers. Breath-hold and non-breath-hold cases were compared. Breathing pure oxygen lead to a statistically significant signal intensity increase (up to 18%) compared to breathing room air. In addition, T(1) maps were acquired during breathing 100% oxygen and room air. Inhalation of pure oxygen reduced the mean T(1) time of the lungs from 1280 (+/-85) msec to 1224 (+/-139) msec without breath-hold and from 1219 (+/-176) to 1074 (+/-92) msec with breath-hold. Therefore, an optimized sequence and measurement protocol provided significant signal intensity changes utilizing 100% oxygen. Magn Reson Med 43:860-866, 2000.