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Editorial. Focuses on the journal 'Clinical Physiology and Functional Imaging'. History of the journal; Objectives of the journal; Call for manuscripts based upon the full range of traditional methods and innovative imaging techniques.

Purpose: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation which is not fully reversible. Despite the heterogeneity of COPD, its diagnosis and staging is currently based solely on forced expiratory volume in 1 s (FEV). FEV does not explain the underlying pathophysiology of airflow limitation. The relationship between FEV, symptoms and emphysema extent is weak. Better diagnostic tools are needed to define COPD. Tomographic lung scintigraphy [ventilation/perfusion single photon emission tomography (V/P SPECT)] visualizes regional V and P. In COPD, relations between V/P SPECT, spirometry, high-resolution computed tomography (HRCT) and symptoms have been insufficiently studied. The aim of this study was to investigate how lung function imaging and obstructive disease grading undertaken using V/P SPECT correlate with symptoms, spirometric lung function and degree of emphysema assessed with HRCT in patients with COPD. Methods: Thirty patients with stable COPD were evaluated with the Medical Research Council dyspnoea questionnaire (MRC) and the clinical COPD questionnaire (CCQ). Spirometry was performed. The extent of emphysema was assessed using HRCT. V/P SPECT was used to assess V/P patterns, total reduction in lung function and degree of obstructive disease. Results: The total reduction in lung function and degree of obstructive disease, assessed with V/P SPECT, significantly correlated with emphysema extent ( r = 0.66-0.69, p < 0.0001) and spirometric lung function ( r = 0.62-0.74, p < 0.0005). The correlation between emphysema extent and spirometric lung function was weaker. No correlation between MRC, CCQ and objective measurements was found. Conclusion: V/P SPECT is sensitive to early changes in COPD. V/P SPECT also has the possibility to identify comorbid disease. V/P SPECT findings show a significant correlation with emphysema extent and spirometric lung function. We therefore recommend that scintigraphic signs of COPD, whenever found, should be reported. V/P SPECT can also be used to categorize the severity of functional changes in COPD as mild, moderate or severe. [ABSTRACT FROM AUTHOR]

Objective. The objective was to analyse relationships between inspiratory and expiratory static and dynamic elastic pressure-volume (Pel/V) curves in healthy pigs. Design. The modulated low flow method was developed to allow studies also of the expiratory Pel/V curves. Static Pel/V (Pel,st/V) and dynamic Pel/V (Pel,dyn/V) loops were studied in healthy pigs. Setting. Animal research laboratory in a university hospital. Material. Ten healthy anaesthetised and paralysed pigs. Interventions and measurements. A computer controlled a Servo Ventilator 900C with respect to respiratory rate, inspiratory flow and expiratory pressure to achieve a sinusoidal modulation of inspiration and expiration for determination of Pel,dyn/V loops from zero end-expiratory pressure (ZEEP) and from a positive end-expiratory pressure (PEEP) of 6 cmH2O to 20, 35 and 50 cmH2O. The same system was used for studies of Pel,st/V loops with the flow-interruption method from ZEEP and PEEP to 35 cmH2O. Recordings were analysed with an iterative technique. Results. The feasibility of automated determination of Pel,dyn/V loops was demonstrated. Differences between Pel,dyn/V and Pel,st/V loops were explained by viscoelastic behaviour. Pel,st/V loops recorded from PEEP to 35 cmH2O showed no significant hysteresis, indicating a non-significant surface tension hysteresis. Pel,dyn/V loops from PEEP and both Pel,st/V and Pel,dyn/V loops from ZEEP to 35 cmH2O showed hysteresis. This indicates that lung collapse/re-expansion caused Pel/V loop hysteresis which, in Pel,dyn/V loops, was augmented by viscoelastic behaviour. Conclusions. Viscoelasticity influences Pel,dyn/V curves. Hysteresis caused by surface tension merits re-evaluation. Lung collapse and re-expansion may be indicated by hysteresis of Pel/V loops. [ABSTRACT FROM AUTHOR]

Elastic pressure/volume ( Pel/ V) and elastic pressure/resistance ( Pel/ R) diagrams reflect parenchymal and bronchial properties, respectively. The objective was to develop a method for determination and mathematical characterization of Pel/ V and Pel/ R relationships, simultaneously studied at sinusoidal flow-modulated vital capacity expirations in a body plethysmograph. Analysis was carried out by iterative parameter estimation based on a composite mathematical model describing a three-segment Pel/ V curve and a hyperbolic Pel/ R curve. The hypothesis was tested that the sigmoid Pel/ V curve is non-symmetric. Thirty healthy subjects were studied. The hypothesis of a non-symmetric Pel/ V curve was verified. Its upper volume asymptote was nearly equal to total lung capacity (TLC), indicating lung stiffness increasing at high lung volume as the main factor limiting TLC at health. The asymptotic minimal resistance of the hyperbolic Pel/ R relationship reflected lung size. A detailed description of both Pel/ V and Pel/ R relationships was simultaneously derived from sinusoidal flow-modulated vital capacity expirations. The nature of the Pel/ V curve merits the use of a non-symmetric Pel/ V model. [ABSTRACT FROM AUTHOR]

Objective: To avoid ventilator induced lung injury, tidal volume should be low in acute lung injury (ALI). Reducing dead space may be useful, for example by using a pattern of inspiration that prolongs the time available for gas distribution and diffusion within the respiratory zone, the mean distribution time (MDT). A study was conducted to investigate how MDT affects CO2 elimination in pigs at health and after ALI.Design and Setting: Randomised crossover study in the animal laboratory of Lund University Biomedical Center.Subjects and Intervention: Healthy pigs and pigs with ALI, caused by surfactant perturbation and lung-damaging ventilation were ventilated with a computer-controlled ventilator. With this device each breath could be tailored with respect to insufflation time and pause time (TI and TP) as well as flow shape (square, increasing or decreasing flow).Measurements and Results: The single-breath test for CO2 allowed analysis of the volume of expired CO2 and the volume of CO2 re-inspired from Y-piece and tubes. With a long MDT caused by long TI or TP, the expired volume of CO2 increased markedly in accordance with the MDT concept in both healthy and ALI pigs. High initial inspiratory flow caused by a short TI or decreasing flow increased the re-inspired volume of CO2. Arterial CO2 increased during a longer period of short MDT and decreased again when MDT was prolonged.Conclusions: CO2 elimination can be enhanced by a pattern of ventilation that prolongs MDT. Positive effects of prolonged MDT caused by short TI and decreasing flow were attenuated by high initial inspiratory flow. [ABSTRACT FROM AUTHOR]

Objectives: To develop a method for automatic recording of multiple dynamic elastic pressure–volume ( Pel/ V) loops. To analyse the relationship between multiple dynamic Pel/ V loops and static Pel/ V loops in a porcine model of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). To test the hypothesis that increasing lung collapse and re-expansion with decreasing positive end expiratory pressure (PEEP) can be characterized by hysteresis of the Pel/ V loops. Material and Interventions: In eight anaesthetized and paralysed pigs, ALI/ARDS was induced by inhalation of dioctyl sodium sulfosuccinate and large tidal volume ventilation. Measurements and Results: The physiological and histopathological findings indicated a status mimicking an early stage of ALI/ARDS. Automatically, a series of dynamic Pel/ V loops from different PEEP levels were recorded with the sinusoidal flow modulation method using a computer-controlled ventilator. During expiration, resistance increased more than twofold. For each step of lower starting pressure, the inspiratory limb was displaced towards lower volume indicating derecruitment. Recruitment occurred between 20 and 40 cm H2O. The expiratory curves, all starting from 50 cm H2O, overlapped. Hysteresis increased significantly in loops recorded from lower PEEP levels. Viscoelasticity explained differences between static and dynamic Pel/ V loops. Conclusions: Automated multiple Pel/ V loop determination is feasible and provides comprehensive information on lung derecruitment and recruitment. It requires determination of volume dependence of expiratory resistance. An expiratory curve serves as a reference to inspiratory curves and provides information about hysteresis. [ABSTRACT FROM AUTHOR]

Planar lung ventilation/perfusion scintigraphy (V/PPLANAR) is a standard method for diagnosis of pulmonary embolism (PE). The goals of this study were to test whether the diagnostic information of ventilation/perfusion tomography (V/PSPET) applied in clinical routine might enhance information compared with V/PPLANAR and to streamline data processing for the demands of clinical routine. This prospective study includes 53 patients suspected for PE referred for lung scintigraphy. After inhalation of99mTc-DTPA planar ventilation imaging was followed by tomography, using a dual-head gamma camera.99mTc-MAA was injected i.v. for perfusion tomography followed by planar imaging. Patients were examined in supine position, unchanged during V/P tomography. Two reviewers evaluated V/PPLANAR and V/PSPET images separately and randomly. Mismatch points were calculated on the basis of extension of perfusion defects with preserved ventilation. Patients were followed up clinically for at least 6 months. With V/PSPET the number of patients with PE was higher and 53% more mismatch points were found. In V/PSPET interobserver variation was less compared with V/PPLANAR. Ancillary findings were observed by both techniques in half of the patients but more precisely interpreted with V/PSPET. V/PSPET shows more and better delineated mismatch defects, improved quantification and less interobserver variation compared with V/PPLANAR. V/PSPET is amenable to implementation for clinical routine and suitable even when there is demand for a high patient throughput. [ABSTRACT FROM AUTHOR]

Detergent given as an aerosol and large tidal volume ventilation (LTVV) have been observed, by us, to promote lung injury by an additive effect on alveolocapillary barrier function. The surfactant system may be further damaged if protein leakage occurs into the alveoli. The aim was to study the effect of detergent and LTVV on the alveolar leakage of albumin and also the effect of detergent on surface activity of lung washings and lung tissue extracts. Technetium-99m-labelled human serum albumin was given intravenously. The alveolar leakage of albumin was measured after perturbing the surfactant system with the detergent dioctyl sodium sulfosuccinate either singly or in combination with LTVV. Four groups of rabbits were studied after 3 h of experimental ventilation. Surface tension measurements of tissue extracts, lung mechanics and gas exchange did not show any differences between groups. Wet lung weight and albumin leakage were significantly increased in the two groups subjected to LTVV compared with groups given normal tidal volume ventilation. Low doses of detergent did not affect surface activity of lung tissue extracts or alveolar leakage of albumin. LTVV increased alveolar leakage of albumin and produced oedema. No additive effect was seen when detergent and LTVV were combined. [ABSTRACT FROM AUTHOR]

Background: Spirometry, the main tool for diagnosis and follow-up of COPD, incompletely describes the disease. Based on volumetric capnography (VCap), an index was developed for the diagnosis and grading of COPD, aimed as a complement or alternative to spirometry., Methods: Nine non-smokers, 10 smokers/former smokers without COPD and 54 smokers/former smokers with COPD were included in the study. Multiple breath washout of N 2 and VCap were studied with Exhalyzer D during tidal breathing. VCap was based on signals for flow rate and CO 2 and was recorded during one breath preceding N 2 washout. Efficiency Index (EFFi) is the quotient between exhaled CO 2 volume and the hypothetical CO 2 volume exhaled from a completely homogeneous lung over a volume interval equal to 15% of predicted total lung capacity., Results: EFFi increased with increased Global initiative for chronic Obstructive Lung Disease (GOLD) stage and the majority of subjects in GOLD 2 and all subjects in GOLD 3 and 4 could be diagnosed as having COPD using the lower 95% confidence interval of the healthy group. EFFi also correlated with N 2 washout (r=-0.73; p <0.001), forced expiratory volume in 1 second (r=0.70; p <0.001) and diffusion capacity for carbon oxide (r=0.69; p <0.001)., Conclusion: EFFi measures efficiency of tidal CO 2 elimination that is limited by inhomogeneity of peripheral lung function. EFFi allows diagnosis and grading of COPD and, together with FEV 1 , may explain limitation of physical performance. EFFi offers a simple, effortless and cost-effective complement to spirometry and might serve as an alternative in certain situations., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Ventilation/perfusion single-photon emission computed tomography (V/Q SPECT) is the scintigraphic technique of choice for the diagnosis of pulmonary embolism and many other disorders that affect lung function. Data from recent ventilation studies show that the theoretic advantages of Technegas over radiolabeled liquid aerosols are not restricted to the presence of obstructive lung disease. Radiolabeled macroaggregated human albumin is the imaging agent of choice for perfusion scintigraphy. An optimal combination of nuclide activities and acquisition times for ventilation and perfusion, collimators, and imaging matrix yields an adequate V/Q SPECT study in approximately 20 minutes of imaging time. The recommended protocol based on the patient remaining in an unchanged position during the initial ventilation study and the perfusion study allows presentation of matching ventilation and perfusion slices in all projections as well as in rotating volume images based upon maximum intensity projections. Probabilistic interpretation of V/Q SPECT should be replaced by a holistic interpretation strategy on the basis of all relevant information about the patient and all ventilation/perfusion patterns. PE is diagnosed when there is more than one subsegment showing a V/Q mismatch representing an anatomic lung unit. Apart from pulmonary embolism, other pathologies should be identified and reported, for example, obstructive disease, heart failure, and pneumonia. Pitfalls exist both with respect to imaging technique and scan interpretation., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: Left heart failure (LHF) is a common and frequently overlooked condition owing to insufficient diagnostic methods. This can potentially delay onset of treatment. Our clinical experience with ventilation/perfusion single photon emission computed tomography (V/P SPECT) indicates that perfusion shows an antigravitational distribution pattern in LHF. The aim of the study was to test the hypothesis that LHF diagnosis can be made on the basis of V/P SPECT, and to develop and perform a first evaluation of objective parameters for LHF diagnostics in terms of perfusion gradients., Methods: This retrospective study included 247 consecutive patients with clinical suspicion of pulmonary embolism (PE), who were examined with V/P SPECT. Perfusion gradients were developed and quantified in dorso-ventral and cranio-caudal directions. Quantitative results were compared with visual interpretation of patients with normal and heart failure patterns. Patients with LHF pattern were retrospectively followed up by review of medical records to confirm or discard heart failure diagnosis at the time of V/P SPECT examination., Results: LHF pattern on V/P SPECT was identified in 36 patients (15%), normal ventilation/perfusion pattern was found in 67 patients (27%), and PE in 62 patients (25%). The follow-up confirmed heart failure diagnosis in 32 of the 36 cases with LHF pattern, leading to a positive predictive value of 88% for LHF diagnosis based on V/P SPECT. Dorso-ventral perfusion gradients discriminated normal from LHF patients., Conclusion: In patients with suspected PE, LHF is common. Appropriate V/P SPECT pattern recognition, supported by objectively determined dorso-ventral perfusion gradients, allows the diagnosis of LHF. A positive perfusion gradient in the dorso-ventral direction should lead to consideration of heart failure as a possible explanation for the symptoms in these patients.

Background: Out-of-hospital treatment of patients with deep-vein thrombosis (DVT) is routine in many countries regardless of frequent concomitant asymptomatic pulmonary embolism (PE) in this group. However, patients with symptoms and verified PE are still regularly treated in hospital. The objectives were to test a model for outpatient tinzaparin therapy and to evaluate its safety and efficacy in patients with symptomatic, small or medium-sized PE using quantitative ventilation/perfusion scintigraphy (qV/P SCINT) for patient selection and follow up., Material/methods: This prospective study included 102 patients treated with tinzaparin and warfarin for 5 days at a patient hotel. PE was quantified scintigraphically as loss of perfusion with preserved ventilation at segmental or subsegmental levels (mismatch). Points were attributed to segments of reduced ventilation (RoVent) and perfusion (RoPer). A holistic principle of interpretation was applied. Patients were excluded if they had >14 RoPer points (7 segments) or >7 RoVent points. Clinical follow-up and scintigraphy were repeated at discharge in 100 patients and after 13 months on average., Results: Embolism diminished by 44% after 5 days and demanding symptoms declined. There was no thromboembolic mortality in the trial. At late follow-up, PE had not recurred in patients with resolution after 5 days. In those with insufficient early response, persistent perfusion defects were usually observed., Conclusions: The results indicate the safety and efficacy of outpatient treatment of PE according to our model and merit larger, multicenter, controlled studies.

Background: The principal features of elastic pressure-volume curves of lungs or the respiratory system (P(el)/V curves) recorded during reexpansion of collapsed lungs and subsequent deflation have been known since the 1950s. In acute respiratory failure and acute respiratory distress syndrome such curves have recently attracted increasing interest because new knowledge can be acquired from them, and because such curves may be useful as guidelines in setting the ventilator so as to avoid ventilator-induced lung injury., Discussion: This article reviews recording methods, underlying physiology and utility of P(el)/V curves in research and clinical work.

Study Objective: To address the question whether ventilation/perfusion scintigraphy (SCINT) or helical computed tomography (CT) should be the first hand method for diagnosis of pulmonary embolism (PE)., Setting: Departments of radiology, nuclear medicine and internal medicine of a large university hospital., Patients: During 3 years all 128 patients examined for PE with both methods were analysed. The strategy of interpretation behind original clinical reports, i.e. clinical CT and clinical SCINT, was based upon basic criteria for PE, ancillary findings and information from the referring doctor and from previous examinations. Reviewed SCINT and CT reports were obtained from experts in each field blinded to clinical and laboratory data. The findings with respect to PE were classified as no PE, PE or non-diagnostic. Other pathology than PE was described. A final diagnosis serving as reference was based upon CT, SCINT and other information including clinical follow for 6-24 months., Methods: Planar SCINT was made with ventilation always preceding perfusion. CT was made with contrast injection using 3 mm collimation and table feed of 3 mm s-1., Results: PE was diagnosed in 32 patients. For clinical and reviewed SCINT sensitivity was 91 and 97%, specificity 96 and 100% and rate of non-diagnostic findings 10 and 9%, respectively. For clinical and reviewed CT sensitivity was 81 and 78%, specificity 99 and 100% and non-diagnostic findings was observed in 8 and 1%, respectively. In patients with PE, concordant positive results were obtained with both modalities in 23 of 32 patients (72%)., Conclusion: SCINT remains the first hand method because its high sensitivity, general feasibility, low radiation burden and low rate of non-diagnostic findings in our setting. CT is indispensable when SCINT is not available or its result non-diagnostic.

Background: Conventional insulin therapy with subcutaneous injections of regular insulin at meal-times result in plasma insulin peaks that are lower and appear later than meal related insulin peaks in healthy individuals. The present study was designed in order to evaluate the resulting insulin concentrations in peripheral blood after inhalation of micro crystalline human insulin together with an absorption enhancer [dioctyl sodium sulphosuccinate (DOSS)] via a powder inhaler., Methods: Ten insulin dependent middle-aged non-obese diabetic patients (mean diabetes duration 21 years) were included. Blood samples for glucose and insulin were taken immediately before and 13 times, up to 300 min, after insulin inhalation. The mass median aerodynamic diameter of the particles was 3.2 microm. The inhaled insulin dose was 39 U., Results: Within 5 min after the end of the 2 min inhalation procedure the mean increase of insulin was 7.0 microU ml-1, and the mean maximum concentration, 12.1 microU ml-1, was reached between 20 and 30 min. There was then a slow decline until base-line was reached after around 210 min and there were no adverse events., Conclusions: Inhalation of a mixture of 39 U of insulin and enhancer resulted in a rapid plasma insulin peak with a slow decline, similar to the normal postprandial insulin profile.