Lung mechanics in the aging lung and in acute lung injury. Studies based on sinusoidal flow modulation.

Knowledge about lung mechanics is of interest in intensive care to adjust mechanical ventilation and in the lung laboratory for diagnostics and evaluation of patients with various kinds of respiratory diseases. In mechanical ventilation a single inspiratory elastic pressure-volume (Pel/V) curve is difficult to interpret due to continuing re-expansion of collapsed lung units over a large pressure interval. However, the volume shifts between multiple inspiratory Pel/V curves recorded at different levels of positive end-expiratory pressure (PEEP) give information about lung collapse and re-expansion. Methods based on flow interruption for measurement of Pel/V curves have limitations due to continuing gas exchange, the need for disconnection from the ventilator or the fact that they are time consuming. Recordings during constant or sinusoidal flow can be obtained using a computer-controlled ventilator. Sinusoidal flow modulation provides the possibility to separate the elastic and resistive pressure components of measured pressure, thereby providing more accurate inspiratory Pel/V curves and simultaneous data of resistance (R) in short time. The sinusoidal flow modulation method was further developed to allow recording and analysis of both inspiratory and expiratory limbs of Pel/V loops and to allow automatic recording of Pel/V loops from multiple PEEP levels. Pel/V loops obtained by the sinusoidal flow modulation method and by the flow-interruption method were compared in healthy pigs and in pigs with acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Viscoelastic phenomena caused differences in Pel/V loops and influenced hysteresis. Lung collapse and re-expansion at decreasing PEEP levels could, however, be estimated by hysteresis of the Pel/V loops recorded from zero end-expiratory pressure as well as by the volume shifts between multiple inspiratory Pel/V curves recorded at different levels of PEEP. In ALI/ARDS pigs, expiratory R increased during expiration warranting determination of its volume dependence to obtain as accurate dynamic expiratory Pel/V curves as possible. In the lung laboratory lung parenchyma properties and intrinsic bronchial properties are uniquely reflected in the Pel/V and elastic pressure-resistance (Pel/R) diagrams, respectively, measured at regulated flow rate. The flow-regulation method, previously based on square wave flow modulation (V'square method), was further developed applying sinusoidal flow rate adapted to body size (V'sine method) and iterative parameter estimation for mathematical characterization of Pel/V, Pel/C and Pel/R curves. The quality of results obtained with the V'sine method was equal to that of the more time consuming V'square method. In healthy subjects no effect of heart artefact correction was found. For the V'sine method representative reference values, based on 60 healthy 20 65 year old never-smokers, are presented for Pel/V, Pel/C and Pel/R curves. After normalization to lung size women and men had similar lung mechanics. By relating the Pel/V, Pel/C and Pel/R curves to age and lung size normal ranges were importantly narrowed. Elastic recoil pressure (Pel) decreased with age to an extent in agreement with the higher rates observed in previous studies. The width of the normal range for the Pel/V curve increased with age indicating individual rate of aging as in the skin. At Pel 5 cmH2O, roughly corresponding to functional residual capacity, compliance (C) increased with age as previously observed. At Pel values ? 10 cmH2O C decreased with age. The findings may suggest that the lower part of the Pel/V curve in old subjects is influenced by collapsing alveoli, while in younger subjects airway closure dominates. Expiratory R in relation to Pel decreased with age. When C and R were related to volume rather than to Pel no age dependence was observed. Accordingly, dimension of the lung rather than the distending pressure Pel seems to be a determinant of C and R

Measurement and mathematical modelling of elastic and resistive lung mechanical properties studied at sinusoidal expiratory flow.

Summary Elastic pressure/volume (P(el)/V) and elastic pressure/resistance (P(el)/R) diagrams reflect parenchymal and bronchial properties, respectively. The objective was to develop a method for determination and mathematical characterization of P(el)/V and P(el)/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 P(el)/V curve and a hyperbolic P(el)/R curve. The hypothesis was tested that the sigmoid P(el)/V curve is non-symmetric. Thirty healthy subjects were studied. The hypothesis of a non-symmetric P(el)/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 P(el)/R relationship reflected lung size. A detailed description of both P(el)/V and P(el)/R relationships was simultaneously derived from sinusoidal flow-modulated vital capacity expirations. The nature of the P(el)/V curve merits the use of a non-symmetric P(el)/V model

Retinyl palmitate is a reproducible marker for chylomicron elimination from blood

To study the individual variation in chylomicron clearance rate, young healthy volunteers were given a p.o. dose of 50,000 IU retinyl palmitate in the morning to label their chylomicrons. Serial blood samples were then obtained in the time interval 4-8 h after retinyl palmitate intake, to closely monitor the clearance of retinyl ester from the blood. The procedure was repeated in an identical way two days later. The calculated individual halflives for retinyl palmitate clearance ranged from 1.54 to 9.90 h, i.e. a more than five-fold variation. The intraindividual variation was much less (relative SD 11%). Retinyl palmitate clearance (and probably chylomicron clearance) is, thus, relatively constant within the same individual on different occasions but varies considerably between individuals

Comprehensive ventilation/perfusion SPECT

Lung scintigraphy is the primary tool for diagnostics of pulmonary embolism. A perfusion study is often complemented by a ventilation study. Intermediate probability scans are frequent. Our goal was to develop a fast method for tomographic ventilation and perfusion scintigraphy to improve the diagnostic value of lung scintigraphy. METHODS: SPECT was performed with a dual-head gamma camera. Acquisition parameters were determined using a thorax phantom. Ventilation tomography after inhalation of 30 MBq (99m)Tc-diethylenetriaminepentaacetate (DTPA) aerosol was, without patient movement, followed by perfusion tomography after an intravenous injection of 100 MBq (99m)Tc-labeled macroaggregated albumin (MAA). Total SPECT acquisition time was 20 min. (99m)Tc-DTPA clearance, calculated from initial and final SPECT projections, was used for correction of the ventilation projection set before iterative reconstruction of ventilation and perfusion. The ventilation background was subtracted from the perfusion tomograms. A normalized ventilation/perfusion quotient (V/P quotient) image set was calculated. The method was evaluated on a trial group of 15 patients. RESULTS: Ventilation and perfusion images had adequate quality and showed ventilation/perfusion (V/Q quotient) relationships more clearly than did planar images. Frontal and sagittal slices were superior to planar scintigraphy for characterization of embolized areas. The V/Q quotient was supportive, particularly in the patients with chronic obstructive pulmonary disease. CONCLUSION: Fast, high-quality, ventilation/perfusion SPECT with standard isotopes doses is feasible and may contribute to higher objectivity in evaluating lung embolism as well as other lung diseases. The costs for the procedure and patient care until diagnosis are low because of the comprehensive system for the study and, particularly, the short time for its completion

Comparison between silicon photomultiplier-based and conventional PET/CT in patients with suspected lung cancer—a pilot study

Background: Lung cancer is one of the most common cancers in the world. Early detection and correct staging are fundamental for treatment and prognosis. Positron emission tomography with computed tomography (PET/CT) is recommended clinically. Silicon (Si) photomultiplier (PM)-based PET technology and new reconstruction algorithms are hoped to increase the detection of small lesions and enable earlier detection of pathologies including metastatic spread. The aim of this study was to compare the diagnostic performance of a SiPM-based PET/CT (including a new block-sequential regularization expectation maximization (BSREM) reconstruction algorithm) with a conventional PM-based PET/CT including a conventional ordered subset expectation maximization (OSEM) reconstruction algorithm. The focus was patients admitted for 18F-fluorodeoxyglucose (FDG) PET/CT for initial diagnosis and staging of suspected lung cancer. Patients were scanned on both a SiPM-based PET/CT (Discovery MI; GE Healthcare, Milwaukee, MI, USA) and a PM-based PET/CT (Discovery 690; GE Healthcare, Milwaukee, MI, USA). Standardized uptake values (SUV) and image interpretation were compared between the two systems. Image interpretations were further compared with histopathology when available. Results: Seventeen patients referred for suspected lung cancer were included in our single injection, dual imaging study. No statically significant differences in SUVmax of suspected malignant primary tumours were found between the two PET/CT systems. SUVmax in suspected malignant intrathoracic lymph nodes was 10% higher on the SiPM-based system (p = 0.026). Good consistency (14/17 cases) between the PET/CT systems were found when comparing simplified TNM staging. The available histology results did not find any obvious differences between the systems. Conclusion: In a clinical setting, the new SiPM-based PET/CT system with a new BSREM reconstruction algorithm provided a higher SUVmax for suspected lymph node metastases compared to the PM-based system. However, no improvement in lung cancer detection was seen

Dynamic elastic pressure-volume loops in healthy pigs recorded with inspiratory and expiratory sinusoidal flow modulationRelationship to static pressure-volume loops.

Objective: The objective was to analyse relationships between inspiratory and expiratory static and dynamic elastic pressure-volume (P-el/V) curves in healthy pigs. Design: The modulated low flow method was developed to allow studies also of the expiratory P-el/V curves. Static P-el/V (P-el,P-st/V) and dynamic P-el/V (P-el,P-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 P-el,P-dyn/V loops from zero end-expiratory pressure (ZEEP) and from a positive end-expiratory pressure (PEEP) of 6 cmH(2)O to 20, 35 and 50 cmH(2)O. The same system was used for studies of P-el,P-st/V loops with the flow-interruption method from ZEEP and PEEP to 35 cmH(2)O. Recordings were analysed with an iterative technique. Results: The feasibility of automated determination of P-el,P-dyn/V loops was demonstrated. Differences between P-el,P-dyn/V and P-el,P-st/V loops were explained by viscoelastic behaviour. P-el,P-st/V loops recorded from PEEP to 35 cmH(2)O showed no significant hysteresis, indicating a non-significant surface tension hysteresis. P-el,P-dyn/V loops from PEEP and both P-el,P-st/V and P-el,P-dyn/V loops from ZEEP to 35 cmH(2)O showed hysteresis. This indicates that lung collapse/re-expansion caused P-el/V loop hysteresis which, in P-el,P-dyn/V loops, was augmented by viscoelastic behaviour. Conclusions: Viscoelasticity influences P-el,P-dyn/V curves. Hysteresis caused by surface tension merits re-evaluation. Lung collapse and re-expansion may be indicated by hysteresis of P-el/V loops

11C-Metomidate PET/CT Detected Multiple Ectopic Adrenal Rest Tumors in a Woman with Congenital Adrenal Hyperplasia

Context: Women with congenital adrenal hyperplasia (CAH) may present with androgen excess that is difficult to control with conventional suppressive doses of glucocorticoids. Clinical management is challenging, and the woman is at great risk of developing steroid-induced complications. Patients and Methods: A 32-year-old woman with salt-wasting CAH due to 21-hydroxylase deficiency underwent right-sided adrenalectomy because of a large myelolipoma. Over the years, androgens became increasingly difficult to suppress on prednisolone 5+0+2.5 mg daily, and at age 39 years the left adrenal with an enlarging myelolipoma was removed. A month later serum testosterone levels had increased from 4.1 preoperatively to 18.3 nmol/L (reference 0.2-1.8 nmol/L), and adrenocorticotropin levels from 32 to 283 pmol/L (reference <14 pmol/L). No adrenal parenchyma was visualized on computed tomography (CT). In the further search for the source of the markedly elevated testosterone, positron emission tomography (PET) was performed with 2 different tracers, 18fluorodeoxyglucose (18FDG) reflecting glucose metabolism and 11C-metomidate, an inhibitor of 11-β-hydroxylase targeting adrenocortical tissue. Results: 18FDG-PET/CT with cosyntropin stimulation showed ovarian/paraovarian hypermetabolism, suggestive of adrenal rest tumors. Further characterization with 11C-metomidate PET/CT showed uptakes localized to the ovaries/adnexa, behind the spleen, and between the right crus diaphragmaticus and inferior vena cava. Conclusion: Adrenal rest tumors can give rise to high androgen levels in spite of suppressive supraphysiological glucocorticoid doses. This case illustrates, for the first time, the value of 11C-metomidate PET as a sensitive method in documenting adrenal rest tumors, currently considered rare in women with CAH

Optimization of [18F]PSMA-1007 PET-CT using regularized reconstruction in patients with prostate cancer

Background: Prostate-specific membrane antigen (PSMA) radiotracers such as [18F]PSMA-1007 used with positron emission tomography-computed tomography (PET-CT) is promising for initial staging and detection of recurrent disease in prostate cancer patients. The block-sequential regularization expectation maximization algorithm (BSREM) is a new PET reconstruction algorithm, which provides higher image contrast while also reducing noise. The aim of the present study was to evaluate the influence of different acquisition times and different noise-suppressing factors in BSREM (β values) in [18F]PSMA-1007 PET-CT regarding quantitative data as well as a visual image quality assessment. We included 35 patients referred for clinical [18F]PSMA-1007 PET-CT. Four megabecquerels per kilogramme were administered and imaging was performed after 120 min. Eighty-four image series per patient were created with combinations of acquisition times of 1–4 min/bed position and β values of 300–1400. The noise level in normal tissue and the contrast-to-noise ratio (CNR) of pathological uptakes versus the local background were calculated. Image quality was assessed by experienced nuclear medicine physicians. Results: The noise level in the liver, spleen, and muscle was higher for low β values and low acquisition times (written as activity time products (ATs = administered activity × acquisition time)) and was minimized at maximum AT (16 MBq/kg min) and maximum β (1400). There was only a small decrease above AT 10. The median CNR increased slowly with AT from approximately 6 to 12 and was substantially lower at AT 4 and higher at AT 14–16. At AT 4–6, many images were regarded as being of unacceptable quality. For AT 8, β values of 700–900 were considered of acceptable quality. Conclusions: An AT of 8 (for example as in our study, 4 MB/kg with an acquisition time of 2 min) with a β value of 700 performs well regarding noise level, CNR, and visual image quality assessment

Protective ventilation in experimental acute respiratory distress syndrome after ventilator-induced lung injury: a randomized controlled trial

Low tidal volume (V-T), PEEP, and low plateau pressure (P-PLAT) are lung protective during acute respiratory distress syndrome (ARDS). This study tested the hypothesis that the aspiration of dead space (ASPIDS) together with computer simulation can help maintain gas exchange at these settings, thus promoting protection of the lungs. ARDS was induced in pigs using surfactant perturbation plus an injurious ventilation strategy. One group then underwent 24 h protective ventilation, while control groups were ventilated using a conventional ventilation strategy at either high or low pressure. Pressurevolume curves (P-el/V), blood gases, and haemodynamics were studied at 0, 4, 8, 16, and 24 h after the induction of ARDS and lung histology was evaluated. The P-el/V curves showed improvements in the protective strategy group and deterioration in both control groups. In the protective group, when respiratory rate (RR) was approximate to 60 bpm, better oxygenation and reduced shunt were found. Histological damage was significantly more severe in the high-pressure group. There were no differences in venous oxygen saturation and pulmonary vascular resistance between the groups. The protective ventilation strategy of adequate pH or Pa-CO2 with minimal V-T, and high/safe P-PLAT resulting in high PEEP was based on the avoidance of known lung-damaging phenomena. The approach is based upon the optimization of V-T, RR, PEEP, I/E, and dead space. This study does not lend itself to conclusions about the independent role of each of these features. However, dead space reduction is fundamental for achieving minimal V-T at high RR. Classical physiology is applicable at high RR. Computer simulation optimizes ventilation and limiting of dead space using ASPIDS. Inspiratory P-el/V curves recorded from PEEP or, even better, expiratory P-el/V curves allow monitoring in ARDS