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- Broche, Ludovic, et al.
(author)
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Dynamic Mechanical Interactions Between Neighboring Airspaces Determine Cyclic Opening and Closure in Injured Lung
- 2017
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In: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 45:4, s. 687-694
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Journal article (peer-reviewed)abstract
- Objectives: Positive pressure ventilation exposes the lung to mechanical stresses that can exacerbate injury. The exact mechanism of this pathologic process remains elusive. The goal of this study was to describe recruitment/derecruitment at acinar length scales over short-time frames and test the hypothesis that mechanical interdependence between neighboring lung units determines the spatial and temporal distributions of recruitment/derecruitment, using a computational model. Design: Experimental animal study. Setting: International synchrotron radiation laboratory. Subjects: Four anesthetized rabbits, ventilated in pressure controlled mode. Interventions: The lung was consecutively imaged at - 1.5-minute intervals using phase-contrast synchrotron imaging, at positive end expiratory pressures of 12, 9, 6, 3, and 0 cm H2O before and after lavage and mechanical ventilation induced injury. The extent and spatial distribution of recruitment/derecruitment was analyzed by subtracting subsequent images. In a realistic lung structure, we implemented a mechanistic model in which each unit has individual pressures and speeds of opening and closing. Derecruited and recruited lung fractions (F-derecruaed, F-recruited) were computed based on the comparison of the aerated volumes at successive time points. Measurements and Main Results: Alternative recruitment/derecruitment occurred in neighboring alveoli over short-time scales in all tested positive end-expiratory pressure levels and despite stable pressure controlled mode. The computational model reproduced this behavior only when parenchymal interdependence between neighboring acini was accounted for. Simulations closely mimicked the experimental magnitude of F-derecruited and F-recruited when mechanical interdependence was included, while its exclusion gave F-recruited values of zero at positive end -expiratory pressure greater than or equal to 3 cm H2O. Conclusions: These findings give further insight into the microscopic behavior of the injured lung and provide a means of testing protective-ventilation strategies to prevent recruitment/derecruitment and subsequent lung damage.
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- Broche, Ludovic, et al.
(author)
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Individual Airway Closure Characterized In Vivo by Phase-Contrast CT Imaging in Injured Rabbit Lung
- 2019
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In: Critical Care Medicine. - : LIPPINCOTT WILLIAMS & WILKINS. - 0090-3493 .- 1530-0293. ; 47:9, s. E774-E781
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Journal article (peer-reviewed)abstract
- Objectives: Airway closure is involved in adverse effects of mechanical ventilation under both general anesthesia and in acute respiratory distress syndrome patients. However, direct evidence and characterization of individual airway closure is lacking. Here, we studied the same individual peripheral airways in intact lungs of anesthetized and mechanically ventilated rabbits, at baseline and following lung injury, using high-resolution synchrotron phase-contrast CT.Design: Laboratory animal investigation.Setting: European synchrotron radiation facility.Subjects: Six New-Zealand White rabbits.Interventions: The animals were anesthetized, paralyzed, and mechanically ventilated in pressure-controlled mode (tidal volume, 6 mL/kg; respiratory rate, 40; Fio(2), 0.6; inspiratory:expiratory, 1:2; and positive end-expiratory pressure, 3 cm H2O) at baseline. Imaging was performed with a 47.5 x 47.5 x 47.5 mu m voxel size, at positive end-expiratory pressure 12, 9, 6, 3, and 0 cm H2O. The imaging sequence was repeated after lung injury induced by whole-lung lavage and injurious ventilation in four rabbits. Cross-sections of the same individual airways were measured.Measurements and Main Results: The airways were measured at baseline (n = 48; radius, 1.7 to 0.21 mm) and after injury (n = 32). Closure was observed at 0 cm H2O in three of 48 airways (6.3%; radius, 0.350.08 mm at positive end-expiratory pressure 12) at baseline and five of 32 (15.6%; radius, 0.28 +/- 0.09 mm) airways after injury. Cross-section was significantly reduced at 3 and 0 cm H2O, after injury, with a significant relation between the relative change in cross-section and airway radius at 12 cm H2O in injured, but not in normal lung (R = 0.60; p < 0.001).Conclusions: Airway collapsibility increases in the injured lung with a significant dependence on airway caliber. We identify "compliant collapse" as the main mechanism of airway closure in initially patent airways, which can occur at more than one site in individual airways.
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- Porra, Liisa, et al.
(author)
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Synchrotron Imaging Shows Effect of Ventilator Settings on Intrabreath Cyclic Changes in Pulmonary Blood Volume
- 2017
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In: American Journal of Respiratory Cell and Molecular Biology. - : AMER THORACIC SOC. - 1044-1549 .- 1535-4989. ; 57:4, s. 459-467
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Journal article (peer-reviewed)abstract
- Despite the importance of dynamic changes in the regional distributions of gas and blood during the breathing cycle for lung function in the mechanically ventilated patient, no quantitative data on such cyclic changes are currently available. We used a novel gated synchrotron computed tomography imaging to quantitatively image regional lung gas volume (Vg), tissue density, and blood volume (Vb) in six anesthetized, paralyzed, and mechanically ventilated rabbits with normal lungs. Images were repeatedly collected during ventilation and steady-state inhalation of 50% xenon, or iodine infusion. Data were acquired in a dependent and nondependent image level, at zero end-expiratory pressure (ZEEP) and 9 cm H2O (positive end-expiratory pressure), and a tidal volume (V-T) of 6ml/kg(V(T)1) or 9ml/kg(V(T)2) at an Inspiratory: Expiratory ratio of 0.5 or 1.7 by applying an end-inspiratory pause. A video showing dynamic decreases in Vb during inspiration is presented. Vb decreased with positive end-expiratory pressure (P = 0.006; P = 0.036 versus V(T)1-ZEEP and V(T)2-ZEEP, respectively), and showed larger oscillations at the dependent image level, whereas a 45% increase in VT did not have a significant effect. End-inspiratory Vb minima were reduced by an end-inspiratory pause (P = 0.042, P = 0.006 at nondependent and dependent levels, respectively). Normalized regional Vg:Vb ratio increased upon inspiration. Our data demonstrate, for the first time, within-tidal cyclic variations in regional pulmonary Vb. The quantitative matching of regional Vg and Vb improved upon inspiration under ZEEP. Further study is underway to determine whether these phenomena affect intratidal gas exchange.
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- Remes, Tiina Maria, et al.
(author)
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Radiation-induced accelerated aging of the brain vasculature in young adult survivors of childhood brain tumors
- 2020
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In: Neuro-Oncology Practice. - : Oxford University Press (OUP). - 2054-2577 .- 2054-2585. ; 7:4, s. 415-427
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Journal article (peer-reviewed)abstract
- BackgroundCranial radiotherapy may damage the cerebral vasculature. The aim of this study was to understand the prevalence and risk factors of cerebrovascular disease (CVD) and white matter hyperintensities (WMHs) in childhood brain tumors (CBT) survivors treated with radiotherapy.MethodsSeventy CBT survivors who received radiotherapy were enrolled in a cross-sectional study at a median 20 years after radiotherapy cessation. The prevalence of and risk factors for CVD were investigated using MRI, MRA, and laboratory testing. Tumors, their treatment, and stroke-related data were retrieved from patients’ files.ResultsForty-four individuals (63%) had CVD at a median age of 27 years (range, 16-43 years). The prevalence rates at 20 years for CVD, small-vessel disease, and large-vessel disease were 52%, 38%, and 16%, respectively. Ischemic infarcts were diagnosed in 6 survivors, and cerebral hemorrhage in 2. Lacunar infarcts were present in 7, periventricular or deep WMHs in 34 (49%), and mineralizing microangiopathy in 21 (30%) survivors. Multiple pathologies were detected in 44% of the participants, and most lesions were located in a high-dose radiation area. Higher blood pressure was associated with CVD and a presence of WMHs. Higher cholesterol levels increased the risk of ischemic infarcts and WMHs, and lower levels of high-density lipoprotein and higher waist circumference increased the risk of lacunar infarcts.ConclusionsTreating CBTs with radiotherapy increases the risk of early CVD and WMHs in young adult survivors. These results suggest an urgent need for investigating CVD prevention in CBT patients.
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- Remes, Tiina M., et al.
(author)
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Radiation-Induced Meningiomas After Childhood Brain Tumor : A Magnetic Resonance Imaging Screening Study
- 2019
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In: Journal of Adolescent and Young Adult Oncology. - : Mary Ann Liebert. - 2156-5333 .- 2156-535X. ; 8:5, s. 593-601
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Journal article (peer-reviewed)abstract
- Purpose: Childhood brain tumors (CBTs) and their treatment increase the risk of secondary neoplasms (SNs). We studied the incidence of secondary craniospinal tumors with magnetic resonance imaging (MRI) screening in a national cohort of survivors of CBT treated with radiotherapy, and we analyzed the Finnish Cancer Registry (FCR) data on SNs in survivors of CBT with radiotherapy registered as a part of the primary tumor treatment. Methods: A total of 73 survivors of CBT participated in the MRI study (mean follow-up of 19 +/- 6.2 years). The incidence of SNs in a cohort of CBT patients (N = 569) was retrieved from the FCR (mean follow-up of 11 +/- 12.9 years). Brain tumors were diagnosed at age <= 16 years between the years 1970 and 2008 in the clinical study and the years 1963 and 2010 in the FCR population. Results: Secondary brain tumors, meningiomas in all and schwannoma in one, were found in 6 of the 73 (8.2%) survivors with a mean of 23 +/- 4.3 years after the diagnosis of the primary tumor. The cumulative incidence was 10.2% (95% confidence interval [CI] 3.9-25.1) in 25 years of follow-up. In the FCR data, the 25-year cumulative incidence of SNs was 2.4% (95% CI 1.3-4.1); only two brain tumors, no meningiomas, were registered. Conclusion: Survivors of CBT treated with radiotherapy have a high incidence of meningiomas, which are rarely registered in the FCR.
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- Scaramuzzo, Gaetano, et al.
(author)
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Regional Behavior of Airspaces During Positive Pressure Reduction Assessed by Synchrotron Radiation Computed Tomography
- 2019
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In: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 10
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Journal article (peer-reviewed)abstract
- Introduction: The mechanisms of lung inflation and deflation are only partially known. Ventilatory strategies to support lung function rely upon the idea that lung alveoli are isotropic balloons that progressively inflate or deflate and that lung pressure/volume curves derive only by the interplay of critical opening pressures, critical closing pressures, lung history, and position of alveoli inside the lung. This notion has been recently challenged by subpleural microscopy, magnetic resonance, and computed tomography (CT). Phase-contrast synchrotron radiation CT (PC-SRCT) can yield in vivo images at resolutions higher than conventional CT.Objectives: We aimed to assess the numerosity (ASden) and the extension of the surface of airspaces (ASext) in healthy conditions at different volumes, during stepwise lung deflation, in concentric regions of the lung. Methods: The study was conducted in seven anesthetized New Zealand rabbits. They underwent PC-SRCT scans (resolution of 47.7 mu m) of the lung at five decreasing positive end expiratory pressure (PEEP) levels of 12, 9, 6, 3, and 0 cmH(2)O during end-expiratory holds. Three concentric regions of interest (ROIs) of the lung were studied: subpleural, mantellar, and core. The images were enhanced by phase contrast algorithms. ASden and ASext were computed by using the Image Processing Toolbox for MatLab. Statistical tests were used to assess any significant difference determined by PEEP or ROI on ASden and ASext.Results: When reducing PEEP, in each ROI the ASden significantly decreased. Conversely, ASext variation was not significant except for the core ROI. In the latter, the angular coefficient of the regression line was significantly low.Conclusion: The main mechanism behind the decrease in lung volume at PEEP reduction is derecruitment. In our study involving lung regions laying on isogravitational planes and thus equally influenced by gravitational forces, airspace numerosity and extension of surface depend on the local mechanical properties of the lung.
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- Scaramuzzo, Gaetano, et al.
(author)
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The Effect of Positive End-Expiratory Pressure on Lung Micromechanics Assessed by Synchrotron Radiation Computed Tomography in an Animal Model of ARDS
- 2019
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In: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 8:8
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Journal article (peer-reviewed)abstract
- Modern ventilatory strategies are based on the assumption that lung terminal airspaces act as isotropic balloons that progressively accommodate gas. Phase contrast synchrotron radiation computed tomography (PCSRCT) has recently challenged this concept, showing that in healthy lungs, deflation mechanisms are based on the sequential de-recruitment of airspaces. Using PCSRCT scans in an animal model of acute respiratory distress syndrome (ARDS), this study examined whether the numerosity (ASnum) and dimension (ASdim) of lung airspaces change during a deflation maneuver at decreasing levels of positive end-expiratory pressure (PEEP) at 12, 9, 6, 3, and 0 cmH(2)O. Deflation was associated with significant reduction of ASdim both in the whole lung section (passing from from 13.1 +/- 2.0 at PEEP 12 to 7.6 +/- 4.2 voxels at PEEP 0) and in single concentric regions of interest (ROIs). However, the regression between applied PEEP and ASnum was significant in the whole slice (ranging from 188 +/- 52 at PEEP 12 to 146.4 +/- 96.7 at PEEP 0) but not in the single ROIs. This mechanism of deflation in which reduction of ASdim is predominant, differs from the one observed in healthy conditions, suggesting that the peculiar alveolar micromechanics of ARDS might play a role in the deflation process.
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