Search

The authors review the results of 249 patients treated with boron neutron capture therapy (BNCT) at the Helsinki University Hospital, Helsinki, Finland, from May 1999 to January 2012 with neutrons obtained from a nuclear reactor source (FiR 1) and using l-boronophenylalanine-fructose (l-BPA-F) as the boron delivery agent. They also describe a new hospital BNCT facility that hosts a proton accelerator-based neutron source for BNCT. Most of the patients treated with nuclear reactor-derived neutrons had either inoperable, locally recurrent head and neck cancer or malignant glioma. In general, l-BPA-F-mediated BNCT was relatively well tolerated with adverse events usually similar to those of conventional radiotherapy. Twenty-eight (96.6%) out of the evaluable 29 patients with head and neck cancer and treated within a clinical trial either responded to BNCT or had tumor growth stabilization for at least 5 months, suggesting efficacy of BNCT in the treatment of this patient population. The new accelerator-based BNCT facility houses a nuBeam neutron source that consists of an electrostatic Cockcroft–Walton-type proton accelerator and a lithium target that converts the proton beam to neutrons. The proton beam energy is 2.6 MeV operating with a current of 30 mA. Treatment planning is based on Monte Carlo simulation and the RayStation treatment planning system. Patient positioning is performed with a 6-axis robotic image-guided system, and in-room imaging is done with a rail-mounted computed tomography scanner. Under normal circumstances, the personnel can enter the treatment room almost immediately after shutting down the proton beam, which improves the unit capacity. ClinicalTrials.gov ID: NCT00114790. [ABSTRACT FROM AUTHOR]

Despite the prevalence of active smoking in asthmatics, data on the short-term effect of acute mainstream tobacco smoke exposure on airway responsiveness are very scarce. The aim of this study was to assess the immediate effect of acute exposure to mainstream cigarette smoke on airway reactivity to subsequent nonspecific and allergenic challenges in healthy control (n = 5) and ovalbumin-sensitized rabbits (n = 6). We combined low-frequency forced oscillations and synchrotron radiation CT imaging to differentiate central airway and peripheral airway and lung parenchymal components of the response to airway provocation. Acute exposure to smoke generated by four successive cigarettes (CS) strongly inhibited the central airway response to subsequent IV methacholine (MCh) challenge. In the sensitized animals, although the response to ovalbumin was also inhibited in the central airways, mainstream CS did not blunt the peripheral airway response in this group. In additional groups of experiments, exposure to HEPA-filtered CS (n = 6) similarly inhibited the MCh response, whereas CO (10,000 ppm for 4 min, n = 6) or nitric oxide inhalation instead of CS (240 ppm, 4 x 7 min, n = 5) failed to blunt nonspecific airway responsiveness. Pretreatment with [alpha]-chymotrypsin to inhibit endogenous VIP before CS exposure had no effect (n = 4). Based on these observations, the gas phase of mainstream cigarette smoke may contain one or more short-term inhibitory components acting primarily on central airways and inhibiting the response to both specific and nonspecific airway provocation, but not on the lung periphery where both lung mechanical parameters, and synchrotron-imaging derived parameters, showed large changes in response to allergen challenge in sensitized animals. asthma; smoking; tomography; X-ray computed; synchrotrons; respiratory mechanics doi: 10.1152/ajplung.00033.2010.

Ventilation is inhomogeneous in the lungs across species. It has been hypothesized that ventilation inhomogeneity is largely determined by the design of the airway branching network. Because exchange of gases at the alveolar barrier is more efficient when gas concentrations are evenly distributed at subacinar length scales, it is assumed that a 'functional unit' of ventilation exists within the lung periphery, where gas concentration becomes uniform. On the other hand, because the morphology of pulmonary airways and alveoli, and the distribution of inhaled fluorescent particles show self‐similar fractal properties over a wide range of length scales, it has been predicted that fractal dimension of ventilation approaches unity within an internally homogeneous functional unit of ventilation. However, the existence of such a functional unit has never been demonstrated experimentally due to lack of in situ gas concentration measurements of sufficient spatial resolution in the periphery of a complex bifurcating network. Here, using energy‐subtractive synchrotron radiation tomography, we measured the distribution of an inert gas (Xe) in the in vivo rabbit lung during Xe wash‐in breathing manoeuvres. The effects of convective flow rate, diffusion and cardiac motion were also assessed. Fractal analysis of resulting gas concentration and tissue density maps revealed that fractal dimension was always smaller for Xe than for tissue density, and that only for the gas, a length scale existed where fractal dimension approached unity. The length scale where this occurred was seen to correspond to that of a rabbit acinus, the terminal structure comprising only alveolated airways. Key points: Gas ventilation is inhomogeneous in the lung of many species. However, it is not known down to what length scales this inhomogeneity persists.It is generally assumed that ventilation becomes homogeneous at subacinar length scales, beyond the spatial resolution of commonly available imaging techniques, hence this has not been demonstrated experimentally.Here we measured the distribution of inhaled Xe gas in the rabbit lung using synchrotron radiation energy‐subtractive imaging and used fractal analysis to show that ventilation becomes internally uniform within regions about the size of rabbit lung acini. [ABSTRACT FROM AUTHOR]

Background Cranial 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. Methods Seventy 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. Results Forty-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. Conclusions Treating 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 μm) of the lung at five decreasing positive end expiratory pressure (PEEP) levels of 12, 9, 6, 3, and 0 cmH2O 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. [ABSTRACT FROM AUTHOR]

Background: It is not well understood how different ventilation modes affect the regional distribution of ventilation, particularly within the injured lung.Objectives: We compared respiratory mechanics, lung aeration and regional specific ventilation ((Equation is included in full-text article.)) distributions in healthy and surfactant-depleted rabbits ventilated with pressure-regulated volume control (PRVC) mode with a decelerating inspiratory flow or with volume control (VC) mode.Design: Randomised experimental study.Animals and Interventions: New Zealand white rabbits (n = 8) were anaesthetised, paralysed and mechanically ventilated either with VC or PRVC mode (tidal volume: 7 ml kg; rate: 40 min; positive end-expiratory pressure (PEEP): 3 cmH2O), at baseline and after lung injury induced by lung lavage.Main Outcome Measures: Airway resistance (Raw), respiratory tissue damping (G) and elastance (H) were measured by low-frequency forced oscillations. Synchrotron radiation computed tomography during stable xenon wash-in was used to measure regional lung aeration and specific ventilation and the relative fraction of nonaerated, trapped, normally, poorly and hyperinflated lung regions.Results: Lung lavage significantly elevated peak inspiratory pressure (PIP) (P < 0.001). PIP was lower on PRVC compared with VC mode (-12.7 ± 1.7%, P < 0.001). No significant differences in respiratory mechanics, regional ventilation distribution, strain or blood oxygenation could be detected between the two ventilation modes.Conclusion: A decelerating flow pattern (PRVC) resulted in equivalent regional ventilation distribution, respiratory mechanics and gas exchange, in both normal and mechanically heterogeneous lungs with, however, a significantly lower peak pressure. Our data suggest that the lower PIP on PRVC ventilation was because of the decelerating flow pattern rather than the ventilation distribution. [ABSTRACT FROM AUTHOR]

We assessed the changes in regional lung function following instillation of surfactant in a model of respiratory distress syndrome (RDS) induced by whole lung lavage and mechanical ventilation in eight anaesthetized, paralyzed, and mechanically ventilated New Zealand White rabbits. Regional specific ventilation (s...) was measured by K-edge subtraction synchrotron computed tomography during xenon washin. Lung regions were classified as poorly aerated (PA), normally aerated (NA), or hyperinflated (HI) based on regional density. A functional category was defined within each class based on s... distribution (High, Normal, and Low). Airway resistance (Raw), respiratory tissue damping (G), and elastance (H) were measured by forced oscillation technique at low frequencies before and after whole lung saline lavage-induced (100 ml/kg) RDS, and 5 and 45 min after intratracheal instillation of beractant (75 mg/kg). Surfactant instillation improved Raw, G, and H (P < 0.05 each), and gas exchange and decreased atelectasis (P < 0.001). It also significantly improved lung aeration and ventilation in atelectatic lung regions. However, in regions that had remained normally aerated after lavage, it decreased regional aeration and increased s... (P < 0.001) and s... heterogeneity. Although surfactant treatment improved both central airway and tissue mechanics and improved regional lung function of initially poorly aerated and atelectatic lung, it deteriorated regional lung function when local aeration was normal prior to administration. Local mechanical and functional heterogeneity can potentially contribute to the worsening of RDS and gas exchange. These data underscore the need for reassessing the benefits of routine prophylactic vs. continuous positive airway pressure and early "rescue" surfactant therapy in very immature infants. [ABSTRACT FROM AUTHOR]

Highlights: [•] We imaged rabbit lungs using functional synchrotron CT imaging. [•] Inhaled and IV Mch effects on airways and peripheral gas distribution were compared. [•] Inhaled Mch induced more uneven peripheral, but less central bronchial constriction. [•] Heterogeneous inhaled Mch distribution contributes to peripheral heterogeneity. [•] Differences may be due to central–peripheral airway dynamic interdependence. [Copyright &y& Elsevier]

It is not known whether local factors within the airway wall or parenchyma may influence the emergence and spatial distribution of ventilation defects (VDs), thereby modulating the dynamic system behavior of the lung during bronchoconstriction. We assessed the relationship between the distribution of cellular effectors and the emergence of defects in regional ventilation distribution following allergen challenge. We performed high-resolution K-edge subtraction (KES) synchrotron imaging during xenon inhalation and measured the forced oscillatory input impedance in ovalbumin (OVA)-sensitized Brown-Norway rats (n = 12) at baseline and repeatedly following OVA challenge. Histological slices with best anatomic matching to the computed tomographic images were stained with a modified May-Grunwald Giemsa and immunohistochemical staining with monoclonal anti-rat CD68, in six rats. Slides were digitized and total cells and eosinophils were counted in the walls of bronchi and vessels randomly selected within and outside of VDs on the basis of xenon-KES images. Ventilated alveolar area decreased and ventilation heterogeneity, Newtonian resistance, tissue damping, and elastance increased following OVA challenge. Eosinophil, total cell, and CD68+ counts were significantly higher in the bronchial and vascular walls within vs. outside of the VDs. The minimal central airway diameters during OVA-induced bronchoconstriction were correlated with eosinophil (R =-0.85; P = 0.031) and total cell densities (R=-0.82; P = 0.046) in the airway walls within the poorly ventilated zones. Our findings suggest that allergic airway inflammation is locally heterogeneous and is topographically associated with the local emergence of VDs following allergen challenge. [ABSTRACT FROM AUTHOR]

Background: Ventilator-induced lung injury occurs due to exaggerated local stresses, repeated collapse, and opening of terminal air spaces in poorly aerated dependent lung, and increased stretch in nondependent lung. The aim of this study was to quantify the functional behavior of peripheral lung units in whole-lung lavage-induced surfactant depletion, and to assess the effect of positive end-expiratory pressure. Methods: The authors used synchrotron imaging to measure lung aeration and regional specific ventilation at positive end-expiratory pressure of 3 and 9 cm H2O, before and after whole-lung lavage in rabbits. Respiratory mechanical parameters were measured, and helium-washout was used to assess end-expiratory lung volume. Results: Atelectatic, poorly, normally aerated, hyperinflated, and trapped regions could be identified using the imaging technique used in this study. Surfactant depletion significantly increased atelectasis (6.3 3.3 [mean ± SEM]% total lung area; P = 0.04 vs. control) and poor aeration in dependent lung. Regional ventilation was distributed to poorly aerated regions with high (16.4±4.4%; P < 0.001), normal (20.7±5.9%; P < 0.001 vs. control), and low (5.7 ±1.2%; P < 0.05 vs. control) specific ventilation. Significant redistribution of ventilation to normally aerated nondependent lung regions occurred (41.0 ± 9.6%; P = 0.03 vs. control). Increasing positive end-expiratory pressure level to 9 cm H2O significantly reduced poor aeration and recruited atelectasis, but ventilation redistribution persisted (39.2±9.5%; P< 0.001 vs. control). Conclusions: Ventilation of poorly aerated dependent lung regions, which can promote the local concentration of mechanical stresses, was the predominant functional behav¬ior in surfactant-depleted lung. Potential tidal recruitment of atelectatic lung regions involved a smaller fraction of the imaged lung. Significant ventilation redistribution to aerated lung regions places these at risk of increased stretch injury. [ABSTRACT FROM AUTHOR]

The article presents a study that assessed the effects of positive end-expiratory pressure on regional ventilation distribution in normal lung and after histamine-induced bronchoconstriction. The experiment involved 6 healthy New Zealand rabbits that were tracheostomized, paralyzed, and mechanically ventilated. Results showed that in a mechanically ventilated rabbit with severely heterogeneous bronchoconstriction, a positive end-expiratory pressure of five centimeter (cm) water significantly improves regional ventilation homogeneity.

We studied both central conducting airway response and changes in the distribution of regional ventilation induced by inhaled histamine in healthy anesthetized and mechanically ventilated rabbit using a novel xenon- enhanced synchrotron radiation computed tomography (CT) imaging technique, K-edge subtraction imaging (KES). Images of specific ventilation were obtained using serial KES during xenon washin, in three axial lung slices, at baseline and twice after inhalation of histamine aerosol (50 or 125 mg/ml) in two groups of animals (n = 6 each). Histamine inhalation caused large clustered areas of poor ventilation, characterized by a drop in average specific ventilation (sVm), but an increase in sVm in the remaining lung zones indicating ventilation redistribution. Ventilation heterogeneity, estimated as co- efficient of variation (CV) of sVm significantly increased following histamine inhalation. The area of ventilation defects and CV were significantly larger with the higher histamine dose. In conducting airways, histamine inhalation caused a heterogeneous airway response. combining narrowing and dilatation in individual airways of different generations, with the probability for constriction increasing peripherally. This finding provides further in vivo evidence that airway reactivity in response to inhaled histamine is complex and that airway response may vary substantially with location within the bronchial tree. [ABSTRACT FROM AUTHOR]

One of the most fascinating objects in the Rijksmuseum (Amsterdam, The Netherlands) is an early 16th century prayer nut. This spherical wooden object measures 4 cm in diameter and consists of two hemispheres connected with a small hinge so that it can be opened. The interior of the nut holds wood carvings with scenes from the life of Christ. These miniature reliefs show an incredible degree of finish with carving details well beyond the millimetre scale. In the present paper it is shown how synchrotron-based computer X-ray tomography revealed the structure and fabrication method of the bead. The central part of the relief was cut from a single piece of wood, rather than assembled from multiple components, underlining the extraordinary manual dexterity of its maker. In addition, a piece of fibrous material contained in the inner structure of the bead is revealed. This may have served as a carrier for an odorous compound, which would be in line with the religious function of the prayer nut. [ABSTRACT FROM AUTHOR]

Abstract: There is a growing interest in imaging techniques as non-invasive means of quantitatively measuring regional lung structure and function. Abnormalities in lung ventilation due to alterations in airway function such as those observed in asthma and COPD are highly heterogeneous, and experimental methods to study this heterogeneity are crucial for better understanding of disease mechanisms and drug targeting strategies. In severe obstructive diseases requiring mechanical ventilation, the optimal ventilatory strategy to achieve recruitment of poorly ventilated lung zones remains a matter of considerable debate. We have used synchrotron radiation computed tomography (SRCT) for the in vivo study of regional lung ventilation and airway function. This imaging technique allows direct quantification of stable Xenon (Xe) gas used as an inhaled contrast agent using K-edge subtraction imaging. Dynamics of Xe wash-in can be used to calculate quantitative maps of regional specific lung ventilation. More recently, the development of Spiral-CT has allowed the acquisition of 3D images of the pulmonary bronchial tree and airspaces. This technique gives access to quantitative measurements of regional lung volume, ventilation, and mechanical properties. Examples of application in an experimental model of allergic asthma and in imaging lung recruitment as a function of mechanical ventilation parameters will be presented. The future orientations of this tecnique will be discussed. [Copyright &y& Elsevier]

We studied the kinetics of proximal and distal bronchial response to histamine aerosol in healthy anesthetized and mechanically ventilated rabbits up to 60 mm after histamine administration using a novel xenon-enhanced synchrotron radiation computed tomography imaging technique. Individual proximal airway constriction was assessed by measuring the luminal cross-sectional area. Distal airway obstruction was estimated by measuring the ventilated alveolar area after inhaled xenon administration. Respiratory system conductance was assessed continuously. Proximal airway cross-sectional area decreased by 57% of the baseline value by 20 mm and recovered gradually but incompletely within 60 mm. The ventilated alveolar area decreased immediately after histamine inhalation by 55% of baseline value and recovered rapidly thereafter. The results indicate that the airway reaction to inhaled histamine and the subsequent recovery are significantly slower in proximal than in distal bronchi in healthy rabbit. The findings suggest that physiological reaction mechanisms to inhaled histamine in the airway walls of large and small bronchi are not similar. [ABSTRACT FROM AUTHOR]

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 cmH2O. 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. [ABSTRACT FROM AUTHOR]