Palliative intensity modulated radiotherapy of bone metastases based on diagnostic instead of planning computed tomography scans.

Background and purpose: Radiotherapy (RT) treatment planning is as a standard based on a computed tomography (CT) scan obtained at the planning stage (pCT), while most of the decisions whether to treat by RT are based on diagnostic CT scans (dCT). Bone metastases (BM) are the most common palliative RT target. The objective of this study was to investigate if a palliative RT treatment plan of BMs could be made based on a dCT with sufficient accuracy and safety, without sacrificing any treatment quality. Materials and methods: A retrospective study with 60 BMs of 8 anatomical sites was performed. RT planning was performed using intensity-modulated radiation therapy/volumetric modulated arc therapy techniques in dCT and transferred to pCT. The dose of clinical target volumes (CTVs), D(CTVV95%, V50%), were compared between plans for dCT and pCT. Patient setup was investigated in cone-beam CT scans. Results: The differences of D(CTVV95%, V50%) between dCT and pCT plans were the lowest in the pelvis (1.0%, 1.1%), lumbar spine (0.6%, 0.7%) and thoracic spine (0.7%, 2.1%), while the differences were higher in cervical spine (3.7%, 1.9%), long bones (2.3%, 0.8%), and costae (1.6%, 1.4%). The patient set-up was acceptable for 100% of the pelvic and lumbar, for 92% of thoracic spine cases, and for <80% of cases in other sites. Conclusion: This study showed the feasibility of using dCT images in palliative RT planning of BMs in thoracic, lumbar spine and pelvic sites, indicating the potential suitability of this strategy for clinical use.

Fractal dimension of pulmonary gas and blood distribution assessed by synchrotron K-edge subtraction imaging: effect of bronchoconstriction.

We analyzed the fractal dimension (Df) of lung gas and blood distribution imaged with synchrotron radiation K-edge subtraction (KES), in six anesthetized adult New Zealand White rabbits. KES imaging was performed in upright position during stable Xe gas (64% in O2) inhalation and iodine infusion (Iomeron, 350 mg/mL), respectively, at baseline and after induced bronchoconstriction by aerosolized methacholine (125 mg/mL, 90 s) and bronchodilator (salbutamol, 10 mg/mL, 90 s) inhalation, at two axial image levels. Lung Xe and iodine images were segmented, and maps of regional lung gas and blood fractions were computed. The Df of lung gas (DfXe) and blood (DfIodine) distribution was computed based on a log-log plot of variation coefficient as a function of region volume. DfXe decreased significantly during bronchoconstriction (P < 0.0001), and remained low after salbutamol. DfIodine depended on the axial image level (P < 0.0001), but did not change with bronchoconstriction. DfXe was significantly associated with arterial [Formula: see text] (R = 0.67, P = 0.002), and negatively associated with [Formula: see text] (R = -0.62, P = 0.006), respiratory resistance (R = -0.58, P = 0.011), and elastance (R = -0.55, P = 0.023). These data demonstrate the reduced Df of gas distribution during acute bronchoconstriction, and the association of this parameter with physiologically meaningful variables. This finding suggests a decreased complexity and space-filling properties of lung ventilation during bronchoconstriction, and could serve as a functional imaging biomarker in obstructive airway diseases.NEW & NOTEWORTHY Here, we used an energy-subtractive imaging technique to assess the fractal dimension (Df) of lung gas and blood distribution and the effect of acute bronchoconstriction. We found that Df of gas significantly decreases in bronchoconstriction. Conversely, Df of blood exhibits gravity-dependent changes only, and is not affected by acute bronchoconstriction. Our data show that the fractal dimension of lung gas detects the emergence of clustered rather than scattered loss of ventilatory units during bronchoconstriction.

CONTEMPORARY RADIATION DOSES IN INTERVENTIONAL CARDIOLOGY: A NATIONWIDE STUDY OF PATIENT SKIN DOSES IN FINLAND.

In contemporary interventional cardiology, for typical elderly patients, the most severe radiation-related harm to patients can be considered to come from skin exposures. In this paper, maximum local skin doses in cardiological procedures are explored with Gafchromic film dosimetry. Film and reader calibrations and reading were performed at the Secondary Standards Dosimetry Laboratory of the Radiation and Nuclear Safety Authority (STUK), and data were gathered from seven hospitals in Finland. As alert levels for early transient erythema, 200 Gycm2 kerma area product (KAP) and 2000 mGy air kerma levels for transcatheter aortic valve implantations (TAVI) procedures are proposed. The largest doses were measured in TAVI (4158.8 mGy) and percutaneous coronary interventions (PCI) (941.68 mGy). Accuracies of the GE DoseWatch and Siemens CareMonitor skin dose estimates were reasonable, but more results are needed to reliably assess and validate the tools' capabilities and reliabilities. Uncertainty of the Gafchromic dosimetry was estimated as 9.1% for a calibration with seven data points and 19.3% for a calibration with five data points.

CONTEMPORARY RADIATION DOSES IN INTERVENTIONAL CARDIOLOGY: A NATIONWIDE STUDY OF PATIENT DOSES IN FINLAND.

The amount of interventional procedures such as percutaneous coronary intervention (PCI), transcatheter aortic valve implantation (TAVI), pacemaker implantation (PI) and ablations has increased within the previous decade. Simultaneously, novel fluoroscopy mainframes enable lower radiation doses for patients and operators. Therefore, there is a need to update the existing diagnostic reference levels (DRLs) and propose new ones for common or recently introduced procedures. We sought to assess patient radiation doses in interventional cardiology in a large sample from seven hospitals across Finland between 2014 and 2016. Data were used to set updated national DRLs for coronary angiographies (kerma-air product (KAP) 30 Gycm2) and PCIs (KAP 75 cm2), and novel levels for PIs (KAP 3.5 Gycm2), atrial fibrillation ablation procedures (KAP 25 Gycm2) and TAVI (KAP 90 Gycm2). Tentative KAP values were set for implantations of cardiac resynchronization therapy devices (CRT, KAP 22 Gycm2), electrophysiological treatment of atrioventricular nodal re-entry tachycardia (6 Gycm2) and atrial flutter procedures (KAP 16 Gycm2). The values for TAVI and CRT device implantation are published for the first time on national level. Dose from image acquisition (cine) constitutes the major part of the total dose in coronary and atrial fibrillation ablation procedures. For TAVI, patient weight is a good predictor of patient dose.

Pressure-regulated volume control vs. volume control ventilation in healthy and injured rabbit lung: An experimental study.

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 ±â€Š1.7%, 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.

Effect of surfactant on regional lung function in an experimental model of respiratory distress syndrome in rabbit.

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 (sV̇) 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 sV̇ 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 sV̇ (P < 0.001) and sV̇ 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.

Differences in the pattern of bronchoconstriction induced by intravenous and inhaled methacholine in rabbit.

We measured bronchoconstriction in central bronchi, and in small peripheral airways causing the emergence of ventilation defects (VD), through two delivery routes: intravenous (IV) and inhaled MCh, in 2 groups of rabbits (A: n=5; B: n=4), using synchrotron imaging of regional lung structure and ventilation. We assessed the effect an initial IV challenge on a subsequent inhaled challenge in group B. Inhaled MCh decreased central airway cross-sections (CA) by 13-22%, but increased VD area by 25-49%. IV MCh decreased CA by 44% but increased the area of ventilation defects (VD) by 13% only. An initial IV MCh challenge reduced regional ventilation heterogeneity following a subsequent inhaled MCh challenge, suggesting the role of agonist-receptor interaction in the response pattern. Heterogeneous agonist distribution due to uneven aerosol deposition could explain the different patterns of response between IV and inhaled routes. This mechanism could participate in the emergence of ventilation heterogeneities during bronchial challenge, or exposure to allergen in asthmatic patients.

Effect of positive end-expiratory pressure on regional ventilation distribution during mechanical ventilation after surfactant depletion.

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 behavior 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.

Acute cigarette smoke inhalation blunts lung responsiveness to methacholine and allergen in rabbit: differentiation of central and peripheral effects.

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.

Methacholine and ovalbumin challenges assessed by forced oscillations and synchrotron lung imaging.

RATIONALE: Methacholine (Mch) is routinely used to assess bronchial hyperreactivity; however, little is known about the differences in the lung response pattern between this provocation and that observed with ovalbumin (Ova) after allergic sensitization. OBJECTIVES: To compare (1) the central versus peripheral effects of Mch and Ova within the lung by combining measurements of airway and tissue mechanics with synchrotron radiation (SR) imaging, and (2) to assess the extent to which mechanical and imaging parameters are correlated. METHODS: We used the low-frequency forced oscillation technique and SR imaging in control (n = 12) and ovalbumin-sensitized (n = 13) rabbits, at baseline, during intravenous Mch infusion (2.5 microg/kg/min, 5.0 microg/kg/min, or 10.0 microg/kg/min), after recovery from Mch, and after intravenous Ova injection (2.0 mg). We compared intravenous Mch challenge with inhaled Mch (125 mg/ml, 90 s) in a separate group of control animals (n = 5). MEASUREMENTS AND MAIN RESULTS: Airway conductance and tissue elastance were measured by low-frequency forced oscillation technique. The central airway cross-sectional area, the ventilated alveolar area, and the heterogeneity of specific ventilation were quantified by SR imaging. Mch infusion induced constriction predominantly in the central airways, whereas Ova provocation affected mainly the peripheral airways, leading to severe ventilation heterogeneities in sensitized animals. Mch inhalation affected both conducting and peripheral airways. The correlations between airway conductance and central airway cross-sectional area (R = 0.71) and between tissue elastance and ventilated alveolar area (R = -0.72) were strong. CONCLUSIONS: The pattern of lung response caused by intravenous Mch and Ova are fundamentally different. Although inhaled Mch induces a heterogeneous lung response similar to that observed with intravenous allergen, these similar patterns are due to different mechanisms.

Linac-based isocentric electron-photon treatment of radically operated breast carcinoma with enhanced dose uniformity in the field gap area.

BACKGROUND AND PURPOSE: Isocentric treatment technique is a standard method in photon radiotherapy with the primary advantage of requiring only a single patient set-up procedure for multiple fields. However, in electron treatments the size of the standard applicators does not generally allow to use an isocentric treatment technique. In this work we have modified and dosimetrically tested electron applicators for isocentric treatments in combination with photons. An isocentric treatment technique with photons and electrons for postmastectomy radiation therapy (PMRT) has been developed with special emphasis on improving the dose uniformity in the field gap area. MATERIALS AND METHODS: Standard electron applicators of two Varian Clinac 2100CD linear accelerators were shortened by 10cm allowing isocentric treatments of 90cm

Imaging of lung function using synchrotron radiation computed tomography: what's new?

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 technique will be discussed.