Investigating the Incidence of Pulmonary Abnormalities as Identified by Parametric Response Mapping in Patients With Lung Cancer Before Radiation Treatment.

Purpose: Parametric response mapping (PRM) of high-resolution, paired inspiration and expiration computed tomography (CT) scans is a promising analytical imaging technique that is currently used in diagnostic applications and offers the ability to characterize and quantify certain pulmonary pathologies on a patient-specific basis. As one of the first studies to implement such a technique in the radiation oncology clinic, the goal of this work was to assess the feasibility for PRM analysis to identify pulmonary abnormalities in patients with lung cancer before radiation therapy (RT). Methods and Materials: High-resolution, paired inspiration and expiration CT scans were acquired from 23 patients with lung cancer as part of routine treatment planning CT acquisition. When applied to the paired CT scans, PRM analysis classifies lung parenchyma, on a voxel-wise basis, as normal, small airways disease (SAD), emphysema, or parenchymal disease (PD). PRM classifications were quantified as a percent of total lung volume and were evaluated globally and regionally within the lung. Results: PRM analysis of pre-RT CT scans was successfully implemented using a workflow that produced patient-specific maps and quantified specific phenotypes of pulmonary abnormalities. Through this study, a large prevalence of SAD and PD was demonstrated in this lung cancer patient population, with global averages of 10% and 17%, respectively. Moreover, PRM-classified normal and SAD in the region with primary tumor involvement were found to be significantly different from global lung values. When present, elevated levels of PD and SAD abnormalities tended to be pervasive in multiple regions of the lung, indicating a large burden of underlying disease. Conclusions: Pulmonary abnormalities, as detected by PRM, were characterized in patients with lung cancer scheduled for RT. Although further study is needed, PRM is a highly accessible CT-based imaging technique that has the potential to identify local lung abnormalities associated with chronic obstructive pulmonary disease and interstitial lung disease. Further investigation in the radiation oncology setting may provide strategies for tailoring RT planning and risk assessment based on pre-existing PRM-based pathology.

State-of-the-art review of the application and development of various methods of aerosol therapy.

Aerosol therapy is a rapidly developing field of science. Due to a number of advantages, the administration of drugs to the body with the use of aerosol therapy is becoming more and more popular. Spraying drugs into the patient's lungs has a significant advantage over other methods of administering drugs to the body, including injection and oral methods. In order to conduct proper and effective aerosol therapy, it is necessary to become familiar with the basic principles and applications of aerosol therapy under various conditions. The effectiveness of inhalation depends on many factors, but most of all on: the physicochemical properties of the sprayed system, the design of the medical inhaler and its correct application, the dynamics of inhalation (i.e. the frequency of breathing and the volume of inhaled air). It is worth emphasizing that respiratory system diseases are one of the most frequently occurring and fastest growing diseases in the world. Accordingly, in recent years, a significant increase in the number of new spraying devices and pharmaceutical drugs for spraying has appeared on the market. It should also be remembered that the process of spraying a liquid is a complicated and complex process, and its efficiency is very often characterized by the use of micro- and macro parameters (including average droplet diameters or the spectrum of droplet diameter distribution). In order to determine the effectiveness of the atomization process and in the delivery of drugs to the patient's respiratory tract, the analysis of the size of the generated aerosol droplets is most often performed. Based on the proposed literature review, it has been shown that many papers dealt with the issues related to aerosol therapy, the selection of an appropriate spraying device, the possibility of modifying the spraying devices in order to increase the effectiveness of inhalation, and the possibility of occurrence of certain discrepancies resulting from the use of various measurement methods to determine the characteristics of the generated aerosol. The literature review presented in the paper was prepared in order to better understand the spraying process. Moreover, it can be helpful in choosing the right medical inhaler for a given liquid with specific rheological properties. The experimental data contained in this study are of great cognitive importance and may be of interest to entities involved in pharmaceutical product engineering (in particular in the case of the production of drugs containing liquids with complex rheological properties).

Functionally weighted airway sparing (FWAS): a functional avoidance method for preserving post-treatment ventilation in lung radiotherapy.

Recent changes to the guidelines for screening and early diagnosis of lung cancer have increased the interest in preserving post-radiotherapy lung function. Current investigational approaches are based on spatially mapping functional regions and generating regional avoidance plans that preferentially spare highly ventilated/perfused lung. A potentially critical, yet overlooked, aspect of functional avoidance is radiation injury to peripheral airways, which serve as gas conduits to and from functional lung regions. Dose redistribution based solely on regional function may cause irreparable damage to the 'supply chain'. To address this deficiency, we propose the functionally weighted airway sparing (FWAS) method. FWAS (i) maps the bronchial pathways to each functional sub-lobar lung volume; (ii) assigns a weighting factor to each airway based on the relative contribution of the sub-volume to overall lung function; and (iii) creates a treatment plan that aims to preserve these functional pathways. To evaluate it, we used four cases from a retrospective cohort of SAbR patients treated for lung cancer. Each patient's airways were auto-segmented from a diagnostic-quality breath-hold CT using a research virtual bronchoscopy software. A ventilation map was generated from the planning 4DCT to map regional lung function. For each terminal airway, as resolved by the segmentation software, the total ventilation within the sub-lobar volume supported by that airway was estimated and used as a function-based weighting factor. Upstream airways were weighted based on the cumulative volumetric ventilation supported by corresponding downstream airways. Using a previously developed model for airway radiosensitivity, dose constraints were determined for each airway corresponding to a <5% probability of airway collapse. Airway dose constraints, ventilation scores, and clinical dose constraints were input to a swarm optimization-based inverse planning engine to create a 3D conformal SAbR plan (CRT). The FWAS plans were compared to the patients' prescribed CRT clinical plans and the inverse-optimized clinical plans. Depending on the size and location of the tumour, the FWAS plan showed superior preservation of ventilation due to airflow preservation through open pathways (i.e. cumulative ventilation score from the sub-lobar volumes of open pathways). Improvements ranged between 3% and 23%, when comparing to the prescribed clinical plans, and between 3% and 35%, when comparing to the inverse-optimized clinical plans. The three plans satisfied clinical requirements for PTV coverage and OAR dose constraints. These initial results suggest that by sparing pathways to high-functioning lung subregions it is possible to reduce post-SAbR loss of respiratory function.

The thermostated medical jet nebulizer: Aerosol characteristics.

The sudden expansion of gas at the outlet of the jet (pneumatic) nebulizer significantly reduces the temperature of the solution, which may provoke bronchospasm, therefore it is recommended to use modern pneumatic inhalers equipped with a thermostat or a universal thermal attachment that allow to obtain a higher temperature aerosol, i.e. thermo-aerosol. The research was carried out for model Newtonian fluids. The droplet diameters of the aerosol spray were investigated using a Spraytec aerosol particle size measurement system. Analysis of the obtained results showed that the increase in solution viscosity caused a decrease in mean droplet diameters and prolonged nebulization time. The analysis of experimental data made it possible to propose a correlation equation describing the mean diameter of the droplets depending on the properties of the liquid and the flow conditions in the thermostated medical nebulizer. The obtained data contributes to a better understanding of the complex liquid atomisation process and can be helpful in the design of medical nebulizers and pharmaceutical preparations.

Treatment data and technical process challenges for practical big data efforts in radiation oncology.

The term Big Data has come to encompass a number of concepts and uses within medicine. This paper lays out the relevance and application of large collections of data in the radiation oncology community. We describe the potential importance and uses in clinical practice. The important concepts are then described and how they have been or could be implemented are discussed. Impediments to progress in the collection and use of sufficient quantities of data are also described. Finally, recommendations for how the community can move forward to achieve the potential of big data in radiation oncology are provided.

Levels of polybrominated diphenyl ethers in house dust in Central Poland.

Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in numerous products, from which they are emitted to the environment, including house dust. House dust is a source of human exposure to these compounds by ingestion. The aim of this article was to determine the levels of selected PBDEs in the house dust and indicate their potential sources of origin. PBDE congeners: BDE-47, BDE-99, BDE-153 and BDE-209, were analyzed in 129 samples. The geometric mean levels (and 95% CIs) of the aforementioned congeners amounted to 3.8 (3.1-4.7) ng/g, 4.5 (3.5-5.6) ng/g, 2.2 (2.1-2.4) ng/g and 345 (269-442) ng/g respectively. BDE-209 was the dominant congener in the majority of tested samples. We found a statistically significant correlation between the concentrations of BDE-47 and the computer operating time per day (rs - 0.18) and the living area (rs - 0.20). Statistically significant higher levels of BDE-99 were found in homes where the floor was not replaced during the last 2 years.

The effect of additional aeration of liquid on the atomization process for a pneumatic nebulizer.

At this paper the effect of aeration on the droplet size distribution of the aerosol have been analyzed. The atomization process was carried out using a pneumatic nebulizer which was equipped with a modified nebulizer cup. This modified nebulizer cup was combined with an additional source of gas bubbles. The measurements of the droplet sizes obtained by the use of the digital microphotography method and analyzed by Image-Pro Plus software. The analysis of the experimental studies proved that an increase in the flow rates of additional gas leads to the increase in the number of small droplets and the decrease of the number of drops of large diameter. Additionally, the mean droplet diameter decreases with the increase of the flow rate of aeration gas. A correlation equation was proposed, which describes the relationship between the mean diameter of droplet and the volumetric flow rate of additional gas. The increase in the bubble volume discharging through a single orifice causes the increase of the flow rate of aeration gas. The modifications of construction of atomizer lead to the better effectiveness of nebulization.

Characterization of sprays for thermo-stabilized pneumatic nebulizer.

The research presents the nebulizer spray chamber temperature controller responsible for controlling temperature of aerosol produced as a result of nebulizing process. The motivation to make an attempt to improve modern pneumatic devices was the shortage of this kind of apparatuses on the market allowing the production of thermos aerosol. A designed temperature controlling system for pneumatic nebulizers aims at increasing and stabilizing temperature of produced aerosols and increasing aerosol therapy safety. The system is intended for producing aerosol in the process of pneumatic nebulization with the temperature similar to that of the human body. Experiments that were carried out confirmed good performance of the device. It was proved that with the increase of temperature the amount of big droplets fall and the entire spectrum of the droplet diameter moves towards smaller droplet diameter values. Reduction of liquid viscosity related to the increase of temperature leads to the reduction of droplet diameter and, as a result, the reduction of the Sauter mean diameter value.

Extracting the normal lung dose-response curve from clinical DVH data: a possible role for low dose hyper-radiosensitivity, increased radioresistance.

In conventionally fractionated radiation therapy for lung cancer, radiation pneumonitis' (RP) dependence on the normal lung dose-volume histogram (DVH) is not well understood. Complication models alternatively make RP a function of a summary statistic, such as mean lung dose (MLD). This work searches over damage profiles, which quantify sub-volume damage as a function of dose. Profiles that achieve best RP predictive accuracy on a clinical dataset are hypothesized to approximate DVH dependence.Step function damage rate profiles R(D) are generated, having discrete steps at several dose points. A range of profiles is sampled by varying the step heights and dose point locations. Normal lung damage is the integral of R(D) with the cumulative DVH. Each profile is used in conjunction with a damage cutoff to predict grade 2 plus (G2+) RP for DVHs from a University of Michigan clinical trial dataset consisting of 89 CFRT patients, of which 17 were diagnosed with G2+ RP.Optimal profiles achieve a modest increase in predictive accuracy--erroneous RP predictions are reduced from 11 (using MLD) to 8. A novel result is that optimal profiles have a similar distinctive shape: enhanced damage contribution from low doses (<20 Gy), a flat contribution from doses in the range ~20-40 Gy, then a further enhanced contribution from doses above 40 Gy. These features resemble the hyper-radiosensitivity / increased radioresistance (HRS/IRR) observed in some cell survival curves, which can be modeled using Joiner's induced repair model.A novel search strategy is employed, which has the potential to estimate RP dependence on the normal lung DVH. When applied to a clinical dataset, identified profiles share a characteristic shape, which resembles HRS/IRR. This suggests that normal lung may have enhanced sensitivity to low doses, and that this sensitivity can affect RP risk.

The effect of shear and extensional viscosities on atomization of Newtonian and non-Newtonian fluids in ultrasonic inhaler.

The paper contains results of the experimental study on atomization process of aqueous solutions of glycerol and aqueous solutions of glycerol-polyacrylamide (Rokrysol WF1) in an ultrasonic inhaler. In experiments the different concentration aqueous solutions of glycerol and glycerol-polyacrylamide have been tested. The results have been obtained by the use of laser diffraction technique. The differences between characteristics of ultrasonic atomization for test liquids have been observed. The analysis of drop size histograms shows that the different sizes of drops have been formed during atomization process. The present study confirmed the previous reports which suggested that the drops size changes with the increase in viscosity of solution changes in spray characteristics were also observed. It has been shown that the shear and extensional viscosities affect the process of atomization.

The effect of shear and extensional viscosity on atomization in medical inhaler.

The paper contains the results of experimental studies of water, aqueous solutions of glycerol and aqueous solutions of glycerol-polyethylene oxide (PEO) atomization process in a medical inhaler obtained by the use of the digital microphotography method. The effect of the shear and extensional viscosity on the drop size, drop size histogram and mean drop diameter has been analyzed. The obtained results have shown that the drop size increases with the increase in shear and extensional viscosity of liquid atomized. Extensional viscosity has a greater impact on the spraying process. It has been shown that the change in liquid viscosity leads to significant changes in drop size distribution. The correlation for Sauter mean diameter as function of the shear and extensional viscosity was proposed.

Sensitivity analysis for lexicographic ordering in radiation therapy treatment planning.

PURPOSE: To introduce a method to efficiently identify and calculate meaningful tradeoffs between criteria in an interactive IMRT treatment planning procedure. The method provides a systematic approach to developing high-quality radiation therapy treatment plans. METHODS: Treatment planners consider numerous dosimetric criteria of varying importance that, when optimized simultaneously through multicriteria optimization, yield a Pareto frontier which represents the set of Pareto-optimal treatment plans. However, generating and navigating this frontier is a time-consuming, nontrivial process. A lexicographic ordering (LO) approach to IMRT uses a physician's criteria preferences to partition the treatment planning decisions into a multistage treatment planning model. Because the relative importance of criteria optimized in the different stages may not necessarily constitute a strict prioritization, the authors introduce an interactive process, sensitivity analysis in lexicographic ordering (SALO), to allow the treatment planner control over the relative sequential-stage tradeoffs. By allowing this flexibility within a structured process, SALO implicitly restricts attention to and allows exploration of a subset of the Pareto efficient frontier that the physicians have deemed most important. RESULTS: Improvements to treatment plans over a LO approach were found by implementing the SALO procedure on a brain case and a prostate case. In each stage, a physician assessed the tradeoff between previous stage and current stage criteria. The SALO method provided critical tradeoff information through curves approximating the relationship between criteria, which allowed the physician to determine the most desirable treatment plan. CONCLUSIONS: The SALO procedure provides treatment planners with a directed, systematic process to treatment plan selection. By following a physician's prioritization, the treatment planner can avoid wasting effort considering clinically inferior treatment plans. The planner is guided by criteria importance, but given the information necessary to accurately adjust the relative importance at each stage. Through these attributes, the SALO procedure delivers an approach well balanced between efficiency and flexibility.

MO-F-BRA-01: A Biomechanical Constraint for Intensity-Driven Deformable Alignment of Skeletal Components in the Head and Neck Region.

PURPOSE: To introduce a biomechanical constraint into an intensity-based deformable image registration (DIR) method in order to limit nonphysical deformations of skeletal components in the neck region. METHODS: On the reference image, vertebral bodies were segmented. A penalty term, based on the differences in squared inter-voxel distances within each vertebra before and after deformation, was introduced into a routinely used (ITK) intensity-based B-spline alignment algorithm. To assess accuracy, deformable image registration was performed on five pairs of cone-beam CT scans of a head and neck cancer patient. Surface registrations of individual vertebrae established their true displacements (translations and rotations). Orthogonal Procrustes analysis of transformed points within each vertebra established the estimated rotations and translations from the resultant deformation vector fields with and without the penalty term. RESULTS: The registration errors across all points within the vertebrae with the penalty term (0.2±0.2, 0.2±0.2, 0.3±0.2) [mm] were significantly lower than without (2.8±2.6, 3.2±2.9, 2.8±3.0) [mm], indicating that employing the penalty term successfully restricted local deformation in the region of the cervical vertebrae. The errors of the bulk translations and rotations of individual vertebrae were similarly reduced: (0.7±0.4, 0.9±0.7, 0.5±0.4) to (O.1±0.1, 0.l+0.1, 0.2±0.2) [mm] for translation and (3.4±2.6, 1.3±1.1, 1.4±1.1) to (0.7±0.6, 0.3±0.2, 0.3±0.3) [°] for rotation. CONCLUSIONS: The introduction of a local rigidity penalty improved the integrity of skeletal alignment under neck articulation. Further research will explore biomechanical penalties that will more realistically constrain the changes of other tissues (e.g. muscles) in the neck region. Supported by NIHR01CA59827.