Biomedical subjects

T B Martonen

Publications and source records attributed to T B Martonen.

At least 37 records · Page 2Linked to original sources

PubMed1998

Evaluation of the accuracy and precision of lung aerosol deposition measurements from planar radionuclide imaging using simulation.

Planar images of known, theoretical distributions of radioaerosol in the lung have been simulated using lung models derived from magnetic resonance studies on human subjects. Total lung activity was evaluated from the simulated images together with the absolute penetration index (PI) and a relative value expressed as a fraction of that in a simulated ventilation image. The accuracy and precision of these measurements were calculated by comparison with the true values used in the simulation. Total activity was assessed with systematic errors within 5% and precision within 6.5%. Measured PIs varied only slowly with true PI and inter-model variation masked changes between measurements on the different distributions. The relative PI reduced inter-model variation and provided significant differences between all the distributions. PI was significantly affected by misalignment of the lung region of interest. The conducting airways deposition fraction (CADF) used in the simulation correlated linearly with the fractional activity in a central lung region, allowing CADF to be estimated with a precision of 21%.

Aerosols↗

PubMed1998

Supercomputer description of human lung morphology for imaging analysis.

A supercomputer code that describes the three-dimensional branching structure of the human lung has been developed. The algorithm was written for the Cray C94. In our simulations, the human lung was divided into a matrix containing discrete volumes (voxels) so as to be compatible with analyses of SPECT images. The matrix has 3840 voxels. The matrix can be segmented into transverse, sagittal and coronal layers analogous to human subject examinations. The compositions of individual voxels were identified by the type and respective number of airways present. The code provides a mapping of the spatial positions of the almost 17 million airways in human lungs and unambiguously assigns each airway to a voxel. Thus, the clinician and research scientist in the medical arena have a powerful new tool to be used in imaging analyses. The code was designed to be integrated into diverse applications, including the interpretation of SPECT images, the design of inhalation exposure experiments and the targeted delivery of inhaled pharmacologic drugs.

Computer Simulation↗

PubMed1997

Computer simulations of lung morphologies within planar gamma camera images.

A mathematical model and computer code have been developed to unambiguously interpret planar gamma camera images. Specifically, the algorithm permits airway composition of the central, intermediate and peripheral partitions of scans to be determined quantitatively. The algorithm unambigously identifies the spatial coordinates of each of the millions of airways within the adult human lung, and assigns every individual airway to a precise location within the gamma camera image format prescribed by the clinician. This is done on a patient-by-patient basis. The algorithm has evolved from clinical applications of the previous work of Martonen et al. [1]. The objective of the current work was to advance the original protocol and derive an algorithm that was: (1) from a medical perspective, more physiologically realistic; and (2) from a technical perspective, easier to apply in the medical arena. Regarding (1), the major elements of the algorithm are that the outer boundary of the lung is formulated directly from lung perfusion imaging data and that the lung is divided into distinct left and right components. Regarding (2), the algorithm has been written for use with common workstations. It is our hope that the improvements will facilitate applications of the new model-code into aerosol therapy regimens.

Adult↗

PubMed1996

Theoretical relationship of lung deposition to the fine particle fraction of inhalation aerosols.

Pharmaceutical inhalation aerosols intended to deliver drugs to the lungs may be sampled by inertial devices, that divide particle distributions into pre-calibrated diameters. A characteristic particle diameter (D50) is prescribed, below which the aerosol mass is designated the 'respirable fraction'. The following studies compare designated respirable fractions with predicted lower lung deposition. Designated respirable fractions (% of particulate matter < 6.4 microns or alternatively < 9.8 microns) of 30, 40 and 50% were selected to represent typical inhalation aerosols. The compendial inertial samplers used to aerodynamically characterize the particle size of pharmaceutical aerosols operate at approximately 30 or 60 l/min. These values were selected as the volumetric flow rates (Qv) for a mathematical model of lung deposition. The model was employed to predict the lung deposition of particle size distributions giving rise to each designated respirable fraction. Nominal tidal volumes (Tv) of 500 and 1622 ml were adopted at appropriate breathing frequencies to accommodate the designated Qv. Predicted lung depositions (+/- range due to particle size) of 1.4 +/- 0.6%, at a respirable fraction of 30% (Qv = 60 l/min, Tv = 500 ml, D50 = 9.8 microns), and 20.9 +/- 3.6%, at a respirable fraction of 50% (Qv = 30 l/min., Tv = 1622 ml, D50 = 6.4 microns) illustrate the range of results obtained. Under well defined conditions there appeared to be a qualitative correlation between respirable fraction and predicted lower lung deposition. However, this was influenced by the aerosol particle size distribution and breathing parameters.

Aerosols↗

PubMed1996

Assessment of deposition of inhaled aerosol in the respiratory tract of man using three-dimensional multimodality imaging and mathematical modeling.

Multimodality medical imaging enables measurement of the three-dimensional spatial distribution of a radiolabeled aerosol within the lung. Using a conceptual spatial morphological model these data may be transformed to provide information on deposition per airway generation. This methodology has been used to study the intrapulmonary deposition patterns of two formulations of a metered dose inhaler and two nebulizers in control subjects. The nebulizer study has also been stimulated using a computer model of deposition. The comparison between derived experimental results and those from computer modeling shows areas of agreement, although there are also areas of discrepancy. The new methodology has considerable potential value in the fields of inhalation therapy and deposition modeling, although more detailed validation is still required.

Administration, Inhalation↗

PubMed1996

Three-dimensional fluid particle trajectories in the human larynx and trachea.

A computational fluid dynamics software package (FIDAP) has been employed to obtain three-dimensional flow data, which are used herein to calculate the trajectories of fluid particles. Our computations have demonstrated that the flow fields inside the larynx are very complex including eddies in the lumen and reverse motion along the surface. The effects of such flow fields will be to increase the residence times of entrained drug particles. Our computations have also demonstrated that the larynx has pronounced effects on the motion of air in the trachea.

Aerosols↗

PubMed1996

Three-dimensional description of pulmonary deposition of inhaled aerosol using data from multimodality imaging.

UNLABELLED: Three-dimensional assessment of pulmonary deposition of inhaled aerosol may be performed using SPECT. The use of aligned anatomical images enables improved accuracy of quantification and anatomical localization of deposition. METHODS: Techniques of analyzing these data and their application to deposition studies of two nebulizer-generated aerosols (mass median diameter 1.5 and 6.5 microM respectively) in 12 normal subjects are described. The deposition data were transformed to a standard hemispherical shape and the mean distribution pattern for each aerosol evaluated. Deposition by airway generation was then calculated using a spatial model of airway morphology. The results were compared to those from planar image analysis. RESULTS: The hemispherical transform yielded considerably more qualitative information on deposition pattern. The central-to-peripheral concentration ratio between conducting and alveolated airways was 5.27 for the coarser aerosol and 2.43 for the fine. The two-dimensional spatial estimates of the ratio were 2.61 and 2.03 respectively. CONCLUSION: Analysis of multimodality imaging data considerably enhanced information on deposition compared to planar imaging. It provides new data on aerosol deposition which will be of value to physicians involved in drug inhalation therapy.

Aerosols↗

PubMed1995

Computer simulations of human lung structures for medical applications.

Knowledge of the structure of the human lung has salient health effects applications. The clinical issues encompass: (1) aerosol therapy, the targeted delivery of inhaled particles to enhance the efficacies of pharmacologic drugs; and (2) nuclear medicine, where planar gamma camera imaging, Single Photon Emission Computer Tomography (SPECT) and Positron Emission Tomography (PET) assess the distribution patterns of radiolabeled diagnostic particles and gases. If the resolution of such images could be enhanced, medical regimens would greatly benefit. Therefore, the focused objective of our work was to develop 3-D mathematical descriptions of the complex airway networks within the lung. A Silicon Graphics workstation was used to depict the daedal structures. The computer-generated color illustrations presented herein are intended to complement medical investigation. They will assist the clinician by serving as templates for the lung and, thereby, providing a real basis for the analysis of relatively abstract images. The illustrations identify individual airways and could be of great importance to physicians in the treatment of airway diseases occurring at well defined locations (e.g. bronchogenic carcinomas). To demonstrate that computers can be actively integrated into medical research and practice we have addressed SPECT images of a subject. Computer templates will aid future clinical investigators in two major ways: (1) the interpretation of a planar gamma camera, SPECT and PET images; and (2) the design of drug testing protocols using inhalation exposures. Considering their usefulness for demonstration, the lung simulations have the potential of playing a substantive role in education.

Administration, Inhalation↗

PubMed1995

Computer model of human lung morphology to complement SPECT analyses.

Aerosol therapy protocols could be improved if inhaled pharmacologic drugs were selectively deposited within the human lung. The targeted delivery to specific sites, such as receptors and sensitive airway cells, would enhance the efficacies of airborne pharmaceuticals. The high spatial discrimination of deposition patterns of inhaled particles can be determined via Single Photon Emission Computer Tomography (SPECT). However, major problems continue to compromise SPECT protocols. Our work focuses on two issues: how can the spatial discrimination be improved; and how are the images to be interpreted? We present a methodology, described by a mathematical model and supercomputer code, for systematically slicing through the human lung in a prescribed manner that is conducive to implementation into SPECT analyses. The lung is divided into concentric shells, or annuli, and the airway generation-by-generation composition of the respective shells determined. This identification was accomplished by superimposing the new shell structure with the 3-D branching network presented by Martonen et al. [23]. Perhaps the key aspect of the model-code is that the supercomputer is instructed to determine the 3-D spatial coordinates of each of the airways (over 16 million) of the lung with respect to the clinician-selected contours of shells within the lung.

Administration, Inhalation↗

PubMed1994

Mapping the human lung using Delaunay tessellation.

A computer protocol is (1) developed and (2) applied to the human body for medical research. Delaunay tessellation is used to derive an algorithm to describe the structure of the lung. This may be the first application of that mathematical concept to a physiological system. The lung is a complex yet systematic network of pathways described herein with cited dimensions and angles. Its terminal points are the most distal airways, alveolar sacs, defined by their (x, y, z) coordinates. We have addressed that spatial array as a set of points in 3-D space, and, visualized the physical boundary of a lung as the surface of the convex hull of that set in R3. As documented, the enveloping surface of the computer lung closely describes the outer contours of human lungs depicted in clinical studies. Therefore, the model has immediate and salient implications to problems in medicine where respiratory function and morphology have integral roles, specifically, thoracic surgery and aerosol therapy. Examples include the removal of lobes damaged by respiratory diseases such as cystic fibrosis and cancer, and the definition of lung boundaries for gamma camera, PET, and SPECT images. Importantly, the model can be varied to simulate the intersubject differences that physicians experience among a patient population. The mathematical simulations performed in this work are intended to be complementary to laboratory investigations in the medical arena. By providing accurate 3-D, quantitative descriptions of human lungs the supercomputer can be actively integrated into the clinical environment.

Algorithms↗

PubMed1994

Definition of airway composition within gamma camera images.

The efficacies of inhaled pharmacologic drugs in the prophylaxis and treatment of airway diseases could be improved if particles were selectively directed to appropriate sites. In the medical arena, planar gamma scintillation cameras may be employed to study factors affecting such particle deposition patterns within the lung. The value and versatility of such instruments, however, are compromised by the limited resolution of their images. Specifically, it is not possible to determine the composition of their central (C) or large airway, intermediate (I), and peripheral (P) or small airway zones. We present an analytical model to assist the clinician in the systematic analysis and interpretation of gamma camera images. Using the Cray Y-MP supercomputer, a range of human lung morphologies has been mapped to function as templates that can be superimposed on scans. The model is intended to complement laboratory regimens by providing a previously unavailable method to define the C, I, and P zones of the human lung generation by generation. A quantitative value now can be assigned to the degree of overlapping that exists in the images. For example, for a "typical" lung morphology consisting of 16,777,215 airways (total), the C zone itself may contain 1,608,246 airways, of which 1,595,940, or 99.2%, are alveolated airways. By identifying composition, our intent is to integrate the model into future aerosol therapy protocols and thereby assist procedures that target delivery of airborne pharmaceuticals.

Administration, Inhalation↗

PubMed1993

Mathematical model for the selective deposition of inhaled pharmaceuticals.

To accurately assess the potential therapeutic effects of airborne drugs, the deposition sites of inhaled particles must be known. Herein, an original theory is presented for physiologically based pharmacokinetic modeling and related prophylaxis of airway diseases. The mathematical model describes the behavior and fate of particles in the lungs of adult human subjects under various breathing conditions. Their deposition patterns are calculated via superposition of the separate but not independent processes of inertial impaction, sedimentation, and diffusion. The related computer code is designed to calculate total and compartmental (tracheobronchial and pulmonary) distributions of inhaled aerosols. In this manuscript, the model is first tested via comparisons of predicted deposition patterns with laboratory data from human inhalation exposure experiments and then it is applied to determine which factors most influence the dosimetry of inhaled particles. In this format, deposition patterns are explicitly related to particle characteristics, ventilatory parameters, and intersubject variabilities of lung morphologies. The dosimetric model was developed to improve the efficacy of aerosol therapy via the selective deposition of inhaled pharmaceuticals at prescribed lung locations to elicit optimum effects.

Administration, Inhalation↗

PubMed1993

Deposition patterns of aerosolized drugs within human lungs: effects of ventilatory parameters.

A mathematical model for inhaled aerosolized drugs is validated by comparisons of predicted particle deposition values with experimental data from adult subject inhalation exposure tests. The model is subsequently used to study the effects of ventilatory parameters on particle deposition patterns within the human lung. By altering breathing profiles, deposition values can be affected regarding quantity delivered and spatial location. Increased tidal volumes and breath-holding times increase deposition in the pulmonary region, while increased inspiratory flow rates increase deposition in the tracheobronchial region. Based upon fluid dynamics considerations (Reynolds numbers), an original method of partitioning the lung is also presented. The model has implications with regard to aerosol therapy, indicating that the efficacies of inhaled pharmacological drugs in the prophylaxis and treatment of airway diseases can be improved by regulating breathing profiles to deposit particles selectively at prescribed sites within the lung.

Adult↗

PubMed1993

Behavior of hygroscopic pharmaceutical aerosols and the influence of hydrophobic additives.

The high temperature and relative humidity in the lung can result in the hygroscopic growth of susceptible aerosol particles or droplets. The term hygroscopic growth describes the increase in particle diameter which occurs as the result of association with water vapor. The influence of hygroscopicity upon lung deposition of aerosols has been a productive area of research in industrial hygiene, environmental sciences, and inhalation toxicology. Many pharmaceutical inhalation aerosols display hygroscopic behavior in their passage through the airways; however, the effect has been neglected. Controlling the phenomenon of hygroscopic growth and, thus, the related lung deposition of aerosols might result in the therapeutic advantage of targeting the site of action. Such an approach might also allow identification of the location of pharmacologic receptor sites in the lung. This Review discusses an approach to achieving control of hygroscopic growth of aerosol particles. Theoretical and experimental studies have indicated that inhaled particle diameters increased significantly for drugs commonly administered to the lung. The presence of certain additives, notably glycerol, cetyl alcohol, and lauric and capric acids, has been demonstrated to reduce the growth of particles under conditions approaching those in the lung. Very few quantitative studies of the nature discussed herein have appeared in the literature. It is conceivable that an aerosol particle could be fabricated of known initial size and density, and by implication, deposition characteristic, and this might be induced to follow specific growth kinetics to enhance deposition in a particular region of the lung. Thus, physical targeting of regions within the lung might be achieved.

Aerosols↗

PubMed1992

Use of analytically defined estimates of aerosol respirable fraction to predict lung deposition patterns.

Analytical estimates of the respirable fractions on inhaled pharmaceutical aerosols are obtained by inertial sampling techniques. The respirable fraction may be defined as that portion of the particle size distribution less than a designated diameter. The diameter size below which particles were considered respirable in these studies was 6.4 microns. In clinical practice, a variety of particle size distributions may be related to a single respirable fraction. Herein, three respirable fractions were each defined by six particle size distributions. The deposition patterns of aerosols exhibiting these particle size characteristics were examined in a mathematical model. The analytically defined respirable fractions were compared with predicted lung deposition values. Under clearly defined breathing conditions, there is a correlation between the nominal respirable fraction and deposition. However, it was concluded that the variations which occur in breathing parameters within patient populations may not allow a single analytically derived respirable fraction to be appropriate for all individual subjects.

Adult↗

PubMed1992

Deposition patterns of cigarette smoke in human airways.

Experimental deposition patterns of cigarette smoke in surrogate human airway systems are very heterogeneous. Particle deposits are enhanced at predictable, well-defined morphological regions; most specifically, carinal ridges within bifurcation zones and along posterior sections of tubular airways. The efficiency of the mucociliary transport mechanism in vivo is also reduced at airway branchings. The geometrical sites of preferential particle deposition and impaired clearance can be correlated with clinically observed anatomical sites exhibiting increased incidences of bronchogenic carcinomas. These locations are not compatible with current theoretical models simulating only the usual particle deposition processes of inertial impaction, sedimentation, and diffusion, while intending to account for particle hygroscopicity. Moreover, data from human subject exposures indicate that heretofore unknown factors affect the distribution of inhaled cigarette smoke. Herein, a new mathematical model is presented that explains cigarette smoke deposition patterns, including bifurcation "hot spots," in terms of composition and cumulative density. The behavior of mainstream cigarette smoke can be related to physicochemical parameters of its particulate and vapor-gas phases and is a result of two distinct effects: (1) particle cloud motion and (2) vapor-gas behavior. In lung airways, Effect 1 is the most prominent. The high particle number,ns approximately equal to 3 x 10(9) cm-3, and mass,rho s approximately equal to 10(-4) g cm-3, concentrations of smoke dictate that a bolus of it has kinetic properties of an entity (Effect 1 above), independent of the aerodynamic size characteristics of individual constituent particles. This motion may be exacerbated by the bulk movement (Effect 2 above) of the vapor-gas phase density of smoke.

Bronchi↗

PubMed1989

Structural differences between human and rat lungs: implications for Monte Carlo modeling of aerosol deposition.

The geometrical structure of the lung is one of the main factors governing inhaled particle deposition; structural differences among different species are, therefore, of great importance for extrapolation modeling. A statistical analysis of morphometric data for the human and rat tracheobronchial tree reveals significant interspecies differences in airway branching patterns: compared to the relatively dichotomous and symmetric structure of the human lung, the rat lung displays a more monopodial airway branching pattern. Thus, for the rat lung, we recommend characterizing the properties of a given airway, i.e., its size, physiologic function, and distance from the trachea, by its diameter rather than by a theoretically assigned generation number. A Monte Carlo method is used to construct an airway geometry along each inhaled particle's path by randomly selecting airway parameters from their frequency distributions and the correlations among them. While the airway geometry is selected randomly, particle deposition in individual airways is calculated analytically. These stochastic deposition calculations allow for structural differences between the human and rat lung, and the variability of the airway system within each species.

Aerosols↗

PubMed1989

Human subject age and activity level: factors addressed in a biomathematical deposition program for extrapolation modeling.

A deterministic aerosol deposition model, previously validated by data from adult inhalation exposure experiments, is used to study particle deposition within the developing human lung. Here, two age-dependent lung morphologies are presented, in which the number of tracheobronchial (TB) generations is complete at birth but airway dimensions vary with age; the number of pulmonary (P) generations, however, changes with age, as do the alveolated airway dimensions. Deposition patterns within the two morphologies are compared. For the light and heavy respiratory-activity levels considered, regional TB and P, and total (TB + P) lung deposition fractions are calculated. For all particle sizes (0.2-9.0 microns diameters) tested, total deposition in both morphologies was minimal for the 30-y-old adult and maximal for either of the youngest subjects (7 and 22 mo old). A breakdown of total deposition into lung compartments was specifically addressed for one morphological model. Age-dependent deposition models are intended to aid in future extrapolation efforts to assess the threat to human health from airborne contaminants.

Adult↗