Rochester Institute of Technology RIT Scholar Works

Theses

2008

Imaging the airways

Betsy Skrip

Follow this and additional works at: https://scholarworks.rit.edu/theses

Recommended Citation Skrip, Betsy, "Imaging the airways" (2008). Thesis. Rochester Institute of Technology. Accessed from

This Thesis is brought to you for free and open access by RIT Scholar Works. It has been accepted for inclusion in Theses by an authorized administrator of RIT Scholar Works. For more information, please contact [email protected]. ROCHESTER INSTITUTE OF TECHNOLOGY

A Thesis Submitted to the Faculty of The College of Imaging Arts and Sciences In Candidacy for the Degree of MASTER OF FINE ARTS

IMAGING THE AIRWAYS 3D Modeling of a Complete Respiratory Airway for Use in Computational Flow Dynamics Studies of Particle Deposition in the Lungs

Creation of an Educational Animation about the Respiratory System for Use in the Human Visualization Project and CollaboRITorium

ETSY SKRIP Medical Illustration

Date Approved: October 7, 2008 IMAGING THE AIRWAYS 3D Modeling of a Complete Respiratory Airway for Use in Computational Flow Dynamics Studies of Particle Deposition in the Lungs Creation of an Educational Animation about the Respiratory System for Use in the Human Visualization Project and CollaboRITorium

Betsy Skrip Medical Illustration, Rochester Institute of Technology

ABSTRACT CONTENTS

The IMAGING THE AIRWAYS thesis project is a multidiscipline and INTRODUCTION 1 multimedia endeavor consisting of two main parts: I. 3D Modeling of a Complete Respiratory Airway for Use in Computational Flow Dynamics Part I.I Bronchi/Bronchiole Model Studies of Particle Deposition in the Lungs and II. Creation of an Educational ORIGINAL THESIS STATEMENT 2 Animation about the Respiratory System for Use in RIT’s Human Visualization BACKGROUND 2 Project and CollaboRITorium. THE BODY OF WORK 4 CONCLUSIONS 8 Part I involved collaboration with RIT’s Mechanical Engineering Department to construct a 3D model of one complete respiratory pathway, from the Part I.2 Respiratory Membrane oral cavity to the site of gas exchange between the lungs and the blood. ORIGINAL THESIS STATEMENT 10 The project is a continuation of thesis work completed by Jackie Russo, MS BACKGROUND 10 Mechanical Engineering, Class of 2007 and Jessica Weisman, MFA Medical THE BODY OF WORK 12 Illustration, Class of 2007. Russo and Weisman constructed a model of the CONCLUSIONS 16 upper respiratory tract, from the oral cavity to generation 5 (as defined by Des Jardins, 2007). Weisman also constructed a model of a respiratory Part I.3 Promotional Materials acinus (generation 20-28). ORIGINAL THESIS STATEMENT 17 BACKGROUND 17 Part I of the IMAGING THE AIRWAYS thesis project involved creating a THE BODY OF WORK 17 Maya model of generations 6-19 to bridge the two existing models and CONCLUSIONS 38 creating a Maya model of the respiratory membrane to study nanoparticle translocation from the lungs to the blood. Part I of the project also involved Part II Respiratory System creating promotional materials that were featured in the March 17-April 9, Animation 2008 thesis show and at the 2008 Imagine RIT Innovation and Creativity ORIGINAL THESIS STATEMENT 39 Festival. The promotional materials consist of a 35” x 43” poster, a postcard, BACKGROUND 39 a website, and a one-minute promotional video. THE BODY OF WORK 40 CONCLUSIONS 46 Part II of the project involved creating a 5-minute animation about the respiratory system for use by RIT’s Human Visualization Project (HVP) and CollaboRITorium, as well as an HVP website. OVERALL CONCLUSIONS 50 ACKNOWLEDGEMENTS 50 REFERENCES 50 INTRODUCTION

The IMAGING THE AIRWAYS proj- Studies of Particle Deposition in Part I.I Bronchi/Bronchiole Model ect consists of two main parts, with the Lungs Modeling of the respiratory path be- the first part further separated into The main thesis project, conducted for tween the upper tract and a respira- three sections. RIT’s Mechanical Engineering Depart- tory acinus. ment under the direction of thesis su- Part I. 3D Modeling of a Com- pervisors Dr. Risa Robinson, Jim Perkins, Part I.2 Respiratory Membrane plete Respiratory Airway for Use and Glen Hintz, as well as professors Modeling of the respiratory membrane in Computational Flow Dynamics Nancy Ciolek and Ann Pearlman. at the cellular and molecular levels in

1 IMAGING THE AIRWAYS Part I.I ORIGINAL THESIS STATEMENT, BACKGROUND order to visualize nanoparticle trans- el will then be meshed to the two Jackie Russo (MS Mechanical Engi- port from the lungs into the blood- existing models to form one com- neering, Class of 2007) and Jessica stream. plete model. Weisman (MFA Medical Illustration, Class of 2007)–designed their thesis Part I.3 Promotional Materials The complete model will be im- projects to model parts of the re- Creation of promotional materials for ported into two computational flow spiratory system using 3D comput- the project to educate the RIT commu- dynamic engineering software pro- er software. The models were then nity and other interested audiences. grams (Fluent and Comsol) in order analyzed using engineering compu- to study particle flow and deposi- tational flow dynamics software in Part II. Creation of an Educational tion in the lungs. order to study fluid flow and par- Animation about the Respiratory ticle deposition in the respiratory System for Use in the Human Vi- Effectiveness and accuracy of the system. model will be evaluated based on sualization Project and CollaboRI- comparisons to published data, Russo and Weisman produced the Torium such as that derived from biological following models: An animation and website created for specimens. RIT’s Human Visualization Project and 1. A model of the upper respira- CollaboRITorium under the direction of Current methods for creating an ac- tory tract thesis supervisors, as well as Dr. Rich- curate model of the respiratory air- Created by Russo (2007) and Weis- ard Doolittle, Shaun Foster, and Dr. ways include scanning and creating man (2007) Jake Noel-Storr. casts from cadavers; however, these This model consists of three mod- methods create only a static model. els, each created using different The main contribution of working methods: (1) the oral cavity, (2) the in Maya is the ability to generate a oropharynx, laryngeopharynx, and Part I.I Bronchi/Bronchiole Model modifiable model in which research- larynx, and (3) the trachea through Modeling of the respiratory path be- ers can vary different parameters of bronchi generation 5. tween the upper tract and a respira- the tract’s morphometry and exam- tory acinus. ine the effects of those variations. 2. A model of a respiratory aci- nus The ability to alter different param- Created by Weisman (2007) ORIGINAL THESIS STATEMENT eters of an airway model will en- This model was constructed us- hance research to better define the ing the same overall methods and The aim of this project is to create mechanics of breathing and changes consists of generations 20-28 (the a 3D computer-generated model of in particle flow and deposition respiratory bronchioles, alveolar generations 6-19 of a single respira- among different disease states, such ducts, and alveolar sacs). tory airway. as asthma and emphysema. Several systems exist for number- The model will bridge existing com- Maya also allows for the creation of a ing the structures of the respira- puter-generated models created for more organically shaped model than tory tree. Differences among these use by the Mechanical Engineer- current engineering CAD (Com- systems result in part because the ing Department: models extending puter-Aided Design) programs. number of branches beyond the from the oral cavity to generation 5 bronchi differ among individuals and and a model of a single acinus (gen- among the lungs’ regions. For this erations 20-28). BACKGROUND project, Des Jardin’s (2007) system was used, in which the structures The end product of this project will Over several years, Dr. Risa Robin- are numbered as follows: be a complete model of a respira- son in RIT’s Mechanical Engineering tory airway extending from the oral Department and Dr. Richard Doo- Generation cavity to the alveoli. little in RIT’s Allied Health Sciences Trachea 0 Department have spearheaded stu- Main stem bronchi 1 The model will be constructed in dent research to better understand Lobar bronchi 2 Maya from published data of airway the mechanics of breathing. Segmental bronchi 3 dimensions (e.g., papers authored Subsegmental bronchi 4-9 by Weibel and Horsfield). The mod- In 2006, two graduate students– Bronchioles 10-15

2 IMAGING THE AIRWAYS Part I.I BACKGROUND

Terminal bronchioles 16-19 Using Gambit, Russo calculated a them with Russo and Weisman’s Respiratory bronchioles 20-23 higher air velocity and turbulence in models. This effort would thereby Alveolar ducts 24-27 the smoker model. For the particle establish a complete pathway from Alveolar sacs 28 deposition analysis, Russo injected the oral cavity (the site of gas ex- 0.1-µm (micrometer), 1-µm, 3-µm, change between the atmosphere Generations 0-19 are termed “con- 5-µm, 9-µm, and 10-µm particles and the lungs) to the respiratory ducting” structures, for they channel into both models and calculated membrane (the site of gas exchange air from the mouth and nose to the deposition in five regions: the oral between the lungs and the blood). respiratory acini (as well as in the cavity, throat (i.e, the oropharynx, To the best of our knowledge, such opposite direction from the acini laryngeopharynx, and larynx), tra- a model has never before been cre- to the atmosphere). Gas exchange chea, left main bronchi, and right ated. with the blood occurs within the main bronchi. respiratory acini, which each consist Completing the pathway would in- of generations 20-28. Russo found that over twice as many volve creating a model of genera- particles deposited in the smoker tions 6-19 (to connect the models Previous Research model than in the non-smoker of the upper respiratory tract and In her study, 3D Reconstruction of a model. Specifically, Russo found the respiratory acinus) and a model Female Lung Using the Visible Human that in the smoker model, 45% of all of the respiratory membrane (see Data Set to Predict Cigarette Smoke particles deposited in the upper air- Part 1.2). Particle Deposition, Russo utilized way, and in the non-smoker model, two upper respiratory models: one only 21% of the particles deposited In order to provide more detail with the normal oral cavity model in the airway. about the overall, collaborative (meant to represent a non-smoker) modeling project and to establish a and one with an oral cavity model Russo’s results suggest that the clearer understanding of the meth- in which the casting material was si- greater air velocity and turbulence ods used to construct Parts I.1 and phoned through a straw (represent- in the smoker airway somehow in- I.2, the following is a summary of the ing the mouth structure of a smoker fluence particle deposition. Russo methods used to create the origi- at the time of inhalation). hypothesizes that, instead of flow- nal model’s individual parts. (Note: ing smoothly along the contours of These descriptions, with some varia- Russo’s procedure for importing the airway as they would in a non- tions, also appear on the IMAGING the upper respiratory models into smoker, the particles in a smoker’s THE AIRWAYS website, http://www. the computational flow dynamics lungs become forcefully propelled betsyskrip.com/thesis.) software involves three main steps: into the airway walls, where they then remain. The oral cavity models 1. Importing the original models Created by Russo (2007) generated with Maya or 3D Doc- Russo’s results further suggest that The oral cavity models were made tor into VP-Sculpt for refinement in a smoker, more particles are likely from a cast of a female student’s and to combine the separate model to become trapped in the upper air- mouth. Aquasil Ultra LV Smart components into one model. way, whereas in a non-smoker, more Wetting Impression Material was particles are likely to continue flow- spooned into the student’s mouth 2. Importing the VP-Sculpt models ing to deeper parts of the respira- and allowed to dry. For the non- into Solid Works in order to con- tory system. smoker model, the mouth was left vert the models from a surface tex- slightly open and at rest. For the ture to a closed volume. (The sur- For future research, Russo pro- smoker model, the casting mate- face model represents the physical, poses analyzing airflow and particle rial was also siphoned through a hollow-interior airway, whereas the deposition in those deeper regions, straw placed in the student’s mouth closed volume model represents such as in Jessica Weisman’s model (in order to represent the mouth the space inside the airway.) of the acinus. structure of a smoker at the time of inhalation). 3. Importing the Solid Works mod- Therefore, the IMAGING THE AIR- els into computational flow dynam- WAYS thesis project (specifically, After the impressions were made, ics software, such as Gambit, Com- Parts I.1 and I.2) sought to construct they were scanned at a resolution sol, or Fluent. models of the deeper regions of the of 0.003 inches using the Model respiratory system and to combine Maker Z140 3D Scanner with a

3 IMAGING THE AIRWAYS Part I.I BACKGROUND, THE BODY OF WORK

Romer Cimcore Infinite Arm. The The acinus model deposition at the farthest regions of arm attachment was used to trace Created by Weisman (2007) the respiratory system. over the surface of the casts and Dimensions of the acinus were ob- tranferred the data into the com- tained through scanning electron A complete pathway model in gen- puter to create a 3D model. microscopy. The acinus from a male eral would also allow for the deter- human lung was observed through mination of the transition point at The oropharynx, laryngophar- a scanning electron microscope which particles stop moving by con- ynx, and larynx model (SEM), and the dimensions of the vection and begin moving by diffu- Created by Weisman (2007) respiratory bronchioles, alveolar sion. Broadly, this phenomenon re- The oropharynx, laryngopharynx ducts, and alveolar sacs were mea- sults from the mixing of inhaled air and larynx model was based on sured. and residual air (i.e., air that remains dimensions taken from multiple in the lungs even after a forceful ex- sagittal and anterior medical pho- Sketches were made and used in halation). It is suspected that each tographs of cadavers and a partial Maya to create a 3D model. lobe has its own transition point; cadaver cast of the throat. therefore, our model would en- Present Research able determination of the transition The cadaver of an elderly woman As previously mentioned, the upper point in the lower posterior lobe of was prepared, and silicone rubber respiratory model extends to only the left lung. was injected through the bottom of the 5th generation of branching. the trachea and through the mouth. Branches beyond the 5th genera- tion were indistinguishable on the THE BODY OF WORK The casting material was then al- Female Visible Human slices. There- lowed to dry and removed from the fore another method was devised to Horsfield et al. (1971) categorize cadaver. Sketches were made and create a model of generations 6-19 the branches into orders, which they used in Maya to create a 3D model. (subsegmental bronchi, bronchioles, describe as follows: “...the most dis- and terminal bronchioles) to bridge tal branches comprise the first or- The trachea to generation 5 the models of the upper respiratory der, two of these meet to form a model tract and the respiratory acinus. second-order branch, and so on.” Created by Russo (2007) Whereas the branching generations The trachea/bronchi model was cre- Without access to a human cast, defined by Des Jardins (2007) are ated using slices of the thoracic cav- the best solution was to use data numbered from top-down (i.e., with ity from the Female Visible Human published by Horsfield et al. (1971). the trachea labeled as 0, the main Project. The slices were imported The researchers created a resin cast bronchi as 1, and so forth), orders into 3D Doctor and converted to of the respiratory tree from a male are numbered from bottom-up. greyscale in order to increase con- cadaver and measured the lengths, trast among the different anatomical diameters, and angles of branching For our model, the required Hors- structures. Outlines of the desired for all structures down to 0.7 mm field et al. (1971) data were orga- structures were then generated by in diameter. They then broke off a nized into Table 1. A sketch was the software based on those con- single branch to measure structures also made in order to visualize the trasts. Some boundaries were also smaller than 0.7 mm in diameter. correlation between the Des Jar- drawn and refined by hand. dins’ (2007) branch generations and For our model, the data set chosen Horsfield et al.’s system of orders The software rendered a 3D surface was for the pathway corresponding (Figure 1). model by connecting the defined to what Horsfield et al. define as the outlines from all of the segmented lower posterior lobe of the left lung. Modeling in Maya images using polygon-based surfac- The left lung was chosen arbitrarily; Each branch was first modeled sep- es. The file was exported as an OBJ however, the pathway to the lower arately as a polygon cube with the and imported into VP-Sculpt for posterior lobe was selected specifi- correct length and width (which be- further processing. VP-Sculpt was cally because of its length. From the came the diameter once the model used to smooth the surface and to oral cavity, air must flow the great- was smoothed). Edge loops were trim or delete incomplete branches. est distance to reach the lower pos- inserted at the top and bottom of Specifically, branches beyond the terior lobe than to any other lobe. each model to prevent reduction 5th generation were trimmed off. Therefore, our model would allow of the central diameter when the for analysis of airflow and particle models were smoothed.

4 IMAGING THE AIRWAYS Part I.I THE BODY OF WORK

Horsfield et al.’s data provide the Table 1 Dimensions for the pathway supplying the lower poste- numerical values for each angle of rior lobe of the left lung branching, which they define as “the Branch Order Diameter Length Angle angle by which the line of the axis of Gen. (mm) (mm) (°) the daughter branch deviates from the line of the axis of the parent 6 23 5.50 10.20 32 branch.” In this system, the branch- 7 22 3.90 7.60 30 es are categorized from top-down, 8 21 4.80 10.00 32 with parent branches being a lower 9 20 3.30 8.93 30 order number than their daughter branches. 10 19 3.37 8.00 30 11 18 3.14 13.68 30 However, Horsfield et al. (1971) 12 17 2.87 9.05 36 do not indicate in which direction 13 16 2.60 7.12 36 (right or left) each branch deviates 14 15 2.46 7.26 36 from the parent axis. Several imag- es were used as references in order 15 14 2.33 6.90 36 to determine the directions, such as 16 13 2.16 5.50 36 images from Pernkopf (1980) and 17 12 1.95 4.91 43 Des Jardins (2007). However, dif- 18 11 1.70 4.83 43 ferences existed among the differ- ent models, and many of the lower 19 10 1.43 4.01 43 branches were either obscured by other branches or too small to dis- cern. Orders Gen.

In addition, Horsfield et al.’s data 23a 23a 6 also do not include the branch an- gles’ deviation from the parent axis 22a 19b 22a, 19b 7 anteriorly or posteriorly.

21a 18b 21a, 18b 8 Therefore, in order to estimate the branching angle directions, a model of the left lung was constructed in 20a 17b 20a, 17b 9 3D Doctor, and the bronchi/bron- 19a, 16b 10 chiole model was constructed to 19a 16b fit within the lower posterior lobe. 18a 15b 18a, 15b 11 Specifically, the individual branch models were placed inside of the lung model and adjusted to fit with- 17a 14b 17a, 14b 12 in the lower posterior region. The final directions and angles are listed 16a 13b 16a, 13b 13 in Table 2. 15a 12b 15a, 12b 14

After the angles of branching were 14a 11b 14a, 11b 15 set in the x-axis for each individual branch model, the models were 13a 10b 13a, 10b 16 12a, 9b 17 combined (Mesh > Combine). The 12a 9b 11a 8b 11a, 8b 18 bottom face of each parent branch 10a 7b 10a, 7b 19 was cut in the z-axis, and the two resulting faces were deleted, leav- Figure 1 An initial sketch of the bronchi/bronchiole model comparing the order ing UVs in the center of the two numbers to the generation numbers. The “a” and “b” designations were not parallel edges. The face of the top used by Horsfield et al.; they were implemented to facilitate keeping track of the 27 branches. of each daughter branch was also

5 IMAGING THE AIRWAYS Part I.I THE BODY OF WORK deleted, and the top UVs on each Figure 2. the z-axis (anteriorly or posterior- daughter branch were then merged ly) in order to fit the model within to their corresponding UVs on the The overall model was then the boundaries of the lung model. bottom of the parent branch. smoothed, and a rig was created with a joint at each point of bifurca- The history for the bronchi/bron- The combined, unsmoothed indi- tion. The model was bound to the chiole model was then deleted (in vidual branch models are shown in rig, and the joints were rotated in order for the model to keep its

Table 2 Angles of branching The individual branch models for each order were first positioned roughly within the lung model in order to estimate their directions of branching–either right (+) or left (-) from the parent branch from edge loop an anterior view. The final angles were then calculated by adding Horsfield et al.’s (1971) angles of branching to the calculated final edge loop angles of the parent branches. The final angles were then entered into the “Rotate x” field in Maya for each of the branch models.

Order Horsfield Direc- (Angle x direction) Final et al. tion + final angle of angle (°) angle (°) (+/-) parent branch (°)

23a 32 - -32 + 0 -32 22a 30 + 30 + (-32) -2 21a 32 + 32 + (-2) 30 20a 30 - -30 + 30 0 19a 30 + 30 + 0 30 18a 30 - -30 + 30 0 17a 36 + 36 + 0 36 16a 36 - -36 + 36 0 15a 36 + 36 + 0 36 14a 36 - -36 + 36 0 13a 36 + 36 + 0 36 12a 43 - -43 + 36 -7 11a 43 + 43 + (-7) 36 10a 43 - -43 + 36 -7

19b 30 - -30 + (-32) -62 18b 30 - -30 + (-2) -32 17b 36 + 36 + 30 66 16b 36 - -36 + 0 -36 15b 36 + 36 + 30 66 Figure 2 Left side view of the initial bronchi/bronchi- ole model. The indivial orders (branches) were mod- 14b 36 - -36 + 0 -36 eled as polygon cubes, with lengths and widths entered 13b 36 + 36 + 36 42 from Horsfield et al.’s (1971) data. Edge loops are vis- ible around the top and bottom edges of the topmost 12b 43 - -43 + 0 -43 branch. The edge loops served to maintain the branch 11b 43 + 43 + 36 79 diameters when the model was smoothed. Afterwards, 10b 43 - -43 + 0 -43 a rig was attached to the model, with a joint at each point of bifurcation (i.e., the point at which 2 daughter 9b 43 + 43 + 36 79 branches deviate from a parent branch). The model was 8b 50 - -50 + (-7) -57 then smoothed and given an overall white color. 7b 50 + 50 + 36 86

6 IMAGING THE AIRWAYS Part I.I THE BODY OF WORK

Joint Angle (°) 23a 1 -27.295 23a 19b 19b 22a 2 0 22a 21a 21a 18b 3 0 17b 4 -16.437 18b 17b 20a 20a 16b 19a 19a 5 31.400 15b 6 -4.887 16b 15b 18a 18a 17a 14b 7 -18.957 17a 14b 13b 16a 8 6.272 13b 16a 12b 9 0 15a 15a 11b 12b 11b 14a 10 25.688 14a 10b 13a 13a 11 -5.560 9b 10b 9b 12a 12a 12 -17.706 11a 11a 8b 8b 7b 13 0 7b 10a 10a 14 0

Figure 3 Anterior view of the final Figure 4 Left side view of the final bronchi/bronchiole model, with the bronchi/bronchiole model, with the Figure 5 Left side view of the final branch orders labelled. The sequence branch orders labelled. A rig was bronchi/bronchiole model. A Maya of orders remains the same as in Figure created with a joint at each point of rig was created in the model, with 1, however the directions of the branch- bifurcation, and the joints were rotated a joint at each point of bifurcation. es was altered to fit the model within in the z-axis in order to fit the model Each joint’s angle of rotation in the lower posterior region of the left- within the lower posterior region of the Maya’s z-axis is listed. lung model created with 3D Doctor. left-lung model created in 3D Doctor.

shape once the rig was removed). For approximately 600 slices, 6th generation branch of the bron- The rig was deleted, and the model boundary lines were hand-drawn chi/bronchiole model fit to the 5th was exported as an OBJ to be im- around the edges of the left lung, as generation branch of Russo’s mod- ported into VP-Sculpt. well as around the trachea and dis- el, and so that the 19th generation cernible bronchi (Figures 6 and 7). branch reached the bottom edge of Figures 3 and 4 show the final model The computer then generated a 3D the lung model (leaving some space from the anterior and side views. model from the stack of boundary for generations 20-28). lines, and the model was saved as an Figure 3 lists the joints and their OBJ file and imported into Maya. The lung model, trachea/bronchi angles of rotation (in Maya) in the model, and bronchi/bronchiole z-axis. In order to ensure that the bron- model (with rig) are shown in Fig- chi/bronchiole model and the lung ure 8. 3D Doctor Lung Model model were approximately the The model of the left lung was con- same scale, Russo’s (2007) tra- structed in 3D Doctor using slices chea/bronchi model was used as a from the thoracic region of the Fe- guide. The 3D Doctor model was male Visible Human Project (VHP), scaled in Maya so that its trachea similar to Jackie Russo’s methods and bronchi portions fit directly for constructing the trachea/bron- over Russo’s model. The two mod- chi model. els were then scaled so that the

7 IMAGING THE AIRWAYS Part I.I THE BODY OF WORK, CONCLUSIONS

Figure 6 In 3D Doctor, boundaries (green lines) were drawn Figure 7 A screen shot from 3D Doctor with the list of slices (top around the edges of the lungs, as well as around the trachea and left), the boundary outline from an anterior view (bottom right), and discernible bronchi, for approximately 600 Female Visible Human the boundary outline from a side view (bottom left). At this stage, Project slices. boundaries for only the top portion of the lung were completed.

CONCLUSIONS

Creation of the bronchi/bronchiole (generations 6-19) model provided valuable experience in problem solving, as multiple challenges were overcome: • where to obtain data since the lower generations are not discern- ible in the VHP slices, and no cast of those structures was available for SEM analysis • how to arrange the branches and angle them anteriorly and posteri- orly, since the Horsfield et al. (1971) article does not provide such data.

The project was also a reinforce- ment of modeling skills using Maya and a learning experience using 3D Doctor.

After the bronchi/bronchiole model was completed in Maya, it was ex- ported as an OBJ file and success- fully imported into VP-Sculpt. Cur- rent RIT students in Mechanical Engineering and Medical Illustration will connect the model to the up- per respiratory and acinus models and conduct computational flow Figure 8 3/4 view in Maya of the left-lung model created in 3D Doctor, Russo’s trachea/ dynamics (CFD) studies with the bronchi model, and the bronchi/bronchiole model (with joints, which are colored). The complete airway model. trachea and bronchi portions of the lung model were scaled to fit over Russo’s trachea/ bronchi model, and the bronchi/bronchiole model was angled to fit within the lung model. To the best of our knowledge, this model will be the first model of a

8 IMAGING THE AIRWAYS Par t I.I CONCLUSIONS

complete respiratory pathway–one that extends from where oxygen enters to where gas exchange oc- curs with the blood.

Future plans with the complete air- way model include studying the ef- fects of changes in lung morphom- etry due to certain disease states, such as asthma. In an asthmatic, the airways become contricted; in Maya, the dimensions of the airway model components can be altered (e.g., di- ameters reduced) to represent the airway of an asthmatic.

Knowledge of how airflow and par- ticle deposition compare between asthmatic and healthy airways would aid in the treatment of asthma, in- cluding the design of more effective inhalation therapy methods.

Future plans also include using more of Horsfield et al.’s data to constuct a pathway model for each lobe of the left and right lungs. CFD research with such models would show how and where air flows and particles deposit not only within each pathway, but also throughout the respiratory tree. Mechanical Engineering researchers would also be able to determine the transition point (i.e, the point at which parti- cles stop moving by convection and begin moving by diffusion) for each lobe.

Also, once more of the airways are constructed, a 3D printout of the entire model will be generated for demonstration purposes.

9 IMAGING THE AIRWAYS Par t I.2 ORIGINAL THESIS STATEMENT, BACKGROUND

gram used in common practice to NPs are manufactured, or engi- Part I.2 Respiratory Membrane study particle deposition. neered, particles, created through Modeling of the respiratory membrane the growing field of nanotechnology. at the cellular and molecular levels in Knowles (2006) defines nanotech- order to visualize nanoparticle trans- BACKGROUND nology as: “the design, character- port from the lungs into the blood- ization, production, and application stream. Research for the IMAGING THE of structures, devices, and systems AIRWAYS thesis project was initi- by controlling shape and size at the ated in Summer 2007. An extensive nanometer scale.” Further, Orber- ORIGINAL THESIS STATEMENT literature review about the respi- dorster et al. (2005) state that the ratory system was conducted, and term NP “includes only spherical Gas exchange in the lung requires several articles of current interest [particles]; other engineered nano- the diffusion of molecules across an were selected as references. Spe- sized structures will be labeled ac- extremely thin membrane, known as cifically, articles were chosen con- cording to their shape, for example, the blood-air barrier. With a thick- cerning nanoparticle translocation nanotubes, nanofibers, nanowires, ness of only 500 nm (nanometers) across the respiratory membrane. nanorings, and so on.” or less, this membrane represents the interface between a capillary According to Orberdorster et al. UFPs are created unintentionally as lumen and a pulmonary alveolar air (2005), “Berry et al. (1977) were the by-products of natural and anthro- space. first to describe the translocation of pogenic processes. Gwinn and Val- NSPs (nanosized particles) across lyathan (2006) state that the term Other 3D models of the respira- the alveolar epithelium.” Berry et ultrafine “is frequently used to de- tory system do not extend beyond al. (1977) reported that 30 minutes scribe nanometer-size particles that the alveolar level (~250,000 nm in after injecting 30-nm colloid gold have not been intentionally pro- diameter). The goal of this project particles into the tracheas of rats, duced but are the incidental prod- is to continue this visual reduction the particles were found within ucts of processes involving industri- to the nanoscale level (less than platelets of the alveolar capillaries. al, combustion, welding, automobile, 100 nm), in an effort to model cel- diesel, soil, and volcanic activities.” lular and molecular detail of the In more recent studies with rats respiratory membrane’s five main and humans, UFPs (ultrafine par- Nanoparticles and NSPs are general components: (1) surfactant (a lipid ticles) have been shown to cross terms that include NPs and UFPs. monolayer), (2) surface lining fluid, from the lungs into the systemic cir- Knowles (2006) defines nanopar- (3) alveolar epithelial cells, (4) base- culatory system to reach the liver, ticles as particles that are “found ment membrane, and (5) endothe- heart, spleen, lymph nodes, kidneys, widely in the natural world as prod- lial cells. and bone marrow (Orberdorster et ucts of photochemical and volcanic al. 2005). activity, created in plants and algae, Recent research has shown that and from products of combustion, nanoparticles (particles less than Nanoparticles, NSPs, NPs, food cooking, and diesel exhaust; 100 nm in at least one dimension) and UFPs also manufactured particles such as can cross the respiratory mem- According to McShane (2006), “No metal oxides (titanium dioxide, zinc brane; however, the mechanisms of standard definitions have been es- oxide); used in cosmetics, textiles, transport are not well known. tablished for the terms UFPs and paints, targeted drug delivery sys- nanoparticles, which has led to tems, and sunscreens.” In order to understand the pos- some confusion because the words sible health effects and medical ap- are often used interchangeably.” Health Effects of Nanopar- plications of nanoparticle inhalation, From the articles researched, four ticles use of virtual and real models will terms were encountered: nanopar- The physical and chemical proper- help to define these mechanisms of ticles, NSPs (nanosized particles), ties of a material differ between the transport. NPs (engineered nanoparticles), macroscopic and nanoscale levels. and UFPs (ultrafine particles). All In particular, nanoparticles have a In particular, respiratory membrane four terms refer to particles with much larger surface area per unit models created in Maya will serve diameters <100 nm. However, the mass, which is considered to make as models in a computational flow origin of the particles differ. them more reactive. According to dynamic engineering software pro- Orberdorster et al. (2005), “This

10 IMAGING THE AIRWAYS Part I.2 BACKGROUND increased biologic activity can be poor.” Gwinn and Vallyathan (2006) • Geiser et al. (2005): “To date, the either positive and desirable (e.g., state: “One major challenge facing mechanisms by which UFPs pen- antioxidant activity, carrier capacity industry and government is the lack etrate boundary membranes...are for therapeutics, penetration of cel- of information on the possible ad- largely unknown.” lular barriers for drug delivery) or verse health effects caused by ex- negative and undesirable (e.g., toxic- posure to different nanomaterials.” • Gwinn and Vallyathan (2006): ity, induction of oxidative stress or Therefore, as Yacobi et al. (2007) “...currently the process of UFP of cellular dysfunction), or a mix of summarize, “Further knowledge translocation is poorly under- both.” about the mechanisms by which stood...” particles injure, interact with and/or Harmful effects of UFPs to the are transported across the alveo- • Rothen-Rutishauer et al. (2006): respiratory system and extrapul- lar epithelium is thus of consider- “So far, little is known about the in- monary organs have already been able importance for understanding teraction of nanoparticles with lung documented through studies with health effects related to inhalation cells, the entering of nanoparticles, humans, rats, and in vitro cell cul- of ultrafine [and engineered nano-] and their transport through the tures. Adverse respiratory and particles in ambient air.” blood stream [sic] to other organs. cardiovascular effects resulting in ...The entering mechanisms for morbidity and mortality have been Mechanisms of Transport nanoparticles into cells are still not associated with UFPs in air pollution While numerous studies have yet known.” (Orberdorster et al. 2005; Gwinn shown that nanoparticles cross the and Vallyathan 2006). In laboratory respiratory membrane to enter the Such statements indicate a sig- experiments, UFPs have induced in- bloodstream and extrapulmonary nificant need for research about flammatory responses in rats and in organs, many studies also state that nanoparticle mechanisms of trans- vitro cell cultures, and caused oxida- little is known about how nanopar- port across the respiratory mem- tive stress to in vitro cell cultures, ticles cross the respiratory mem- brane. Therefore, it was decided for resulting in changes to gene expres- brane: the IMAGING THE AIRWAYS thesis sion and cell signalling pathways project to create a model of the re- (Orberdorster et al. 2005). • Berry et al. (1977): “The pathways spiratory membrane using available by which inhaled metallic particles data and to study fluid flow and par- While such effects may be undesir- cross the gas exchanging surface in ticle movement through the model able for normal cells, they could be the pulmonary alveoli (where only using CFD (compuational flow dy- utilized through NPs for anticancer the finest particles are deposited), namics) analysis. treatments and gene therapy appli- must be identified in order to study cations. Also, because NPs can be the action of those contaminants on Maya models were created of the coated with biological micromol- the respiratory system and on the respiratory membrane’s five main ecules such as antibodies and pro- body generally. The mechanism of layers: surfactant (a lipid monolay- teins and can travel to target organs this migration still remains uncer- er), surface lining fluid, an alveolar from the respiratory system, they tain and controversial.” Type I epithelial cell (with lipid bi- are being developed for drug deliv- layer and caveolae), basement mem- ery and as in vivo and in vitro immu- • Churg (2000): “The determinants brane (made of proteins perlecan, nofluorescent probes (Gwinn and of particle uptake remain poorly laminin, entactin, and collagen IV), Vallyathan 2006). defined....It is still impossible to and an endothelial cell (with lipid provide any generalized explana- bilayer and caveolae). The potential for NPs to cause tion of the marked differences in adverse health effects still exists, uptake seen with different types of However, challenges existed to us- however, particularly for NPs that particles, and little is known of the ing the model in Mechanical Engi- may be released into the environ- mechanisms of this process.” neering CFD studies: ment through maufacturing pollu- tion and degradation of products • Hoet et al. (2004): “The litera- (1) Mechanisms of transport through through normal use and disposal. ture on the translocation of very or between cells According to McShane (2006), “... small particles from the lung into Numerous methods have been pro- the current state of knowledge the blood circulation is limited and posed for how nanoparticles move concerning the exposure risks as- often conflicting.” across cell boundaries. Examples sociated with nanotechnology are include:

11 IMAGING THE AIRWAYS Par t I.2 BACKGROUND, THE BODY OF WORK

• diffusion with experts in biology, chemistry, face lining fluid, an alveolar Type • caveolae transport (transcytosis) and nanotechnology–people who I epithelial cell (with lipid bilayer • receptor-mediated transcytosis could not only generate new data and caveolae), basement membrane • movement between cellular tight for us to work from, but to also (made of proteins perlecan, laminin, junctions help us interpret existing data. entactin, and collagen IV), and an en- dothelial cell (with lipid bilayer and Diffusion and movement through With these concerns in mind, a caveolae). cellular tight junctions could easily meeting was established in the be studied through CFD analysis. Fall 2007 quarter with Dr. Gunter The models were constructed from However, the current model rep- Orberdorster, Professor of Environ- available data and are to scale. resents only a representative sec- mental Medicine at the University of tion of an alveolar Type I cell and an Rochester and author of numerous Table 3 lists the dimensions of each endothelial cell; therefore, another papers about nanotoxicology. Dr. respiratory membrane component model would have to be construct- Orberdorster was shown the respi- and the references from which the ed in order to include cellular tight ratory membrane model; however, data was obtained. Table 4 shows junctions. Further, CFD cannot eas- he confirmed that much informa- some of the models and their rela- ily be used to study transcytosis be- tion is lacking in the scientific com- tive sizes, and Figure 9 shows the cause the process involves biologi- munity in terms of understanding basement membrane model. Fig- cal and chemical factors, including how nanoparticles cross the respi- ure 10 shows the complete respi- caveolae movement along cytoskel- ratory membrane. ratory membrane model in scale etal elements. compared to a model of one red The decision was eventually made blood cell, and Figure 11 labels the (2) Properties of basement membrane to change the focus of the thesis components of the complete respi- proteins research from nanoparticle translo- ratory membrane model. Although the basement membrane cation across the respiratory mem- proteins were modeled based on brane to completing the respiratory Orientation of the basement available data, the representations pathway model using data that was membrane components are more iconic than literal. Even known to exist. Other Mechanical The basement membrane models space-filling, ball-and-stick, and sur- Engineering students could then were organized according to de- face models are representations of follow Russo’s (2007) methods for scriptions by Crouch et al. (1991) the spaces occupied by electrons, conducting the computational flow and from an illustration of a base- and do not represent molecules as dynamics studies, and Russo’s data ment membrane by David Goodsell literal solid structures. Therefore, in could be compared with the newly (2000). order to run CFD analysis through generated data. the basement membrane model, we The entactin models were placed to would need to learn more about Research using the respiratory link the collagen IV models to the the chemical properties of the indi- membrane model would be con- laminin models where the short vidual proteins (such as polarity and ducted when more resources and arms of laminin intersect. other factors that could influence background data became avail- interactions with nanoparticles). able. In the meantime, the model The core protein of the perlecan was used for promotional materials models were placed within the base- (3) Properties of nanoparticles about the IMAGING THE AIRWAYS ment membrane meshwork, with Different nanoparticle properties, project and in the Human Visualiza- the heparan sulfate chains extending such as size, charge, surface chem- tion Project animation about the along the surface of the basement istry, and concentration of particles structure of the respiratory sys- membrane adjacent to the epithe- may influence which mechanism of tem. lial cells. According to Crouch et al. transport is used. Therefore, for (1991), the heparan sulfate chains our study, we would need to learn form a negatively charged barrier more about the properties of cer- THE BODY OF WORK that prevents the passage of nega- tain types of nanoparticles. tively charged molecules greater Over Summer 2007, Maya models than 3-5 nm in diameter. Moving Forward were constructed of the respiratory In order for our research to be membrane’s five main components: The perlecan models were arranged credible, we would need to work surfactant (a lipid monolayer), sur- in groups of three, according to the

12 IMAGING THE AIRWAYS Par t I.2 THE BODY OF WORK

Goodsell (2000) illustration. nally arranged with bonds between collagen IV was based on a diagram the globules of two molecules and by Crouch et al. (1991); however, The laminin models were connect- between the N-terminals of four the authors state that their model ed by the globules at the ends of the molecules. However, the models represents “the most extended four arms. The models were rigged were rearranged in order to bet- structure, which is likely to be very with a Maya joint system in order to ter simulate the greater density of much condensed via lateral aggrega- bend them around the other base- collagen IV molecules beneath the tion.” Therefore, the original col- ment membrane protein models. meshwork of entactin, laminin, and lagen IV models could be modified, perlecan, as illustrated by David such as with a Maya joint system, in Future Work Goodsell (2000). order to create a more condensed In the current model, the heparan collagen IV meshwork. sulfate chains extend only toward As shown in Figure 9, the collagen the alveolar Type I epithelial cell. IV models are still arranged with Future research could also involve Future work with the model should bonds between two globules; how- using protein models from the Pro- involve creating a second layer of ever, the ends of the models are no tein Data Bank (PDB) and other perlecan models oriented in the op- longer arranged in groups of four. public-domain molecular imaging posite direction, with the heparan Future work with the model should sites. At the time the IMAGING sulfate chains facing the endothelial involve using the collagen IV models THE AIRWAYS protein models cell. in their orginal orientation. were constructed in Maya, no com- plete models of the proteins were The collagen IV models were origi- The orginal, rigid arrangement of found on the PDB, only specific do- mains of those proteins. Table 3 Dimensions used to create the respiratory membrane model *The thickness of the basement membrane was calculated using the following formula: ([thickness of respiratory membrane] - [(thickness of surfactant) + (thickness of surface lining fluid) + (thickness of alveolar Type I epithe- lial cell) + (thickness of endothelial cell)]). STRUCTURE DIMENSIONS REFERENCE Respiratory Membrane thickness = 0.5 µm (500 nm) Fawcett (1986) Basement Membrane thickness = 80 nm calculated* Surfactant thickness (length of lipid) = 3.5 nm lipid bilayer thickness)/2 Surface Lining Fluid thickness = 15-20 nm Patton (1996) Alveolar Type I epithelial cell diameter = 81 µm (81, 000 nm) Patton (1996) thickness = 0.2 µm (200 nm) Fawcett (1986) Endothelial cell length = 36 µm (36, 000 nm) Patton (1996) thickness = 200 nm Simionescu (1991) Caveolae opening diameters ≈ 40 nm Patton (1996) internal diameters ≈ 50-100 nm Patton (1996) Lipid Bilayer thickness (from polar head to polar Campbell and Reece (2002) head) = 7-8 nm Entactin length = 20 nm Rohrbach and Timpl (1993) Perlecan core protein length = 80 nm www.uku.fi/anatomialPG/perlecan.htm Perlecan Heparin Sulfate Chains thickness = 3-4 nm Rohrbach and Timpl (1993) length = 50 nm Rohrbach and Timpl (1993) Laminin long arm length = 75 nm Hay (1981) 3 short arm lengths = 35 nm Hay (1981) arm diameters = 2 nm Hay (1981) globule lengths = 5-7 nm Hay (1981) Collagen IV length = 300 nm www.answers.com/topic/collagen?cat=health diameter = 1.5 nm www.answers.com/topic/collagen?cat=health Red Blood Cell diameter = 7 µm (7,000 nm) Knowles (2006) 13 IMAGING THE AIRWAYS Par t I.2 THE BODY OF WORK

Table 4 Maya models of respiratory- membrane components

Lipid bilayer (7 nm)

Magnified view

Nanoparticle (20 nm)

Entactin (20 nm)

Perlecan

Heparan sulfate chain Figure 9 The basement membrane model (view from below, as the joining of three (50 nm) perlecan molecules can be seen)

Core protein (80 nm)

Laminin (110 nm)

Figure 10 The respiratory membrane model and a model of a red blood cell, to scale

Collagen (300 nm)

14 IMAGING THE AIRWAYS Part I.2 THE BODY OF WORK

Surfactant Surface lining fluid Lipid bilayer

Alveolar Type I epithelial cell

Caveolae

Lipid bilayer

Basement membrane Lipid bilayer

Endothelial cell

Caveolae

Lipid bilayer

Nanoparticle

Blood plasma

Figure 11 Complete model of the respiratory membrane

15 IMAGING THE AIRWAYS PART I.2 CONCLUSIONS

CONCLUSIONS

Creating the respiratory membrane model honed valuable research skills, as well as modeling skills in Maya.

The respiratory membrane model and its use in the Human Visualiza- tion Project animation were signifi- cant first steps into this area of re- search, not only for RIT researchers, but also for the scientific community at large. As previously stated, little is known about the mechanisms by which nanoparticles cross the respiratory membrane. However, piecing together what data is cur- rently available has allowed for the creation of a model that will serve as the foundation for RIT’s future studies about the respiratory mem- brane. In fact, such research is being conducted over the Summer 2008 quarter, where the model was suc- cessfully imported into VP-Sculpt.

Again, to the best of our knowledge, this model is the first model of the respiratory membrane–one that in- cludes all layers and their compo- nents (i.e., surfactant; surface lining fluid; an alveolar epithelial cell with lipid bilayer and caveolae; the base- ment membrane with proteins per- lecan, laminin, entactin, and collagen IV; and an endothelial cell with lipid bilayer and caveolae).

The model will not only be used for CFD analysis, but also serves as a visual aid for helping researchers to better understand the structure of the respiratory membrane.

16 IMAGING THE AIRWAYS Part I.3 ORIGINAL THESIS STATEMENT, BACKGROUND, THE BODY OF WORK

THE BODY OF WORK Image color, size, and resolution PART I.3 Promotional Materials were also considered and adjusted Creation of promotional materials for Promotional materials for the IM- for printing in CMYK at a relatively the project to educate the RIT commu- AGING THE AIRWAYS thesis proj- large size. nity and other interested audiences. ect consist of a poster, a postcard, a website, and a one-minute video. THE POSTCARD These materials were presented Figures 13-14 ORIGINAL THESIS STATEMENT in the March 17-April 9, 2008 the- Dimensions: 4.25” x 6” sis show in the Bevier Art Gallery. Media: Illustrator, Photoshop No written proposal was submitted The poster, website, and video were for Part 1.3 of the project. Howev- also presented at Imagine RIT, May The postcard was designed specifi- er, it was discussed with thesis advi- 3, 2008. cally to advertise the March 17-April sors that the promotional materials, 9, 2008, thesis show and for visitors featured in the March 17-April 9, Images associated with the upper to take. The design of the front of 2008 thesis show, would be a poster, respiratory and acinus models were the postcard mimics the design of a website, and a video. acquired from a PowerPoint de- the poster. signed by Jackie Russo for her thesis defense. All other research images BACKGROUND were created from Parts 1.1 and THE WEBSITE I.2 of the IMAGING THE AIRWAYS Figures 15-29 The poster, postcard, website, and thesis project. Media: Flash, Illustrator, Photoshop video were inspired and created http://www.betsyskrip.com/thesis through assignments in two classes: 1. An independent study in Nancy THE POSTER The IMAGING THE AIRWAYS web- Ciolek’s Information Design class Figure 12 site was first designed as a Power- 2. Ann Pearlman’s Digital Video Dimensions: 35” x 43” Point in Professor Nancy Ciolek’s class Media: Illustrator, Photoshop Information Design class. The im- ages, text, and design elements were The Information Design class greatly The IMAGING THE AIRWAYS then transferred into Flash. helped to reinforce the principles of poster was designed in Professor good design, such as structure (e.g., Nancy Ciolek’s Information Design The design for the original Power- alignment through use of the grid class. Many design principles were Point also influenced the design for system), emphasis (e.g., of words applied, such as: all of the IMAGING THE AIRWAYS and images with use of color, size, • alignment of text and images promotional materials. The colors, and style), and information flow. through use of the grid system fonts, project logo, and other ele- Principles were reinforced with ex- • establishment of information hier- ments are consistent among the amples from innovators in informa- archy through use of font size and website, poster, postcard, and video. tion design, such as Edward Tufte, as color well as through class critiques, both • establishment of relationships The website buttons were designed throughout the design process and among pieces of information using Photoshop and Illustrator. on project due dates. through use of color (e.g., all mod- Some button logos were created els created as part of the IMAGING in Photoshop by altering the origi- The Digital Video class was an in- THE AIRWAYS thesis project are nal images (i.e., isolating the models valuable introduction to Final Cut highlighted in orange-red to match from their backgrounds and making Pro and helped to reinforce the the title along the left side of the the models solid white). All other principles of filming and documen- poster) logos were created in Illustrator tary design, such as digital-video- • information flow (e.g., the com- either with the pen tool or with camera use, lighting, sound, story- plete pathway model is the largest Wingding and Apple Symbols char- boarding, titling, and editing. Virginia and most prominent image, drawing acters. Orzel, an RIT alum and currently an attention first to the center/upper independent filmmaker, also assisted left of the poster; the eye is then (outside of class) with aspects such drawn around the poster in a clock- as image enhancement (e.g., size and wise direction.) color correction).

17 IMAGING THE AIRWAYS Part I.3 THE BODY OF WORK: POSTER

Figure 12 IMAGING THE AIRWAYS Poster 35” x 43” Illustrator, Photoshop

18 IMAGING THE AIRWAYS Part I.3 THE BODY OF WORK: POSTCARD

Figure 13 IMAGING THE AIRWAYS Postcard (front) 4.25” x 6” Illustrator, Photoshop

19 IMAGING THE AIRWAYS Part I.3 THE BODY OF WORK: POSTCARD

Figure 14 IMAGING THE AIRWAYS Postcard (back) 4.25” x 6” Illustrator

20 IMAGING THE AIRWAYS Part I.3 THE BODY OF WORK: WEBSITE

Figure 15 IMAGING THE AIRWAYS Website: Homepage 780 x 600 px Flash, Illustrator, Photoshop 21 IMAGING THE AIRWAYS Part I.3 THE BODY OF WORK: WEBSITE

Figure 16 IMAGING THE AIRWAYS Website: Anatomy 780 x 600 px Flash, Illustrator, Photoshop 22 IMAGING THE AIRWAYS Part I.3 THE BODY OF WORK: WEBSITE

Figure 17 IMAGING THE AIRWAYS Website: Model 780 x 600 px Flash, Illustrator, Photoshop 23 IMAGING THE AIRWAYS Part I.3 THE BODY OF WORK: WEBSITE

Figure 18 IMAGING THE AIRWAYS Website: Oral Cavity Model 780 x 600 px Flash, Illustrator, Photoshop 24 IMAGING THE AIRWAYS Part I.3 THE BODY OF WORK: WEBSITE

Figure 19 IMAGING THE AIRWAYS Website: Larynx Model 780 x 600 px Flash, Illustrator, Photoshop 25 IMAGING THE AIRWAYS Part I.3 THE BODY OF WORK: WEBSITE

Figure 20 IMAGING THE AIRWAYS Website: Trachea Model 780 x 600 px Flash, Illustrator, Photoshop 26 IMAGING THE AIRWAYS Part I.3 THE BODY OF WORK: WEBSITE

Figure 21 IMAGING THE AIRWAYS Website: Bronchi Model 780 x 600 px Flash, Illustrator, Photoshop 27 IMAGING THE AIRWAYS Part I.3 THE BODY OF WORK: WEBSITE

Figure 22 IMAGING THE AIRWAYS Website: Acinus Model 780 x 600 px Flash, Illustrator, Photoshop 28 IMAGING THE AIRWAYS Part I.3 THE BODY OF WORK: WEBSITE

Figure 23 IMAGING THE AIRWAYS Website: Maya to CFD 780 x 600 px Flash, Illustrator, Photoshop 29 IMAGING THE AIRWAYS Part I.3 THE BODY OF WORK: WEBSITE

Figure 24 IMAGING THE AIRWAYS Website: Future Work 780 x 600 px Flash, Illustrator, Photoshop 30 IMAGING THE AIRWAYS Part I.3 THE BODY OF WORK: WEBSITE

Figure 25 IMAGING THE AIRWAYS Website: Respiratory Membrane 780 x 600 px Flash, Illustrator, Photoshop 31 IMAGING THE AIRWAYS Part I.3 THE BODY OF WORK: WEBSITE

Figure 26 IMAGING THE AIRWAYS Website: Thesis Show 780 x 600 px Flash, Illustrator, Photoshop 32 IMAGING THE AIRWAYS Part I.3 THE BODY OF WORK: WEBSITE

Figure 27 IMAGING THE AIRWAYS Website: Video 780 x 600 px Flash, Illustrator 33 IMAGING THE AIRWAYS Part I.3 THE BODY OF WORK: WEBSITE

Figure 28 IMAGING THE AIRWAYS Website: Poster 780 x 600 px Flash, Illustrator, Photoshop 34 IMAGING THE AIRWAYS Part I.3 THE BODY OF WORK: WEBSITE

Figure 29 IMAGING THE AIRWAYS Website: Mentors and Modelers 780 x 600 px Flash, Illustrator, Photoshop 35 IMAGING THE AIRWAYS Part I.3 THE BODY OF WORK: VIDEO

THE VIDEO • the project’s purpose creation of this video: Title: IMAGING THE AIRWAYS Dr. Doolittle explains that the proj- Promotional Video ect involves looking at particle de- • Overlapping animations Duration: 1 min position in the human lung; Dr. Rob- Still images were animated in Final Medium: FInal Cut Pro inson explains that the model will Cut by keyframing image proper- be a pathway from the upper airway ties such as location, scale, and http://www.betsyskrip. to the site of gas exchange. opacity. The animations were then com/thesis overlapped with each other or with (Movie section) • the models still images. Examples include the Models of the airway, respiratory nanoparticle moving across the re- The IMAGING THE AIRWAYS Pro- membrane (Figure 32), and alveolar spiratory membrane (Figure 32, left) motional Video is a “sneak peek” at sacs with capillaries (Figure 33) are and the project logo moving with the overall thesis work, meant to at- featured. the acinus model (Figure 33, right). tract people’s attention and interest. The video does not fully explain the • how the models were created • Importing QuickTime movies research or the images presented. Images from 3D Doctor are shown The movie of the alveolar sacs (Fig- (Figure 30); they are explained else- ure 33) is a QuickTime file import- However, the video is contained where on the website. ed into Final Cut Pro. Discovery of within the website where such in- this method for bringing Maya- and formation can be obtained and does • significant aspects of the project Flash-generated animations into Fi- summarize the project, condensing Dr. Doolittle highlights the model of nal Cut made creation of the HVP all of the most important informa- the basement membrane; Dr. Rob- and CollaboRITorium animation tion into a one-minute, visually and inson states that the project is the possible. aurally aesthetic presentation. Spe- first to create a complete model of cifically, images of the models and the airways from the atmosphere to • Importing a QuickTime movie into segments from interviews with Dr. the site of gas exchange. Flash Doolittle and Dr. Robinson were Once the video was completed in Fi- carefully selected to highlight the Methods nal Cut, it was exported as a Quick- most important aspects of the the- The video was created in Professor Time file and imported into the sis research. Ann Pearlman’s Digital Video class Flash website. Importing involves using Final Cut Pro. Many meth- converting the QuickTime file to an The video presents: ods had been learned in previous FLV (Flash Video) file. Learning this • the project’s participants class assignments (e.g., principles method fascilitated importing the Interviews introduce Dr. Doolittle of digital-video-camera use, light- HVP and CollaboRITorium anima- and Dr. Robinson (Figure 31), and ing, sound, storyboarding, titling, and tion into the HVP website. Dr. Doolittle mentions those in- editing). Some methods, however, volved. were learned specifically through

Figure 30 Images from 3D Doctor

36 IMAGING THE AIRWAYS Part I.3 THE BODY OF WORK: VIDEO

Figure 31 Interviews with Dr. Richard Doolittle and Dr. Risa Robinson

Figure 32 Left, nanoparticle crossing respiratory membrane; right, basement membrane proteins

Figure 33 Acinus QuickTime file imported into Final Cut Pro

37 IMAGING THE AIRWAYS Par t I.3 CONCLUSIONS

CONCLUSIONS

The Poster and Postcard Creation of the poster and postcard as part of Professor Nancy Ciolek’s Information Design class was an in- valuable learning experience in the principles of design. Projects fol- lowing the thesis project have been greatly influenced by the experience and knowledge gained through the Information Design class.

The Website Design principles were reinforced through creation of the website as well, which was first designed as a PowerPoint presentation in Pro- fessor Ciolak’s Information Design class. The PowerPoint was created before the poster; therefore, de- signing the PowerPoint was also a worthwhile experience in gathering and summarizing information for presentation to a specific audience and inspired the style for all of the project’s promotional materials.

Creating the website reinforced skills in Flash, as well as in Photo- shop and Illustrator (particularly with designing the buttons). The procedure for importing a Quick- Time movie into Flash as an FLV (Flash Video) file was also learned.

The Video Creation of the promotional video in Professor Ann Pearlman’s Digital Video class was an invaluable expe- rience in learning Final Cut Pro and, again, worthwhile practice in sum- marizing information. The knowl- edge gained using Final Cut Pro allowed for the creation of the Hu- man Visualization Project animation.

38 IMAGING THE AIRWAYS Part II ORIGINAL THESIS STATEMENT, BACKGROUND

dents explore a topic of current and faculty. II. Creation of an Educational research on campus through inter- Animation about the Respiratory actions with faculty and research Spearheaded by Dr. Jon Schull in In- System for Use in the Human Vi- groups while learning about aspects formation Technology and his class sualization Project and CollaboRI- of science communication and pre- Innovation and Invention, the project sentation and developing a digital in- currently features three immersive Torium teractive, immersive, science learn- DOMEs (Digital Omnidirectional ing experience.” Multimedia Environments). Each DOME consists of four screens that ORIGINAL THESIS STATEMENT This project will help to greatly en- can be folded into a cube. Viewers hance my skills with Maya, particu- stand inside of the cube as images In previous quarters, Maya (a 3D larly in texturing and creating realis- are projected onto each of the four computer graphics program) was tic environments. Such a large-scale walls, thus creating an immersive used to create models of the re- teaching project will also test and environment. spiratory tract and the respiratory greatly increase my medical illustra- membrane’s five main components: tion skills—particularly the art of Furthermore, most images and ani- (1) surfactant (a lipid monolayer), organizing and presenting informa- mations projected in the cubes are (2) surface lining fluid, (3) alveolar tion in easy-to-understand, easy-to- interactive. Using a Wii remote, epithelial cells, (4) basement mem- navigate, and attractive formats. viewers can navigate through a vir- brane, and (5) endothelial cells. tual landscape or an educational game and rotate, zoom, and pan In the Spring 2008 quarter, an ani- BACKGROUND through 3D models. mation will be made using the pre- viously created models in order to The Human Vizualization Proj- Independent Studies educate viewers about the respira- ect (HVP) The IMAGING THE AIRWAYS ani- tory system and about current stud- The HVP is a collaboration to cre- mation and revised Human Visualiza- ies in nanoparticle transport across ate an interactive model of the hu- tion Project website were created the respiratory membrane into the man body and an online learning in the Spring 2008 quarter through bloodstream. platform available for students and two independent studies: teachers both within and outside 1. A three-credit independent study The work will be projected in RIT’s the RIT community. The project with Shaun Foster from the Com- CollaboRITorium, a specialized will consist of models and anima- puter Graphics Design Department classroom designed by RIT students. tions of the body’s systems (e.g., 2. A one-credit independent study in The CollaboRITorium features four skeletal, muscular, cardiovascular, Dr. Jake Noel-Storr’s Honors class, large (wall-height) screens whose respiratory, urinary, endocrine, and Frontiers of Science II. orientation can be changed to form digestive), both at the macroscopic a cube, making the learning experi- and microscopic levels. For the animation, several new ence immersive. The work will also methods using Maya were learned be available online as part of RIT’s The team spans different graduat- and implemented through working Human Visualization Project, an in- ing classes and disciplines: Biological with Shaun Foster: teractive learning tool created by Sciences and Chemistry (College of • use of the Paint Effects tool and RIT students. Science), Medical Illustration (Col- manipulation of the resulting mod- lege of Imaging Arts and Sciences), els to create the bronchial tree (Fig- The project will be created through Computer Gaming and Information ure 38) two independent studies: the ani- Technology (College of Computing • the creation and animation of mation and website will be created and Imaging Sciences), and Mechani- glowing edges (e.g., the texture on through collaboration with profes- cal Engineering (College of Engi- the human figure) using a ramp sor Shaun Foster from the Com- neering). shader puter Graphics Design Department; • the creation of metallic-looking projection in the CollaboRITorium The CollaboRITorium surfaces for the basement mem- will be accomplished through an in- The CollaboRITorium is an immer- brane proteins using an environ- dependent study in Dr. Jake Noel- sive learning environment and an in- mental ball shader (Figures 51 and Storr’s Honors class Frontiers of cubator for the design of new tech- 53) Science II, a course in which “stu- nologies, designed by RIT students • video compression using the

39 IMAGING THE AIRWAYS Part II BACKGROUND, THE BODY OF WORK: ANIMATION

H.264 codec The video contains six main sec- tings on the brush were altered to tions: increase the number of branches Professor Foster also provided valu- 1. Introduction and to eliminate any flowers, leaves, able feedback about the aesthetics, 2. O2 and CO2 Exchange and other botanical features except pace, and understandability of the 3. The Respiratory Membrane buds. Buds were kept to represent animation at its various stages of 4. Current Research the alveolar sacs, and their size and development. 5. The Basement Membrane color were altered to increase their 6. Summary prominence. The Frontiers of Science II class re- quired students to research a topic Methods Once the bronchial tree model of their choice and develop content The overall animation consists of was created using the Paint Effects to present their research in the Col- many smaller animations created in brush, it was converted to polygons, laboRITorium classroom (A-400). Maya and Flash. These short anima- and faces were deleted to make the tions were exported from Flash as overall structure fit the shape of the Work completed as part of the in- QuickTime files and imported into lungs. Specifically, the bronchial tree dependent study included: Final Cut Pro, where they were ar- model was placed inside the lung • creating an interactive platform ranged and compiled with narration model in Maya, and any branches (i.e., the revised Human Visualiza- and music. extending outside of the lung model tion Project website) to feature the were trimmed off. animation Introduction • designing part of the animation to The animation first provides an O2 and CO2 Exchange extend to all four walls of the cube. orientation of the lungs inside the A green highlight at the edges of the human body (Figures 34 and 35). bronchial tree (Figure 39) helps to The lung models were created in introduce the alveolar sacs–a model THE BODY OF WORK Maya in Summer 2007 using Netter created in Summer 2007 in Maya. illustrations (Netter, 1979) as ref- Animated masking layers were again Animation and website at: erences. The model of the human used in Flash to show the flow of http://www.betsyskrip. body was purchased by the Human CO2-rich blood to the sac and O2- com/hvp Visualization Project and has been rich blood away from the sac (Fig- (Note: The animation is located in the used in other student animations ure 41). Respiratory section.) for the HVP. The larynx model was created by Weisman (2007), and the The Respiratory Membrane trachea/bronchi model was created The respiratory membrane section THE ANIMATION by Russo (2007). features artwork made in Summer Duration: 5 min 2007: a cross-sectional view of an Media: Flash, Final Cut Pro To visually explain the inhalation of alveolus and a capillary made in Il- oxygen and exhalation of carbon lustrator, and a Maya model of a red The HVP and CollaboRITorium dioxide, the thoracic wall and lungs blood cell (Figures 42, 43, 44, and animation is a video to educate were animated in Maya to expand 45). viewers about the structure and and contract (Figures 34 and 35), function of the respiratory system and colored layers were animated in The cross-sectional Illustrator and about current research (i.e., Flash to highlight the path between drawing first appears directly over nanoparticles and the respiratory the atmosphere, lungs, and body an alveolus and capillary on the 3D membrane model). Unlike in the (Figures 36 and 37). The expansion model, thus establishing the rela- thesis promotional video, the im- and contraction were achieved with tionship between the two views. ages in the animation are explained the flare nonlinear deformer in Maya. The cross-sectional drawing then through narration. The path highlights were achieved in enlarges to feature the respiratory Flash by animating shapes placed on membrane, whose parts are high- The animation illustrates gas ex- masking layers. lighted (using Flash) as they are change at the macroscopic level named in the narration. Flash text (Figures 36 and 37) and microscopic The animation next shows the and arrows illustrate the movement level (Figure 44) and guides view- bronchial tree—a model created of O2 and CO2 across the mem- ers through this visual reduction in in Spring 2008 using a tree Paint brane (Figure 44). size. Effects brush in Maya. The set-

40 IMAGING THE AIRWAYS Part II THE BODY OF WORK: ANIMATION

Current Research The Basement Membrane four files were altered by going to In order to illustrate a nanoparticle The basement membrane model Window > Show Movie Properties, crossing the respiratory membrane (Figures 48 and 51) of proteins col- selecting the Resources tab, select- and entering the bloodstream (Fig- lagen, laminin, perlecan, and entactin ing the file names, and then, under ures 45 and 46), a buckyball model was created in Summer 2007. The the Visual Settings tab, changing the was obtained from the public-do- metallic-looking surface (Figure “offset x” value for each file by the main site www.3dchem.com. The 51) was created using a technique file widths. For example, because file was saved as a PDB (Protein taught by Professor Shaun Foster. each video was 800 pixels wide, the Data Bank) file and opened in Chi- offset x values were: mera, the University of California The technique involves taking a San Francisco’s Molecular Modeling photograph of a reflective surface video 1 offset x = 0 System. From Chimera, the model (e.g., a garden globe), cropping and video 2 offset x = 800 was exported as a VRML and im- coloring the photograph in Photo- video 3 offset x = 1600 ported into Cinema 4D. shop, and applying the image to an video 4 offset x = 2400 Environmental Ball shader in Maya. The model in Figure 45 was ren- The Environmental Ball shader is The resulting video, therefore, was dered in Cinema 4D as a PNG then connected to the color, specu- 3200 pixels wide, with the four and animated in Final Cut Pro. The lar color, and reflected color inputs separate videos aligned horizontally model in Figure 46 was exported of a Phong shader. (Figure 53). from Chimera as an FBX and im- ported into Maya, where it was par- CollaboRITorium animation In Summer 2007 it was found that, ented to the rear red blood cell to For the CollaboRITorium anima- in order for the four images to line flow through the blood vessel. The tion, the basement-membrane fly- up properly, the shutter angle of the blood-vessel animation was created through was constructed to span Maya cameras must be set to 90 and in Winter 2007 as an assignment in all four screens of the DOME. The the angle of view set to 97 (Figure the class 3D Bio and Organic Forms process was learned in Summer 52). This formula worked with the II. The buckyball model was ac- 2007 from Julia Lehman, MFA Medi- lung model, but was not success- quired in Spring 2008. cal Illustration, Class of 2007. Four ful with the respiratory membrane cameras were created in Maya and model (Figure 53). Larger angles The nanoparticle in Figures 47 and rotated at 90° from each other. of view were tried, but to no avail. 49 appears as a solid sphere, as it The reason for this misalignement is was created before knowledge of The cameras were then grouped, currently unclear; however, the Col- other molecular imaging sites (such and the group was animated to laboRITorium team will be working as 3dchem.com) was gained. As move throughout the basement on the file over the Summer 2008 described for Part I.2, the respira- membrane model. JPEGs were quarter to resolve the issue. tory membrane model components rendered from each camera and were constructed in Maya and are imported into four separate Quick- Narration and Music to scale (based on available data). Times files. The four QuickTime The animation was narrated by files were then assembled into one Ryan Fuller, a first-year graduate In the animation, the layers of the QuickTime file using the following student in RIT’s Electrical Engineer- respiratory membrane model are procedure: ing Department. The narration was explained nonverbally. An image of recorded using Soundtrack Pro and the respiratory membrane model 1. Adding one QuickTime file to an- imported into Final Cut Pro as AIFF was animated in Final Cut Pro to other files. overlap the Illustrator diagram (Fig- For three of the files, all of the ure 50). Therefore, layers of the frames were selected and copied. All music was acquired from Garage respiratory model (i.e., surfactant, In the fourth file, the playhead was Band. The files were imported into alveolar epithelial cell, basement set to the beginning of the movie, iTunes, saved as AIFF files, and im- membrane, and endothelial cell) lay and the frames from videos 1-3 ported into Final Cut Pro. directly over their corresponding were pasted into it (Edit > Add To layers in the Illustrator diagram–lay- Movie). ers that were identified earlier in the narration. 2. Positioning the movies In the fourth file, the positions of all

41 IMAGING THE AIRWAYS Part II THE BODY OF WORK: ANIMATION

Figure 34 Figure 35 Exterior surface of lungs (exhalation) Exterior surface of lungs (inhalation)

Figure 36 Figure 37 Oxygen moving from the lungs to the body Carbon dioxide moving from the body to the lungs

Figure 38 Figure 39 Bronchial tree Green highlight to indicate branch ends (like leaves)

42 IMAGING THE AIRWAYS Part II THE BODY OF WORK: ANIMATION

Figure 40 Figure 41 A single alveolus of an alveolar sac Capillaries carrying CO2 to and O2 away from the sacs

Figure 42 Figure 43 Cross section of an alveolus and a capillary The respiratory membrane (highlighted in yellow)

Figure 44 Figure 45 O2 and CO2 crossing the respiratory membrane A nanoparticle crossing the respiratory membrane

43 IMAGING THE AIRWAYS Part II THE BODY OF WORK: ANIMATION

Figure 46 Figure 47 A nanoparticle flowing in the blood with red blood cells A nanoparticle and caveolae in an alveolar epithelial cell

Figure 48 Figure 49 Basement membrane proteins A nanoparticle and caveolae in an endothelial cell

Figure 50 Figure 51 3D model of the respiratory membrane Basement membrane proteins

44 IMAGING THE AIRWAYS Part II THE BODY OF WORK: ANIMATION

seam seam

(a)

(b)

(c)

Figure 52 Different angles of view for the cameras in Maya affect how images from the four cameras align. The above images of the lung model each consist of three images, rendered in Maya by three cameras set at 90° from each other. These images were assembled in Photoshop to test which angle of view was needed for the images to align properly. (a) The angle of view for the cameras was set at 90°. The angle of view is not wide enough, therefore a harsh line of contrast (seam) results where part of the model is missing (i.e., in an area neither of two cameras was able to capture). (b) The angle of view was set at 95°. More of the model was captured, but a line of contrast is still discernible. (c) The angle of view was set at 97°. No lines of contrast are visible.

seam seam seam

Figure 53 Although the angle of view was set to 97° for the respiratory membrane fly-through, lines of contrast are still visible.

45 IMAGING THE AIRWAYS Part II THE BODY OF WORK: HVP WEBSITE, CONCLUSIONS

THE HVP WEBSITE digestive). Thumbnail buttons (Fig- ing Soundtrack Pro Medium: Flash ure 57) and a slideshow (Figure 58) http://www.betsyskrip.com/hvp were created by taking screen shots Methods for creating a four-panel of the animations on the Summer QuickTime movie for display in the The design for the HVP website 2007 site and altering the image CollaboRITorium were also learned was inspired by another HVP sizes in Photoshop. and applied. Although setting the website created in Summer 2007 angle of view to 97 for each of the by Randall Church (Figure 54), four Maya cameras did not produce http://www.rit.edu/~ez-viz/adobe. CONCLUSIONS a seamless image for the respira- Church’s site was designed spe- tory membrane fly-through (Figure cifically to document the Summer The Animation 35), the CollaboRITorium team will 2007 research. The site also fea- Many skills were learned and rein- be analyzing the files to devise a so- tures all other student animations forced through creation of the ani- lution. created for the HVP as of that mation: summer. • script-writing and storyboarding The HVP Website • using input and output connec- Creating the HVP website was an- The new HVP website (Figure tions in Maya to create attractive other valuable reinforcement of 55) not only features the respira- surface textures Flash web design skills, including im- tory animation (Figure 56), but • animating with Flash porting video. The experience also also organizes the other student • stitching Flash animations together reinforced information design skills, animations into their respective with Final Cut Pro as it involved reorganizing much of systems (skeletal, cardiovascular, • working with a narrator and re- the information on the Summer respiratory, urinary, endocrine, and cording in a soundproof booth us- 2007 HVP site into a new format.

Figure 54 The Human Visualization Project Summer 2007 website (http://www.rit.edu/~ez-viz/adobe); created by Randall Church.

46 IMAGING THE AIRWAYS Part II THE BODY OF WORK: HVP WEBSITE

Figure 55 HUMAN VISUALIZATION PROJECT Website: Homepage 800 x 600 px Flash, Photoshop

47 IMAGING THE AIRWAYS Part II THE BODY OF WORK: HVP WEBSITE

Figure 56 HUMAN VISUALIZATION PROJECT Website: Respiratory section 800 x 600 px Flash, Photoshop

48 IMAGING THE AIRWAYS Part II THE BODY OF WORK: HVP WEBSITE

Figure 57 Thumbnail buttons created by taking screen shots of the animations on the Summer 2007 HVP site and al- tering the image sizes in Photoshop.

(a) Skeletal animations created by Erin Topley, Multidisciplinary Studies and Corrine Grande, Biology.

(b) Endocrine animations created by Britney Peters, BFA Medical Illustration, Class of 2007. (a) (b) (c) Heart animation created by Nathan Skinner, Jamestown Community Col- lege, Class of 2007. Hemoglobin anima- tion created by Laura Garell, MS Bioin- formatics, Class of 2007 and Paul Yacci, MS Bioinformatics, Class of 2009.

(d) Liver animations created by Thomas Nowaki, MFA Medical Illustration, Class (c) (d) of 2006.

(a)

(b)

(c)

(d)

(e)

Figure 58 The above images were created by taking screen shots of the animations on the Summer 2007 HVP site and altering the image sizes in Photoshop. The images were then compiled into a slideshow in Flash for the Human Visualization Project website. (a) Pancreas animation created by Britney Peters, BFA Medical Illustration, Class of 2007. (b) Kidney animation created by Katie Tower, BFA Medical Illustration, Class of 2006 and Mylissa Kowalski, BFA Medical Illustration, Class of 2006. (c) Liver animation created by Thomas Nowaki, MFA Medical Illustration, Class of 2006. (d) Hemoglobin animation created by Laura Garell, MS Bio- informatics, Class of 2007 and Paul Yacci, MS Bioinformatics, Class of 2009. (e) Insulin animation created by Britney Peters, BFA Medical Illustration, Class of 2007.

49 IMAGING THE AIRWAYS OVERALL CONCLUSIONS, ACKNOWLEDGEMENTS, REFERENCES

OVERALL CONCLUSIONS • Glen Hintz, thesis advisor in Medi- Modeling of the Respiratory System cal Illustration animation The IMAGING THE AIRWAYS proj- ect was an invaluable experience to- • Dr. Richard Doolittle, advisor in • Donald Arday, School of Art De- ward earning a Master of Fine Arts the Allied Health Sciences Depart- partment Chairperson degree in Medical Illustration. Many ment and with the Human Visualiza- skills were learned and reinforced, tion Project creating a strong foundation for a REFERENCES career in the discipline and in the • Nancy Ciolek, Information Design arts in general. Overall, the project professor Berry, J.P., B. Arnoux, G. Stanislas, P. Galle, helped to strengthen several abili- and J. Chretien. 1977. A Microana- ties that are critical to being a Sci- • Ann Pearlman, Digital Video pro- lytic Study of Particles Transport entific/Medical Illustrator: fessor Across the Alveoli: Role of Blood Platelets. Biomedicine. 27: 354-357. • Virginia Orzel, for her assistance • The ability to locate and interpret Campbell, Neil A. and Jane B. Reece. with editing the Part I promotional available data and images and to use 2002. BIOLOGY, 6th edition. San one’s imagination and critical think- video Francisco, CA: Benjamin Cum- ing skills to create artwork that is mings. unique. To the best of our knowl- • Shaun Foster, independent-study edge, the complete respiratory professor in Computer Graphics Churg, Andrew. Particle Uptake by Epi- pathway model and the respiratory Design thelial Cells. In: Particle-Lung Inter- membrane model are the first of actions (Gehr, Peter, and Joachim their kind and will help to advance • Dr. Jake Noel-Storr, Frontiers of Heyder, eds). 2000. New York: Mar- cel Dekker, 401-435. current research about the respira- Science II professor tory system. Crouch, Edmond C., George R. Martin, • Dr. Jon Schull, Associate Professor and Jerome S. Brody. Basement • The ability to collaborate with in Information Technology; head of Membranes. In: THE LUNG: Sci- researchers, understand their re- the CollaboRITorium project entific Foundations, Vol. 1 (Crys- search, and create artwork that tal, R.G, J.B. West et al., eds). 1991. meets their needs and vision. • Jackie Russo, MS Mechanical Engi- New York: Raven Press, Ltd. neering, Class of 2007: Created the • The ability to problem-solve and oral cavity model and the trachea Des Jardins, Terry. 2007. Cardiopulmo- to bronchi generation 5 model; sup- nary Anatomy: Essentials for Re- to find new ways of working that spiratory Care, 3rd edition. Albany, plied images for Part I promotional are more efficient and produce bet- NY: Delmar Publishers. ter-quality results. materials Fawcett, Don Wayne. 1986. A Textbook • The ability to organize informa- • Jessica Weisman, MFA Medical Il- of Histology, 11th edition. Philadel- tion into different types of presen- lustration, Class of 2007: Created phia, PA: W. B. Saunders Company. tations that span across the media the larynx and acinus models (i.e., print, web, and video). Geiser, Marianne, Barbara Rothen-Ru- • Julia Lehman, MFA Medical Illus- tishauser, Nadine Kapp, Samuel tration, Class of 2007: Established Schürch, Wolfgang Kreyling, Holger Schultz, Manuela Semmler, Vinzenz a formula for creating a four-panel ACKNOWLEDGEMENTS Im Hof, Joachim Heyder, and Pe- animation for display in the Colla- ter Gehr. 2005. Ultrafine Particles This work was supported by the boRITorium Cross Cellualr Membranes by American Cancer Society. Nonphagocytic Mechanisms in • Valerie Henry, MFA Medical Illus- Lungs and Cultured Cells. Envi- Special thanks and recognition to: tration, Class of 2009: for her as- ronmental Health Perspectives. sistance over Summer 2008 and for 113(11): 1555-1560. • Dr. Risa Robinson, thesis advisor continuing the IMAGING THE AIR- WAYS project as part of her thesis Gwinn, Maureen R. and Val Vallyathan. in Mechanical Engineering 2006. Nanoparticles: Health Ef- research fects–Pros and Cons. Environmen- • Jim Perkins, thesis advisor in Medi- tal Health Perspectives. 114(12): cal Illustration • Ryan Fuller, narrator for the 3D 1818-1825.

50 IMAGING THE AIRWAYS REFERENCES

Hay, Elizabeth D. 1981. Cell biology of Rothen-Rutishauser, Barbara M., Samuel extracellualr matrix. New York: Schürch, Beat Haenni, Nadine Kapp, Plenum Press. and Peter Gehr. 2006. Interaction of Fine Particles and Nanopar- Hoet, Peter HM, Irene Brüske-Hohlfeld, ticles with Red Blood Cells Visu- and Oleg V Salata. 2004. Nanopar- alized with Advanced Microscopic ticles–known and unknown health Techniques. Environmental Science risks. Journal of Nanobioltechnol- Technology. 40(14): 4353-4359. ogy. 2(1): 12. Russo, Jackie. 2007. 3D Reconstruction Horsfield, Keith, Gladys Dart, Dan E. of a Female Lung Using the Visible Olson, Giles F. Filley, and Gordon Human Data Set to Predict Ciga- Cumming. 1971. Models of the Hu- rette Smoke Particle Deposition. man Bronchial Tree. Journal of Ap- Thesis dissertation. plied Physiology. 31(2): 207-217. Simionescu, Maya. Lung Endothelium: Knowles III, Emory E. Nanotechnology: Structure-Funtion Correlates. In: Evolving occupational safety, health, THE LUNG: Scientific Foundations, and environmental issues. Associ- Vol. 1 (Crystal, R.G, J.B. West et al., ated with Nanotechnology. Journal eds). 1991. New York: Raven Press, of the American Society of Safety Ltd. Engineers. March 2006: 20-27. Weisman, Jessica. 2007. Using organic McShane, Brian. 2006. Nanotechnology: modeling techniques to create Is there cause for concern? Profes- scientific models for flow analysis sional Safety: Journal of the Ameri- in biomechanical research: Explor- can Society of Safety Engineers. ing 3D software typically used in March 2006: 28-34. creative media for model creation. Thesis dissertation. Netter, Frank H. 1979. The CIBA Col- lection of Medical Illustrations; Vol. Yacobi, Nazanin R., Harish C. Phuleria, 7 The Respiratory System. New Lucas Demaio, Chi H. Liang, Ching- Jersey: CIBA Pharmaceutical Com- An Peng, Constantinos Sioutas, Zea pany. Borok, Kwang-Jin Kim, and Edward D. Crandall. Nanoparticle effects Orberdorster, Günter, Eva Orberdor- on rat alveolar epithelial cell mono- ster, and Jan Orberdorster. 1995. layer barrier properties. Toxicology Nanotoxicology: An Emerging Dis- in Vitro. 21(8): 1373-1381. cipline Evolving from Studies of Ultrafine Particles. Environmental Health Perspectives. 113(7): 823- 839.

Patton, John S. 1996. Mechanisms of macromolecule absorption by the lungs. Advanced Drug Delivery Re- views. 19: 3-36.

Pernkopf, Eduard. 1980. Atlas of Topo- graphical and Applied Human Anatomy; Volume II Thorax, Abdo- men and Extremities. (Ferner, M.D., Helmut, ed). Philadelphia: W.B. Saunders Company.

Rohrbach, D. H. and R. Timpl. 1993. Molecular and Cellular Aspects of Basement Membranes. San Diego: Academic Press, Inc.

51 IMAGING THE AIRWAYS APPROVAL PAGE

Chief Advisor Jim Perkins, Medical Illustration

Signature

Date

Associate Advisor Glen Hintz, Medical Illustration

Signature

Date

Associate Advisor Dr. Risa Robinson, Mechanical Engineering

Signature

Date

Department Chairperson Donald Arday

Signature

Date

52