Image Functional Modeling: Combining Lung Models with Imaging Modalities and Mechanical Measures

Nora T. Tgavalekos, Jose G. Venegas, Mitchell Albert,

Allison Bell, and K. R. Lutchen

October 14, 2004

BMES Conference

Stimuli Cell activation Inflammatorymediators

Airway Changes

Airway Obstruction

(Allergens,outdoor pollutants and viruses)

(mast cells, eosinophils, neutrophils)

Size and Location Distribution

? ?

(proinflammatory mediators: histamine)

(inflammation, remodeling, bronchoconstriction)

Asthma

http://www.merckfrosst.ca/e/health/asthma/sum_01.html

Mechanical Heterogeneity in Asthma

Which airways are most responsible for degradation inWhich airways are most responsible for degradation in function and hyperresponsiveness?function and hyperresponsiveness?

Apnea

Time (secs)

Washout

PET Imaging: Tracer Kinetics

Apnea

Time (secs)

Washout

PET Imaging: Tracer Kinetics

PET Imaging

apex

base

Images from Mass General Hospital

Pre Challenge Post Challenge

Hyperpolarized 3He MRI Imaging

Images from Brigham and Women’s Hospital

Pre Challenge Post Challenge

Image-Functional Modeling (IFM)

Goal:

To synthesize the imaging and mechanical information in To synthesize the imaging and mechanical information in order to identify which airways are responsible for the order to identify which airways are responsible for the degradation in the mechanics and ventilation distribution on a degradation in the mechanics and ventilation distribution on a patient specific basis. patient specific basis.

Method:

Combine the imaging and mechanical data with 3D anatomically Combine the imaging and mechanical data with 3D anatomically consistent multi-scale lung models. consistent multi-scale lung models.

Advancing 3D Models for Computation of Mechanical Function

Zw(n)

Z(n-1)

Z(n-1- )

Z(n) R(n)/2 I(n)/2

Cg(n)

R(n)/2 I(n)/2

• Impedance of a Single Airway

• Airways Terminate on Alveoli with Viscoelastic Tissue

Tawhai et al, 1999

IFM:Mapping PET Ventilation Defects into 3D Model

Post Washout:Tracer Retention

Pre Washout:Baseline

d < 2.5 mm

0 2 4 6 8

Res

ista

nce(

cmH

20/l/

s)

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Ela

stan

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Baseline

Frequency (Hz)

0 2 4 6 8

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Ela

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BaselinePost Challenge

Frequency (Hz)

0 2 4 6 8

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BaselinePost Challenged< 0.6 mm

Frequency (Hz)

0 2 4 6 8

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BaselinePost Challenged< 0.9mmd< 0.6 mm

Frequency (Hz)

Size Range of Allowable Closed Airways: 0.3-2.5 mm.Size Range of Allowable Closed Airways: 0.3-2.5 mm.

0 2 4 6 8

Res

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cmH

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BaselinePost Challenged<2.5 mmd< 0.9mmd< 0.6 mm

Frequency (Hz)

d< .9 mm

PET: IFM Application

0 closed

100 open

Percent of Baseline Airway Diameter

80

60

40

20

d <.6 mm

Hyperpolarized MRI : IFM Application

2

1.6

1.2

.8

.4

0

Ventilation Spectrum: Fraction of Baseline Ventilation

normal

over

under

PET Based Model Based

Image and Model Based Ventilation Images

Summary

We identified constriction conditions, which are consistent with both the lung mechanics and imaging information for 4 asthmatics:

Maximum airway size for closures: 0.9 -2.4 mmMean airway sizes affected: <1 mm and belowConstriction Conditions: = 60% , SD= 20%

The IFM paradigm provides a platform for multi-scale sensitivity analysis regarding how the integrated components of lung structure determined the degradation in function during airway disease.

AcknowledgementsAnesthesia & Critical Care,MGH

Jose G. Venegas

R. Scott Harris

Marcos Vidal Melo

Guido Musch

Tilo Winkler

Giacomo Bellani

BU Respiratory Lab

Kenneth R. Lutchen

Carissa Bellardine

Derek Affonce

Brian Szender

Allison Bell

Mike Hamilton

Jen Kenyon

Adam LaPrad

University of Auckland, New ZealandMerryn Tawhai

Brigham and Women’s HospitalMitchell AlbertYang- Sheng Tzeng

Funding Sources

AAUW Selected Professions FellowshipNIHBMES

PET: IFM Application

d < 2.5 mm

0 2 4 6 8

Res

ista

nce(

cmH

20/l/

s)

0

9

18

27

36

45

0 2 4 6 8

Ela

stan

ce(c

mH

20/l)

0

100

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300

Baseline

Frequency (Hz)

0 2 4 6 8

Res

ista

nce(

cmH

20/l/

s)

0

9

18

27

36

45

0 2 4 6 8

Ela

stan

ce(c

mH

20/l)

0

100

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300

BaselinePost Challenge

Frequency (Hz)

0 2 4 6 8

Res

ista

nce(

cmH

20/l/

s)

0

9

18

27

36

45

0 2 4 6 8

Ela

stan

ce(c

mH

20/l)

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100

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300

BaselinePost Challenged< 0.6 mm

Frequency (Hz)

0 2 4 6 8

Res

ista

nce(

cmH

20/l/

s)

0

9

18

27

36

45

0 2 4 6 8

Ela

stan

ce(c

mH

20/l)

0

100

200

300

BaselinePost Challenged< 0.9mmd< 0.6 mm

Frequency (Hz)

Size Range of Allowable Closed Airways: 0.3-2.5 mm.Size Range of Allowable Closed Airways: 0.3-2.5 mm.

0 2 4 6 8

Res

ista

nce(

cmH

20/l/

s)

0

9

18

27

36

45

0 2 4 6 8

Ela

stan

ce(c

mH

20/l)

0

100

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300

BaselinePost Challenged<2.5 mmd< 0.9mmd< 0.6 mm

Frequency (Hz)

d< .9 mm

100 open

Percent of Baseline Airway Diameter

80

60

40

20

0 closed

d <.6 mm