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)
0
9
18
27
36
45
0 2 4 6 8
Ela
stan
ce(c
mH
20/l)
0
100
200
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
200
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)
0
100
200
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
200
300
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
200
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
200
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)
0
100
200
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
200
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