Abstract

In 1926, Cecil D. Murray published a fundamental law of physiology relating the form and function of branched vessels. Murray's Law predicts that the diameter of a parent vessel branching into two child branches is mathematically related by a cube law based on parabolic flow and power minimization with vascular volume. This law is foundational for computational analyses of branching vascular structures. However, pulmonary arteries exhibit morphometric and hemodynamic characteristics that may deviate from classical predictions. This study investigates the morphometry of pulmonary arterial networks, examining relationships between parent and child vessel diameters across species. We analyzed three-dimensional segmentations of pulmonary arterial geometries from healthy subjects across four species: human (n = 7), canine (n = 5), swine (n = 4), and murine (n = 3). Our findings reveal an average exponent value of 2.31(±0.60) in human, 2.13(±0.54) in canine, 2.10(±0.49) in swine, and 2.59(±0.58) in murine, all lower than the predicted value of 3.0 from Murray's Law. Extending Murray's Law to fully developed pulsatile flow based on minimal impedance, we show that mean flow is proportional to radius raised to a power between 2.1 and 3, depending on the Womersley number. Our findings suggest that while Murray's Law provides a useful baseline, pulmonary artery (PA) branching follows a different optimization principle depending on Womersley number. This study contributes to a deeper understanding of pulmonary arterial structure–function relationships and implications for vascular disease modeling.

References

1.
Murray
,
C. D.
,
1926
, “
The Physiological Principle of Minimum Work: I. The Vascular System and the Cost of Blood Volume
,”
Proc. Natl. Acad. Sci.
,
12
(
3
), pp.
207
214
.10.1073/pnas.12.3.207
2.
Zamir
,
M.
,
1978
, “
Nonsymmetrical Bifurcations in Arterial Branching
,”
J. Gen. Physiol.
,
72
(
6
), pp.
837
845
.10.1085/jgp.72.6.837
3.
Uylings
,
H. B. M.
,
1977
, “
Optimization of Diameters and Bifurcation Angles in Lung and Vascular Tree Structures
,”
Bull. Math. Biol.
,
39
(
5
), pp.
509
520
.10.1016/S0092-8240(77)80054-2
4.
Olufsen
,
M. S.
,
Peskin
,
C. S.
,
Kim
,
W. Y.
,
Pedersen
,
E. M.
,
Nadim
,
A.
, and
Larsen
,
J.
,
2000
, “
Numerical Simulation and Experimental Validation of Blood Flow in Arteries With Structured-Tree Outflow Conditions
,”
Ann. Biomed. Eng.
,
28
(
11
), pp.
1281
1299
.10.1114/1.1326031
5.
Taber
,
L. A.
,
1998
, “
An Optimization Principle for Vascular Radius Including the Effects of Smooth Muscle Tone
,”
Biophys. J.
,
74
(
1
), pp.
109
114
.10.1016/S0006-3495(98)77772-0
6.
Kassab
,
G. S.
,
2006
, “
Scaling Laws of Vascular Trees: Of Form and Function
,”
Am. J. Physiol.-Heart Circ. Physiol.
,
290
(
2
), pp.
H894
H903
.10.1152/ajpheart.00579.2005
7.
Stephenson
,
D.
, and
Lockerby
,
D. A.
,
2016
, “
A Generalized Optimization Principle for Asymmetric Branching in Fluidic Networks
,”
Proc. R. Soc. A: Math., Phys. Eng. Sci.
,
472
(
2191
), p.
20160451
.10.1098/rspa.2016.0451
8.
West
,
G. B.
,
Brown
,
J. H.
, and
Enquist
,
B. J.
,
1997
, “
A General Model for the Origin of Allometric Scaling Laws in Biology
,”
Science
,
276
(
5309
), pp.
122
126
.10.1126/science.276.5309.122
9.
Painter
,
P. R.
,
Edén
,
P.
, and
Bengtsson
,
H.-U.
,
2006
, “
Pulsatile Blood Flow, Shear Force, Energy Dissipation and Murray's Law
,”
Theor. Biol. Med. Modell.
,
3
, p.
31
.10.1186/1742-4682-3-31
10.
Shumal
,
M.
,
Saghafian
,
M.
,
Shirani
,
E.
, and
Nili-Ahmadabadi
,
M.
,
2024
, “
A General Scaling Law of Vascular Tree: Optimal Principle of Bifurcations in Pulsatile Flow
,”
J. Appl. Fluid Mech.
,
17
(
10
), pp.
2203
2214
.10.47176/JAFM.17.10.2370
11.
Sherman
,
T. F.
,
1981
, “
On Connecting Large Vessels to Small. The Meaning of Murray's Law
,”
J. Gen. Physiol.
,
78
(
4
), pp.
431
453
.10.1085/jgp.78.4.431
12.
McCulloh
,
K. A.
,
Sperry
,
J. S.
, and
Adler
,
F. R.
,
2003
, “
Water Transport in Plants Obeys Murray's Law
,”
Nature
,
421
(
6926
), pp.
939
942
.10.1038/nature01444
13.
Zhou
,
B.
,
Cheng
,
Q.
,
Chen
,
Z.
,
Chen
,
Z.
,
Liang
,
D.
,
Munro
,
E. A.
,
Yun
,
G.
, et al.,
2024
, “
Universal Murray's Law for Optimised Fluid Transport in Synthetic Structures
,”
Nat. Commun.
,
15
(
1
), p.
3652
.10.1038/s41467-024-47833-0
14.
Ritman
,
E. L.
, and
Zamir
,
M.
,
2012
,
The Physics of Pulsatile Flow
, Springer, New York, NY.
15.
Updegrove
,
A.
,
Wilson
,
N. M.
,
Merkow
,
J.
,
Lan
,
H.
,
Marsden
,
A. L.
, and
Shadden
,
S. C.
,
2017
, “
SimVascular: An Open Source Pipeline for Cardiovascular Simulation
,”
Ann. Biomed. Eng.
,
45
(
3
), pp.
525
541
.10.1007/s10439-016-1762-8
16.
Seiter
,
D. P.
,
Allen
,
B.
,
Tabima
,
D. M.
,
Hacker
,
T. A.
,
Corrado
,
P.
,
Oechtering
,
T. H.
,
Reeder
,
S. B.
,
Chesler
,
N. C.
, and
Wieben
,
O.
,
2022
, “
4D Flow MRI Analysis of Flow, Velocity, and Cardiac Flow Compartments in a Swine Model of Pulmonary Hypertension
,”
31st Annual Meeting ISMRT-ESMRMB
, London, UK, May 7--12.https://archive.ismrm.org/2022/0797.html
17.
Mulchrone
,
A.
,
Kellihan
,
H. B.
,
Forouzan
,
O.
,
Hacker
,
T. A.
,
Bates
,
M. L.
,
Francois
,
C. J.
, and
Chesler
,
N. C.
,
2019
, “
A Large Animal Model of Right Ventricular Failure Due to Chronic Thromboembolic Pulmonary Hypertension: A Focus on Function
,”
Front. Cardiovasc. Med.
,
5
, p.
189
.10.3389/fcvm.2018.00189
18.
Vanderpool
,
R. R.
,
Kim
,
A. R.
,
Molthen
,
R.
, and
Chesler
,
N. C.
,
2011
, “
Effects of Acute Rho Kinase Inhibition on Chronic Hypoxia-Induced Changes in Proximal and Distal Pulmonary Arterial Structure and Function
,”
J. Appl. Physiol.
,
110
(
1
), pp.
188
198
.10.1152/japplphysiol.00533.2010
19.
Fedorov
,
A.
,
Beichel
,
R.
,
Kalpathy-Cramer
,
J.
,
Finet
,
J.
,
Fillion-Robin
,
J.-C.
,
Pujol
,
S.
,
Bauer
,
C.
, et al.,
2012
, “
3D Slicer as an Image Computing Platform for the Quantitative Imaging Network
,”
Magn. Reson. Imaging
,
30
(
9
), pp.
1323
1341
.10.1016/j.mri.2012.05.001
20.
Hernandez-Cerdan, P., 2024, “SGEXT: Spatial Graph Extractor,” GitHub, Inc., San Francisco, CA, accessed Aug. 2024, https://github.com/phcerdan/SGEXT
21.
Chambers
,
M. J.
,
Colebank
,
M. J.
,
Qureshi
,
M. U.
,
Clipp
,
R.
, and
Olufsen
,
M. S.
,
2020
, “
Structural and Hemodynamic Properties of Murine Pulmonary Arterial Networks Under Hypoxia-Induced Pulmonary Hypertension
,”
Proc. Inst. Mech. Eng., Part H: J. Eng. Med.
,
234
(
11
), pp.
1312
1329
.10.1177/0954411920944110
22.
Avram
,
R.
,
Tison
,
G. H.
,
Aschbacher
,
K.
,
Kuhar
,
P.
,
Vittinghoff
,
E.
,
Butzner
,
M.
,
Runge
,
R.
, et al.,
2019
, “
Real-World Heart Rate Norms in the Health eHeart Study
,”
NPJ Digital Med.
,
2
(
1
), p.
58
.10.1038/s41746-019-0134-9
23.
Janssen
,
P. M.
,
Biesiadecki
,
B. J.
,
Ziolo
,
M. T.
, and
Davis
,
J. P.
,
2016
, “
The Need for Speed: Mice, Men, and Myocardial Kinetic Reserve
,”
Circ. Res.
,
119
(
3
), pp.
418
421
.10.1161/CIRCRESAHA.116.309126
24.
Aroesty
,
J.
, and
Gross
,
J. F.
,
1972
, “
The Mathematics of Pulsatile Flow in Small Vessels I. Casson Theory
,”
Microvasc. Res.
,
4
(
1
), pp.
1
12
.10.1016/0026-2862(72)90012-X
25.
Bartolo
,
M. A.
,
Taylor-LaPole
,
A. M.
,
Gandhi
,
D.
,
Johnson
,
A.
,
Li
,
Y.
,
Slack
,
E.
,
Stevens
,
I.
, et al.,
2024
, “
Computational Framework for the Generation of One-Dimensional Vascular Models Accounting for Uncertainty in Networks Extracted From Medical Images
,”
J. Physiol.
,
602
(
16
), pp.
3929
3954
.10.1113/JP286193
26.
Martin
,
Y. N.
, and
Pabelick
,
C. M.
,
2014
, “
Sex Differences in the Pulmonary Circulation: Implications for Pulmonary Hypertension
,”
Am. J. Physiol.-Heart Circ. Physiol.
,
306
(
9
), pp.
H1253
H1264
.10.1152/ajpheart.00857.2013
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