Abstract

Alzheimer's disease is a progressive degenerative condition that has various levels of effect on one's memory. It is thought to be caused by a buildup of protein in small fluid-filled spaces in the brain called perivascular spaces (PVS). The PVS often takes on the form of an annular region around arteries and is used as a protein-clearing system for the brain. To analyze the modes of mass transfer in the PVS, a digitized scan of a mouse brain PVS segment was meshed and used for computational fluid dynamics (CFD) studies. Tandem analyses were then carried out and compared between the mouse PVS section and a cylinder with commensurate dimensionless parameters and hydraulic resistance. The geometry pair was used to first validate the CFD model and then assess mass transfer in various advection states: no-flow, constant flow, sinusoidal flow, sinusoidal flow with zero net solvent flux, and an anatomically correct asymmetrical periodic flow. Two mass transfer situations were considered, one being a protein build-up and the other being a protein blend-down using a multitude of metrics. Bulk arterial solute transport was found to be advection-controlled. The consideration of temporal evolution and trajectories of contiguous protein bolus volumes revealed that flow pulsation was beneficial at bolus break-up and that additional local wall curvature-based geometry irregularities also were. Using certain measures, local solute peak concentration blend-down appeared to be diffusion-dominated even for high Peclet numbers; however, bolus size evolution analyses showed definite advection support.

References

1.
Hunt
,
B.
,
1977
, “
Diffusion in Laminar Pipe Flow
,”
Int. J. Heat Mass Transfer
,
20
(
4
), pp.
393
401
.10.1016/0017-9310(77)90160-0
2.
Azer
,
K.
,
2005
, “
Taylor Diffusion in Time-Dependent Flow
,”
Int. J. Heat Mass Transfer
,
48
(
13
), pp.
2735
2740
.10.1016/j.ijheatmasstransfer.2005.02.007
3.
Cebull
,
H. L.
,
Aremu
,
O. O.
,
Kulkarni
,
R. S.
,
Zhang
,
S. X.
,
Samuels
,
P.
,
Jermy
,
S.
,
Ntusi
,
N. A. B.
, and
Goergen
,
C. J.
,
2023
, “
Simulating Subject-Specific Aortic Hemodynamic Effects of Valvular Lesions in Rheumatic Heart Disease
,”
ASME J. Biomech. Eng.
,
145
(
11
), p.
111003
.10.1115/1.4063000
4.
Williamson
,
P. N.
,
Docherty
,
P. D.
,
Yazdi
,
S. G.
,
Khanafer
,
A.
,
Kabaliuk
,
N.
,
Jermy
,
M.
, and
Geoghegan
,
P. H.
,
2021
, “
Review of the Development of Hemodynamic Modeling Techniques to Capture Flow Behavior in Arteries Affected by Aneurysm, Atherosclerosis, and Stenting
,”
ASME J. Biomech. Eng.
,
144
(
4
), p.
040802
.10.1115/1.4053082
5.
Khani
,
M.
,
Sass
,
L. R.
,
McCabe
,
A. R.
,
Zitella Verbick
,
L. M.
,
Lad
,
S. P.
,
Sharp
,
M. K.
, and
Martin
,
B. A.
,
2019
, “
Impact of Neurapheresis System on Intrathecal Cerebrospinal Fluid Dynamics: A Computational Fluid Dynamics Study
,”
ASME J. Biomech. Eng.
,
142
(
2
), p.
021006
.10.1115/1.4044308
6.
Fan
,
H.
,
Cai
,
Q.
, and
Qin
,
Z.
,
2023
, “
Measurement and Modeling of Transport Across the Blood–Brain Barrier
,”
ASME J. Biomech. Eng.
,
145
(
8
), p.
080802
.10.1115/1.4062737
7.
Prichard
,
R.
,
Gibson
,
M.
, and
Joseph
,
C.
,
2022
,
Multiscale Biomechanical Modeling of the Brain
,
Academic Press
, Cambridge, MA, pp.
209
238
.
8.
Asgari
,
M.
,
de Zélicourt
,
D.
, and
Kurtcuoglu
,
V.
,
2016
, “
Glymphatic Solute Transport Does Not Require Bulk Flow
,”
Sci. Rep.
,
6
(
1
), p.
38635
.10.1038/srep38635
9.
Rey
,
J.
, and
Sarntinoranont
,
M.
,
2018
, “
Pulsatile Flow Drivers in Brain Parenchyma and Perivascular Spaces: A Resistance Network Model Study
,”
Fluids Barriers CNS
,
15
(
1
), p.
20
.10.1186/s12987-018-0105-6
10.
Keith Sharp
,
M.
,
Carare
,
R. O.
, and
Martin
,
B. A.
,
2019
, “
Dispersion in Porous Media in Oscillatory Flow Between Flat Plates: Applications to Intrathecal, Periarterial and Paraarterial Solute Transport in the Central Nervous System
,”
Fluids Barriers CNS
,
16
(
1
), p.
13
.10.1186/s12987-019-0132-y
11.
Daversin-Catty
,
C.
,
Vinje
,
V.
,
Mardal
,
K.-A.
, and
Rognes
,
M. E.
,
2020
, “
The Mechanisms Behind Perivascular Fluid Flow
,”
Plos One
,
15
(
12
), p.
e0244442
.10.1371/journal.pone.0244442
12.
Bohr
,
T.
,
Hjorth
,
P. G.
,
Holst
,
S. C.
,
Hrabětová
,
S.
,
Kiviniemi
,
V.
,
Lilius
,
T.
,
Lundgaard
,
I.
, et al.,
2022
, “
The Glymphatic System: Current Understanding and Modeling
,”
iScience
,
25
(
9
), p.
104987
.10.1016/j.isci.2022.104987
13.
Kelley
,
D. H.
, and
Thomas
,
J. H.
,
2023
, “
Cerebrospinal Fluid Flow
,”
Annu. Rev. Fluid Mech.
,
55
(
1
), pp.
237
264
.10.1146/annurev-fluid-120720-011638
14.
Bojarskaite
,
L.
,
Vallet
,
A.
,
Bjørnstad
,
D. M.
,
Gullestad Binder
,
K. M.
,
Cunen
,
C.
,
Heuser
,
K.
,
Kuchta
,
M.
,
Mardal
,
K.-A.
, and
Enger
,
R.
,
2023
, “
Sleep Cycle-Dependent Vascular Dynamics in Male Mice and the Predicted Effects on Perivascular Cerebrospinal Fluid Flow and Solute Transport
,”
Nat. Commun.
,
14
(
1
), p.
953
.10.1038/s41467-023-36643-5
15.
Troyetsky
,
D. E.
,
Tithof
,
J.
,
Thomas
,
J. H.
, and
Kelley
,
D. H.
,
2021
, “
Dispersion as a Waste-Clearance Mechanism in Flow Through Penetrating Perivascular Spaces in the Brain
,”
Sci. Rep.
,
11
(
1
), p.
4595
.10.1038/s41598-021-83951-1
16.
Vinje
,
V.
,
Bakker
,
E. N. T. P.
, and
Rognes
,
M. E.
,
2021
, “
Brain Solute Transport is More Rapid in Periarterial Than Perivenous Spaces
,”
Sci. Rep.
,
11
(
1
), p.
16085
.10.1038/s41598-021-95306-x
17.
Kedarasetti
,
R. T.
,
Drew
,
P. J.
, and
Costanzo
,
F.
,
2022
, “
Arterial Vasodilation Drives Convective Fluid Flow in the Brain: A Poroelastic Model
,”
Fluids Barriers CNS
,
19
(
1
), p.
34
.10.1186/s12987-022-00326-y
18.
Elliott
,
W.
,
Guo
,
D.
,
Veldtman
,
G.
, and
Tan
,
W.
,
2019
, “
Effect of Viscoelasticity on Arterial-Like Pulsatile Flow Dynamics and Energy
,”
ASME J. Biomech. Eng.
,
142
(
4
), p.
041001
.10.1115/1.4044877
19.
Novo
,
M.
,
Freire
,
S.
, and
Al-Soufi
,
W.
,
2018
, “
Critical Aggregation Concentration for the Formation of Early Amyloid-Β (1–42) Oligomers
,”
Sci. Rep.
,
8
(
1
), p.
1783
.10.1038/s41598-018-19961-3
20.
Boster
,
K. A. S.
,
Cai
,
S.
,
Ladrón-de-Guevara
,
A.
,
Sun
,
J.
,
Zheng
,
X.
,
Du
,
T.
,
Thomas
,
J. H.
,
Nedergaard
,
M.
,
Karniadakis
,
G. E.
, and
Kelley
,
D. H.
,
2023
, “
Artificial Intelligence Velocimetry Reveals In Vivo Flow Rates, Pressure Gradients, and Shear Stresses in Murine Perivascular Flows
,”
Proc. Natl. Acad. Sci.
,
120
(
14
), p.
e2217744120
.10.1073/pnas.2217744120
21.
Kacinski
,
R.
,
Strasser
,
W.
,
Leonard
,
S.
,
Prichard
,
R.
, and
Truxel
,
B.
,
2023
, “
Validation of a Human Upper Airway Computational Fluid Dynamics Model for Turbulent Mixing
,”
ASME J. Fluids Eng.
,
145
(
12
), p.
121203
.10.1115/1.4063061
22.
Strasser
,
W.
,
2022
, “
The Nature of “Searching” Vortices in Fluidic Logic Driven by a Switching Jet
,”
ASME J. Fluids Eng.
,
144
(
8
), p.
081303
.10.1115/1.4053786
23.
Strasser
,
W.
,
Kacinski
,
R.
, and
Wilson
,
D.
,
2023
,
It's About Time: Jet Interactions in an Asymmetrical Plenum
,
Nuclear Engineering Technology
, Westmont, IL.
24.
Raicevic
,
N.
,
Forer
,
J. M.
,
Ladrón-de-Guevara
,
A.
,
Du
,
T.
,
Nedergaard
,
M.
,
Kelley
,
D. H.
, and
Boster
,
K.
,
2023
, “
Sizes and Shapes of Perivascular Spaces Surrounding Murine Pial Arteries
,”
Fluids and Barriers CNS
,
20
(
1
), p.
56
.10.1186/s12987-023-00454-z
25.
Strasser
,
W.
,
2007
, “
CFD Investigation of Gear Pump Mixing Using Deforming/Agglomerating Mesh
,”
ASME J. Fluids Eng.
,
129
(
4
), pp.
476
484
.10.1115/1.2436577
26.
Bekhti
,
Y.
,
Lucka
,
F.
,
Salmon
,
J.
, and
Gramfort
,
A.
,
2018
, “
A Hierarchical Bayesian Perspective on Majorization-Minimization for Non-Convex Sparse Regression: Application to M/EEG Source Imaging
,”
Inverse Probl.
,
34
(
8
), p.
085010
.10.1088/1361-6420/aac9b3
27.
Yoder
,
E.
,
Strasser
,
W.
,
Kacinski
,
R.
, and
Jones
,
B.
, “Hot Spot Induced Thermal Runaway Map for Polymerization Reactors,” Macromol. React. Eng., Accepted for Publication.
28.
Yoder
,
E.
,
Strasser
,
W.
,
Kacinski
,
R.
, and
Jones
,
B.
, “Unrestraining The Biot Number for Systems With Internal Heat Generation,” J. Sol. Energy Eng., Accepted for Publication.
29.
Dougherty
,
G.
, and
Varro
,
J.
,
2000
, “
A Quantitative Index for the Measurement of the Tortuosity of Blood Vessels
,”
Med. Eng. Phys.
,
22
(
8
), pp.
567
574
.10.1016/S1350-4533(00)00074-6
30.
Kashyap
,
V.
,
Gharleghi
,
R.
,
Li
,
D. D.
,
McGrath-Cadell
,
L.
,
Graham
,
R. M.
,
Ellis
,
C.
,
Webster
,
M.
, and
Beier
,
S.
,
2022
, “
Accuracy of Vascular Tortuosity Measures Using Computational Modelling
,”
Sci. Rep.
,
12
(
1
), p.
865
.10.1038/s41598-022-04796-w
31.
Boster
,
K. A. S.
,
Sun
,
J.
,
Shang
,
J. K.
,
Kelley
,
D. H.
, and
Thomas
,
J. H.
,
2024
, “
Hydraulic Resistance of Three-Dimensional Pial Perivascular Spaces in the Brain
,”
Fluids Barriers CNS
,
21
(
1
), p.
7
.10.1186/s12987-023-00505-5
32.
Hurry
,
A. S.
,
Hayward
,
K.
,
Guzzomi
,
F.
,
Rauthan
,
K.
, and
Vafadar
,
A.
,
2023
, “
Thermo-Hydraulic Performance Evaluation of a NACA 63-015 Heat Exchanger With Shark Denticles as Surface Textures
,”
Int. J. Heat Mass Transfer
,
216
, p.
124591
.10.1016/j.ijheatmasstransfer.2023.124591
33.
Ho
,
D.
,
Zhao
,
X.
,
Gao
,
S.
,
Hong
,
C.
,
Vatner
,
D. E.
, and
Vatner
,
S. F.
,
2011
, “
Heart Rate and Electrocardiography Monitoring in Mice
,”
Curr. Protoc. Mouse Biol.
,
1
(
1
), pp.
123
139
.10.1002/9780470942390.mo100159
34.
Hablitz
,
L. M.
,
Vinitsky
,
H. S.
,
Sun
,
Q.
,
Stæger
,
F. F.
,
Sigurdsson
,
B.
,
Mortensen
,
K. N.
,
Lilius
,
T. O.
, and
Nedergaard
,
M.
,
2019
, “
Increased Glymphatic Influx is Correlated With High EEG Delta Power and Low Heart Rate in Mice Under Anesthesia
,”
Sci. Adv.
,
5
(
2
), p.
eaav5447
.10.1126/sciadv.aav5447
You do not currently have access to this content.