Graphical Abstract Figure
Graphical Abstract Figure
Close modal

Abstract

Physiological closed-loop control algorithms play an important role in the development of autonomous medical care systems, a promising area of research that has the potential to deliver healthcare therapies meeting each patient's specific needs. Computational approaches can support the evaluation of physiological closed-loop control algorithms considering various sources of patient variability that they may be presented with. In this article, we present a generative approach to testing the performance of physiological closed-loop control algorithms. This approach exploits a generative physiological model (which consists of stochastic and dynamic components that represent diverse physiological behaviors across a patient population) to generate a select group of virtual subjects. By testing a physiological closed-loop control algorithm against this select group, the approach estimates the distribution of relevant performance metrics in the represented population. We illustrate the promise of this approach by applying it to a practical case study on testing a closed-loop fluid resuscitation control algorithm designed for hemodynamic management. In this context, we show that the proposed approach can test the algorithm against virtual subjects equipped with a wide range of plausible physiological characteristics and behavior and that the test results can be used to estimate the distribution of relevant performance metrics in the represented population. In sum, the generative testing approach may offer a practical, efficient solution for conducting preclinical tests on physiological closed-loop control algorithms.

References

1.
Pappalardo
,
F.
,
Russo
,
G.
,
Tshinanu
,
F. M.
, and
Viceconti
,
M.
,
2019
, “
In Silico Clinical Trials: Concepts and Early Adoptions
,”
Briefings Bioinf.
,
20
(
5
), pp.
1699
1708
.
2.
Viceconti
,
M.
,
Emili
,
L.
,
Afshari
,
P.
,
Courcelles
,
E.
,
Curreli
,
C.
,
Famaey
,
N.
,
Geris
,
L.
, et al
,
2021
, “
Possible Contexts of Use for In Silico Trials Methodologies: A Consensus-Based Review
,”
IEEE J. Biomed. Health Inform.
,
25
(
10
), pp.
3977
3982
.
3.
Snider
,
E. J.
,
Berard
,
D.
,
Vega
,
S. J.
,
Hernandez Torres
,
S. I.
,
Avital
,
G.
, and
Boice
,
E. N.
,
2022
, “
An Automated Hardware-in-Loop Testbed for Evaluating Hemorrhagic Shock Resuscitation Controllers
,”
Bioengineering
,
9
(
8
), p.
373
.
4.
Mirinejad
,
H.
,
Parvinian
,
B.
,
Ricks
,
M.
,
Zhang
,
Y.
,
Weininger
,
S.
,
Hahn
,
J. O.
, and
Scully
,
C. G.
,
2020
, “
Evaluation of Fluid Resuscitation Control Algorithms Via a Hardware-in-the-Loop Test Bed
,”
IEEE Trans. Biomed. Eng.
,
67
(
2
), pp.
471
481
.
5.
Parvinian
,
B.
,
Pathmanathan
,
P.
,
Daluwatte
,
C.
,
Yaghouby
,
F.
,
Gray
,
R. A.
,
Weininger
,
S.
,
Morrison
,
T. M.
, and
Scully
,
C. G.
,
2019
, “
Credibility Evidence for Computational Patient Models Used in the Development of Physiological Closed-Loop Controlled Devices for Critical Care Medicine
,”
Front. Physiol.
,
10
(
Mar.
), p.
220
.
6.
Tivay
,
A.
,
Kramer
,
G. C.
, and
Hahn
,
J. O.
,
2022
, “
Collective Variational Inference for Personalized and Generative Physiological Modeling: A Case Study on Hemorrhage Resuscitation
,”
IEEE Trans. Biomed. Eng.
,
69
(
2
), pp.
666
677
.
7.
Kao
,
Y. M.
,
Sampson
,
C. M.
,
Shah
,
S. A.
,
Salsbury
,
J. R.
,
Tivay
,
A.
,
Bighamian
,
R.
,
Scully
,
C. G.
,
Kinsky
,
M.
,
Kramer
,
G. C.
, and
Hahn
,
J. O.
,
2023
, “
A Mathematical Model for Simulation of Vasoplegic Shock and Vasopressor Therapy
,”
IEEE Trans. Biomed. Eng.
,
70
(
5
), pp.
1565
1574
.
8.
Arabidarrehdor
,
G.
,
Tivay
,
A.
,
Meador
,
C.
,
Kramer
,
G. C.
,
Hahn
,
J. O.
, and
Salinas
,
J.
,
2022
, “
Mathematical Modeling, In-Human Evaluation and Analysis of Volume Kinetics and Kidney Function After Burn Injury and Resuscitation
,”
IEEE Trans. Biomed. Eng.
,
69
(
1
), pp.
366
376
.
9.
Arabidarrehdor
,
G.
,
Tivay
,
A.
,
Bighamian
,
R.
,
Meador
,
C.
,
Kramer
,
G. C.
,
Hahn
,
J. O.
, and
Salinas
,
J.
,
2021
, “
Mathematical Model of Volume Kinetics and Renal Function After Burn Injury and Resuscitation
,”
Burns
,
47
(
2
), pp.
371
386
.
10.
Dalla Man
,
C.
,
Micheletto
,
F.
,
Lv
,
D.
,
Breton
,
M.
,
Kovatchev
,
B.
, and
Cobelli
,
C.
,
2014
, “
The UVA/PADOVA Type 1 Diabetes Simulator: New Features
,”
J Diabetes Sci Technol
,
8
(
1
), pp.
26
34
.
11.
Visentin
,
R.
,
Campos-Náñez
,
E.
,
Schiavon
,
M.
,
Lv
,
D.
,
Vettoretti
,
M.
,
Breton
,
M.
,
Kovatchev
,
B. P.
,
Dalla Man
,
C.
, and
Cobelli
,
C.
,
2018
, “
The UVA/Padova Type 1 Diabetes Simulator Goes From Single Meal to Single Day
,”
J. Diabetes Sci. Technol.
,
12
(
2
), pp.
273
281
.
12.
Viceconti
,
M.
,
Juarez
,
M. A.
,
Curreli
,
C.
,
Pennisi
,
M.
,
Russo
,
G.
, and
Pappalardo
,
F.
,
2020
, “
Credibility of in Silico Trial Technologies—A Theoretical Framing
,”
IEEE J. Biomed. Health Inform.
,
24
(
1
), pp.
4
13
.
13.
Viceconti
,
M.
,
Pappalardo
,
F.
,
Rodriguez
,
B.
,
Horner
,
M.
,
Bischoff
,
J.
, and
Musuamba Tshinanu
,
F.
,
2021
, “
In Silico Trials: Verification, Validation and Uncertainty Quantification of Predictive Models Used in the Regulatory Evaluation of Biomedical Products
,”
Methods
,
185
(
1
), pp.
120
127
.
14.
Jang
,
K. J.
,
Pant
,
Y. V.
,
Zhang
,
B.
,
Weimer
,
J.
, and
Mangharam
,
R.
,
2019
, “
Robustness Evaluation of Computer-Aided Clinical Trials for Medical Devices
,”
ICCPS 2019—Proceedings of the 2019 ACM/IEEE International Conference on Cyber-Physical Systems
,
Montreal, Quebec, Canada
,
Apr. 16–18
, pp.
163
173
.
15.
Bighamian
,
R.
,
Hahn
,
J. O.
,
Kramer
,
G.
, and
Scully
,
C.
,
2021
, “
Accuracy Assessment Methods for Physiological Model Selection Toward Evaluation of Closed-Loop Controlled Medical Devices
,”
PLoS One
,
16
(
4
), p.
e0251001
.
16.
Kanal
,
V.
,
Pathmanathan
,
P.
,
Hahn
,
J. O.
,
Kramer
,
G.
,
Scully
,
C.
, and
Bighamian
,
R.
,
2022
, “
Development and Validation of a Mathematical Model of Heart Rate Response to Fluid Perturbation
,”
Sci. Rep.
,
12
(
1
), pp.
1
16
.
17.
Julier
,
S.
,
Uhlmann
,
J.
, and
Durrant-Whyte
,
H. F.
,
2000
, “
A New Method for the Nonlinear Transformation of Means and Covariances in Filters and Estimators
,”
IEEE Trans. Autom. Control
,
45
(
3
), pp.
477
482
.
18.
Wan
,
E. A.
, and
van der Merwe
,
R.
,
2001
, “The Unscented Kalman Filter,”
Kalman Filtering and Neural Networks
,
S.
Haykin
, ed.,
John Wiley & Sons, Ltd
,
Hoboken, NJ
, pp.
221
280
.
19.
Transtrum
,
M. K.
,
Machta
,
B. B.
,
Brown
,
K. S.
,
Daniels
,
B. C.
,
Myers
,
C. R.
, and
Sethna
,
J. P.
,
2015
, “
Perspective: Sloppiness and Emergent Theories in Physics, Biology, and Beyond
,”
J. Chem. Phys.
,
143
(
1
), p.
010901
.
20.
Avital
,
G.
,
Snider
,
E. J.
,
Berard
,
D.
,
Vega
,
S. J.
,
Hernandez Torres
,
S. I.
,
Convertino
,
V. A.
,
Salinas
,
J.
, and
Boice
,
E. N.
,
2022
, “
Closed-Loop Controlled Fluid Administration Systems: A Comprehensive Scoping Review
,”
J. Pers. Med.
,
12
(
7
), p.
1168
.
You do not currently have access to this content.