This article has been accepted for publication in IEEE Journal of Biomedical and Health Informatics.

This is the author's version which has not been fully edited and
content may change prior to final publication. Citation information: DOI 10.1109/JBHI.2023.3240460

M. Jung et al.: Prediction of Serious Intracranial Hypertension from Low-Resolution Neuromonitoring in Traumatic Brain Injury: An Explainable Machine Learning Approach

Prediction of Serious Intracranial Hypertension

from Low-Resolution Neuromonitoring in
Traumatic Brain Injury: An Explainable Machine
Learning Approach
Min-Kyung Jung, Daesun Ahn, Chan Min Park, Eun Jin Ha, Tae Hoon Roh, Nam Kyu You,
Dukyong Yoon, Hakseung Kim, Se-Hyuk Kim and Dong-Joo Kim

 could be used to predict mortality (AUROC = 0.893, p <

Abstract— There is a strong association between
intracranial hypertension (IH) that occurs following the
acute phase of traumatic brain injury (TBI) and negative
outcomes. This study proposes a pressure–time dose
(PTD)-based parameter that may specify a possible serious
IH (SIH) event and develops a model to predict SIH. The
minute-by-minute signals of arterial blood pressure (ABP)
and intracranial pressure (ICP) of 117 TBI patients were
utilized as the internal validation dataset. The SIH event
was explored through the prognostic power of the IH event
variables for the outcome after 6 months, and an IH event
with thresholds that included an ICP of 20 mmHg and PTD
> 130 mmHg * minutes was considered an SIH event. The
physiological characteristics of normal, IH and SIH events
were investigated. LightGBM was employed to forecast an
SIH event from various time intervals using physiological
parameters derived from the ABP and ICP. Training and
validation were conducted on 1,921 SIH events. External
validation was performed on two multi-center datasets
containing 26 and 382 SIH events. The SIH parameters
This work was supported in part by a National Research Foundation
of Korea (NRF) grant funded by the Korean government (Ministry of
Science and ICT, MSIT) under Grant 2022R1A2C1013205
(Co-corresponding authors: Dukyong Yoon; Hakseung Kim.).
Min-Kyung Jung and Hakseung Kim are with the Department of Brain
and Cognitive Engineering, Korea University, 02841, South Korea
(e-mail: mkjung@korea.ac.kr; mkhsm@korea.ac.kr)
Daesun Ahn is with the Department of Molecular and Cell Biology,
University of California, Berkeley, 94720, USA (e-mail:
dsahn22@berkeley.edu)
Chan Min Park and Dukyong Yoon are with the Department of
Biomedical Systems Informatics, Yonsei University College of Medicine,
03722, South Korea (e-mail: jeff4273@yonsei.ac.kr;
dukyong.yoon@yonsei.ac.kr)
Eun Jin Ha is with the Department of Critical Care Medicine, Seoul
National University Hospital, 03080, South Korea (e-mail:
65932@snuh.org)
Tae Hoon Roh, Nam Kyu You, and Se-Hyuk Kim are with the
Department of Neurosurgery, Ajou University School of Medicine,
16499, South Korea (e-mail: Throh@ajou.ac.kr; nkyou@ajou.ac.kr;
nsksh@ajou.ac.kr)
Dong-Joo Kim is with the Department of Brain and Cognitive
Engineering, Korea University, 02841, South Korea, and with the
Department of Neurology, Korea University College of Medicine, 02841,
South Korea, Department of Artificial Intelligence, Korea University,
02841, South Korea and NeuroTx Co., Ltd., 02841, South Korea
(e-mail: dongjookim@korea.ac.kr).
0.001) and favorability (AUROC = 0.858, p < 0.001). The
trained model robustly forecasted SIH after 5 and 480
minutes with an accuracy of 86.95% and 72.18% in internal
validation. External validation also revealed a similar
performance. This study demonstrated that the proposed
SIH prediction model has reasonable predictive capacities.
A future intervention study is required to investigate
whether the definition of SIH is maintained in multi-center
data and to ensure the effects of the predictive system on
TBI patient outcomes at the bedside.
Index Terms— Clinical outcome; Intracranial hypertension;
Traumatic brain injury; Low-resolution neuromonitoring;
Explainable machine learning
I. INTRODUCTION
I ntracranial hypertension (IH) commonly occurs during the
acute phase of traumatic brain injury (TBI) and has been
shown to contribute to the worsening of a secondary
ischemic-edematous insult after TBI and subsequently negative
outcomes [1-3]. Thus, despite the lack of Class I evidence, the
Brain Trauma Foundation (BTF) guidelines [4] recommend
intracranial pressure (ICP) monitoring in severe TBI patients to
rapidly detect and manage IH events. Furthermore, by
analyzing the recorded ICP data with advanced signal
processing and machine learning techniques, the forecasting of
upcoming IH events during the monitoring of TBI patients has
become an important, viable research objective [5-13].
However, most previously proposed IH forecasting models rely
on a rather simple IH definition (e.g., ICP over 20, 22, or 25
mmHg for more than 5 minutes [14-16]), which may
potentially hinder the efficacy of the models.
The limited prognostic value of a static ICP threshold during
the management of TBI has long been recognized [17-19], and
there have been a wide variety of attempts to address the issue.
Among those, the concept of pressure–time dose (PTD)
provides an alternative approach for evaluating the severity of
an IH event by considering both the duration and the magnitude
(i.e., raw ICP value) of the IH event [20, 21]. The findings from
related prior studies indicate that a higher PTD is associated
with worse outcomes and hence may offer higher prognostic

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 This article has been accepted for publication in IEEE Journal of Biomedical and Health Informatics. This is the author's version which has not been fully edited and
content may change prior to final publication. Citation information: DOI 10.1109/JBHI.2023.3240460
M. Jung et al.: Prediction of Serious Intracranial Hypertension from Low-Resolution Neuromonitoring in Traumatic Brain Injury: An Explainable Machine Learning Approach
value compared to using only ICP thresholds [20, 22, 23]. In
this context, it would be worthwhile to employ PTD thresholds,
rather than the ICP thresholds, for the development of IH
forecasting systems; however, such an attempt has rarely been
made [13].
Another important yet rarely discussed limitation of the prior
IH forecasting models is their dependence on high-frequency
(high-resolution) neurophysiological data. In reality, most
(neuro)intensive care units worldwide have difficulty storing
physiological signals with high frequency and hence export
data in a minute-by-minute fashion [24, 25]. With these two
shared limitations, i.e., the reliance on simple ICP thresholds
and high-frequency data, the previously proposed IH
forecasting models may not be readily applicable in clinical
practice, except for a few research-oriented institutes. Thus,
this study aimed to 1) determine a PTD threshold and the
corresponding magnitude of ICP that is most negatively
associated with outcomes after TBI (serious IH event, hereafter
SIH), 2) construct an “interpretable” machine learning model
that reliably forecasts an upcoming SIH event, and 3) utilize
low-frequency ICP data. To this aim, we validated the
performance of the constructed model against a separate,
external dataset.
II. RELATED WORK
A. Identifying IH events associated with a worse
outcome after TBI
While the literature suggests that a PTD threshold offers a
higher prognostic value than the raw ICP threshold [20-23], an
intuitive PTD threshold and the corresponding magnitude of
ICP associated with worse outcomes after TBI have yet to be
reported. F. Gu¨iza et al. [26] assessed the impact of the
duration and intensity of IH episodes on 6-month neurological
outcomes. The authors noted that episodes of higher
intracranial pressure can only be tolerated for shorter durations
of time. C.A. Å kerlund et al. [23] used PTD to consider the size
of the event when defining IH. After dividing the two groups by
the outcome, the authors searched for the ICP threshold at
which the difference in PTD was most prominent. Statistically,
the difference between the two groups was remarkable when
the ICP threshold was 20 mmHg. However, since only the
threshold for calculating the PTD was determined, it was not
possible to state at what scale an event was negative for the
patient outcome. In other words, the method could not specify a
single event definition that negatively affected the patient
outcome. HJ Lee et al. [13] defined “life-threatening
hypertension (LTH)” as IH events that have life-threatening
effects on patients, and this was evaluated using a combination
of PTD and PRx (which is known to reflect cerebral
autoregulation [27]). Nonetheless, while LTH could be helpful
in identifying refractory IH events, it relies on a fixed, constant
PTD value (PTD > 5 [13]).
B. Forecasting IH events
In clinical settings, IH events are usually detected after their
occurrence, and because delayed treatment poses a significant
risk, various attempts have been made to predict IH events.
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Fig. 1. Consort diagrams of the subject inclusion/exclusion process.
ABP=arterial blood pressure; ICP=intracranial pressure; TBI=traumatic
brain injury; MIMIC-III WFDB= Medical Information Mart for Intensive
Care III waveform database; NAN ratio=the proportion of missing
values.
Early attempts have utilized simple statistical techniques,
including univariate analysis, such as the area under the
receiver operating characteristic curve (AUROC) [5] and
logistic regression [6]. Later studies employed more advanced
machine learning algorithms, such as Gaussian process,
decision tree, and quadratic discriminator models [7-10], and
more recently, gradient boosting decision tree-based advanced
machine learning models (e.g., XGBoost and CatBoost)
yielded improved performance for predicting IH events [11].
The decision tree-variants approach is of particular interest in
clinical practice since it offers the interpretability of a model’s
output, which would undoubtedly be more helpful than
black-box models in the clinical decision-making process [12].
III. MATERIALS AND METHODS
A. Cohort selection and data acquisition
1) Ajou University Hospital
This study used three separate databases to train and validate
the IH forecasting model. For the construction of the model,
physiological signals and clinical data from 124 TBI patients
collected at Ajou University Hospital were used. The database
contains demographic information, the minute-by-minute
arterial blood pressure (ABP) and ICP readings, the 6-month
Glasgow Outcome Scale Extended (GOSE) score, etc. The data
from seven patients were excluded because their ICP records
were not available or they were younger than 16 years of age.
Finally, a total of 117 patient records met our inclusion criteria,
as shown in Fig. 1. This study was approved by the institutional
review board of Ajou University Hospital
(AJIRB-MED-MDB-19-420). ABP was monitored invasively
using an arterial line positioned in the radial artery and a
standard pressure monitoring kit (pediatric jugular
catheterization set, Arrow International). ICP was acquired at
subdural or intraparenchymal locations (Codman ICP express
monitor, Codman & Shurtleff). ABP and ICP were measured
with the Life Scope G9 CSM-1901 (Nihon Kohden).
2) MIMIC-III WFDB
For one external validation, the Medical Information Mart
for Intensive Care III waveform database (MIMIC-III WFDB)
 This article has been accepted for publication in IEEE Journal of Biomedical and Health Informatics. This is the author's version which has not been fully edited and
content may change prior to final publication. Citation information: DOI 10.1109/JBHI.2023.3240460

M. Jung et al.: Prediction of Serious Intracranial Hypertension from Low-Resolution Neuromonitoring in Traumatic Brain Injury: An Explainable Machine Learning Approach

Fig. 2. Illustration of a previous serious intracranial hypertension (SIH) segment, from our Ajou’s Univ. Hospital database. For each segment of 30
minutes in length, the mean value of a physiological parameter is calculated to extract a representative characteristic of the neuromonitoring signal.
To predict SIH events, the LightGBM model is trained with segments derived from various time intervals.
[28], which contains 9,774 patient records, was utilized. To
match the format with the Ajou Univ. Hospital data, the ABP
and ICP values measured at 125 Hz were downsampled to 1/60
Hz. The inclusion criteria were as follows: 1) ABP and ICP data
were available, 2) the patient was diagnosed with TBI, 3) the
ratio of missing values was less than 25%, and 4) the patient
was younger than 16 years of age. The records of 16 patients
met the above criteria, as shown in Fig. 1. ABP and ICP values
were acquired through the bedside IntelliVue Patient
Monitoring System (Philips Healthcare, The Netherlands).
3) Seoul National University Hospital
For the other external validation, data from 116 patients
acquired from VitalDB at Seoul National University Hospital
(SNUH) were retrieved [29]. The database measured ABP and
ICP at 200 Hz and resampled to minute-by-minute. The
inclusion criteria for MIMIC-III were applied. Finally, the
neuro-monitoring signal obtained from 33 TBI patients was
used to verify the model as shown in Fig. 1. ABP and ICP was
measured with the bedside IntelliVue Patient Monitoring
System (Philips Healthcare, The Netherlands) or
Analog-to-digital converters (SNUADC, VitalLab, Korea).
These data have been approved by the Seoul National
University Hospital Institutional Review Board (IRB No.
H-2210-146-1373).
B. Determination of SIH events
In this study, numerous IH events were defined based on
PTD (defined as an area above the threshold and below the ICP
curve [21]). PTD is indicative of both the duration and
amplitude of an IH event and hence could be a better alternative
to using only ICP values for identifying severe IH events [20,
21]. The association between cumulative PTD and mortality
following TBI has been shown to be significant [20-22].
Defined as the area above an ICP threshold and below the ICP
curve [21, 22], PTD can be expressed by the following formula:
PTD(mmHg  minute) =  i =1 ( ICPi − ICPth )  t
n
(1)
where n is the number of data points included in the IH event,
ICPi is the average ICP of the i-th point, ICPth is the threshold of
the ICP, and Δt is the time (1 minute) between each data point.
Employing different ICP thresholds yields a wide range of PTD
and severe IH candidates.
By employing an ICP threshold of 1-40 mmHg and a PTD
threshold of 10-1,000 mmHg·min (10, 20, …, 990,1,000), a
total of 4,000 combinations of severe IH definitions were
generated (Supplementary Section A). Next, this study aimed
to determine an SIH event, i.e., the combination of ICP and
PTD values that is most negatively associated with the outcome,
by evaluating the prognostic power of IH event variables (i.e.,
count, duration, proportion) for mortality (6-month GOSE, 1 vs.
2-8) and favorability (6-month GOSE, 1-3 vs. 4-8 [30])
calculated from the 4,000 combinations. The number, duration
(i.e., total length of IH event time), and proportion (i.e., the
ratio of IH event time) of events were calculated. For each
patient, the IH event variables for various definitions were
derived. For all IH-related variables, AUROCs between
outcome and IH event were calculated. The SIH event was
identified by evaluating a total of 24,000 AUROC values
(4,000 severe IH definitions * 3 variables derived from events *
2 outcomes). To minimize the impact of artifacts and outliers,
the minimum length of SIH was set as 5 minutes.
In addition, to mitigate the possible data dependency issue, a
bootstrapping technique used in a previous study with a similar
design was employed [23]. By creating 1,000 new cohorts from
a random selection of 100 patients, the average AUROC for
each IH definition was used as the standard for the SIH
definition.
C. Prediction model for SIH forecasting
This study utilized 30-minute signal segments to predict
whether SIH events would start after various time intervals (Fig.
2). Data segments 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 360,
and 480 minutes prior to the SIH episode were labeled positive.
The number of positive segments for each time interval was
1,470, 1,366, 1,281, 1,070, 926, 801, 610, 507, 382, 316, 235,
and 191, respectively. The SIH events that occurred during the
interval were excluded from the analyses. Hence, the number of
positive segments tended to decrease as the length of the time
interval increased. Negative segments were randomly extracted
for the cases in which an SIH event did not occur for 24 hours.
Therefore, the segment of the model that receives input does
not contain the beginning or end of the SIH event.

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 This article has been accepted for publication in IEEE Journal of Biomedical and Health Informatics. This is the author's version which has not been fully edited and
content may change prior to final publication. Citation information: DOI 10.1109/JBHI.2023.3240460

M. Jung et al.: Prediction of Serious Intracranial Hypertension from Low-Resolution Neuromonitoring in Traumatic Brain Injury: An Explainable Machine Learning Approach

TABLE Ⅰ
DESCRIPTION OF THE TIME AND CORRELATION INPUT PARAMETERS.
Parameter Description
MAP Mean ABP
PP Pulse amplitude of ABP
MICP Mean ICP
AMP Pulse amplitude of ICP
CPP Cerebral perfusion pressure, MAP - MICP
PTD Pressure time dose
PRx Pearson correlation coefficient between the MAP and ICP
PAx Pearson correlation coefficient between the MAP and AMP
RAC Pearson correlation coefficient between the CPP and AMP
RAP Pearson correlation coefficient between the ICP and AMP
wICP Compensatory-reserve-weighted ICP, ICP x (1-RAP)
PRx=pressure reactivity index; PAx=pulse amplitude index; RAC=correlation of AMP and CPP; RAP=correlation of AMP and ICP;
wICP=compensatory-reserve-weighted ICP.
For prediction, the ABP- and ICP-based parameters, which
are known to reflect the neurophysiological status, were
utilized as the model input features (Table 1, adapted from prior
work [13]). The types of parameters are largely divided into
three categories: time-series, correlation, and demographics.
For time-series parameters, MAP [31], PP [32, 33], MICP [34],
AMP [34], CPP [35], wICP [36], and PTD [20-22] were
utilized. In the case of correlation parameters, PRx [27], PAx
[37], RAC [38], and RAP [39] were utilized. Following the
methods employed by previous studies that analyzed the
minute-by-minute signal, these indicators were derived through
a window size of 20 minutes and an update period of 1 minute
to acquire sufficient data points. The amplitude of the pulse
waveform was calculated using the values of the systolic and
diastolic peaks, stored together when exporting
minute-by-minute data. For demographics, age, Glasgow Coma
Scale (GCS), Revised Trauma Score (RTS), and sex
information were used. Among these parameters, the time
series and correlation parameters, as shown in Fig. 2, were used
as input features for the mean of a segment. For ABP and ICP,
the standard deviation (SD) of the segment was also used.
Among the categorical variables, sex (male and female) was
conveyed to the predictive model as features through one-hot
encoding.
In this study, to utilize the interpretability and low
computational complexity of a gradient boosting model,
LightGBM was used as the predictive model [40]. As one of the
notable gradient boosting algorithms, it minimizes predictive
error loss by using leaf-centered tree segmentation that
continuously divides leaf nodes with maximum loss values
without balancing trees. Compared to other machine learning
methods, LightGBM has several strengths. First, it has a short
learning and prediction time. Second, memory usage is
relatively low. Finally, parallel learning through a graphics
process unit (GPU) is possible. For these reasons, the
LightGBM model is being widely used in medical
classification and prediction tasks [41, 42].
D. SHAP values
To analyze the precursor pattern of a patient’s condition
before an SIH event occurrence, SHapley Additive
Clinical relevance
Can cause severe and linear changes in cerebral blood flow [29]
Related with cardiac output [30, 31]
Related with intracranial compensatory reserve [32]
Related with intracranial compensatory reserve [32]
Related with cerebral blood flow [33]
Related with worse outcome [19-21]
Related with cerebral autoregulation [26]
Related with cerebral autoregulation robust at lower ICP [35]
Related with cerebral autoregulation and intracranial compensatory reserve [36]
Related with intracranial compensatory reserve [37]
Related with the absolute ICP and cerebrovascular regulation [34]
exPlanations (SHAP) was utilized [43]. The SHAP method
provides not only an analysis of a single prediction result but
also a holistic analysis based on the sum of Shapley values. It
can derive feature importance by calculating the effect of a
feature on the model and enables us to understand the effect of a
feature on the prediction result of the model. Due to these
advantages, other IH prediction studies have also used SHAP
[11, 13]. This study employed TreeSHAP [44], a SHAP variant
that calculates Shapley values more quickly and accurately. To
obtain information on the feature that is important in prediction,
internal validation datasets were used. In the summary plot,
features important for prediction were visualized and aligned
according to importance.
E. Model implementation
The LightGBM model was executed through scikit-learn and
LightGBM libraries in Python 3.6 environments. To strictly
verify the model performance, 10-repeated 5-group fold
cross-validation was performed on the internal dataset. The
stratified technique was applied to adjust the proportion of
labels to be similar in each segment. The data imbalance
problem was solved by undersampling the negative segment
and equally matching the ratio of labels. The hyperparameters
of the LightGBM model were optimized through grid search.
The dropout rate was used as one of (0.2, 0.3, and 0.4) using the
Dart method. The tree depth was set to one of (5, 7, and 9), and
the number of leaf nodes was selected from (16, 32, and 64).
Finally, for external validation, the model learned from the
internal dataset was additionally verified in MIMIC-III WFDB.
F. Statistical analysis
AUROC analysis was conducted to examine the prognostic
capacity of the IH event variables. To investigate the
characteristics of the SIH event, data normality was tested
using the Kolmogorov–Smirnov test, and differences between
three groups (i.e., normal, IH, and SIH) were compared using
one-way analysis of variance (ANOVA) and Scheffe’s post hoc
test. In all analyses, p < 0.05 was considered statistically
significant. All statistical analyses were performed in SPSS
version 25 (IBM SPSS, IBM Corp.).

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 This article has been accepted for publication in IEEE Journal of Biomedical and Health Informatics. This is the author's version which has not been fully edited and
content may change prior to final publication. Citation information: DOI 10.1109/JBHI.2023.3240460

M. Jung et al.: Prediction of Serious Intracranial Hypertension from Low-Resolution Neuromonitoring in Traumatic Brain Injury: An Explainable Machine Learning Approach

TABLE Ⅱ
PATIENT DEMOGRAPHIC INFORMATION.
Ajou Univ. Hospital MIMIC-III WFDB SNUH
Survived (n=83) Died (n=34) Survived (n=9) Died (n=7) Survived (n=22) Died (n=11)
Demographic characteristics
Age, median (IQR) 46 (32-59) 60 (49.25-68.75) 66 (60-72) 59 (56.5-63) 58.5 (40.75-67.5) 61 (43-76)
Sex, N (% male) 69 (83.13) 28 (82.35) 8 (88.88) 5 (71.43) 13 (59.09) 5 (45.45)
Hospital LOS [day], median (IQR) 37 (26.5-58) 9 (3.25-13.5) 31.63 (16.34-44.26) 3.98 (3.65-7.98) 17.82 (11.41-20.21) 10.23 (4.7-15.35)
Monitoring time [day], median (IQR) 6 (4-9) 5 (1.25-8) 2.56 (2.12-3.4) 3.01 (2.71-4.14) 5.14 (2.76-8.3) 3.79 (2.49-6.03)
Clinical presentation, median (IQR)
RTS 5.97 (4.09-5.97) 4.09 (4.09-5.89) 4.99 (4.06-5.93) 4.09 (4.06-5.93) 5.97 (5.03-6.9) 5.97 (5.97-6.9)
GCS 7 (5-8) 4.5 (3-6.75) 5 (3-7) 3 (3-6.5) 8.5 (5.5-9) 8 (7-10.5)
GCS eye 1 (1-2) 1 (1-1) 1 (1-1) 1 (1-1) 1.5 (1-2) 1 (1-2.5)
GCS motor 4 (3-4) 2 (1-4) 3 (1-5) 1 (1-4.5) 5 (1.75-5) 4 (4-5)
GCS verbal 1 (1-2) 1 (1-2) 1 (1-1) 1 (1-1) 3 (2-3) 3 (3-3)
CT findings, N (%)
Contusion hemorrhage (CH) 90 (76.92) 34 (29.06) 6 (37.5) 3 (18.75) 15 (45.45) 11 (33.33)
Subarachnoid hemorrhage (SAH) 70 (59.83) 32 (27.35) 2 (12.5) 5 (31.25) 7 (21.21) 2 (6.06)
Subdural hematoma (SDH) 65 (55.56) 32 (27.35) 3 (18.75) 3 (18.75) 4 (12.12) 3 (9.09)
Epidural hematoma (EDH) 24 (20.51) 3 (2.56) 0 (0) 0 (0) 2 (6.06) 0 (0)
Diffuse axonal injury (DAI) 10 (8.55) 0 (0) 0 (0) 0 (0) 1 (3.03) 0 (0)

IV. RESULTS
A. Basic demographics
Data from 117 TBI patients were analyzed for the
investigation and prediction of SIH; the values are provided as
the median and interquartile range (Table 2). The median age of
all the patients was 50 years and ranged from 17 to 82. The
median GCS score was 6, and 91 patients had a GCS under 7.
B. AUROCs between IH parameters and outcome
Among the IH event-related parameters (i.e., count, duration,
and proportion), the proportion of IH events yielded the highest
predictive power (Supplementary Section B) and was hence
subjected to further analyses. Fig. 3 displays the AUROC
relationship of the IH proportion derived from various IH and
outcome definitions, which were visualized as heatmaps.
The purple–blue and yellow–red regions represent the IH
definitions with low and high prognostic power, respectively;
the IH definitions with significantly high prognostic capacity
are represented as white regions. The IH definitions with ICP
thresholds and PTD values that are too high or too low tended
to have lower prognostic capacity for outcome prediction. For
mortality and unfavorable outcomes, when the ICP threshold
was 20 mmHg and the PTD was 130 mmHg·min, the AUROC
values for the IH proportion were the highest at 0.8928 and
0.8582, respectively (p < 0.001, p < 0.001). In addition, the
statistically derived cutoff values were 0.1989 and 0.1780 for
mortality and unfavorable outcomes, respectively. Accordingly,
SIH was defined as an IH event exhibiting an ICP = 20 mmHg
and a PTD > 130 mmHg·min over 5 minutes.
C. Characteristics of SIH events
SIH events were identified in 87 out of 117 TBI patients.
non-IH (n=8,795), IH (n=4,485), and SIH (n=1,921) events
were compared via one-way ANOVA and Scheffe's post hoc
test to investigate the physiological characteristics of SIH
events (Table 3). Statistically significant differences were
observed in MAP, MICP, AMP, CPP, wICP, PRx, and PAx for
differentiating all three events; there were no statistically
significant differences in the PP and RAP between IH and SIH
events. Intriguingly, there was no statistically significant
difference in the RAC when comparing all three groups.
D. Forecasting SIH events via LightGBM
In the internal validation, for predicting SIH events after 30
minutes, the model demonstrated a stable performance with an
accuracy of 83.63 ± 0.54%, F1 of 83.86 ± 0.57%, sensitivity of
85.51 ± 1.11%, specificity of 81.75 ± 1.18%, positive
predictive value (PPV) of 82.91 ± 0.82% and negative
predictive value (NPV) of 85.38 ± 0.76%. Previous studies that
predicted the IH event after 30 minutes showed 77.4% and
77.6%, respectively [45, 46]. When tested against varying time
windows (i.e., from 5 to 480 minutes), the prediction
performance tended to decrease as time intervals increased (Fig.
4 and Table 4).
The overall model performance through external validation
was similar to the results of internal validation on both datasets
(Fig. 4). For example, the prediction accuracy after 5 minutes
was 86.45 ± 0.27% and 85.8 ± 0.27%, respectively, for the
MIMIC-III WFDB and SNUH datasets, which was
approximately 0.5% and 1.15% lower than that of the internal
validation. In addition, since the difference between the
accuracy and F1 score was not large, it was confirmed that the
model showed stable performance without focusing on the
class (Table 4).
E. Interpretation of the SIH prediction model through
SHAP analysis
Fig. 5. is a summary plot derived through SHAP from the
internal validation dataset. The y-axis indicates the relevance of
different features, arranged in descending order. The x-axis
shows the SHAP value of each feature. Each point resembles a
single prediction, in which pink represents a high feature value
and blue a low feature value. For example, if the color turns
pink from blue when it goes from left to right within a feature, it

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M. Jung et al.: Prediction of Serious Intracranial Hypertension from Low-Resolution Neuromonitoring in Traumatic Brain Injury: An Explainable Machine Learning Approach

Fig. 3. Visualization of AUROC relationship between outcome and IH event proportion across different ICP and PTD thresholds. ICP threshold 1-40
mmHg and PTD threshold 0-1000 mmHg·min, ICP threshold 15-25 mmHg and PTD threshold 80-180 mmHg·min were shown on the left and right,
respectively. (a) mortality (GOSE, 1 vs. 2-8), (b) favorability (GOSE, 1-3 vs. 4-8).
signifies a higher value of the feature and higher SIH event information on the patient sex tended to be less significant in
occurrence prediction by the model. Among the features, when the occurrence prediction.
the values of ICP-related features such as PTD, MICP, MICP
SD, MAP, PRx, RAP, PAx and CPP were higher, the V. DISCUSSION
probability of predicting SIH occurrence increased. Conversely, In this study, the ABP and ICP that were recorded from
when features such as AMP, PP and RAC increased, the low-resolution signals were used to define SIH related to the
probability of predicting normal status maintenance increased. negative outcome of a patient, and explainable artificial
For SIH prediction, the patient information feature increased intelligence was used to predict the occurrence of the event.
the likelihood of occurrence with increasing age and decreased The proposed SIH events had high prognostic predictive
the likelihood with higher GCS scores and RTSs. Furthermore, capacity, and the constructed artificial intelligence model
TABLE Ⅲ
ONE-WAY ANOVA AND SCHEFFE’S POST HOC TEST ABOUT PARAMETERS IN NORMAL, IH, AND SIH EVENTS. THE VALUES ARE PROVIDED AS THE AVERAGE AND
INTERQUARTILE RANGE.
Mean (95% CI) Scheffe’s post hoc p-value
ANOVA
Normal IH SIH p-value Nor vs. IH Nor vs. SIH IH vs. SIH
(No. of event=8,795) (No. of event=4,485) (No. of event=1,921)
MAP (mmHg) 92.51 (92.22-92.8) 93.75 (93.45-94.05) 95.49 (95.19-95.79) <0.001 <0.001 <0.001 <0.001
MICP (mmHg) 15.86 (15.79-15.93) 23.12 (23.05-23.18) 28.33 (27.99-28.68) <0.001 <0.001 <0.001 <0.001
PP (mmHg) 67.82 (67.4-68.24) 69 (68.55-69.45) 68.39 (67.95-68.82) <0.001 0.001 0.006 0.888
AMP (mmHg) 7.97 (7.89-8.05) 11.5 (11.39-11.61) 13.21 (12.96-13.45) <0.001 <0.001 <0.001 <0.001
CPP (mmHg) 77.8 (77.5-78.1) 69.8 (69.5-70.1) 65.82 (65.36-66.29) <0.001 <0.001 <0.001 <0.001
wICP (mmHg) 4.69 (4.57-4.81) 6.7 (6.52-6.88) 8.11 (7.64-8.59) <0.001 <0.001 <0.001 <0.001
PRx (a.u.) 0 ((-0.01)-0.01) 0.03 (0.02-0.04) 0.09 (0.08-0.1) <0.001 <0.001 <0.001 <0.001
PAx (a.u.) -0.02 ((-0.03)-(-0.01)) 0.04 (0.03-0.04) 0.09 (0.09-0.1) <0.001 <0.001 <0.001 <0.001
RAP (a.u.) 0.66 (0.66-0.67) 0.72 (0.71-0.72) 0.72 (0.71-0.72) <0.001 0.004 0.003 0.653
RAC (a.u.) -0.38 ((-0.39)-(-0.37)) -0.41 ((-0.42)-(-0.4)) -0.4 ((-0.4)-(-0.39)) 0.319 0.956 0.32 0.492
CI=confidence interval; Normal=ICP < 20 mmHg; IH=ICP>20 mmHg & 5 > minutes; Nor=Normal; MAP=mean arterial blood pressure; MICP=mean
intercranial pressure; PP=pulse pressure; AMP=amplitude of ICP; CPP=cerebral perfusion pressure; wICP= compensatory-reserve-weighted ICP;
PRx=pressure reactivity index; PAx=pulse amplitude index; RAP=correlation of AMP and ICP; RAC=correlation of AMP and CPP.

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M. Jung et al.: Prediction of Serious Intracranial Hypertension from Low-Resolution Neuromonitoring in Traumatic Brain Injury: An Explainable Machine Learning Approach

Fig. 4. Mean and 95% confidence interval performance of the prediction LightGBM models for SIH events according prediction interval time. Red and
blue lines mean the model performance at internal validation and external validation, respectively. (a) Accuracy, (b) F1 score, (c) Sensitivity, (d)
Specificity, (e) Positive predictive value (PPV), (f) Negative predictive value (NPV).
TABLE IV
MEAN INTERVAL PERFORMANCE OF THE PREDICTION LIGHTGBM MODELS FOR SIH EVENTS ACCORDING PREDICTION INTERVAL TIME IN INTERNAL / EXTERNAL
VALIDATION DATASET.
Prediction Ajou Univ. Hospital MIMIC-III SNUH
Interval Accuracy F1 Accuracy F1 Accuracy F1
5 86.95 87.22 86.45 86.25 85.8 86.29
10 85.68 85.9 86.2 87.29 84.97 85.86
15 85.59 85.78 85.25 85.89 83.97 84.9
30 83.63 83.86 84.35 85.65 82.96 83.33
45 82.75 83.1 81.11 80.66 82.7 83.21
60 81.33 81.87 82.23 82.84 82.64 83.31
90 81.39 81.38 77.29 77.68 79.62 79.91
120 80.28 80.83 80.59 81.47 77.33 77.92
180 75.28 75.71 78.28 77.36 75.72 77.28
240 74.52 74.68 77.74 76.43 74.38 74.73
360 72.71 72.72 73.8 71.65 72.31 73.56
480 72.18 72.2 74.23 71.95 74.2 76.14
demonstrated reliable performance and warrants further the ICC is more complicated; nonetheless, the pulse amplitude
discussion. of ICP (AMP) [34] and AMP-derived parameters (e.g., RAP
[39] and wICP [36]) have been devised and employed to
A. Physiological characteristics of SIH
evaluate the pressure-volume compensatory status. RAC is a
The results indicate that the proportion of IH events recent addition to the long list of ICP-derived parameters and is
exhibiting ICP threshold 20 mmHg and PTD > 130 mmHg·min speculated to reflect both the CA and ICC [38].
yielded the highest prognostic power in both mortality and Compared to normal and IH conditions, patients with SIH
favorability (Fig. 3.). With the SIH events identified via events demonstrated significant differences in various CA- and
statistical analysis, this study further investigated the ICC-related indices (Table 3). The simultaneous elevation of
physiological characteristics of the SIH events. ABP and ICP that is observed as the event becomes more
Cerebral autoregulation (CA) and intracranial compliance severe suggests that the cerebrovascular reactivity became
(ICC) are concepts that are of utmost importance in passive [52], as indicated by the increase in the PRx and PAx
understanding the neurophysiological status of TBI patients [47, [27, 37, 38]. However, the increase in AMP and wICP values
48]. The worsening of CA and ICC is highly associated with a during an SIH event implies a deteriorated ICC [34, 36, 38];
negative prognosis [49-51]; hence, various methods have been furthermore, the RAP values in the three states were
developed to evaluate CA and ICC. The monitoring of ICP approximately 0.6, with no statistical significance between IH
allows for a continuous, albeit indirect, evaluation of CA and and SIH. This finding might imply that the compensatory
ICC. PRx, which is defined as the moving correlation reserve was already poor before the occurrence of SIH [39].
coefficient between ABP and ICP, is the most widely validated Overall, the analyses suggest that during an SIH event, the
parameter that reflects the status of CA [27], and PAx is a worsening of both CA and ICC simultaneously occurs.
variant of PRx that is designed to better reflect the CA within a Regarding the benefits of defining SIH based on the data
relatively intact ICC [37]. Compared with CA, the evaluation of

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M. Jung et al.: Prediction of Serious Intracranial Hypertension from Low-Resolution Neuromonitoring in Traumatic Brain Injury: An Explainable Machine Learning Approach

Fig. 5. SHAP summary plots for each of the top 18 feature in LightGBM model in the internal validation. Each point indicates IH cases included in the
test dataset. (a) time interval of 5 minutes, (b) 60 minutes, (c) 8 hours.

available, rather than previous literature or clinical expertise,
we defined SIH as an intracranial hypertension event that is
likely associated with worse outcome. Though ICP values of 20,
22, or 25 mmHg for more than 5 minutes are widely accepted as
thresholds for identifying intracranial hypertension, it has long
been known that such specific thresholds have limited
prognostic value [17-19]. The concept of PTD was developed
to address this issue; however, while previous studies indicate
that a higher PTD is associated with worse outcome [20, 22, 23],
a specific threshold of PTD has not been determined. As a more
recent study illustrates in detail, PTD can be obtained with
varying ICP thresholds [23]. In this context, the task of
identifying SIH, i.e., finding the combination of ICP and PTD
that is best associated with a worse outcome, is not an act of
disregarding the previous literature; rather, we believe that this
study is a continuation of the on-going investigations for
enhancing the prognostic value of ICP in neurocritical care.
B. SIH prediction: Technical implications and practical
significance
To date, one of the previous IH prediction studies worth
noting defined a life-threatening IH based on high-frequency
ABP and ICP signals and predicted the corresponding events
[13]. Unlike a typical IH prediction model, this system
generates an alarm by predicting a life-threatening IH. Active
intervention based on this system not only enhances the
efficiency of medical resource distribution but also increases
the expectation of a positive patient outcome. Despite the high
clinical significance, the model was trained based on the
high-resolution signal. In fact, most attempts to predict IH [7, 9,
11] have been conducted based on high-frequency data.
However, because the extraction and processing of waveform
quality data require additional software and equipment [53, 54],
the acquisition of high-resolution signals is limited to
specialized neurocritical care units; thus, the majority of
existing IH prediction systems are not readily applicable in
most neurointensive care units worldwide.
The recently published work of Carra, Georgia, et al. [10]
shows similarities to this study in terms of the use of
multicenter database and external validation, the remarkable
performance of the developed IH prediction model, and most
importantly, defining the prediction target as a broad range of
episodes of doses of IH rather than the threshold value. The
similarities found in the two studies provide implications for
future studies not limited to IH prediction but also systems that
make early detection for clinically important events, on the
direction in which they should pursue. On the contrary, this
study is differentiated in the following ways: 1) PTD and
AUROC were used to narrow the definition of events that
negatively affect the prognosis of patients, 2) Physiological
parameters were used to investigate SIH characteristics, 3) The
robustness of the model performance at various prediction
intervals was verified, 4) The XAI technique was applied to
understand the mechanism of the prediction system.
The proposed LightGBM model, compared to previous
models, does not require high computing power since it was
trained with features that could be derived simply through
low-frequency signals and Pearson's correlation. Hence, it can
easily be integrated into most ICU bedside monitoring
environments without much effort. With minute-by-minute
data, the learned model demonstrated good performance by
predicting the occurrence of SIH after 5 minutes and 8 hours in
internal validation with accuracies of 86.45 ± 0.27% and 72.18
± 0.75%, respectively. Additionally, external validation of two
types of data sets confirmed the similarity between the overall
metrics of the model and internal validation. This result
suggests that the proposed system can perform robustly even
with unlearned data.
The developed system predicts whether SIH events will
occur after various prediction intervals and is utilizable in
clinical environments. For the model with a prediction interval
of 5 to 15 minutes, the alarm would be highly reliable due to its
relatively high accuracy. In addition, considering that the
effects of mannitol and hypertonic saline are generally
significant 30 to 60 minutes after administration, models with a
prediction interval of 30 to 120 minutes could be helpful in
determining the timing and dose of osmotic agents [55-57]. The
models with prediction intervals longer than a few hours could
be helpful in preparing more time-consuming interventions.
In recent clinical systems, both performance and
interpretability are crucial in supporting clinical decisions [12].
The proposed prediction model was created based on features
that indirectly reflect the CA, ICC, and pressure-volume
compensatory reserve. In this study, SHAP was applied to the
prediction system to analyze the precursor symptoms of an SIH
event. Similar to the results of previous studies, when there are
higher values of ICP, PTD, MICP SD, PRx and PAx, the
likelihood of SIH occurrence increases [7, 9, 13, 58, 59]. These
results signify the increased vulnerability of a patient to SIH
under deteriorated CA and ICC. In the case of PP and RAC, the

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 This article has been accepted for publication in IEEE Journal of Biomedical and Health Informatics. This is the author's version which has not been fully edited and
content may change prior to final publication. Citation information: DOI 10.1109/JBHI.2023.3240460
M. Jung et al.: Prediction of Serious Intracranial Hypertension from Low-Resolution Neuromonitoring in Traumatic Brain Injury: An Explainable Machine Learning Approach
risk of event occurrence decreased as the value of the features
increased. Among patient demographics, age increased the
likelihood of SIH occurrence, and the GCS score and RTS
lowered the likelihood of SIH occurrence, and these results are
consistent with the results of previous literature [60, 61].
Furthermore, sex tended to have lower significance in
prediction. Since treatment methods vary depending on the
cause of IH occurrence [62], the analyses of these models are
expected to help clinicians take appropriate preemptive action
before the occurrence of an SIH.
C. Limitations and suggestions
Some limitations of this study must be noted. First, a
relatively small number of patients were used for analysis.
Although strict cross-validation was employed, further
validation is needed. The proposed SIH is essentially a
combination of ICP and PTD thresholds that are most highly
associated with the worse outcome, and thresholds derived
from a small dataset are bound to be data dependent. Second,
the management of patients with elevated ICP was performed
through various protocols, but the effects of these protocols
were not considered. To further analyze these effects in detail,
prospectively collected data that document all of the clinical
interventions and provide information on IH events are needed.
Third, the retrospectively derived definition of SIH indicates an
association with the patient outcome but does not signify a
causal relationship. This is because other unmeasured factors
may have caused a disturbance such as secondary
complications when evaluating the association between SIH
events and outcome. Fourth, SIH was derived from univariate
analysis and, hence, does not fully incorporate the various
factors that may affect outcomes after TBI. Finally, the
proposed model assumes that pulse amplitude of ICP can be
calculated from minute-by-minute diastolic and systolic
pressures ICP; for settings that such information is unavailable,
appropriate modification should be made for the proposed SIH
prediction model. Therefore, in future validation studies, the
proposed SIH event and prediction system need to be further
investigated to address the following issues: (1) large datasets
should be used for SIH event rediscovery; (2) other cerebral
pathologies and situations (e.g., stroke, post-DC, etc.) should
be analyzed; and (3) prospective studies (e.g., patient outcome)
should be performed for the validation of the clinical efficacy
of the SIH prediction systems.
VI. CONCLUSION
This study aimed, through univariate analysis of
minute-by-minute data acquired from a single center, to define
SIH events, namely, IH events with an ICP threshold = 20
mmHg and PTD threshold > 130 mmHg·min, which may be
associated with negative outcomes in TBI patients. The SIH
event signified a state of CA and ICC impairment following a
large elevation in ICP. For the early prediction of SIH events
related to negative outcomes and the pathophysiological status
of patients, we designed the LightGBM model using features
derived from the ABP and ICP signals. The performance of the
learned model was compliant and consistent in both the internal
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and external validation datasets. The proposed system, through
explainable artificial intelligence techniques, presents an
analysis of predictions so that clinicians can provide more
appropriate interventions in treating TBI patients. Future
interventional studies are needed to investigate whether the
definition of SIH is maintained in multicenter data and to
evaluate the effects of the predictive system on patient
outcomes in clinical practice.
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