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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Hum. Neurosci.</journal-id>
<journal-title>Frontiers in Human Neuroscience</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Hum. Neurosci.</abbrev-journal-title>
<issn pub-type="epub">1662-5161</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fnhum.2022.834427</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Human Neuroscience</subject>
<subj-group>
<subject>Original Research</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>The Effect of Hemoglobin Concentration on Hyperbaric Oxygen and Non-hyperbaric Oxygen in the Treatment of Hypertensive Intracerebral Hemorrhage After Operation at the High Altitude</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name><surname>Wei</surname> <given-names>Linjie</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x002A;</sup></xref>
<xref ref-type="author-notes" rid="fn002"><sup>&#x2020;</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/1595953/overview"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Lin</surname> <given-names>Chi</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="author-notes" rid="fn002"><sup>&#x2020;</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Xue</surname> <given-names>Xingsen</given-names></name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
<xref ref-type="author-notes" rid="fn002"><sup>&#x2020;</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Jila</surname> <given-names>Shiju</given-names></name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Dai</surname> <given-names>Yalan</given-names></name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Pan</surname> <given-names>Li</given-names></name>
<xref ref-type="aff" rid="aff4"><sup>4</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Wei</surname> <given-names>Wei</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Dun</surname> <given-names>Guodong</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Shen</surname> <given-names>Yong</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Zong</surname> <given-names>Taoxi</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Wu</surname> <given-names>Jingjing</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Li</surname> <given-names>Yafang</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Wu</surname> <given-names>Lixia</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Xian</surname> <given-names>Jishu</given-names></name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name><surname>Yu</surname> <given-names>Anyong</given-names></name>
<xref ref-type="aff" rid="aff5"><sup>5</sup></xref>
<xref ref-type="corresp" rid="c002"><sup>&#x002A;</sup></xref>
</contrib>
</contrib-group>
<aff id="aff1"><sup>1</sup><institution>Department of Neurosurgery, PLA 956th Hospital</institution>, <addr-line>Linzhi</addr-line>, <country>China</country></aff>
<aff id="aff2"><sup>2</sup><institution>Department of Neurosurgery, First People&#x2019;s Hospital of Honghe City</institution>, <addr-line>Honghe</addr-line>, <country>China</country></aff>
<aff id="aff3"><sup>3</sup><institution>Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University)</institution>, <addr-line>Chongqing</addr-line>, <country>China</country></aff>
<aff id="aff4"><sup>4</sup><institution>Medical Imaging Department, General Hospital of Tibet Military Region</institution>, <addr-line>Lhasa</addr-line>, <country>China</country></aff>
<aff id="aff5"><sup>5</sup><institution>Department of Emergency, Affiliated Hospital of Zunyi Medical University</institution>, <addr-line>Zunyi</addr-line>, <country>China</country></aff>
<author-notes>
<fn fn-type="edited-by"><p>Edited by: Anna-Sophia Wahl, University of Zurich, Switzerland</p></fn>
<fn fn-type="edited-by"><p>Reviewed by: Mona Laible, Ulm University, Germany; Denise Becker, University Hospital Zurich, Switzerland</p></fn>
<corresp id="c001">&#x002A;Correspondence: Linjie Wei, <email>weilinjie8888@163.com</email></corresp>
<corresp id="c002">Anyong Yu, <email>anyongyu@163.com</email></corresp>
<fn fn-type="equal" id="fn002"><p><sup>&#x2020;</sup>These authors have contributed equally to this work</p></fn>
<fn fn-type="other" id="fn004"><p>This article was submitted to Brain Health and Clinical Neuroscience, a section of the journal Frontiers in Human Neuroscience</p></fn>
</author-notes>
<pub-date pub-type="epub">
<day>30</day>
<month>06</month>
<year>2022</year>
</pub-date>
<pub-date pub-type="collection">
<year>2022</year>
</pub-date>
<volume>16</volume>
<elocation-id>834427</elocation-id>
<history>
<date date-type="received">
<day>13</day>
<month>12</month>
<year>2021</year>
</date>
<date date-type="accepted">
<day>31</day>
<month>05</month>
<year>2022</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x00A9; 2022 Wei, Lin, Xue, Jila, Dai, Pan, Wei, Dun, Shen, Zong, Wu, Li, Wu, Xian and Yu.</copyright-statement>
<copyright-year>2022</copyright-year>
<copyright-holder>Wei, Lin, Xue, Jila, Dai, Pan, Wei, Dun, Shen, Zong, Wu, Li, Wu, Xian and Yu</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p></license>
</permissions>
<abstract>
<sec>
<title>Background</title>
<p>The prognosis of hypertensive intracerebral hemorrhage (HICH) is poor at high altitudes. The objective of this study was to explore whether hyperbaric oxygen (HBO) can improve the results of computed tomography perfusion (CTP) imaging and the neurological function of patients with HICH, and influence the hemoglobin concentration.</p>
</sec>
<sec>
<title>Method</title>
<p>The patients with HICH were treated with puncture and drainage. Twenty-one patients (51.22% of 41 patients in total) were treated with HBO after the operation, and the other patients received conventional treatment. CTP was performed twice, and all indices were measured. Scatter plots were used to determine the effect of hemoglobin concentration on CTP imaging. Receiver operating characteristic (ROC) curves were plotted to analyze the effects of hemoglobin concentration and hematoma volume on recovery results. The patients were followed up for 6 months.</p>
</sec>
<sec>
<title>Results</title>
<p>Forty-one patients with HICH were treated with puncture and drainage. In total, 21 were treated with HBO after the operation, and 20 received conventional treatment as the control group. No significant differences in the CBV and CBF values of the two groups were noted before treatment. After 10 days, the values of CBV and CBF in the HBO group were significantly higher than those in the control group. A scatter diagram showed there was no significant in the HBO group, but significant correlation for the CBV and CBF values in the control group&#x2019;s hematoma center and margin. The ROC curves showed that hematoma volume had an influence on prognosis of the control group. The Glasgow Coma Scale (GOS) scores of the HBO group were significantly higher than those of the control group (<italic>p</italic> &#x003C; 0.05).</p>
</sec>
<sec>
<title>Conclusions</title>
<p>HBO therapy can improve the postoperative CBV and CBF values of patients with HICH and ameliorate their prognoses. There was no significant correlation between HBO group and hemoglobin concentration on admission.</p>
</sec>
</abstract>
<kwd-group>
<kwd>high altitude</kwd>
<kwd>puncture and drainage hematoma</kwd>
<kwd>hyperbaric oxygen</kwd>
<kwd>computed tomography perfusion imaging</kwd>
<kwd>hemoglobin concentration</kwd>
</kwd-group>
<contract-sponsor id="cn001">National Natural Science Foundation of China<named-content content-type="fundref-id">10.13039/501100001809</named-content></contract-sponsor>
<counts>
<fig-count count="5"/>
<table-count count="3"/>
<equation-count count="0"/>
<ref-count count="17"/>
<page-count count="8"/>
<word-count count="4328"/>
</counts>
</article-meta>
</front>
<body>
<sec id="S1" sec-type="intro">
<title>Introduction</title>
<p>At high altitude regions the hemoglobin concentrations will increase because of hypoxia. However, if the hemoglobin levels increase too much, the viscosity of the blood will increase, and blood flow will be slowed. Thus the hypoxia of brain tissue will further accelerate. Hyperbaric oxygen (HBO) therapy can effectively improve the partial pressure and dispersion rate of blood oxygen, thus leading to nerve function recovery (<xref ref-type="bibr" rid="B5">Li et al., 2017</xref>). The literature reports that HBO can significantly improve the recovery of neurological function after cerebral hemorrhage (<xref ref-type="bibr" rid="B7">Peng et al., 2014</xref>; <xref ref-type="bibr" rid="B10">Wang et al., 2020</xref>). High-altitude areas are more prone to hypertensive cerebral hemorrhage (HICH) than low-altitude areas. Due to the lack of oxygen in high-altitude areas, functional recovery after cerebral hemorrhage is poor (<xref ref-type="bibr" rid="B17">Zhu et al., 2015</xref>; <xref ref-type="bibr" rid="B12">Wei et al., 2019</xref>). Studies have in particular shown, that there is decreased cerebral blood flow (CBF) after craniocerebral injury at high altitudes (<xref ref-type="bibr" rid="B16">Yu et al., 2014</xref>). At present, an effective method to improve self-reliance after cerebral hemorrhage is lacking. It is not clear whether HBO can improve the CBV and thus ameliorate certain neurological functions. In addition, it remains elusive, whether there would be an effect of the hyperbaric or non-hyperbaric oxgen on the hemoglobin concentration in the treatment of hypertensive intracerebral hemorrhage. Therefore, our team conducted a retrospective analysis on the use of HBO in high-altitude areas.</p>
</sec>
<sec id="S2" sec-type="materials|methods">
<title>Materials and Methods</title>
<sec id="S2.SS1">
<title>Patient Selection</title>
<p>This study was approved by our local ethics committee. These case data were obtained retrospectively. From February 2018 to December 2020, the patients who had HICH as determined by computed tomography (CT) (GE Lightspeed 64, United States) scans and related examinations were enrolled. The selection criteria were as follows: (1) History of hypertension; (2) Altitude (1,500&#x2013;4,000 m) (2,873.45 &#x00B1; 745.99 m); (3) Time spent at these altitudes &#x2265; 5 years; (4) Hematoma volume 30&#x2013;50 ml; (5) Good liver and kidney function; (6) Stable vital signs; (7) Hypertensive basal ganglia hemorrhage; and (8) Complete case data. Patients were excluded according to <xref ref-type="fig" rid="F1">Figure 1</xref>. Twenty-one patients were treated with HBO after the operation (HBO group), and the other patients received conventional treatment (Control group) (<xref ref-type="fig" rid="F1">Figure 1</xref>). The relevant data of the patients, including sex, age, medication history, hematoma size, hemoglobin concentration, and Glasgow Coma Scale (GCS), were collected and recorded in detail on admission. When the patient were admitted to the hospital, we asked the medical history. If the patient had used anticoagulant and antiplatelet drugs, we tested the patient&#x2019;s coagulation function. If the patient were seriously affected by coagulation, we treated it conservatively and evaluated that it would not have a great impact on coagulation. We also conducted surgical treatment. All data were independently and blindly reviewed by two senior neurosurgeons.</p>
<fig id="F1" position="float">
<label>FIGURE 1</label>
<caption><p>A flow chart for the identification process of eligible patients.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnhum-16-834427-g001.tif"/>
</fig>
</sec>
<sec id="S2.SS2">
<title>Therapeutic Method</title>
<p>Puncture and drainage hematoma: The largest hematoma plane was selected as the positioning point for drilling (<xref ref-type="fig" rid="F2">Figures 2A</xref>, <xref ref-type="fig" rid="F3">3A</xref>). All patients were placed under local anesthesia, and a YL-1 puncture needle (Beijing Wan Fu Tie Medical Apparatus Co., Ltd., China) was used for drilling after selecting the positioning point (<xref ref-type="bibr" rid="B15">Xia et al., 2019</xref>; <xref ref-type="fig" rid="F2">Figures 2D</xref>, <xref ref-type="fig" rid="F3">3D)</xref>. After puncture and drainage, CT examination revealed that the hematoma was enlarged, and a craniotomy was performed to remove the hematoma. After 3&#x2013;5 days of drainage, head CT was repeated and indicated that the hematoma had been reduced by 50&#x2013;100%. The drainage tube was removed. Then, the patients in the HBO group were treated with HBO (100% oxygen at 2.2 ATA for 60 min for 10 days). In the control group, all treatments were the same, except HBO treatment was lacking. If the hematoma expanded more than 50 ml, we performed craniotomy to remove the hematoma. If the enlarged hematoma was less than 50 ml, but the GCS score decreased by 2 points, craniotomy was also considered.</p>
<fig id="F2" position="float">
<label>FIGURE 2</label>
<caption><p>CTP scan from a patient in the HBO group: <bold>(A)</bold> Preoperative left basal ganglia hemorrhage. <bold>(B,C,E,F)</bold> The yellow line denotes the hematoma area, the white star (&#x002A;) denotes the hematoma center, the purple line denotes the hematoma margin, and the outer layer yellow line denotes the cortical area of the hematoma. <bold>(D)</bold> Application of a YL-1 puncture needle after puncture and drainage. <bold>(G)</bold> Normal CTA.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnhum-16-834427-g002.tif"/>
</fig>
<fig id="F3" position="float">
<label>FIGURE 3</label>
<caption><p>CTP scan from a patient in the control group: <bold>(A)</bold> Preoperative right basal ganglia hemorrhage. <bold>(B,C,E,F)</bold> The yellow line denotes the hematoma center area, the white star (&#x002A;) denotes the hematoma center, and the outer layer yellow line denotes the cortical area of the hematoma. <bold>(D)</bold> Application of a YL-1 puncture needle after puncture and drainage. <bold>(G)</bold> Normal CTA.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnhum-16-834427-g003.tif"/>
</fig>
</sec>
<sec id="S2.SS3">
<title>Imaging Data Measurement</title>
<p>Before puncture and drainage, CT angiography (CTA) was completed, and the result was normal (<xref ref-type="fig" rid="F2">Figures 2G</xref>, <xref ref-type="fig" rid="F3">3G</xref>). CT perfusion (CTP) imaging was performed after written informed consent was obtained from the patients or their relatives. CTP imaging was performed twice. The first imaging scan was performed before HBO treatment for the HBO group and before standard treatment for the control group (<xref ref-type="fig" rid="F2">Figures 2B,C</xref>, <xref ref-type="fig" rid="F3">3B,C</xref>); both groups underwent scans on the same number of days prior to the start of their respective treatments. The second CTP imaging scan was performed 10 days after HBO treatment for the HBO group and 10 days after the corresponding treatment for the control group (<xref ref-type="fig" rid="F2">Figures 2E,F</xref>, <xref ref-type="fig" rid="F3">3E,F</xref>). A high-pressure syringe was used to inject iohexol (Yangtze River Pharmaceutical Group Co., Ltd., Production) through the anterior elbow vein (17.5 g in 50 ml, flow rate: 5 ml/s) (<xref ref-type="bibr" rid="B9">Wang et al., 2017</xref>). In the hematoma center, different regions of interest (ROIs) for the hematoma margin (defined as the area around the hematoma with a CT value at least 5 U less than of normal brain tissue or the area 1 cm away from the hematoma if the CT value was less than 5 U that of the brain tissue) and cortical area on the hematoma side (measuring the same length as the hematoma and edema) were selected for qualitative analysis. The mean perfusion parameters (cerebral blood volume (CBV) and (CBF) were calculated. The above parameters were also calculated for the control group. After 10 days, CTP imaging was performed again, and the parameters were recalculated. The above parameters were transferred to 4D Brain Perfusion (Vitrea, Japan) for ROI analysis. The formula ABC/2 was used to calculate the volume of the hematoma (<xref ref-type="bibr" rid="B4">Kothari et al., 1996</xref>). All data were independently and blindly reviewed by two senior neurosurgeons.</p>
</sec>
<sec id="S2.SS4">
<title>Evaluation and Follow-Up</title>
<p>The CBV and CBF values of the two groups were measured and compared. A scatter diagram was plotted to demonstrate the relationship between the hemoglobin concentration on admission and the second set of CBV and CBF values. Receiver operating characteristic (ROC) curves were used to measure the cutoff values at which hematoma volume and hemoglobin concentration predicted a good outcome and the corresponding specificities and sensitivities. After a 6-month follow-up, the patients were scored using the Glasgow Outcome Scale (GOS). The scoring criteria were as follows: Good recovery (5), Moderate disability (4), Severe disability (3), Vegetative state (2), and Death (1). The patients were divided into 2 outcome groups: a good outcome group, which was defined as independent (GOS scores, 4-5), and a poor outcome group, which was defined as dependent (GOS scores, 3-1) (<xref ref-type="bibr" rid="B3">Dunatov et al., 2011</xref>).</p>
</sec>
<sec id="S2.SS5">
<title>Statistical Analysis</title>
<p>All analyses were performed using SPSS 19 (IBM Corp., Armonk, NY, United States). Normally distributed data are expressed as the mean &#x00B1; standard deviation. Quantitative data were analyzed between the two groups using separate <italic>T</italic>-tests and analysis of variance. Differences were considered significant at <italic>p</italic> &#x003C; 0.05. A scattergram with a regression line was generated to determine the association between the hemoglobin concentration and CBV and CBF. ROC curve analysis was used to investigate the diagnostic relationship between risk factors and a good outcome. The Youden index was used to determine the optimal cutoff value as previously described (<xref ref-type="bibr" rid="B11">Wei et al., 2020</xref>).</p>
</sec>
</sec>
<sec id="S3" sec-type="results">
<title>Results</title>
<sec id="S3.SS1">
<title>Participant Characteristics</title>
<p>A total of 41 patients were included in the study, of whom 21 received HBO treatment and 20 received conventional therapy. No significant differences in the basic characteristics of the two groups were noted (<xref ref-type="table" rid="T1">Table 1</xref>). Partial hematomas could not be extracted from two patients in the HBO group and three patients in the control group, resulting in success rates of 90.48 and 85%, respectively. The hematoma could not be extracted for several patients in the two groups, but their conditions were stable. Later, treatment was performed, and these data on the two groups were included. There were no significant differences in the success rate of the two groups (<italic>p</italic> &#x003E; 0.05). No intracranial infection was found among the 41 patients.</p>
<table-wrap position="float" id="T1">
<label>TABLE 1</label>
<caption><p>Patient characteristics of the HBO and control groups.</p></caption>
<table cellspacing="5" cellpadding="5" frame="hsides" rules="groups">
<thead>
<tr>
<td valign="top" align="left">Characteristics</td>
<td valign="top" align="center">HBO group (n)<break/> 21</td>
<td valign="top" align="center">Control group(n)<break/> 20</td>
<td valign="top" align="center">t/&#x03C7;<sup>2</sup></td>
<td valign="top" align="center"><italic>P</italic>-value</td>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Age (y) (Mean &#x00B1; SD)</td>
<td valign="top" align="center">53.35&#x00B1;10.85</td>
<td valign="top" align="center">50.75&#x00B1;7.31</td>
<td valign="top" align="center">0.721</td>
<td valign="top" align="center">0.477</td>
</tr>
<tr>
<td valign="top" align="left">Men (n)</td>
<td valign="top" align="center">15</td>
<td valign="top" align="center">13</td>
<td valign="top" align="center">0.196</td>
<td valign="top" align="center">0.744</td>
</tr>
<tr>
<td valign="top" align="left"><bold>Ethnicity</bold></td>
<td valign="top" align="left"/><td valign="top" align="left"/><td/>
<td/>
</tr>
<tr>
<td valign="top" align="left">Ethnic minorities (n)</td>
<td valign="top" align="center">12</td>
<td valign="top" align="center">9</td>
<td valign="top" align="center">0.605</td>
<td valign="top" align="center">0.538</td>
</tr>
<tr>
<td valign="top" align="left">Han Chinese (n)</td>
<td valign="top" align="center">9</td>
<td valign="top" align="center">11</td>
<td/>
<td/>
</tr>
<tr>
<td valign="top" align="left">Hematoma volume (ml) (Mean &#x00B1; SD)</td>
<td valign="top" align="center">39.43&#x00B1;5.95</td>
<td valign="top" align="center">39.55&#x00B1;6.48</td>
<td valign="top" align="center">0.063</td>
<td valign="top" align="center">0.950</td>
</tr>
<tr>
<td valign="top" align="left"><bold>Comorbidities</bold></td>
<td valign="top" align="left"/><td valign="top" align="left"/><td/>
<td/>
</tr>
<tr>
<td valign="top" align="left">Diabetes (n)<xref ref-type="table-fn" rid="t1fns1">&#x002A;</xref></td>
<td valign="top" align="center">3</td>
<td valign="top" align="center">4</td>
<td/>
<td valign="top" align="center">0.697</td>
</tr>
<tr>
<td valign="top" align="left">Heart disease (n)</td>
<td valign="top" align="center">6</td>
<td valign="top" align="center">5</td>
<td valign="top" align="center">0.067</td>
<td valign="top" align="center">0.796</td>
</tr>
<tr>
<td valign="top" align="left">Pulmonary disease (n)<xref ref-type="table-fn" rid="t1fns1">&#x002A;</xref></td>
<td valign="top" align="center">4</td>
<td valign="top" align="center">5</td>
<td/>
<td valign="top" align="center">0.719</td>
</tr>
<tr>
<td valign="top" align="left">Other diseases (n)</td>
<td valign="top" align="center">5</td>
<td valign="top" align="center">5</td>
<td valign="top" align="center">0.008</td>
<td valign="top" align="center">0.929</td>
</tr>
<tr>
<td valign="top" align="left">GCS, median (IQR)<sup>&#x0394;</sup></td>
<td valign="top" align="center">12 (7,15)</td>
<td valign="top" align="center">11(6,14)</td>
<td/>
<td/>
</tr>
<tr>
<td valign="top" align="left"><bold>Time from onset to admission</bold></td>
<td valign="top" align="left"/><td valign="top" align="left"/><td/>
<td/>
</tr>
<tr>
<td valign="top" align="left">(h) (Mean &#x00B1; SD)</td>
<td valign="top" align="center">4.47&#x00B1;1.67</td>
<td valign="top" align="center">3.95&#x00B1;1.93</td>
<td valign="top" align="center">0.936</td>
<td valign="top" align="center">0.355</td>
</tr>
<tr>
<td valign="top" align="left"><bold>Hemoglobin concentration</bold></td>
<td valign="top" align="left"/><td valign="top" align="left"/><td/>
<td/>
</tr>
<tr>
<td valign="top" align="left">(g/L) (Mean &#x00B1; SD)</td>
<td valign="top" align="center">179.67&#x00B1;18.25</td>
<td valign="top" align="center">178.10&#x00B1;23.28</td>
<td valign="top" align="center">0.24</td>
<td valign="top" align="center">0.811</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="t1fns1"><p><italic>&#x002A;Fisher&#x2019;s exact test; y, year; GCS, Glasgow coma scale; h, hour; <sup>&#x0394;</sup>Mann&#x2013;Whitney U test.</italic></p></fn>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="S3.SS2">
<title>CTP Imaging and Follow-Up Results</title>
<p>No significant differences in the CBV and CBF values obtained from the first CTP scans were noted between the two groups (<xref ref-type="table" rid="T2">Table 2</xref>). CBV and CBF values of the hematoma centers and margins from the second scan in the HBO group were significantly higher than those in the control group (<xref ref-type="table" rid="T2">Table 2</xref>). In both groups, we analyzed the correlation between the hemoglobin concentration on admission and the CBV and CBF values extracted from the second CTP scan by generating a scatter diagram. The correlations between the hemoglobin concentration on admission and the CBV and CBF values from the hematoma center, margin and cortical area on the hematoma side were not significant in the HBO group (hematoma center: CBV: <italic>R</italic><sup>2</sup> = 0.00, <italic>p</italic> = 0.96; CBF: <italic>R</italic><sup>2</sup> = 0.00, <italic>P</italic> = 0.86; hematoma margin: CBV: <italic>R</italic><sup>2</sup> = 0.03, <italic>p</italic> = 0.44; CBF: <italic>R</italic><sup>2</sup> = 0.15, <italic>p</italic> = 0.07; cortical area on the hematoma side: CBV: <italic>R</italic><sup>2</sup> = 0.09, <italic>p</italic> = 0.19 and CBF: <italic>R</italic><sup>2</sup> = 0.03, <italic>p</italic> = 0.45) (<xref ref-type="fig" rid="F4">Figures 4A&#x2013;F</xref>). The correlations between the hemoglobin concentration on admission and the CBV and CBF values from the hematoma center, margin were significant in the control group (hematoma center: CBV: <italic>R</italic><sup>2</sup> = 0.21, <italic>p</italic> = 0.04 and CBF: <italic>R</italic><sup>2</sup> = 0.22, <italic>p</italic> = 0.04; hematoma margin: CBV: <italic>R</italic><sup>2</sup> = 0.24, <italic>p</italic> = 0.03 and CBF: <italic>R</italic><sup>2</sup> = 0.25, <italic>p</italic> = 0.02) (<xref ref-type="fig" rid="F4">Figures 4A&#x2013;D</xref>) group, but the correlations with the CBV and CBF values from the cortical area on the hematoma side were not significant in the control group (CBV: <italic>R</italic><sup>2</sup> = 0.04, <italic>p</italic> = 0.38 and CBF: <italic>R</italic><sup>2</sup> = 0.04, <italic>p</italic> = 0.39) (<xref ref-type="fig" rid="F4">Figures 4E,F</xref>). ROC curve analysis showed that the AUC was 0.847 for hematoma volume and 0.653 for hemoglobin concentration (<xref ref-type="table" rid="T3">Table 3</xref> and <xref ref-type="fig" rid="F5">Figure 5A</xref>) in the HBO group. Similarly, the AUC was 0.844 for hematoma volume and 0.771 for hemoglobin concentration (<xref ref-type="table" rid="T3">Table 3</xref> and <xref ref-type="fig" rid="F5">Figure 5B</xref>) in the control group. ROC curve analysis showed that the specificity and sensitivity of hematoma volume were higher than those of hemoglobin concentration in the two groups (<xref ref-type="fig" rid="F5">Figures 5A,B</xref>). The follow-up duration was 6 months. The GOS score of the HBO group was significantly higher than that of the control group (<xref ref-type="fig" rid="F5">Figure 5C</xref>) (<italic>p</italic> &#x003C; 0.05). However, there was no significant difference in the percentages of good outcomes between the two groups (<xref ref-type="fig" rid="F5">Figure 5D</xref>).</p>
<table-wrap position="float" id="T2">
<label>TABLE 2</label>
<caption><p>Comparison of perfusion parameters in the central, marginal and cortical areas of the hematoma.</p></caption>
<table cellspacing="5" cellpadding="5" frame="hsides" rules="groups">
<thead>
<tr>
<td valign="top" align="left">Observation area</td>
<td valign="top" align="center" colspan="2">FCBV (mL&#x22C5;100 g<sup>&#x2013;1</sup>)<hr/></td>
<td valign="top" align="center" colspan="2">FCBF (mL&#x22C5;100 g<sup>&#x2013;1</sup>&#x22C5;min<sup>&#x2013;1</sup>)<hr/></td>
<td valign="top" align="center" colspan="2">SCBV (mL&#x22C5;100 g<sup>&#x2013;1</sup>)<hr/></td>
<td valign="top" align="center" colspan="2">SCBF (mL&#x22C5;100 g<sup>&#x2013;1</sup>&#x22C5;min<sup>&#x2013;1</sup>)<hr/></td>
</tr>
<tr>
<td valign="top" align="left"/><td valign="top" align="center">HBO group</td>
<td valign="top" align="center">Control group</td>
<td valign="top" align="center">HBO group</td>
<td valign="top" align="center">Control group</td>
<td valign="top" align="center">HBO group</td>
<td valign="top" align="center">Control group</td>
<td valign="top" align="center">HBO group</td>
<td valign="top" align="center">Control group</td>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Hematoma center</td>
<td valign="top" align="center">0.66 &#x00B1; 0.21</td>
<td valign="top" align="center">0.58 &#x00B1; 0.19<sup>&#x0394;</sup></td>
<td valign="top" align="center">9.25 &#x00B1; 2.05</td>
<td valign="top" align="center">8.83 &#x00B1; 1.92<sup>&#x0394;</sup></td>
<td valign="top" align="center">1.40 &#x00B1; 0.24</td>
<td valign="top" align="center">0.89 &#x00B1; 0.18&#x002A;&#x002A;&#x002A;</td>
<td valign="top" align="center">18.68 &#x00B1; 1.81</td>
<td valign="top" align="center">13.86 &#x00B1; 1.82&#x002A;&#x002A;&#x002A;</td>
</tr>
<tr>
<td valign="top" align="left">Hematoma margin</td>
<td valign="top" align="center">1.01 &#x00B1; 0.38</td>
<td valign="top" align="center">0.96 &#x00B1; 0.27<sup>&#x0394;</sup></td>
<td valign="top" align="center">16.70 &#x00B1; 0.52</td>
<td valign="top" align="center">17.28 &#x00B1; 1.83<sup>&#x0394;</sup></td>
<td valign="top" align="center">1.88 &#x00B1; 0.44</td>
<td valign="top" align="center">1.50 &#x00B1; 0.37&#x002A;&#x002A;</td>
<td valign="top" align="center">22.76 &#x00B1; 6.02</td>
<td valign="top" align="center">19.18 &#x00B1; 4.48&#x002A;</td>
</tr>
<tr>
<td valign="top" align="left">Cortical area of the hematoma</td>
<td valign="top" align="center">2.74 &#x00B1; 0.08</td>
<td valign="top" align="center">2.52 &#x00B1; 0.49<sup>&#x0394;</sup></td>
<td valign="top" align="center">27.86 &#x00B1; 2.88</td>
<td valign="top" align="center">27.17 &#x00B1; 4.58<sup>&#x0394;</sup></td>
<td valign="top" align="center">3.59 &#x00B1; 0.60</td>
<td valign="top" align="center">3.21 &#x00B1; 0.74<sup>&#x0394;</sup></td>
<td valign="top" align="center">34.47 &#x00B1; 3.05</td>
<td valign="top" align="center">33.94 &#x00B1; 1.24<sup>&#x0394;</sup></td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn><p><italic>FCBV, FCBF obtained from the first CTP scan; SCBV, SCBF obtained from the second CTP scan. (HBO group vs Control group:&#x0394;: p &#x003E; 0.05; &#x002A;p &#x003C; 0.05, &#x002A;&#x002A;p &#x003C; 0.01, &#x002A;&#x002A;&#x002A;p &#x003C; 0.001).</italic></p></fn>
</table-wrap-foot>
</table-wrap>
<fig id="F4" position="float">
<label>FIGURE 4</label>
<caption><p>A scatter diagram of black dots are depicted for the association between hematoma volume and the second set of CTP parameters in the HBO group. The relationship was not linear for the CBV and CBF values of the hematoma center, hematoma margin and cortical area of the hematoma <bold>(A&#x2013;F)</bold>. A scatter diagram of red box are depicted for the correlation between hematoma volume and the second set of CTP parameters in the control group. The relationship was linear for the CBV and CBF values of the hematoma center <bold>(E,F)</bold> nor for the CBV and CBF values of hematoma margin <bold>(A&#x2013;D)</bold>. However, no significant linear correlation was observed for the CBV and CBF values of the cortical area of the hematoma <bold>(E,F)</bold>.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnhum-16-834427-g004.tif"/>
</fig>
<table-wrap position="float" id="T3">
<label>TABLE 3</label>
<caption><p>Indices of lowest relative factors for predicting good outcome.</p></caption>
<table cellspacing="5" cellpadding="5" frame="hsides" rules="groups">
<thead>
<tr>
<td valign="top" align="left">Indices</td>
<td valign="top" align="center" colspan="2">HBO group (<italic>n</italic> = 21)<hr/></td>
<td valign="top" align="center" colspan="2">Control group (<italic>n</italic> = 20)<hr/></td>
</tr>
<tr>
<td/>
<td valign="top" align="center">Hematoma volume</td>
<td valign="top" align="center">Hg</td>
<td valign="top" align="center">Hematoma volume</td>
<td valign="top" align="center">Hg</td>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Cutoff value (%)</td>
<td valign="top" align="center">64.28%</td>
<td valign="top" align="center">35.71%</td>
<td valign="top" align="center">58.33%</td>
<td valign="top" align="center">45.83%</td>
</tr>
<tr>
<td valign="top" align="left">AUC</td>
<td valign="top" align="center">0.847</td>
<td valign="top" align="center">0.653</td>
<td valign="top" align="center">0.844</td>
<td valign="top" align="center">0.771</td>
</tr>
<tr>
<td valign="top" align="left">95% CI</td>
<td valign="top" align="center">(0.635&#x2013;1.000)</td>
<td valign="top" align="center">(0.405&#x2013;0.901)</td>
<td valign="top" align="center">(0.663&#x2013;1.000)</td>
<td valign="top" align="center">(0.561&#x2013;0.980)</td>
</tr>
<tr>
<td valign="top" align="left">Sensitivity (%)</td>
<td valign="top" align="center">85.71%</td>
<td valign="top" align="center">71.42%</td>
<td valign="top" align="center">58.33%</td>
<td valign="top" align="center">83.33%</td>
</tr>
<tr>
<td valign="top" align="left">Specificity (%)</td>
<td valign="top" align="center">78.58%</td>
<td valign="top" align="center">64.29%</td>
<td valign="top" align="center">100%</td>
<td valign="top" align="center">62.5%</td>
</tr>
<tr>
<td valign="top" align="left"><italic>p</italic>-Value</td>
<td valign="top" align="center">&#x003C;0.05</td>
<td valign="top" align="center">&#x003E;0.05</td>
<td valign="top" align="center">&#x003C;0.05</td>
<td valign="top" align="center">&#x003C;0.05</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn><p><italic>Hg: hemoglobin concentration.</italic></p></fn>
</table-wrap-foot>
</table-wrap>
<fig id="F5" position="float">
<label>FIGURE 5</label>
<caption><p>ROC curve analysis was used to determine the cutoff values for hematoma volume and hemoglobin concentration in predicting the outcome after surgery. Specificity and sensitivity were used as measures of outcome accuracy. Analyses were performed in the HBO group <bold>(A)</bold> and the control group <bold>(B)</bold>. The outcome was estimated using the area under the ROC curve (AUC). The GOS scores of the HBO and control groups were obtained 6 months after cerebral hemorrhage and were significantly higher in the HBO group than in the control group <bold>(C)</bold>. However, NS indicates that there was no significant difference in the percentage of good outcomes between the groups <bold>(D)</bold>. Statistically significant differences, indicated by &#x002A;<italic>P</italic> &#x003C; 0.05.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnhum-16-834427-g005.tif"/>
</fig>
</sec>
</sec>
<sec id="S4" sec-type="discussion">
<title>Discussion</title>
<p>HBO treatment for HICH was conducive to the improvement of neurological function. The results showed that the CBV and CBF values and the GOS scores of the HBO group were significantly higher than those of the control group. In addition, the volume of the hematoma on admission was negatively correlated with the CBV and CBF values extracted 10 days later. And intriguingly, hyperbaric oxygen therapy can reduce the effect of hemoglobin concentration on CBV and CBF. The larger the hematoma volume was, the longer it took for CBV and CBF to return to normal. HBO therapy has demonstrated a good effect on postoperative HICH at low altitudes. However, the hemoglobin concentration increases at high altitudes, and the pathophysiology is different from that at low altitudes (<xref ref-type="bibr" rid="B16">Yu et al., 2014</xref>; <xref ref-type="bibr" rid="B1">Cavalcante and Ormond, 2018</xref>). HBO treatment can transport oxygen to hypoxic tissue through higher-than-normal atmospheric pressure, reduce brain edema, improve oxygen diffusion ability and ameliorate nerve cell function (<xref ref-type="bibr" rid="B14">Wu et al., 2018</xref>). In addition, studies have shown that intracerebral hemorrhage is essentially an inflammatory reaction (<xref ref-type="bibr" rid="B13">Weng et al., 2015</xref>). HBO reduces inflammatory reactions and improves neurological function (<xref ref-type="bibr" rid="B8">Qian et al., 2017</xref>). Moreover, elevated hemoglobin levels increase blood viscosity and reduce oxygen delivery, thus leading to insufficient blood supply and even cerebral infarction (<xref ref-type="bibr" rid="B2">Chen et al., 2017</xref>). Our team reviewed the case results and found that HBO treatment could significantly improve the CBV and CBF values extracted from the hematoma center and margin at high altitudes. The greater the CBV and CBF values were, the better the circulation of the brain tissue. The main reason is that HBO alleviates the hypoxic condition of compressed brain tissue, ameliorates the function of nerve cells, and reduces tissue ischemia and hypoxia (<xref ref-type="bibr" rid="B6">Matchett et al., 2009</xref>), thus enhancing CBV and CBF. The preoperative size of the hematoma had an impact on the postoperative CBV and CBF values. Our results showed that larger hematomas were associated with worse CBV and CBF recovery, greater intracranial pressure, heavier edemas, and worse neurological function recovery. Therefore, through CTP examination, it was clear that HBO improved the postoperative CBV and CBF values and thus neurological function. Through HBO treatment and improved brain tissue perfusion and neurological function, the GOS scores of the HBO group increased. However, there was no difference in the percentage of patients with a good outcome, which might be due to the small number of patients, making the results unclear.</p>
</sec>
<sec id="S5" sec-type="conclusion">
<title>Conclusion</title>
<p>HBO could significantly ameliorate CBV and CBF and improve the recovery of neurological function. A large preoperative hematoma might affect CBV and CBF recovery and HBO can reduce the effect of hemoglobin concentration on CBV and CBF.</p>
<sec id="S5.SS1">
<title>Limitations</title>
<p>This study was limited by the case load, its retrospective design, and the fact that the analysis was restricted to basal ganglia hemorrhages. These limitations might restrict the generalizability of our findings.</p>
</sec>
</sec>
<sec id="S6" sec-type="data-availability">
<title>Data Availability Statement</title>
<p>The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.</p>
</sec>
<sec id="S7">
<title>Ethics Statement</title>
<p>This study was approved by PLA 956th Hospital and First People&#x2019;s Hospital of Honghe City Ethics Committee. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.</p>
</sec>
<sec id="S8">
<title>Author Contributions</title>
<p>AY designed the study. LW, CL, XX, SJ, YD, LP, WW, GD, YS, TZ, JW, YL, and LW collected the case data. LW and JX revised the manuscript to the final draft. LW contributed to the important discussion and interpretation of the results. All authors read and approved the final version of this manuscript.</p>
</sec>
<sec id="conf1" sec-type="COI-statement">
<title>Conflict of Interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec id="pudiscl1" sec-type="disclaimer">
<title>Publisher&#x2019;s Note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
</body>
<back>
<sec id="S9" sec-type="funding-information">
<title>Funding</title>
<p>This work was supported by grants from National Natural Science Foundation of China (82060245), Chinese Ministry of Education (2020-39), and Science and Technology Project of Guizhou Province [no. (2020)4Y149].</p>
</sec>
<ack><p>We acknowledge our colleagues (PLA 956th Hospital) for this study provided for this work.</p>
</ack>
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<glossary>
<title>Abbreviations</title>
<def-list id="DL1">
<def-item><term>CT</term><def><p>Computed tomography</p></def></def-item>
<def-item><term>GCS</term><def><p>Glasgow Coma Scale</p></def></def-item>
<def-item><term>CTP</term><def><p>Computed tomography perfusion</p></def></def-item>
<def-item><term>GOS</term><def><p>Glasgow Outcome Scale</p></def></def-item>
<def-item><term>ROI</term><def><p>Region of interest</p></def></def-item>
<def-item><term>CBV</term><def><p>Cerebral blood volume</p></def></def-item>
<def-item><term>CBF</term><def><p>Cerebral blood flow</p></def></def-item>
<def-item><term>CTA</term><def><p>Computed tomography angiography</p></def></def-item>
<def-item><term>HICH</term><def><p>Hypertensive cerebral hemorrhage</p></def></def-item>
<def-item><term>HBO</term><def><p>Hyperbaric oxygen.</p></def></def-item>
</def-list>
</glossary>
</back>
</article>
