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ORIGINAL ARTICLE
Year : 2018  |  Volume : 21  |  Issue : 2  |  Page : 236-241

Evaluation of Brain Volume Changes by Magnetic Resonance Imaging in Obstructive Sleep Apnea Syndrome


1 Department of Radiology, Burdur State Hospital, Adiyaman, Turkey
2 Department of Family Medicine, Adiyaman University School of Medicine, Adiyaman, Turkey
3 Department of Radiology, Adana Numune Training and Research Hospital, Adiyaman, Turkey
4 Department of Radiology, Uludag University School of Medicine, Adiyaman, Turkey

Date of Acceptance01-Jan-2017
Date of Web Publication21-Feb-2018

Correspondence Address:
A B Öztürk
Department of Family Medicine, School of Medicine, Adiyaman University, Adiyaman
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njcp.njcp_379_16

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   Abstract 


Background and Objectives: The objective of this study was to evaluate potential morphological changes in the brain tissue of patients with severe obstructive sleep apnea syndrome (OSAS) in comparison with normal subjects by using T1-weighted magnetic resonance imaging (MRI) technique. Material and Methods: This study comprised subjects with severe OSAS with an apnea-hypopnea index (AHI) more than 30 and normal subjects with AHI less than 5 according to polysomnography findings. The study subjects were evaluated using Three Dimensional Magnetization Prepared Rapid Acquisition Gradient Echo sequence on T1-weighted MRI. FreeSurfer morphometric procedure was used as the automated segmentation method and in both cerebral and cerebellar hemsipheres and segmental volumes of brain were analyzed. Results: Of the 22 patients with severe OSAS, 19 were male, three were female and their ages ranged between 40 and 60 years (mean age 50.27 ± 5.3 years). Of the 22 control subjects 19 were male, three were female and their ages ranged between 40 and 60 years (mean age 49.36 ± 6.95 years). There were no statistically significant differences in terms of age and sex properties between the groups. There was a statistically significant difference in BMI between the OSAS patients and the control group. There were statistically significant differences in polysomnographic features (time elapsed below 90% SaO2 (min), Epworth Sleepiness Scale, AHI, mean minimum SaO2 (%), mean O2 desaturation (%), and arousal index values) between the OSAS patients and the control group. Conclusions: The findings of our study indicated that even if severe, no structural changes occur in the course of mild, moderate, and severe OSAS.

Keywords: Apnea–hypopnea index, brain volume, FreeSurfer, obstructive sleep apnea syndrome, polysomnography


How to cite this article:
Ozturk S B, Öztürk A B, Soker G, Parlak M. Evaluation of Brain Volume Changes by Magnetic Resonance Imaging in Obstructive Sleep Apnea Syndrome. Niger J Clin Pract 2018;21:236-41

How to cite this URL:
Ozturk S B, Öztürk A B, Soker G, Parlak M. Evaluation of Brain Volume Changes by Magnetic Resonance Imaging in Obstructive Sleep Apnea Syndrome. Niger J Clin Pract [serial online] 2018 [cited 2022 Nov 30];21:236-41. Available from: https://www.njcponline.com/text.asp?2018/21/2/236/225944




   Introduction Top


Sleep-related breathing disorders are one of the most important health problems as these can result in high morbidity and mortality.[1],[2] More than 90% of the patients having sleep-related breathing disorders constitutes obstructive sleep apnea syndrome (OSAS).[3]

OSAS is a syndrome characterized by full or partial upper airway obstruction episodes and a frequent decrease in blood oxygen saturation that is repetitive during sleep.[4],[5] During OSAS, changes are seen in the cerebellum, basal ganglia, and the limbic neurons that have a specific impact on autonomic and cognitive functions and mood.[6] The risk of hypertension and cardiac arrhythmia increases with the increase of sympathetic tonus in brain regions, and at the same time it impairs concentration and short-term memory, and increases anxiety.[7] OSAS causes a wide range of neuropsychological dysfunctions that cause a decrease in the quality of life, negatively impacts on the workforce, and increases the risk of vehicular and industrial accidents.[8],[9] In the literature, there are very few studies that examine hypoxia and hypercapnia in OSAS and the metabolism and the morphology of the brain.[10],[11],[12],[13]

The objective of our study was to compare possible morphological changes in the brain due to OSAS by assessing the brain volume obtained with T1-weighted MRI in patients experiencing extreme OSAS with an automatic volume measurement system, and a healthy group.


   Materials and Methods Top


Selection of Subjects

Our study was conducted prospectively between January and June 2011. From the subjects on whom polysomnography was made, those appropriate for the study were determined in and scheduled for MRI. The patients diagnosed with OSAS disease were included in our research in accordance with our criteria.

Inclusion Criteria

  1. Between the ages of 40 and 60
  2. Subjects (patient group) with OSAS, with an AHI over 30
  3. Subjects (control group) with normal sleep test with AHI below 5


Exclusion Criteria

  1. Ages below 40 and above 60
  2. Subjects having mild and medium OSAS
  3. Patients with diabetes mellitus (DM), hypertension (HT), neurodegenerative disease, head trauma, pulmonary disease, addiction to alcohol and drugs, cerebral vascular accident (CVA), and epilepsy
  4. Patients having contraindications for magnetic resonance (MR) examinations (cardiac pacemaker, metallic or cochlear implants, presence of intraocular metallic foreign objects, claustrophobia, among others)


Our study was approved by the hospital ethics committee.

MRI Technique

All the selected volunteers were assessed using circular polarized head dressings at 1.5 T of superconductivity magnets (Magnetom Vision Plus; Siemens, Erlangen, Germany) with the application of the cranial MRI protocol.

Noncontrast MRI examinations of subjects were made using an axial platform T1-weighted spin echo (SE), T2-weighted fast spin echo (FSE), and on flair and sagittal platform T2-weighted FSE. For brain volume, T1-weighted Three Dimensional Magnetization Prepared Rapid Acquisition Gradient Echo (3D MP-RAGE) sequence was used. The parameters of this sequence, varying in accordance with the head shape of the patient, were chosen as FOV (field of view): 30 × 30 cm, no spaces between sections, section thickness 1.3 mm, image matrix 200 ×256, TR (repetition time): 9.7 ms, TE (echo time): 4 ms, FA (flip angle): 12 °, S/N: 1. Total imaging period was approximately 15-20 min.

Morphometric Assessment

The high-resolution images obtained from MRI, in Digital Imaging and Communications in Medicine (DICOM) format were transferred to a Linux-based computer for analyses.

During the morphometric analyses process, Free Surfer program was used.[14],[15] First, the lapses caused by patient movements were corrected. The variations in brightness caused by the changes in B1 magnetic area were removed. Afterward, the images were placed on Talairach coordinate system. This transition increased the success of segmentation method that was previously placed hand using the standard ready brain template, which enabled the prelabeling process. Thus, faults caused by pathologies were decreased. The Tabula was deleted automatically and the remaining part was used for brain mask during labeling and segmentation processes [Figure 1],[Figure 2],[Figure 3].
Figure 1: T1A MP-RAGE images on sagittal platform. (a) First image before segmentation, (b) cranium-deleted image, (c) colored image displaying the measured areas after segmentation

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Figure 2: T1A MP-RAGE images on sagittal platform. (a) First image before segmentation, (b) cranium-deleted image, (c) colored image displaying the measured areas after segmentation

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Figure 3: T1A MP-RAGE images from Lateral ventricles level to axial platform A. First image before segmentation, B. Cranium-deleted image C. Colored image displaying the measured areas after segmentation

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The results of automatic labeling and segmentation processes were assessed in accordance with success. The unsuccessful parts were corrected manually by an expert radiologist and the volume calculations were repeated.

The brain volumes obtained from more than 40 different regions of brain per each volunteer were normalized by dividing the individual's own brain volume and values obtained from cerebral white matter, cerebral cortex, cerebellar white matter, cerebellar cortex, thalamus, caudate, putamen, pallidum, hippocampus, hippocampus amygdala, accumbens, lateral ventricles, choroid plexus, 3rd ventricle, 4th ventricle, vascular structure, optic chiasm, corpus callosum (posterior, central-posterior, central and anterior), white matter hyperintensity, off-white matter hyperintensity, and brain segmentation volume.

Statistical Analyses

The analyses of the study were conducted on Statistical Package for the Social Sciences (SPSS) 13.0 (Chicago, Illinois, USA) program. The continuous variables in the study were the mean, standard deviation, median, minimum and maximum values, and categorical variables were numbers and percentage values. The congruence of continuous variables to normal distribution were analyzed with the Shapiro–Wilk test and according to test results, for the comparisons between patient and control group t test and Mann–Whitney U test were used for independent double sampling. The comparison between groups in accordance with sex was made with exact chi-square test. In the study, P < 0.05 was accepted as statistically significant difference.


   Results Top


Of the 22 severe OSAS patients included into the study, 19 were men and three were women and the ages were between 40 and 60 (mean age 50.27 ± 5.3 years). Of the 22 control group, 19 were men and three were women and the ages were between 40 and 60 (mean age 49.36 ± 6.95 years). There was no statistically significant difference between the groups in terms of age and sex (P > 0.05).

As the subjects determined with intracranial pathological signal intensity were excluded, the conventional axial and sagittal images of all the subjects included in the study were normal.

There were no additional systematic diseases in either the patient or control group. There were statistically significant differences between the patients with OSAS and control group in terms of body mass index (BMI) demographically and from the data of polysomnography SaO2 period (minutes) below than 90%, Epworth Sleepiness Scale (ESS) AHI, mean minimum SaO2 (%), mean O2 desaturation (%), and arousal index (P < 0.05). The demographical and polysomnography data of patient and control group are given in [Table 1].
Table 1: Demographical and polysomnography data of subjects.

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In the subcortical brain volume measurements conducted with the automatic segmentation method from the images obtained in DICOM format, all the segments obtained from both hemispheres of the two groups were cerebral white matter, cerebral cortex, cerebellar white matter, cerebellar cortex, thalamus, caudate, putamen, pallidum, hippocampus, hippocampus amygdala, accumbens, lateral ventricles, choroid plexus, 3rd ventricle, 4th ventricle, vascular structure, optic chiasm, corpus callosum (posterior, central-posterior, central and anterior), white matter hyperintensity, off-white matter hyperintensity and brain segmentation volumes; and in all, there were no differences in terms of volume between the patients and control group (P > 0.05).

The statistical assessment of the segmental volumes of the patient and healthy groups are given in [Table 2] in percentages. Case examples are displayed in [Figure 1] and [Figure 3].
Table 2: The ratio in statistical percentages of segmental volumes of patient and healthy groups to their own brain volumes in percentages and P values

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   Discussion Top


In subjects with OSAS, the differences in the metabolite concentrations of white matter were examined by conducting specific research. In the measurements done with magnetic resonance spectroscopy (MRS), the decreased N-acetyl aspartate (NAA) and choline (Cho) concentration determined in prefrontal white matter had the future of supporting the early structural changes such as the neuronal loss and axon damage.[17],[18] In a few OSAS patients, MRS changes were determined in the left hippocampus and the decrease of compounds containing creatine (Cr ) showed a correlation with OSAS severity and cognitive disorders. These data have the future of supporting the sensitivity of hippocampal tissue to intermittent hypoxia in patients with OSAS.[19]

In a study conducted by Macey et al.,[20] conducted using alternative MR analyses, such as diffusion imaging, they determined early structural changes in axons and myelin sheath. They determined axonal damage in hippocampal, cerebellar, and pontine neurons in OSAS patients, earlier than the loss of gray matter.

In some studies assessing gray matter concentration using VBM method, Joo et al.,[12] when OSAS patients were compared with health volunteers, in some regions (left gyrus rectus, anterior singulate gyrus, right insular gyrus, caudate nucleus, thalamus, amygdala-hippocampus, inferior temporal gyrus, and cerebellum), they determined a significant decrease in gray matter concentration. Morrell et al., determined seriously low gray matter concentrations in the left hippocampus. No important focal gray matter differences were determined in the left hippocampus and in regions of the brain. It was indicated that the gray matter segment of the T1 signal, when the gray matter concentration was at its maximum, was 6% less in OSAS patients.[11]

In the study conducted by Macey, the high severity of disease and they did not externalize the patients with additional diseases may have impact on brain structure and afferent the results.[10] In study conducted by Yaouhi et al.,[16] significant loss of gray matter was found in bilateral inferior parietal gyrus, right temporal cortex, occipital cortex, right thalamus, left putamen, left caudate nucleus and left pallidum, right hippocampal gyrus, right cerebellar hemisphere, and vermis. Morrell et al.[21] has determined decrease in gray matter in right central temporal gyrus. At the same time, loss of gray matter was determined in left lobe specifically, central and right lobe of cerebellum.

Torelli et al.,[22] conducted studies on same subjects by using FreeSurfer and VBM (voxel-based morphometry) methods; when FreeSurfer morphometric method was used, and when compared with OSAS patients with control groups, they determined decreased gray matter volume. The right hippocampus was determined to be smaller when compared with the control group. When age, BMI, sex, ESS and comorbidities were checked, there was significant difference. The bilateral caudate nucleus volume was smaller when compared with the control group. But when the BMI, sex, hypertension, age, cigarette usage was checked, there were no differences in caudate volume. There were no differences in cerebellum, putamen, amygdala, and thalamus. In the same study, when VBM analyses were used, decrease in gray matter was determined in right hippocampus.

In our study, we did not determine any decrease in volume of gray matter. Apart from this, in some of the studies where the volume decrease was determined, it was thought that the comorbid diseases that were not excluded cob have impact on brain volume with OSAS and the sensitivity of chosen statistical threshold value for VBM analyses methods were effective. In addition, used differently according to us, VBM could be considered as more sensitive technique at mild parenchymal damages with no volume loss that could be determine automatic subdivision and volumetric methods for the subcortical structures.

In the studies conducted by Joo et al.,[12] differences were not determined between the OSAS patients and control groups in terms of gray matter volume with VBM. In addition, Morrell et al.[11] did not determine volume difference in gray matter. Macey et al.[10] also did not determine any regional differences in terms of white matter or ventricles. In the study conducted by Torelli et al.,[13] the white matter volume was decreased at both regions in right temporal lobe. One of these two regions was localized right next to hippocampal region where there was loss of gray matter. In the same study, when the FreeSurfer was used, the difference in white matter volume was not significant.

In our study, we did not determine significant difference between the white matter, gray matter segments, and Brain-spinal fluid (BOS) volumes in OSAS patients when compared with the control group. In our study, we did not determine any volume differences; this could be because there were no statistical significant difference between ages and sex of groups and the patients comorbid diseases that could have impact on brain volume changes were excluded, and as there were not any parenchymal lesion in MR images. Furthermore, the structural changes in brain MRI, could determine the chronic condition of the disease rather than the regional blood flow or functional changes of glucose metabolisms.[12]

In our study, having relatively less numbers of groups was an important limitation. We could not conduct concentration measurement with FreeSurfer method; this has caused an absence in assessments in terms of early structural changes such as neuronal loss and axonal damage.

As a result, between the OSAS patients and control group, as volume difference was not determined in a large number of segments of brain, in both cerebral and cerebellar gray matter and white matter segments, in ventricles and in all brain volume, has showed did not causes any structural changes in mild, moderate, severe OSAS. Further studies are required to confirm these findings.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2]



 

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