White matter structural differences in OSA patients experiencing residual daytime sleepiness with high CPAP use: a non-Gaussian diffusion MRI study

Jiaxuan Zhang, Terri E. Weaver, Zheng Zhong, Robyn A. Nisi, Kelly R. Martin, Alana Steffen, M. Muge Karaman, Xiaohong J. Zhou

Research output: Contribution to journalArticle

Abstract

Objectives: To investigate factors associated with residual sleepiness in patients who were highly adherent to continuous positive airway pressure (CPAP). Nocturnal inactivity, comorbidities, concomitant medications, and, in particular, white matter (WM) differences using diffusion magnetic resonance imaging (MRI) were explored using a continuous-time random-walk (CTRW) model. Methods: Twenty-seven male patients (30–55 years of age) with obstructive sleep apnea (OSA) received CPAP as the only treatment (CPAP ≥ 6 h/night) for at least 30 days. Based on the Psychomotor Vigilance Task (PVT) results, participants were divided into a non-sleepy group (lapses ≤ 5; n = 18) and a sleepy group (lapses > 5; n = 9). Mean nocturnal inactivity (sleep proxy) was measured using actigraphy for one week. Diffusion-weighted imaging (DWI) with high b-values, as well as diffusion tensor imaging (DTI), was performed on a 3 T MRI scanner. The DWI dataset was analyzed using the CTRW model that yielded three parameters: temporal diffusion heterogeneity α, spatial diffusion heterogeneity β, and an anomalous diffusion coefficient Dm. The differences in α, β, and Dm between the two groups were investigated by a whole-brain analysis using tract-based spatial statistics (TBSS), followed by a regional analysis on individual fiber tracts using a standard parcellation template. Results from the CTRW model were compared with those obtained from DTI. The three CTRW parameters were also correlated with the clinical assessment scores, Epworth Sleepiness Scale (ESS), PVT lapses, and PVT mean reaction time (MRT) in specific fiber tracts. Results: There were no differences between groups in mean sleep duration, comorbidities, and the number or type of medications, including alerting and sedating medications. In the whole-brain DWI analysis, the sleepy group showed higher α (17.27% of the WM voxels) and Dm (17.14%) when compared to the non-sleepy group (P < 0.05), whereas no significant difference in β was observed. In the regional fiber analysis, the sleepy and non-sleepy groups showed significant differences in α, β, or their combinations in a total of 12 fiber tracts; whereas similar differences were not observed in DTI parameters, when age was used as a covariate. Additionally, moderate to strong correlations between the CTRW parameters (α, β, or Dm) and the sleepiness assessment scores (ESS, PVT lapses, or PVT MRT) were observed in specific fiber tracts (|R| = 0.448–0.654, P = 0.0003–0.019). Conclusions: The observed differences in the CTRW parameters between the two groups indicate that WM alterations can be a possible mechanism to explain reversible versus residual sleepiness observed in OSA patients with identical high level of CPAP use. The moderate to strong correlations between the CTRW parameters and the clinical scores suggest the possibility of developing objective and quantitative imaging markers to complement clinical assessment of OSA patients.

LanguageEnglish (US)
Pages51-59
Number of pages9
JournalSleep Medicine
Volume53
DOIs
StatePublished - Jan 1 2019

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Diffusion Magnetic Resonance Imaging
Continuous Positive Airway Pressure
Obstructive Sleep Apnea
Diffusion Tensor Imaging
Reaction Time
Comorbidity
Sleep
Actigraphy
White Matter
Brain
Proxy
Magnetic Resonance Imaging

Keywords

  • CPAP
  • Diffusion imaging
  • MRI
  • Non-Gaussian diffusion model
  • Obstructive sleep apnea
  • Residual sleepiness

ASJC Scopus subject areas

  • Medicine(all)

Cite this

White matter structural differences in OSA patients experiencing residual daytime sleepiness with high CPAP use : a non-Gaussian diffusion MRI study. / Zhang, Jiaxuan; Weaver, Terri E.; Zhong, Zheng; Nisi, Robyn A.; Martin, Kelly R.; Steffen, Alana; Karaman, M. Muge; Zhou, Xiaohong J.

In: Sleep Medicine, Vol. 53, 01.01.2019, p. 51-59.

Research output: Contribution to journalArticle

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abstract = "Objectives: To investigate factors associated with residual sleepiness in patients who were highly adherent to continuous positive airway pressure (CPAP). Nocturnal inactivity, comorbidities, concomitant medications, and, in particular, white matter (WM) differences using diffusion magnetic resonance imaging (MRI) were explored using a continuous-time random-walk (CTRW) model. Methods: Twenty-seven male patients (30–55 years of age) with obstructive sleep apnea (OSA) received CPAP as the only treatment (CPAP ≥ 6 h/night) for at least 30 days. Based on the Psychomotor Vigilance Task (PVT) results, participants were divided into a non-sleepy group (lapses ≤ 5; n = 18) and a sleepy group (lapses > 5; n = 9). Mean nocturnal inactivity (sleep proxy) was measured using actigraphy for one week. Diffusion-weighted imaging (DWI) with high b-values, as well as diffusion tensor imaging (DTI), was performed on a 3 T MRI scanner. The DWI dataset was analyzed using the CTRW model that yielded three parameters: temporal diffusion heterogeneity α, spatial diffusion heterogeneity β, and an anomalous diffusion coefficient Dm. The differences in α, β, and Dm between the two groups were investigated by a whole-brain analysis using tract-based spatial statistics (TBSS), followed by a regional analysis on individual fiber tracts using a standard parcellation template. Results from the CTRW model were compared with those obtained from DTI. The three CTRW parameters were also correlated with the clinical assessment scores, Epworth Sleepiness Scale (ESS), PVT lapses, and PVT mean reaction time (MRT) in specific fiber tracts. Results: There were no differences between groups in mean sleep duration, comorbidities, and the number or type of medications, including alerting and sedating medications. In the whole-brain DWI analysis, the sleepy group showed higher α (17.27{\%} of the WM voxels) and Dm (17.14{\%}) when compared to the non-sleepy group (P < 0.05), whereas no significant difference in β was observed. In the regional fiber analysis, the sleepy and non-sleepy groups showed significant differences in α, β, or their combinations in a total of 12 fiber tracts; whereas similar differences were not observed in DTI parameters, when age was used as a covariate. Additionally, moderate to strong correlations between the CTRW parameters (α, β, or Dm) and the sleepiness assessment scores (ESS, PVT lapses, or PVT MRT) were observed in specific fiber tracts (|R| = 0.448–0.654, P = 0.0003–0.019). Conclusions: The observed differences in the CTRW parameters between the two groups indicate that WM alterations can be a possible mechanism to explain reversible versus residual sleepiness observed in OSA patients with identical high level of CPAP use. The moderate to strong correlations between the CTRW parameters and the clinical scores suggest the possibility of developing objective and quantitative imaging markers to complement clinical assessment of OSA patients.",
keywords = "CPAP, Diffusion imaging, MRI, Non-Gaussian diffusion model, Obstructive sleep apnea, Residual sleepiness",
author = "Jiaxuan Zhang and Weaver, {Terri E.} and Zheng Zhong and Nisi, {Robyn A.} and Martin, {Kelly R.} and Alana Steffen and Karaman, {M. Muge} and Zhou, {Xiaohong J.}",
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TY - JOUR

T1 - White matter structural differences in OSA patients experiencing residual daytime sleepiness with high CPAP use

T2 - Sleep Medicine

AU - Zhang, Jiaxuan

AU - Weaver, Terri E.

AU - Zhong, Zheng

AU - Nisi, Robyn A.

AU - Martin, Kelly R.

AU - Steffen, Alana

AU - Karaman, M. Muge

AU - Zhou, Xiaohong J.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objectives: To investigate factors associated with residual sleepiness in patients who were highly adherent to continuous positive airway pressure (CPAP). Nocturnal inactivity, comorbidities, concomitant medications, and, in particular, white matter (WM) differences using diffusion magnetic resonance imaging (MRI) were explored using a continuous-time random-walk (CTRW) model. Methods: Twenty-seven male patients (30–55 years of age) with obstructive sleep apnea (OSA) received CPAP as the only treatment (CPAP ≥ 6 h/night) for at least 30 days. Based on the Psychomotor Vigilance Task (PVT) results, participants were divided into a non-sleepy group (lapses ≤ 5; n = 18) and a sleepy group (lapses > 5; n = 9). Mean nocturnal inactivity (sleep proxy) was measured using actigraphy for one week. Diffusion-weighted imaging (DWI) with high b-values, as well as diffusion tensor imaging (DTI), was performed on a 3 T MRI scanner. The DWI dataset was analyzed using the CTRW model that yielded three parameters: temporal diffusion heterogeneity α, spatial diffusion heterogeneity β, and an anomalous diffusion coefficient Dm. The differences in α, β, and Dm between the two groups were investigated by a whole-brain analysis using tract-based spatial statistics (TBSS), followed by a regional analysis on individual fiber tracts using a standard parcellation template. Results from the CTRW model were compared with those obtained from DTI. The three CTRW parameters were also correlated with the clinical assessment scores, Epworth Sleepiness Scale (ESS), PVT lapses, and PVT mean reaction time (MRT) in specific fiber tracts. Results: There were no differences between groups in mean sleep duration, comorbidities, and the number or type of medications, including alerting and sedating medications. In the whole-brain DWI analysis, the sleepy group showed higher α (17.27% of the WM voxels) and Dm (17.14%) when compared to the non-sleepy group (P < 0.05), whereas no significant difference in β was observed. In the regional fiber analysis, the sleepy and non-sleepy groups showed significant differences in α, β, or their combinations in a total of 12 fiber tracts; whereas similar differences were not observed in DTI parameters, when age was used as a covariate. Additionally, moderate to strong correlations between the CTRW parameters (α, β, or Dm) and the sleepiness assessment scores (ESS, PVT lapses, or PVT MRT) were observed in specific fiber tracts (|R| = 0.448–0.654, P = 0.0003–0.019). Conclusions: The observed differences in the CTRW parameters between the two groups indicate that WM alterations can be a possible mechanism to explain reversible versus residual sleepiness observed in OSA patients with identical high level of CPAP use. The moderate to strong correlations between the CTRW parameters and the clinical scores suggest the possibility of developing objective and quantitative imaging markers to complement clinical assessment of OSA patients.

AB - Objectives: To investigate factors associated with residual sleepiness in patients who were highly adherent to continuous positive airway pressure (CPAP). Nocturnal inactivity, comorbidities, concomitant medications, and, in particular, white matter (WM) differences using diffusion magnetic resonance imaging (MRI) were explored using a continuous-time random-walk (CTRW) model. Methods: Twenty-seven male patients (30–55 years of age) with obstructive sleep apnea (OSA) received CPAP as the only treatment (CPAP ≥ 6 h/night) for at least 30 days. Based on the Psychomotor Vigilance Task (PVT) results, participants were divided into a non-sleepy group (lapses ≤ 5; n = 18) and a sleepy group (lapses > 5; n = 9). Mean nocturnal inactivity (sleep proxy) was measured using actigraphy for one week. Diffusion-weighted imaging (DWI) with high b-values, as well as diffusion tensor imaging (DTI), was performed on a 3 T MRI scanner. The DWI dataset was analyzed using the CTRW model that yielded three parameters: temporal diffusion heterogeneity α, spatial diffusion heterogeneity β, and an anomalous diffusion coefficient Dm. The differences in α, β, and Dm between the two groups were investigated by a whole-brain analysis using tract-based spatial statistics (TBSS), followed by a regional analysis on individual fiber tracts using a standard parcellation template. Results from the CTRW model were compared with those obtained from DTI. The three CTRW parameters were also correlated with the clinical assessment scores, Epworth Sleepiness Scale (ESS), PVT lapses, and PVT mean reaction time (MRT) in specific fiber tracts. Results: There were no differences between groups in mean sleep duration, comorbidities, and the number or type of medications, including alerting and sedating medications. In the whole-brain DWI analysis, the sleepy group showed higher α (17.27% of the WM voxels) and Dm (17.14%) when compared to the non-sleepy group (P < 0.05), whereas no significant difference in β was observed. In the regional fiber analysis, the sleepy and non-sleepy groups showed significant differences in α, β, or their combinations in a total of 12 fiber tracts; whereas similar differences were not observed in DTI parameters, when age was used as a covariate. Additionally, moderate to strong correlations between the CTRW parameters (α, β, or Dm) and the sleepiness assessment scores (ESS, PVT lapses, or PVT MRT) were observed in specific fiber tracts (|R| = 0.448–0.654, P = 0.0003–0.019). Conclusions: The observed differences in the CTRW parameters between the two groups indicate that WM alterations can be a possible mechanism to explain reversible versus residual sleepiness observed in OSA patients with identical high level of CPAP use. The moderate to strong correlations between the CTRW parameters and the clinical scores suggest the possibility of developing objective and quantitative imaging markers to complement clinical assessment of OSA patients.

KW - CPAP

KW - Diffusion imaging

KW - MRI

KW - Non-Gaussian diffusion model

KW - Obstructive sleep apnea

KW - Residual sleepiness

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