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<meta name="DC.Title" content="The Effects of Acetazolamide on the Evaluation of Cerebral Hemodynamics and Functional Connectivity Using Blood Oxygen Level–Dependent MR Imaging in Patients with Chronic Steno-Occlusive Disease of the Anterior Circulation" />
<meta name="DC.Identifier" content="10.3174/ajnr.A4973" />
<meta name="DC.Date" content="2016-10-06" />
<meta name="DC.Publisher" content="American Journal of Neuroradiology" />
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<meta name="DC.Description" content="BACKGROUND AND PURPOSE: Measuring cerebrovascular reactivity with the use of vasodilatory stimuli, such as acetazolamide, is useful for chronic cerebrovascular steno-occlusive disease. The purpose of this study was to evaluate the effects of acetazolamide on the assessment of hemodynamic impairment and functional connectivity by using noninvasive resting-state blood oxygen level–dependent MR imaging.

MATERIALS AND METHODS: A 20-minute resting-state blood oxygen level–dependent MR imaging scan was acquired with infusion of acetazolamide starting at 5 minutes after scan initiation. A recently developed temporal-shift analysis technique was applied on blood oxygen level–dependent MR imaging data before and after acetazolamide infusion to identify regions with hemodynamic impairment, and the results were compared by using contrast agent–based DSC perfusion imaging as the reference standard. Functional connectivity was compared with and without correction on the signal by using information from temporal-shift analysis, before and after acetazolamide infusion.

RESULTS: Visually, temporal-shift analysis of blood oxygen level–dependent MR imaging data identified regions with compromised hemodynamics as defined by DSC, though performance deteriorated in patients with bilateral disease. The Dice similarity coefficient between temporal-shift and DSC maps was higher before (0.487 ± 0.150 by using the superior sagittal sinus signal as a reference for temporal-shift analysis) compared with after acetazolamide administration (0.384 ± 0.107) ( P = .006, repeated-measures ANOVA). Functional connectivity analysis with temporal-shift correction identified brain network nodes that were otherwise missed. The accuracy of functional connectivity assessment decreased after acetazolamide administration ( P = .015 for default mode network, repeated-measures ANOVA).

CONCLUSIONS: Temporal-shift analysis of blood oxygen level–dependent MR imaging can identify brain regions with hemodynamic compromise in relation to DSC among patients with chronic cerebrovascular disease. The use of acetazolamide reduces the accuracy of temporal-shift analysis and network connectivity evaluation.

### Abbreviations

ACZ
:   acetazolamide
BOLD
:   blood oxygen level–dependent MR imaging
DMN
:   default mode network
SMN
:   sensorimotor network
SSS
:   superior sagittal sinus
Tmax
:   time-to-maximum of the residue function
TS
:   temporal-shift" />
<meta name="DC.Contributor" content="J. Wu" />
<meta name="DC.Contributor" content="S. Dehkharghani" />
<meta name="DC.Contributor" content="F. Nahab" />
<meta name="DC.Contributor" content="J. Allen" />
<meta name="DC.Contributor" content="D. Qiu" />
<meta name="article:published_time" content="2016-10-06" />
<meta name="article:section" content="FUNCTIONAL" />
<meta name="citation_title" content="The Effects of Acetazolamide on the Evaluation of Cerebral Hemodynamics and Functional Connectivity Using Blood Oxygen Level–Dependent MR Imaging in Patients with Chronic Steno-Occlusive Disease of the Anterior Circulation" />
<meta name="citation_abstract" lang="en" content="&lt;h3&gt;BACKGROUND AND PURPOSE:&lt;/h3&gt;
&lt;p&gt;Measuring cerebrovascular reactivity with the use of vasodilatory stimuli, such as acetazolamide, is useful for chronic cerebrovascular steno-occlusive disease. The purpose of this study was to evaluate the effects of acetazolamide on the assessment of hemodynamic impairment and functional connectivity by using noninvasive resting-state blood oxygen level–dependent MR imaging.&lt;/p&gt;&lt;h3&gt;MATERIALS AND METHODS:&lt;/h3&gt;
&lt;p&gt;A 20-minute resting-state blood oxygen level–dependent MR imaging scan was acquired with infusion of acetazolamide starting at 5 minutes after scan initiation. A recently developed temporal-shift analysis technique was applied on blood oxygen level–dependent MR imaging data before and after acetazolamide infusion to identify regions with hemodynamic impairment, and the results were compared by using contrast agent–based DSC perfusion imaging as the reference standard. Functional connectivity was compared with and without correction on the signal by using information from temporal-shift analysis, before and after acetazolamide infusion.&lt;/p&gt;&lt;h3&gt;RESULTS:&lt;/h3&gt;
&lt;p&gt;Visually, temporal-shift analysis of blood oxygen level–dependent MR imaging data identified regions with compromised hemodynamics as defined by DSC, though performance deteriorated in patients with bilateral disease. The Dice similarity coefficient between temporal-shift and DSC maps was higher before (0.487 ± 0.150 by using the superior sagittal sinus signal as a reference for temporal-shift analysis) compared with after acetazolamide administration (0.384 ± 0.107) (&lt;i&gt;P&lt;/i&gt; = .006, repeated-measures ANOVA). Functional connectivity analysis with temporal-shift correction identified brain network nodes that were otherwise missed. The accuracy of functional connectivity assessment decreased after acetazolamide administration (&lt;i&gt;P&lt;/i&gt; = .015 for default mode network, repeated-measures ANOVA).&lt;/p&gt;&lt;h3&gt;CONCLUSIONS:&lt;/h3&gt;
&lt;p&gt;Temporal-shift analysis of blood oxygen level–dependent MR imaging can identify brain regions with hemodynamic compromise in relation to DSC among patients with chronic cerebrovascular disease. The use of acetazolamide reduces the accuracy of temporal-shift analysis and network connectivity evaluation.&lt;/p&gt;" />
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<meta name="citation_author" content="J. Wu" />
<meta name="citation_author_institution" content="From the Departments of Radiology and Imaging Sciences (J.W., S.D., J.A., D.Q.) and Neurology (F.N.), Emory University School of Medicine, Atlanta, Georgia." />
<meta name="citation_author_orcid" content="http://orcid.org/0000-0002-7562-2352" />
<meta name="citation_author" content="S. Dehkharghani" />
<meta name="citation_author_institution" content="From the Departments of Radiology and Imaging Sciences (J.W., S.D., J.A., D.Q.) and Neurology (F.N.), Emory University School of Medicine, Atlanta, Georgia." />
<meta name="citation_author_orcid" content="http://orcid.org/0000-0002-3141-1094" />
<meta name="citation_author" content="F. Nahab" />
<meta name="citation_author_institution" content="From the Departments of Radiology and Imaging Sciences (J.W., S.D., J.A., D.Q.) and Neurology (F.N.), Emory University School of Medicine, Atlanta, Georgia." />
<meta name="citation_author_orcid" content="http://orcid.org/0000-0003-1710-9881" />
<meta name="citation_author" content="J. Allen" />
<meta name="citation_author_institution" content="From the Departments of Radiology and Imaging Sciences (J.W., S.D., J.A., D.Q.) and Neurology (F.N.), Emory University School of Medicine, Atlanta, Georgia." />
<meta name="citation_author_orcid" content="http://orcid.org/0000-0002-5274-1105" />
<meta name="citation_author" content="D. Qiu" />
<meta name="citation_author_institution" content="From the Departments of Radiology and Imaging Sciences (J.W., S.D., J.A., D.Q.) and Neurology (F.N.), Emory University School of Medicine, Atlanta, Georgia." />
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<meta name="twitter:title" content="The Effects of Acetazolamide on the Evaluation of Cerebral Hemodynamics and Functional Connectivity Using Blood Oxygen Level–Dependent MR Imaging in Patients with Chronic Steno-Occlusive Disease of the Anterior Circulation" />
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<meta name="twitter:description" content="BACKGROUND AND PURPOSE: Measuring cerebrovascular reactivity with the use of vasodilatory stimuli, such as acetazolamide, is useful for chronic cerebrovascular steno-occlusive disease. The purpose of this study was to evaluate the effects of acetazolamide on the assessment of hemodynamic impairment and functional connectivity by using noninvasive resting-state blood oxygen level–dependent MR imaging.

MATERIALS AND METHODS: A 20-minute resting-state blood oxygen level–dependent MR imaging scan was acquired with infusion of acetazolamide starting at 5 minutes after scan initiation. A recently developed temporal-shift analysis technique was applied on blood oxygen level–dependent MR imaging data before and after acetazolamide infusion to identify regions with hemodynamic impairment, and the results were compared by using contrast agent–based DSC perfusion imaging as the reference standard. Functional connectivity was compared with and without correction on the signal by using information from temporal-shift analysis, before and after acetazolamide infusion.

RESULTS: Visually, temporal-shift analysis of blood oxygen level–dependent MR imaging data identified regions with compromised hemodynamics as defined by DSC, though performance deteriorated in patients with bilateral disease. The Dice similarity coefficient between temporal-shift and DSC maps was higher before (0.487 ± 0.150 by using the superior sagittal sinus signal as a reference for temporal-shift analysis) compared with after acetazolamide administration (0.384 ± 0.107) ( P = .006, repeated-measures ANOVA). Functional connectivity analysis with temporal-shift correction identified brain network nodes that were otherwise missed. The accuracy of functional connectivity assessment decreased after acetazolamide administration ( P = .015 for default mode network, repeated-measures ANOVA).

CONCLUSIONS: Temporal-shift analysis of blood oxygen level–dependent MR imaging can identify brain regions with hemodynamic compromise in relation to DSC among patients with chronic cerebrovascular disease. The use of acetazolamide reduces the accuracy of temporal-shift analysis and network connectivity evaluation.

### Abbreviations

ACZ
:   acetazolamide
BOLD
:   blood oxygen level–dependent MR imaging
DMN
:   default mode network
SMN
:   sensorimotor network
SSS
:   superior sagittal sinus
Tmax
:   time-to-maximum of the residue function
TS
:   temporal-shift" />
<meta name="og-title" property="og:title" content="The Effects of Acetazolamide on the Evaluation of Cerebral Hemodynamics and Functional Connectivity Using Blood Oxygen Level–Dependent MR Imaging in Patients with Chronic Steno-Occlusive Disease of the Anterior Circulation" />
<meta name="og-url" property="og:url" content="http://ajnr-stage2.stage.highwire.org/content/early/2016/10/06/ajnr.A4973" />
<meta name="og-site-name" property="og:site_name" content="American Journal of Neuroradiology" />
<meta name="og-description" property="og:description" content="BACKGROUND AND PURPOSE: Measuring cerebrovascular reactivity with the use of vasodilatory stimuli, such as acetazolamide, is useful for chronic cerebrovascular steno-occlusive disease. The purpose of this study was to evaluate the effects of acetazolamide on the assessment of hemodynamic impairment and functional connectivity by using noninvasive resting-state blood oxygen level–dependent MR imaging.

MATERIALS AND METHODS: A 20-minute resting-state blood oxygen level–dependent MR imaging scan was acquired with infusion of acetazolamide starting at 5 minutes after scan initiation. A recently developed temporal-shift analysis technique was applied on blood oxygen level–dependent MR imaging data before and after acetazolamide infusion to identify regions with hemodynamic impairment, and the results were compared by using contrast agent–based DSC perfusion imaging as the reference standard. Functional connectivity was compared with and without correction on the signal by using information from temporal-shift analysis, before and after acetazolamide infusion.

RESULTS: Visually, temporal-shift analysis of blood oxygen level–dependent MR imaging data identified regions with compromised hemodynamics as defined by DSC, though performance deteriorated in patients with bilateral disease. The Dice similarity coefficient between temporal-shift and DSC maps was higher before (0.487 ± 0.150 by using the superior sagittal sinus signal as a reference for temporal-shift analysis) compared with after acetazolamide administration (0.384 ± 0.107) ( P = .006, repeated-measures ANOVA). Functional connectivity analysis with temporal-shift correction identified brain network nodes that were otherwise missed. The accuracy of functional connectivity assessment decreased after acetazolamide administration ( P = .015 for default mode network, repeated-measures ANOVA).

CONCLUSIONS: Temporal-shift analysis of blood oxygen level–dependent MR imaging can identify brain regions with hemodynamic compromise in relation to DSC among patients with chronic cerebrovascular disease. The use of acetazolamide reduces the accuracy of temporal-shift analysis and network connectivity evaluation.

### Abbreviations

ACZ
:   acetazolamide
BOLD
:   blood oxygen level–dependent MR imaging
DMN
:   default mode network
SMN
:   sensorimotor network
SSS
:   superior sagittal sinus
Tmax
:   time-to-maximum of the residue function
TS
:   temporal-shift" />
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    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">J. Wu</span>, <span class="highwire-citation-author" data-delta="1">S. Dehkharghani</span>, <span class="highwire-citation-author" data-delta="2">F. Nahab</span>, <span class="highwire-citation-author" data-delta="3">J. Allen</span> and <span class="highwire-citation-author" data-delta="4">D. Qiu</span></span></div>
  
    	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-journal highwire-cite-metadata">American Journal of Neuroradiology </span><span  class="highwire-cite-metadata-date highwire-cite-metadata">October 2016,  </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A4973 </span></div>
  
  
  
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Dehkharghani </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>From the Departments of Radiology and Imaging Sciences (J.W., S.D., J.A., D.Q.) and Neurology (F.N.), Emory University School of Medicine, Atlanta, Georgia.</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=S.%2BDehkharghani%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Dehkharghani%20S&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AS.%2BDehkharghani%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0002-3141-1094" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for S. 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      <div class="highwire-cite-title">The Effects of Acetazolamide on the Evaluation of Cerebral Hemodynamics and Functional Connectivity Using Blood Oxygen Level–Dependent MR Imaging in Patients with Chronic Steno-Occlusive Disease of the Anterior Circulation</div>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">J.</span> <span class="nlm-surname">Wu</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">S.</span> <span class="nlm-surname">Dehkharghani</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">F.</span> <span class="nlm-surname">Nahab</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">J.</span> <span class="nlm-surname">Allen</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">D.</span> <span class="nlm-surname">Qiu</span></span></span></div>
  
    	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-journal highwire-cite-metadata">American Journal of Neuroradiology </span><span  class="highwire-cite-metadata-date highwire-cite-metadata">Oct 2016, </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A4973 </span></div>
  
  
  
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      <div class="highwire-cite-title">The Effects of Acetazolamide on the Evaluation of Cerebral Hemodynamics and Functional Connectivity Using Blood Oxygen Level–Dependent MR Imaging in Patients with Chronic Steno-Occlusive Disease of the Anterior Circulation</div>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">J.</span> <span class="nlm-surname">Wu</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">S.</span> <span class="nlm-surname">Dehkharghani</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">F.</span> <span class="nlm-surname">Nahab</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">J.</span> <span class="nlm-surname">Allen</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">D.</span> <span class="nlm-surname">Qiu</span></span></span></div>
  
    	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-journal highwire-cite-metadata">American Journal of Neuroradiology </span><span  class="highwire-cite-metadata-date highwire-cite-metadata">Oct 2016, </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A4973 </span></div>
  
  
  
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