Blood Vessel Anatomy and Blood Flow Regulation

NCT05396287 | Active Not Recruiting

• 4 other identifiers: 2020-04231RF1NS117746-01Protocol Version 4/6/2022A176000
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Brain blood flow regulation will be measured in response to environmental changes using MRI.

Conditions

Brain Blood Flow; Healthy

Keywords

MRI; Brain blood flow

Outcome Measures

Primary Outcomes (2)

• Cerebral Vascular Reactivity to Hypercapnia

  The change in brain blood flow using MRI will be measured in response to a hypercapnic breathing test. The participants cerebral vascular reactivity to hypercapnia will be compared between the controls (without VAH) and those with VAH.

  One study visit, up to 120 minutes in the MRI

• Cerebral Blood Flow Response to Hypoxia

  The change in brain blood flow using MRI will be measured in response to a hypoxic breathing test. The participants cerebral blood flow response to hypoxia will be compared between the controls (without VAH) and those with VAH.

  One study visit, up to 120 minutes in the MRI

Study Arms (2)

Controls

Healthy controls

Device: MRI

Vertebral Artery Hypoplasia

Healthy individuals with vertebral artery hypoplasia

Device: MRI

Interventions

MRI DEVICE

Participants will undergo an MRI scan while participating in two breathing tests (hypercapnia and hypoxia) to measure brain blood flow.

Controls; Vertebral Artery Hypoplasia

Eligibility Criteria

• Age: 55 Years - 69 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Subjects for this study, will include healthy adults enrolled in the Wisconsin Alzheimer's Disease Research Clinical Core. Both men and women are eligible to participate in this study.

You may qualify if:

• BMI ≤38.5 kg/m2
• Nonsmoker
• Female subjects: postmenopausal
• Currently enrolled in the Wisconsin Alzheimer's Disease Research Clinical Core

You may not qualify if:

• Diagnosis of mild cognitive impairment or Alzheimer's disease
• Uncontrolled hypertension
• History or evidence of hepatic disease, hematological disease, or peripheral vascular disease
• Severe kidney injury requiring hemodialysis
• Cardiovascular disease including: severe congestive heart failure, coronary artery disease, ischemic heart disease (stents, coronary artery bypass grafts) and tachycardia
• History of clinically significant ischemic or hemorrhagic stroke, or significant cerebrovascular disease
• History of HIV/AIDS
• Severe untreated obstructive sleep apnea
• History of diabetes with HbA1c greater than 9.5%
• Major neurologic disorders other than dementia (e.g., multiple sclerosis, amyotrophic lateral sclerosis, brain surgery, etc.)
• Current or recent (\<1 year) major psychiatric condition (Axis I) or addictive disorders
• Contraindications to MRI

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

University of Wisconsin-Madison

Madison, Wisconsin, 53706, United States

Location

Related Publications (32)

• Kisler K, Nelson AR, Montagne A, Zlokovic BV. Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease. Nat Rev Neurosci. 2017 Jul;18(7):419-434. doi: 10.1038/nrn.2017.48. Epub 2017 May 18.

  PMID: 28515434 BACKGROUND

• Switzer AR, Cheema I, McCreary CR, Zwiers A, Charlton A, Alvarez-Veronesi A, Sekhon R, Zerna C, Stafford RB, Frayne R, Goodyear BG, Smith EE. Cerebrovascular reactivity in cerebral amyloid angiopathy, Alzheimer disease, and mild cognitive impairment. Neurology. 2020 Sep 8;95(10):e1333-e1340. doi: 10.1212/WNL.0000000000010201. Epub 2020 Jul 8.

  PMID: 32641520 BACKGROUND

• Iadecola C. Neurovascular regulation in the normal brain and in Alzheimer's disease. Nat Rev Neurosci. 2004 May;5(5):347-60. doi: 10.1038/nrn1387. No abstract available.

  PMID: 15100718 BACKGROUND

• Scheel P, Puls I, Becker G, Schoning M. Volume reduction in cerebral blood flow in patients with vascular dementia. Lancet. 1999 Dec 18-25;354(9196):2137. doi: 10.1016/S0140-6736(99)04016-7.

  PMID: 10609827 BACKGROUND

• Marshall RS, Lazar RM. Pumps, aqueducts, and drought management: vascular physiology in vascular cognitive impairment. Stroke. 2011 Jan;42(1):221-6. doi: 10.1161/STROKEAHA.110.595645. Epub 2010 Dec 9.

  PMID: 21148438 BACKGROUND

• Wierenga CE, Hays CC, Zlatar ZZ. Cerebral blood flow measured by arterial spin labeling MRI as a preclinical marker of Alzheimer's disease. J Alzheimers Dis. 2014;42 Suppl 4(Suppl 4):S411-9. doi: 10.3233/JAD-141467.

  PMID: 25159672 BACKGROUND

• Park JH, Kim JM, Roh JK. Hypoplastic vertebral artery: frequency and associations with ischaemic stroke territory. J Neurol Neurosurg Psychiatry. 2007 Sep;78(9):954-8. doi: 10.1136/jnnp.2006.105767. Epub 2006 Nov 10.

  PMID: 17098838 BACKGROUND

• Thierfelder KM, Baumann AB, Sommer WH, Armbruster M, Opherk C, Janssen H, Reiser MF, Straube A, von Baumgarten L. Vertebral artery hypoplasia: frequency and effect on cerebellar blood flow characteristics. Stroke. 2014 May;45(5):1363-8. doi: 10.1161/STROKEAHA.113.004188. Epub 2014 Apr 3.

  PMID: 24699051 BACKGROUND

• Peterson C, Phillips L, Linden A, Hsu W. Vertebral artery hypoplasia: prevalence and reliability of identifying and grading its severity on magnetic resonance imaging scans. J Manipulative Physiol Ther. 2010 Mar-Apr;33(3):207-11. doi: 10.1016/j.jmpt.2010.01.012.

  PMID: 20350674 BACKGROUND

• Kulyk C, Voltan C, Simonetto M, Palmieri A, Farina F, Vodret F, Viaro F, Baracchini C. Vertebral artery hypoplasia: an innocent lamb or a disguise? J Neurol. 2018 Oct;265(10):2346-2352. doi: 10.1007/s00415-018-9004-7. Epub 2018 Aug 16.

  PMID: 30116939 BACKGROUND

• Chen G, Ward BD, Xie C, Li W, Wu Z, Jones JL, Franczak M, Antuono P, Li SJ. Classification of Alzheimer disease, mild cognitive impairment, and normal cognitive status with large-scale network analysis based on resting-state functional MR imaging. Radiology. 2011 Apr;259(1):213-21. doi: 10.1148/radiol.10100734. Epub 2011 Jan 19.

  PMID: 21248238 BACKGROUND

• Bangen KJ, Nation DA, Clark LR, Harmell AL, Wierenga CE, Dev SI, Delano-Wood L, Zlatar ZZ, Salmon DP, Liu TT, Bondi MW. Interactive effects of vascular risk burden and advanced age on cerebral blood flow. Front Aging Neurosci. 2014 Jul 7;6:159. doi: 10.3389/fnagi.2014.00159. eCollection 2014.

  PMID: 25071567 BACKGROUND

• Barnes JN, Schmidt JE, Nicholson WT, Joyner MJ. Cyclooxygenase inhibition abolishes age-related differences in cerebral vasodilator responses to hypercapnia. J Appl Physiol (1985). 2012 Jun;112(11):1884-90. doi: 10.1152/japplphysiol.01270.2011. Epub 2012 Mar 22.

  PMID: 22442028 BACKGROUND

• Barnes JN, Harvey RE, Miller KB, Jayachandran M, Malterer KR, Lahr BD, Bailey KR, Joyner MJ, Miller VM. Cerebrovascular Reactivity and Vascular Activation in Postmenopausal Women With Histories of Preeclampsia. Hypertension. 2018 Jan;71(1):110-117. doi: 10.1161/HYPERTENSIONAHA.117.10248. Epub 2017 Nov 20.

  PMID: 29158356 BACKGROUND

• Tchistiakova E, Crane DE, Mikulis DJ, Anderson ND, Greenwood CE, Black SE, MacIntosh BJ. Vascular risk factor burden correlates with cerebrovascular reactivity but not resting state coactivation in the default mode network. J Magn Reson Imaging. 2015 Nov;42(5):1369-76. doi: 10.1002/jmri.24917. Epub 2015 Apr 17.

  PMID: 25884110 BACKGROUND

• Alwatban M, Murman DL, Bashford G. Cerebrovascular Reactivity Impairment in Preclinical Alzheimer's Disease. J Neuroimaging. 2019 Jul;29(4):493-498. doi: 10.1111/jon.12606. Epub 2019 Feb 12.

  PMID: 30748053 BACKGROUND

• Moskowitz MA, Lo EH, Iadecola C. The science of stroke: mechanisms in search of treatments. Neuron. 2010 Jul 29;67(2):181-98. doi: 10.1016/j.neuron.2010.07.002.

  PMID: 20670828 BACKGROUND

• Wong SM, Jansen JFA, Zhang CE, Hoff EI, Staals J, van Oostenbrugge RJ, Backes WH. Blood-brain barrier impairment and hypoperfusion are linked in cerebral small vessel disease. Neurology. 2019 Apr 9;92(15):e1669-e1677. doi: 10.1212/WNL.0000000000007263. Epub 2019 Mar 13.

  PMID: 30867275 BACKGROUND

• Peng SL, Chen X, Li Y, Rodrigue KM, Park DC, Lu H. Age-related changes in cerebrovascular reactivity and their relationship to cognition: A four-year longitudinal study. Neuroimage. 2018 Jul 1;174:257-262. doi: 10.1016/j.neuroimage.2018.03.033. Epub 2018 Mar 19.

  PMID: 29567504 BACKGROUND

• Miller KB, Howery AJ, Rivera-Rivera LA, Johnson SC, Rowley HA, Wieben O, Barnes JN. Age-Related Reductions in Cerebrovascular Reactivity Using 4D Flow MRI. Front Aging Neurosci. 2019 Oct 17;11:281. doi: 10.3389/fnagi.2019.00281. eCollection 2019.

  PMID: 31680935 BACKGROUND

• Iqbal S. A comprehensive study of the anatomical variations of the circle of willis in adult human brains. J Clin Diagn Res. 2013 Nov;7(11):2423-7. doi: 10.7860/JCDR/2013/6580.3563. Epub 2013 Nov 10.

  PMID: 24392362 BACKGROUND

• Hays CC, Zlatar ZZ, Wierenga CE. The Utility of Cerebral Blood Flow as a Biomarker of Preclinical Alzheimer's Disease. Cell Mol Neurobiol. 2016 Mar;36(2):167-79. doi: 10.1007/s10571-015-0261-z. Epub 2016 Feb 22.

  PMID: 26898552 BACKGROUND

• Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. doi: 10.1016/0165-1781(89)90047-4.

  PMID: 2748771 BACKGROUND

• Slessarev M, Han J, Mardimae A, Prisman E, Preiss D, Volgyesi G, Ansel C, Duffin J, Fisher JA. Prospective targeting and control of end-tidal CO2 and O2 concentrations. J Physiol. 2007 Jun 15;581(Pt 3):1207-19. doi: 10.1113/jphysiol.2007.129395. Epub 2007 Apr 19.

  PMID: 17446225 BACKGROUND

• Poublanc J, Sobczyk O, Shafi R, Sayin ES, Schulman J, Duffin J, Uludag K, Wood JC, Vu C, Dharmakumar R, Fisher JA, Mikulis DJ. Perfusion MRI using endogenous deoxyhemoglobin as a contrast agent: Preliminary data. Magn Reson Med. 2021 Dec;86(6):3012-3021. doi: 10.1002/mrm.28974. Epub 2021 Oct 22.

  PMID: 34687064 BACKGROUND

• Mikhail Kellawan J, Harrell JW, Roldan-Alzate A, Wieben O, Schrage WG. Regional hypoxic cerebral vasodilation facilitated by diameter changes primarily in anterior versus posterior circulation. J Cereb Blood Flow Metab. 2017 Jun;37(6):2025-2034. doi: 10.1177/0271678X16659497. Epub 2016 Jan 1.

  PMID: 27406213 BACKGROUND

• Barton GP, Corrado PA, Francois CJ, Chesler NC, Eldridge MW, Wieben O, Goss KN. Exaggerated Cardiac Contractile Response to Hypoxia in Adults Born Preterm. J Clin Med. 2021 Mar 10;10(6):1166. doi: 10.3390/jcm10061166.

  PMID: 33802149 BACKGROUND

• Mardimae A, Balaban DY, Machina MA, Battisti-Charbonney A, Han JS, Katznelson R, Minkovich LL, Fedorko L, Murphy PM, Wasowicz M, Naughton F, Meineri M, Fisher JA, Duffin J. The interaction of carbon dioxide and hypoxia in the control of cerebral blood flow. Pflugers Arch. 2012 Oct;464(4):345-51. doi: 10.1007/s00424-012-1148-1. Epub 2012 Sep 9.

  PMID: 22961068 BACKGROUND

• Miller KB, Howery AJ, Harvey RE, Eldridge MW, Barnes JN. Cerebrovascular Reactivity and Central Arterial Stiffness in Habitually Exercising Healthy Adults. Front Physiol. 2018 Aug 17;9:1096. doi: 10.3389/fphys.2018.01096. eCollection 2018.

  PMID: 30174609 BACKGROUND

• Barnes JN, Harvey RE, Eisenmann NA, Miller KB, Johnson MC, Kruse SM, Lahr BD, Joyner MJ, Miller VM. Cerebrovascular reactivity after cessation of menopausal hormone treatment. Climacteric. 2019 Apr;22(2):182-189. doi: 10.1080/13697137.2018.1538340. Epub 2019 Jan 21.

  PMID: 30661405 BACKGROUND

• Ahmed M, Giesbrecht GG, Serrette C, Georgopoulos D, Anthonisen NR. Ventilatory response to hypoxia in elderly humans. Respir Physiol. 1991 Mar;83(3):343-51. doi: 10.1016/0034-5687(91)90053-l.

  PMID: 2052762 BACKGROUND

• Vovk A, Smith WD, Paterson ND, Cunningham DA, Paterson DH. Peripheral chemoreceptor control of ventilation following sustained hypoxia in young and older adult humans. Exp Physiol. 2004 Nov;89(6):647-56. doi: 10.1113/expphysiol.2004.027532. Epub 2004 Jul 15.

  PMID: 15258116 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum blood samples will be retained for future analysis.

Study Officials

• Jill N Barnes, PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2022
• First Posted: May 31, 2022
• Study Start: July 19, 2022
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: July 18, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)