HP Xenon-129 fMRI of Healthy Volunteers and Participants With Alzheimer's Disease

NCT02638519 | Terminated Early Phase 1

• 1 other identifier: RP-307-08312015
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

This study involves imaging participants' brains using MRI. The goal is to develop a high-resolution, high-sensitivity imaging tool, hyperpolarized xenon functional brain magnetic resonance imaging, which can provide more sensitive measurement of brain function, facilitating the development of drugs for more successful treatment of Alzheimer's disease.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• Signal-to-Noise Ratio (SNR)

  All scans will be optimized for the highest SNR possible; No aggregation of data

  Three years

Secondary Outcomes (1)

• P-Value

  Three years

Study Arms (2)

Healthy Volunteers

OTHER

Healthy volunteers will inhale NeuroXene using various breathing methods. The CMRS 1H-129Xe dual-tuned quadrature head coil will be used to acquire MRI images of the human brain after inhalation of NeuroXene. The coil permits the acquisition of both conventional proton and HP xenon gas images. Two types of MRI scans will be performed: Traditional proton fMRI and Hyperpolarized Xenon-129 fMRI. The order of scans will be randomized to account for bias caused by scan order.

Other: Traditional Proton fMRI; Other: Hyperpolarized Xenon-129 fMRI; Drug: Hyperpolarized Xenon-129; Device: 1H-129Xe Dual-Tuned Quadrature Head Coil

Alzheimer's Disease Participants

OTHER

Alzheimer's disease participants will inhale NeuroXene using various breathing methods. The CMRS 1H-129Xe dual-tuned quadrature head coil will be used to acquire MRI images of the human brain after inhalation of NeuroXene. The coil permits the acquisition of both conventional proton and HP xenon gas images. Two types of MRI scans will be performed: Traditional proton fMRI and Hyperpolarized Xenon-129 fMRI. The order of scans will be randomized to account for bias caused by scan order.

Other: Traditional Proton fMRI; Other: Hyperpolarized Xenon-129 fMRI; Drug: Hyperpolarized Xenon-129; Device: 1H-129Xe Dual-Tuned Quadrature Head Coil

Interventions

Traditional Proton fMRI OTHER

Conventional proton fMRI will be performed. During the functional imaging acquisitions, the participant will be asked by the research team to perform simple tasks. These tasks will be completed while the participant breathes air (normal breathing).

Alzheimer's Disease Participants; Healthy Volunteers

Hyperpolarized Xenon-129 fMRI OTHER

HP 129Xe fMRI data will be acquired from all participants. Hyperpolarized xenon (NeuroXene) is expected to produce images that provide more clinically relevant information than traditional proton scans. Simple tasks will be performed by participants while breathing NeuroXene according to several inhalation procedures.

Also known as: HP 129Xe fMRI

Alzheimer's Disease Participants; Healthy Volunteers

Hyperpolarized Xenon-129 DRUG

Participants will be asked to inhale specified amounts of NeuroXene according to several inhalation procedures. NeuroXene is the trade name for hyperpolarization of xenon-129 balanced with oxygen and nitrogen using a Xemed LLC polarizer. Hyperpolarization does not change the chemical or physical properties of xenon gas.

Also known as: NeuroXene

Alzheimer's Disease Participants; Healthy Volunteers

1H-129Xe Dual-Tuned Quadrature Head Coil DEVICE

A 1H-129Xe dual-tuned quadrature head coil (Clinical MR Solutions, LLC) will be used in this study. The RF coil will be used to acquire MRI images of the human brain after inhalation of hyperpolarized xenon-129 gas, and permits the acquisition of both conventional proton and HP xenon gas images.

Alzheimer's Disease Participants; Healthy Volunteers

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Self-reported proficiency in English language.
• Equal to or more than 8 years of education.
• Normal or corrected to normal vision.
• Able to provide informed consent.
• Able to hold their breath for 20 seconds.
• Preserved independence in functional abilities.
• MoCA score no less than 26.
• Males and non-lactating females of 18 to 85 years of age.
• Participants meet National Institute on Aging-Alzheimer's Association for probable or possible Alzheimer's Disease dementia.
• MoCA score no less than 16.
• Males and non-lactating females of 60 to 85 years of age.
• Have a family member, close friend, or LAR that can be present for the informed consent process and study visits.

You may not qualify if:

• A participant is ineligible for the study if the individual meets any of the following criteria:
• Serious underlying medical condition, other, then the condition being investigated, which may affect cognitive function of the participant (in the opinion of the investigator): substance abuse, psychotic or depressive disorder, advanced or poorly controlled cardiac, pulmonary, hepatic, renal, neurological disorders in which the patient has significant speech, visual, motor or cognitive deficit, seizure disorders, endocrine or infectious disease or active malignancy.
• MRI incompatibility as determined by MR Technologist during MRI screening.
• Self-identifies as claustrophobic.
• Is a student currently enrolled in a course at Lakehead University where the Principal Investigator (PI) is the instructor.
• Is a student currently enrolled in a degree program at Lakehead University where the PI is their direct thesis supervisor.
• Is currently an employee of the PI at the Thunder Bay Regional Research Institute (TBRRI) and/or Lakehead University.
• \. History of diagnosed neurological disease or injury.
• Existing diagnosis of dementia of etiology other than Alzheimer's disease.
• Acute Delirium on the day of scanning (CAM tool assessment)

Sponsors & Collaborators

• Thunder Bay Regional Health Research Institute: lead
• Lakehead University: collaborator
• Thunder Bay Regional Health Sciences Centre: collaborator

Study Sites (1)

Thunder Bay Regional Health Sciences Centre

Thunder Bay, Ontario, P7B 6V4, Canada

Location

Related Publications (7)

• Agosta F, Pievani M, Geroldi C, Copetti M, Frisoni GB, Filippi M. Resting state fMRI in Alzheimer's disease: beyond the default mode network. Neurobiol Aging. 2012 Aug;33(8):1564-78. doi: 10.1016/j.neurobiolaging.2011.06.007. Epub 2011 Aug 3.

  PMID: 21813210 BACKGROUND

• Albert MS, Cates GD, Driehuys B, Happer W, Saam B, Springer CS Jr, Wishnia A. Biological magnetic resonance imaging using laser-polarized 129Xe. Nature. 1994 Jul 21;370(6486):199-201. doi: 10.1038/370199a0.

  PMID: 8028666 BACKGROUND

• Hane FT, Li T, Plata JA, Hassan A, Granberg K, Albert MS. Inhaled Xenon Washout as a Biomarker of Alzheimer's Disease. Diagnostics (Basel). 2018 Jun 6;8(2):41. doi: 10.3390/diagnostics8020041.

  PMID: 29882765 RESULT

• Grynko V, Shepelytskyi Y, Li T, Hassan A, Granberg K, Albert MS. Hyperpolarized 129 Xe multi-slice imaging of the human brain using a 3D gradient echo pulse sequence. Magn Reson Med. 2021 Dec;86(6):3175-3181. doi: 10.1002/mrm.28932. Epub 2021 Jul 17.

  PMID: 34272774 RESULT

• Shepelytskyi Y, Grynko V, Rao MR, Li T, Agostino M, Wild JM, Albert MS. Hyperpolarized 129 Xe imaging of the brain: Achievements and future challenges. Magn Reson Med. 2022 Jul;88(1):83-105. doi: 10.1002/mrm.29200. Epub 2022 Mar 7.

  PMID: 35253919 RESULT

• Shepelytskyi Y, Grynko V, Li T, Hassan A, Granberg K, Albert MS. The effects of an initial depolarization pulse on dissolved phase hyperpolarized 129 Xe brain MRI. Magn Reson Med. 2021 Dec;86(6):3147-3155. doi: 10.1002/mrm.28918. Epub 2021 Jul 13.

  PMID: 34254356 RESULT

• Shepelytskyi Y, Hane FT, Grynko V, Li T, Hassan A, Albert MS. Hyperpolarized 129Xe Time-of-Flight MR Imaging of Perfusion and Brain Function. Diagnostics (Basel). 2020 Aug 25;10(9):630. doi: 10.3390/diagnostics10090630.

  PMID: 32854196 RESULT

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Mitchell Albert, Ph.D.

  Thunder Bay Regional Health Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2015
• First Posted: December 23, 2015
• Study Start: June 27, 2016
• Primary Completion: April 19, 2022
• Study Completion: April 19, 2022
• Last Updated: October 15, 2024

Record last verified: 2024-08

Locations

CA (1)