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Unable to reach the target enrollment of 40 participants with Alzheimer's disease.
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| Name | Class |
|---|---|
| Lakehead University | OTHER |
| Thunder Bay Regional Health Sciences Centre | OTHER |
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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.
The described study is a pilot study in which the investigators aim to develop an enhanced sensitivity tool for assessment of neural function. Participation involves at least two study visits no longer than three hours in length each. During visit 1, informed consent and screening for eligibility will take place. During visit 2, fMRI scanning will take place in which participants will complete simple tasks. Two types of MRI scans will be performed: traditional proton fMRI and hyperpolarized xenon-129 fMRI (HP 129Xe fMRI) scans. The trade name for xenon-129 hyperpolarized with a Xemed LLC polarizer is NeuroXene.
Participants will be placed in the 3T MRI at the Thunder Bay Regional Research Institute with a Clinical MR Solutions (CMRS) Dual Brain Coil that fits over their head like a helmet. Several inhalation procedures will be performed by participants when breathing NeuroXene from a tube in the scanner. Preparation and administration of NeuroXene and the CMRS Dual Brain Coil will be carried out according to the SOP's developed by the TBRRI and Xemed LLC.
MRI scanning will be performed with a MR Tech and Registered Respiratory Therapist present. Dispensing of 129Xe will be monitored using a gas dispensing form and a drug accountability log. This study will have a monitor assigned to it from the TBRRI that is not involved in this clinical trial. This is to ensure participant safety and adherence to the protocol.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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). |
| Measure | Description | Time Frame |
|---|---|---|
| Signal-to-Noise Ratio (SNR) | All scans will be optimized for the highest SNR possible; No aggregation of data | Three years |
| Measure | Description | Time Frame |
|---|---|---|
| P-Value | To be calculated from a students paired t-test for signal change between healthy participant scans and participants with Alzheimer disease | Three years |
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Inclusion Criteria:
A participant is eligible for inclusion in the study if the individual meets all of the following criteria:
Normal cognition for healthy participant group inclusion criteria:
Alzheimer's disease group inclusion criteria:
Exclusion Criteria:
A participant is ineligible for the study if the individual meets any of the following criteria:
Normal cognition group exclusion criteria:
1. History of diagnosed neurological disease or injury.
Alzheimer's disease group exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mitchell Albert, Ph.D. | Thunder Bay Regional Health Research Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Thunder Bay Regional Health Sciences Centre | Thunder Bay | Ontario | P7B 6V4 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21813210 | Background | 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. | |
| 8028666 | 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. |
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| 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. |
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| 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. |
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| 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. |
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| 29882765 | Result | 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. |
| 34272774 | 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. |
| 35253919 | 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. |
| 34254356 | 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. |
| 32854196 | 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. |
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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