Amide Proton Transfer-Weighted MRI Might Help Distinguish Amnestic Mild Cognitive Impairment From a Normal Elderly Population

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Abstract

Objectives: To evaluate whether 3D amide proton transfer weighted (APTw) imaging based on magnetization transfer analysis can be used as a novel imaging marker to distinguish amnestic mild cognitive impairment (aMCI) patients from the normal elderly population by measuring changes in APTw signal intensity in the hippocampus and amygdala.

Materials and Methods: Seventy patients with aMCI and 74 age- and sex-matched healthy volunteers were recruited for routine MRI and APT imaging examinations. Magnetic transfer ratio asymmetry (MTRasym) of the amide protons (at 3.5 ppm), or APTw values, were measured in the bilateral hippocampus and amygdala on three consecutive cross-sectional APT images and were compared between the aMCI and control groups. The independent sample t-test was used to evaluate the difference in APTw values of the bilateral hippocampus and amygdala between the aMCI and control groups. Receiver operator characteristic analysis was used to assess the diagnostic performance of the APTw. The paired t-test was used to assess the difference in APTw values between the left and right hippocampus and amygdala, in both the aMCI and control groups.

Results: The APTw values of the bilateral hippocampus and amygdala in the aMCI group were significantly higher than those in the control group (left hippocampus 1.01 vs. 0.77% p < 0.001; right hippocampus 1.02 vs. 0.74%, p < 0.001; left amygdala 0.98 vs. 0.70% p < 0.001; right amygdala 0.94 vs. 0.71%, p < 0.001). The APTw values of the left amygdala had the largest AUC (0.875) at diagnosis of aMCI. There was no significant difference in APTw values between the left and right hippocampus and amygdala, in either group. (aMCI group left hippocampus 1.01 vs. right hippocampus 1.02%, p = 0.652; healthy control group left hippocampus 0.77 vs. right hippocampus 0.74%, p = 0.314; aMCI group left amygdala 0.98 vs. right amygdala 0.94%, p = 0.171; healthy control group left amygdala 0.70 vs. right amygdala 0.71%, p = 0.726).

Conclusion: APTw can be used as a new imaging marker to distinguish aMCI patients from the normal elderly population by indirectly reflecting the changes in protein content in the hippocampus and amygdala.

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Most cited references 36

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Mild cognitive impairment as a diagnostic entity.

R C Petersen, George Perry (2005)

The concept of cognitive impairment intervening between normal ageing and very early dementia has been in the literature for many years. Recently, the construct of mild cognitive impairment (MCI) has been proposed to designate an early, but abnormal, state of cognitive impairment. MCI has generated a great deal of research from both clinical and research perspectives. Numerous epidemiological studies have documented the accelerated rate of progression to dementia and Alzheimer's disease (AD) in MCI subjects and certain predictor variables appear valid. However, there has been controversy regarding the precise definition of the concept and its implementation in various clinical settings. Clinical subtypes of MCI have been proposed to broaden the concept and include prodromal forms of a variety of dementias. It is suggested that the diagnosis of MCI can be made in a fashion similar to the clinical diagnoses of dementia and AD. An algorithm is presented to assist the clinician in identifying subjects and subclassifying them into the various types of MCI. By refining the criteria for MCI, clinical trials can be designed with appropriate inclusion and exclusion restrictions to allow for the investigation of therapeutics tailored for specific targets and populations.

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Mild cognitive impairment: clinical characterization and outcome.

R Petersen, G. Smith, S. Waring … (1999)

Subjects with a mild cognitive impairment (MCI) have a memory impairment beyond that expected for age and education yet are not demented. These subjects are becoming the focus of many prediction studies and early intervention trials. To characterize clinically subjects with MCI cross-sectionally and longitudinally. A prospective, longitudinal inception cohort. General community clinic. A sample of 76 consecutively evaluated subjects with MCI were compared with 234 healthy control subjects and 106 patients with mild Alzheimer disease (AD), all from a community setting as part of the Mayo Clinic Alzheimer's Disease Center/Alzheimer's Disease Patient Registry, Rochester, Minn. The 3 groups of individuals were compared on demographic factors and measures of cognitive function including the Mini-Mental State Examination, Wechsler Adult Intelligence Scale-Revised, Wechsler Memory Scale-Revised, Dementia Rating Scale, Free and Cued Selective Reminding Test, and Auditory Verbal Learning Test. Clinical classifications of dementia and AD were determined according to the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria, respectively. The primary distinction between control subjects and subjects with MCI was in the area of memory, while other cognitive functions were comparable. However, when the subjects with MCI were compared with the patients with very mild AD, memory performance was similar, but patients with AD were more impaired in other cognitive domains as well. Longitudinal performance demonstrated that the subjects with MCI declined at a rate greater than that of the controls but less rapidly than the patients with mild AD. Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD. They appear to constitute a clinical entity that can be characterized for treatment interventions.

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Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI.

Jinyuan Zhou, Jean-Francois Payen, David A H Wilson … (2003)

In the past decade, it has become possible to use the nuclear (proton, 1H) signal of the hydrogen atoms in water for noninvasive assessment of functional and physiological parameters with magnetic resonance imaging (MRI). Here we show that it is possible to produce pH-sensitive MRI contrast by exploiting the exchange between the hydrogen atoms of water and the amide hydrogen atoms of endogenous mobile cellular proteins and peptides. Although amide proton concentrations are in the millimolar range, we achieved a detection sensitivity of several percent on the water signal (molar concentration). The pH dependence of the signal was calibrated in situ, using phosphorus spectroscopy to determine pH, and proton exchange spectroscopy to measure the amide proton transfer rate. To show the potential of amide proton transfer (APT) contrast for detecting acute stroke, pH effects were noninvasively imaged in ischemic rat brain. This observation opens the possibility of using intrinsic pH contrast, as well as protein- and/or peptide-content contrast, as diagnostic tools in clinical imaging.

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Author and article information

Contributors

Zixuan Guo: URI : http://loop.frontiersin.org/people/1322584/overview

Zhuoni Meng: URI : http://loop.frontiersin.org/people/1426505/overview

Xiqi Zhu: URI : http://loop.frontiersin.org/people/1414239/overview

Journal

Journal ID (nlm-ta): Front Neurol

Journal ID (iso-abbrev): Front Neurol

Journal ID (publisher-id): Front. Neurol.

Title: Frontiers in Neurology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1664-2295

Publication date (Electronic): 12 October 2021

Publication date Collection: 2021

Volume: 12

Electronic Location Identifier: 707030

Affiliations

[1] ¹Department of Medical Imaging, Guilin Medical University , Guilin, China

[2] ²Department of Medical Imaging, Nanxishan Hospital of Guangxi Zhuang Autonomous Region , Guilin, China

[3] ³Department of Neurology, Nanxishan Hospital of Guangxi Zhuang Autonomous Region , Guilin, China

Author notes

Edited by: Deqiang Qiu, Emory University, United States

Reviewed by: Chiara Bianca Maria Platania, University of Catania, Italy; Jinyuan Zhou, Johns Hopkins University, United States

*Correspondence: Xiqi Zhu xiqi.zhu@ 123456163.com

This article was submitted to Applied Neuroimaging, a section of the journal Frontiers in Neurology

†These authors have contributed equally to this work

Article

DOI: 10.3389/fneur.2021.707030

PMC ID: 8545995

PubMed ID: 34712196

SO-VID: 57ebbb62-0410-473a-bab1-53510ba0cc44

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 08 May 2021

Date accepted : 09 September 2021

Page count

Figures: 4, Tables: 4, Equations: 3, References: 36, Pages: 9, Words: 6207

Funding

Funded by: Guilin Science and Technology Bureau, doi 10.13039/501100017693;

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Amide Proton Transfer-Weighted MRI Might Help Distinguish Amnestic Mild Cognitive Impairment From a Normal Elderly Population

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Alternative approaches to Alzheimer's Disease

Most cited references 36

Mild cognitive impairment as a diagnostic entity.

Mild cognitive impairment: clinical characterization and outcome.

Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI.

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