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

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.

Isolation of amide proton transfer effect and relayed nuclear Overhauser enhancement effect at ‐3.5ppm using CEST with double saturation powers

“…Usually, the frequency offset of saturation RF pulse is varied to acquire a Z-spectrum that plots the labeled water signals as a function of the frequency offset such that multiple types of exchangeable/coupling protons that are associated with different molecules or chemical groups and therefore, possess distinct chemical shifts can be detected. Amide proton transfer (APT), a variant of CEST imaging, seeks to detect the backbone amide of mobile proteins/peptides as CEST signals at 3.5 ppm, 6 which has demonstrated great potential in diagnosing tumors, 7-10 ischemic stroke, [11][12][13] multiple sclerosis, 14,15 traumatic brain injury, 16 Alzheimer's disease, [17][18][19][20][21] and Parkinson's disease, 22,23 etc. The APT imaging relies on slow chemical exchanges and therefore, can be conducted with low saturation RF powers (e.g., B 1 < 1 μT).…”

Evaluation of the molecular origin of amide proton transfer–weighted imaging

“…Previous studies have suggested that it can be indicative of various pathologies, such as tumors [16][17][18][19] and neurological disorders. [20][21][22][23][24][25][26][27][28][29] However, the APT signal may overlap with other effects, such as direct water saturation (DS), magnetization transfer (MT), and other CEST effects with broad peaks, especially in clinical MRI where the magnetic field is usually low, and in situations where high saturation powers (ω 1 ) are used. In addition, the MT is asymmetric.…”

Amide Proton Transfer MRI Could Be Used to Evaluate the Pathophysiological Status of White Matter Hyperintensities

“…16,17 At present, APT technology has been used in brain tumors, ischemic stroke, and neurodegeneration. [18][19][20][21][22] Previous studies have confirmed that APT technique can be used to study cerebral white matter. 18,19,23,24 Unlike the signal derived from tumors, which depends mainly on the amount of unstable amide proton tissue in mobile proteins, pH value may play a decisive role in the APT signals of WMH.…”

“…Since body temperature remains relatively constant, the APT effect depends mainly on the intracellular proteins and pH 16,17 . At present, APT technology has been used in brain tumors, ischemic stroke, and neurodegeneration 18–22 . Previous studies have confirmed that APT technique can be used to study cerebral white matter 18,19,23,24 .…”