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PH-sensitive amide proton transfer effect dominates the magnetization transfer asymmetry contrast during acute ischemia-quantification of multipool contribution to in vivo CEST MRI.

ABSTRACT: PURPOSE:To determine the origins of in vivo magnetization transfer asymmetry contrast during acute ischemic stroke, particularly in the diffusion lesion, perfusion lesion, and their mismatch using a middle cerebral artery occlusion rat model of acute stroke. METHODS:Adult male Wistar rats underwent multiparametric MRI of diffusion, perfusion, T1 , and amide proton transfer (APT) imaging at 4.7?T following a middle cerebral artery occlusion procedure. A multipool Lorentzian model, including the nuclear Overhauser effect, magnetization transfer, direct water saturation, amine and amide chemical exchange saturation transfer effects, was applied for Z-spectrum fitting to determine the sources of in vivo magnetization transfer asymmetry following acute stroke. RESULTS:We showed that changes in amine chemical exchange saturation transfer (2?ppm) and APT (3.5?ppm) effects, particularly the APT MRI effect, dominate the commonly used magnetization transfer asymmetry analysis and hence confer pH sensitivity to APT imaging of acute stroke. Also, the nuclear Overhauser effect and magnetization transfer show small changes that counteracted each other, contributing less than 0.3% to magnetization transfer asymmetry at 3.5?ppm. Moreover, we showed that diffusion lesion had worsened acidosis from perfusion/diffusion lesion mismatch (P?

SUBMITTER: Wu Y

PROVIDER: S-EPMC5775916 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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pH-sensitive amide proton transfer effect dominates the magnetization transfer asymmetry contrast during acute ischemia-quantification of multipool contribution to in vivo CEST MRI.

Wu Yin Y Zhou Iris Yuwen IY Lu Dongshuang D Manderville Emiri E Lo Eng H EH Zheng Hairong H Sun Phillip Zhe PZ

Magnetic resonance in medicine 20170721 3

<h4>Purpose</h4>To determine the origins of in vivo magnetization transfer asymmetry contrast during acute ischemic stroke, particularly in the diffusion lesion, perfusion lesion, and their mismatch using a middle cerebral artery occlusion rat model of acute stroke.<h4>Methods</h4>Adult male Wistar rats underwent multiparametric MRI of diffusion, perfusion, T<sub>1</sub> , and amide proton transfer (APT) imaging at 4.7 T following a middle cerebral artery occlusion procedure. A multipool Lorentz ...[more]

PMID: 28733991

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Project description:BACKGROUND:Amide proton transfer (APT) imaging may help identify the ischaemic penumbra in stroke patients, the classical definition of which is a region of tissue around the ischaemic core that is hypoperfused and metabolically stressed. Given the potential of APT imaging to complement existing imaging techniques to provide clinically-relevant information, there is a need to develop analysis techniques that deliver a robust and repeatable APT metric. The challenge to accurate quantification of an APT metric has been the heterogeneous in-vivo environment of human tissue, which exhibits several confounding magnetisation transfer effects including spectrally-asymmetric nuclear Overhauser effects (NOEs). The recent literature has introduced various model-free and model-based approaches to analysis that seek to overcome these limitations. OBJECTIVES:The objective of this work was to compare quantification techniques for CEST imaging that specifically separate APT and NOE effects for application in the clinical setting. Towards this end a methodological comparison of different CEST quantification techniques was undertaken in healthy subjects, and around clinical endpoints in a cohort of acute stroke patients. METHODS:MRI data from 12 patients presenting with ischaemic stroke were retrospectively analysed. Six APT quantification techniques, comprising model-based and model-free techniques, were compared for repeatability and ability for APT to distinguish pathological tissue in acute stroke. RESULTS:Robustness analysis of six quantification techniques indicated that the multi-pool model-based technique had the smallest contrast between grey and white matter (2%), whereas model-free techniques exhibited the highest contrast (>30%). Model-based techniques also exhibited the lowest spatial variability, of which 4-pool APTR? was by far the most uniform (10% coefficient of variation, CoV), followed by 3-pool analysis (20%). Four-pool analysis yielded the highest ischaemic core contrast-to-noise ratio (0.74). Four-pool modelling of APT effects was more repeatable (3.2% CoV) than 3-pool modelling (4.6% CoV), but this appears to come at the cost of reduced contrast between infarct growth tissue and normal tissue. CONCLUSION:The multi-pool measures performed best across the analyses of repeatability, spatial variability, contrast-to-noise ratio, and grey matter-white matter contrast, and might therefore be more suitable for use in clinical imaging of acute stroke. Addition of a fourth pool that separates NOEs and semisolid effects appeared to be more biophysically accurate and provided better separation of the APT signal compared to the 3-pool equivalent, but this improvement appeared be accompanied by reduced contrast between infarct growth tissue and normal tissue.

Project description:ImportanceThe process of brain development in children with developmental delay is not well known. Amide proton transfer-weighted (APTw) imaging is a novel molecular magnetic resonance imaging (MRI) technique that can noninvasively detect cytosolic endogenous mobile proteins and peptides involved in the myelination process, and may be useful for providing insights into brain development.ObjectiveTo assess the contribution of amide proton transfer-weighted (APTw) imaging and magnetization transfer (MT) imaging to the evaluation of children with developmental delay (DD).MethodsFifty-one patients with DD were recruited to this study. The patients were divided into two groups according to the state of myelination assessed on conventional magnetic resonance imaging (MRI). Thirty patients (10 girls, 20 boys; age range: 1-8 months; median age: 4 months) in group A showed delayed myelination on MRI, while 21 patients (3 girls, 18 boys; age range: 12-36months; median age: 25months) in group B showed normal myelination on MRI. Fifty-one age- and sex-matched children with normal developmental quotient (DQ) and normal MRI appearance were recruited as normal controls. Three-slice APTw/MT axial imaging was performed at the level of the centrum semiovale, the basal ganglia and the pons. Quantitative data of the MT ratio (MTR) and APTw were analyzed for multiple brain regions. Independent-sample t-tests were used to compare differences in APTw and MTR signals between the two DD groups and normal controls. Analysis of Covariance was conducted to correct the statistical results. The level of statistical significance was set to P < 0.05.ResultsFor group A, the MTR values were lower in all regions (P = 0.004-0.033) compared with the normal controls, while the APTw values were higher in the pons, middle cerebellar peduncle, corpus callosum, frontal white matter, occipital white matter and centrum semiovale (P = 0.004-0.040 ). For Group B, the MTR values were slightly reduced, and the APTw values were slightly increased compared with the normal controls, but the differences were not statistically significant (P > 0.05).InterpretationFor DD patients showing signs of delayed myelination on MRI, MTR and APTw imaging can help to diagnose myelination delay by quantifying semi-solid macromolecules and cytosolic endogenous mobile proteins and peptides at a molecular level, providing a new method for comprehensive evaluation of DD. For DD patients with normal myelination on MRI, the clinical values of MTR and APTw imaging remain to be explored.

Project description:Objectives:To define normal signal intensity values of amide proton transfer-weighted (APTw) magnetic resonance (MR) imaging in different brain regions. Materials and Methods:Twenty healthy subjects (9 females, mean age 29 years, range 19 - 37 years) underwent MR imaging at 3 Tesla. 3D APTw (RF saturation B1,rms = 2 ?T, duration 2 s, 100% duty cycle) and 2D T2-weighted turbo spin echo (TSE) images were acquired. Postprocessing (image fusion, ROI measurements of APTw intensity values in 22 different brain regions) was performed and controlled by two independent neuroradiologists. Values were measured separately for each brain hemisphere. A subject was scanned both in prone and supine position to investigate differences between hemispheres. A mixed model on a 5% significance level was used to assess the effect of gender, brain region and side on APTw intensity values. Results:Mean APTw intensity values in the hippocampus and amygdala varied between 1.13 and 1.57%, in the deep subcortical nuclei (putamen, globus pallidus, head of caudate nucleus, thalamus, red nucleus, substantia nigra) between 0.73 and 1.84%, in the frontal, occipital and parietal cortex between 0.56 and 1.03%; in the insular cortex between 1.11 and 1.15%, in the temporal cortex between 1.22 and 1.37%, in the frontal, occipital and parietal white matter between 0.32 and 0.54% and in the temporal white matter between 0.83 and 0.89%. APTw intensity values were significantly impacted both by brain region (p < 0.001) and by side (p < 0.001), whereby overall values on the left side were higher than on the right side (1.13 vs. 0.9%). Gender did not significantly impact APTw intensity values (p = 0.24). APTw intensity values between the left and the right side were partially reversed after changing the position of one subject from supine to prone. Conclusion:We determined normal baseline APTw intensity values in different anatomical localizations in healthy subjects. APTw intensity values differed both between anatomical regions and between left and right brain hemisphere.

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PH-sensitive amide proton transfer effect dominates the magnetization transfer asymmetry contrast during acute ischemia-quantification of multipool contribution to in vivo CEST MRI.

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pH-sensitive amide proton transfer effect dominates the magnetization transfer asymmetry contrast during acute ischemia-quantification of multipool contribution to in vivo CEST MRI.

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