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. 2018 Feb;79(2):806-814.
doi: 10.1002/mrm.26736. Epub 2017 May 5.

Amide proton transfer CEST of the cervical spinal cord in multiple sclerosis patients at 3T

Samantha By  1   2 , Robert L Barry  3   4 , Alex K Smith  1   2   5 , Bailey D Lyttle  2 , Bailey A Box  2 , Francesca R Bagnato  6 , Siddharama Pawate  6 , Seth A Smith  1   2   7
Affiliations

Amide proton transfer CEST of the cervical spinal cord in multiple sclerosis patients at 3T

Samantha By et al. Magn Reson Med. 2018 Feb.

Abstract

Purpose: The ability to evaluate pathological changes in the spinal cord in multiple sclerosis (MS) is limited because T1 - and T2 -w MRI imaging are not sensitive to biochemical changes in vivo. Amide proton transfer (APT) chemical exchange saturation transfer (CEST) can indirectly detect amide protons associated with proteins and peptides, potentially providing more pathological specificity. Here, we implement APT CEST in the cervical spinal cord of healthy and MS cohorts at 3T.

Methods: APT CEST of the cervical spinal cord was obtained in a cohort of 10 controls and 10 MS patients using a novel respiratory correction methodology. APT was quantified using two methods: 1) APTw , based off the conventional magnetization transfer ratio asymmetry, and 2) ΔAPT, a spatial characterization of APT changes in MS patients relative to the controls.

Results: Respiratory correction yielded highly reproducible z-spectra in white matter (intraclass correlation coefficient = 0.82). APTw signals in normal-appearing white matter (NAWM) of MS patients were significantly different from healthy controls (P = 0.04), whereas ΔAPT of MS patients highlighted large APT differences in NAWM.

Conclusion: Respiration correction in the spinal cord is necessary to accurately quantify APT CEST, which can provide unique biochemical information regarding disease processes within the spinal cord. Magn Reson Med 79:806-814, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Keywords: CEST; amide proton transfer; multiple sclerosis; normal-appearing white matter; spinal cord.

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Figures

Figure 1
Figure 1. Image Processing Pipeline
The CEST data is registered to the anatomical, which is segmented into white and gray matter. The respiration volume per unit time (RVT) is regressed out of the CEST data, scaled by a weighting factor calculated from the 13 interspersed S0 images. The resulting z-spectrum is shifted using WASSR.
Figure 2
Figure 2. Effect of Respiration Correction in White Matter
Mean z-spectra over all controls without correction (black), with the Jones method correction (green), and with our proposed correction (blue) demonstrate that features in the z-spectrum are confounded by physiological noise. The APT effect can be appreciated when the respiration correction is applied.
Figure 3
Figure 3. Respiration Correction in Phantom
No adverse effects were produced in the z-spectrum of a non-breathing egg white phantom, as indicated by the good agreement between the z-spectrum of the three comparing methods.
Figure 4
Figure 4. Histogram Analysis of APTw Measurement
a) Histogram of white matter voxels over all MS patients (yellow) overlaid onto histogram of all controls (blue). b) Large overlap is observed between the controls and MS patients with EDSS of 0 (n=5). c) Patients with an EDSS greater than 0 (green) show a larger deviation from the control histogram and follow a more bimodal distribution, which can be explained by the distributions of distinct types of white matter (lesions vs. NAWM).
Figure 5
Figure 5. Spatial Characterization of APT in MS Patients
Spinal cord changes in MS patients with varying disease intensity, with anatomical imaging in left column, APT difference maps (ΔAPT) with respect to mean controls in middle column, and corresponding z-spectrum on the right. ΔAPT changes in the NAWM are observed throughout all patients, along with significant heterogeneity between patients.
See this image and copyright information in PMC

References

    1. Bot JC, Barkhof F, Polman CH, Lycklama a Nijeholt GJ, de Groot V, Bergers E, Ader HJ, Castelijns JA. Spinal cord abnormalities in recently diagnosed MS patients: added value of spinal MRI examination. Neurology. 2004;62(2):226–233. - PubMed
    1. Kearney H, Miller DH, Ciccarelli O. Spinal cord MRI in multiple sclerosis-diagnostic, prognostic and clinical value. Nat Rev Neurol. 2015;11(6):327–338. - PubMed
    1. Bergers E, Bot JC, De Groot CJ, Polman CH, Lycklama a Nijeholt GJ, Castelijns JA, van der Valk P, Barkhof F. Axonal damage in the spinal cord of MS patients occurs largely independent of T2 MRI lesions. Neurology. 2002;59(11):1766–1771. - PubMed
    1. Bakshi R, Thompson AJ, Rocca MA, Pelletier D, Dousset V, Barkhof F, Inglese M, Guttmann CRG, Horsfield MA, Filippi M. MRI in multiple sclerosis: current status and future prospects. Lancet Neurol. 2008;7(7):615–625. - PMC - PubMed
    1. Zhou J, Payen J-F, Wilson DA, Traystman RJ, van Zijl PCM. Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI. Nat Med. 2003;9(8):1085–1090. - PubMed

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