Comparing different analysis methods for quantifying the MRI amide proton transfer (APT) effect in hyperacute stroke patients

Amide proton transfer (APT) imaging is a pH mapping method based on the chemical exchange saturation transfer phenomenon that has potential for penumbra identification following stroke. The majority of the literature thus far has focused on generating pH‐weighted contrast using magnetization transfer ratio asymmetry analysis instead of quantitative pH mapping. In this study, the widely used asymmetry analysis and a model‐based analysis were both assessed on APT data collected from healthy subjects (n = 2) and hyperacute stroke patients (n = 6, median imaging time after onset = 2 hours 59 minutes). It was found that the model‐based approach was able to quantify the APT effect with the lowest variation in grey and white matter (≤ 13.8 %) and the smallest average contrast between these two tissue types (3.48 %) in the healthy volunteers. The model‐based approach also performed quantitatively better than the other measures in the hyperacute stroke patient APT data, where the quantified APT effect in the infarct core was consistently lower than in the contralateral normal appearing tissue for all the patients recruited, with the group average of the quantified APT effect being 1.5 ± 0.3 % (infarct core) and 1.9 ± 0.4 % (contralateral). Based on the fitted parameters from the model‐based analysis and a previously published pH and amide proton exchange rate relationship, quantitative pH maps for hyperacute stroke patients were generated, for the first time, using APT imaging. © 2014 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.

[1]  Jinyuan Zhou,et al.  Defining an Acidosis-Based Ischemic Penumbra from pH-Weighted MRI , 2011, Translational Stroke Research.

[2]  Mark W. Woolrich,et al.  Variational Bayesian Inference for a Nonlinear Forward Model , 2020, IEEE Transactions on Signal Processing.

[3]  Per Capita,et al.  About the authors , 1995, Machine Vision and Applications.

[4]  Michael Brady,et al.  Improved Optimization for the Robust and Accurate Linear Registration and Motion Correction of Brain Images , 2002, NeuroImage.

[5]  Phillip Zhe Sun,et al.  Association between pH-Weighted Endogenous Amide Proton Chemical Exchange Saturation Transfer MRI and Tissue Lactic Acidosis during Acute Ischemic Stroke , 2011, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[6]  R. Kauppinen,et al.  Increased macromolecular resonances in the rat cerebral cortex during severe energy failure as detected by 1H nuclear magnetic resonance spectroscopy , 1996, Neuroscience Letters.

[7]  M. Chappell,et al.  Evaluating the use of a continuous approximation for model-based quantification of pulsed chemical exchange saturation transfer (CEST) , 2012, Journal of magnetic resonance.

[8]  Jinyuan Zhou,et al.  Simplified quantitative description of amide proton transfer (APT) imaging during acute ischemia , 2007, Magnetic resonance in medicine.

[9]  Stephen M Smith,et al.  Fast robust automated brain extraction , 2002, Human brain mapping.

[10]  Jerry S. Cheung,et al.  Imaging acute ischemic tissue acidosis with pH-sensitive endogenous amide proton transfer (APT) MRI—Correction of tissue relaxation and concomitant RF irradiation effects toward mapping quantitative cerebral tissue pH , 2012, NeuroImage.

[11]  Stephen M. Smith,et al.  Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm , 2001, IEEE Transactions on Medical Imaging.

[12]  Jinyuan Zhou,et al.  Chemical exchange saturation transfer imaging and spectroscopy , 2006 .

[13]  Craig K. Jones,et al.  Four‐pool modeling of proton exchange processes in biological systems in the presence of MRI–paramagnetic chemical exchange saturation transfer (PARACEST) agents , 2008, Magnetic resonance in medicine.

[14]  Kimberly L Desmond,et al.  Understanding quantitative pulsed CEST in the presence of MT , 2012, Magnetic resonance in medicine.

[15]  David C Alsop,et al.  Amide proton transfer imaging with improved robustness to magnetic field inhomogeneity and magnetization transfer asymmetry using saturation with frequency alternating RF irradiation , 2011, Magnetic resonance in medicine.

[16]  Risto A Kauppinen,et al.  Proton transfer ratio, lactate, and intracellular pH in acute cerebral ischemia , 2007, Magnetic resonance in medicine.

[17]  A. Pastuszyn,et al.  Magnetic resonance lipid signals in rat brain after experimental stroke correlate with neutral lipid accumulation , 2001, Neuroscience Letters.

[18]  Peter Jezzard,et al.  Quantitative Bayesian model‐based analysis of amide proton transfer MRI , 2013, Magnetic resonance in medicine.

[19]  M. Chappell,et al.  Quantification of amide proton transfer effect pre‐ and post‐gadolinium contrast agent administration , 2014, Journal of magnetic resonance imaging : JMRI.

[20]  Daniel L. Polders,et al.  Chemical Exchange Saturation Transfer MR Imaging: Potential Clinical Applications. , 2013, PET clinics.

[21]  Nirbhay N. Yadav,et al.  Chemical exchange saturation transfer (CEST): What is in a name and what isn't? , 2011, Magnetic resonance in medicine.

[22]  A Dean Sherry,et al.  Paramagnetic lanthanide complexes as PARACEST agents for medical imaging. , 2006, Chemical Society reviews.

[23]  Matthew E Merritt,et al.  Numerical solution of the Bloch equations provides insights into the optimum design of PARACEST agents for MRI , 2005, Magnetic resonance in medicine.

[24]  Jinyuan Zhou,et al.  Quantitative description of the asymmetry in magnetization transfer effects around the water resonance in the human brain , 2007, Magnetic resonance in medicine.

[25]  Vaibhav A. Janve,et al.  Optimizing pulsed‐chemical exchange saturation transfer imaging sequences , 2011, Magnetic resonance in medicine.

[26]  Max Wintermark,et al.  A trial of imaging selection and endovascular treatment for ischemic stroke. , 2013, The New England journal of medicine.

[27]  Leif Østergaard,et al.  Assessment of ischemic penumbra in patients with hyperacute stroke using amide proton transfer (APT) chemical exchange saturation transfer (CEST) MRI , 2014, NMR in biomedicine.

[28]  Jinyuan Zhou,et al.  Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI , 2003, Nature Medicine.

[29]  S J Payne,et al.  Optimal sampling schedule for chemical exchange saturation transfer , 2013, Magnetic resonance in medicine.

[30]  Tao Jin,et al.  MR imaging of the amide‐proton transfer effect and the pH‐insensitive nuclear overhauser effect at 9.4 T , 2013, Magnetic resonance in medicine.

[31]  Xuna Zhao,et al.  Saturation power dependence of amide proton transfer image contrasts in human brain tumors and strokes at 3 T , 2011, Magnetic resonance in medicine.

[32]  Jinyuan Zhou,et al.  Detection of the Ischemic Penumbra Using pH-Weighted MRI , 2007, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[33]  Jing Yuan,et al.  APT‐weighted and NOE‐weighted image contrasts in glioma with different RF saturation powers based on magnetization transfer ratio asymmetry analyses , 2013, Magnetic resonance in medicine.

[34]  B. Siesjö,et al.  Thresholds in cerebral ischemia - the ischemic penumbra. , 1981, Stroke.

[35]  K. Hossmann Viability thresholds and the penumbra of focal ischemia , 1994, Annals of neurology.

[36]  Jinyuan Zhou,et al.  In vivo three‐dimensional whole‐brain pulsed steady‐state chemical exchange saturation transfer at 7 T , 2012, Magnetic resonance in medicine.

[37]  Jinyuan Zhou,et al.  Quantifying exchange rates in chemical exchange saturation transfer agents using the saturation time and saturation power dependencies of the magnetization transfer effect on the magnetic resonance imaging signal (QUEST and QUESP): Ph calibration for poly‐L‐lysine and a starburst dendrimer , 2006, Magnetic resonance in medicine.

[38]  Richard A. E. Edden,et al.  Nuclear Overhauser enhancement (NOE) imaging in the human brain at 7T , 2013, NeuroImage.

[39]  E. Terreno,et al.  Methods for an improved detection of the MRI-CEST effect. , 2009, Contrast media & molecular imaging.