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Gopal Varma¹, Jane Fergusson², Asma Hassani², Aaron K Grant¹, Aron S Buchman³, David C Alsop¹, and Veronique VanderHorst^2
1Radiology, Division of MR Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States, ²Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States, ³Department of Neurological Sciences, Rush University Medical Center, Rush Alzheimer's Disease Center, Chicago, IL, United States

Keywords: Magnetization transfer, Neuro, Brainstem

Application of neuromelanin MRI (NM-MRI) in the brainstem has been utilized in studies of neurological disorders such as Parkinson's disease. Acquisition of two types of MT preparation for inhomogeneous MT, MT applied at a single offset and then dual off-resonance frequencies, presents an advancement to NM-MRI by providing an acquisition with a myelin sensitive signal for complementary information. We demonstrate this in ex-vivo brainstem samples at 9.4 T, which allows comparison with other MRI microstructural techniques, as well as in-vivo at 3 T, where MT images provide a contrast comparable to NM-MRI by fast-spin-echo.

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Luke Pleva¹, John Farrant^1,2, Christopher Miller^1,2, and Josephine Naish^1,2
1The University of Manchester, Manchester, United Kingdom, ²MCMR, Manchester University NHS Foundation Trust, Manchester, United Kingdom

Keywords: Magnetization transfer, Cardiovascular

Patients with chronic kidney disease often suffer from cardiac complications where increased diffuse myocardial fibrosis is present. Gadolinium is contraindicated in these patients, so cannot benefit from techniques such as ECV.

We present a bSSFP based quantitative magnetisation transfer technique to assess diffuse myocardial fibrosis through the calculation of a pool size ratio and compare against ECV.

6 bSSFP images, T₁, and T₂ maps were acquired where a two pool model was fitted. No significant correlation between PSR and T₁ in healthy patients was found. Significant correlations were found between PSR and T₁ and PSR and ECV in clinical patients.

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Yuxi Pang^1
1University of Michigan, Ann Arbor, MI, United States

Keywords: Relaxometry, White Matter

Quantitative magnetization transfer (qMT) imaging can indirectly probe $$$R_2$$$ orientation dependence in WM for semisolid methylene protons from lipid bilayers. Prior experimental and simulation studies indicate that the long lipid chain not only rotates rapidly around itself, but it also wobbles in a cone. The existing  modeling methods, however, did not take the latter motional mode into account, potentially leading to a biased measure of myelin-specific anisotropic $$$R_2$$$ relaxation. This work thus proposes a new model encompassing both motional modes for better characterizing an anisotropic $$$R_2$$$ profile of semisolid protons in WM.

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Shahrokh Abbasi-Rad^1,2,3,4 and David Norris^1,2
1Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands, ²Erwin L. Hahn Institute for Magnetic Resonance Imaging, University Duisburg-Essen, Essen, Germany, ³Department of Radiology, Harvard Medical School, Boston, MA, United States, ⁴Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlsetown, MA, United States

Keywords: Magnetization transfer, RF Pulse Design & Fields, Adiabatic Null Passage

On-resonance bound pool saturation is the most efficient way of generating MTC. However, it suffers from excessive direct free water saturation due to RF pulse instabilities, and potential T2-weighting. We proposed a time-reversed adiabatic pulse (adiabatic null passage) for on-resonance MT preparation, by reversing the time-domain phase modulation function of a symmetric adiabatic pulse at its mid-point. We compared the MTC performance of ANP with binomial pulses using their MTR images. MTR values were reported through lines crossing CSF, showing high values at GM/WM and zero at CSF voxels. ANP improved the excessive saturation at regions with high B0 inhomogeneity. 

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Jiaen Liu^1
1Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States

Keywords: Magnetization transfer, Neurofluids

Imaging mass exchange between cerebrospinal fluid (CSF) and brain parenchyma tissue is promising for enhancing our understanding about the role of CSF in clearance of metabolic waste and contributes to clinical diagnosis of neurological disorders and degeneration. In this study, we evaluated the feasibility of achieving this goal based on the magnetization transfer effect and CSF-selective spin echo contrast at 3 T in human subjects. The results suggested that techniques with low sensitivity to flow and partial volume effect are required for robust clinical application.

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Munendra Singh¹, Peter van Zijl¹, Shanshan Jiang¹, Jinyuan Zhou¹, and Hye-Young Heo^1
1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States

Keywords: CEST & MT, CEST & MT

Conventional saturation transfer MRI approaches, such as magnetization transfer contrast (MTC) and chemical exchange saturation transfer (CEST) MRI, acquire qualitative contrast weighted images, without specific information on the quantitative parameters affecting contrast, namely proton exchange rate and concentration. In addition, the contrast weighted images are highly dependent on scan parameters and data acquisition strategies. Here, we developed a fast, quantitative saturation transfer (ST) imaging technique based on MR fingerprinting principles to simultaneously estimate free bulk water, semisolid macromolecule, and amide proton-related parameters. The approach was evaluated with Bloch simulation and synthetic MRI analysis using in vivo human brains.  

Wenwen Yu¹, Ying-Hua Chu², Changyong Xie³, Shuanghong Chen³, Jianping Zhang³, Zidong Yang¹, He Wang^1,4, and Yuchuan Qiao^1,4
1Institute of Science and Technology for Brain-inspired Intelligence,Fudan university, Shanghai, China, ²MR Collaboration, Siemens Healthineers Ltd., Shanghai, China, ³Center of Naval Special Medicine, Naval Medical University, Shanghai, China, ⁴Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, Shanghai, China

Keywords: CEST & MT, Magnetization transfer, locus coeruleus, magnetization transfer ratio, neuromelanin sensitive MRI

Neuromelanin (NM), mainly found in locus coeruleus (LC), is a well-known biomarker for neurodegenerative diseases such as Parkinson's disease (PD) and can be detected with neuromelanin-sensitive MRI (NM-MRI). However, whether NM content is associated with sleep disorders is largely unclear. We acquired 3D turbo flash MTC images from 20 normal and four dyssomnia adult males in a 7T scanner to examine the relationship between the sleep quality scores and the NM content in LC. Our preliminary results reveal that the magnetization transfer ratio (MTR), an indicator of NM concentration, of bilateral LC is significantly asymmetric in the dyssomnia group, and the mean value of MTR is lower in the left LC and higher in the right LC in dyssomnia group than normal group.

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Mengying Chen¹, Yupeng Wu¹, Qifan Pang¹, Haodong Zhong¹, Gaiying Li¹, Yang Song², Yi Wang³, and Jianqi Li^1
1Shanghai Key Laboratory of Magnetic Resonance, East China Normal University, Shanghai, China, ²MR Scientific Marketing, Siemens Healthineers, Shanghai, China, ³Department of Radiology, Weill Medical College of Cornell University, New York, NY, United States

Keywords: CEST & MT, Magnetization transfer, Neuromelanin

Although 3D magnetization transfer contrast (MTC) GRE sequence can image neuromelanin and magnetic susceptibility simultaneously, MTC saturation pulse takes too long time, and whether MTC affects accuracy of the susceptibility is unclear. Six subjects were scanned using 3D multi-echo GRE sequences with different durations of MTC pulse. 3D GRE sequence with 5ms of MTC pulse provided same saturation effects in highlighting neuromelanin as 10ms of MTC pulse, and yielded susceptibility values in the deep gray matter nuclei similar to sequence without MTC pulse. Short MTC pulse provides a practical means to simultaneously image the neuromelanin and magnetic susceptibility.

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Zhitao Li¹, Johe Pauly², and Shreyas Vasanawala^1
1Department of Radiology, Stanford University, Stanford, CA, United States, ²Electrical Engineering, Stanford University, Stanford, CA, United States

Keywords: CEST & MT, Brain, T1

A model-based technique for rapid magnetization transfer corrected T1 mapping is proposed, the T1 maps generated from the proposed technique is free of the under-estimation caused by MT effect. The technique is validated in both simulation and in-vivo experiments.

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Munendra Singh¹ and Hye-Young Heo^1
1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States

Keywords: CEST & MT, CEST & MT

An optimal saturation transfer MR fingerprinting (ST-MRF) acquisition schedule is critical for efficient and accurate tissue parameter mapping. To optimize RF saturation-encoded MRF acquisitions to a minimal number of saturation scan parameters for magnetization transfer contrast (MTC) and chemical exchange saturation transfer (CEST) parameter determination, we developed an optimization framework using a support vector regression-recursive feature elimination (SVR-RFE) method. Bloch simulations and in vivo studies showed that the proposed optimization method outperformed the quantification accuracy compared to existing methods. The SVR-RFE-based optimization method allowed us to reduce scan time by ~50% without sacrificing reconstruction accuracy.

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Morwarid Mayar^1,2, Mart de Vries¹, Paul Smeets^2,3, John van Duynhoven¹, and Camilla Terenzi^1
1Laboratory of Biophysics, Wageningen University & Research, Wageningen, Netherlands, ²Human Nutrition and Health, Wageningen University & Research, Wageningen, Netherlands, ³Image Sciences Institute, University Medical Centre Utrecht, Utrecht, Netherlands

Keywords: CEST & MT, Body, in vitro

Gastric digestion of dietary protein is commonly studied using in vitro digestion models, which need to be verified with in vivo data. Here, we used MT and CEST MRI to monitor in vitro gastric digestion of milk proteins. We show that MT and CEST measurements can be used to monitor the breakdown of the initially-formed semi-solid protein coagulum and hydrolysis of soluble proteins. We also demonstrate that RF-based ratiometric CEST analysis can be used for pH mapping in both acid- and base-catalyzed regions.  Our results open the way to quantification of in vivo protein digestion with the use of MRI. 

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Aisling Fothergill¹, David Higgins², Owen Thomas³, David Coope⁴, Ibrahim Djoukhadar³, and Laura Parkes^1
1Geoffrey Jefferson Brain Research Centre, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom, ²Philips, Farnborough, United Kingdom, ³Department of Radiology, Geoffrey Jefferson Brain Research Centre, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom, ⁴Department of Academic Neurological Surgery, Geoffrey Jefferson Brain Research Centre, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Manchester, United Kingdom

Keywords: CEST & MT, Quantitative Imaging, APT

Amide Proton Transfer MRI shows clinical benefit in glioma imaging. Clinically useful APTw metrics should be sensitive to changes in amide concentration, a potential marker of tumour proliferation, and insensitive to T₁ changes. To investigate sensitivity, simulations and in-vitro studies were performed over a range of amide concentrations and T₁ values. In-vitro data included two varied concentration series, with and without T₁-maintenance, and a constant concentration T₁-vaired series. In-vitro results showed APT* had poor sensitivity, MTR_rex was most sensitive to concentration and T₁, AREX may overcorrect for T₁, and MTR_asym appears least sensitive to T₁ while remaining sensitive to concentration.

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Mengdi Yan¹, Chongxue Bie¹, Yibin Chen¹, Xiaowei He¹, and Xiaolei Song^2
1Northwest University, Xi'an, Shanxi, China, ²Tsinghua University, Beijing, China

Keywords: CEST & MT, Data Analysis

Z-spectrum acquired under ultra-high field (> 3T) features stronger and better isolated CEST peaks than those under 3T. But from imaging aspect, 3T scanners perform better and are clinically accessible. Herein, we built a deep neural network (DNN) for predicting Z-spectrum under higher B₀ from the corresponding measurement at 3T. The network was trained by 10 million Z-spectra calculated from Bloch-equation models. Simulations with various B₀ shifts and noise suggested that 3T Z-spectra could be rapidly and accurately transformed to those under 7T or 9.4T. This network may help improve signal extraction and interpretation of CEST data acquired at 3T.

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Bárbara Schmitz-Abecassis^1,2, Chloé Najac¹, Jaimy Plugge¹, Matthias J.P. van Osch^1,2, and Ece Ercan^1,3
1Department of Radiology, Leiden University Medical Center, Leiden, Netherlands, ²Medical Delta Cancer Diagnostics 3.0, South-Holland, Netherlands, ³Philips Healthcare, Best, Netherlands

Keywords: CEST & MT, High-Field MRI

Amine chemical exchange saturation transfer (CEST) is highly sensitive for imaging metabolites in vivo. However, it lacks specificity. We aimed to develop and validate optimal CEST protocols to image creatine and glutamate in the human brain at 7T. Simulations were used to define optimal acquisition parameters, followed by in vitro validation. The optimal B₁rms and total saturation (t_sat) parameters were determined for creatine (B₁rms = 2.5μT &  t_sat = 1500ms) and glutamate (B₁rms = 3.5μT & t_sat = 1000ms).  These protocols were then used in healthy volunteers to investigate the correlation of glutamate- and creatine-weighted CEST with magnetic resonance spectroscopy results.

Eleni Demetriou^1,2, Ivan E Dimitrov^1,3, Peter van Zijl^4,5, Hans Hoogduin⁶, Elena Vinogradov⁷, Bei Zhang⁸, and Anke Henning^8
1Advanced imaging research center, University of Texas Southwestern Medical Center, Dallas, TX, United States, ²Brain repair and Rehabilitation, UCL, London, United Kingdom, ³Philips healthcare, Florida, FL, United States, ⁴F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, United Kingdom, ⁵Department of Radiology, Johns Hopkins University, Baltimore, MD, United States, ⁶Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands, Ultrecht, Netherlands, ⁷Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, United States, ⁸Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States

Keywords: CEST & MT, Brain, B1 inhomogeneities

In this work, we sought to evaluate CEST in combination with RF shimming that is based on the modulation of the amplitudes and phases of the RF pulses transmitted by an eight channel 7T MR system.

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Shahrokh Abbasi-Rad^1,2,3,4 and David Norris^1,2
1Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands, ²Erwin L. Hahn Institute for Magnetic Resonance Imaging, University Duisburg-Essen, Essen, Germany, ³Department of Radiology, Harvard Medical School, Boston, MA, United States, ⁴Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States

Keywords: fMRI, Magnetization transfer, Arterial Blood Contrast

Arterial blood contrast (ABC) uses on-resonance binomial pulse for magnetization transfer preparation to saturate the tissue signal and highlights the contribution of arterioles. Previously, using Bloch-McConnel simulations, we showed that Binomial MT contaminates ABC with T2 contrast. We suggested the use of adiabatic null passage to decrease the T2 effect. We performed Bloch-McConnel simulations at 3T and 7T comparing the performance of binomial and ANP pulses. ANP increased the arterial contribution from 32% to 42% at 3T and from 18% to 30% at 7T. This study concludes that ANP reduces the T2-contamination imposed by binomial MT block and improves ABC. 

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Leif Schröder¹, Hen Amit Morik¹, and Patrick Schuenke^2
1Translational Molecular Imaging, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany, ²Biomedical Magnetic Resonance, Physikalisch-Technische Bundesanstalt (PTB), Berlin, Germany

Keywords: Contrast Agent, CEST & MT

The full potential of the ultra-sensitive approach of HyperCEST MRI crucially depends on host structures with efficient release of hyperpolarized ¹²⁹Xe. Cucurbit[n]urils (CB6 and CB7) have been proposed as promising candidates but a quantitative analysis of CEST signatures yet remained an open question. Here, we use MRI-derived z-spectra of multiple samples which provide strong evidence that CB7 is unsuitable as CEST agent and that previously observed signals are solely assigned to CB6 which is also side product in CB7 synthesis. Image acquisition with >20-fold acceleration for the 4-dimensional datasets is possible without compromising a detailed quantitative analysis.

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Vira Grynko^1,2, Viktoriia Batarchuk^2,3, Yurii Shepelytskyi^2,3, Hannah Aalto⁴, Joseph Deschamps⁴, Iulian Constantin Russet⁵, and Mitchell Albert^2,3,6
1Chemistry and Materials Science Program, Lakehead University, Thunder Bay, ON, Canada, ²Thunder Bay Regional Health Research Institute, Thunder Bay, ON, Canada, ³Chemistry, Lakehead University, Thunder Bay, ON, Canada, ⁴Applied Life Science Program, Lakehead University, Thunder Bay, ON, Canada, ⁵Xemed LCC, Durham, NH, United States, ⁶Northern Ontario School of Medicine, Thunder Bay, ON, Canada

Keywords: Hyperpolarized MR (Gas), Contrast Agent

Cucurbit[6]uril is a well-studied contrast agent for hyperpolarized ¹²⁹Xe (HP ¹²⁹Xe) MRI. Although the in vivobiodistribution of CB6 was measured with hyperpolarized chemical exchange saturation transfer (HyperCEST), there were no previous studies reported for maximization of the HyperCEST effect by optimization of depolarization pre-pulse trains. In the present work, we maximized the CB6 HyperCEST effect in bovine blood, and found for the first time, a HyperCEST depletion of the RBC resonance.  In addition, the minimum detectable concentration was found to be four times lower than previously reported.

Jingcheng Huang¹, Chengshi Hou¹, Qingqing Wen², Weiqiang Dou², and Xianfu Luo^1
1Clinical Medical School of Yangzhou University, Northern Jiangsu People’s Hospital, Yangzhou, China, Yangzhou City, China, ²GE Healthcare, MR Research China, Beijing, P.R. China, Beijing City, China

Keywords: Quantitative Imaging, CEST & MT, APTw

Conventional MRI methods are difficult to reveal histologic and molecular characteristic of HCC. In this study, we aimed to e explore the feasibility of amide proton transfer weighted (APTw) imaging for predicting microvascular invasion (MVI) of hepatocellular carcinoma. Significant difference in APTw values were observed for MVI positive and negative lesions. With these findings, APTw imaging can be considered a potential technique for noninvasive preoperational assessment of MVI in hepatocellular carcinoma.