Anna Orzylowska¹, Tymoteusz Słowik², Agata Chudzik¹, Anna Pankowska³, Wilfred W Lam⁴, and Greg J Stanisz^1,4,5
1Department of Neurosurgery and Paediatric Neurosurgery, Medical University of Lublin, Lublin, Poland, ²Center of Experimental Medicine, Medical University of Lublin, Lublin, Poland, ³Department of Radiography, Medical University of Lublin, Lublin, Poland, ⁴Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada, ⁵Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

The study compares the differences between Z-spectra derived from CEST imaging of rat brain in vivo and after post-mortem CLARITY lipids removal procedure. The lipids removal nulled-out MT macromolecular-originating signal measured with B₁ saturation amplitudes of 3 and 5 µT as compared to in vivo, and resulted in negligible MT contribution to CEST Z-spectra acquired with B₁s of 0.5 and 0.75 µT, as opposite to living tissue, where the MT effect was significant. Our results showed that the macromolecular MT contribution into in vivo Z-spectra originates mostly from lipids, since the CLARITY technique removed the MT component from the spectrum.

Sarah Rosemary Morris^1,2,3, Rebecca Frederick¹, Alex L MacKay^1,2,4, Cornelia Laule^1,2,3,5, and Carl A. Michal^1
1Physics & Astronomy, University of British Columbia, Vancouver, BC, Canada, ²Radiology, University of British Columbia, Vancouver, BC, Canada, ³International Collaboration on Repair Discoveries, Vancouver, BC, Canada, ⁴UBC MRI Research Centre, Vancouver, BC, Canada, ⁵Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada

Inhomogeneous magnetization transfer ratio (ihMTR) is reported to have significant orientation dependence in the brain, likely due to the anisotropy of dipolar couplings between methylene protons on the oriented lipids in myelin bilayers. We measured the orientation dependence of linewidth, dipolar relaxation time (T_1D) and ihMTR in an aligned phospholipid bilayer sample at 9.4T. ihMTR was maximized when the bilayers were parallel to B₀ and minimized near the magic angle (~54.7°) despite the fact that T_1D is maximized there. This is in contrast to previous in vivo results which show maximal ihMTR for bilayers perpendicular to B₀.

Yang Zhou^1,2, Peter C.M. van Zijl^1,2, Jiadi Xu^1,2, and Nirbhay N. Yadav^1,2
1The Russell H. Morgan Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²F.M. Kirby Research Center for Functional, Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

Recently a new MRI method was developed for the sensitivity enhanced detection of glycogen based on magnetization transfer between glycogen aliphatic protons and water, yet the mechanism of this transfer pathway is still not well understood. Here, we show that the magnetization transfer occurs via the relayed-NOE (rNOE) CEST effect. A theoretical model is proposed to quantitatively describe the rNOE signal in these magnetization transfer MRI experiments. This study provides insight into the rNOE mechanism that commonly occurs in magnetization transfer MRI on systems such as proteins and carbohydrate polymers. 

Stefano Casagranda¹, Laura Mancini^2,3, Guillaume Gautier¹, Philippe Peter¹, Bruno Lopez¹, Sebastian Brandner^4,5, Enrico De Vita^2,6, Xavier Golay^2,3, and Sotirios Bisdas^2,3
1Olea Medical, La Ciotat, France, ²Lysholm Dept of Neuroradiology, University College of London Hospitals NHS Foundation Trust, London, United Kingdom, ³Institute of Neurology UCL, London, United Kingdom, ⁴National Hospital for Neurology & Neurosurgery, University College of London Hospitals NHS Foundation Trust, London, United Kingdom, ⁵Department of Neurodegenerative Disease, Institute of Neurology UCL, London, United Kingdom, ⁶Biomedical Engineering Department, School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom

CEST is a novel MR technique helpful for predicting IDH and 1p/19q status in gliomas. The asymmetry-based methods however are sensitive to fluid signal and recent studies have shown that a significant proportion of IDH-mutant 1p/19q retained gliomas have T2-FLAIR mismatch, indicating the presence of a more fluid microenvironment. This work shows how fluid-suppressed CEST imaging metrics have an impact on amide and amine signals in glioma, with highest effect on IDH-mutant 1p/19q retained with T2-FLAIR mismatch. The combined use of asymmetry-based and fluid-suppressed CEST metrics could be a valuable tool for glioma staging more robust than asymmetry-based metrics alone.

Jingwen Yao^1,2,3, Chencai Wang^1,2, and Benjamin M. Ellingson^1,2,3
1Brain Tumor Imaging Laboratory (BTIL), Center of Computer Vision and Imaging Biomarker, David Geffen School of Medicine, UCLA, Los Angeles, CA, United States, ²Department of Radiological Sciences, David Geffen School of Medicine, UCLA, Los Angeles, CA, United States, ³Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, UCLA, Los Angeles, CA, United States

Effects of the catalytic in vivo chemical environment have often been neglected or underestimated in CEST-MRI studies. Phosphate is the predominant exchange catalyst in intracellular fluid and is essential for biosynthesis and bioenergetics. In this study, we evaluated the influence of phosphate on amine and amide CEST contrast using Bloch-McConnell simulations applied to physical phantom data. We demonstrate that amine proton exchange is greatly catalyzed by phosphate, under a physiological concentration range. We propose that catalytic agents should be considered as confounding factors in future CEST-MRI researches. This new dimension may also benefit the development of novel phosphate-sensitive imaging method.

Or Perlman¹, Hirotaka Ito², Kai Herz^3,4, Hiroshi Nakashima², Moritz Zaiss^3,5, E. Antonio Chiocca², Christopher Nguyen¹, Ouri Cohen⁶, Matthew S. Rosen^1,7, and Christian T. Farrar^1
1Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States, ²Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, United States, ³Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany, ⁴IMPRS for Cognitive and Systems Neuroscience, University of Tübingen, Tübingen, Germany, ⁵Department of Neuroradiology, University Clinic Erlangen, Erlangen, Germany, ⁶Memorial Sloan Kettering Cancer Center, New York, NY, United States, ⁷Department of Physics, Harvard University, Cambridge, MA, United States

Oncolytic virotherapy (OV) is a promising treatment for high mortality cancers. To optimize the clinical outcome, non-invasive monitoring is essential. The goal of this work was to develop a deep-learning-based technique for quantitative and rapid molecular imaging of OV treatment response. Two CEST MR-fingerprinting protocols were sequentially implemented (105s each) and incorporated within a deep-reconstruction-network, trained to output the quantitative semi-solid and amide pool exchange parameters. The resulting molecular maps allowed early apoptosis detection in brain tumor OV mouse models. Clinical translation of CEST-MRF is demonstrated in a normal human subject and yielded parameters in good agreement with literature values.

Hatef Mehrabian¹, Wilfred W Lam¹, Hany Soliman^1,2,3, Sten Myrehaug^2,3, Arjun Sahgal^1,2,3, and Greg J Stanisz^1,4
1Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada, ²Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ³Radiation Oncology, University of Toronto, Toronto, ON, Canada, ⁴Medical Biophysics, University of Toronto, Toronto, ON, Canada

Previous animal studies have shown differences in CEST properties of radio-resistant and radio-sensitive renal cell carcinoma xenografts. The current study probed the differences in CEST and MT properties of brain metastases from radio-resistant and radio-sensitive primary tumours. We observed significantly lower amount of magnetization transfer, RM_0B/R_A, and direct water saturation effect, 1/(R_AT_2A) in brain metastases from radio-resistant tumours compared to those from radio-sensitive tumours. However, the CEST effects of the two cohorts were not different. Such information should be considered when investigating brain metastases and their response to treatment.

Jie Liu¹, Xiaofei Lv², Chao Ke³, Zongwei Xu¹, Long Qian⁴, Shijie Xu³, Xin Liu¹, Hairong Zheng¹, and Yin Wu^1
1Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China, ²Department of Medical Imaging, Sun Yat-Sen University Cancer Center, Guangzhou, China, ³Department of Neurosurgery, Sun Yat-Sen University Cancer Center, Guangzhou, China, ⁴GE Healthcare, Beijing, China

Early identification of glioma prognostic characteristics is of great clinical importance. This study aims to evaluate the feasibility of APT in the prediction of tumor grade, IDH mutation and MGMT promoter methylation status at 3 Tesla. A total of 50 patients were recruited. Results show that although APTw effect exhibits no substantial difference based on MGMT methylation status, it enables the discrimination of histopathological grade and IDH mutant status with AUCs higher than 0.88. The results suggest APTw is a valuable imaging biomarker for prediction of tumor prognostic parameters, that may benefit accurate diagnosis and prompt treatment decisions.

Yohann Mathieu-Daudé^1,2, Mélissa Vincent^1,2, Julien Valette^1,2, and Julien Flament^1,2
1Molecular Imaging Research Center (MIRCen), Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA), Fontenay-aux-Roses, France, ²UMR 9199, Neurodegenerative Diseases Laboratory, Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud, Université Paris-Saclay, Fontenay-aux-Roses, France

2-Deoxy-D-glucose (2DG), an analogue of glucose similarly transported but with metabolism blocked after the first phosphorylation into 2DG-6-phosphate (2DG6P), has already been used to study glycolytic metabolism using gluCEST. However, origin of glucoCEST signal is still an open question important to be addressed. In this study, we measured for the first time variations of CEST signal in the rat brain at different resonance frequencies following 2DG injection. The richness of CEST signal can help assessing the fate of glycolytic substrates and would constitute a first step toward quantitative measurement of glucose metabolism using CEST method.

Jelena Mihailovic^1,2, Yuegao Huang¹, John Walsh¹, Daniel Coman¹, Sara Samuel³, and Fahmeed Hyder^1,3
1(1)Magnetic Resonance Research Center (MRRC), Yale University, New Haven, CT, United States, ²(2)Department of Diagnostic Radiology, Yale University, New Haven, CT, United States, ³Core Center for Quantitative Neuroscience with Magnetic Resonance (QNMR), Yale University, New Haven, CT, United States

Chemical Exchange Saturation Transfer (CEST) and Biosensor Imaging of Redundant Deviation in Shifts (BIRDS) biosensing methods differ respectively by detecting exchangeable and non-exchangeable protons on the agent. Given that CEST and BIRDS properties observed from the same paramagnetic agent are complimentary, we describe a novel approach for high-resolution pH imaging using dual agents of europium and thulium complexed with DOTA-tetraglycinate. In vitro results test the hypothesis that ratiometric paraCEST attributes are conserved when temperature from paraBIRDS is detected simultaneously, enabling absolute pH imaging. In vivo results in glioblastoma demonstrate feasibility of this dual paraCEST-paraBIRDS biosensing method for high-resolution pH imaging.