Vadim Malis¹, Jirach Kungsamutr², Won Bae¹, Xiaowei Zhang¹, Yoshimori Kassai³, and Mitsue Miyazaki^1
1Radiology, UC San Diego, San Diego, CA, United States, ²Bioengineering, UC San Diego, San Diego, CA, United States, ³Canon Medical Systems Corp., Tochigi, Japan

Chemical exchange saturation transfer (CEST) is a molecular imaging technique for specific exchange of hydroxy (-OH, ~1.0 ppm), amine (-NH₂, ~2 ppm), and amide (-NH, ~3.5 ppm), whereas ZAP is overall exchange protons of relatively free exchange protons (T_2,f) and restricted protons (T_2,r) from a wide frequency range of +/– 100 kHz. Combining CEST and ZAP to measure qualitative values of abdominal organ is aiming to be established.

Chongxue Bie^1,2,3, Yang Zhou^1,2,4, Peter C. M. van Zijl^1,2, Jiadi Xu^1,2, Chao Zou⁴, and Nirbhay N. Yadav^1,2
1F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ²The Russell H. Morgan Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, ³Department of Information Science and Technology, Northwest University, Xi'an, China, ⁴Key Laboratory for Magnetic Resonance and Multimodality Imaging of Guangdong Province, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, ShenZhen, China

Saturation transfer MRI has previously been used to probe molecular binding interactions with signal enhancement via the water signal (IMMOBILISE approach). Here, we detailed the relayed nuclear Overhauser effect (rNOE) based mechanisms of this signal enhancement by a four-pool magnetization transfer model, verified the model both using simulations and experimentally (using small charged molecules: arginine, choline, and acetyl-choline). The analytical model can be used to quantify molecular binding affinity, i.e., the dissociation constant (K_D). The characterization of the transient binding of small natural substrates paves a pathway towards the detection of receptor-substrate binding in vivo using MRI.

Chongxue Bie^1,2,3, Zheng Han^1,2, Peter C. M. van Zijl^1,2, Nirbhay N. Yadav^1,2, and Guanshu Liu^1,2
1F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ²The Russell H. Morgan Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, ³Department of Information Science and Technology, Northwest University, Xi'an, China

Accurate detection of kidney injury is of immense importance for the diagnosis and treatment of acute kidney injury (AKI). While CEST MRI has the potential to reveal the pathophysiological changes on a molecular level, no automatic, CEST-based classification model has been developed. We developed a deep neural network (DNN) to analyze features of the Z-spectral data and to classify injured and healthy renal tissues. The results show that the classification model was capable of reliable prediction of kidney injury among different AKI mouse models. Results correlated well with serum creatinine (SCr) measurement.

Ding Xia¹, Li Feng¹, and Xiang Xu^1
1Biomedical Engineering and Imaging Institute and Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States

In this work, we proposed a novel dynamic CEST MRI framework, which employs golden-angle rotated variable-density Cartesian acquisition with multicoil compressed sensing reconstruction. It enables continuous data acquisition and retrospective reconstruction with desired temporal resolution. We have demonstrated the performance of this new framework for accelerated CEST MRI both in phantom and in human brain at 7T. 

Hahnsung Kim^1,2, Lisa C. Krishnamurthy ^3,4, Kimberly B Hoang⁵, Ranliang Hu², and Phillip Zhe Sun^1,2
1Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States, ²Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, United States, ³Center for Visual and Neurocognitive Rehabilitation, Atlanta VA, Decatur, GA, United States, ⁴Department of Physics & Astronomy, Georgia State University, atlanta, GA, United States, ⁵Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, United States

The multi-slice CEST signal evolution was described by the spin-lock relaxation during saturation duration (T_s) and longitudinal relaxation during the relaxation delay time (T_d) and post-label delay (PLD), from which the QUASS CEST was generalized to fast multi-slice acquisition. In addition, normal human subjects and tumor patients scans were performed to compare the conventional apparent and QUASS CEST measurements with different T_s, T_d, and PLD. Bland-Altman analysis bias of the proposed QUASS CEST effects was much smaller than the PLD-corrected apparent CEST effects (0.03% vs. -0.54%), indicating the proposed fast multi-slice CEST imaging is robust and accurate.   

zhongliang zu^1
1Vanderbilt University Medical Center, Nashville, TN, United States

Magnetization transfer (MT) effect has been analyzed by the MT ratio (MTR) or quantitative MT (qMT). However, because the MTR lacks sensitivity and specificity to MT effect and qMT needs a long scan time, their application into clinical scenarios has been limited. In this paper, we introduce the dopMTR, a new MT data analysis and acquisition method that uses double saturation pulse offsets and powers. Simulations and experiments show that the dopMTR can provide more specific and sensitive quantification of the MT effect than the conventional MTR, with relatively brief acquisition times and easy data processing.

zhongliang zu¹, Fatemeh Adelnia¹, Kevin D Harkins¹, Feng Wang¹, and John C Gore^1
1Vanderbilt University Medical Center, Nashville, TN, United States

Previous research has shown that spin-lock imaging with low locking amplitude can quantify the spatial characteristics of intrinsic susceptibility gradients in tissues which likely reflect vascular microstructure. We evaluated the capability of spin-lock dispersion imaging with weak locking fields to detect vasoconstriction in rat brains under oxygen challenges.

Chi-Hyeon Yoo¹, Nisha Rani¹, Frederick Bagdasarian¹, Sarah Reid¹, Changning Wang¹, and Hsiao-Ying Wey^1
1Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States

The goal of this study was to investigate relationship between hemodynamic responses and underlying neurochemistry targeting cannabinoid receptor 1 (CB1R) in response to the injection of rimonabant in non-human primates using simultaneous positron emission tomography (PET) and function magnetic resonance imaging (fMRI). Following the rimonabant injection, fast and slow hemodynamic responses were identified throughout the brain. The CB1R occupancy estimates suggested that the radiotracer binding to CB1R was blocked by rimonabant highly in cerebellum and several brain regions. Future PET/fMRI studies with other CB1R-agonists/antagonists and more accurate occupancy estimates will provide further understanding about neurovascular coupling to CB1R.

Harikrishna Rallapalli^1,2, N. Sumru Bayin³, Hannah Goldman², Brian J Nieman⁴, Alan P Koretsky¹, Alexandra L Joyner³, and Daniel H Turnbull^2
1NINDS, NIH, Bethesda, MD, United States, ²Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY, United States, ³Developmental Biology, Sloan Kettering Institute, New York, NY, United States, ⁴Research Operations, The Hospital for Sick Children, Toronto, ON, Canada

Manganese enhanced MRI (MEMRI) has been used to generate layer-specific contrast in preclinical neuroimaging studies, especially in the cerebellum. However, the cell types that contribute most to MEMRI signal have not yet been identified. In this study, we registered high resolution MEMRI to immunohistochemistry of the cerebellum to verify layer localization of signal. We found that the Purkinje cell layer (PCL) was the source of hyperintensity. Next, we manipulated cell types of the PCL using genetically engineered mouse models and quantified MEMRI signal changes. These results strongly suggest Purkinje cells are the primary cellular source of hyperintensity in cerebellar MEMRI.

Gustavo Kaneblai¹, Maria Concepcion Garcia Otaduy², Regis Otaviano Franca³, Frederico Perego Costa⁴, Eduardo Figueiredo⁵, Thomas Doring⁶, Marcelo Blois⁵, Claudia da Costa Leite⁷, Giovanni Guido Cerri⁷, and Mitsuharu Miyoshi^8
1Digital Innovation, GE Healthcare, Sao Paulo, Brazil, ²Univesidade de Sao Paulo, Sao Paulo, Brazil, ³Hospital Sirio-Libanes, SAO PAULO, Brazil, ⁴Hosputal Sirio-Libanes, SAO PAULO, Brazil, ⁵GE Healthcare, SAO PAULO, Brazil, ⁶GE Healthcare, RIO DE JANEIRO, Brazil, ⁷Universidade de Sao Paulo, SAO PAULO, Brazil, ⁸GE Healthcare, Tokyo, Japan

A new method to create B0 corrected dynamic MTR_asym glucoCEST maps during glucose administration and uptake without the need of acquiring a full Z-Spectrum with small changes in DGE. Results observed in 3T.

Deva Nishanth Tirukoti¹, Liat Avram-Biton², and Amnon Bar-Shir^1
1Molecular Chemistry and Material Science, Weizmann Institute of Science, Rehovot, Israel, ²Chemical Research Support, Weizmann institute of Science, Rehovot, Israel

The fast clearance of small molecular probes limits their applicability as responsive agent and prevents their use in longitudinal study. We show here the design and implementation of a tripod-type responsive agent for Zn²⁺ mapping that assembled to 100nm nanostructure at physiological temperature. The designed fluorinated probe showed capabilities to monitor Zn²⁺ when combining CEST MRI and ¹⁹F-MRI. Upon its intracranial injection the synthetic probe assembled to large entities in the tissue that prevent its clearance from the injection site. This property allows to map its ¹⁹F-signal for more than 20 hours and will enable longitudinal studies in the future.

Simon Reichert¹, Dennis Kleimaier¹, and Lothar Schad^1
1Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany

This study demonstrates a correlation of protein size with sodium triple-quantum (TQ) signal. The TQ/SQ ratio of several globular proteins increased with protein size. Furthermore, strong sodium binding had a substantial impact on the TQ signal.  The small protein α-Lactalbumin yielded a strong TQ signal due to strong sodium binding to a calcium binding site using a calcium-depleted protein.

Simon Reichert¹, Dennis Kleimaier¹, and Lothar Schad^1
1Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany

This work presents an open source simulation framework of spin-3/2 NMR dynamics for isotropic and anisotropic environments, and hard pulses. The flexible, modular structure provides a computationally efficient framework to investigate in detail MR signal characteristics using arbitrary pulse sequences. Comparison of simulated and measured data showed a good agreement for the TQTPPI sequence using ²³Na. The simulation framework is available as open source on GitHub (https://github.com/SmnReichert/PhaseCycleSim).

Simon Reichert¹, Dennis Kleimaier¹, and Lothar Schad^1
1Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany

This study proposes an inversion recovery TQTPPI pulse sequence to create triple quantum (TQ) coherences utilizing the $$$T_1$$$  relaxation pathway. Different double quantum (DQ) suppression methods provide stable fit results with reasonable SNR. The  $$$T_1$$$-TQ signal is sensitive to faster motion than the conventional  $$$T_2$$$-TQ pathway and thus provides additional information about sodium-protein interactions.