Rohan S. Virgincar¹, Kai H. Barck¹, Mary Ann Go², Geoffrey Del Rosario², Shang-Fan Yu², ManKin Choy¹, Alvin Gogineni¹, Justin Elstrott¹, Herman S. Gill¹, Jan Marik¹, Genee Lee², Mark D. Pagel³, Alex de Crespigny⁴, Teemu T. Junttila⁵, Christoph Spiess⁶, Robby M. Weimer¹, and Luke Xie^1
1Biomedical Imaging, Genentech, South San Francisco, CA, United States, ²Translational Oncology, Genentech, South San Francisco, CA, United States, ³Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, TX, United States, ⁴Early Clinical Development, Genentech, South San Francisco, CA, United States, ⁵In Vivo Pharmacology, Genentech, South San Francisco, CA, United States, ⁶Antibody Engineering, Genentech, South San Francisco, CA, United States

AcidoCEST MRI is a promising technique to directly measure extracellular pH in vivo and is well-suited to imaging tumors, which can exhibit acidosis. However, few studies have demonstrated the conditions and the minimum contrast agent concentrations needed for robust acidoCEST MRI. In this study, we employed micro-CT to determine the uptake of iopamidol in tumors with intratumoral and intravenous delivery of isovue-370, estimated the accuracy of pH measured by MRI vs. a pH meter, demonstrated the minimum iopamidol concentration required for acidoCEST MRI, and reported pH measurements in different tumor xenograft models.

Guangle Zhang¹, Wei Zhu¹, Wei Chen¹, and Xiao-Hong Zhu^1
1University of Minnesota, Minneapolis, MN, United States

In this study, we used a newly developed tri-frequency RF surface coil that enables ¹H MRI and interleaved ²H/¹⁷O MRS measurements to simultaneously assess cerebral glucose and oxygen metabolism, cerebral blood flow and oxygen extraction fraction in rat brain at 16.4T with administration of ²H-labeled glucose and ¹⁷O-labeled oxygen gas. Our results demonstrate that this approach can capture the activities of major pathways relevant to glucose and oxygen metabolism and perfusion in the same brain at the same time, thereby provide comprehensive information crucial for understanding the metabolic and vascular coupling or uncoupling relationship in healthy and diseased brains. 

Yibo Zhao^1,2, Yudu Li^1,2, Rong Guo^1,2, Keith R. Thulborn³, and Zhi-Pei Liang^1,2
1Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana-Champaign, Urbana, IL, United States, ²Department of Electrical and Computer Engineering, University of Illinois, Urbana-Champaign, Urbana, IL, United States, ³Center for Magnetic Resonance Research, University of Illinois at Chicago, Chicago, IL, United States

Sodium MRI can acquire important biological information about cell integrity and tissue viability, but its clinical application has been limited by low SNR and poor spatial resolution. We propose a novel method to reconstruct high-quality sodium images from limited and noisy k-space data. The new method synergistically integrates model-based reconstruction with deep learning. Simulation and experimental results show that the proposed method can reconstruct high-SNR and high-resolution sodium images, which clearly delineate lesions such as brain tumors.

Julius Juhyun Chung¹ and Tao Jin^1
1University of Pittsburgh, Pittsburgh, PA, United States

Average Saturation Efficiency Filter (ASEF) is a fast and intuitive technique for achieving CEST imaging with improved sensitivity removing fast exchanges and semi-solid MT background with minimal loss to sensitivity. Our results in MCAO rodents showed that it can detect the ischemic lesion from CEST signal contrasts at 3.6, 2.6, and 2 ppm which may provide different metabolic-related information with higher sensitivity to 3-point measurement at 3.6 ppm and comparable contrast. Its low requirement on number of imaged signals also opens up possibilities for dynamic imaging or signal averaging.  

Manon Edde^1,2, Guillaume Theaud^1,2, Matthieu Dumont², Antoine Théberge³, Alex Valcourt-Caron^1,2, Stefano Magon⁴, and Maxime Descoteaux^1,2
11Sherbrooke Connectivity Imaging Lab (SCIL), University of Sherbrooke, SCIL, Sherbrooke, QC, Canada, ²Imeka Solutions, Inc., Sherbrooke, QC, Canada, ³Videos & Images Theory and Analytics Laboratory (VITAL), University of Sherbrooke,, Sherbrooke, QC, Canada, ⁴Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland

Longitudinal imaging studies are widely used to capture and characterize progressive brain changes. However, evaluation of the reproducibility and the variation of measures in MRI is crucial to reliably detect or predict brain changes with quantitative MRI measures. Using the coefficient of variation and intraclass correlation, we evaluated the reproducibility of diffusion and myelin-based MRI measures from a multi-shell diffusion and inhomogeneous magnetization transfer MRI dataset of twenty healthy adults, each with five MRI acquisitions over six months. Moderate to high reproducibility of diffusion and myelin measures is observed within white matter tracks of interests.

Tao Jin¹ and Julius Juhyun Chung^1
1University of Pittsburgh, Pittsburgh, PA, United States

Endogenous CEST signal usually has low specificity due to contamination from the magnetization transfer effect and from fast exchanging labile protons with close Larmor frequencies. We propose to improve CEST signal specificity with an ASEF which measures the difference between CEST signals acquired with similar average saturation power but largely different duty cycles (DC), e.g., a continuous wave or a high DC pulse train versus a low DC one. Simulation and creatine phantom studies showed that ASEF can improve the specificity of slow to intermediate exchanging CEST signal with a relatively small loss of sensitivity. 

Rachel W. Chan¹, Hatef Mehrabian¹, Arjun Sahgal², Hanbo Chen², Aimee Theriault², Wilfred W. Lam¹, Sten Myrehaug², Chia-Lin Tseng², Zain Husain², Jay Detsky², Hany Soliman², and Greg J. Stanisz^1,3,4
1Physical Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada, ²Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ³Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada, ⁴Department of Neurosurgery and Pediatric Neurosurgery, Medical University of Lublin, Lublin, Poland

Stereotactic radiosurgery for brain metastases delivers a focal dose of radiation and has excellent local tumour control but leads to radiation necrosis (RN) in up to 22% of patients. This study used saturation transfer MRI for distinguishing between RN and tumour progression (TP), extending our previous work to a larger cohort of 70 patients (75 lesions). Eleven out of 14 metrics (including quantitative MT and CEST) showed statistically significant differences between the RN and TP cohorts, including magnetization transfer ratio (MTR) metrics showing the best separation. Univariable logistic regression resulted in the high-power MTR having the highest AUC=0.88 (with AIC=67.3).

Rachel W. Chan¹, Wilfred W. Lam¹, Patrick Liebig², Leedan Murray¹, Hatef Mehrabian¹, Aimee Theriault³, Ruby Endre¹, Garry Detzler¹, Sten Myrehaug³, Chia-Lin Tseng³, Jay Detsky³, Pejman J. Maralani⁴, Arjun Sahgal³, Hany Soliman³, and Greg J. Stanisz^1,5,6
1Physical Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada, ²Siemens Healthineers, Erlangen, Germany, ³Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ⁴Department of Medical Imaging, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada, ⁵Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada, ⁶Department of Neurosurgery and Pediatric Neurosurgery, Medical University of Lublin, Lublin, Poland

Stereotactic radiosurgery for the treatment of brain metastases delivers a high dose of radiation  with excellent local control, but increases the likelihood of radiation necrosis. CEST is a promising technique for distinguishing radiation necrosis from tumour progression in brain metastases, but its application has been limited to a single MRI system and CEST sequence. This study explores the use of scaling of the magnetization transfer ratio (MTR) by the white matter (WM) of each patient for comparison across vendors/sequences. It was found that the WM-scaled MTR showed improved correspondence across the MR systems, across two CEST sequences.

Pengfei Guo^1,2, Mathias Unberath², Jinyuan Zhou¹, Hye-Young Heo¹, Charles G. Eberhart³, Michael Lim⁴, Jaishri O. Blakeley⁵, Peter van Zijl^1,6, and Shanshan Jiang^1
1Department of Radiology, Johns Hopkins University, Baltimore, MD, United States, ²Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, United States, ³Department of Pathology, Johns Hopkins University, Baltimore, MD, United States, ⁴Department of Neurosurgery, Johns Hopkins University, Baltimore, MD, United States, ⁵Department of Neurology, Johns Hopkins University, Baltimore, MD, United States, ⁶F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

Amide protein transfer weighted (APTw) MRI has been validated to accurately detect recurrent malignant gliomas across different studies. However, APTw image interpretation is time consuming and requires professional knowledge. Therefore, reliable, automated imaging diagnostic tools to assess malignant glioma response to therapies are urgently needed. Here, we develop and verify a CNN-based deep-learning algorithm to identify tumor progression versus response by adding APTw MRI data to structural MR images as the proposed model input. Our results suggest that the use of APTw images can increase the diagnostic accuracy to structural MRI for the treatment response assessment.

Alan E. Rivera-Garcia¹, Juan Uribe², Jay D. Turner², John C. Gore³, and Ping Wang^1
1Translational Neuroscience, Barrow Neurological Institute, Phoenix, AZ, United States, ²Barrow Neurological Institute, Phoenix, AZ, United States, ³Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, United States

Previous studies have demonstrated that at high fields (3T and beyond), dispersion of R1rho with different locking fields may reflect chemical exchange processes in biological tissues. This study aimed to investigate if R1rho dispersion is measurable in the spinal cord and nerve bundles. The results show that the dispersion is significant and measurable in both tissues, suggesting that R1rho dispersion has potential to characterize changes in composition or other physicochemical properties in nerve injuries and/or neurological disorders.

Soo Hyun Shin¹, Michael Wendland², and Moriel Vandsburger^1
1Department of Bioengineering, University of California, Berkeley, Berkeley, CA, United States, ²Berkeley Preclinical Imaging Core (BPIC), University of California, Berkeley, Berkeley, CA, United States

Standardized blood tests lack adequate sensitivity to renal function and its underlying pathophysiology. We examined whether urea CEST, along with NOE CEST and quantitative MT imaging, can be used to quantitatively differentiate cisplatin and aristolochic acid (AA) models of mild and severe nephropathy, respectively. The increase of T₁ relaxation time and decrease of qMT contrast were parallel in two models, while the decreased intrarenal gradient of urea CEST and NOE contrast were only observed in AA models. These results indicate that our integrated approach has the potential to noninvasively quantitate renal injuries and characterize different types of renal pathophysiology.