Michal Rivlin¹, Debbie Anaby^2,3, Noam Nissan^2,3, Moritz Zaiss⁴, Anagha Deshmane⁵, Miri Sklair-Levy^3,6, and Gil Navon^1
1School of Chemistry, Tel-Aviv University, Tel-Aviv, Israel, ²Department of Diagnostic Imaging, Sheba Medical Center, Ramat-Gan, Israel, ³The Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel, ⁴Department of Neuroradiology, University Clinic Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Erlangen, Germany, ⁵Department of Biomedical Magnetic Resonance, University of Tübingen, Tübingen, Germany, ⁶Meirav High Risk Clinic, Department of Diagnostic Imaging, Sheba Medical Center, Ramat-Gan, Israel

In preclinical experiments in implanted breast cancer tumors in mice, glucosamine (GlcN) exhibited enhanced chemical exchange saturation transfer (CEST) MRI signals. Moving toward clinical application, considering the excellent safety profile of GlcN, we examined the feasibility of using the GlcN CEST method to detect human breast cancer on a 3T clinical scanner. Here we report significant CEST MRI signals resulting from the exchangeable protons of GlcN hydroxyls, amine/amide residues as well as nuclear Overhauser enhancement (NOE). Thus, CEST MRI using GlcN has the potential to detect tumors and report their activity, without the use of a gadolinium contrast agent.

Jennifer Lefeuvre¹, Katie MacKey¹, Tsang-Wei Tu², and Joseph Frank^1
1Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, United States, ²Molecular imaging laboratory, Department of Radiology, Howard University College of Medicine, Washington DC, DC, United States

Metabolic changes may occur earlier and/or may help distinguish different type of tumors. We investigated the metabolic changes using CEST MRI and characterized induced metastatic breast cancer in the brain of 10 nude rats. In vivo CEST MRI were performed at 9.4T on 3 slices with 31 frequency offsets to cover the full Z-spectra. A total of 12 tumors were analyzed for CEST signal changes. Different tumor types (solid tumor vs necrosis) showed different metabolites uptakes. Tumors located within the dentate gyrus showed significant increased values compared to the tumors in brainstem, cortex and hippocampus.

Bárbara Schmitz Abecassis¹, Chloé Najac¹, Jeroen de Bresser ¹, Linda Dirven^2,3, Martin J.B. Taphoorn^2,3, Matthias J.P. van Osch¹, Johan A.F. Koekkoek^2,3, and Ece Ercan^1
1Department of Radiology, Leiden University Medical Center, Leiden, Netherlands, ²Department of Neurology, Leiden University Medical Center, Leiden, Netherlands, ³Department of Neurology, Haaglanden Medical Center, The Hague, Netherlands

CEST allows to non-invasively image metabolites and proteins, and the role of APT and NOE CEST in gliomas has been widely investigated. On the other hand, the contribution of amines to the CEST signal at 2 and 3 ppm, and its relationship to creatine and glutamate concentrations, remain unclear. We evaluated the amine CEST contrast in tumor and contralateral white matter in three glioma patients, and compared it to the MRS data. Overall we found a decrease in amine CEST alongside a decrease in total creatine and glutamate in the tumor compared to the contralateral white matter.

Feriel Romdhane¹, Dario Livio Longo¹, Christos Papageorgakis², Eleni Firippi², Laura Mancini^3,4, Sotirios Bisdas^3,4, Moritz Zaiss⁵, and Stefano Casagranda^2
1Institute of Biostructures and Bioimaging (IBB), National Research Council of Italy (CNR), Torino, Italy, ²Department of Research & Innovation, Olea Medical, La Ciotat, France, ³Lysholm Department of Neuroradiology, University College of London Hospitals NHS Foundation Trust, London, United Kingdom, ⁴Institute of Neurology UCL, London, United Kingdom, ⁵Department of Neuroradiology, University Clinic Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Erlangen, Germany

Amide Proton Transfer weighted (APTw) imaging is a promising MR molecular technique for characterizing brain tumors on clinical 3T scanners. However, improving the APT weighted contrast is crucial to translate this approach to clinical practice. In this work we investigated a novel spatial denoising filter in synthetic and clinical APTw data of brain tumor patients.

Philip S Boyd^1,2, Lilli Diederichs^1,2, Johannes Breitling¹, Mark E Ladd^1,2,3, Peter Bachert^1,2, and Steffen Goerke^1
1Division of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, ²Faculty of Physics and Astronomy, University of Heidelberg, Heidelberg, Germany, ³Faculty of Medicine, University of Heidelberg, Heidelberg, Germany

In this study, we present a method for absolute pH mapping using the guanidyl CEST signal. The method is an extension of a previous approach that allowed compensating for various concomitant effects other than pH, but additionally required measuring the amide signal. By optimizing the pulse shape of the pulsed presaturation the pH sensitivity of the guanidyl signal could now be shifted to the physiologically relevant range around pH 7.1. The shift of sensitivity was verified experimentally in a multi-pH creatine phantom at 9.4T. Thus, CEST-based pH mapping with exceptional specificity is now also possible using only the guanidyl signal.

 

Florian Kroh^1,2, Johannes Breitling¹, Nikolaus von Knebel Doeberitz³, Heinz-Peter Schlemmer^3,4, Mark E. Ladd^1,2,4, Peter Bachert^1,2, Daniel Paech^3,5, and Steffen Goerke^1
1Division of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, ²Faculty of Physics and Astronomy, University of Heidelberg, Heidelberg, Germany, ³Division of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, ⁴Faculty of Medicine, University of Heidelberg, Heidelberg, Germany, ⁵Division of Neuroradiology, University Hospital Bonn, Bonn, Germany

Although the underlying mechanisms of APT-weighted (APTw) CEST-MRI are not completely understood, it has been shown to provide valuable information for brain tumor imaging at 3T. To gather more information about the mechanisms, the APTw signal was correlated to relaxation-compensated CEST contrasts in 21 postoperative human glioma patients. A correlation, although being only moderate, was found for the relaxation-compensated APT contrast in the contrast enhancing (CE) tumor region, but not for other tissues, nor rNOE or MT contrast. Differentiation of the CE tumor and normal appearing white matter was strongly dependent on the selective relaxation-compensated CEST evaluation method.

Yulun Wu¹, Sophie H.A.E. Derks^1,2,3, Tobias Wood⁴, Astrid A.M. van der Veldt^1,2, Marion Smits¹, and Esther A.H. Warnert^1
1Department of Radiology & Nuclear Medicine, Erasmus MC, Rotterdam, Netherlands, ²Department of Medical Oncology, Erasmus MC, Rotterdam, Netherlands, ³Department of Neurology, Erasmus MC, Rotterdam, Netherlands, ⁴Centre for Neuroimaging Science, King's College London, London, United Kingdom

To develop detection of glucose contrast enhancement (GCE) with CEST for assessing brain metastases in clinical setting, here we performed a phantom study, scanned 10 healthy volunteers and one patient with brain metastases at 3T. We acquired dynamic GCE at 1.2 and 2 ppm for dynamic B₀ correction and applied principle component analysis (PCA) to perform noise reduction, after which we compared the resulting GCE at both offsets. The developed pipeline resulted in GCE of ~5% in tumor and -5 to 0.05% in healthy tissues after glucose infusion.

Fang Frank Yu¹, James Ratnakar², Jonathan A Brewer¹, Brian Hitt³, A Dean Sherry^1,2, and Elena Vinogradov^1,2
1Radiology, University of Texas Southwestern Medical Center, Dallas, TX, United States, ²Advanced Imaging Reseach Center, University of Texas Southwestern Medical Center, Dallas, TX, United States, ³Neurology, University of California, Irvine Medical Center, Irvine, CA, United States

Alzheimer’s Disease (AD) is defined biologically by the presence of neuritic plaques composed of amyloid-in β (Aβ)peptides and dystrophic neurites, neurofibrillary tangles (NFTs) of hyperphosphorylated tau protein, and neuronal loss. In this study, CEST experiments were performed on purified full-length tau monomer and aggregated tau fibrils. We found differences in CEST z-spectra between purified full-length tau monomers and aggregated tau fibrils. This finding substantiates the potential use of CEST for ultimately monitoring disease progression in AD patients