Johannes Breitling¹, Andreas Korzowski¹, 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 demonstrate the feasibility of obtaining steady-state 3D CEST contrasts of the human brain at 3T using a reduced saturation period. To this end, we applied our previous approach, which utilizes the analytical equation of the CEST signal, to an optimized clinical protocol using a fast volumetric snapshot-CEST acquisition. Measurements on model solutions and a volunteer demonstrated the feasibility with almost identical APT and rNOE contrasts for saturation durations as short as 1 second. Consequently, this facilitates quantitative CEST-MRI in humans within a reasonable and clinically relevant time frame.

Michelle H Lam^1,2, Andrew Yung², Jie Liu³, Wolfram Tetzlaff³, and Piotr Kozlowski^1,2,3,4
1Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada, ²UBC MRI Research Centre, University of British Columbia, Vancouver, BC, Canada, ³International Collaboration on Repair Discoveries, Vancouver, BC, Canada, ⁴Radiology, University of British Columbia, Vancouver, BC, Canada

An MR imaging technique called inhomogeneous magnetization transfer (ihMT) could potentially be used for quantitative myelin imaging by using T_1D filtering to filter out the short dipolar relaxation time (T_1D) components. However, to show that ihMT with T_1D filtering is myelin-specific, we need to confirm that myelin has the longest T_1D in nerve tissue. Here, we combined ihMT and myelin water imaging (MWI) to separate the ihMT signal in myelin water from intra-/extra-cellular water, which we fitted using a four-pool model with dipolar order reservoirs. Our model allowed us to connect myelin with myelin water and measure myelin’s T_1D.

Lukas Kamm¹, Kai Herz², Maria Sedykh¹, Moritz Fabian¹, and Moritz Zaiss^1,2
1Neuroradiology, Friedrich-Alexander-University Erlangen-Nürnberg, University Hospital, Erlangen, Germany, ²Magnetic Resonance Center, Max-Planck-Institute for Biological Cybernetics, Tübingen, Germany

In a clinical setting, it often has to be decided, which CEST sequences to pick of a collection, due to measurement time limitations. Therefore, eventually not all of the desired contrasts can be measured. In this work, we comprehensively combine seven CEST protocols in a single measurement, use a fast single-shot 3D gradient echo readout and remove redundant regions of the experimental parameter space. Hereby, we can half the total measurement time from 35 to 17 minutes. With further parameter reduction, a total measurement time of 10 minutes is conceivable. This allows to design powerful hypothesis generating clinical pilot studies.

Iris Obdeijn^1,2, Lejla Alic², Maarten Lequin^1,3, Sabine Plasschaert³, Wybe van der Kemp¹, Hans Hoogduin¹, Dennis Klomp¹, Jannie Wijnen¹, and Evita Wiegers^1
1Department of Radiology, University of Medical Centre Utrecht, Utrecht, Netherlands, ²Magnetic Detection and Imaging Group, Technical Medical Centre, University of Twente, Enschede, Netherlands, ³Department of paediatric neuro-oncology, Princess Maxima Centre, Utrecht, Netherlands

APTw imaging is a potential imaging biomarker to assess treatment effects in brain tumours, especially at high field MRI (7T) due to improved signal-to-noise-ratio enabling the assessment of APTw values in heterogenous tumours. Embedding of APTw imaging in clinical decision making requires insight in the repeatability of APTw imaging. Therefore, we evaluated the repeatability of APTw imaging at 7T by using a phantom and in vivo in the human brain subjects. Repeatable and specific APTw maps were obtained at 7T, which facilitate the potential of detecting metabolic changes in brain tumours due to treatment.  

Clemens Stilianu¹, Christina Graf¹, Clemens Diwoky², Martin Soellradl¹, Armin Rund³, Moritz Zaiss⁴, and Rudolf Stollberger^1
1Medical Engineering, TU Graz, Graz, Austria, ²647 Institut für Molekulare Biowissenschaften, University of Graz, Graz, Austria, ³Institute for Mathematics and Scientific Computing, University of Graz, Graz, Austria, ⁴Department High-field Magnetic Resonance, Max Planck Institute Tübingen, Tübingen, Germany

We optimized CEST saturation pulse train using an optimal control framework and validated the simulation results on a preclinical scanner that allowed also Gold Standard continuous wave saturation. The optimized pulses almost reached the same saturation as the continuous wave pulse while addressing the allowed duty cycle and SAR limitations of clinical scanners. In measurements, the optimized pulses outperform state-of-the-art Gaussian pulses by over $$$47\%$$$.

Lukas Folle¹, Katharina Tkotz², Andrzej Liebert², Fasil Gadjimuradov¹, Lorenz Kapsner², Moritz Fabian³, Sebastian Bickelhaupt², David Simon⁴, Arnd Kleyer⁴, Gerhard Krönke⁴, Frank Roemer², Moritz Zaiss^3,5, Armin Nagel^2,6, and Andreas Maier^1
1Computer Science, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany, ²Institute of Radiology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany, ³Institute of Neuroradiology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany, ⁴Department of Internal Medicine 3, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany, ⁵Magnetic Resonance Center, Max-Planck-Institute for Biological Cybernetics, Tübingen, Germany, ⁶Division of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

The resolution of chemical exchange saturation transfer (CEST) magnetic resonance imaging is limited by physical constraints. To visualize metabolic processes of small structures using CEST in patients knees, an increased resolution is necessary. In this work, we compared trilinear interpolation and zero-filling to neural network-based approaches to estimate a high-resolution image given the corresponding low-resolution data. We could show that a substantial quantitative improvement using neural networks could be achieved for unsaturated images while maintaining a comparable CEST contrast. Generalization of the method to brain CEST MRI was achieved without retraining of the network.

Oliver Maier¹, Moritz Simon Fabian^2,3, Angelika Barbara Mennecke², Manuel Schmidt², Arnd Dörfler², Kristian Bredies⁴, Moritz Zaiss^2,3, and Rudolf Stollberger^1,5
1Institute of Medical Engineering, Graz University of Technology, Graz, Austria, ²Department of Neuro-radiology, University Clinic of Erlangen, Erlangen, Germany, ³Friedrich-Alexander-University, Erlangen, Germany, ⁴Institute of Mathematics and Scientific Computing, University of Graz, Graz, Austria, ⁵BioTechMed Graz, Graz, Austria

Chemical Exchange Saturation Transfer (CEST) enables characterization of tissue in vivo by measuring a z-spectrum. Quantitative separation of individual contributions to this spectrum is performed by fitting several Lorentzian shaped lines to the acquired data. Current implementations of the fitting procedure suffer from poor SNR and ambiguity of peaks lying close to each other. To this end, we propose to include a joint spatial regularization to the fitting process to counter the poor SNR and thus improve separation of individual peaks in the final reconstruction.

Stefano Casagranda¹, Christos Papageorgakis¹, Feriel Romdhane², Eleni Firippi¹, Timothé Boutelier¹, Laura Mancini^3,4, Moritz Zaiss⁵, Sotirios Bisdas^3,4, and Dario Livio Longo^2
1Department of Research & Innovation, Olea Medical, La Ciotat, France, ²Institute of Biostructures and Bioimaging (IBB), National Research Council of Italy (CNR), Torino, Italy, 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

This work provides a new denoising methodology for multi-acquisition magnetic resonance images (MRI) based on principal components analysis (PCA). We are proposing a new principal component selection criterion that identifies spatial information in the extracted component coefficients, leading to a better preservation of anatomical structures and pathological information. In addition, our adaptive filtering step allows us to further denoise the MRI data, rejecting persistent spatial noise from the extracted component coefficients. In our investigations the proposed method outperformed the eigenvalue based selection criteria on Amide Proton Transfer weighted CEST data.

Paul Samuel Jacobs¹, Ravi Prakash Reddy Nanga¹, Abigail Cember¹, Dylan M Tisdall², Sandhitsu Das³, John Detre^1,3, David Roalf⁴, and Ravinder Reddy^1
1CAMIPM, Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Radiology, University of Pennsylvania, Philadelphia, PA, United States, ³Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States, ⁴Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, United States

Dielectric pads were used to improve the contrast of volumetric (3D) gluCEST via enhanced homogenization of B₁ fields. Effective placement of the pads required additional coverage of the face due to their physical size to achieve the saturated B₁ strength necessary to recover the gluCEST signal from the anterior portions of the brain. The origin of gluCEST's need for high B₁ is discussed, and examples of 3D gluCEST images acquired with and without the use of the dielectric pads are provided and repeatability of the 3D gluCEST in the presence of pad placement was determined.

Alicia Cronin^1,2, Patrick Liebig³, Sarah Detombe⁴, Neil Duggal^1,4, and Robert Bartha^1,2
1Medical Biophysics, Western University, London, ON, Canada, ²Centre for Functional and Metabolic Mapping, Robarts Research Institute, London, ON, Canada, ³Siemens Healthcare GmbH, Erlangen, Germany, ⁴Clinical Neurological Sciences, University Hospital, London Health Sciences Centre, London, ON, Canada

Degenerative cervical myelopathy (DCM) is a degenerative disease of the spine that leads to compression and neurological dysfunction. Recovery after surgery can be impacted by hypoxia in the cord, however the magnitude of this effect is currently unknown. Chemical Exchange Saturation Transfer (CEST) can produce contrast related to tissue pH, an indicator of hypoxia, but the method works best at ultra-high fields. Performing CEST in the spinal cord is also complicated by respiratory and cardiac motion and cerebrospinal fluid flow. The purpose of this work was to optimize pH-weighted CEST imaging in the human spinal cord at 3 Tesla.

Angelika Barbara Mennecke¹, Katrin Khakzar¹, Alexander German¹, Kai Herz², Moritz Fabian¹, Andrzej Liebert³, Armin M. Nagel³, Frederik B. Laun³, Manuel Schmidt¹, Jürgen Winkler⁴, Arnd Dörfler¹, and Moritz Zaiss^1
1Neuroradiology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany, ²Max Planck Institute for Biological Cybernetics, Tübingen, Germany, ³Radiology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany, ⁴Neurology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany

The amide and rNOE CEST amplitudes are negatively correlated with age. Most prominently, the mean gray matter amide CEST amplitude decreases on average by 0.22 % per year of age in the cohort of our study.

Bonnie Lam¹, Mark Velasquez¹, Aaron J. Velasquez-Mao¹, Kevin Godines¹, Wissam AlGhuraibawi¹, and Moriel Vandsburger^1
1Bioengineering, University of California, Berkeley, Berkeley, CA, United States

We hypothesized that AAV2 capsids may generate endogenous CEST contrast similar to LRP. We tested this using NMR CEST under varying pH, density, biological transduction stage, across serotypes and mixed biological media. Subsequent experiments determined the pH-dependent exchange rate and optimized CEST saturation schemes for AAV contrast detection at 7T. The results of this study reveal that AAV capsids generate endogenous CEST contrast around 0.6-0.8ppm. Exchangeable protons are likely from serine and threonine residues on the AAV capsid. Based on calculated fast exchange rates, an optimized CEST saturation scheme generated robust CEST contrast in mixed biological media phantoms at 7T. 

Or Perlman¹, Jaume Coll-Font^1,2, Kai Herz^3,4, Moritz Zaiss^3,5, Christopher Nguyen^1,2,6, and Christian T. Farrar^1
1Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States, ²Cardiovascular Research Center, Cardiology Division, Massachusetts General Hospital, Charlestown, MA, United States, ³Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany, ⁴Department of Biomedical Magnetic Resonance, University of Tübingen, Tübingen, Germany, ⁵Department of Neuroradiology, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), University Hospital Erlangen, Erlangen, Germany, ⁶Health Science Technology, Harvard-MIT, Cambridge, MA, United States

The dynamics of creatine and phosphocreatine distributions provide an important means for assessing metabolic function. While CEST-weighted MRI allows for the imaging of metabolite alterations, it is affected by semisolid-MT, spillover, and T₁ contributions, and is typically analyzed on a two-dimensional image, given the inherently long acquisition times. Here, we performed 3D quantitative mapping of Cr and PCr concentrations in the human calf muscle at 3T, using a rapid snapshot-CEST protocol followed by apparent exchange-dependent relaxation (AREX) analysis. Significant (p<0.001) changes in the concentrations of both creatine and phosphocreatine were measured during exercise, in agreement with the literature.

Patrick Liebig¹, Maria Sedykh², Kai Herz^3,4, Yi-Cheng Hsu⁵, Moritz Fabian², Angelika Mennecke², Manuel Schmidt², Arnd Doerfler², and Moritz Zaiss^2,3
1Siemens Healthcare GmbH, Erlangen, Germany, ²Department of Neuroradiology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany, ³Magnetic Resonance Center, Max-Planck-Institute for Biological Cybernetics, Tuebingen, Germany, ⁴Department of Biomedical Magnetic Resonance, University of Tübingen, Tuebingen, Germany, ⁵MR Collaboration, Siemens Healthineers Ltd., Shanghai, China

CEST MRI suffers from long acquisition times and/or limited volume coverage. Here we suggest using a spatio-temporal variable density Poisson disk design for whole brain APTw snapshot CEST. This enabled us to acquire 1.3 mm isotropic whole brain APTw CEST maps in under 2 minutes. All the reconstruction and necessary adjustment steps were implemented within the scanner software, enabling a push-button B0-corrected CEST measurement.

Maryam Mozaffari¹, Nivin Nystrom², Alex Li², Miranda Bellyou², Timothy Scholl¹, and Robert Bartha^1
1Medical Biophysics, Western Univeristy-Robarts Reserch Institute, London, ON, Canada, ²Western Univeristy-Robarts Reserch Institute, London, ON, Canada

Our objective was to acidify rat C6 gliomas by inhibiting NHE1 with cariporide and to monitor the pH changes with AACID-CEST MRI. AACID-CEST MRI was successfully used to monitor changes in tumor pH_i over time after cariporide injection. Our results showed a pH decrease in both the tumor and the contralateral tissue following cariporide injection. CEST-MRI measurement of tumor response pH could help to enhance the efficacy of this treatment paradigm in different human malignancies.

Fang Frank Yu¹, Natalie M Bell¹, Elizabeth M Davenport^1,2, Spencer Bowen^1,2, Brendan James Kelley³, Ivan Dimitrov^2,4, Jochen Keupp⁵, and Elena Vinogradov^1,2
1Radiology, University of Texas Southwestern Medical Center, Dallas, TX, United States, ²Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States, ³Neurology, University of Texas Southwestern Medical Center, Dallas, TX, United States, ⁴Philips Healthcare, Gainseville, GA, United States, ⁵Philips Research, Hamburg, Germany

Alzheimer’s Disease (AD) is the leading cause of dementia, afflicting over 5 million Americans and 45 million people worldwide. We are developing CEST protocol for the characterization of abnormal protein accumulation and pathological molecular changes in AD. Our results indicate increased CEST in all frequency ranges, with the maximum around 2ppm. While preliminary, this data demonstrates CEST MRI is capable of clear differentiation between patients with AD and healthy individuals.