Zhenxiong Wang^1,2, Mehran Shaghaghi², Yiran Zhou¹, Wenzhen Zhu¹, and Kejia Cai^2
1Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, ²Departments of Radiology, Department of Bioengineering, and the Center for MR Research, University of Illinois at Chicago, Chicago, IL, USA, Chicago, IL, United States

In this study, we demonstrated that in vivo proton exchange rate MRI based on improved omega plot can serve as a novel and independent MRI contrast for assessing ischemic brain tissues of stroke patients.

Anup Singh^1,2, Ayan Debnath^1,3, Rakesh Kumar Gupta⁴, and Ravinder Reddy^3
1Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New Delhi, India, ²Biomedical Engineering, AIIMS, New Delhi, India, ³Radiology, University of Pennsylvania, Philadelphia, PA, United States, ⁴Radiology, Fortis Memorial Research Institute, Gurugram, India

CEST MRI provides high resolution mapping of molecules such as Glutamate, Creatine, labile proteins/peptide, etc. CEST MRI contrast computation using asymmetry analysis require interpolation of data at different frequency offsets for B0 inhomogeneity corrections. In this study, different interpolation methods such as polynomial, cubic, spline and smoothingspline were compared for B0 inhomogeneity correction of various CEST contrasts(GluCEST-w, APT-w, CrCEST-w) at different field strength (3T, 7T). The 2nd and 3rd degree polynomial interpolations provided better B0 inhomogeneity correction for in vivo data from human brain. Polynomial interpolations for APT-w also improved differentiation of high-grade-glioma and low-grade-glioma tumors at 3T.

Tao Jin^1
1University of Pittsburgh, Pittsburgh, PA, United States

Rapid multi-slice CEST MRI can be achieved by the immediate acquisition of multiple slices after a single irradiation pulse. However, the signals from the slices acquired after the 1st slice are contaminated by the T₁-relaxation relaxation effect. In this work, we propose a simple post-acquisition correction method to compensate for the relaxation effect in the multi-slice CEST signals.

Fabian Tobias Gutjahr^1,2, Simon Mayer², and Peter M Jakob^2
1Comprehensive Heart Failure Center, University Hospital Wuerzburg, Wuerzburg, Germany, ²Experimental Physics 5, University Wuerzburg, Wuerzburg, Germany

RACETE-FLEX is a combination of the novel RACETE-method and the spectroscopic FLEX method. RACETE is a method for imaging chemical exchange with positive contrast with concurrent water suppression. Combining the RACETE approach with the FLEX frequency labeling strategy leads to a high sensitivity exchangeable proton spectroscopy method.

Ayan Debnath¹, Manish Awasthi¹, Neha Vats¹, Rakesh Kumar Gupta², and Anup Singh^1,3
1Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New Delhi, India, ²Department of Radiology, 2Fortis Memorial Research Institute, Gurgaon, Haryana, India, ³Department of Biomedical Engineering, All India Institute of Medical Science, New Delhi, India

It is challenging to differentiate between intra-cranial mass lesions (ICMLs) due to similar appearance using conventional MRIs. Amide-proton-transfer-weighted(APT-w) MRI provides differentiation among ICMLs with lower sensitivity ad specificity. The accuracy of classification between neo-plastic mass lesions and infective mass lesions as well as differentiation between low-grade-glioma and high-grade-glioma improves by implementing machine learning classifier based on features from APT-w CEST MRI. An optimized support-vector-machine with 10-fold cross-validation and optimal set of features extracted using Random forest based feature selection provided high accuracy of around 90%. 

Quan Tao¹, Peiwei Yi¹, Zimeng Cai¹, Yingjie Mei², Zhifeng Chen¹, Ruiyuan Liu¹, Wufan Chen¹, and Yanqiu Feng^1
1School of Biomedical Engineering, Southern Medical University, Guangzhou, China, ²Philips healthcare, Guangzhou, China

Chemical exchange saturation transfer (CEST) MRI has been widely investigated for the early diagnosis of neurological diseases, such as brain tumor and neurodegenerative disorders. The goal of this study was to develop an imaging biomarker for the future intervention and treatment of PD in clinic. For such purpose, a novel radial-sampling steady-state CEST sequence based ultrashort echo time (UTE) readout was used to acquire the Z-spectrum in the mouse brain of subacute PD model induced by MPTP.

Karthik Kulanthaivelu¹, Sanita Raju², Jitender Saini¹, Atchayaram Nalini², Nishanth Sadashiva³, Shashank Hegde⁴, Narayana Krishna Rolla⁵, and Indrajit Saha^5
1Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Bengaluru, India, ²Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India, ³Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bengaluru, India, ⁴Philips Healthcare, Bengaluru, India, ⁵Philips Health Systems, Philips India Ltd, Bengaluru, India

Amide proton transfer imaging was investigated for its potential to discriminate tuberculomas from high-grade gliomas. The diagnosis was confirmed by histopathology, CSF examination or response to anti-tubercular therapy.  The MTR_asym value of the Tuberculomas (mean 2.32± 0.50 s.d.) was significantly lower than high-grade gliomas (mean 4.32±0.84s.d.). Lower MTR_asym values in tuberculomas are suggestive of relatively reduced mobile amide protons compared to the tumoral microenvironment. Perilesional elevated APT values in tuberculomas are a unique observation and may reflect a milieu of inflammation.

Lisa Loi¹, Ferdinand Zimmermann², Andreas Korzowski², Jan-Eric Meissner², Johannes Breitling², Peter Bachert², Mark Edward Ladd², Heinz-Peter Schlemmer¹, Sarah Schott³, Sebastian Bickelhaupt⁴, Steffen Goerke², and Daniel Paech^1
1Radiology, German Cancer Research Center, Heidelberg, Germany, ²Medical Physics in Radiology, German Cancer Research Center, Heidelberg, Germany, ³Gynecology, University Hospital Heidelberg, Heidelberg, Germany, ⁴German Cancer Research Center, Heidelberg, Germany

Compared to conventional dynamic contrast-enhanced MR-mammography, which is known to be significantly affected by the phase of the menstrual cycle, the menstrual cycle-related effect on APT CEST MRI in the human breast is still unknown. This is the first study investigating the influence of the menstrual cycle on APT CEST MRI in fibroglandular breast tissue of seven healthy premenopausal women. No significant signal intensity differences in fibroglandular breast tissue between the follicular and the luteal phase of the menstrual cycle were observed, which suggests that APT contrasts are comparable regardless of the phase of the menstrual cycle in premenopausal women.    

Lisa Loi¹, Ferdinand Zimmermann², Andreas Korzowski², Jan-Eric Meissner², Peter Bachert², Mark Edward Ladd², Heinz-Peter Schlemmer¹, Sebastian Bickelhaupt³, Steffen Goerke², Sarah Schott⁴, and Daniel Paech^1
1Radiology, German Cancer Research Center, Heidelberg, Germany, ²Medical Physics in Radiology, German Cancer Research Center, Heidelberg, Germany, ³German Cancer Research Center, Heidelberg, Germany, ⁴Gynecology, University Hospital Heidelberg, Heidelberg, Germany

Relaxation-compensated, fat-corrected and B1-corrected APT CEST MRI is a novel MR imaging technique that generates complementary information to conventional MR-mammography. In this study, the ability of this improved APT CEST metric was investigated in nine patients with newly diagnosed breast cancer. Compared to normal appearing fibroglandular breast tissue, significantly increased APT CEST signal intensities in breast cancer tissue were observed. Consequently, this MRI approach represents a contrast agent-free method that may enable a non-invasive differentiation of breast cancer and normal appearing breast tissue and, therefore, help to increase diagnostic accuracy in breast cancer imaging.

Mehran Shaghaghi¹ and Kejia Cai^1,2,3
1Radiology, University of Illinois - Chicago, Chicago, IL, United States, ²Bioengineering, University of Illinois - Chicago, Chicago, IL, United States, ³Center for MR Research, University of Illinois - Chicago, Chicago, IL, United States

We present a novel method to induced saturation-transfer-recovery steady-states for determining proton exchange (k_ex) with low saturation power, short duration, and hence negligible SAR deposition. Our previous study has demonstrated that omega plotting with direct saturation (DS) signal removed can be used to map k_ex of healthy brains in vivo. However, omega plot, based on steady-state saturation assumption, requires long scanning time and potential high SAR deposition, which makes it non-applicable for clinical studies. Our suggested method, validated by simulations and phantom imaging, shows great promise for in vivo proton exchange rate imaging and clinical applications. 

Catarina Rua¹, Sanne Kaalund², James B Rowe^2,3, Christopher T Rodgers¹, and Guy B Williams^1
1Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom, ²Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom, ³Medical Research Council Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, United Kingdom

The human cortical mantle has distinct non-uniform layers of gray matter. In this study we used ultra high-resolution MT-weighted imaging at 7T with varying mixing times to measure the transient effects of the magnetization suppression through the primary visual cortex (V1). The MT effect was monitored across different cortical depths to evaluate the effect of the macromolecular pool (MP) and myelination.

Julius Juhyun Chung¹, Geun Ho Im², Jung Hee Lee^2,3, Tao Jin¹, and Seong-Gi Kim^2
1Radiology, University of Pittsburgh, Pittsburgh, PA, United States, ²Center for Neuroscience Imaging Research, Suwon, Republic of Korea, ³Radiology, Samsung Medical Center, Seoul, Republic of Korea

CEST has been used as a way to monitor glucose transport as a way of studying uptake as well as permeability. However, signal is not solely affected by exchange but also osmolality shifts with significant intravenous dosage. Using MCAO, we study disparity between these two effects and how they may lead to obfuscate signal sources. With the injection of glucose after the onset of ischemia, +1.2 ppm , -1.2 ppm, and MTR asymmetry curves behave quite differently. Both sides of the spectrum must be scrutinized to have a better picture of what is going on during glucose dosage.

Yu-Wen Chen¹ and Dennis Wenhan Hwang^2
1, IBMS N123, Academia Sinica, Taipei, Taiwan, ²IBMS, Academia Sinica, Taipei, Taiwan

Dynamic glucose-enhanced (DGE) images, detected by CEST, was used to provide direct information on glucose metabolism. It also provides the spatial distribution of the metabolic processes. The time-dependent glucose concentration variation in the striatum of HD shows that the glucose uptake in the HD mice striatum decreases with age. The groups of older than 9-11 weeks HD mice were easy to find the symptoms of HD, and their glucose uptaking also show a significant decrement. By contrast, WT mice show a mild decrease in the glucose uptake for the mice with similar age.  

Jianhua Mo¹, Xiang Xu^2,3, Xianglong Wang¹, Linda Knutsson^2,4, Akansha A Sehgal^2,3, Peter C. M. van Zijl^2,3, and Zhibo Wen^1
1Zhujiang Hospital, Southern Medical University, Guangzhou, China, ²Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ³F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, United States, ⁴Department of Medical Radiation Physics, Lund University, Lund, Sweden

Dynamic glucose-enhanced (DGE) MRI has shown potential for imaging glucose delivery and blood brain barrier permeability. Previous reports focused on the technical development of DGE and only a few clinical brain tumor cases have been reported. Here we incorporated the current DGE protocol into our routine MRI examination at 3T and performed a small-scale clinical observational study on patients with different types of brain tumors. Despite the technical challenges of DGE at clinical scanners, we observed different (non)-enhancement patterns with various brain tumor types.

Dushyant Kumar¹, Ravi Prakash Reddy Nanga¹, Deepa Thakuri¹, Abigail Cember¹, Neil Wilson², Hari Hariharan¹, and Ravinder Reddy^1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Siemens Medical Solutions USA Inc, Malvern, PA, United States

Creatine CEST is a relatively new imaging technique, with the proven potential to assess the systemic energy deficiency in form of delayed creatine recovery in exercised skeletal muscles. However, this 2D method still suffers from limited volume coverage in slice encoding direction. Since the distribution of disease in many musculoskeletal disorders may vary across the muscle, there is a need to increase coverage in slice encoding direction. Towards this goal, we demonstrate the feasibility of 3D CrCEST, while still maintaining 30s time resolution necessary to capture underlying dynamics and also demonstrate its repeatability using data from five healthy volunteers.

Tatsuhiro Wada¹, Chiaki Tokunaga¹, Osamu Togao², Masami Yoneyama³, Yasuo Yamashita¹, Kouji Kobayashi¹, Toyoyuki Kato¹, and Hidetake Yabuuchi^4
1Division of Radiology, Department of Medical Technology, Kyushu University Hospital, Fukuoka, Japan, ²Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, ³Philips Japan, Fukuoka, Japan, ⁴Department of Health Sciences, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan

Multi-slice chemical exchange saturation transfer (CEST) imaging is difficult to use for clinical studies because data acquisition of the full z-spectrum is time-consuming. To accelerate the scan time for obtaining multi-slice CEST imaging, we applied the compressed sensing (CS) and sensitivity encoding (SENSE) technique (CS-SENSE) to 3D CEST imaging. The 3D CEST imaging combined with CS-SENSE was obtained without reducing the image contrast of the 2D CEST imaging. Moreover, 10 slice CEST images could be acquired in approximately 7 minutes including B0 map. 3D CEST imaging combined with CS-SENSE was shown to be useful for clinical study.

Fabian Tobias Gutjahr^1,2, Simon Mayer², and Peter M Jakob^2
1Comprehensive Heart Failure Center, University Hospital Wuerzburg, Wuerzburg, Germany, ²Experimental Physics 5, University Wuerzburg, Wuerzburg, Germany

RACETE is a novel method for positive contrast imaging of chemical exchange. In this work the RACETE sequence is extended to allow steady state imaging by interleaving the preparation with small flip angle RACETE read-outs. It can be shown that the efficiency of the steady state RACETE is improved over the equilibrium RACETE. This is an important step towards speeding up the acquisition process to make RACETE a viable option for future in vivo experiments.

Anina Seidemo¹, Malte Knutsson², Patrick M. Lehmann¹, Pia C. Sundgren^3,4, Anthony Aletras^5,6, Peter C.M. van Zijl^7,8, and Linda Knutsson^1,7
1Department of Medical Radiation Physics, Lund University, Lund, Sweden, ²Procivitas, Malmö, Sweden, ³Department of Diagnostic Radiology, Lund University, Lund, Sweden, ⁴Lund University Bioimaging Center, Lund University, Lund, Sweden, ⁵Department of Clinical Physiology, Clinical Sciences, Lund University and Lund University Hospital, Lund, Sweden, ⁶Laboratory of Computing and Medical Informatics, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece, ⁷Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁸F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

GlucoCEST (chemical exchange saturation transfer imaging using glucose as a contrast agent) has shown potential in tumor imaging. However, glucose enters cells and is rapidly metabolized, leading to disappearance of the glucoCEST signal over time. Inulin, a polysaccharide, is non-toxic and acts like an intravascular tracer when injected intravenously. A phantom including both glucose and inulin at different pH and concentrations was scanned at 3T to investigate the potential of inulin as a CEST agent. This study indicates that inulin shows CEST contrast comparable to glucose on a per-OH-unit basis and has potential as a biodegradable CEST agent.

Ravi Prakash Reddy Nanga¹, Elizabeth A Rosenfeld², Deepa Thakuri¹, Mark Elliott¹, Ravinder Reddy¹, and Diva D De Leon^2
1Radiology, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA, United States, ²Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA, United States

Hyperinsulinism/Hyperammonemia (HI/HA) syndrome is an orphan disease characterized by fasting and protein-induced hypoglycemia, hyperammonemia, and has high prevalence of epilepsy, developmental delays, and learning disabilities. Understanding the mechanism involved in brain phenotype remains limited. Glutamate weighted chemical exchange saturation transfer (GluCEST) imaging was used to spatially map the glutamate levels of hippocampus. We observed a higher GluCEST contrast in the hippocampus of some of these subjects following a unilateral pattern. This preliminary study demonstrates for the first time the application of GluCEST MRI for studying the abnormal function of glutamate dehydrogenase (GDH) enzyme activity in human subjects with HI/HA syndrome.

Shu Zhang¹, Abeer H. Abdelhafez², Jong Bum Son³, Benjamin C. Musall³, Mitsuharu Miyoshi⁴, Xinzeng Wang⁵, Ken-Pin Hwang³, Gaiane M. Rauch², Jingfei Ma³, and Mark D. Pagel^1
1Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, United States, ²Abdominal Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, United States, ³Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States, ⁴Global MR Applications & Workflow, GE Healthcare Japan, Tokyo, Japan, ⁵Global MR Applications & Workflow, GE Healthcare, Houston, TX, United States

In our ongoing study of 13 completed patients, we compared two saturation power levels (2.0 μT vs. 0.9 μT) and two analysis methods (MTR_asym vs. Lorentzian line fitting) of CEST for assessing treatment response to neoadjuvant chemotherapy of triple-negative breast cancer (TNBC). A consistently decreasing trend of the CEST signals was observed with the longitudinal treatment when a higher saturation power of 2.0 μT was used with the amide MTR_asym analysis method. In contrast, the same trend was observed when a lower saturation power of 0.9 μT was used for the Lorentzian line fitting analysis method.

Shu Zhang¹, F. William Schuler¹, Tianzhe Li¹, Ken-Pin Hwang², Mitsuharu Miyoshi³, Xinzeng Wang⁴, and Mark D. Pagel^1
1Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, United States, ²Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States, ³Global MR Applications & Workflow, GE Healthcare Japan, Tokyo, Japan, ⁴Global MR Applications & Workflow, GE Healthcare, Houston, TX, United States

Many clinical CEST MRI methods have been developed and disseminated during the last few years, and the expansion of clinical CEST MRI will likely continue.  A common phantom is needed to standardize the development and implementation of CEST methods. In this study, we have developed a clinical CEST MRI phantom with high-quality gelatin to test a range of concentrations, pH values, and T1 relaxation times. The experimental conditions of the CEST saturation and various post-saturation acquisition methods can be tested. This standard phantom can be used to support many applications within the CEST MRI research community.

Joseph H. C. Lai¹, Jianpan Huang¹, Xiongqi Han¹, Jiadi Xu^2,3, and Kannie W. Y. Chan^1,2
1Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, Hong Kong, ²Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ³F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, United States

There is an urgent need to develop an efficient and noninvasive methods to diagnose AD at an early stage. Artificial neural network (ANN) is a powerful model for prediction and classification of diseases, thus, it has been applied to facilitate prognosis and diagnosis. We propose to apply ANN based on chemical exchange saturation transfer (CEST) MRI at 3T to detect AD. Our phantom and AD mouse results showed that the trained ANN was able to identify AD from age-matched wild-type (WT) mice with high accuracy, which could provide valuable information for AD diagnosis.

Quan Tao¹, Peiwei Yi¹, Zimeng Cai¹, Yingjie Mei², Zhifeng Chen¹, Ruiyuan Liu¹, Wufan Chen¹, and Yanqiu Feng^1
1School of Biomedical Engineering, Southern Medical University, Guangzhou, China, ²Philips healthcare, Guangzhou, China

Chemical exchange saturation transfer (CEST) as a novel molecule MRI technique, was approved to detect some diseases, like tumor grading, kidney injure, osteoarthritis (OA) and etc. However, it is crucial to purify the CEST signal. In this study, we explored the perfusion contribution to the CEST signal acquired by a UTE-CEST sequence.

Ryan T Oglesby^1,2, Wilfred W Lam², and Greg J Stanisz^1,2
1Medical Biophysics, University of Toronto, Toronto, ON, Canada, ²Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada

This study demonstrates the in vitro characterization of tryptophan, 5-HTP, serotonin (5-HT), 5-HIAA (all members of the serotonin biosynthesis pathway), and melatonin at precise pH, temperature, and concentration. At pH 5.5, CEST contrast between 0.6 and 1.9 ppm, originating from the NH₃⁺ side chain, is exhibited by tryptophan, 5-HTP, and 5-HT. All five molecules at pH 7.4 exhibit CEST contrast between 5.11 and 5.47 ppm, originating from the NH proton on the indole ring. If sensitive enough in vivo, these measurements could improve the objectivity of clinically diagnosed psychiatric disorders and could provide a new biological understanding of serotonergic dysfunction.

Jan-Rüdiger Schüre¹, Manoj Shrestha², Eike Steidl³, Ralf Deichmann², Elke Hattingen³, Marlies Wagner³, and Ulrich Pilatus^3
1Neuroradiology, Goethe University Hospital, Frankfurt am Main, Germany, ²Brain Imaging Center (BIC), Frankfurt am Main, Germany, ³Goethe University Hospital, Frankfurt am Main, Germany

We present a fast 2D EPI multislice sequence that allows to acquire the APT-CEST contrast in 16 slices within 8 seconds. The fast CEST-EPI sequence was compared in vitro and in vivo with a steady-state CEST sequence, where the saturation is applied for 4 s for each frequency offset. The reduced acquisition time in the fast sequence can be used for measurement repetitions or additional MR examinations (e.g. MR spectroscopic imaging).

Jie Liu¹, Zongwei Xu¹, Qi Liu², Hui Liu², Jian Xu², 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, ²United Imaging Healthcare America, Houston, TX, United States

Chemical exchange saturation transfer (CEST) using iodinated agents has been tested for extracellular pH imaging on high-field animal scanners. However, the reliability in the pH quantification on low magnetic strengths remains elucidated. In this study, CEST imaging was performed on iobitridol phantom twice with a three-day interval at 3T. pH was quantified by ratioing iobitridol CEST effects at 5.6 ppm under B₁ of 1.0 and 2.0 μT. Results show accurate pH quantification in both scans. Good consistency of paired measures was observed between the two scans, suggesting the reliability of the method and its potential clinical applicability at 3T.

Philip S. Boyd¹, Johannes Breitling¹, Mark E. Ladd¹, Peter Bachert¹, and Steffen Goerke^1
1Division of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

In this study, we developed an absolute pH mapping method based on endogenous amide CEST-MRI which simultaneously compensates for concentration changes, the semi-solid magnetization transfer, and spillover dilution. This was realized by a ratiometric approach of two different B₁ in combination with the inverse metric and polynomial Lorentzian-fitting of the amide signal. Compensation for concomitant effects was theoretically demonstrated in simulations and verified experimentally in protein model solutions and porcine brain lysates. Consequently, amide signal-based absolute pH mapping is now in principle also reliably applicable for tumor imaging which was previously prevented by the concomitant effects.

Richard Dortch^1
1Division of Neuroimaging Research, Barrow Neurological Institute, Phoenix, AZ, United States

MTR offers a measure of myelin content, but is also sensitive to non-physiological parameters. Quantitative MT methods remove these confounding effects; however, they require long scan times and complicated acquisition/analysis strategies. Selective inversion recovery is a simple method that may address many of these limitations, but requires long scan times and specialized inversion recovery sequences. The issue of long scan times was previously addressed through optimized sampling schemes. The need for specialized sequences is addressed herein by using a standard MP-RAGE sequence and modifying the SIR signal model. The resulting “turnkey” approach was tested numerically and applied in the brain.  

Sebastian Mueller¹, Felix Glang¹, Klaus Scheffler^1,2, and Moritz Zaiss^1,3
1High-field Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tuebingen, Germany, ²Department of Biomedical Magnetic Resonance, Eberhard Karls University Tuebingen, Tuebingen, Germany, ³Department of Neuroradiology, University Hospital Erlangen, Erlangen, Germany

The pH value is of major importance for most physiological processes and may change due to altered metabolism in pathologies. In the present work, we exploit the inherent dependency of CEST MR data on pH with a new approach: train neural networks to map voxel-by-voxel from multi-B₁⁺ CEST spectra to pH value. Measurements were performed in homogenate of pig brain tissue at 9.4T ultra high field. Prediction of absolute pH values was possible and predictions were stable against inhomogeneity in B₁⁺. We hope this proof of concept might be a first small step towards high-resolution 3D pH maps in vivo.

Dennis Kleimaier¹, Steffen Goerke², Cordula Nies³, Moritz Zaiss⁴, Patrick Kunz⁵, Eric Gottwald³, and Lothar R. Schad^1
1Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany, ²Division of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, ³Institute of Functional Interfaces, Karlsruhe Institut of Technology, Karlsruhe, Germany, ⁴Neuroradiology, University of Erlangen-Nürnberg, Erlangen, Germany, ⁵Division of Functional Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany

Chemical exchange saturation transfer of the relayed nuclear Overhauser effect(rNOE) enables detection of mobile protein protons via their exchange with the water signal. Recent studies have shown a close relationship between the rNOE-signal and the protein conformation. This study used the -3.5ppm rNOE-signal to monitor the heat shock response of HepG2 cells in a microcavity array-based bioreactor system. A significant drop of the rNOE-signal to 92.4±1.3% and a slow, steady increase of the rNOE-signal for 136.1±13.6min after heat shock were observed. Therefore, the rNOE-signal in CEST spectroscopic imaging is a sensitive readout for the cellular heat shock response.

Huan Minh Luu¹, Dong-Hyun Kim¹, Jae-Woong Kim¹, Seung-Hong Choi², and Sung-Hong Park^1
1Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea, ²Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea

Quantitative magnetization transfer (qMT) imaging overcomes the drawbacks of traditional MT imaging by producing more quantitative parameters. However, data acquisition and processing can be time-consuming, which limits its usage. In this study, an artificial neural network, qMTNet, is proposed to accelerate both the acquisition and fitting of qMT data. For data acquired from both conventional and inter-slice acquisition strategies, our approach demonstrated consistent fitting results with those from a previous dictionary-driven fitting method. The network reduces the time for both data acquisition and qMT fitting by a factor of 3 and 5000 times, respectively, compared to the conventional methods.

Roya Afshari^1,2, Francesco Santini^1,2, Rahel Heule³, Craig H. Meyer⁴, Josef Pfeuffer⁵, and Oliver Bieri^1,2
1Division of Radiological Physics,Department of Radiology, University Hospital Basel, University of Basel, Basel, Switzerland, ²Department of Biomedical Engineering, University of Basel, Basel, Switzerland, ³High Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Tübingen, Germany, ⁴Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, United States, ⁵Siemens Healthcare, Application Development, Erlangen, Germany

Magnetization transfer (MT), reflecting the exchange of magnetization between mobile and bound protons, has shown good potential for the diagnosis and prognosis of various neurological disorders, such as multiple sclerosis. Frequently, MT effects are assessed by measuring the contrast between two scans performed with and without saturation of the bound pool protons. Evidently, saturation is affected by B₁ inhomogeneity and should be accounted for. In this work, we report on a very rapid one-minute whole-brain magnetization transfer ratio (MTR) imaging method offering intrinsic B₁-correction.

Jun Chen Li^1,2, Yu Liu¹, Yongsheng Chen³, Zhijia Jin¹, Naying He¹, Weibo Chen⁴, Fuhua Yan¹, and Ewart Mark Haacke^1,5,6
1Radiology, Ruijin Hospital, Shanghai, China, ²Radiology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, China, ³Neurology, Wayne State University, Detroit, MI, United States, ⁴Philips Healthcare, Shanghai, China, ⁵Radiology, Wayne State University, Detroit, MI, United States, ⁶Biomedical Engineering, Wayne State University, Detroit, MI, United States

Magnetization transfer contrast (MTC) imaging has been used to study neuromelanin (NM) in Parkinson’s disease. By suppressing the background tissue using an MTC pulse in a T1W sequence, the NM becomes visible, supposedly because of its reduced T1. However, we show using STAGE (strategically acquired gradient echo) imaging with/without an MTC pulse that this is not the reason for its visibility. Rather, it is the increased water content relative to surrounding tissue that keeps the signal high. Using the appropriate choice of flip angles and resolution, the NM contrast on MTC images can be significantly increased.

Gopal Varma¹, Hemant Varma², Cody Callahan¹, Olivier M Girard³, Guillaume Duhamel³, Aaron K Grant¹, and David C Alsop^1
1Division of MR Research, Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States, ²Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States, ³CNRS, CRMBM, Aix-Marseille Univ, Marseille, France

Quantitative magnetization transfer (MT) was carried out using inhomogeneous MT (ihMT) data, following optimization of an acquisition protocol. The optimized protocol was applied in ex-vivo brain tissue from a donor with multiple sclerosis (MS), as well as tissue containing an MS plaque. Parameter maps output from quantitative MT showed white and grey matter contrast, as well as a lower restricted or bound pool fraction in the area of the MS plaque from histology. Results from quantitative MT using ihMT were compared with those using selective inversion recovery, as well as quantitative outputs from diffusion tensor MRI.

Christopher D Rowley^1,2, Zhe Wu^2,3, Ilana R. Leppert², Jennifer S.W. Campbell ², David A. Rudko^2,4,5, G. Bruce Pike⁶, and Christine L. Tardif^1,2,4
1Neurology and Neurosurgery, McGill University, Montreal, QC, Canada, ²McConnell Brain Imaging Center, McGill Unversity, Montreal, QC, Canada, ³Techna Institute, University Health Network, Toronto, ON, Canada, ⁴Department of Biomedical Engineering, McGill Unversity, Montreal, QC, Canada, ⁵Department of Neurology and Neurosurgery, McGill Unversity, Montreal, QC, Canada, ⁶Hotchkiss Brain Institute and Departments of Radiology and Clinical Neuroscience, University of Calgary, Calgary, AB, Canada

Inhomogeneous magnetization transfer (ihMT) contrast in the brain has been reported to be a myelin-specific biomarker, but can be impacted by B₁ inhomogeneities, reducing its accuracy. ihMT equations incorporating B₁ correction assume a single excitation and readout, either a k-space line or plane, per saturation module. Here we use an arbitrary number of readout segments collected after an MT saturation preparation module. T₁ and B₁ variations are included in the signal equations to increase specificity of the contrast to the microstructure. The resulting implementation yields a balance between acquisition efficiency and contrast resolution for different brain imaging applications.

Melany McLean¹, R. Marc Lebel^1,2, M. Ethan MacDonald¹, Mathieu Boudreau^3,4, and G. Bruce Pike^1
1Departments of Radiology and Clinical Neuroscience, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada, ²GE Healthcare, Calgary, AB, Canada, ³Montreal Heart Institute, Université de Montreal, Montreal, QC, Canada, ⁴NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, QC, Canada

Quantitative magnetization transfer (qMT) is a Z-spectrum based imaging technique used to study white matter. The need to acquire many images with unique RF saturation pulses leads to long acquisition times. We aim to shorten qMT imaging times using a sparseSENSE technique that combines parallel imaging and compressed sensing to reduce the amount of acquired data. Retrospectively undersampled data was reconstructed for a range of acceleration factors using wavelet and total variation sparsifying domains. Pool size ratio (F) maps were accelerated by a factor of 4×, and acceleration factors of 8-12× may be possible in future work. 

Gabriele Bonanno^1,2,3, Tom Hilbert^4,5,6, Arun Joseph^1,2,3, Emilie Mussard^4,5,6, Christoph Forman⁷, Gian Franco Piredda^4,5,6, and Tobias Kober^4,5,6
1Advanced Clinical Imaging Technology, Siemens Healthcare AG, Bern, Switzerland, ²Translational Imaging Center, sitem-insel AG, Bern, Switzerland, ³Departments of Radiology and Biomedical Research, University of Berne, Bern, Switzerland, ⁴Advanced Clinical Imaging Technology, Siemens Healthcare AG, Lausanne, Switzerland, ⁵Department of Radiology, University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland, ⁶LTS5, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ⁷Magnetic Resonance, Siemens Healthcare GmbH, Erlangen, Germany

Magnetization Transfer Ratio (MTR) imaging may be a valuable tool for the diagnosis and follow-up of demyelinating diseases. However, MTR maps require long scan times for whole-brain coverage and high isotropic resolution. We present a novel MTR imaging method based on a spiral-phyllotaxis Cartesian FLASH sequence and compressed sensing, called MTRSparse, and compare it to fully sampled and parallel-imaging-accelerated acquisitions in healthy volunteers. MTRSparse showed good contrast and similar MTR values in comparison to the reference method with up to 87% reduction in acquisition time. This can help facilitate implementation of MTR imaging in the clinical practice.

Ayan Debnath^1,2, Hari Hariharan², Ravi Prakash Reddy Nanga², Ravinder Reddy², and Anup Singh^1,3
1Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New Delhi, India, ²Center for Magnetic Resonance & Optical Imaging, University of Pennsylvania, Philadelphia, PA, United States, ³Department of Biomedical Engineering, All India Institute of Medical Science, New Delhi, India

Asymmetry in MT causes erroneous GluCEST computation. The study focuses on removal of MT effects from Z-spectra for better quantification of GluCEST contrast using in-vivo human volunteer at 7T and rat brain with tumor at 9.4T. Different lineshapes for modelling and fitting broad MT spectrum has been compared. Lorentzian lineshape provided significant difference between GluCEST contrast before and after MT removal and also preserves the gray-matter to white-matter glutamate concentration ratio validated with MR spectroscopic based estimation. After removal of MT effect using Lorentzian lineshape, the specificity of GluCEST to glutamate concentration increases which can helps better diagnosis of diseases.

Manuel Taso¹, Fanny Munsch¹, Arnaud Guidon², Olivier M. Girard³, Guillaume Duhamel³, David C. Alsop¹, and Gopal Varma^1
1Division of MRI research, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States, ²Global MR Applications and Workflow, GE Healthcare, Boston, MA, United States, ³CRMBM, Aix-Marseille Univ, CNRS, Marseille, France

While the original inhomogeneous magnetization transfer (ihMT) implementations for myelin imaging relied heavily on single-slice imaging, recent developments have enabled volumetric acquisitions using rapid gradient-echo sequences. But in vivo volumetric spin-echo acquisitions have been unexplored so far although they provide a theoretical advantage over GRE. We report here the implementation of a variable-density FSE with Compressed-Sensing for time-efficient volumetric ihMT imaging with high SNR. Provisional experiments show promising results even at high acceleration rates while also identifying areas for potential improvement, paving the way for future use of ihMT FSE for whole brain and potentially spinal cord imaging. 

Jianpan Huang¹, Xiongqi Han¹, Lin Chen^2,3, Xiang Xu^2,3, Peter C. M. van Zijl^2,3, Jiadi Xu^2,3, and Kannie W. Y. Chan^1,2
1Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China, ²Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, ³F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, United States

Relayed nuclear Overhauser enhancement (rNOE) imaging indirectly detects the aliphatic groups of biomolecules and can be used to diagnose protein or lipid signals and related pathology involving such signals. Current rNOE imaging has been studied mainly on high-field MRI scanners (≥7T). When implementing the technique on low clinical MRI fields (≤3T), rNOE contrast is more obscured by semisolid magnetization transfer contrast (MTC) and water direct saturation (DS). We developed a pulsed-CEST/MT method at 3T MRI that can suppress MTC and DS efficiently, not compromising rNOE contrast.

David C Alsop¹, Fanny Munsch¹, Gopal Varma¹, Olivier Girard², and Guillaume Duhamel^2
1Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States, ²CRMBM, Aix Marseille Univ, CNRS, Marseille, France

Methods for quantification of Inhomogeneous Magnetization Transfer (ihMT), are not yet well established. This is especially true for ihMT prepared sequences such as ihMT MPRAGE, where no steady state solution is available. Here we adapt the MTsat approach to quantification of MT and ihMT in an MPRAGE sequence.

Kimberly L. Desmond^1
1Research Imaging Centre, CAMH, Toronto, ON, Canada

Single point magnetization transfer (MT) is a quantitative method which reduces the number of unknowns in the MT signal equation by fixing tissue parameters which are effectively constant such that the macromolecular proton fraction (MPF) is the only remaining variable. In this work, the nonlinear signal equation describing single point MT was inverted to obtain an analytic expression for MPF as a function of observed normalized signal (MT_∆/MT₀). This enables rapid computation of MPF maps from matrix operations performed on the 3D images of the MT-weighted image (MT_∆), the MT reference image, (MT₀), and separately acquired T1 and B1 maps. 

Dvir Radunsky¹, Tamar Blumenfeld-Katzir¹, and Noam Ben-Eliezer^1,2,3
1Bio-medical Engineering, Tel Aviv University, Tel Aviv, Israel, ²Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel, ³Center for Advanced Imaging Innovation and Research (CAI2R), New-York University Langone Medical Center, New York, NY, United States

Mapping of T₂ values is highly valuable for a wide range of applications. Still, accurate mapping is challenging due to the inherent bias of rapid Multi-Echo Spin-Echo (MESE) protocols by stimulated echoes, and also by magnetization transfer (MT). In this work, we investigate the different effects of macromolecular-driven MT (MT_SAT) and direct water saturation (MT_DIR) mechanisms on MESE signals, and their respective influence on T₂ values. The investigation includes quantitative MT measurements between protocols with different scan settings and protocol schemes, aiming to isolate the individual roles of MT_SAT and MT_DIR.

Leedan Murray¹, Wendy Oakden¹, Wilfred W. Lam¹, and Greg J. Stanisz^1
1Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada

The response to radiation treatment of DU145 prostate tumour xenografts was studied by comparing magnetization transfer-weighted Z-spectra before and after treatment. ROIs were drawn in homogenous sections of the tumour and analyzed based on corresponding TUNEL histology images. MTR decreased more than 1 week post-treatment in tumours that responded to treatment but was unchanged for non-responding tumours. The technique introduced in this study could potentially introduce a non-invasive way of determining treatment efficacy based on tumour necrosis/apoptosis.

Elles Elschot¹, Lieke van den Wildenberg¹, Vitaly Khlebnikov¹, Dennis Klomp¹, and Jannie Wijnen^1
1Radiology Department, UMC Utrecht, Utrecht, Netherlands

This study investigates the relation between B₁⁺ and signal amplitude of the APT and MT exchange pools in CEST MRI. We examined 19 breast cancer patients that underwent NAC treatment with CEST MRI at 7T. The data indicates evidence for an extra exchanging pool with strong B₁ dependence, that is more abundant in tumor tissue compared to healthy tissue. By identifying the exchanging components in this pool, a new biomarker for tumor tissue could be found and used to understand changes in response to NAC early during treatment.

Hyunyeol Lee¹, Dongyeop Han², Cheng-Chieh Cheng¹, and Felix W Wehrli^1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Electrical and Electronic Engineering, Yonsei University, Seoul, Korea, Republic of

The relaxation parameter R2’ characterizes susceptibility-induced voxel signal modulations, for example, in the presence of deoxygenated hemoglobin in brain microvasculature or iron deposits in deep gray matter structures. Current R2’ measurement methods build on a spin-echo sequence configuration, and hence require impractically long scan time for volumetric 3D R2’ mapping. Furthermore, large susceptibility gradients around air/tissue interfaces result in signal distortions with increasing echo times, thus making it challenging to achieve accurate R2’ estimation in deep GM regions. Here, we propose an alternating, 3D z-shimmed, unbalanced steady-state-free-precession (SSFP) technique for rapid and B0-corrected R2’ mapping in the human brain. 

Renat Sibgatulin¹, Daniel Güllmar¹, Andreas Deistung², Stefan Ropele³, and Jürgen Rainer Reichenbach^1,4,5,6
1Medical Physics Group, Institute of Diagnostic and Interventional Radiology, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany, ²Department of Radiology, University Hospital Halle (Saale), Halle, Germany, ³Department of Neurology, Medical University of Graz, Graz, Austria, ⁴Michael Stifel Center Jena for Data-Driven and Simulation Science, Friedrich Schiller University Jena, Jena, Germany, ⁵Abbe School of Photonics, Friedrich Schiller University Jena, Jena, Germany, ⁶Center of Medical Optics and Photonics, Friedrich Schiller University Jena, Jena, Germany

The effective transverse relaxation rate (R₂^*) is increasingly used in quantitative MRI, due to its sensitivity to iron and myelin content of the tissue. Separating the contributions from both sources is of particular interest in relation to multiple sclerosis. This work attempts to factor out contribution from myelin using orientation information derived from dMRI, and magnetization transfer saturation (MTS). Application of such correction to a group of multiple sclerosis patients and a control group, suggests that sensitivity of R₂^* to iron might be improved by accounting for fiber orientation in WM, while incorporation of MTS might not show clear benefit.

Véronique Fortier^1,2 and Ives R. Levesque^1,2,3
1Medical Physics Unit, McGill University, Montreal, QC, Canada, ²Biomedical Engineering, McGill University, Montreal, QC, Canada, ³Research Institute of the McGill University Health Centre, Montreal, QC, Canada

The R₁ relaxation rate of fat is a promising biomarker for mapping tissue oxygenation. Existing techniques to map fat R₁ are limited to single-voxel or 2D imaging with long scan times. To address these limitations, this work presents a 3D technique to map fat R₁ using a fat-water-separated variable flip angle (VFA) approach. The sensitivity of this technique to oxygenation variations was evaluated in a phantom. The results showed that fat R₁ can be measured using a technique based on 3D VFA at 3 T and is feasible for MR-oximetry.

Véronique Fortier^1,2 and Ives R. Levesque^1,2,3
1Medical Physics Unit, McGill University, Montreal, QC, Canada, ²Biomedical Engineering, McGill University, Montreal, QC, Canada, ³Research Institute of the McGill University Health Centre, Montreal, QC, Canada

The T₁ relaxation of triglyceride molecules is of interest for fat-water separation and fat quantification. A better understanding of the T₁ of fat could benefit modeling techniques for applications in MR-oximetry and fatty liver disease. In this work, the T₁ relaxation and its dependence on fat content was evaluated for five spectral peaks present in triglyceride molecules, over a range of fat fractions in a homogeneous fat-water mixture. The T₁ of water in mixture was also studied. A model is proposed to describe the two-pool relaxation in a fat-water mixture as a function of the fraction of each pool.  

Hyeong-Geol Shin¹, Se-Hong Oh², Sooyeon Ji¹, Jieun Lee¹, Woojin Jung¹, Eun-Jung Choi¹, and Jongho Lee^1
1Department of Electrical and Computer Engineering, Seoul National University, Seoul, Korea, Republic of, ²Biomedical Engineering, Hankuk University of Foreign Studies, Yongin, Korea, Republic of

In this work, we investigated the effects of initial parameter guess on non-linear least square (NLLS) method for myelin water imaging (MWI). We demonstrated that an inappropriate initial guess induces error in MWI and proposed a multi-seed algorithm to reduce the initial guess-dependent error. To do so, we applied the multi-seed MWI to synthetic and in-vivo data and compared the outcomes with the conventional algorithm (i.e., single-seed MWI). MWI results estimated by the multi-seed algorithm showed better agreement with the model than the single-seed algorithm, suggesting a potential solution to mitigate the ill-posed condition of MWI.

Martin Soellradl¹, Johannes Strasser¹, Stefan Ropele¹, and Christian Langkammer^1
1Department of Neurology, Medical University of Graz, Graz, Austria

Intravoxel dephasing due to macroscopic field variations along the slice-selective direction z can be compensated by application of compensation gradients in z-direction (“z-shimming”). Compensation gradients applied between echo acquisition allow to estimate R2* also in areas with strong field gradients. However, if equally strong compensation gradients are applied in each slice the signal dephases in homogenous areas. We therefore propose an adaptive method where slice-specific compensation gradients are estimated for each slice from a fast pre-scan. With the proposed approach improved R2*-maps, compared to constant compensation gradient strategies, with higher SNR and accuracy can be achieved.

Christa Müller-Axt^1,2, Cornelius Eichner¹, Louise Kauffmann^1,3, Pierre-Louis Bazin^1,4, Henriette Rusch⁵, Markus Morawski⁵, Alfred Anwander¹, and Katharina von Kriegstein^2
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, ²Faculty of Psychology, Technical University of Dresden, Dresden, Germany, ³LPNC, Grenoble Alpes University, Grenoble, France, ⁴Integrative Model-based Cognitive Neuroscience Research Unit, Department of Psychology, University of Amsterdam, Amsterdam, Netherlands, ⁵Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig, Germany

The human lateral geniculate nucleus (LGN) is the central station for visual processing before information reaches the cerebral cortex. It is characterized by subdivisions with distinct cyto- and myeloarchitecture. Due to its small size, imaging of the LGN and especially its subdivisions is challenging. Here, we show that the LGN and its subdivisions can be identified using in-vivo and ex-vivo high-field quantitative MRI with ultra-high resolution. We present the to-date first atlas of the LGN and its estimated subdivisions. This work will serve as a highly valuable tool both for neuroscientists and clinicians investigating the visual system and its disorders.

Amaresha Konar Shridhar¹, Enlin Qian², Sairam Geethanath², Guido Buonincontri³, Maggie M Fung⁴, Nancy A Obuchowski⁵, Pedro Gomez⁶, Rolf Schulte⁷, Lawrence H Schwartz⁸, and Amita Shukla-Dave^1,9
1Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, United States, ²Columbia Magnetic Resonance Research Center, Columbia University, New York, NY, United States, ³Imago7 Foundation, Pisa, Italy, ⁴MR Apps & Workflow, GE Healthcare, New York, NY, United States, ⁵Department of Quantitative Health Sciences, Cleveland Clinic Foundation, Cleveland, OH, United States, ⁶Global Research, GE Healthcare, Munich, Germany, ⁷MR Workflow & Application Team, GE Healthcare, New York, NY, United States, ⁸Department of Radiology, Columbia University Medical Center, New York, NY, United States, ⁹Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, United States

The present study performed the repeatability and reproducibility test for T₁, and T₂ values estimated using MR fingerprinting (MRF) method. MRF data have been acquired over 30 days at three different centers (center-1 (USA): 1.5T and 3T, center-2 (USA): 3T and center-3 (Italy): 1.5T) using ISMRM/NIST MRI system phantom. MRF based estimated T₁ and T₂ values are compared with the vendor provided values and standard inversion recovery spin echo and a multiple single-echo spin-echo method as scanner Ground Truth (GT) values.  The results show that the T₁ and T₂ values estimated using the MRF method are highly repeatable and reproducible.

Mahesh Bharath Keerthivasan¹, Marcel Dominik Nickel², Fei Han³, Xiaodong Zhong³, Maria Altbach⁴, Berthold Kiefer², and Vibhas Deshpande^5
1Siemens Healthcare USA, Tucson, AZ, United States, ²Siemens Healthcare Gmbh, Erlangen, Germany, ³Siemens Healthcare USA, Los Angeles, CA, United States, ⁴University of Arizona, Tucson, AZ, United States, ⁵Siemens Healthcare USA, Austin, TX, United States

There has been renewed interest in the estimation of T1 relaxation times as a quantitative method for characterization of pathologies in the abdomen. While various techniques have been presented for T1 mapping they have not been systematically evaluated. In this work, we present a multi-slice radial Look-Locker FLASH technique for robust and reproducible abdominal T1 mapping. We investigate the effect of various pulse sequence and reconstruction parameters on the T1 estimation performance.  

Marco Fiorito¹, Maksym Yushchenko¹, Mathieu Sarracanie^1,2, and Najat Salameh^1
1Laboratory for Adapatable MRI Technology (AMT lab), Dpt of Biomedical Engineering, University of Basel, Basel, Switzerland, ²Medical Image Analysis Centre (Miac AG), Basel, Switzerland

Low field scanners present several advantages for interventional applications, however no standard method has yet arisen from temperature mapping. In this study we investigated the relationship between T₁ and temperature at 0.1 T. MR images of four water phantoms, characterised by different T₁, were acquired at different temperatures using a multi-slice FLASH sequence based on Look-Locker. Pixel-wise estimation of T₁ relaxation through data fitting showed a growing trend with temperature. In light of the large number of time points, compromising SNR by a factor of 2 produced similar results for an almost 4 times faster acquisition.

Hanwen Liu^1,2, Qing-San Xiang^1,3, Roger Tam^3,4, Piotr Kozlowski³, David K.B. Li³, Alex L. MacKay^1,3, John K. Kramer^2,5, and Cornelia Laule^1,2,3,6
1Physics & Astronomy, University of British Columbia, Vancouver, BC, Canada, ²International Collaboration on Repair Discoveries, Vancouver, BC, Canada, ³Radiology, University of British Columbia, Vancouver, BC, Canada, ⁴Biomedical Engineering, University of British Columbia, Vancouver, BC, Canada, ⁵Kinesiology, University of British Columbia, Vancouver, BC, Canada, ⁶Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada

We propose a novel T₂ relaxation data analysis method called spectrum analysis for multiple exponentials via experimental condition oriented simulation (SAME-ECOS), which was developed based on a combination of information theory and deep learning neural network algorithms. SAME-ECOS is tailored for different MR experimental conditions to decompose the multi-exponential decay data into a T₂ spectrum, which has been considered an ill-posed problem using conventional fitting algorithms including the commonly used non-negative least squares (NNLS). Our results demonstrated that, compared with NNLS, SAME-ECOS can yield much more reliable T₂ spectra in a dramatically shorter time.

Fabian Küppers¹, Seong Dae Yun¹, and Nadim Jon Shah^1,2,3,4
1Institute of Neuroscience and Medicine 4, Forschungszentrum Jülich, Jülich, Germany, ²Department of Neurology, RWTH Aachen, Aachen, Germany, ³Institute of Neuroscience and Medicine 11, Forschungszentrum Jülich, Jülich, Germany, ⁴JARA - BRAIN - Translational Medicine, Aachen, Germany

MRI sequences with a mixed GE/SE signal have been shown to be suitable for a wide range of applications due to the wide variety of accessible parameters. This work presents in vivo results of a 10-echo GESE sequence based on an EPIK readout to demonstrate the feasibility of whole-brain acquisitions below 5min, including T₂ and T₂* maps; comparison is made to reference methods. The generated images are artefact free and the T₂*-maps correspond with conventional multi-echo GE results. The T₂ values are higher than those from conventional SE, but are correctable using a reduced TE and improved fitting.

Guy Shpringer¹ and Noam Ben-Eliezer^1,2,3
1Department of Biomedical Engineering, Tel Aviv University, Tel Aviv, Israel, ²Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel, ³Center for Advanced Imaging Innovation and Research (CAI2R), New-York University Langone Medical Center, New York, NY, United States

Quantification of T₂ values is important for a wide range of research and clinical applications. The Echo modulation Curve Algorithm allows accurate mapping of T₂ values at clinical scan-times based on multi-echo spin echo data. Reconstruction, however, is still done offline and requires 10’s of minutes of processing times, thereby hampering the integration of this technique into real-time applications. We present in this work two approaches for accelerating maps reconstruction, based on PCA and gradient descent search algorithm. These offer up to x20 acceleration in reconstruction time, and can be potentially generalized to other reconstruction procedures involving dictionary search.

Hao Peng^1,2, Liwen Wan¹, Qian Wan¹, Jianxun Lv¹, Chuanli Cheng¹, Xin Liu¹, Hairong Zheng¹, and Chao Zou^1
1Shenzhen Institutes of Advanced Technology,Chinese Academy of Sciences, Shenzhen, China, ²Huazhong University of Science & Technology, Wuhan, China

T₁ quantification is a valuable biomarker for liver function estimation and fibrosis staging. The presence of fat would confound the measurement of tissue T₁. Chemical shift encoded fat-water separation combined variable flip angle (CSE-VFA) T₁ mapping could remove the bias from fat signals, but B₁ inhomogeneity would be a serious problem in abdominal applications. In this work, we proposed to combine the DREAM sequence with CSE-VFA, so that PDFF/T₁/B₁/R^*₂ could be simultaneously estimated. The deviation of the T₁ values between the results with and without B₁ correction verified the necessity of B₁ measurements in the abdominal application.

Hao Peng¹, Liwen Wan¹, Qian Wan¹, Chuanli Cheng¹, Xin Liu¹, Hairong Zheng¹, and Chao Zou^1
1Shenzhen Institutes of Advanced Technology,Chinese Academy of Sciences, Shenzhen, China

T₁ relaxation time has been a valuable biomarker with emerging applications in cardiac diseases and liver function. Traditional inversion-recovery T₁ quantification method is frequently applied as the reference for various T₁ quantification methods. When applied in targets where fat and water signals co-exists, the single component fitting model would be in a dilemma. Combining the inversion-recovery T₁ quantification with existing fat-water quantification methods, this work presented a solution for multi-component T₁ quantification. Proposed method has been tested on fat-water phantoms and showed good consistency over a wide range of fat fractions.

Tobias Streubel¹, Francisco Javier Fritz¹, Herbert Mushumba², Klaus Püschel², and Siawoosh Mohammadi^1
1Institute for Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, ²Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

This work investigates tissue shrinkage during fixation and how it is related to associated changes in three quantitative MRI parameters (longitudinal relaxation $$$R_1$$$  and effective transverse relaxation $$$R_2^*$$$ rates, and magnetization transfer saturation rate MT). We proposed a new model to estimate tissue shrinkage from brain volume changes and found that shrinkage was $$$7.7\%$$$. No apparent relation between changes in MT and tissue shrinkage were found, whereas it was remarkable for $$$R_1$$$ and $$$R_2^*$$$, indicating that mostly the extra-axonal space is reduced during fixation.

Francisco Javier Fritz¹, Luke J. Edwards², Tobias Streubel^1,2, Kerrin J. Pine², Nikolaus Weiskopf², and Siawoosh Mohammadi^1,2
1Institute of System Neuroscience, Universitätklinikum Hamburg-Eppendorf, Hamburg, Germany, ²Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany

We introduced a forward model to simulate the effect of fibre dispersion on the angle-dependent GRE signal decay in different SNR conditions. We compared the classical signal model against three variations of the signal model derived from a second-order Taylor expansion in time of Wharton and Bowtell’s HCFM model, including a new model that accounts for fibre dispersion. We found a noise enhancement in the model parameters when using the second-order models. Moreover, we found that the orientation dependency of the GRE signal diminished for high dispersions.

Tonima S Ali¹, Vaibhavi S Itkyal^1,2, Kiran Thapaliya^1,3, and Markus Barth^1,2,3
1University of Queensland, Brisbane, Australia, ²Indian Institute of Technology, Madras, India, ³Griffith University, Gold Coast, Australia

The use of multi-echo gradient echo (mGRE) with signal compartment modelling is an increasingly popular choice for myelin assessment by measuring myelin T2* (T2*_My), myelin water fraction (MWF) and g-ratio. In this simulation study, we show the effects of varying white matter microstructure and noise levels on GRE and the efficiency of commonly used fitting algorithms for predicting the true T2*_My, MWF and g-ratio.

Chang Gao^1,2,3, Peng Hu^1,2, Brian Dale⁴, Marcel D. Nickel⁵, Stephan A.R. Kannengiesser⁵, Berthold Kiefer⁵, Vibhas Deshpande⁶, and Xiaodong Zhong^3
1Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, United States, ²Physics and Biology in Medicine Inter-departmental Graduate Program, David Geffen School of Medicine, University of California, Los Angeles, CA, United States, ³MR R&D Collaborations, Siemens Healthcare, Los Angeles, CA, United States, ⁴MR Training, Siemens Healthcare, Cary, NC, United States, ⁵MR Application Development, Siemens Healthcare GmbH, Erlangen, Germany, ⁶MR R&D Collaborations, Siemens Healthcare, Austin, TX, United States

Accurate quantification of proton-density fat fraction (PDFF) and R2* requires appropriate compensation of various confounding factors. A stability study was performed to investigate the impacts of different protocols and imaging parameters using both breath-hold Cartesian and free breathing radial sequences on a standardized phantom and a group of 5 same normal subjects at both 1.5T and 3T. This study revealed that flip angle, TE mode and coil usage were important protocol parameters to investigate further in larger patient population.

Yu-Feng Wang^1,2, Gary Liney^2,3, Robba Rai^2,3, Sirisha Tadimalla¹, Jonathan Goodwin⁴, Lois Holloway^2,3, and Annette Haworth^1
1Institute of Medical Physics, The University of Sydney, Camperdown, Australia, ²Ingham Institute for Applied Medical Research, Liverpool, Australia, ³Liverpool and Macarthur Cancer Therapy Centre, Liverpool Hospital, Liverpool, Australia, ⁴Radiation Oncology Department, Calvary Mater Newcastle, Newcastle, Australia

Inter-/intra-scanner differences contribute to uncertainties in results from multi-centre longitudinal imaging studies. The Sequential Imaging Biofocussed Radiotherapy (SI-BiRT) trial is a multi-centre longitudinal imaging clinical trial that aims to develop imaging biomarkers using mpMRI to predict radiation therapy response in prostate cancer. Here we quantify the inter-/intra-scanner variabilities in the mpMRI protocol and scanners used in the SI-BiRT trial using commercial phantoms. ADC measurements were highly accurate while VFA T1 mapping overestimated reference values. ADC and T1 showed high intra-scanner reproducibility while R2* showed higher variability. The quantified uncertainties will be considered when interpreting results from the SI-BiRT trial.

Lucas Soustelle^1,2, Samira Mchinda^1,2, Thomas Troalen³, Maxime Guye^1,2, Jean-Philippe Ranjeva^1,2, Gopal Varma⁴, David C Alsop⁴, Guillaume Duhamel^1,2, and Olivier M Girard^1,2
1Aix-Marseille Univ, CNRS, CRMBM, Marseille, France, ²APHM, Hôpital Universitaire Timone, CEMEREM, Marseille, France, ³Siemens Healthcare SAS, Saint-Denis, France, ⁴Division of MR Research, Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States

Inhomogeneous Magnetization Transfer (ihMT) is a novel myelin imaging technique. As for many other MRI techniques special attention must be paid to local B₁⁺ variations in applications at high field. In this work, a detailed analysis of the ihMT ratio sensitivity to B₁⁺ inhomogeneities is performed in the context of human brain imaging at 3T. It is shown that concentrating RF power is an efficient way to reduce B₁⁺ induced bias and that the overall performance of the technique lies on a tradeoff between high ihMT ratios (sensitivity) and reduced sensitivity to B₁⁺ inhomogeneities.

Chen Solomon¹, Tamar Blumenfeld-Katzir¹, Moti Salti^2,3, Dvir Radunsky¹, Noam Omer¹, Neta Stern¹, and Noam Ben-Eliezer^1,4,5
1Department of Biomedical Engineering, Tel Aviv University, Tel Aviv, Israel, ²Brain Imaging Research Center (BIRC), Soroka Medical Center, Beer Sheva, Israel, ³Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer Sheva, Israel, ⁴Center for Advanced Imaging Innovation and Research (CAI2R), New-York University Langone Medical Center, New York, New York, NY, United States, ⁵Sagol School of Neuroscience, Tel-Aviv University, Tel Aviv, Israel

Quantitative MRI (qMRI) may provide higher sensitivity to early pathological changes than standard qualitative assessment. This advantage, however, is yet to be rigorously compared with conventional diagnostic methods. This study aims to quantify the human ability to detect predefined changes in T₂-weighted images as part of the diagnostic process of multiple sclerosis (MS). A visual diagnostic test was performed on neurosciences students, suggesting that the human vision has lower sensitivity to subtle MS lesions in T₂-weighted images, in comparison to quantitative assessment of the change in T₂ values.

Chiara Casella¹, Elena Kleban¹, and Derek K Jones^1
1Department of Psychology, Cardiff University Brain Research Imaging Centre, Cardiff, United Kingdom

We explored the anatomical variability in reliability of complex mGRE signal, and of parameters estimated by modelling this signal as a superposition of complex myelin, intra- and extra-axonal water signals, in the corpus callosum at 7T. Our data showed to be repeatable in the posterior portion of the corpus callosum, while reliability was lower in more anterior portions. These findings have important implications and need to be considered when investigating callosal microstructure with mGRE in health and disease.

Feng Qi¹, Karla Miller¹, Sean Foxley², Menuka Pallebage-Gamarallage³, Ricarda AL Menke¹, Olaf Ansorge³, Samuel A Hurley⁴, and Benjamin C Tendler^1
1Wellcome Centre for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom, ²Department of Radiology, University of Chicago, Chicago, IL, United States, ³Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom, ⁴School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States

Postmortem imaging allows for validation of the origins of image contrast through comparisons with histology. However, the inclusion of formalin fixative substantially reduces the T₂. This reduction is (approximately) linear with concentration. Prior to scanning, samples are often placed in a fluid that has more favourable properties for imaging (e.g. perfluorocarbon fluids). This may lead to an outflow of fixative and an increase in T₂ at the tissue surface. Here we propose to correct for T₂ inhomogeneity by modelling the outflow of fixative within whole, human brains using a novel kinetic tensor model, which incorporates the effects of diffusion anisotropy.

Mathilde Ripart^1,2, Vincent Gras¹, Rachida Elamrani¹, Lucie Hertz-Pannier¹, and Alexandre Vignaud^1
1CEA, Neurospin, Université Paris-Saclay, Gif-sur-Yvette, France, ²Centrale Lyon, Ecully, France

The T1w/T2w ratio is commonly used at 3T as a biomarker of pathological changes in brain's structure. However, this method faces strong B1⁺ inhomogeneities that induce bias in the contrast. Simulations of this bias at 3T and 7T were done using an EPG model, and reported on the anatomical contours of human brains.  At 3T, only a central part of the brain provides acceptable bias in the contrast (≤5%). At 7T, more than half of the brain gives unreliable contrast values. Therefore, T1w/T2w needs to be employed with cautiousness at 3T, and might not be a reliable method at 7T.

Daiki Tamada¹, Xiaoke Wang¹, Timothy J. Colgan¹, Diego Hernando^1,2, and Scott B. Reeder^1,2,3,4,5
1Radiology, University of Wisconsin-Madison, Madison, WI, United States, ²Medical Physics, University of Wisconsin-Madison, Madison, WI, United States, ³Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, United States, ⁴Medicine, University of Wisconsin-Madison, Madison, WI, United States, ⁵Emergency Medicine, University of Wisconsin-Madison, Madison, WI, United States

The estimation performance of phase-based T2 mapping in the presence of motion was investigated using Bloch equation simulations. The steady-state signal of RF-phase modulated gradient echo imaging in the presence of motion was calculated. Linear, sinusoidal, and random motion were considered for the simulation. The results showed that phase errors induced by motion may lead to underestimation of T2 when using a gradient echo phase-based T2 mapping method.

Nick Zafeiropoulos¹, Stephen Wastling¹, Mary M Reilly², Enrico De Vita³, Tarek Yousry¹, and John Thornton^1
1UCL Queen Square Institute of Neurology, London, United Kingdom, ²MRC Centre for Neuromuscular Diseases, London, United Kingdom, ³King's College London, London, United Kingdom

B₁ field deviations above and below 100% of the nominal prescribed values have been noted by previous authors as a potential source of error in MRI CPMG T₂ relaxometry. We show in simulations of clinically realistic acquisition protocols that this effect causes fit instability and loss of precision, and corroborate this with in vivo lower limb muscle image data. We then introduce a B₁ error polarity spatial regularization scheme, and show that this improves parameter estimation accuracy. 

Nadège Corbin¹ and Martina F Callaghan^1
1Wellcome Centre for Human Neuroimaging, UCL Institute of Neurology, London, United Kingdom

High reproducibility of longitudinal relaxation rate (R₁) estimation using the variable flip angle approach requires unbiased and precise estimation of the transmit field inhomogeneity. In this context, the Bloch-Siegert (BSS)-based B₁⁺ mapping approaches were evaluated at 3T and 7T and compared to the SE/STE approach. R₁ values in grey and white matter were slightly higher with the BSS-based techniques. At 3T, the highest reproducibility was observed with the single-echo BSS approach, using an RF spoiling increment of 90°. At 7T, the reproducibility of the techniques were equivalent in well B₀-shimmed regions but diverged in regions of high B₀ inhomogenity.

Nathan Tibbitts Roberts^1,2, Timothy Colgan¹, and Scott B Reeder^1,3,4,5,6
1Radiology, University of Wisconsin - Madison, Madison, WI, United States, ²Electrical and Computer Engineering, University of Wisconsin - Madison, Madison, WI, United States, ³Medical Physics, University of Wisconsin - Madison, Madison, WI, United States, ⁴Biomedical Engineering, University of Wisconsin - Madison, Madison, WI, United States, ⁵Medicine, University of Wisconsin - Madison, Madison, WI, United States, ⁶Emergency Medicine, University of Wisconsin - Madison, Madison, WI, United States

The effects of RF pulse duration on chemical shift encoded MRI (CSE-MRI) methods is a previously unexplored potential confounder for accurate and precise estimation of proton density fat fraction (PDFF) and R2*. Most signal models of CSE-MRI model RF excitation as instantaneous rotation of bulk magnetization; however, instantaneous excitation is not physically realizable. In this work we use Bloch equation simulations to characterize the effect of pulse duration on PDFF and R2* bias. We found that R2* bias was more sensitive than PDFF bias to RF pulse duration and note that clinically meaningful bias can be observed. 

Rongbiao Tang¹, E. Mark Haacke², Yibin Zhang², Qingrou Wang², Naying He², Weibo Chen³, Ke-min Chen², and Fuhua Yan^2
1Ruijin Hospital, Shanghai, China, ²Ruijin Hosptial, Shanghai, China, ³Philips Healthcare, Shanghai, China

Whole-brain radiotherapy (WBRT) is often performed asynchronously with head contrast-enhanced MRI examination (CEME) in patients with brain metastasis (BM). Data regarding T1 signal intensity (SI) changes in the dentate nucleus (DN) in BM patients after WBRT and repeated exposure to gadolinium (Gd)-based contrast agents (GBCAs) are lacking. In this study, we explored the correlation between T1 SI in the DN and cumulative doses of linear GBCAs in BM patients treated with WBRT.

KIRAN THAPALIYA^1,2, Viktor Vegh², Steffen Bollmann², and Markus Barth^2,3
1Menzies Health Institute Queensland, Griffith University, Gold coast, Australia, ²Centre for Advanced Imaging, The University of Queensland, Brisbane, Australia, ³School of Information Technology and Electrical Engineering, The University of Queensland, Brisbane, Australia

Quantitative assessment of model parameters (water fraction and frequency shift) estimated using a multi-compartment model can be useful to study tissue properties in white matter. In this work, we compared common existing complex signal models for multi-echo gradient echo data acquired at 3T and 7T. We investigate the variation of model parameters that could potentially affect different models (number of compartments and parameters) on the estimation of tissue parameters. We show that the tissue parameters vary across the sub-regions of the corpus callosum and are influenced by different modelling choices. 

Wadha Alyami^1,2, Andre Kyme³, and Roger Bourne^1
1Medical Imaging Sciences, Faculty of Health Sciences, University of Sydney, Sydney, Australia, ²Medical imaging sciences, King Saud University, Riyadh, Saudi Arabia, ³Biomedical Engineering, School of Aerospace Mechanical & Mechatronic Engineering, Faculty of Engineering and IT, University of Sydney, Sydney, Australia

Histology-based validation of magnetic resonance imaging (MRI) is essential to confirm imaging technique specificity and accuracy. One-to-one correspondence is complicated by histological preparation and differences in MRI and histology contrast mechanisms. A new approach, based on local structure orientation (LSO) and using microstructural features, is proposed. LSO facilitates registration based on direct correspondence between tissue fibre structure to emulate a common contrast mechanism. Using a physical phantom derived from a chicken heart with embedded fibrous structures, residual displacement was 14.1 mm for advanced mean squares (AMS), 2.2 mm for modified AMS (AMSR), and 3.3 mm for mutual information (MI).