ISMRM 24th Annual Meeting & Exhibition • 07-13 May 2016 • Singapore

Power Pitch Session: Contrast Mechanisms: Novel Imaging Biomarkers

Thursday, May 12, 2016
Power Pitch Theatre, Exhibition Hall
10:30 - 12:30
Moderators: Jiadi Xu, Karin Markenroth Bloch

Click Here to view the Power Pitch introductory session

Note: The videos below are only the slides from each presentation.
They do not have audio.

    Plasma #

1 Antibody Therapy Against Tau Pathology Improves Neuronal Transport as Assessed In Vivo by Tract-Tracing Manganese-Enhanced MRI
Maria F Baron1, Hameetha Banu Rajamohamed Sait2, Wajitha J RajaMohamed Sait 2, D Minh Hoang1, Einar M Sigurdsson2,3, and Youssef Z Wadghiri1
1Radiology, Center for Advanced Imaging Innovation & Research (CAI2R) and Bernard and Irene Schwartz Center for Biomedical Imaging, NYU School of Medicine, New York, NY, United States,2Neuroscience and Physiology, NYU School of Medicine, New York, NY, United States, 3Psychiatry, NYU School of Medicine, New York, NY, United States
Immunotherapies to target Alzheimer’s pathology have been developed in recent years. Amyloid-ß centric approaches have shown limited efficacy, resulting in emphasis on immunotherapies for clearing pathological tau protein (τ-Thx). Our group has demonstrated that Tract-Tracing Manganese Enhanced MRI (TT-MEMRI) is effective to monitor the deleterious effect of tau pathology on neuronal transport in transgenic (τ-Tg) mice. In this study, our TT-MEMRI protocol was used effectively to show the efficacy of acute tau antibody therapy in an advanced stage of tauopathy in the Tg model we previously characterized with TT-MEMRI. Specifically, neuronal transport can be restored after a four-week treatment period.

2 In-vivo measurement of a new source of tissue contrast, the dipolar relaxation time,T1D, using a modified ihMT sequence
Gopal Varma1, Valentin H Prevost2, Olivier M Girard2, Guillaume Duhamel2, and David C Alsop1
1Radiology, Division of MR Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States, 2CRMBM-CEMEREM UMR 7339, CNRS-AMU, Aix Marseille Université, Marseille, France
The enhanced inhomogeneous magnetization transfer (ihMT) in certain tissues, especially white matter, has recently been explained as a result of longer dipolar relaxation times, T1Ds in those tissues. Measurement of T1D by modeling the frequency and power dependence of steady state ihMT has yielded T1D estimates but with great uncertainty. Here we introduce a dynamic ihMT experiment that switches between positive and negative frequency irradiation at varying times. Fits to the ihMT signal decay curve as a function of switching time at one (absolute) offset frequency and power enabled highly precise mapping of T1D that was largely independent of other MT parameters. A T1D of 6.4±0.5ms for white matter was in good agreement with reported ex-vivo measurements using Jeener-Broekaert echoes.  

3 Imaging Reactive Oxygen Species (ROS) using CEST MRI
Rong-Wen Tain1,2, Alessandro Scotti2,3, Weiguo Li4,5, Xiaohong Joe Zhou1,2,3,6, and Kejia Cai1,2,3
1Radiology, College of Medicine, University of Illinois, Chicago, IL, United States, 23T Research Program, Center for MR Research, College of Medicine, University of Illinois, Chicago, IL, United States,3Bioengineering, College of Engineering, University of Illinois, Chicago, IL, United States, 4Research Resource Center, University of Illinois, Chicago, IL, United States, 5Radiology, Northwestern University, Chicago, IL, United States, 6Neurosurgery, College of Medicine, University of Illinois, Chicago, IL, United States
It is extremely challenging to non-invasively measure tissue ROS due to its low concentration and short lifetime. This study aims to demonstrate a fully non-invasive CEST MRI method to measure ROS concentration. CEST Z-spectra were acquired from egg white samples with and without hydrogen peroxide treatment. In addition, proton exchange rate, T1, and T2 relaxation time maps were acquired for further clarification on CEST contrast origin. We have demonstrated that ROS is paramagnetic and can greatly enhance proton exchange rate leading to reduced CEST contrast.

4 A new NOE-mediated MT signal at -1.6 ppm for detecting ischemic stroke in rat brain
Xiaoyong Zhang1,2, Feng Wang1,2, Aqeela Afzail3, John C. Gore1,2, Daniel F Gochberg1,2, and Zhongliang Zu1,2
1Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States, 2Depatment of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States, 3Department of Neurological Surgery, Vanderbilt University, Nashville, TN, United States
We recently reported a new NOE-mediated MT signal at around -1.6 ppm, named NOE(-1.6). In the present work, we evaluated the changes of this signal that occur early in ischemic stroke and found that both NOE(-1.6) and Amide Proton Transfer (APT) signals from stroke lesions have significant changes after MCAO. Compared with APT, NOE(-1.6) showed much stronger contrast between stroke and contralateral normal tissues. We conclude that a new NOE(-1.6) signal in rat brain could be used as a biomarker for assessment of acute ischemic stroke.

5 3D Amide-Proton-Transfer-Weighted (APTw) Image-Guided Stereotactic Biopsy in Patients with Newly Diagnosed Gliomas
Shanshan Jiang1,2, Jaishri Blakeley3, Charles Eberhart4, Yi Zhang1, Hye-Young Heo1, Zhibo Wen2, Lindsay Blair3, Huamin Qin 4, Michael Lim5, Alfredo Quinones-Hinojosa5, Dong-Hoon Lee1, Xuna Zhao1, Peter C.M. van Zijl1, and Jinyuan Zhou1
1Department of Radiology, Johns Hopkins University, Baltimore, MD, United States, 2Department of Radiology, Southern Medical University Zhujiang Hospital, Guangzhou, China, People's Republic of,3Department of Neurology, Johns Hopkins University, Baltimore, MD, United States, 4Department of Pathology, Johns Hopkins University, Baltimore, MD, United States, 5Department of Neurosurgery, Johns Hopkins University, Baltimore, MD, United States
We evaluated the accuracy of the APTw image-guided tissue biopsy via the neuro-navigation system in newly diagnosed gliomas. Patients (n = 24) with suspected gliomas of varying grades were recruited and scanned. APTw image-guided needle biopsy samples were obtained and analyzed histologically. Results showed that the APTw signal intensities were significantly higher in high-grade gliomas than in low-grade gliomas and that APTw signal intensities had a strong positive correlation with pathologic cellularity and proliferation. APTw image-guided biopsy in newly diagnosed gliomas has the potential to reduce the randomness of surgical decisions due to tumor heterogeneity.

6 Magnetic resonance imaging biomarkers for assessment of vascular pathologies in gliomas
Andreas Stadlbauer1, Max Zimmermann1, Karl Rössler1, Stefan Oberndorfer2, Arnd Dörfler3, Michael Buchfelder1, and Gertraud Heinz4
1Department of Neurosurgery, University of Erlangen, Erlangen, Germany, 2Department of Neurology, University Clinic of St. Pölten, St. Pölten, Austria, 3Department of Neuroradiology, University of Erlangen, Erlangen, Germany, 4Department of Radiology, University Clinic of St. Pölten, St. Pölten, Austria
Knowledge about the tumor microvasculature is important for monitoring of disease progression and treatment response. Forty-six patients with known or suspected brain tumors were examined using the vascular architecture mapping (VAM) technique.  ΔR2,GE versus  (ΔR2,SE)3/2 diagrams were evaluated with new versions of microvessel radius (RU) and density (NU), which showed increased levels of heterogeneous structures in glioblastoma and meningioma. Three new imaging biomarkers were introduced: Microvessel type indicator (MTI), which allowed differentiation between supplying arterial and draining venous microvasculature. Vascular induced peak shift (VIPS), which is more sensitive to early angiogenic activity. Curvature was increased in peritumoral vasogenic edema.

7 Multi-parametric estimation of brain hemodynamics with Fingerprinting ASL
Pan Su1,2, Deng Mao1,2, Peiying Liu1, Yang Li1,2, Ye Qiao1, and Hanzhang Lu1
1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States, 2Graduate School of Biomedical Sciences, The University of Texas Southwestern Medical Center, Dallas, TX, United States
MR Fingerprinting (MRF) based Arterial Spin Labeling (ASL) has the ability to estimate multiple physiological parameters in a single scan. In this study, we explored the potential of this technique by fitting the data to a three-compartment model to get seven hemodynamic parameters concomitantly. Hypercapnia study in healthy subjects and clinical scan in stroke patients were conducted to test these estimations. Results show that this technique is able to provide multi-parametric estimations of hemodynamic markers in healthy and diseased brain.

8 Transit time mapping in the mouse brain using time-encoded pCASL
Lydiane Hirschler1,2,3, Leon P. Munting4,5, Wouter M. Teeuwisse4, Ernst Suidgeest4, Jan M. Warnking1,2, Matthias J. P. van Osch4, Emmanuel L. Barbier1,2, and Louise van der Weerd4,5
1Grenoble Institut des Neurosciences, Université Grenoble Alpes, Grenoble, France, 2Inserm U836, Grenoble, France, 3Bruker Biospin, Ettlingen, Germany, 4Radiology, Leiden University Medical Center, Leiden, Netherlands, 5Human Genetics, Leiden University Medical Center, Leiden, Netherlands
Arterial transit time (ATT) is known to influence CBF-quantification and is interesting in itself, as it may reflect underlying vascular pathologies. Currently, no MRI sequence exists to measure ATT in mice. Recently, time-encoded labeling schemes have been implemented in rats and men, enabling ATT-mapping with higher SNR and less scan-time than multi-delay ASL. In this study, we show that time-encoded pCASL (te-pCASL) enables transit times measurements in mice. Furthermore, ATT was found to be preserved in old WT mice. 

9 Measuring Subtle Leakage in Patients with Cerebrovascular Disease Using Dual Temporal Resolution DCE-MRI: Is it Reproducible?
Sau May Wong1, Jacobus F.A. Jansen1, C. Eleana Zhang2, Julie Staals2, Paul A.M. Hofman1, Joachim E. Wildberger1, Robert J. van Oostenbrugge2, Cécile R.L.P.N. Jeukens1, and Walter H. Backes1
1Radiology & Nuclear Medicine, Maastricht University Medical Centre, Maastricht, Netherlands, 2Neurology, Maastricht University Medical Centre, Maastricht, Netherlands
Measuring subtle leakage through the blood-brain barrier using DCE-MRI is challenging since their magnitude is lower than in high-grade tumors. To have a clinical application, this method has to be reproducible. The reproducibility of the transfer constant (Ki) and fractional plasma volume (vp) using dual temporal resolution DCE-MRI was investigated in 14 patients with cerebrovascular disease. Low CVs and moderate to high ICCs demonstrate that despite the noisy nature of the measurement, the method is moderately reproducible. Still, cautious interpretation of the Ki and vp in individual patients is needed. Day-to-day variations may be partly compensated by using session-averaged VIFs.

10 Modeling demyelination in white matter: the effect of realistic geometries on the susceptibility-weighted MR signal.
Tianyou Xu1, Way Cherng Chen2, Michiel Kleinnijenhuis1, Sean Foxley1, and Karla L Miller1
1University of Oxford, Oxford, United Kingdom, 2Singapore Bioimaging Consortium, Singapore, Singapore
Biophysical modeling of axons has conventionally assumed cylindrical geometries. In reality, axons vary in shape. Models consisting of circles benefit from simplicity, however the consequences of this assumption have not been studied. In this work, simulations incorporating realistic myelin shape derived from electron microscopy are employed to model white matter demyelination. Simulations are compared to a cohort of mice with varying levels of demyelination. Predictions from models that incorporate realistic myelin shape are in better agreement with experimental results in a mouse model of demyelination than those from circular models.

11 Thalamic nuclei-specific deposits of iron and calcium in the epileptogenic rat brain revealed by quantitative susceptibility mapping
Manisha Aggarwal1, Xu Li2, Peter C van Zijl2, Olli Gröhn3, and Alejandra Sierra3
1Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2F. M. Kirby Research Center, Kennedy Krieger Institute, Baltimore, MD, United States,3Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
We investigate microstructural pathological alterations in the epileptogenic rat brain using quantitative susceptibility mapping (QSM). Using the established model of pilocarpine-induced status epilepticus (SE), we show for the first time, localized paramagnetic and diamagnetic alterations in tissue susceptibility in specific thalamic-nuclei. QSM contrasts in SE and control rats were further compared with histological Alizarin and Perls’ stainings, which revealed calcium and iron depositions in areas corresponding to significant (p<0.005) alterations in magnetic susceptibility detected in the SE brains. Findings demonstrate the potential of QSM to sensitively detect and differentiate localized thalamic nuclei-specific iron and calcium deposits in the epileptogenic brain.

12 Functional Quantitative Susceptibility Mapping at 7-Tesla: Resolving Neuronal Activation Localized in Grey-Matter
Pinar Senay Özbay1,2, Lars Kasper2, Klaas Paul Pruessmann2, and Daniel Nanz1
1Department of Radiology, University Hospital Zurich, Zurich, Switzerland, 2Institute of Biomedical Engineering, ETH Zurich, Zurich, Switzerland
Functional-QSM, promises to offer quantitative information more directly related to neuronal-activity than BOLD-fMRI and to partially ameliorate the inherent problem of spatial mismatch between locations of neuronal-activation and apparent BOLD-detected-activation. The data for fQSM and fMRI can be simultaneously acquired and mostly processed with the well-established fMRI toolchains. The current high-field study, evaluates details of the processing-chain, provides clear evidence that fQSM is capable (1) to detect neuronal-activation in well-resolved volumes that unambiguously reside within grey-matter, even after removal of apparent activations associated with larger-veins, and (2) to identify the visual-network in resting-state-experiments, thus highlighting a considerable potential of fQSM.

13 Assessing the (ani)sotropic component of R2 as a mean of studying White Matter properties
Rita Gil1, Diana Khabipova1,2, Marcel Zwiers1, Tom Hilbert3,4,5, Tobias Kober3,4,5, and José P. Marques1
1Donders Institute, Radboud University, Nijmegen, Netherlands, 2Centre d'Imagerie BioMédicale, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, 3Advanced Clinical Imaging Technology (HC CMEA SUI DI BM PI), Siemens Healthcare AG, Lausanne, Switzerland, 4Department of Radiology, University Hospital (CHUV), Lausanne, Switzerland, 5LTS5, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
In this study we investigate the orientation dependence of transverse relaxivity (R2) maps in white matter (WM) due to susceptibility effects of myelin microstructure. Subjects’ heads were rotated along different orientations with respect to B0 and R2 values (within different WM fibre populations) were decomposed into R2 isotropic and anisotropic components (orientation independent and dependent respectively). Differences found in isotropic values were associated with fibres different diameter whereas differences found in anisotropic values were associated with the susceptibility effects from myelin. It was showed that the orientation of WM fibres influences R2 contrast and coherence between hemispheres was also observed.

Francis Hane1, Tao Li1, Peter Smylie1, and Mitchell S Albert1
1Lakehead University, Thunder Bay, ON, Canada
We used the MRI HyperCEST technique to detect the presence of the xenon encapsulating cage molecule cucurbit[6]uril (CB6) in the abdomen of a rat. We believe that this is the first in vivo demonstration of a xenon based biosensor. We were able to observe a HyperCEST signal depletion of 53% within the intraperitoneal space of the rat. Our results demonstrate the feasibility of HyperCEST biosensors to move from in vitro to in vivo studies.

15 Hyperpolarized saline for contrast-enhanced MR at Ultra-Low field - Permission Withheld
Najat Salameh1,2,3, Mathieu Sarracanie1,2,3, Loyd Waites4, David Waddington1,3,5, and Matthew Rosen1,2,3
1MGH/HST Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States, 2Harvard Medical School, Boston, MA, United States, 3Department of Physics, Harvard University, Cambridge, MA, United States, 4Rensselaer Polytechnic Institute, Troy, NY, United States, 5ARC Center for Engineered Quantum Systems, School of Physics, University of Sydney, Sydney, Australia
Radiologists routinely use contrast-enhanced MRI with applications mainly in oncology and abdominal imaging. Over the last decade, researchers have put significant efforts in developing new probes for molecular imaging where contrast agents would target only specific cells and/or regions. In all cases, one main question remains:  what is the potential toxicity of this new contrast agent? We propose here a safe approach to contrast-enhanced MRI, using pre-polarized biocompatible saline combined with imaging at ultra-low field (0.0065 T).

The International Society for Magnetic Resonance in Medicine is accredited by the Accreditation Council for
Continuing Medical Education to provide continuing medical education for physicians.