Maria F Baron¹, Hameetha Banu Rajamohamed Sait², Wajitha J RajaMohamed Sait ², D Minh Hoang¹, Einar M Sigurdsson^2,3, and Youssef Z Wadghiri^1
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.

Gopal Varma¹, Valentin H Prevost², Olivier M Girard², Guillaume Duhamel², and David C Alsop^1
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, T_1Ds in those tissues. Measurement of T_1D by modeling the frequency and power dependence of steady state ihMT has yielded T_1D 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 T_1D that was largely independent of other MT parameters. A T_1D of 6.4±0.5ms for white matter was in good agreement with reported ex-vivo measurements using Jeener-Broekaert echoes.  

Rong-Wen Tain^1,2, Alessandro Scotti^2,3, Weiguo Li^4,5, Xiaohong Joe Zhou^1,2,3,6, and Kejia Cai^1,2,3
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.

Xiaoyong Zhang^1,2, Feng Wang^1,2, Aqeela Afzail³, John C. Gore^1,2, Daniel F Gochberg^1,2, and Zhongliang Zu^1,2
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.

Shanshan Jiang^1,2, 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 Zhou^1
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.

Andreas Stadlbauer¹, Max Zimmermann¹, Karl Rössler¹, Stefan Oberndorfer², Arnd Dörfler³, Michael Buchfelder¹, and Gertraud Heinz^4
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.  ΔR_2,GE versus  (ΔR_2,SE)^3/2 diagrams were evaluated with new versions of microvessel radius (R_U) and density (N_U), 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.

Pan Su^1,2, Deng Mao^1,2, Peiying Liu¹, Yang Li^1,2, Ye Qiao¹, and Hanzhang Lu^1
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.

Lydiane Hirschler^1,2,3, Leon P. Munting^4,5, Wouter M. Teeuwisse⁴, Ernst Suidgeest⁴, Jan M. Warnking^1,2, Matthias J. P. van Osch⁴, Emmanuel L. Barbier^1,2, and Louise van der Weerd^4,5
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. 

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. Backes^1
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 (K_i) and fractional plasma volume (v_p) 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 K_i and v_p in individual patients is needed. Day-to-day variations may be partly compensated by using session-averaged VIFs.

Tianyou Xu¹, Way Cherng Chen², Michiel Kleinnijenhuis¹, Sean Foxley¹, and Karla L Miller^1
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.

Manisha Aggarwal¹, Xu Li², Peter C van Zijl², Olli Gröhn³, and Alejandra Sierra^3
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.

Pinar Senay Özbay^1,2, Lars Kasper², Klaas Paul Pruessmann², and Daniel Nanz^1
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.

Rita Gil¹, Diana Khabipova^1,2, Marcel Zwiers¹, Tom Hilbert^3,4,5, Tobias Kober^3,4,5, and José P. Marques^1
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 Albert^1
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.

Najat Salameh^1,2,3, Mathieu Sarracanie^1,2,3, Loyd Waites⁴, David Waddington^1,3,5, and Matthew Rosen^1,2,3
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).