Yuning Gu¹, Yun Wu², Hongyi Yang², Yong Chen³, Jesse I. Hamilton⁴, Nicole Seiberlich^3,4, Charlie Androjna⁵, Kai Zhong², and Xin Yu^1,3,6
1Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States, ²High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, China, ³Department of Radiology, Case Western Reserve University, Cleveland, OH, United States, ⁴Department of Radiology, University of Michigan, Ann Arbor, MI, United States, ⁵Cleveland Clinic Pre-Clinical Magnetic Resonance Imaging Center, Cleveland Clinic Foundation, Cleveland, OH, United States, ⁶Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, United States

This study demonstrates the development of a 3D T₂-prepared MRF sequence, in combination with a stack-of-spirals trajectory, for simultaneous T₁ and T₂ mapping of an ex vivo macaque monkey (Macaca mulatta) brain with a voxel size of 0.35x0.35x1 mm³. Retrospective evaluation of the undersampling accuracy showed that, for an undersampling rate of up to 16, the normalized root mean square error was within 6% and 15% in T₁ and T₂ mapping, respectively. These results suggest that 3D simultaneous T₁ and T₂ mapping can be in <30 min with unprecedented spatial resolution.

J Scott McNally¹, Adam de Havenon¹, Seong-Eun Kim¹, Chuanzhuo Wang², Matthew Zabriskie¹, Dennis Parker¹, Hediyeh Baradaran¹, and Matthew David Alexander^3
1University of Utah, Salt Lake City, UT, United States, ²Shengjing Hospital of China Medical University, Shenyang, China, ³Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT, United States

Two rabbit model types (Watanabe Heritable Hyperlipidemic and Apolipoprotien E knockout) were studied with vessel wall MRI (vwMRI) and confirmatory histopathological analysis to evaluate for presence of intracranial atherosclerosis (ICAD). Disease was reliably produced in both rabbit types. Sensitivity and specificity of vwMRI for detection of ICAD were 89.5% and 91.9%, respectively. When excluding mild cases to assess accuracy vwMRI for detecting moderate to severe ICAD lesions, sensitivity improved to 100% with unchanged specificity.

Fumiko Seki^1,2, Seiji Shiozawa², Sho Yoshimatsu², Yuji Komaki¹, Marin Nishio³, Erika Sasaki¹, and Hideyuki Okano^2
1Central Institute for Experimental Animals, Kawasaki, Japan, ²Department of Physiology, Keio University School of Medicine, Tokyo, Japan, ³Department of Radiological Science, Tokyo Metropolitan University, Tokyo, Japan

This study investigated whether MRI could detect brain abnormalities in transgenic marmoset models of Alzheimer’s disease (AD). Magnetization transfer (MT) contrast-MRI have a potential to detect the presence of amyloid plaques, which could be present in the early stage of the diseases. Voxel-based analysis was conducted to explore whether any difference existed between AD models and healthy marmosets (young-to-middle-aged adults). Significant increase of MT-ratios imaging was observed in posterior cingulate cortex whereas decrease was observed in unilateral inferior temporal cortex. This result supported MT-imaging was sensitive to early abnormalities. Continuous evaluation until old age is worthwhile to be clinically relevant.

Lijuan Wang¹, Qingqiang Zhu¹, Weiqiang Dou², Jing Ye¹, and Jingtao Wu^1
1Northern Jiangsu People’s Hospital, Yangzhou, China, ²GE Healthcare, Beijing, China

We aimed to investigate if diffusion kurtosis imaging (DKI) can be applied to differentiate different types of renal cell carcinoma (RCC). For MD, a significant higher value was shown in CCRCC (3.12±0.26) than the rest RCCs (1.03±0.25 for PRCC, 1.78±0.31 for ChRCC and 1.68±0.30 for CDC, p<0.05). For MK，KA and RK, a significant higher value was shown in PRCC (1.52±0.27, 1.93±0.36, 1.21±0.37) than the rest RCCs (1.16±0.23 1.29±0.26, 0.83±0.31 for ChRCC; 0.88±0.21, 1.19±0.33, 0.62±0.29 for CDC and 0.41±0.09, 0.53±0.13, 0.36±0.10 for CCRCC, p<0.05).

Jin Zhang¹, Karl Kiser¹, and Sungheon Gene Kim^1
1New York University School of Medicine, New York, NY, United States

It remains challenging to acquire 3D isotropic high resolution T₁ mapping in in vivo MRI experiments. The increase of T₁ mapping resolution and coverage are typically limited by the scan time. The purpose of this study is to investigate the feasibility of estimate 3D isotropic high resolution T₁ mapping using the variable flip angle (VFA) method¹ and 3D-UTE-GRASP sequence² for small animal imaging at 7T within 3 minutes. 

Dana C Peters¹, Jonatan C. Ferm¹, Lynn Savic¹, Steffen Huber¹, John Walsh¹, Daniel Coman¹, Fahmeed Hyder¹, Mingde Lin¹, James S Duncan¹, Douglas Rothman¹, Albert J Sinuas¹, Julius Chapiro¹, and R. Todd Constable^1
1Yale University, New Haven, CT, United States

In this work, we studied a VX2 tumor in rabbits, which provides a model for hepatocellular carcinoma.   The rabbits were imaged with T1 mapping (pre- and post-contrast), which was used to generate extracellular volume fraction (ECV) maps.  The average ECV for normal liver and tumor was 20 +/-11 % and 18 +/- 7%, respectively.  One week after TACE, tumor ECVs fell to zero, but recovered slightly at two weeks, while normal liver ECV values changed variably after TACE. This preliminary study shows that ECV mapping can depict the highly heterogeneous tumor morphology.

Azadeh Nazemorroaya¹, Ali Aghaeifar¹, Hildegard Schulz¹, Thomas Shiozawa-Bayer², Bernhard Hirt², Klaus Scheffler^3,4, and Gisela Hagberg^4,5
1Max Planck Institute for Biological Cybernetics, Tuebingen, Germany, ²Clinical Anatomy, University of Tübingen, Tuebingen, Germany, ³High Field Magnetic Resonance,, Max Planck Institute for Biological Cybernetics, Tuebingen, Germany, ⁴Biomedical Magnetic Resonance, University of Tübingen, Tuebingen, Germany, ⁵High Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Tuebingen, Germany

Post-mortem brain MRI can yield valuable information. However, tissue preservation and MR-compatibility of fixation agents are challenging. Here we investigated the effect of four MR-compatible formalin-based fixatives on the MR properties of pig brains at several timepoints after start of fixation up to one month. The inclusion agents known to improve the dielectric properties of the fixatives lead to greater R₂^* difference between GM-WM than conventional fixatives. Vice versa these agents lead to a decrease in T₁ contrast.

Niklas Daniel Åke Persson¹, Evan Hunter Stanton ¹, Björn Sigurdsson¹, Tuomas Lilius¹, Humberto Mestre², Maiken Nedergaard^1,2, and Yuki Mori^1,3
1Division of Glial Disease and Therapeutics, University of Copenhagen, Center for Translational Neuromedicine, Copenhagen, Denmark, ²Division of Glial Disease and Therapeutics, University of Rochester Medical Center, Center for Translational Neuromedicine, Rochester, NY, United States, ³Faculty of Health and Medical Sciences, University of Copenhagen, Panum NMR Core Facility, Copenhagen, Denmark

The glymphatic pathway is a novel pathway for interstitial solute clearance. Previous reports note that glymphatic patterns differ according to brain activity. Due to the motion-induced image blurring effects, DCE-MRI in the awake animal is difficult. We aimed to determine the feasibility of FISP-based fast DCE-MRI to assess the glymphatic pathway in awake mice. Head-fixed mice were habituated to restraint and received a cisterna magna cannulation. Awake DCE-MRI was performed 24 hours post surgery. Dynamic tracer distribution maps were calculated, and tracer distribution was measured in each brain segmentation. We successfully obtain DCE-MRI and demonstrate glymphatic dynamics in awake mice.

Henk M. De Feyter¹, Monique A. Thomas¹, Peter B. Brown¹, Akshay Khunte¹, and Robin A. de Graaf^1
1Dept. of Radiology and Biomedical Imaging, Yale University, New Haven, CT, United States

Deuterium Metabolic Imaging (DMI) is a novel approach providing high spatial resolution 3D metabolic data by combining ²H MRSI with administration of ²H-labeled substrates (1). Mapping of brain glucose metabolism has so far been focused on human and rat. Here we report the implementation of DMI for mapping of glucose metabolism in mouse brain. We described the dedicated radiofrequency coil, explore how different glucose administration approaches affect SNR, and illustrate mapping of glucose metabolism in a mouse model of glioblastoma.

Antoine Cherix¹, Bernard Lanz¹, and Hongxia Lei^2
1Laboratory for Functional and Metabolic, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ²Animal Imaging and Technology Core (AIT), Center for Biomedical Imaging (CIBM), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

With increased interests in understanding the hippocampal regulation of  hypothalamic-pituitary-adrenocortical (HPA) axis, this study shows for the first time an in vivo comparison of metabolic fluxes in the mouse dorsal hippocampus and hypothalamus using indirect ¹H-[¹³C] MRS upon [1,6-¹³C₂] glucose infusion at 14.1T. This study provides foundation for investigating relevant evidence to the underlying mechanism of hippocampal regulation of HPA axis.

Illsung Joo¹, Margaret Koletar¹, Wilfred W Lam¹, Wendy Oakden¹, Greg J Stanisz¹, JoAnne McLaurin¹, and Bojana Stefanovic^1
1Physical Sciences, University of Toronto, Toronto, ON, Canada

Alzheimer’s disease (AD) has complex underlying mechanism associated with progressive decline in multiple aspects of brain functions. This work aims to characterize cerebral metabolic alteration in presymptomatic AD in terms of glucose uptake and β-hydroxybutyrate (βHB) concentration in hippocampus (HC) and entorhinal cortex (EC) of rat model of AD using MR imaging and spectroscopic techniques. Glucose uptake was significantly reduced in HC and trending toward decrease in EC with signs of elevated HC βHB concentration in AD transgenic rat when compared to metabolic markers in healthy subjects, demonstrating that metabolic alteration precedes onset of AD cognitive symptoms.

Aline M. Thomas^1,2 and Jeff W.M. Bulte^1,2
1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²Institute for Cell Engineering, Imaging Section and Vascular Biology Program, Johns Hopkins University School of Medicine, Baltimore, MD, United States

In amyotrophic lateral sclerosis (ALS), genetic abnormalities damage motor neurons, resulting in rapidly-progressing neurodegeneration, muscle wasting, and irreversible disability. Current imaging strategies (T2w, DTI, fMRI) monitor structural changes to motor neurons. Here, we investigated continuous wave chemical exchange saturation transfer (CEST) MRI to monitor molecular changes resulting from these abnormalities as a potentially complementary imaging biomarker for monitoring ALS disease progression.

YUTONG LIU¹, Saumi Mathews², Ed Makarov², Lili Guo², Mariano Uberti¹, Balasrinivasa Sajja¹, Larisa Poluektova², Howard Gendelman², and Santhi Gorantla^2
1Radiology, University of Nebraska Medical Center, Omaha, NE 68198, NE, United States, ²Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, NE, United States

In this study, we performed DTI and MRS on a newly created mouse model of brain HIV infection. MRS results showed neuronal damage on hippocampus, and DTI showed diffuse neuroinflammation caused by HIV infection. White matter changes was also observed using DTI.

Suk-Ki Chang¹, JeongYeong Kim², DongKyu Lee³, Chang Hyun Yoo⁴, Jin San Lee⁵, Hak Young Rhee⁶, Chang-Woo Ryu⁷, HyungJoon Cho³, and Geon-Ho Jahng^7
1Radiology, Hallym University medical center, Hwasung, Kyung-gi-Do, Republic of Korea, ²Department of physics, Kyung Hee University, Seoul, Republic of Korea, ³Department of Biomedical Engineering, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea, ⁴Department of Physics and Research Institute for Basic Sciences, Graduate School, Kyung Hee University, Seoul, Republic of Korea, ⁵Department of Neurology, Kyung Hee University Hospital, Seoul, Republic of Korea, ⁶Department of Neurology, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea, ⁷Department of Radiology, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea

To characterize and evaluate microvascular architectures presented by brain microvascular indices obtained with a 7T animal MRI system in the transgenic (Tg) AD-model mice and the non-Tg mice using monocrystalline iron oxide nanoparticle (MION) contrast agent, seven non-transgenic (Tg) mice and ten 5xFAD Tg mice were scanned to measure the R2 and R2* relaxation rates before and after injection of MION contrast agent. ΔR2, ΔR2*, BVf, mVD, VSI, and MvWI were greater in the Tg mouse group than in the non-Tg mouse group. ADC and mean vessel density Q were not significantly different between the two groups.

David Hike^1,2, Taylor Ariko^1,2, Alina Stimmell³, Aaron Wilber³, and Samuel Colles Grant^1,2
1Chemical & Biomedical Engineering, Florida State University, Tallahassee, FL, United States, ²CIMAR, National High Magnetic Field Laboratory, Tallahassee, FL, United States, ³Psychology, Florida State University, Tallahassee, FL, United States

This study utilizes DTI and graph theory as a method for early detection of structural changes inconnectivity related to Alzheimer’s Disease. As a function of phenotype and age, DTI analysis was implemented on 3xTgAD female mouse brains and wild type controls at 11.75-T. Current hemisphere dependent data shows differences between hemispheres within the age and phenotype for the parameters observed.