Peng Xiao¹, Jianpan Huang¹, Xiongqi Han¹, Jacinth Wing-Sum Cheu², Joseph Lai¹, Lok Hin Law¹, Carmen Chak-Lui Wong^2,3, and Kannie Wai Yan Chan^1,4,5
1Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, Hong Kong, ²Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong, ³State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, Hong Kong, ⁴City University of Hong Kong Shenzhen Research Institute, Shen Zhen, China, ⁵Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States

Iodinated CT contrast agents(CA) had been investigated as CEST contrast agent while high dose of CA and quick clearance could limit their potential for monitoring pH longitudinally. Here, we aim to introduce CT-lipobeads to address this issue. The CT-lipobeads showed 10% CEST contrast and good pH dependency at pH 6.0-7.0, which is sensitive to distinguish hypoxic medium from normoxic medium. Moreover, CT-lipobeads generated CEST contrast of 9% in the subcutaneous compartment, and contrast remained constant over a week. These findings demonstrated a robust approach for fabrication of CT-lipobeads with decent CEST contrast for longitudinal pH imaging.

Dana C. Peters¹, Stefan Markovic², Qingjia Bao², Dina Preise², Keren Sasson², Lilach Agemy², Avigdor Scherz², and Lucio Frydman^2
1Radiology and Biomed Eng., Yale University, New Haven, CT, United States, ²Weizmann Institute of Science, Rehovot, Israel

Deuterium metabolic imaging (DMI) is a new method to map abnormal metabolism of tumors. bSSFP might provide high SNR for DMI, due to the high T2/T1 ratios of the injected deuterated glucose, and the lactate, which arises from abnormal metabolism. We developed a linear-combination balanced SSFP method for spectrally resolving glucose, lactate and water, using predicted signal evolutions for different bSSFP phase-cyclings.  Our method was able to generate images of the individual compounds in phantoms and in vivo. 

Wan-Ting Zhao^1,2,3, Karl-Heinz Herrmann¹, Martin Krämer¹, Renat Sibgatulin¹, Ali Nahardani^1,2, Jürgen R. Reichenbach¹, and Verena Hoerr^1,2,4
1Medical Physics Group,Institute of Diagnostic and Interventional Radiology, University Hospital Jena, Jena, Germany, ²Center for Sepsis Control and Care, University Hospital Jena, Jena, Germany, ³Institute of Medical Microbiology, University Hospital Jena, Jena, Germany, ⁴Clinic for Radiology, University Hospital Muenster, Muenster, Germany

Acute kidney injury (AKI) is a highly lethal complication of sepsis that is frequently asymptomatic with versatile physiological alterations. As diet has gain recognition in the regulation of immune response, we aim to investigate the dietary impact on the course and outcome of sepsis by multiparametric MRI using perfusion, as well as T1 and T2 relaxation time. Cortical T1 and T2 relaxation time was found to differ significantly in animals having received protein-rich diet compared to healthy controls. By combining the cortical T2 relaxation time with perfusion, additional information could be gained, which allowed to distinguish between non-survivors and survivors.

Lin Chen^1,2 and Jiadi Xu^1,2
1Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States, ²F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, United States

We compared the sensitivity of several chemical exchange saturation transfer (CEST) contrasts in detecting altered pH at 11.7 T MRI. Studies with egg white phantom revealed that amide and guanidium CEST contrasts in protein are suitable for pH mapping at the physiological relevant range (6.5-7.5), while amineCEST works well for pH lower than 6.5. Hypercapnia (20%) study in mouse brain indicated that creatineCEST showed both higher pH sensitivity and signal intensity compared with amide and guanidium CEST at the physiological pH range and is more suitable for in vivo pH studies at high field.

Natalia Ziółkowska^1,2, Ladislav Androvič³, Lucie Woldřichová³, Martin Vít^1,4, David Červený^1,5, Olga Šebestová Janoušková³, Richard Laga³, and Daniel Jirák^1,2
1Site of Computed Tomography, Magnetic Resonance Imaging, and Clinical and Experimental Spectroscopy, Institute for Clinical and Experimental Medicine, Prague, Czech Republic, ²Institute of Biophysics and Informatics, First Faculty of Medicine, Charles University, Prague, Czech Republic, ³Institute of Macromolecular Chemistry, Czech Academy of Sciences, Prague, Czech Republic, ⁴Faculty of Mechatronics Informatics and Interdisciplinary Studies, Technical University of Liberec, Liberec, Czech Republic, ⁵Faculty of Health Studies, Technical University of Liberec, Prague, Czech Republic

Our work is focused on the development and investigation of novel polymer-based contrast agent for ³¹P magnetic resonance (³¹P MR). The proposed diagnostics is a methacrylate-type polymer containing a phosphorothioate group (p(TMPC)), which causes a significant chemical shift of phosphorus, making it easily distinguishable from other biological phosphorus components, and is thus easily traceable by ³¹P MRI. Results from ³¹P MR imaging, spectroscopy and relaxometry obtained at 4.7T show very good MR properties, thus p(TMPC) represent a very promising diagnostic tool for in vivo use. 

Xiaohan Zhou^1,2, Yi Hou³, Wentao Liu¹, and Dong Han^1,2
1National Centre for Nanoscience and Technology, Beijing, China, ²University of Chinese Academy of Sciences, Beijing, China, ³Beijing University Of Chemical Technology, Beijing, China

Interstitium space and interstitial stream compartmentalize organs distributed in different regions and compose human body among parenchymal tissues.  The increase in interests to investigate the behavior and function of interstitial stream, combined with new methodologies propose the demand in new agent to visualize the path itself. A macromolecule gadolinium-based agent PAA-Gd was introduced to outline the path while mass transportation was driven in Balb/c via interstitial stream and  histology study was combined to perform in microscopic view as tracer. The novel agent can display its high efficiency to visualize the stream in radiology and pathology study as a versatile enhancer.

Ayesha Bharadwaj Das¹, James Andrew Tranos², Jin Zhang¹, Youssef Zaim Wadghiri², and Gene Kim^1
1Radiology, Weill Cornell Medicine, New York, NY, United States, ²Radiology, New York University School of Medicine, New York, NY, United States

The purpose of this study is to assess the accuracy of Gadolinium-based contrast agent (GBCA) concentration measured using the novel DCE-MRI method with two flip angles, without using the pre-contrast T₁ measurement. The accuracy of the proposed method was assessed using the conventional approach with pre-contrast T₁ measurement as well as the Gd concentration measurement using Inductively coupled plasma-mass spectrometry using the blood samples collected at the end of each scan. The results exhibited a strong correlation and agreement between the Gd concentration from the proposed two flip angle method and those from the conventional MRI method and ICP-MS analysis. 

Olivia C Sehl^1,2 and Paula J Foster^1,2
1Imaging Research Laboratories, Robarts Research Institute, London, ON, Canada, ²Medical Biophysics, University of Western Ontario, London, ON, Canada

Fluorine-19 (¹⁹F) MRI and magnetic particle imaging (MPI) are both quantitative modalities used for cell tracking. We evaluated the cellular sensitivity of MPI using ferucarbotran on a preclinical MPI system and ¹⁹F MRI using perfluorocarbons on a 3 Tesla clinical system. For both modalities, significant linear increases in ¹⁹F and MPI signal were detected with increasing number of mesenchymal stem cells (MSC). As few as 4000 MSC were reliably detected with MPI and 256 x 10³ MSC with ¹⁹F MRI using the same scan time (1.5 minutes/cell pellet). Both of these detection limits were improved with longer imaging times. 

Xiaoyang Han¹, Yuting Zhai¹, Botao Zhao¹, and Xiao-Yong Zhang^1
1Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China

Detection of small lesions in magnetic resonance (MR) images is currently one of the most challenging tasks. Compared with detection in natural images, existing methods cannot accurately detect small lesions with a limited amount of information in MR images. To solve the problems, we propose a novel multi-task convolutional neural network, which simultaneously regresses the lesion number and detects the lesion location. We train and evaluate the end-to-end network to count and locate extreme small lesions within 3-5 voxels on a mouse brain MR image dataset with point annotations. Our network outperforms other methods on sensitivity and precision.

Kianush Karimian-Jazi¹, Ulf Neuberger¹, Katharina Schregel¹, Gianluca Brugnara¹, Daniel Schwarz¹, Laura Jäger², Wolfgang Wick², Martin Bendszus¹, and Michael Oliver Breckwoldt^1
1Neuroradiology, University Clinic of Heidelberg, Heidelberg, Germany, ²Neurology, University Clinic of Heidelberg, Heidelberg, Germany

Our study shows that patients with a stable, spinal T2 lesion load do not benefit from the administration of GBCAs. In contrast to our previous cerebral study, there was no indication of spinal lesion re-activation. The T2 signal ratio has a high sensitivity and specificity to “predict” contrast enhancement of a given lesion and could be used as a predictive marker for “lesion activity”. In combination with previously published studies on the limited value of Gd-administration in cerebral MS follow-up investigations, we propose a “single-shot” MS protocol to combine cerebral and spinal MRI investigations in one standardized single MR protocol.

Travis Salzillo¹, Yongying Jiang², Yuri Mackeyev³, Clifton David Fuller¹, Caroline Chung¹, Seungtaek Choi¹, Neil Hughes¹, Yao Ding⁴, Jinzhong Yang⁴, Sastry Vedam⁵, Sunil Krishnan³, and Jihong Wang^4
1Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, United States, ²Institute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, TX, United States, ³Radiation Oncology, Mayo Clinic, Jacksonville, FL, United States, ⁴Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, TX, United States, ⁵Radiation Oncology, University of Maryland, Baltimore, MD, United States

Gadolinium-based MRI contrast agents are deemed safe to use in diagnostic exams. Their use would bring value to radiation oncology applications such as daily replanning on the MR-Linac. However, their stability and safe use in the presence of high-energy radiation remains unknown. We analyzed the chemical composition stability of two common MRI contrast agents that were irradiated to various doses using mass spectrometry. We found no detectable amounts of degradation compounds or conformational alterations as a result of irradiation. This is the first step towards demonstrating the safe use of gadolinium-based MRI contrast agents in radiation oncology applications.

Iichiro Osawa¹, Eito Kozawa¹, Yuya Yamamoto¹, Sayuri Tanaka¹, Taira Shiratori¹, Akane Kaizu¹, Kaiji Inoue¹, and Mamoru Niitsu^1
1Saitama Medical University Hospital, Saitama, Japan

The infundibular recess (IR) is a cerebrospinal fluid (CSF) space in the third ventricle floor, and its function remains unclear. We retrospectively evaluated contrast enhancement of the normal IR using heavily T2-weighted 3D FLAIR. The enhancement of IR was the strongest on post-contrast images, followed by 4-h delayed post-contrast images. It was also stronger than that of other CSF spaces. This is the first study to report the enhancement of IR after an intravenous gadolinium injection. Evaluations of the enhancement of IR may clarify substance transport, such as gadolinium or hormones into the CSF.

Yuran Zhu¹, Yuning Gu¹, Kihwan Kim¹, Charlie Androjna², Chris A. Flask^1,3,4,5, Yong Chen^3,6, and Xin Yu^1,3,7
1Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States, ²Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, United States, ³Department of Radiology, Case Western Reserve University, Cleveland, OH, United States, ⁴Department of Pediatrics, Case Western Reserve University, Cleveland, OH, United States, ⁵Cancer Imaging Program, Case Western Reserve University, Cleveland, OH, United States, ⁶Biomedical Research Imaging Center (BRIC), University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, ⁷Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, United States

We present a 3D MR fingerprinting (MRF) sequence for simultaneous T₁ and T₂ mapping in mouse. Data acquisition and reconstruction covered a field of view (FOV) of 30 × 30 × 9 mm³ with a matrix size of 128 x 128 x 9, yielding a spatial resolution of 0.23 × 0.23 × 1 mm³. Retrospective undersampling analysis was performed on fully-sampled phantom and mouse data to examine the undersampling capacity of the proposed sequence, demonstrating that the method supports up to 16-fold in-plane undersampling with a 3-fold through-plane undersampling.

Alexandru V Korotcov^1,2, Caroline A Browne³, Andrew K Knutsen^1,2, Dara L Dickstein^2,4, Juan Wang⁴, Xiufen Xu^2,5, Kathleen Whiting^2,5, Shalini Jaiswal^1,2, Allison Nathanael¹, Daniel P Perl⁴, Zygmunt Galdzicki^2,5, and Bernard J Dardzinski^1,2
1Radiology and Radiological Sciences, Uniformed Services University, Bethesda, MD, United States, ²Center for Neuroscience and Regenerative Medicine, Henry M. Jackson Foundation, Bethesda, MD, United States, ³Department of Pharmacology & Molecular Therapeutics, Uniformed Services University, Bethesda, MD, United States, ⁴Department of Pathology, Uniformed Services University, Bethesda, MD, United States, ⁵Department of Anatomy, Physiology and Genetics, Neuroscience Program, Uniformed Services University, Bethesda, MD, United States

Prolonged stays in high-altitude (HA) environments produce pro- and maladaptive physiological and pathological changes.  Microglia depletion has been utilized in recovery from a spectrum of neurodegenerative diseases abnormalities. Advanced neuroimaging techniques demonstrate great promise to detect subtle changes in brain activity and morphology related to impairments induced by HA. In this work, we applied advanced MRI and modern behavioral tests to investigate neuropathological consequences of hypobaric hypoxia and the use of microglial regeneration as a novel approach to treat the maladaptive effect of HA.

Adil Bashir¹, Jianyi Zhang², and Thomas S Denney^3
1Department of Electrical and Computer Engineering, Auburn University, Auburn, AL, United States, ²Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, AL, United States, ³Electrical and Computer Engineering, Auburn University, Auburn, AL, United States

Direct measurement of ATP hydrolysis (ATP-->Pi) were elusive in the in vivo myocardium because the level of Pi in the heart is low and the peak attributed to Pi overlaps with the much larger peak for 2,3-disphosphoglycerate (2,3 DPG). We have demonstrated an approach to measure ATP utilization rate indirectly by measuring total ATP utilization and subtracting out the measurable component that can be attributed to ATP flux via CK. The technique was applied in swine and human hearts at 7T. This method can facilitate important insights into biological mechanisms of impaired bioenergetics in myocardium.

Patrick Metze¹, Hao Li², and Volker Rasche^1,2
1Internal Medicine II, Ulm University Medical Center, Ulm, Germany, ²Core Facility Small Animal Imaging (CF-SANI), Ulm University, Ulm, Germany

Radial tiny golden angle MRI is a versatile tool for different applications in the small animal model. Changes on short time-scales can be visualized by sliding-window (and Compressed Sensing) reconstructions, while respiratory and cardiac self-gating enable high-resolution images for cyclic motion patterns – all from the same acquisition.

Aurea B Martins-Bach¹, Mohamed Tachrount¹, Cristiana Tisca¹, Lily Qiu¹, Shoshana Spring², Jacob Ellegood², Brian J Nieman², John G. Sled², Remya Raghavan-Nair ³, Elizabeth Fisher⁴, Thomas Cunningham³, Jason Lerch¹, and Karla Miller^1
1Wellcome Centre for Integrative Neuroimaging, University of Oxford, Oxford, United Kingdom, ²Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON, Canada, ³Mammalian Genetics Unit, MRC Harwell Institute, Oxford, United Kingdom, ⁴Department of Neuromuscular Diseases, Institute of Neurology, University College London, London, United Kingdom

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease, characterized by aggregates of TDP-43 protein in the brain of most patients. The TDP-M323K mouse has a mutation in the gene encoding the Tdp-43 protein, and presents progressive motor and neurological phenotypes. In this study, we assessed structural and microstructural alterations in the brain of TDP-M323K mice with preclinical MRI (7 tesla). High resolution images showed brain atrophy, but relative volume changes included hypertrophy in the cortex and hippocampus. Diffusion MRI revealed alterations compatible with neurodegeneration in the white matter and striatum. TDP-M323K mice recapitulate brain imaging phenotypes observed in ALS patients.

Chang-Soo Yun¹, Yoon Ho Hwang², Min-Hee Lee³, Wooseung Kim², Jehyeong Yeon¹, Hyeon-Man Baek⁴, Dong Youn Kim², and Bong Soo Han^1
1Radiation Convergence Engineering, Yonsei University, Wonju-si, Gangwon-do, Korea, Republic of, ²Biomedical Engineering, Yonsei University, Wonju-si, Gangwon-do, Korea, Republic of, ³Institute of Human Genomic Study, Korea University, Ansan-si, Gyeonggi-do, Korea, Republic of, ⁴Gachon Advanced Institute for Health Sciences and Technology, Gachon University, Incheon-si, Korea, Republic of

We investigated the changes in correlation between mouse brain metabolites due to acute restraint stress using magnetic resonance spectroscopy (MRS). Acquired time series MRS data of the control and acute stress groups were quantified using LCModel. Correlation coefficients between metabolites were calculated from time series metabolite concentration and metabolite pairs with statistically significant correlations were selected using one-sample Sign Test ( p < 0.05 ). We found that Gln-GSH, NAA-Glu and NAA-GSH showed new significant correlations in the acute stress group. Our findings suggest that correlation can be a useful measurement in assessing the effects of stress.

Mark David Platt¹, Harish Poptani¹, Antonius Plagge², and Mahon Maguire^1
1Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom, ²Cellular and Molecular Physiology, University of Liverpool, Liverpool, United Kingdom

Loss of function mutations in the TRAPPC9 gene causes autosomal recessive intellectual disability and microcephaly. A mouse model was generated to investigate the effects of TRAPPC9 knockout in mice. In vivo and ex vivo MRI were used alongside behavioural tests to probe differences in brain volume and learning ability. In vivo MRI demonstrated significant differences between the whole brain, cerebellar and corpus callosum volumes of adult TRAPPC9 knockout mice and wildtype controls. Behavioural assays also revealed significant differences in learning ability. These results align with the human condition and suggest the model is appropriate for further study of TRAPPC9 knockout.

Puneet Bagga¹, Jeffrey Steinberg², Walter Akers², Zoltan Patay¹, Beth McCarville¹, Chitra Subramanian³, Charles O Rock³, and Suzanne Jackowski^3
1Department of Diagnostic Imaging, St Jude Children's Research Hospital, Memphis, TN, United States, ²Center for In Vivo Imaging and Therapeutics (CIVIT), St Jude Children's Research Hospital, Memphis, TN, United States, ³Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN, United States

Pantothenate kinase (PanK) is a metabolic enzyme that is the first and rate-controlling step in the only pathway for cellular coenzyme A (CoA) biosynthesis. A rare, life-threatening neurological disorder known as pantothenate kinase-associated neurodegeneration (PKAN), formerly known as Hallervorden-Spatz disease, arises from mutations in the human PANK2 gene. Here, we studied the neurochemical effects of a drug capable of allosterically activating PanK protein isoforms as a potential PKAN therapeutic. We applied ¹HMRS to quantify changes in cerebral metabolites including Glx, GABA, lactate, and NAA in a mouse model of CoA deficiency employing the neuron-specific deletion of Pank1 and Pank2 genes.