Begona Lavin Plaza¹, Alkystis Phinikaridou¹, Marcelo Andia², Silvia Lorrio Gonzalez¹, and Rene Botnar^1
1King's College London, London, United Kingdom, ²Pontificia Universidad Catolica de Chile, Santiago de Chile, Chile

Atherothrombosis is a systemic arterial disease mainly involving the intima of large- and medium-sized arteries including the carotid, aorta, coronary, and peripheral arteries. Although it has long been known that atherosclerosis is a systemic disease, the effects of vascular alteration distally from the site of injury and the underlying mechanisms responsible for the systemic response have not been elucidated. In this study, we used an albumin-binding contrast agent to assess whether (1) vascular injury in the abdominal aorta triggers plaque progression in the brachiocephalic artery located distally to the site of injury and (2) whether neutrophils can be the link involved in this systemic response. 

Jeff M Gaudet^1,2, Corby Fink^3,4, Matthew S Fox¹, Gregory A Dekaban^3,4, and Paula J Foster^1,2
1Imaging Research Laboratories, Robarts Research Institute, London, ON, Canada, ²Medical Biophysics, Western University, London, ON, Canada, ³Molecular Medicine, Robarts Research Institute, London, ON, Canada, ⁴Microbiology and Immunology, Western University, London, ON, Canada

Cellular MRI can be used to improve outcomes of cancer immunotherapy by tracking the fate of these cells after their administration.  In this study, we used fluorine-19 MRI to track and quantify migration of antigen-presenting peripheral blood mononuclear cells (PBMC).  Mice were imaged at both high-field and clinical field strengths. PBMC migration to the node was quantified and compared under different conditions. This study is the first to report on fluorine-19 imaging of PBMC and demonstrates the potential of cellular MRI to aid in the optimization of cellular therapy.    

Mukundan Ragavan¹, Xiaorong Fu², Shawn C Burgess², and Matthew E Merritt^1
1Department of Biochemistry & Molecular Biology, University of Florida, Gainesville, FL, United States, ²University of Texas Southwestern Medical Center, Dallas, TX, United States

In this study, the utility of sodium propionate for accentuating changes in cardiac metabolism is evaluated. The study is performed using a murine model of cardiac hypertrophy and employs hyperpolarized magnetic resonance spectroscopy, mass spectrometry and a biochemical assay to determine the cardiac redox state. Results show propionate modulates cardiac metabolism across a range of different concentrations.

Rong-Wen Tain^1,2, Ahlke Heydemann^3,4, Alessandro Scotti^1,5,6, Weiguo Li^7,8, Xiaohong Joe Zhou^1,5,6,9, and Kejia Cai^1,5,6
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,³Physiology & Biophysics,College of Medicine, University of Illinois, Chicago, IL, United States, ⁴Center for Cardiovascular Research, College of Medicine, University of Illinois, Chicago, IL, United States,⁵3T Research Program, Center for MR Research, University of Illinois, Chicago, IL, United States, ⁶Bioengineering, University of Illinois, Chicago, IL, United States, ⁷Research Resource Center, University of Illinois, Chicago, IL, United States, ⁸Radiology, Northwestern University, Chicago, IL, United States, ⁹Neurosurgery, University of Illinois, Chicago, IL, United States

This study aims to measure hypometabolism in the muscle due to muscular dystrophy using creatine CEST MRI. We acquired images of the lower limbs from the diseased and wild-type mice. Differences in the Z-spectrum and creatine CEST contrast map were seen between fibrotic and normal muscles. This suggested that CrCEST MRI may serve as a sensitive imaging biomarker for metabolic changes associated with muscular dystrophy.

Hsin-Yu Chen¹, Peder E.Z. Larson^1,2, Jeremy W. Gordon², Robert A. Bok², Marcus Ferrone³, Mark van Criekinge², Lucas Carvajal², Peng Cao², Ilwoo Park², Rahul Aggarwal⁴, Sarah J. Nelson^1,2, John Kurhanewicz^1,2, and Daniel B. Vigneron^1,2
1Graduate Program in Bioengineering, UCSF and UC Berkeley, University of California, San Francisco, San Francisco, CA, United States, ²Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States, ³Department of Clinical Pharmacy, University of California, San Francisco, San Francisco, CA, United States, ⁴Department of Medicine, Division of Hematology/Oncology, University of California, San Francisco, San Francisco, CA, United States

To measure the 3D spatial and temporal dynamics of hyperpolarized [1-¹³C]pyruvate for patient studies, a new compressed-sensing EPSI sequence was developed for prostate cancer clinical research. Utilizing multiband, variable flip angle RF excitation, this sequence provided high temporal (2s) and spatial (0.5cm³) resolution data detecting pyruvate uptake and its rate of conversion to lactate. This approach provided a significant advance over initial human HP-¹³C studies in which just 1D or 2D dynamics were measured and 15s single-timepoint 3D spectra were acquired. Following phantom tests, patient data demonstrated high pyruvate to lactate conversion in regions corresponding to biopsy-confirmed prostate cancer.

Sadi Loai¹, Inga E. Haedicke^2,3, Zahra Mirzaei¹, Craig Simmons^1,4, Xiao-an Zhang^2,3, and Hai-Ling Margaret Cheng^1,5
1Institute of Biomaterials & Biomedical Engineering, University of Toronto, Toronto, ON, Canada, ²Department of Physical and Environmental Sciences, University of Toronto Scarborough, Toronto, ON, Canada, ³Chemistry, University of Toronto, Toronto, ON, Canada, ⁴Mechanical and Industrial Engineering, University of Toronto, Toronto, ON, Canada, ⁵The Edward S. Rogers Sr. Department of Electrical & Computer Engineering, University of Toronto, Toronto, ON, Canada

Embryonic stem (ES) cells offer promise for regenerating a variety of tissue types. One difficult aspect to advancing this technology is determining the fate of these cells once they are introduced inside the body. MRI can play an important role for non-invasive monitoring in patients, but conventional methods based on iron oxides have limited specificity. In this study, a novel, highly efficient T1 agent is investigated for labelling mouse ES cells. A drastic decrease in T1 was obtained and sustained for at least 24 hours. Viability and proliferation were unaffected, and labelled ES cells were differentiated into beating cardiomyocytes.

Shubhangi Agarwal¹, Carlos Renteria¹, Xiangxing Kong², Yanqing Tian², and Vikram Kodibagkar^1
1School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, United States, ²Biodesign Institute, Arizona State University, Tempe, AZ, United States

Tumor hypoxia is a severe problem in oncology, leading to enhanced metastatic potential and poor response to therapies. The advent of GdDO3NI—a hypoxia-binding contrast agent, serves to facilitate therapies by highlighting hypoxic regions on tumors. Relaxivity studies were performed and image registration were executed between modalities to validate the efficacy of this novel contrast agent to pimonidazole: the gold standard for immunohistochemical hypoxia imaging. Results showed a strong correlation in tumor boundaries and hypoxic fractions between modalities. The hypoxic regions showed lower correlation than expected however, attributed to the difference in tissue content resulting from discrepancies in slice thickness.

Alexander A. Kislukhin¹, Hongyan Xu¹, Stephen R. Adams², Kazim H. Narsinh¹, Roger Y. Tsien^2,3, and Eric T. Ahrens^1
1Radiology, University of California San Diego, La Jolla, CA, United States, ²Chemistry & Biochemistry, University of California San Diego, La Jolla, CA, United States, ³Howard Hughes Medical Institute, La Jolla, CA, United States

Fluorine-19 magnetic resonance imaging (MRI) probes are used to label cells for quantitative in vivo tracking of cell therapies and visualizing inflammation. To reduce the ¹⁹F spin-lattice relaxation time (T₁) and enable rapid imaging and improved cell detection sensitivity, we prepared metal-binding fluorinated nanoemulsions, and then metalated them with a panel of transition and lanthanide ions. Iron(III) tris-β-diketonate PFPE nanoemulsion was observed to have superior MRI properties (¹⁹F T₁ as low as 6 ms). Overall, these agents can yield a multifold improvement in detection sensitivity over previously employed ¹⁹F MRI methods to track transplanted cells.

Deepti Upadhyay¹, Uma Sharma¹, Govind Makharia ², Prasenjit Das³, Siddharth Datta Gupta³, and Naranamangalam R Jagannathan^1
1Department of NMR & MRI Facility, All India Institute of Medical Sciences, New Delhi, India, ²Department of Gastroenterology and human Nutrition, All India Institute of Medical Sciences, New Delhi, India, ³Department of Pathology, All India Institute of Medical Sciences, New Delhi, India

Metabonomics study on blood plasma of patients with Celiac disease (CeD) using NMR spectroscopy revealed gender and age specific variations. The concentrations of acetate, pyruvate, creatine and glycine were significantly higher in males with CeD compared to healthy males. While, levels of β-hydroxybutyrate, glycine and alanine were significantly elevated in females with CeD than healthy females. These metabolic differences indicated impairment in both catabolic and anabolic pathways of carbohydrate metabolism in CeD patients of both genders, however, fuel preference for energy requirement was gender specific, fatty acids were used in males while ketone bodies were preferred in females. 

Poonam Rana¹, Ritu Tyagi¹, Apurva Watve¹, Sujeet Kumar Mewar², Uma Sharma², N. R. Jagannathan², and Subash Khushu^1
1NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, Delhi, India, ²Department of NMR, All India Institute of Medical Sciences (AIIMS), Delhi, India

Increasing radiation exposure is a big threat to population worldwide. The present study predicts the early predictive biomarker for radiation injury using ¹H NMR based metabolomics. The animals were exposed to 7.5 Gy whole body radiation. The variable importance of projection (VIP) score showed six most significant metabolites having VIP score of >1. The partial least square discriminant analysis (PLS-DA) based receiver-operating characteristic (ROC) curve of all the six metabolites showed taurine with highest area under curve (AUC) value of 0.996 and with sensitivity (100%) and specificity (90%). It could be used as early prognostic biomarker for radiation injury. 

Ashish Gupta¹, Deepak Kumar¹, Anil Mandhani², and Satya Narain Sankhwar^3
1metabolomics, Centre of Biomedical Research, Lucknow, India, ²Urology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India, ³Urology, King George’s Medical University, Lucknow, India

To address the shortcomings of clinical indexes for the precise identification of prostate cancer (PC) and differentiation from benign prostatic hyperplasia (BPH) and healthy controls (HC), we applied 1H NMR spectroscopy as a surrogate tactic for probing of PC and BPH. The study comprises filtered sera from PC (n=75), BPH (n=70) and the HC (n=65). NMR-measured metabolites and clinical evaluation data were examined separately using multivariate discriminant function analysis (DFA) to probe the signature descriptors for each cohort. DFA reveals that filtered serum based metabolic profiling can differentiate not only HC from BPH and PC but also BPH from PC.   

Sarah Calvert¹, Steven Reynolds², Martyn Paley², and Allan Pacey^1
1Department of Oncology & Metabolism, University of Sheffield, Sheffield, United Kingdom, ²Academic Unit of Radiology, University of Sheffield, Sheffield, United Kingdom

Sperm movement is necessary for reproduction and low sperm motility can impede fertilization. There is a need for greater understanding of the metabolic processes that drive sperm motility. In this study, we examined differences in sperm metabolite profiles between high and low quality sperm in order to identify possible intracellular biomarkers of sperm quality and motility. Sperm motility was significantly different between the two fractions and fell either side of the WHO lower reference limit. Low quality sperm contained higher concentrations of choline, methyls, citrate and lactate, indicative of increased cell membrane and altered metabolism towards glycolysis.

Uma Sharma¹, Deepti Upadhyay¹, Govind Makharia², Siddharth Datta Gupta³, Prasenjit Das³, and Naranamangalam R Jagannathan^1
1Department of NMR and MRI Facility, All India Institute of Medical Sciences, New Delhi, India, ²Department of Gastroenterology and human Nutrition, All India Institute of Medical Sciences, New Delhi, India, ³Department of Pathology, All India Institute of Medical Sciences, New Delhi, India

Present in vitro proton NMR study demonstrated the metabolic changes associated with villous abnormalities and its recovery following gluten free diet (GFD) in patients with Celiac disease (CeD). The concentration of glutamate and glutamine was significantly reduced in intestinal mucosa of CeD patients after GFD, indicating the use of these metabolites as oxidative fuels for energy generation. The level of glycerophosphocholine was significantly increased after GFD in CeD patients suggesting increased turnover of enterocytes essential for healing of intestinal mucosa in CeD patients. The results may have implications in determining the alternative biomarker/s for diagnosis and treatment management of CeD.

Ashish Gupta¹, Keerti Ameta², Deepak Ameta³, Rishi Sethi³, Deepak Kumar¹, and Abbas A Mahdi^2
1metabolomics, Centre of Biomedical Research, Lucknow, India, ²Biochemistry, King George's Medical University, lucknow, India, ³Cardiology, King George's Medical University, lucknow, India

This study addresses myocardial ischemia in patients presenting with unstable angina using 1H NMR metabolomics of filtered serum. The study includes serum samples from 65 unstable angina patients (UA) and 62 healthy controls (HC). Principal component analysis and orthogonal partial least square discriminant analysis were applied to generate a prediction model. Results revealed that five biomarkers—valine, alanine, glutamine, inosine and adenine—could differentiate 95% of UA from HC with utmost sensitivity and specificity. 1H NMR-based filtered serum metabolic profiling appears to be an assuring, least invasive and faster way to screen and identify myocardial ischemia in UA patients.

Emmanuel Amabebe¹, Steven Reynolds², Victoria Stern¹, Jennifer Parker³, Graham Stafford³, Martyn Paley², and Dilly Anumba^1
1Academic unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield, United Kingdom, ²Academic unit of Radiology, University of Sheffield, Sheffield, United Kingdom, ³School of Dentistry, University of Sheffield, Sheffield, United Kingdom

Magnetic Resonance Spectroscopy (¹H-MRS) can detect the metabolite profile of the vaginal microniche and reflects the vaginal bacterial community function. This study assessed the correlation between ¹H-MRS vaginal fluid metabolites and maternal parameters related to preterm birth. As expected, vaginal pH, fetal fibronectin, and cervical length correlated with gestational age at delivery (GAAD).  Vaginal pH also correlated with lactate and acetate integrals in all study cohorts. Additionally, lactate and glutamine/glutamate integrals in women studied at 20-22 gestational weeks; and succinate/lactate ratio in women studied at 26-28 gestational weeks, correlated modestly with GAAD. Further correlations between metabolites were found.