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

Power Pitch Session: Molecular Imaging & Metabolomics

Thursday, May 12, 2016
Power Pitch Theatre, Exhibition Hall
13:30 - 15:30
Moderators: Kevin Bennett

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 Vascular injury triggers a systemic response that promotes atherosclerosis progression at a remote site of injury.
Begona Lavin Plaza1, Alkystis Phinikaridou1, Marcelo Andia2, Silvia Lorrio Gonzalez1, and Rene Botnar1
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. 


2 Translation of high-field fluorine-19 cell tracking techniques into the clinical realm
Jeff M Gaudet1,2, Corby Fink3,4, Matthew S Fox1, Gregory A Dekaban3,4, and Paula J Foster1,2
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.    


3 Propionate as a Probe For Myocardial Metabolism – A Biochemical and Hyperpolarized MR Study
Mukundan Ragavan1, Xiaorong Fu2, Shawn C Burgess2, and Matthew E Merritt1
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.


4 In-vivo evaluation of hypometabolism associated with muscular dystrophy using Creatine CEST MRI
Rong-Wen Tain1,2, Ahlke Heydemann3,4, Alessandro Scotti1,5,6, Weiguo Li7,8, Xiaohong Joe Zhou1,5,6,9, and Kejia Cai1,5,6
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.


5 3D Dynamic Hyperpolarized 13C-Pyruvate MR Metabolic Imaging of Human Prostate Cancer
Hsin-Yu Chen1, Peder E.Z. Larson1,2, Jeremy W. Gordon2, Robert A. Bok2, Marcus Ferrone3, Mark van Criekinge2, Lucas Carvajal2, Peng Cao2, Ilwoo Park2, Rahul Aggarwal4, Sarah J. Nelson1,2, John Kurhanewicz1,2, and Daniel B. Vigneron1,2
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.


6 Positive-contrast cellular MRI of embryonic stem cells for tissue regeneration using a highly efficient T1 MRI contrast agent - Permission Withheld
Sadi Loai1, Inga E. Haedicke2,3, Zahra Mirzaei1, Craig Simmons1,4, Xiao-an Zhang2,3, and Hai-Ling Margaret Cheng1,5
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.


7 Testing the Efficacy of GdDO3NI: A Novel Hypoxia-Targeting T1 Contrast Agent
Shubhangi Agarwal1, Carlos Renteria1, Xiangxing Kong2, Yanqing Tian2, and Vikram Kodibagkar1
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.


8 Tracking transplanted cells with paramagnetic fluorinated nanoemulsions - Permission Withheld
Alexander A. Kislukhin1, Hongyan Xu1, Stephen R. Adams2, Kazim H. Narsinh1, Roger Y. Tsien2,3, and Eric T. Ahrens1
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.


9 Influence of Gender and Age on the Metabolic Profile of Blood Plasma in Celiac Disease Using  Proton NMR Spectroscopy
Deepti Upadhyay1, Uma Sharma1, Govind Makharia 2, Prasenjit Das3, Siddharth Datta Gupta3, and Naranamangalam R Jagannathan1
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. 


10 Specificity and sensitivity of early predictive urinary metabolic biomarker of radiation injury: a 1H NMR based metabolomic study
Poonam Rana1, Ritu Tyagi1, Apurva Watve1, Sujeet Kumar Mewar2, Uma Sharma2, N. R. Jagannathan2, and Subash Khushu1
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. 


11 Filtered serum-based metabolomics of prostate cancer using 1H NMR spectroscopy - Permission Withheld
Ashish Gupta1, Deepak Kumar1, Anil Mandhani2, and Satya Narain Sankhwar3
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.   


12 Increased metabolites in lower quality sperm suggest altered metabolism and increased cytoplasm compared to higher quality sperm
Sarah Calvert1, Steven Reynolds2, Martyn Paley2, and Allan Pacey1
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.


13 Assessment of changes in metabolic profile of small intestinal mucosal biopsy of Celiac Disease patients after gluten-free diet: An in-vitro Proton NMR Spectroscopy study
Uma Sharma1, Deepti Upadhyay1, Govind Makharia2, Siddharth Datta Gupta3, Prasenjit Das3, and Naranamangalam R Jagannathan1
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.


14 Filtered Serum Metabolomics of Myocardial Ischemia in Unstable Angina Patients - Permission Withheld
Ashish Gupta1, Keerti Ameta2, Deepak Ameta3, Rishi Sethi3, Deepak Kumar1, and Abbas A Mahdi2
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.


15 Correlations between cervicovaginal fluid metabolites and gestational age at delivery
Emmanuel Amabebe1, Steven Reynolds2, Victoria Stern1, Jennifer Parker3, Graham Stafford3, Martyn Paley2, and Dilly Anumba1
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.

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