Dimitra Flouri^1,2, Jack RT Darby³, Stacey L Holman³, Sunthara R Perumal⁴, Sebastien Ourselin¹, Anna L David^5,6, Andrew Melbourne^1,2, and Janna L Morrison^3
1School of Biomedical Engineering & Imaging Sciences, King's College London, London, United Kingdom, ²Department of Medical Physics & Biomedical Engineering, University College London, London, United Kingdom, ³Early Origins of Adult Health Research Group, University of South Australia, Adelaide, Australia, ⁴Preclinical Imaging and Research Laboratories, South Australian Health and Medical Research Institute, Adelaide, Australia, ⁵Institute for Women's Health, University College London, London, United Kingdom, ⁶NIHR Biomedical Research Center, University College London Hospitals, London, United Kingdom

Abnormalities of placental development and function underlie many pathologies of pregnancy including preeclampsia and fetal growth restriction (FGR). Advances in MRI techniques provide capacity to obtain additional placental in vivo information to support clinical decision-making. Animal models are used in invasive validation studies are possible in animal models and allow for controlled experiments during pregnancy. Here, we investigated whether MRI technology could be used to study the anatomical morphology of placentae in vivo in sheep; and we characterise diffusion and perfusion properties in normal pregnancies and those complicated by induced FGR.

Dimitra Flouri^1,2, Jack RT Darby³, Stacey L Holman³, Georgia K Williams⁴, Sebastien Ourselin¹, Anna L David^5,6, Janna L Morrison³, and Andrew Melbourne^1,2
1School of Biomedical Engineering & Imaging Sciences, King's College London, London, United Kingdom, ²Department of Medical Physics & Biomedical Engineering, University College London, London, United Kingdom, ³Early Origins of Adult Health Research Group, University of South Australia, Adelaide, Australia, ⁴Preclinical Imaging and Research Laboratories, South Australian Health and Medical Research Institute, Adelaide, Australia, ⁵Institute for Women's Health, University College London, London, United Kingdom, ⁶NIHR Biomedical Research Center, University College London Hospitals, London, United Kingdom

Abnormalities of placenta development and function may result in fetal growth restriction (FGR). Advances in MRI technology enable estimation of quantitative indices that reflect tissue diffusivity and oxygenation. We investigated the physiological impact of maternal hyperoxygenation on the placenta pregnant sheep. We applied a multi-compartment MRI signal model to measure the changes in oxygenation caused by changes in maternal blood oxygen level. The expected increase in feto-placental blood relaxation and feto-placental oxygen saturation with maternal hyperoxygenation was observed. Results suggested that diffusion and relaxation-based MRI is sensitive to acute changes in maternal and feto-placental oxygen level.

Zhiliang Wei^1,2, Yuguo Li^1,2, Xirui Hou³, Zheng Han^1,2, Jiadi Xu^1,2, Michael T. McMahon^1,2, Wenzhen Duan^4,5, Guanshu Liu^1,2, and Hanzhang Lu^1,2,3
1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, United States, ³Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁴Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁵The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Cerebrovascular reactivity (CVR), which denotes brain’s vasodilatory capacity, is broadly utilized in cerebrovascular and neurodegenerative diseases. However, the most popular hypercapnia method in human studies is unsuitable for small animals due to the difficulty in measuring end-tidal CO2. Here, we took a different approach using a pharmacological vasodilatory stimulus, acetazolamide. Plasma level of acetazolamide and vascular responses were quantified by high-performance liquid chromatography and perfusion MRI, respectively. Evidences of feasibility, safety, temporal characteristics, and dose-dependence have been demonstrated. This new CVR technique may open several avenues for preclinical research on cerebrovascular diseases and therapeutic testing in different animal models.

Anthony Mancuso¹, Mehrdad Pourfathi², Ryan M. Kiefer², Michael C Noji², Sarmad Siddiqui², Enri Profka², Stephen J Kadlecek², Rahim Rizi², and Terence PF Gade^1,2
1Cancer Biology, University of Pennsylvania, Philadelphia, PA, United States, ²Radiology, University of Pennsylvania, Philadelphia, PA, United States

We have developed new methods for studying cultured cancer cell metabolism with hyperpolarized ¹³C magnetic resonance spectroscopy (HP ¹³C MRS) at low oxygen concentrations.  Cells grown on the surfaces of microcarriers inside the spectrometer were perfused radially (rather than axially) in a modified NMR tube at controlled oxygen levels. Computational and experimental results demonstrated that cell mass oxygen profiles with radial flow were much more uniform than with conventional axial flow.  The metabolism of HP [1-¹³C]pyruvate was markedly different between the two flow configurations, demonstrating the importance of avoiding large oxygen gradients in cell perfusion experiments. 

Yonni Friedlander^1,2, Brandon Zanette¹, Andras Lindenmaier^1,2, Daniel Li¹, Stephen Kadlecek³, Giles Santyr^1,2, and Andrea Kassner^1,2
1Hospital for Sick Children, Toronto, ON, Canada, ²University of Toronto, Toronto, ON, Canada, ³University of Pennsylvania, Philadelphia, PA, United States

Hyperpolarized 129Xe RBC chemical shift in the rat brain was measured to be higher during hypoxic ventilation than during normoxic ventilation.

Shiyu Tang^1,2, Su Xu^1,2, Li Jiang^1,2, Donna Wilder³, Joseph Long³, Alexandre E. Medina⁴, Xin Li^1,2, Gary Fiskum^5,6, Venkata Siva Sai Sujith Sajja³, and Rao P. Gullapalli^1,2
1Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, United States, ²Center for Advanced Imaging Research (CAIR), University of Maryland School of Medicine, Baltimore, MD, United States, ³Blast Induced Neurotrauma Branch, Walter Reed Army Institute of Research, Silver Spring, MD, United States, ⁴Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, United States, ⁵Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD, United States, ⁶Shock, Trauma, and Anesthesiology Research Center, University of Maryland School of Medicine, Baltimore, MD, United States

Compared to rodents, the ferret model has greater similarities to humans in terms of developmental process, brain structure and sophisticated behavior. In this study, we assessed the longitudinal changes in brain metabolism and impulsivity behavior in a ferret model that closely mimics the blast exposure conditions encountered by Warfighters. Ferrets demonstrated concomitantly increased behavioral impulsivity and metabolite alterations in prefrontal cortex following blast exposure. Our findings agree with clinical observations in patients, suggesting that this model is a good gyrencephalic animal model to study brain biochemical profile changes and neuropsychiatric alterations associated with blast exposure.

Raúl Tudela¹, Emma Muñoz-Moreno², Xavier López-Gil², Federico Varriano³, and Guadalupe Soria^1,3
1Biomedical Imaging Group, Consorcio Centro de Investigación Biomédica en Red (CIBER) de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain, ²Experimental 7T MRI Unit, Magnetic Resonance Imaging Core Facility, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain, ³Laboratory of Surgical Neuroanatomy, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, Barcelona, Spain

TgF344-AD rat model has been revealed as an interesting animal model for investigating Alzheimer's disease. About two thirds of persons diagnosed with AD dementia are women, suggesting important sex and gender differences in risk factors for the development of AD. Therefore, it is of high interest to also investigate this issue in the AD animal models. In this study we present preliminary results regarding the effect of sex difference in the functional default mode network between young TgF344-AD rats and Wild-type.

Shanshan Tan¹, Zhihang Chen¹, Yelena Mironchik¹, Noriko Mori¹, Marie-France Penet¹, Balaji Krishnamachary¹, and Zaver M. Bhujwalla^1,2,3
1The Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States, ²Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, United States, ³Department of Radiation Oncology and Molecular Radiation Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Effective tumor delivery is a major challenge in achieving small interfering RNA (siRNA) mediated gene silencing. Poor tumor vascularization can limit the delivery of therapeutic siRNA. Here, we used a VEGF overexpression breast cancer murine model and its wildtype counterpart to investigate the influence of increasing tumor vasculature on choline kinase-alpha siRNA nanoparticle delivery.

Wan-Ting Zhao^1,2,3, Karl-Heinz Herrmann¹, Martin Krämer¹, Daniel Güllmar¹, Jürgen R. Reichenbach¹, and Verena Hoerr^1,4,5
1Institute 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, ⁵Heart Center, University Hospital Bonn, Bonn, Germany

While relaxation rate estimation substantially varies on the chosen fitting method, a tissue-specific T2 fitting scheme for the kidney is lacking. The current study aims to compare multiple T2 fitting methods, including square signal and mono-exponential with constant offsets, in high SNR and low SNR scenarios from identical data points. We compare standard deviations for fitting robustness and RMSE for the goodness of fit. Our finding suggests a mono-exponential with constant offsets is the most suitable method, for it yielded the lowest RMSE both in high and low SNR.

Ruvini Navaratna^1,2, Daiki Tamada², Sarvesh Periyasamy^2,3, Jennifer J Meudt⁴, Paul Laeseke^2,3, Dhanansayan Shanmuganayagam^4,5,6, Scott B Reeder^1,2,3,7,8, and Ali Pirasteh^1,2
1Medical Physics, University of Wisconsin-Madison, Madison, WI, United States, ²Radiology, University of Wisconsin-Madison, Madison, WI, United States, ³Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, United States, ⁴Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, WI, United States, ⁵Surgery, University of Wisconsin-Madison, Madison, WI, United States, ⁶Center for Biomedical Swine Research and Innovation, University of Wisconsin-Madison, Madison, WI, United States, ⁷Medicine, University of Wisconsin-Madison, Madison, WI, United States, ⁸Emergency Medicine, University of Wisconsin-Madison, Madison, WI, United States

Fibrosis is the sequela of and the most important outcome predictor in chronic liver disease. MRI T2 mapping can provide safe and noninvasive detection/staging of liver fibrosis. However, current T2 mapping techniques suffer from prolonged acquisition times, prohibiting widespread clinical utilization. To address this unmet need, we evaluated the feasibility of a whole-liver, single-breath-hold, phase-based T2 mapping technique to assess liver fibrosis in a human-sized porcine model of liver fibrosis. We demonstrated a strong correlation between our phase-based liver T2 values and liver uptake of the fibroblast activation protein inhibitor on PET as well as the reference spin-echo T2 estimates.

Braden Miller¹, Lauren Powlovich², David Moore², Linda Martin¹, and Jaime Mata^1
1University of Virginia, Charlottesville, VA, United States, ²Focused Ultrasound Foundation, Charlottesville, VA, United States

 This new technique has the potential to increase lung cancer survival rates while decreasing morbidity associated with current practices as it allows a less invasive manner for ablation or tumor debulking. 

Yinfeng Dong¹, Yanting Gu¹, Jianhua Lu², Jieru Wan¹, Shanshan Jiang², Raymond C. Koehler¹, and Jinyuan Zhou^2
1Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, United States, ²Department of Radiology, Johns Hopkins University, Baltimore, MD, United States

After TBI, secondary injury severity is difficult to determine. The objective of this study was to investigate the capacity of noninvasive APTw MRI to assess TBI injury in different brain regions and predict long-term neurobehavior outcomes. Fifty-five male and female rats were subjected to a controlled cortical impact with one of three different impactor depths to produce different degrees of TBI, and scanned on a 4.7 T horizontal bore animal imager. Our results suggest that APTw imaging can be used for detecting the level of inflammation and as a potential predictor of long-term outcomes from TBI.

Margaret Caroline Stapleton¹, Philipp Boehm-Sturm², Stefan Koch², Susanne Mueller², Devin Raine Everaldo Cortes¹, and Yijen Wu^1
1Developmental Biology, University of Pittsburgh, Pittsburgh, PA, United States, ²Department of Experimental Neurology, Charite University Medicine Berlin, Berlin, Germany

Allelic difference in Apolipoprotein-E (APOE) is a well-known risk factor for the late-onset Alzheimer’s disease (AD) but how APOE affects brain functions and the subsequent cognitive declination remains unclear.  Diffusion MRI followed by network topology analysis found that APOE deficiency in knockout mice resulted in altered neuronal network in the brain regions known to be affected by Alzheimer’s Disease.  This study suggests the possible role of APOE in neuronal network organization, which might predispose brains to differential AD vulnerability.