Contrast Agents & Preclinical Studies
Cancer/Spectroscopy/Molecular Imaging/Pre-Clinical Monday, 17 May 2021

Oral Session - Contrast Agents & Preclinical Studies
Cancer/Spectroscopy/Molecular Imaging/Pre-Clinical
Monday, 17 May 2021 14:00 - 16:00
  • Altered pH in early Alzheimer’s disease detected by creatine chemical exchange saturation transfer magnetic resonance imaging
    Lin Chen1,2, Peter C.M. van Zijl1,2, Zhiliang Wei1,2, Hanzhang Lu1,2, Wenzhen Duan3, Philip C. Wang4,5, Tong Li4,5, and Jiadi Xu1,2
    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, 3Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, United States, 4Department of Pathology, Johns Hopkins University, Baltimore, MD, United States, 5Department of Neuroscience, Johns Hopkins University, Baltimore, MD, United States
    Young AD mice have reduced intracellular pH compared to WT mice, which preceded the tangle and plaque formation. pH has the potential to be a biomarker for early diagnosis of AD.
    Figure 1: Typical S0 (a, b, c), CrCEST (d, e, f), T1 (g, h, i) and T2 maps (k,l,m) for WT (a, d, g, k), Tau (b, e, h, l), and APP (c, f, i, m) mice. The CrCEST maps (RCr) of Tau and APP mice showed clear reduction compared to that of WT mice, while the T1 and T2 maps were closely resembled among the three types of mice. The typical ROIs used to extract regional values are indicated in (a).
    Figure 2. The CrCEST values (RCr) represented by Cr apparent relaxation rate for cortex (a ), thalamus (b), and corpus callosum (c) regions in WT (green square), Tau (red circle) and APP (blue diamond) mice. The T1 values for cortex (d), thalamus (e), and corpus callosum regions (f) in WT (green square), Tau (red circle) and APP (blue diamond) mice. The T2 values for cortex (g), thalamus (h), and corpus callosum regions (i) in WT (green square), Tau (red circle) and APP (blue diamond) mice.
  • DTI and gluCEST imaging reveal the key role of white matter alteration in the pathogenesis in a mouse model of Huntington’s Disease
    Jean-Baptiste Perot1, Marina Célestine1, Marc Dhenain1, Sandrine Humbert2, Emmanuel Brouillet1, and Julien Flament1
    1Université Paris-Saclay, Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA), Centre National de la Recherche Scientifique (CNRS), Molecular Imaging Research Center (MIRCen), Laboratoire des Maladies Neurodégénératives, Fontenay-aux-Roses, France, 2Université Grenoble-Alpes, Grenoble Institute of Neurosciences (GIN), INSERM U1216, Grenoble, France
    Our longitudinal study including gluCEST, DTI, MT and rs-fMRI in a mouse model of Huntington's disease allowed detection of vulnerable brain networks. Early defects detected in white matter highlight its importance in the progression of the disease.
    Figure 4: Summary of main results overlaid with axonal projection atlas of the mouse brain. Grey arrows and dots represent axonal projections and regions respectively. Colored dots represent affected regions according to our results. Colored arrows represent axonal projections between affected regions and can be associated with white matter alteration.
    Figure 1: Variation maps between Ki140 and WT mice. a) Volume variation maps, green regions show atrophy in Ki140. b) GluCEST variation maps, blue regions show decreased level in Ki140. c) MT variation maps, violet regions show decreased level in Ki140. * p < 0.05, ** p<0.01.
  • Multimodal MRI study of multiple sclerosis: the therapeutic role of complement system
    Abdullah Althobity1,2, Nemat Khan3, Trent Woodruff3, Gary Cowin1,4, Ian Brereton1,4, and Nyoman Kurniawan1
    1Centre for Advanced imaging, University of Queensland, Brisbane, Australia, 2Ministry of Education, Riyadh, Saudi Arabia, 3Faculty of Medicine, School of Biomedical Sciences, University of Queensland, Brisbane, Australia, 4National Imaging Facility, Brisbane, Australia
    MRS and DTI can detect pathological changes in EAE lumbar spinal cord. Distinct metabolite and diffusion changes showed that complement protein C5aR1 and C5L2 receptors play major roles in the progression of EAE.
    Figure 2. Anatomical and DTI analysis of the mouse lumbar spinal cord. (A) Coronal view showing the enlarged lumbar region. Blue circles indicate the positions for L1, L3 and L6. (B) High-resolution PD axial images. (C) GM/WM segmentation using SCT. (D) Affine registration of ROIs into DTI maps using b0. DTI parameters: number diffusion gradient directions = 9; b value = 1200 s/mm2 ; TR/TE = 800/18 ms; Resolution = 78 x 78 µm; Slice thickness = 0.5 mm; NSA = 1.
    Figure 1. MRS of the lumbar spinal cord. High-resolution PD was used to locate enlarged lumbar spinal cord GM area. The dimension of MRS voxel is 2.8 x 1.6 x 0.9 mm as Z, X & Y directions as shown on A, B and C (coronal, sagittal and axial). PRESS was used with the following parameters: TR/TE = 2500/14 ms; number of signal averages (NSA) = 128; RF pulse band width = 8400Hz.
  • In vivo methemoglobin modulation as an intravascular contrast agent for magnetic resonance imaging: Rabbit Model with T1 measurement
    Seong-Eun Kim1, J Scott McNally1, Matthew Alexander1, Dennis L Parker1, Matthew S Zabriskie 1, and Ronald Day2
    1UCAIR, Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT, United States, 2Department of Pediatrics, University of Utah, Salt Lake City, UT, United States
    Methemoglobin(MetHb) modulated from sodium nitrite has a great potential for an alternative intravenous contrast agent. Our results demonstrated that in vivo MetHb modulation resulted T1 shortening of blood and soft tissue enhancement. 
    Fig 2. Dynamic T1 map of in vivo MetHb induction at baseline(t=0), t=2, 8, 30 mins after SN treatment and typical ROI selections for mean T1 measurement.
    Fig 3. In vivo T1 changes in vascular structures were plotted as a function of time after SN injection. Plots at baseline, and different time delay (4, 8, 12, 14, 16, 20, 26 and 30 minutes) from SN injection from four rabbit studies.
  • CEST-MRI guided sequential drug delivery using injectable hydrogel for local treatment in the brain
    Xiongqi Han1, Jianpan Huang1, and Kannie Wai Yan Chan1,2,3
    1Biomedical Engineering, City University of Hong Kong, Hong Kong, Hong Kong, 2Biomedical Engineering, Shenzhen Research Institute, City University of Hong Kong, Shenzhen, China, 3Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
    We developed a dual chemotherapeutics loaded MGLH hydrogel, which showed brain compatibility, sequential and sustainable release, combined cytotoxicity on U87 cells and non-labeling CEST detectability, demonstrating a promising approach for image-guided local treatment in brain.
    Figure 4. Drug release, longitudinally CEST monitoring, cytotoxicities and swelling of the MGLH (n=3). (A) MTX and Gem release profiles by UV-vis measurements. (B) the longitudinal CEST tracking of drug release and hydrogel matrix using contrast at 2.4 ppm (drugs) and -3.6 ppm (hydrogel matrix) on day 0, 1, 2, 3, and 7, respectively. (C) the relative cell viabilities treated with these hydrogels, using PBS treated group (100%) for normalization. (D) the swelling tests by gravimetric measurement. P > 0.05, NS; P < 0.05,*; P<0.01,**; P<0.001,***; P<0.0001,****.
    Figure 3. CEST contrast and rheology of MGLH (n=3). The Z-spectra and corresponding CEST contrast (A), and maps (B) under 1.0 μT. The frequency sweep measurements of MGLH hydrogel (C).
  • Fluorine Magnetic Resonance Imaging for Natural Killer Cell Tracking  with a Dual Tuned 1H/19F Torso Coil at 3T
    Paul Begovatz1, Lawrence Lechuga1, Monica Cho2, Mallery Olsen2, Rachel McMahon3, David Vail3,4, and Sean Fain1,5,6
    1Medical Physics, Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States, 2Pediatrics, Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States, 3Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, United States, 4Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, United States, 5Radiology, Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States, 6Biomedical Engineering, Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
    This phantom feasibility study found that concentrations of perfluoropolyether (PFPE), and fewer than one million PFPE labeled NK cells were reliably detected through 19F-MRI with the combination of a cartesian 3D fast spin echo imaging sequence, and a dual tuned 1H/19F torso coil at 3T.
    Figure 1. (A.) Dual tuned 1H/19F torso coil (MRI Tools, Berlin, Germany), with (B.) agar spacer/loading phantoms, and (C.) 1.5 ml PFPE phantoms (white) and 2 ml 19F labeled canine NK cell phantoms (pink). PFPE phantoms were fixed to upper coil array elements under a single 4L agar loading phantom approximately 2 cm from coil surface to simulate typical in vivo osteosarcoma placement, and (D.) loaded in MRI with additional agar phantoms (4L, 8L) to create spacing approximate to canine body.
    Figure 3. (A.) Coronal image of 2 cm thick 4L agar spacer and pelleted NK cell phantoms. (B.) Typical 19F-image obtained from the cartesian 3D fast spin echo sequence of the NK cell phantoms, with (C.) 19F-MRI overlay (red) of 1H-image depicting the presence of 19F-signal within the tips of the pelleted NK cell phantoms.
  • A Mn-based probe targeted towards organic-anion transporting polypeptides
    Nivin N Nyström1, Hanlin Liu2, Francisco Martínez-Santiesteban1, Xiao-an Zhang2, Timothy J Scholl1, and John A Ronald1
    1Robarts Research Institute, London, ON, Canada, 2University of Toronto, Toronto, ON, Canada
    Here, we introduce a Mn(III) porphyrin construct MnTriCP-PhOEt that allows for targeted imaging of cells expressing liver-specific Oatp1 transporters. 
    Liver Uptake of MnTriCP-PhOEt at 3 Tesla. a) T1-weighted images of a representative mouse before and up to 60 minutes post intraperitoneal injection of 0.025 mmol/kg MnTriCP-PhOEt. b) In vivo signal intensity of various organs over time of a representative mouse. c) Average in vivo signal enhancement of liver (n=3). d) Ex vivo nuclear magnetic relaxation dispersion (NMRD) profiles of various tissues 44 minutes post injection. e) Differences in spin-lattice relaxation rates of various tissues between mice injected 0.025 mmol/kg MnTriCP-PhOEt or saline, 44 minutes post injection.
    MnTriCP-PhOEt Structure and Synthesis. a) Molecular structure of MnTriCP-PhOEt. b) 3-dimensional geometry of MnTriCP-PhOEt. q, hydration number. c) Synthesis and yield of MnTriCP-PhOEt. Yields shown in brackets.
  • MR Measurements of Placental Perfusion in Normal Sheep Pregnancies
    Dimitra Flouri1,2, Jack RT Darby3, Stacey L Holman3, Sunthara R Perumal4, Anna L David5,6, Janna L Morrison3, and Andrew Melbourne2,7
    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, 5Elizabeth Garrett Anderson Institute for Women’s Health, University College London, London, United Kingdom, 6NIHR Biomedical Research Centre, University College London Hospitals, London, United Kingdom, 7School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom
    Here we characterised diffusion and perfusion properties of normal sheep placenta such as apparent diffusion coefficient, T2 measurements and fractional anisotropy analysis.  We also presented the first application of multi-compartment MRI model to normal sheep placenta. 
    Figure 1: Example of MR images illustrating the placentomes from a single sheep at mid and late gestation.
    Figure 2: Boxplots summarising results over all singleton pregnancies at mid and late gestation. Each plot shows: the median (red line), the 25th and 75th percentile (purple box) and individual means of each sheep (pink circles).
  • Detectable velocity range in single-cell tracking by time-lapse MRI
    Enrica Wilken1, Felix Freppon1, Max Masthoff1, and Cornelius Faber1
    1Translational Research Imaging Center, Clinic of Radiology, University Hospital Muenster, Muenster, Germany
    Repetitive T2*-weighted imaging of mice brain and simulations of velocity-dependent blurring of contrast were used to show that single iron-labeled cells can be resolved and tracked non-invasively by time-lapse MRI. Cell dynamics up to 1 µm/s are detectable.
    Figure 1: Principle of how image contrast of moving cells with different velocities is simulated by creating synthetic k space.
    Figure 3: Image sections of an overlay of a T2*-weighted image obtained by the time-lapse MRI protocol and the contrast simulation for different cell motion velocities, showing a real (red arrowhead) and a simulated (blue arrowhead) cell in the brain cortex. Simulations used a (a) cartesian and (b) radial sampling scheme.
  • Investigating the microglial metabolome with high resolution 1H NMR
    Lydia M. Le Page1, Jayson Ball2, Linda Watkins2, and Myriam Chaumeil1
    1Physical Therapy and Rehabilitation Science, Radiology and Biomedical Imaging, UCSF, San Francisco, CA, United States, 2Department of Psychology & Neuroscience & the Center for Neuroscience, University of Colorado, Boulder, CO, United States
    We have optimized a protocol for NMR analysis of metabolites from freshly isolated adult rat brain microglia, and can distinguish creatine, creatine phosphate, o-phosphoethanolamine, taurine, glutamate and aspartate. We will apply this protocol to neuroinflammatory disease models.
    Microglial isolation protocol followed by metabolite extraction for NMR. Brains were removed from healthy rats, minced with a razor blade and homogenized before straining and centrifugation. Layers of 70% and 50% Percoll solution and PBS were added. Centrifugation separated microglia from the other CNS elements. Microglia was added to ice-cold methanol, chloroform and water. The metabolite layer was then lyophilized before resuspension in 200μl D2O and acquisition of NMR spectra at 800MHz. Created in BioRender.com
    (A) Spectral fitting of six microglia-specific metabolites shown on spectrum from 3 rats combined, using Chenomx software: PE = o-phosphoethanolamine, PCr = creatine phosphate, Asp = apartate, Glu = glutamate, Tau = taurine (B) Total concentration of the six microglia-specific metabolites in all brain samples, expressed in mM. These graphs show that the levels of metabolites are linearly increasing with cell number, with good reproducibility. (C) Concentration of the six microglia specific metabolites expressed as mM/cell.
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Digital Poster Session - Contrast Agents & Preclinical Studies I
Cancer/Spectroscopy/Molecular Imaging/Pre-Clinical
Monday, 17 May 2021 15:00 - 16:00
  • Microfluidic preparation of liposomal hydrogel microbeads containing CT agents (CT-lipobeads) to longitudinally monitor pH using CEST MRI
    Peng Xiao1, Jianpan Huang1, Xiongqi Han1, Jacinth Wing-Sum Cheu2, Joseph Lai1, Lok Hin Law1, Carmen Chak-Lui Wong2,3, and Kannie Wai Yan Chan1,4,5
    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
    CT-lipobeads were prepared using microfluidics. It generates ~10% CEST contrast at 4.2ppm with pH dependency. CEST contrast remains constant over a week in vivo at 3T.
    Figure 1 Microfluidic preparation of alginate microbeads incorporated with Iopamiro or Iohexol-loaded liposome. (a) Microfluidics design for preparation of microbeads. 1, 2, 3 were inlets for water phase, oil phase and oil/acid phase, respectively, and 4 was outlet. (b) Schematic of liposomal hydrogel beads, i.e. alginate microbeads containing liposomes loaded with CT contrast agent (CT-lipobead). Prepared lipobeads(c). Chemical structure of Iohexol (d) and Iopamiro (e), and protons that can be detected by CEST are in red circles.
    Figure 2 Power optimization and pH dependency for CT-lipobeads showing that CEST contrast at 4.2ppm reach the highest value at 1.6uT and 2.0uT for both beads and capability to distinguish HM from NM. CEST contrast for Iopamiro liposome beads and Iohexol liposome beads at different B1 at neutral pH(a). CEST contrast at 4.2ppm in saline with different pH at 1.6 uT(b). CEST contrast at 4.2ppm in Iopamiro lipobeads in HM, NM and FM at 1.6 uT (c) and corresponded CEST map(d). pH of HM, NM and FM are 6.8, 7.1 and 7.2, respectively. HM: Hypoxic medium. NM: Normoxic medium. FM: Fresh medium
  • Linear combination SSFP for multi-site chemical shift imaging: Applications to Deuterium Metabolic Imaging
    Dana C. Peters1, Stefan Markovic2, Qingjia Bao2, Dina Preise2, Keren Sasson2, Lilach Agemy2, Avigdor Scherz2, and Lucio Frydman2
    1Radiology and Biomed Eng., Yale University, New Haven, CT, United States, 2Weizmann Institute of Science, Rehovot, Israel
    Linear combination bSSFP is useful for deuterium metabolic imaging.
    Figure 1: A) Plot of the modulus of SSFP’s signal vs. frequency offset under the four phase-cyclings, shifting the “banding“ pattern as indicated for TR=5.7ms. Also shown are the frequencies expected for deuterated lactate, glucose and water (green lines) at the utilized field. B) 2H MRI acquisition of bSSFP images with multiple phase-cyclings on a three-metabolite phantom. C) The images can be analyzed as a sum of complex signals (shown in A) arising from each metabolite, based on the phase-cycling; the contribution of each metabolite is then determined by matrix inversion.
    Figure 5: LC-SSFP of deuterated water and glucose in a pancreatic cancer tumor, 30 minutes after injection of deuterated glucose (i.e, before the generation of substantial 2H-lactate). A) Magnitude/phase signal evolutions of water (top) and glucose (bottom), comparing measured values to predicted values. The TR was 5.7ms, and carrier offset 4.3ppm (between glucose and water). B) Metabolites separated using LC-SSFP’s theoretical weights. T=tumor. Left: Raw 2H images. Right: 2H images overlaid on 1H MRI anatomy.
  • Multiparametric MRI of Renal Tissue Shows Dietary Differences Between Survivors and Non-survivors in Sepsis-associated Acute Kidney Injury
    Wan-Ting Zhao1,2,3, Karl-Heinz Herrmann1, Martin Krämer1, Renat Sibgatulin1, Ali Nahardani1,2, Jürgen R. Reichenbach1, and Verena Hoerr1,2,4
    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
    (1.   Animals having received protein-rich diet showed lowest mortality rate.(2.   Survivors having received protein-rich diet showed increased cortical T1 and T2 value compared to healthy rat.Scatter plot of cortical T2 and perfusion can distinguish between survivors and non-survivors
    Figure 4: Compilation of cortical and medullary results of perfusion as well as T1 and T2 relaxation time for all experimental groups (survivors, non-survivors, healthy sham group) and statistical evaluation using the Mann-Whitney U-test(*: p<0.05, **:p<0.01).
    Figure 3:Cortical and medullary perfusion as well as T1 and T2 values in correlation with the severity score based on data from all experimental groups (3 different diets in both the PCI- and sham-group).
  • The sensitivity of amide, amine, creatine and guanidinium CEST in detecting pH at high MRI field
    Lin Chen1,2 and Jiadi Xu1,2
    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 demonstrated that  creatine CEST is a highly pH-sensitive method at high field.
    Figure 2. Representative Z-spectra for the GuanCEST experiments (a) pre and (b) post-CO2 inhalation for the cortex region. The PCr peak is observable and is indicated. Representative Z-spectrum of amideCEST experiment (c) pre and (d) post-CO2 inhalation and CrCEST experiment (e) pre and (f) post-CO2 inhalation for the cortex region. Solid lines are the fitted background using the PLOF method. (g) Scatter plots showing the CEST contrast difference for CrCEST, amideCEST and GuanCEST experiments obtained by PLOF (n= 5) and the corresponding contrast changes (h).
    Figure 1: (a) The typical Z-spectra of egg white that titrated to 6.0, 6.5, 7 and 7.5 pH. The spectrum was recorded using CW-CEST with 1μT and 3s saturation at 37°C by an air heater. The CEST peaks from amide, amine, guanidinium, amideNOE are indicated. The simulated DS spectrum for egg white with pH 7.5 is also plotted.
  • Novel phosphorous-based polymer for 31P-magnetic resonance imaging
    Natalia Ziółkowska1,2, Ladislav Androvič3, Lucie Woldřichová3, Martin Vít1,4, David Červený1,5, Olga Šebestová Janoušková3, Richard Laga3, and Daniel Jirák1,2
    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
    MR measurements of polymer-based 31P contrast agent confirmed its good MR sensitivity with high signal-to-noise ratio in 31P MR spectra and images, even for short acquisition times. 31P MR spectroscopy confirmed large frequency offset of its Larmor frequency from biological 31P signal.
    Fig. 2 MRI measured at 4.7T scanner using 1H/31P RF surface coil. Phantoms (cP=100mmol/L; V=1.4ml in H2O) positioning is visible on 1H MR image (RARE sequence; ST=1min; coronal plane) with probes containing a phosphoester (P=O) group on the left and a phosphorothioate (P=S) group on the right with water reference between them (A). Next, 31P MRI (CSI sequence; ST=3h) of polymers (B: P=O; C: P=S) are presented. In the last image, overlapped 1H/31P MR images are shown (D); 31P signal is highlighted by green colour. SNR resulting from 31P MR images is 5.4 for P=O polymer and 13.6 for P=S polymer.
    Fig.1 31P MR spectra measured at 4.7T scanner using 1H/31P RF surface coil. Single-pulse sequence (TR=200ms; ST=3h) was used for the measurement and spectra from both p(TMPC) and p(MPC) polymers (cP=100mmol/L; V=1.4ml in H2O) were obtained during one measurement. Peak on the left with slightly lower amplitude represents a polymer with a phosphoester group (P=O) with SNR=163.7; peak on the right represents a polymer with a phosphorothioate group (P=S) with SNR=195.1. The chemical shift between the peaks is 56.07ppm.
  • PAA-g-(DTPA-Gadolinium): A Versatile Agent to Visualize the Effiencient Interstitial Stream at 7 Tesla
    Xiaohan Zhou1,2, Yi Hou3, Wentao Liu1, and Dong Han1,2
    1National Centre for Nanoscience and Technology, Beijing, China, 2University of Chinese Academy of Sciences, Beijing, China, 3Beijing University Of Chemical Technology, Beijing, China
     The novel agent PAA-Gd can display its high efficiency to visualize the stream in radiology and pathology study as a versatile enhancer.
    Fig1. (A) The synthetic scheme of zwitterionic MCP contrast agent PAA-Gd. (B) Viability of HUVE cells treated by PAA-Gd and Gd-DTPA. (C) Signal intensity map of T1 weighted MR images (TE= 10 ms, TR= 300 ms) of aqueous solution of PAA-Gd in 200 μL Eppendorf tubes according to different Gd3+ concentration from 0 to 1mM. (D) Linear regression fitting curve (solid line) of calculated R1 value (‘■’ points) was performed.
    Fig2. The image obtained immediately (A) and 12 minutes (B) after intravenous injection of PAA-Gd. DCE images of pre-injection (C), post-injection (D) and the final status of mouse after 30 minutes (E) on the kidney plane. A long distance transportation trace is depicted and emphasized with white arrow in (F) on centric section.
  • Assessment of Gd concentration estimated in DCE-MRI with multiple flip angles
    Ayesha Bharadwaj Das1, James Andrew Tranos2, Jin Zhang1, Youssef Zaim Wadghiri2, and Gene Kim1
    1Radiology, Weill Cornell Medicine, New York, NY, United States, 2Radiology, New York University School of Medicine, New York, NY, United States

    This study results suggest the feasibility of using the two-flip angle approach during DCE-MRI scan to estimate pre-contrast T1 without using an extra scan in order to perform T1 measurement, when assessed in terms of Gd concentration estimation. 

    Figure 4. (A) Accuracy in image derived Gd estimation versus ICPMS measurement. The average error for T1M method was 14.3%. The average error for T1T method was 17%. (B) [Gd] from MRI measurement using T1M method and T1T method (C) vs. ICP-MS measured [Gd]. (B) has a correlation coefficient of 0.84. (C) has a correlation coefficient of 0.85. The gray dash lines are unity lines.
    Figure 2. Example of signal intensity to [Gd] conversion using the top 10 most enhanced vessels from IAUC selection. (A) Normalized vessel signal enhancement curves. (B) Signal enhancement curves converted to [Gd] using T1M. (C) Signal enhancement curves converted to [Gd] from T1T. (D) All signal enhancement curves overlaid with a dashed box over the tail end. (E) A zoomed-in image for the tail end of the signal enhancement curves. The concentrations at last time point (610 s) were used to cross validation with ICP-MS method.
  • Evaluation of cellular sensitivity for magnetic particle imaging and fluorine-19 magnetic resonance imaging
    Olivia C Sehl1,2 and Paula J Foster1,2
    1Imaging Research Laboratories, Robarts Research Institute, London, ON, Canada, 2Medical Biophysics, University of Western Ontario, London, ON, Canada
    The detection of stem cells using 19F MRI and MPI with common cell labeling agents (perfluorocarbon and ferucarbotran) was evaluated. There were significant increases in 19F and MPI signal with cell number and fewer cells were detected with MPI.
    Figure 1: A picture of the (A) 3 Tesla clinical MRI (MR750, General Electric) and dual-tuned (1H/19F) surface coil (MR Solutions) used for 19F imaging, and (B) preclinical MomentumTM MPI scanner (Magnetic Insight Inc.). (C) The relationship between MPI signal and iron mass is determined for MPI signal calibration by imaging known amounts of ferucarbotran with 3.0 T/m gradients.
    Figure 4: MPI detection of ferucarbotran-labeled MSC. (A) 2D MPI of individual MSC pellets containing various cell numbers (M = 106, k = 103). As few as 2000 MSC was detected in 6 of 9 replicates, however with low SNR (2.51). The detection limit of 4000 MSC is reliable and quantifiable (9/9 replicates, SNR = 3.77). (B) 2D MPI signal (and the associated iron content) significantly increases with number of MSC. (D) In 3D (35 projections), 2000 cells can be reliably detected (9/9 replicates, SNR = 6.42) and as few as 1000 cells were detected in 2 of 9 replicates (SNR = 4.69, signal volume 116mm3).
  • Detecting Extreme Small Lesions in MR images with Point Annotations via Multi-task Learning
    Xiaoyang Han1, Yuting Zhai1, Botao Zhao1, and Xiao-Yong Zhang1
    1Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China
    We develop a multi-task learning model for extreme small lesion detection tasks to detect magnetic particle deposition in MR images. The proposed end-to-end network can simultaneously detect the number and the location of small lesions with acceptable precision and sensitivity. 
     
    Figure 1. Multi-task learning structure. The input images are on the left; the output count of lesions is on the bottom right; the output map is on the top right: distance map for point annotation dataset and segmentation map for full segmentation dataset. After each convolutional layer, a rectified linear unit activation is applied. In the regression network, after the last convolutional layer, a global max-pooling layer is added to connect the following fully connected layers.
    Figure 4. Representative detection results. In the prediction image (right column): green circle for true positive, red circle for false positive and orange circle for false negative.
  • Diagnostic value of Gd-contrast administration for spinal cord MRI in MS patients and T2 signal ratio as a predictive marker of lesion activity
    Kianush Karimian-Jazi1, Ulf Neuberger1, Katharina Schregel1, Gianluca Brugnara1, Daniel Schwarz1, Laura Jäger2, Wolfgang Wick2, Martin Bendszus1, and Michael Oliver Breckwoldt1
    1Neuroradiology, University Clinic of Heidelberg, Heidelberg, Germany, 2Neurology, University Clinic of Heidelberg, Heidelberg, Germany
    Gd-contrast administration is dispensable in follow-up spinal MRI of MS patients if no new T2 lesions are present. We show high sensitivity and specificity of the T2 signal ratio as a predictor for enhancing, “active” lesions and propose a shortened, single MRI protocol for routine follow-up MRI
    Fig. 3 Representative MRI images of axial T2-w and T1-w CE images showing different lesion morphologies. (A) T2 lesion without corresponding enhancement and a low T2 signal ratio (SR: 1.54). (B) Ring-enhancing lesion with a T2 SR of 1.78. (C) T2 lesion with a high T2 signal ratio (SR: 1.93) and clear contrast-enhancement. (D) Nodularenhancing lesions (n=33) showed significantly higher T2 signal ratios than nonenhancing (n=185, ****p<0.0001) and ring-shaped enhancing lesions (n=5 ****p<0.0001). NASC: normal appearing spinal cord.
    Fig. 2 T2-w and T1-w contrast enhanced images (A, B). Size of the T2 lesion weakly correlates with the size of the contrast enhancement (C). Pearson correlation analysis, r2 = 0.17, **p < 0.01, n = 44 lesions).
  • Is MRI Contrast Stable in High-Energy Radiation of MR-Linac?
    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 Wang4
    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
    There was no visible change in LC-HRMS spectra between the irradiated samples and unirradiated/reference samples for either contrast agent. The quantification of the peak areas was uniform among all the samples, and there was no significant correlation of peak area with dose.
    Liquid chromatography-high-resolution mass spectrometry (LC-HMRS) chromatograms of gadobutrol samples exposed to various doses of radiation. The entire profile is displayed in (A) where 5 peaks are visible. Peak P3 was identified as gadobutrol, which is enlarged and quantified in (B).
    Liquid chromatography-high-resolution mass spectrometry (LC-HMRS) chromatograms of gadobenate dimeglumine samples exposed to various doses of radiation. The entire profile is displayed in (A) where 5 peaks are visible. Peak P2 was identified as gadobenate dimeglumine, which is enlarged and quantified in (B).
  • Contrast enhancement of the normal infundibular recess using 3D FLAIR
    Iichiro Osawa1, Eito Kozawa1, Yuya Yamamoto1, Sayuri Tanaka1, Taira Shiratori1, Akane Kaizu1, Kaiji Inoue1, and Mamoru Niitsu1
    1Saitama Medical University Hospital, Saitama, Japan
    The infundibular recess (IR) was enhanced on HT2-FLAIR after an intravenous gadolinium injection. Enhancement was stronger on post-contrast images than on 4-h delayed post-contrast images. IR showed stronger enhancement than other CSF spaces.
    Figure 1. Contrast enhancement of the infundibular recess. The infundibular recess is hyperintense on axial (A, arrow) and midsagittal reformatted (B, arrow) MR cisternography (MRC). It shows contrast enhancement on axial (C, arrow) and midsagittal reformatted (D, arrow) post-contrast HT2-FLAIR.
    Figure 2. Chronological changes in contrast enhancement in the infundibular recess. The infundibular recess (IR) is hyperintense on MR cisternography (MRC) (A, arrow). On HT2-FLAIR, compared with a pre-contrast image (B), a post-contrast image (C, arrow) of IR shows stronger enhancement. A 4-h delayed post-contrast image (D, arrow) shows weaker enhancement. We fuse MRC and each HT2-FLAIR into one image (E, F, and G), and enhancement on post-contrast HT2-FLAIR (F) corresponds to IR hyperintensity on MRC.
  • Whole-Brain T1 and T2 Mapping in Mouse by 3D Magnetic Resonance Fingerprinting
    Yuran Zhu1, Yuning Gu1, Kihwan Kim1, Charlie Androjna2, Chris A. Flask1,3,4,5, Yong Chen3,6, and Xin Yu1,3,7
    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
    A 3D MRF sequence was developed for simultaneous T1 and T2 mapping of the entire mouse brain. Our results demonstrate that up to 16-fold in-plane and 3-fold through-plane undersampling can be achieved with adequate accuracy, allowing whole-brain T1 and T2 mapping in 3 to 5 minutes.
    Figure 2. Retrospective undersampling analysis on a fully-sampled mouse brain. A. T1 maps of fully sampled (Rxy=1, Rz=1) mouse brain and prospectively undersampled data (Rxy=8, Rz=1; Rxy=8, Rz=3; Rxy=16, Rz=1; Rxy=16, Rz=3) of three central axial views. B. T2 maps of fully sampled and undersampled results.
    Figure 1. Retrospective undersampling analysis of fully-sampled phantom data. A. Images of the 120th frame image of a central axial view reconstructed from fully sampled data (Rxy=1, Rz=1) and undersampled data (Rxy=8, Rz=1; Rxy=8, Rz=3; Rxy=16, Rz=1; Rxy=16, Rz=3). B. Plots of fingerprints vs. dictionary matching results for the pixel highlighted in A. C. T1 maps of fully sampled and undersampled results. D. T2 maps of fully sampled and undersampled results. E. Normalized RMSE (NRMSE) of T1 and T2 estimations with different undersampling factors.
  • In vivo characterization of effect of microglia regeneration after high altitude exposure by quantitative MRI in mice
    Alexandru V Korotcov1,2, Caroline A Browne3, Andrew K Knutsen1,2, Dara L Dickstein2,4, Juan Wang4, Xiufen Xu2,5, Kathleen Whiting2,5, Shalini Jaiswal1,2, Allison Nathanael1, Daniel P Perl4, Zygmunt Galdzicki2,5, and Bernard J Dardzinski1,2
    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
    Behavioral tests and MRI preliminary analysis suggest that novel treatment with microglial regeneration could restore spatial memory, enhance cued fear memory and reverse some neuropathological deficits induced by chronic high-altitude exposure.
    Representative T2-weighted high resolution image overlayed with manually drawn ROIs, T2 map, T1 map, FA, TR and the template MR image.
    The T2, T1, FA, and TR ROIs values in four brain regions are shown on the panel. The analysis of the derived results showing elevated trace values in all selected regions in HA conditioned mice which was reversed by PLX treatment.
  • Measurement of ATP Hydrolysis Rates in the In Vivo Heart at 7T
    Adil Bashir1, Jianyi Zhang2, and Thomas S Denney3
    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
    We demonstrate the application of indirect technique to measure Adenosine Triphosphate (ATP) hydrolysis reaction rate constant in the in vivo heart, without the need to quantify inorganic phosphate (Pi) concentration. The technique was applied in human and swine hearts.
    Three representative spectra from magnetization saturation transfer (MST) experiment in swine heart to measure myocardial 31P reaction rates. Control spectrum (middle) without saturation pules to measure $$$ M_{o,PCr} $$$ , and $$$ M_{o,γATP} $$$. Single resonance (γ-ATP) saturated spectrum (left) to quantify $$$ M_{s,PCr} $$$. Dual resonance(PCr and Pi) saturated spectrum (right) to quantify $$$ M_{s,γATP} $$$ .
    (a) BISTRO based saturation transfer pulse sequence. Tsat is the saturation time (b) Simulationof single saturation (green) and dual saturation (blue) BISTRO RF pulse at various power levels overlaid over spectrum from heart demonstrating saturation of γ-ATP (single saturation) and PCr and Pi (dual saturation) frequencies.
  • Radial tiny golden angle MRI combined with Cardiac and Respiratory Self-Gating in the Small Animal model – one acquisition, many possibilities
    Patrick Metze1, Hao Li2, and Volker Rasche1,2
    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 allows for reconstruction of high-quality respiratory and cardiac gated images and sliding-window real-time imaging from the same continuous acquisition, enabling e.g. simultaneous perfusion and function assessment.
    Figure 4: Continuous tyGA acquisition with simultaneous administration of contrast agent. a) and c) show image ROI and k-space intensities over the whole acquisition, b) shows the image intensities around the timepoint of administration. d) shows example sliding-window images and e) and f) correspond to dual gated reconstructions before and after contrast administration. Row-wise differences indicate different respiration stages, column-wise differences show the influence of the cardiac phase.
    Figure 3: Self-gated reconstructions of an exemplary cardiac (SAx) and lung (coronal) acquisition. Due to the properties of the tyGA trajectory, artefact levels for respiratory ungated cardiac imaging is very low. However, differences to respiratory gated imaging can not only be seen in the vessels, but also in the heart itself. Cardiac gating seems mandatory for lung imaging, as shape and position of vessels clearly change with the heartbeat and could influence functional measurements.
  • Anatomical and microstructural brain alterations in the TDP-M323K mouse model of amyotrophic lateral sclerosis
    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 Miller1
    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
    ALS is a devastating disease characterized by aggregates of TDP-43 protein in the brain. We assessed structural and microstructural alterations in the brain of TDP-M323K mice with preclinical MRI. This mouse model of ALS presented imaging alterations compatible with neurodegeneration.
    Figure 1. Representative images and diffusion MRI maps. (a) T2w structural image for volumetric analysis. b-d: Parametric maps extracted from diffusion MRI after modelling the signal to the diffusion kurtosis model: FA: fractional anisotropy (b), MD: mean diffusivity (c), and MK: mean kurtosis (d). e,f: Parametric maps extracted using the NODDI model: OD: orientation dispersion (e) and ICVF: intracellular volume fraction (f). Scale bar: 5 mm.

    Figure 3. Effect of genotype in brain volume in TDP-M323K mice. (a) When compared directly to WT mice, TDP-M323K mice showed smaller volumes in almost all regions of the brain. (b) When volumes relative to the whole brain size were compared, TDP-M323K mice showed atrophy mainly in the white matter, while regions in the cortex and hippocampus had relatively increased volume. Most of the spatial patterns in t-statistics maps are bilaterally symmetric. Atrophic regions in TDP-M323K mice are show in blue and hypertrophic regions are show in red/yellow. False discovery rate of 5%.

  • Changes in Correlation Between Brain Metabolites Due to Acute Stress in Mouse Hippocampus using Proton Magnetic Resonance Spectroscopy
    Chang-Soo Yun1, Yoon Ho Hwang2, Min-Hee Lee3, Wooseung Kim2, Jehyeong Yeon1, Hyeon-Man Baek4, Dong Youn Kim2, and Bong Soo Han1
    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
    To observe changes in correlations between metabolites from the glutamatergic and aspartate systems due to acute stress using MRS.
    Fig. 1. The 256 FID MRS data acquisition protocol in the acute stress experiment using 9.4T Bruker equipment.
    Fig. 2. Non-parametric sign test about correlation coefficient value both of two experimental groups. The orange box is satisfied with the statistically significant sign test p < 0.05. The Control group has not significant correlation coefficient between all metabolites. However, acute stress group have significant between Gln-GSH, Glu-NAA, GSH-NAA.
  • Phenotyping a Mouse Model of TRAPPC9-Associated Intellectual Disability using Magnetic Resonance Imaging
    Mark David Platt1, Harish Poptani1, Antonius Plagge2, and Mahon Maguire1
    1Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom, 2Cellular and Molecular Physiology, University of Liverpool, Liverpool, United Kingdom
    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.
    Figure 1: Example slices of the in vivo T2-weighted images with segmentation masks for the cerebellum (A) and corpus callosum (B) overlaid in ITK-Snap (http://www.itksnap.org).
    Figure 2: Boxplots showing the full range, median and average (+) values for brain volumes in neonates (A), young adults (B), aged adults (C) and regional volumes of corpus callosum (D) and cerebellum (E). Significance levels are indicated by: ns = P > 0.05, * = P ≤ 0.05, **= P ≤ 0.01, ***= P ≤ 0.001, ****= P ≤ 0.0001.
  • Cerebral metabolic derangements as translatable biomarkers in pantothenate kinase-associated neurodegeneration mouse model via 1H MRS
    Puneet Bagga1, Jeffrey Steinberg2, Walter Akers2, Zoltan Patay1, Beth McCarville1, Chitra Subramanian3, Charles O Rock3, and Suzanne Jackowski3
    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
    1H MRS detectable metabolic derangements in a preclinical model of pantothenate kinase-associated neurodegeneration (PKAN) as biomarkers of drug response.
    Figure 2. Representative 1H MR spectra from three groups Left. Wild Type, Mid. Pank1,2 neuronal KO, and Right. Pank1,2 neuronal KO mouse treated with BBP-671
    Figure 3. Metabolite to total creatine ratios of glutamate+glutamine (Glx), γ-amino butyric acid, N-acetyl aspartate, and lactate
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Digital Poster Session - Contrast Agents & Preclinical Studies II
Cancer/Spectroscopy/Molecular Imaging/Pre-Clinical
Monday, 17 May 2021 15:00 - 16:00
  • Deuterium MRI for HDO Imaging of the Rat Brain Following Metabolism of [2H7]glucose
    Rohit Mahar1, Huadong Zeng2, Anthony Giacalone3, Mukundan Ragavan3, Thomas H. Mareci3, and Matthew E. Merritt3
    1Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, United States, 2Advanced Magnetic Resonance Imaging and Spectroscopy (AMRIS) Facility, University of Florida, Gainesville, FL, United States, 3Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, United States
    The gradient echo methods demonstrate the first efficacious use of HDO generated from [2H7]glucose as a means for producing metabolically sensitive MR images. The HDO image should serve as an accurate biomarker of glycolytic flux and recapitulate glx kinetics in the functioning brain.
    Figure 2: Multi-gradient echo (MGE) imaging to separate the contribution of [2H7]glucose and HDO to DMRI image of the rat brain. Image (d) represents the deuterium image of HDO-only and (e) is the overlaid images of (a) proton (grey) and (d) deuterium (green) images due to HDO-only in the rat brain. Image (f) represents the deuterium image from the contribution of [2H7]glucose-only and image (g) is the overlaid image of (a) proton and (f) deuterium [2H7]glucose-only images.
    Figure 3: Schematic representation of the production of deuterated lactate, glutamate/glutamine (glx), and HDO from [2H7]glucose during glycolysis and the TCA cycle. Deuterium (2H) loss has been shown in the form of 2HOH, and NAD2H. Small and large red filled circles represent 1 and 2 deuterium atoms respectively, black filled, and empty circles represent hydrogen atoms and quaternary carbons, respectively.
  • Tracking cancer cells in the mouse brain with magnetic resonance imaging (MRI) and magnetic particle imaging (MPI)
    Natasha N Knier1,2 and Paula J Foster1,2
    1University of Western Ontario, London, ON, Canada, 2Robarts Research Institute, London, ON, Canada
    In this study, we demonstrate that brain metastatic breast cancer cells can be labeled with Synomag-D™ and detected in vivo in the mouse brain with MPI. Iron content within was quantified, addressing a major limitation of iron-based MRI cell tracking.
    Figure 3: MPI of mouse brains injected with 2x105 Synomag-D labeled 231BR cells at day 0, imaged with a FOV of 6 cm x 4 cm.
    Figure 4: Representative MRI with a FOV of 1.5 cm x 1.5 cm of mouse brains injected with 2.5 x 105 231BR cells labeled with MPIO at Day 0. Discrete signal voids representing iron labeled cancer cells appear throughout the brain (white arrows).
  • Consolidated simulation of 23Na Dynamics in Biological Tissue
    Chengchuan Wu1, Yasmin Blunck1, and Leigh A. Johnston1
    1Department of Biomedical Engineering, The University of Melbourne, Parkville, Australia
    This work presents a mathematical framework that enables the simulation for the dynamics of the spin-3/2 23Na density operator.
    Figure 1: The SBE system matrix, $$$\mathbf{L}$$$, colour-coded to indicate source of terms: Red-shaded entries are associated with RF excitation; Yellow-shaded entries are off-resonance terms; Green-shaded terms are associated with residual quadrupolar oscillation; Blue-shaded terms are associated with the fluctuating quadrupolar interaction.
    Figure 3: (a) Shape of the WURST inversion pulse, and the evolution of bulk magnetisation in (b) saline, (c) xanthan.
  • α-ATP suppression in 31P MR spectroscopy by homonuclear BIRD filter: An approach to quantify NAD+ and NADH at 3T in vivo
    Julian Mevenkamp1, Yvonne M.H. Bruls1,2, Robin A. de Graaf3, Joachim E. Wildberger1, Matthijs K.C. Hesselink2, Lucas Lindeboom1,2, and Vera B. Schrauwen-Hinderling1,2
    1Department of Radiology & Nuclear Medicine, Maastricht University Medical Center, Maastricht, Netherlands, 2Department of Nutrition & Movement Sciences, Maastricht University, Maastricht, Netherlands, 3Department of Radiology & Biomedical Imaging, Yale School of Medicine, New Haven, CT, United States
    Our newly developed homonuclear BIRD filter suppresses α-ATP resonances in 31P MRS and therefore allows the quantification of NADH and NAD+ resonances on clinical scanners at 3T. However, separation of NADH and NAD+ resonances remains challenging.
    Figure 1: Schematics of homonuclear BIRD (HB) filter. After an initial adiabatic 90⁰ hard pulse and two adiabatic 180⁰ pulses, α-ATP spins acquire a phase of 90⁰ with respect to uncoupled spins at t=TEj =1/2J and end up aligned with y’ (t=TEj). At t90-x a non-selective 90⁰ block pulse flips spins with J-coupling constants different from that of α-ATP about the y’-axis back towards the z-axis. Spins remaining spins in the x’-y’ plane are then dephased by GSpoil. Zero quantum coherences (ZQC) are removed by co-adding signals acquired with a variable delay Td.
    Figure 3: Comparison between NAD+/H fitting results from (A) FID and (B) HB filtered spectra. NAD+/H resonances are clearly more separated from α-ATP in HB filtered spectra than in the FID.
  • Validation of OxFlow Measurements of Whole-Brain CBF, OEF and CMRO2 by Simultaneous PET/MRI
    Lucas Narciso1,2, Tracy Ssali1,2, Linshan Liu1, Heather Biernaski1, John Butler1, Laura Morrison1, Jennifer Hadway1, Jeffrey Corsaut1, Justin W. Hicks1, Michael C. Langham3, Felix W. Wehrli3, Hidehiro Iida4, and Keith St Lawrence1,2
    1Lawson Health Research Institute, London, ON, Canada, 2Department of Medical Biophysics, Western University, London, ON, Canada, 3University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States, 4University of Turku and Turku PET Centre, Turku, Finland
    Whole-brain cerebral blood flow, oxygen extraction fraction, and cerebral metabolic rate of oxygen measurements from OxFlow-MRI and PET were in good agreement. OxFlow was sensitive to reduced metabolism due to increased anesthetics.
    Figure 2. Comparison between (A) CBF, (B) OEF and (C) CMRO2 estimates from DBFM (PET-only technique) and OxFlow (n = 8). No significant difference was observed for all three measurements. The dashed and solid lines represent the identify and regression lines, respectively. A significant anesthetics-induced reduction in (D) WB CBF (27.3 ± 7.0 mL/100g/min) was accompanied by an increase in (E) WB OEF (0.38 ± 0.12), resulting in a significant decrease in (F) CMRO2 (1.15 ± 0.33 mLO2/100g/min).
    Figure 1. Magnitude and phase images from the slices used to estimate (A)-(B) WB CBF and (C)-(D) SvO2. The regions-of-interest (red dashed) were transferred from the magnitude to the phase image (in white). Images are from one representative animal.
  • CNS Involvement in a Non-human Primate Model Infected with Aerosolized Ebola Virus
    Byeong-Yeul Lee1, Jeffrey M. Solomon2, Marcelo Castro1, Dong-Yun Kim3, Joseph Laux1, Matthew G. Lackemeyer1, Jordan K. Bohannon4, Anna N. Hanko5, Dima Hammoud6,7, and Ji Hyun Lee1
    1Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD, United States, 2Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD, United States, 3Office of Biostatistics Research, National Heart, Lung and Blood Institute, Bethesda, MD, United States, 4National Biodefense Analysis and Countermeasures Center, Frederick, MD, United States, 5Microbiology, Boston University School of Medicine, Boston, MA, United States, 6Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, United States, 7Center for Infectious Disease Imaging, National Institutes of Health, Bethesda, MD, United States

    In this work, we found significant increases in T1 and R2* values in the multiple brain regions in a nonhuman primate model of aerosolized Ebola virus (EBOV) infection,  including the cerebellum and occipital lobe, which provides in vivo evidence of brain involvement with EBOV. 

    Figure 1. Averaged T1 map (n=7) of the rhesus macaque brain before and after EBOV exposure: Compared to pre-exposure (top row), the post-exposure T1 map (bottom row) showed noticeable increases in multiple regions, including cerebellum, occipital lobes, deep gray matter, and frontal cortices (white arrows and dotted circles).
    Figure 2. A voxel-based statistical comparison of T1 of the rhesus macaque brain before and after EBOV exposure: There were significant increases in T1 values in various brain regions, in particular in the cerebellum and occipital lobes. Statistical significance was considered at corrected p < 0.001 (one-tailed paired t-test, false discovery rate correction). The colorbar shows a T-score range.
  • Characterization of a Novel Hypomyelination Mouse Model Using Microstructural Imaging of Myelin Volume Fraction and Axon g-ratio
    Vladimir Grouza1,2, Zhe Wu1,3, Marius Tuznik1,2, Hooman Bagheri4, Dan Wu5, Alan C Peterson2,4,6, and David Rudko1,2,7
    1McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, Montreal, QC, Canada, 2Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada, 3Techna Institute, University Health Network, Toronto, ON, Canada, 4Department of Human Genetics, McGill University, Montreal, QC, Canada, 5Russell H. Morgan Department of Radiology & Radiological Science, Johns Hopkins University, Baltimore, MD, United States, 6Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada, 7Department of Biomedical Engineering, McGill University, Montreal, QC, Canada
    The application of BSS-rPCA MWF estimation was evaluated with the aide of a well characterized hypomyelinating mouse model. Resultant estimates were found to correlate well with Mbp/Golli mRNA expression levels.
    Figure 1: Coronal slices showing FA, AVF, MVF, and g-ratio parameter maps in WT and M1M3M5KO mice. Selected slices in the top two rows permit visualization of the genu of the corpus callosum and the anterior commissure white matter tract. The bottom two rows display the internal capsule and the splenium of the corpus callosum in the mouse brain. The difference myelin volume fraction signal between WT and M1M3M5KO is evident based on red arrows overlaid on the mouse brain images.
    Associations between myelin volume fraction, derived from BSS rPCA-based multi-component T2* analysis, and relative myelin basic protein mRNA levels in three major white matter tracts of the mouse brain. Mbp mRNA levels were derived using qRT-PCR as described in Bagheri et al.1 In anterior commissure, splenium of the corpus callosum and internal capsule white matter, MVF scales linearly with relative Mbp mRNA. This supports the conjecture that Mbp mRNA level is a critical determinant of MRI-sensitive myelin bilayer properties.
  • Thalamic reticular nucleus injury as the cause of thalamocortical dysrhythmia in mild traumatic brain injury: a rodent model DTI study
    Duen-Pang Kuo1,2, Yi-Tien Li1,3, Chen-Yin Ou1, Yung-Chieh Chen1,2, and Cheng-Yu Chen1,2
    1Translational Imaging Research Center, Taipei Medical University Hospital, Taipei, Taiwan, 2Department of Medical Imaging, Taipei Medical University Hospital, Taipei, Taiwan, 3Neuroscience Research Center, Taipei Medical University, Taipei, Taiwan
    Significant DTI changes were found at the boundary of bilateral thalami where high shear stress was expected, suggesting that disinhibition of inhibitory circuits from the thalamic reticular nucleus may play a role in thalamocortical dysrhythmia. 
    Figure 1 Statistical parametric maps of the FA changes between pre- and post-impact Significantly increases in FA at bilateral thalamic borders (green arrows) were observed post-impact as compared with pre-impact. The dark blue indicated the location of bilateral TRN. These maps were further masked by the threshold of group-averaged FA > 0.15.
    Figure 3. Longitudinal changes in DTI metrics after impact (A) Bilateral segmented ROIs showing the areas of thalamus (red),cortex (yellow), TRN(blue) and WM(green) (B) Longitudinal follow-up during the first 35 days shows that FA increased in thalamus, WM and TRN at day 7 as well as during the follow-up. Contrary to FA, MD, AD and RD decreased with time except for AD in TRN. (thalamus comparison with baseline[before impact]: # P <0.01; cortex comparison with baseline: * P <0.01; WM comparison with baseline: ǂ P <0.05; TRN comparison with baseline: + P <0.05 ; data presented as mean ± sd)
  • HIV Theranostics Based on Intrinsic CEST Contrasts of Antiretroviral Drugs
    Aditya Bade1, Howard Gendelman1, and Yutong Liu2
    1Pharmacology and Exp Neuroscience, University of Nebraska Medical Center, Omaha, NE, United States, 2Radiology, University of Nebraska Medical Center, Omaha, NE, United States

    1) The CEST effects of  antiretroviral drugs 3TC (lamivudine) and FTC (emtricitabine) were detected at 1 and 2 ppm. 2) In mice administered with 3TC, MRI data was analyzed using Lorentzian functions, and  CEST signal of amino protons of 3TC was detected at ~ 2 ppm on thalamus region.

    Figure 1. CEST signals of 3TC. (A) Chemical structure of 3TC. The hydroxyl group is in red circle, and the amino group in blue circle. (B) MTR plots of 3TC in PBS at 37oC. MTR increases at 2 ppm with the 3TC concentration. (C) MTR@2ppm increases linearly with 3TC concentration (R2 = 0.95). (D) Pixel-by-pixel color maps of 3TC samples.
    Figure 3. (A) Lorentzian functions of CEST signals of amino protons on thalamus from a mouse scanned before 3TC administration (baseline), 6 hours after 1st drug administration and after 5 days of daily administration. (B) CEST signal integrals of 3TC on thalamus. (C) Color maps of CEST signal integrals of 3TC superimposed on anatomical images of the mouse brain.
  • Deep Learning of ADC Maps from Under-sampled Diffusion-Weighted Radially Sampled MRI
    Yuemeng Li1, Hee Kwon Song1, Miguel Romanello Giroud Joaquim1, Stephen Pickup1, Rong Zhou1, and Yong Fan1
    1Radiology, University of Pennsylvania, Philadelphia, PA, United States
    Comparisons with standard ADC extraction and acceleration methods are made to support this concept.
    Figure-2: A densely connected Encoder-Decoder network of CNNs (top and middle), enhanced by spatial-attention and channel-attention layers (bottom), for computing ADC maps from undersampled complex image-space data.
    Figure-1 : Representative diffusion-weighted images and ADC map. The tumor is indicated by the red arrow.
  • Multiparametric functional magnetic resonance imaging for longitudinal evaluation of liver regeneration after 70% hepatectomy in a rat model
    shuangshuang xie1, caixin qiu1, yajie sun1, jinxia zhu2, Robert Grimm3, and wen shen1
    1Tianjin First Central Hospital, Tianjin, China, 2MR Collaboration, Siemens Healthcare Ltd., Beijing, China, 3MR Application Development, Siemens Healthcare GmbH, Erlangen, Germany
    IVIM-derived D* and DKI-derived MK can be used as non-invasive indices to monitor liver regenerative activity.
    Figure 2. Longitudinal follow-up magnetic resonance imaging (MRI) measurements of liver. Intravoxel incoherent motion (IVIM)-derived parameters (D, D*, PF), diffusion kurtosis imaging (DKI)-derived parameters (MD, MK), and the blood oxygen level-dependent (BOLD)-derived parameter (R2*) of the liver parenchyma all showed regular changes from days 0 to 21 after surgery, and finally returned to baseline (bs)
    Figure 1. Longitudinal changes of hepatocyte Ki - 67 indices (A) and sizes (B) from baseline (bs) to 21 days (d21) after 70% hepatectomy in rats
  • Investigating differences in lung cancer cells with induced and de-induced cisplatin resistance by 1H HR-MAS NMR metabolomics
    Martina Vermathen1, Hendrik von Tengg-Kobligk2,3, Martin Nils Hungerbühler2,3, Christoph Kempf2,3, Peter Vermathen2,3, and Nico Ruprecht2,3
    1Department of Chemistry and Biochemistry, University Bern, Bern, Switzerland, 2University Institute of Diagnostic, Interventional and Pediatric Radiology, University Bern, Bern, Switzerland, 3Department of BioMedical Research, University Bern, Bern, Switzerland
    More than 40 metabolites were identified in lung cancer cells and in induced and de-induced cisplatin (cisPt) resistant cells. CisPt-resistant cells demonstrated metabolic adaptations that were maintained in de-induced counterparts.

    Figure 4:

    A) oPLS scores plot (LV1 – LV2) using the resistance as scaled prior knowledge (y-table).

    B) Description of the PLS model showing the measured compared to the predicted resistance values.

    Figure 3:

    PCA scores plot (PC1 – PC2) of all samples using the color and form coding introduced in Fig.1.

  • Characterization of cardiac function in early-stage pulmonary arterial hypertension in asymptomatic BMPR2 mutant rats by MRI and 31P MRS
    Dounia El Hamrani1,2, Julie Magat1,2, Jérôme Naulin1,2, Frédéric Perros3, Marilyne Campagnac2, David Benoist1,2, Christelle Guibert2, and Bruno Quesson1,2
    1IHU LIRYC, Bordeaux, France, 2INSERM U1045, CRCTB, Bordeaux, France, 3INSERM UMR_S 999, Université Paris–Saclay, Le Kremlin Bicêtre, France
    Asymptomatic transgenic rats with Bmpr2 mutation showed a decrease in end-diastolic and end-systolic volumes of ventricles leading to a reduced stroke volume. These results indicate a significant decrease in cardiac output but without hypertrophy of ventricles at this early stage.
    Figure 1: Representative short-axis cine FLAH images obtained at end-systolic stage and end-diastolic stage in wild-type (WT) and transgenic (TG) rats (resolution 0.3x0.3x1mm3).
    Figure 5: (A) Typical cardiac localized 31P MRS spectrum obtained in control rat; (B) Ratio phoshocreatine/ATPβ of wild type (WT, n=11) and transgenic (TG, n=12) rats for a duration of 35min prior and after dobutamine injection (10µg/kg). Mean±SEM and Groups were compared by nonparametric t test Mann-Whitney.
  • A pilot study of socially deprivated brain alterations using fMRI and dMRI in domestic dogs
    Xueru Liu1,2, Huilin Hong3, Zhentao Zuo1,2,4, Hui Zhao3, Rui Tian3, Yongqing Zhang2,3,4, and Yan Zhuo1,2,4
    1State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, BeiJing, China, 2University of Chinese Academy of Sciences, Beijing, China, 3State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China, 4CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Beijing, China
    Socially deprived dogs strengthened brain function connectivity within frontal cortex and weakened function connectivity between PFC with the visual and auditory cortex. Diffusion metrics observed demyelination in frontal, temporal, and insula regions after 4 weeks social deprivation.
    Figure 4. Statistics of FA values of 86 ROIs in the cortex, white matter, and subcortical nucleus between SD and WT groups. The t values were obtained by unpaired t-test of FA maps from two groups.
    Figure 3. Comparison of connectivity strength between social deprivation and wild type groups. The r values of 86 ROIs were compared between SD and WT. The two charts showed ROIs with significant differences. The red arrows indicated that the FA values in the temporal lobe and nucleus caudatus of socially deprived were significantly reduced compared with WT.
  • Vcan mutation leads to sex-specific changes in white matter microstructure in mice
    Cristiana Tisca1, Mohamed Tachrount 1, Frederik Lange1, Chaoyue Wang1, Lily Qiu1, Javier Barallobre-Barreiro2, Marika Fava2, Manuel Mayr2, Jason Lerch1,3,4, Aurea Martins-Bach1, and Karla Miller1
    1Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom, 2British Heart Foundation Centre of Research Excellence, King's College London, London, United Kingdom, 3Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada, 4Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
    We show that male Vcan mice display related dMRI phenotypes to those associated with mutations in VCAN in humans. This gives us the ability to investigate the biological interpretations of human genome-wide association studies results using histology.  

    Figure 3. Violin plots of median FA, OD and ICVF values within 7 ROIs for male mice. *: p-value ≤0.05, FDR-corrected (5%).

    Figure 1. Illustration of the dMRI pipeline. All 64 volumes are corrected for Gibbs ringing6. The data was first corrected for susceptibility-induced off-resonance field distortions and movement using topup7 and eddy8. The diffusion tensor model (FSL DTIFIT) and the NODDI12 model (FSL cuDIMOT13 implementation; d||=5.6x10-4, diso=1x10-3mm2/s, dot compartment included) were fit to the data to produce FA, MD, OD, ICVF and isotropic volume fraction (ISOVF) maps.
  • Metabolic Responses of HeLa Cells upon addition of the Photosensitizer Chlorin e4 and Carriers in the Dark by 1H HR-MAS NMR
    Martina Vermathen1, Tobias Emmanuel Kämpfer1,2, and Peter Vermathen2
    1Department of Chemistry and Biochemistry, University Bern, Bern, Switzerland, 2Departments of BioMedical Research and Radiology, University Bern, Bern, Switzerland
    The photosensitizer chlorin e4 induces already in the dark a dose dependent metabolic response in cells that is attenuated by PVP and block-copolymer micelle carriers shown by HR-MAS NMR. Direct interaction of Ce4 with cellular GPC was detected indicating membrane localization.

    FIGURE 2

    PCA applied to all samples and buckets from 1D projected spectra (259 x 39) (A). Excerpts from the PCA plot in (A) for better visibility of the subclasses, i.e. samples without carriers (B), samples with KP as carrier (C) and samples with PVP as carrier (D).

    FIGURE 5

    (A) HR-MAS 1H-diffusion-edited NMR spectra (1D-DOSY) of lysed HeLa cell suspensions in PBS incubated with different concentrations of Ce4 without carrier or encapsulated into KP or PVP. Shown is the spectral region where the choline containing resonances appear. The GPC resonance exhibits upfield shifts;

    (B) Chemical shift of the GPC-choline resonance as function of condition (Ce4 concentration and carrier)

  • Absolute quantification of cardiac 31P metabolites using surface loop and dipole array coils at 7T
    Jabrane Karkouri1, Stanislav Frištyk2, Lucian AB Purvis3, Christopher T. Rodgers*1, and Ladislav Valkovic*3
    1Wolfson Brain Imaging Center, University of Cambridge, Cambridge, United Kingdom, 2Department of Electromagnetic and Biomedical Engineering, University of Žilina, Zilina, Slovakia, 3Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, Oxford, United Kingdom
    Phosphorus magnetic resonance spectroscopy delivers unique information to aid our understanding of cardiac metabolism. In this study, we investigate the feasibility of absolute concentration of phosphorus metabolites in the human heart at 7T. 
    Figure 5: Results obtained in oxford with the array 16-channel coil. On the right, ATP concentration map overlaid on the heart localizer for better visualization. On the left, an example of fitting using AMARES algorithm (OXSA toolbox, MatLab). In the figure A there is a fitted spectrum. In figure B individual peaks are depicted. Residuals are shown in figure C and in the figure D the initial values for non-linear fit are depicted.
    Figure 4: Results obtained in Cambridge with the dipole array coil from Tesla DC. In A), the placement of the csi grid is shown. In B), an example of fitting using AMARES algorithm (OXSA toolbox, MatLab) from the highlighted pixel. In the figure, there is a fitted spectrum, individual peaks are depicted. In C), The ATP concentration map is overlaid on the heart localizer for better visualization.
  • Deuterium MRI brain mapping of absence seizure medication: ethosuximide illustration
    Andrey N. Pravdivtsev1, Arne Brahms2, Jens Gröbner3, Rosa Rojas4, Eva Peschke1, Anna-Sophia Buschhoff4, Frowin Ellermann1, Rainer Herges2, Jan-Bernd Hövener1, and Peer Wulff4
    1Section Biomedical Imaging, MOIN CC, Kiel University, Kiel, Germany, 2Otto Diels Institute for Organic Chemistry, Kiel University, Kiel, Germany, 3Fachhochschule Südwestfalen, Fachbereich Elektrotechnik und Informationstechnik, Lüdenscheid, Germany, 4Institute of Physiology, Kiel University, Kiel, Germany

     

    We investigated the feasibility of 2H-MRS to assess the distribution of the anti-absence epilepsy drugs. The fast relaxation time and small magnetogyric ratio of deuterium allowed measuring of 2H-PRESS spectra of 4mm x 4mm x 4mm voxel with 9 mM of ethosuximide-D4,4' with SNR of 9 in 40 minutes.

    Figure 5. 1H T2-TurboRARE image (a) 1H- (b) and 2H-PRESS spectra (c). The phantom consists of six 5 mm NMR tubes with ETX-D4,4’ (0, 9, 18, 27, 36 and 45 mM) in aqueous 100 mM PBS buffer. Red boxes represent the PRESS voxels: 4mm*4mm*4mm. 1H-PRESS parameters are: TE=16.5ms, TR=2000ms, NS=1200, acquisition time AQ=467ms, experiment time ET=40min, spectral bandwidth SW=4386 Hz. 2H-PRESS parameters are TE=14.2ms, TR=300ms, NS=8000, AQ=247ms, SW=8196Hz, ET=40min. Exponential line broadening was 4 Hz. Spectra were zero-filled to achieved nominal spectral resolution per point of 1 Hz.
    Figure 4. ETX-D4,4’ 2H-PRESS signal as a function of TE (a, TR = 200 ms), TR (b, TE = 14.2 ms) and 2H-PRESS signal divided by TR0.5 (c). The later reveals the most efficient for SNR value of TR with the fixed scanning time. This value is predicted to be close to 1.25*T1 = 300 ms. Lines are fitting of experimentally measured integrals of ETX-D4,4’, fitting equations are given on the plots.
  • Correlating patterns in tumor cytoarchitecture with multiparametric MR signal in preclinical models of sarcoma
    Stephanie J Blocker1, James Cook1, Yvonne M Mowery2, Jeffrey I Everitt3, Yi Qi1, Kathryn Hornburg1, Gary P Cofer1, Fernando Zapata1, Alex M Bassil2, Cristian T Badea1, David G Kirsch2, and G. Allan Johnson1
    1Radiology, Duke University, Durham, NC, United States, 2Radiation Oncology, Duke University, Durham, NC, United States, 3Pathology, Duke University, Durham, NC, United States
    We have constructed a preclinical pipeline for registration of in vivo MRI, MR histology, and digitized pathology.  Correlative analyses identified a selection of cytometric features in murine sarcomas which demonstrate linear trends with ex vivo and in vivo MR, including ADC and T2*.
    Figure 1: Schematic for co-registration of high-resolution 3D MRH with cytometric property maps derived from 2D H&E histology slides. Demonstration of the four phases for correlative MR studies: (1) Registration of MR to H&E slides; (2) Implementation of a multi-step algorithm for nuclear segmentation over entire histology slides; (3) Measurement of segmented nuclei and generation of quantitative cytometric feature maps; (4) Correlative studies of tumor MR signal and cytometric features.
    Figure 4: Relationships between MR and pathology features. Shown is an in vivo T2* sarcoma image (A). A map of variance in Delaunay triangle area (VDta) shows variable tumor cell organization (B). Correlation of VDta and T2* shows non-zero relationships in both ex vivo T2* (C; p < 0.0001, R2 = 0.27) and in vivo T2* (D; p = 0.0004, R2 = 0.18). R2 values reflect small pilot size (n=8).
  • PET-MR imaging of reactive macrophages in an orthotopic model of ovarian cancer
    Catherine Foss1, Desmond Jacob1, Flonné Wildes1, and Marie-France Penet1
    1The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
    Using PET-MRI in an orthotopic model of ovarian cancer, specific uptake of [124I]iodo-DPA-713 was observed in reactive macrophage, within and proximal to the primary tumor at early stages, and in ascitic fluid and lung metastases at later stages.
    PET images of a tumor bearing mouse (A,C) and a sham mouse (B,D) with coronal (A,B) and corresponding axial slices (C,D). Corresponding fused PET-MR images (E-H).
    Bioluminescent images of 5 orthotopic ID8-Defb29-VEGF tumor bearing mice