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Biomedical Magnetic Resonance: Molecular Imaging and Metabolism
 
March 2 - 5
Carlos Geraldes (geraldes@bioq.uc.pt), John Jones

CENTER FOR NEUROSCIENCE AND CELL BIOLOGY (CNC)
Ph. D. Program in Experimental Biology and Biomedicine (BEB)
 
PhD. Course: BIOMEDICAL MAGNETIC RESONANCE:
MOLECULAR IMAGING AND METABOLISM
 
Area: New Techniques in Biomedicine
 
Duration: 2- 5 March 2010
 
Location: Anfiteatro 2.º andar - CNC, Edifício FMUC
 
Coordinators: Carlos Geraldes (geraldes@bioq.uc.pt), John Jones
(jones@cnc.cj.uc.pt)
(CNC, Coimbra)
 
Lecturers:
Kevin Bridle  
Cancer Research UK,University of Cambridge, UK
 
Arend Heerschap            
Department of Radiology, Radboud University Nijmegen Medical Centre,
Nijmegen, The Netherlands                        
 
Enzo Terreno                  
Molecular Imaging Center, University of Torino, Italy
 
 
Objectives and Scope
The objectives of this course are to introduce the PhD students to current important applications of Nuclear Magnetic Resonance (NMR) in Biomedicine, both in spectroscopy and imaging. These are very dynamic and exciting research fields, where new developments are expanding the applicability of Biomedical NMR for noninvasive analyses of animal disease models and humans. The topics to be covered are: a) application of the NMR methodology with the use of stable isotope tracers (eg. 13C, 2H, 15N) to metabolic studies, from basic to clinical applications in health and disease; new hyperpolarization techniques, which make NMR competitive with PET, will be illustrated; b) In vivo 1H and 13C MRS studies of human physiology pathologies; c) MRI-based and multimodal molecular imaging studies, including magnetic cell labelling and tracking, which are currently of very high interest; the use of Nanosciences (eg. liposomes) in the development of contrast agents for Molecular Imaging and image-guided therapy using MRI and multimodal approaches.
This course will be included in the programmed proposed activities of the National NMR Network, to which the CNC participates through the NMR Laboratory.
 
 
Organization of the course
There will be lectures, where informal format, and Journal Club-like Discussions. All students will have access to representative papers published by the Faculty Members and are strongly encouraged to read them beforehand. This Course in mandatory for Ph.D. students following the CNC Program in Experimental Biology and Biomedicine (BEB), but is also open to all other students, members of the National NMR Network and the general public.
BEB students (and other Ph.D. students who wish to participate for credit) will be asked to present assigned papers (i.e., PowerPoint presentations). Assignments will be discussed by the Invited Lecturers according to the program and these will form a significant part of each student´s evaluation.
PhD students that are not in the BEB Program are welcome to participate in this course for credit. In order to be admitted they must register for the Course with the organizer two weeks before the Course starts (i.e. 16 February 2010) organizer for an assignment.

 

 

Course Program
 
 
Tuesday, March 2:     MRI, MRS and Hyperpolarization   
 
9.30 -11.00 h              
Monitoring tumour responses to treatment using magnetic resonance imaging
and spectroscopy
Kevin Brindle
 
11.30-13.00 h
Imaging tumour cell metabolism with hyperpolarized C-13-labelled cell substrates
Kevin Brindle
 
15.00-17.30 h
Analysis and discussion of papers by the students
 
 
Wednesday, March 3: In vivo 13C NMR and Metabolism
 
9.30 -11.00 h              
In vivo 13C NMR studies of metabolism: History and Introductory concepts
Arend Heerschap
 
11.30-13.00 h             
Applications of in vivo 13C NMR spectroscopy to human metabolic studies
Arend Heerschap
                                               
15.00-17.30 h
Analysis and discussion of papers by the students


Thursday, March 4:  MRI and Molecular Imaging
 
19.30 -11.00 h            
Innovative MRI probes for Molecular Imaging
Enzo Terreno
 
11.30-13.00 h
Cell labeling/tracking protocols by MRI 
Enzo Terreno
 
15.00-17.30 h
Analysis and discussion of papers by the students
 
 
Friday, March 5:
 
10.00-12.00 h         
Free
 
16.00-17.30 h: CNC Seminar
“In vivo NMR Metabolic Studies of Human Heath and Disease”
Prof. Arend Heerschap                      
Department of Radiology,  Radboud University Nijmegen Medical Centre,
Nijmegen, The Netherlands

Invited Lecturers
                 
1. Professor Kevin M. Brindle
Department of Biochemistry, University of Cambridge, and Cancer Research UK, Cambridge Research
Institute, Li Ka Shing Centre,
Cambridge, United Kingdom
e-mail: kmb@mole.bio.cam.ac.uk
 
Papers for evaluation
Sam E Day, Mikko I Kettunen, Ferdia A Gallagher, De-En Hu, Mathilde Lerche, Jan Wolber, Klaes Golman, Jan Henrik Ardenkjaer-Larsen and Kevin M Brindle
Nature Medicine, 13: 1382-1387 (2007)
 
Ferdia A. Gallagher, Mikko I. Kettunen, Sam E. Day, De-En Hu, Jan Henrik Ardenkjær-Larsen, René in ‘t Zandt, Pernille R. Jensen, Magnus Karlsson, Klaes Golman, Mathilde H. Lerche and Kevin M. Brindle
Nature, 453: 940- 943 (2008)
 
Ferdia A. Gallagher, Mikko I. Kettunen, De-En Hu, Pernille R. Jensen, Rene´ in ‘t Zandt, Magnus Karlsson, Anna Gisselsson, Sarah K. Nelson, Timothy H. Witney, Sarah E. Bohndiek, Georg Hansson, Torben Peitersen, Mathilde H. Lerche, and Kevin M. Brindle
PNAS : 106, 19801–19806 (2009)
 
Other papers
Kevin Brindle
Nature Reviews Cancer : 8, 94 – 107 (2008)
 
F.A. Gallagher, M.I. Kettunen, K.M. Brindle
Progress in Nuclear Magnetic Resonance Spectroscopy : 55,285–295 (2009)
 
2.  Professor Arend Heerschap                     
Department of Radiology
Radboud University Nijmegen Medical Centre,
Nijmegen, The Netherlands                        
 
 
Papers for evaluation
H.E. Kan, M. van der Graaf, D.W.J. Klomp, M.H.M. Vlak, G.W. Padberg and
A. Heerschap
Magnetic Resonance in Medicine, 56: 953–957 (2006)
 
C.I.H.C. Nabuurs, D.W.J. Klomp, A. Veltien, H.E. Kan and A. Heerschap
Magnetic Resonance in Medicine, 59: 626–630 (2008)
 
Marinette van der Graaf, Cees J. Tack, Jacco H. de Haan, Dennis W. J. Klomp and Arend Heerschap
NMR in Biomedicine, in press (2009) DOI:10.1002/nbm.1433
 
3. Professor Enzo Terreno
Associate Professor of General and Inorganic Chemistry - (Italy)
Department of Chemistry and Molecular Imaging Center
University of Torino, Torino, Italy
e-mail: enzo.terreno@unito.it
 
Papers for evaluation
Giuseppe Digilio, Valeria Catanzaro, Franco Fedeli, Eliana Gianolio, Valeria Menchise,Roberta Napolitano, Concetta Gringeri and Silvio Aime
Chem. Commun., 893–895 (2009)
 
Daniela Delli Castelli, Enzo Terreno, Claudia Cabella, Linda L. Chaabane, Stefania Lanzardo, Lorenzo Tei, Massimo Visigalli, Silvio Aime
 NMR in Biomedicine22: 1084-1092 (2009) 
 
Karen C. Briley-Saebo, Simonetta Geninatti-Crich, David P. Cormode,
Alessandra Barazza, Willem J. M. Mulder, Wei Chen, Giovanni B. Giovenzana, Edward A. Fisher, Silvio Aime, and Zahi A. Fayad
J. Phys. Chem. B, 113:6283–6289 (2009)
 
 
Other papers
Enzo Terreno, Simonetta Geninatti Crich, Simona Belfiore, Luigi Biancone,
Claudia Cabella, Giovanna Esposito, Andrea D. Manazza, and Silvio Aime
Magnetic Resonance in Medicine55: 491–497 (2006)
 
Mark Woods, Donald E. Woessner and A. Dean Sherry
Chem. Soc. Rev., 35: 500–511 (2006)
 
Enzo Terreno, Daniela Delli Castelli, Claudia Cabella, Walter Dastrú, Alberto Sanino,Joseph Stancanell, Lorenzo Tei, and Silvio Aime
Chemistry & Biodiversity, 5: 1901-1912 (2008)
 
Daniela Delli Castelli, Eliana Gianolio, Simonetta Geninatti Crich, Enzo Terreno, Silvio Aime
Coordination Chemistry Reviews 252: 2424–2443 (2008)



Assigments and papers for students:

 

1) “Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy”

Sam E Day, Mikko I Kettunen, Ferdia A Gallagher, De-En Hu, Mathilde Lerche, Jan Wolber, Klaes Golman, Jan Henrik Ardenkjaer-Larsen and Kevin M Brindle

Nature Medicine, 13: 1382-1387 (2007)

 

Helena Leitão & Joaquim Pereira

 

2) “Magnetic resonance imaging of pH in vivo using hyperpolarized 13C-labelled bicarbonate”

Ferdia A. Gallagher, Mikko I. Kettunen, Sam E. Day, De-En Hu, Jan Henrik Ardenkjær-Larsen, René in ‘t Zandt, Pernille R. Jensen, Magnus Karlsson, Klaes Golman, Mathilde H. Lerche and Kevin M. Brindle

Nature, 453: 940- 943 (2008)

 

Miranda Mele

 

3) “Production of hyperpolarized [1,4-13C2]malate from [1,4-13C2]fumarate is a marker of cell necrosis and treatment response in tumors

Ferdia A. Gallagher, Mikko I. Kettunen, De-En Hu, Pernille R. Jensen, Rene´ in ‘t Zandt, Magnus Karlsson, Anna Gisselsson, Sarah K. Nelson, Timothy H. Witney, Sarah E. Bohndiek, Georg Hansson, Torben Peitersen, Mathilde H. Lerche, and Kevin M. Brindle

PNAS : 106, 19801–19806 (2009)

 

Marília Cordeiro  & Paula Banca

 

4) “Intake of 13C-4 Creatine Enables Simultaneous Assessment of Creatine and Phosphocreatine Pools in Human Skeletal Muscle by 13C MR Spectroscopy”

H.E. Kan, M. van der Graaf, D.W.J. Klomp, M.H.M. Vlak, G.W. Padberg and

A. Heerschap

Magnetic Resonance in Medicine, 56: 953–957 (2006)

 

Ana Moreira & Rui Batista

 

5) “Localized Sensitivity Enhanced In Vivo 13C MRS to Detect Glucose Metabolism in the Mouse Brain”

C.I.H.C. Nabuurs, D.W.J. Klomp, A. Veltien, H.E. Kan and A. Heerschap

Magnetic Resonance in Medicine, 59: 626–630 (2008)

 

Carlos Rodrigues

 

6) “Magnetic Resonance Spectroscopy Shows an Inverse Correlation Between Intramyocellular Lipid Content in Human Calf Muscle and Local Glycogen Synthesis Rate”

Marinette van der Graaf, Cees J. Tack, Jacco H. de Haan, Dennis W. J. Klomp and Arend Heerschap

NMR in Biomedicine, in press (2009) DOI:10.1002/nbm.1433

 

Humberto Ferreira & Ana Eufrásio

 

7) “Targeting exofacial protein thiols with GdIII complexes. An efficient procedure for MRI cell labelling”.

Giuseppe Digilio, Valeria Catanzaro, Franco Fedeli, Eliana Gianolio, Valeria Menchise,

Roberta Napolitano, Concetta Gringeri and Silvio Aime

Chem. Commun., 893–895 (2009)

 

Ana Martins

 

8) “Evidence for in vivo macrophage mediated tumor uptake of paramagnetic/fluorescent liposomes”

Daniela Delli Castelli, Enzo  Terreno, Claudia Cabella, Linda L. Chaabane, Stefania Lanzardo, Lorenzo Tei, Massimo Visigalli, Silvio Aime

 NMR in Biomedicine,  22: 1084-1092 (2009) 

 

Cláudio Roque & Elizabete Jorge

 

9) “High-Relaxivity Gadolinium-Modified High-Density Lipoproteins as Magnetic Resonance Imaging Contrast Agents”

Karen C. Briley-Saebo, Simonetta Geninatti-Crich, David P. Cormode,

Alessandra Barazza, Willem J. M. Mulder, Wei Chen, Giovanni B. Giovenzana,

Edward A. Fisher, Silvio Aime, and Zahi A. Fayad

J. Phys. Chem. B, 113: 6283–6289 (2009)

 

Ana Pinho & Patrícia Monteiro

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