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Cho Cre Cit RESEARCH GROUP QUANTITATIVE MRI IN MEDICINE AND BIOLOGY Yves De Deene Ghent University, Belgium Quantitative MRI in Medicine and Biology A.

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Presentation on theme: "Cho Cre Cit RESEARCH GROUP QUANTITATIVE MRI IN MEDICINE AND BIOLOGY Yves De Deene Ghent University, Belgium Quantitative MRI in Medicine and Biology A."— Presentation transcript:

1 Cho Cre Cit RESEARCH GROUP QUANTITATIVE MRI IN MEDICINE AND BIOLOGY Yves De Deene Ghent University, Belgium Quantitative MRI in Medicine and Biology A short overview of topics and research perspectives

2 Cho Cre Cit RESEARCH GROUP QUANTITATIVE MRI IN MEDICINE AND BIOLOGY Past and recent research topics at the Ghent University (Belgium)

3 Past research topics QMRI Non-invasive MRI thermometry by use of molecular self-diffusion and the proton resonance frequency (PRF) shift method De Poorter et al, Magn Reson Med 33: (1995) Validation methods for diffusion weighted MRI in brain white matter Fieremans et al, J Magn Reson 190: (2008) Sparse spiral k-space sampling reconstruction Desplanques et al, IEEE Transactions on Nuclear Science 49: (2002) Dose [Gy] De Deene et al, Magn Reson Med 43: (2000) 3D radiation dosimetry using polymer gels and quantitative MRI R2 mapping In vivo quantitative proton MRS Özdemir et al, Phys Med Biol 52: (2007) RESEARCH GROUP QUANTITATIVE MRI IN MEDICINE AND BIOLOGY Dynamic contrast enhanced MRI First-pass imaging Verstraete et al, Radiology 192: (1994)  (°)

4 Quantitative Fluor-19 MRI for oxymetry Gel dosimetry and optical laser CT scanning Dose [Gy] Bone segmentation on UTE MR images Quantitative in vivo MRS Diffusion in brain white matter Relaxometry in lung equiv. tissue Construction of a hyperpolarization generator Quantitative MRI & 3D radiation dosimetry Quantitative MRI of tissue microstructure Quantitative MR spectroscopy PET / MRI multimodality imaging Gel dosimetry Hyperpolarized gas MRI Multi-nuclear MRI RESEARCH GROUP QUANTITATIVE MRI IN MEDICINE AND BIOLOGY Recent / Current Research UGent Overview PhD finished (MEDISIP) PhD finished (MEDISIP) Part time (MEDISIP)

5 RESEARCH GROUP QUANTITATIVE MRI IN MEDICINE AND BIOLOGY MR images (Signal intensity) MR spectra Optimize MR imaging sequences MRI sequence analysis Increase sensitivity through hyperpolarization Computer-aided modeling of MRI properties (Monte-Carlo simulations) (Bloch-Torrey eqn.) Overall research rationale of QMRI MRI quantitative property (T1, T2, D, K trans, MTR, etc.) Metabolite concentration Tracer concentration R1 R2 MT K trans D Quantitative physiological maps (clonogen density, pO 2 cellular size distribution) Biochemical properties Molecular receptors pO 2 ρ cell pH P vasc [Cho] Treatment optimization Prescribed radiation dose distribution Molecular radiobiology Biophysical modeling Chemotherapy prescription S pO 2 D (Gy) 3D radiation dosimetry

6 GifMI & Radiology RevakiMedisip / ElisIbitech Gynecology & Pharmacy Gastrointestinal surgery Pulmonology Waegener (company) RESEARCH GROUP QUANTITATIVE MRI IN MEDICINE AND BIOLOGY Support to other research groups DCE MRI modeling Elastography (WIP – prelim.) Bimodal MRI contrast agent Fluorescence / MRI (Eu DTPA/ Gd DTPA) Pharmaceutical drug release Hyperpolarized gas MRI (functional imaging) Temperature mapping Cooling pads Quantitative metabolic MRS in migraine Coil design for 31 P MRS Quant. functional R 2 relaxometry in lumbar muscles. Quantitative Fat/Water MRI UTE MRI sequence for bone segmentation Eddy current imaging sequence for EEG Oil Water

7 Proposed research projects at the University of Sydney

8 Four main research lines Dose [Gy] Hyperpolarized gas MRI for lung perfusion and molecular imaging FA D D(  ) HH KD()KD() T1 T2(  TE) MT(f) T1  Water content Protein concentration Membrane permeability Cellular density Cell morphology Interstititial water Macromolecules Quantitative mapping of tumor physiology by use of multi-nuclear MRI Non-invasive microstructure analysis by use of quantitative MRI 3D radiation dosimetry using polymer gel dosimetry

9 Treatment-planning & optimization Patient / Gel dosimeter MR-scan CT-scan Image date set Simulation + localization Conformal radiation treatment Rationale: 3D radiation dosimetry can be used to safeguard the whole radiation treatment chain of conformal radiotherapy. The 3D gel dosimeter is treated similarly as the patient (from imaging to readout of the recorded dose distribution). I. 3D radiation dosimetry using polymer gel dosimeters

10 Gel fabrication Radiation Treatment qMRI 0 Gy 0.5 Gy 1 Gy 2 Gy 3 Gy 4 Gy 6 Gy 8 Gy 10 Gy 15 Gy 20 Gy 25 Gy 30 Gy Dose [Gy] R2 [s -1 ] Dose [Gy] Principle: Radiation sensitive hydrogel poured in a humanoid shaped cast is read out after radiation treatment by use of quantitative MRI or optical CT I. 3D radiation dosimetry using polymer gel dosimeters

11 Improve and assess the accuracy and precision of gel dosimeters. Construction of a low magnetic field (~ 0.2 T) benchtop MRI system for readout. Construction of a fast optical CT scanner using a CCD camera and telecentric lens configuration. Multi-center dosimetry study of IMRT by distributing 3D gel dosimeters to several radiotherapy centers. Optical and MRI readout is performed by the research group. Improve user-friendliness of gel dosimetry University of Sydney Med. Phys. research team Royal North Shore Hospital Westmead Hospital Prince of Wales Hospital Royal Prince Alfred Hospital Liverpool Hospital Optical scanning MRI Project goals: I. 3D radiation dosimetry using polymer gel dosimeters

12 FA D D(  ) HH KD()KD() T1 T2 (TE i ) MT(f) T1  Water content Protein concentration Membrane permeability Cellular density Cell morphology Interstititial water Macromolecules II. Non-invasive microstructure analysis by use of quantitative MRI Rationale: MRI contrast parameters are determined by the tissue microstructure. Quantitative MRI allows the assessment of microstructural parameters.

13 II. Non-invasive microstructure analysis by use of quantitative MRI COMPUTATIONAL MODELING SYNTHETIC TEST PHANTOM ANIMAL MODEL HUMAN STUDIES Degree of heterogeneity & complexity Molecular self-diffusion Relaxation Magnetization transfer Perfusion Proton density Oxygen consumption Approach: Numerical modeling of the correlation between the MRI contrast parameter and the tissue microstructure (Bloch-Torrey equation). Example: Human lung tissue Micro-CT of hydrogel foam  B 0 (ppm) Microscopic magnetic field calculations (Maxwell) Random walk simulation R 2 dispersion Diffusive dispersion ~ Alveolar size can be determined from R 2 (  TE) (J. Magn. Reson., 193(2): , 2008)

14 III. Non-invasive mapping of tumor physiology by use of quantitative multi-nuclear MRI/MRS and DCE MRI Rationale: Physiological maps displaying oxygen tension (pO2), acidity (pH) and metabolite concentrations can be obtained by use of quantitative multinuclear MR imaging and MR spectroscopy. Cellular size / Extracellular space Metabolite concentration Vascular permeability Tumor hypoxia (oxygen tension) t B0B0 M f RF = MHz/T 19 F - MRI relaxometry Restricted Diffusion: D(  ) Acidity (pH) 31 P – MRS:  (P i )-  (PCr) t S t DCE-MRI: K trans,  Cit/Cho Cho / NAA In vivo MR spectra

15 III. Non-invasive mapping of tumor physiology by use of quantitative multi-nuclear MRI/MRS and DCE MRI healthy cells hypoxic cells dead cells blood vessel Normal blood vesselsTumor blood vesselsTumor neovascularization Carcinogenesis prognosis: Treatment response: Hypoxic tumor cells are dormant. Hypoxia promotes cells that are resistant to apopthosis. Hypoxia activates HIF which plays also a role in angiogenesis. Hypoxic cells are more resistant to apopthosis. Hypoxic cells contain less oxygen resulting in less radicalar damage upon irradiation. O2O2 O*O* Rationale: (Example) Tumoral oxygen tension (pO 2 ) is a prognostic parameter for cancer progression and for radiation treatment response.

16 III. Non-invasive mapping of tumor physiology by use of quantitative multi-nuclear MRI/MRS and DCE MRI t (min) Estimated capillary flow rate 50  m/s 100  m/s 0  m/s A-H I J K ABCD EFGH IJK pO 2 (atm) Approach: Dedicated test phantoms can be used to simulate the in vivo situation. Gel containing yeast cells Semi-permeable hollow fibers PFC + O 2 Fluoroptic oxygen glass fiber sensor pO 2 MRI slice 1 H MRI images

17 III. Non-invasive mapping of tumor physiology by use of quantitative multi-nuclear MRI/MRS and DCE MRI Approach: Numerical simulations are used to assess the correlation between physiological properties and measured MRI parameters. Blood plasma Extravascular extracellular space Oxygen carrier (PFC) Clearance Cellular oxygen consumption model DIFFUSIVE TRANSPORT Intra-voxel oxygen map and pO 2 distribution Cell survival upon radiation treatment Radiobiological model incorporating oxygen effect Extravascular extracellular space

18 IV. Hyperpolarized gas MRI for lung perfusion and molecular imaging X-ray 1 μm 10 μm 100 μm 1 mm 1 cm 1 dm 1 mM 1 μM 1 nM 1 pM MRI Spatial resolution Sensitivity In vivo molecular targets SPECT Sensitivity increase with hyperpolarized MRI PET Rationale: The MR sensitivity can be increased by a factor of by use of hyperpolarization.

19 3T ) Hyperpolarized substance IV. Hyperpolarized gas MRI for lung perfusion and molecular imaging Rationale: Hyperpolarized substances can be injected or inhaled.

20 The spin exchange optical pumping (SEOP) hyperpolarization generator Under construction at the Ghent University NMR unit electromagnet with cache of Faraday (first detection) NMR unit Rx/Tx cabinet Xe-129 / N 2 gas supply and regulator (Vacuum pump) POLARIZER With: - magnet (5 mT) - polarization cell - thermometry - pressure control - heating element - cooling element - NMR acquisition - Optical spectrometer POLARIZATION OPTICS CONTROL UNIT - Magnet - Laser - Pressure - Temperature - Heater - Cooler - Vacuum IV. Hyperpolarized gas MRI for lung perfusion and molecular imaging

21 High-res lung imaging Ventilation imaging 3D lung imaging microstructure imagingVentilation/perfusion scans Motion tagging IV. Hyperpolarized gas MRI for lung perfusion and molecular imaging Physiological lung MRI (Images are from other research groups)

22 Molecular imaging by use of HyperCEST MRI Schröder et al, Science 314: 446-9, 2006 Breathing hyperpolarized Xe-129 gas 50 ppm 200 ppm100 ppm Chemical shift CHEMICAL EXCHANGE Injection of Xe-129 tracer Saturation RF pulse Saturation RF pulse Saturation RF pulse IV. Hyperpolarized gas MRI for lung perfusion and molecular imaging

23 I visited Copenhagen frequently after the war. At one point, I gave a talk in Copenhagen, and then afterwards we met with Bjerrum. Bjerrum was a chemist and a great friend of Niels Bohr… Bohr said to him: “You know, what these people do is really very clever. They put little spies into the molecules and send radio signals to them, and they have to radio back what they are seeing.” I thought that was a very nice way of formulating it. That was exactly how they were used. It was not anymore the protons as such. But from the way they reacted, you wanted to know in what kind of environment they are, just like spies that you send out. That was a nice formulation. - Felix Bloch -


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