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Quantitative MRI in Medicine and Biology
Cho Cre Cit RESEARCH GROUP QUANTITATIVE MRI IN MEDICINE AND BIOLOGY Quantitative MRI in Medicine and Biology A short overview of topics and research perspectives Yves De Deene Ghent University, Belgium
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Past and recent research topics at the Ghent University (Belgium)
Cho Cre Cit RESEARCH GROUP QUANTITATIVE MRI IN MEDICINE AND BIOLOGY Past and recent research topics at the Ghent University (Belgium)
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Past research topics QMRI
RESEARCH GROUP QUANTITATIVE MRI IN MEDICINE AND BIOLOGY Past research topics QMRI Non-invasive MRI thermometry by use of molecular self-diffusion and the proton resonance frequency (PRF) shift method Dynamic contrast enhanced MRI First-pass imaging Verstraete et al, Radiology 192: (1994) (°) 30 20 10 -10 -20 -30 De Poorter et al, Magn Reson Med 33: (1995) Sparse spiral k-space sampling reconstruction Desplanques et al, IEEE Transactions on Nuclear Science 49: (2002) 3D radiation dosimetry using polymer gels and quantitative MRI R2 mapping Dose [Gy] 4 8 12 16 20 De Deene et al, Magn Reson Med 43: (2000) Validation methods for diffusion weighted MRI in brain white matter In vivo quantitative proton MRS Özdemir et al, Phys Med Biol 52: (2007) Fieremans et al, J Magn Reson 190: (2008)
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Recent / Current Research Topics @ UGent
RESEARCH GROUP QUANTITATIVE MRI IN MEDICINE AND BIOLOGY Recent / Current Research UGent Overview Relaxometry in lung equiv. tissue Diffusion in brain white matter 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 PhD finished (MEDISIP) Quantitative Fluor-19 MRI for oxymetry Quantitative in vivo MRS Construction of a hyperpolarization generator PhD finished (MEDISIP) Bone segmentation on UTE MR images Gel dosimetry and optical laser CT scanning Dose [Gy] 4 8 12 16 20 Part time (MEDISIP)
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Overall research rationale of QMRI
RESEARCH GROUP QUANTITATIVE MRI IN MEDICINE AND BIOLOGY Overall research rationale of QMRI Optimize MR imaging sequences MRI sequence analysis Increase sensitivity through hyperpolarization Computer-aided modeling of MRI properties (Monte-Carlo simulations) (Bloch-Torrey eqn.) Prescribed radiation dose distribution Molecular radiobiology Biophysical modeling Chemotherapy prescription S pO2 D (Gy) Quantitative physiological maps (clonogen density, pO2 cellular size distribution) Biochemical properties Molecular receptors pO2 ρcell pH Pvasc [Cho] MR images (Signal intensity) MR spectra MRI quantitative property (T1, T2, D, Ktrans, MTR, etc.) Metabolite concentration Tracer concentration R1 R2 MT Ktrans D Treatment optimization 3D radiation dosimetry
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Support to other research groups
RESEARCH GROUP QUANTITATIVE MRI IN MEDICINE AND BIOLOGY Support to other research groups GifMI & Radiology Revaki Medisip / Elis Ibitech Gynecology & Pharmacy Gastrointestinal surgery Pulmonology Waegener (company) DCE MRI modeling Elastography (WIP – prelim.) Quantitative metabolic MRS in migraine Quant. functional R2 relaxometry in lumbar muscles. UTE MRI sequence for bone segmentation Coil design for 31P MRS Quantitative Fat/Water MRI Eddy current imaging sequence for EEG Oil Water Pharmaceutical drug release Bimodal MRI contrast agent Fluorescence / MRI (Eu DTPA/ Gd DTPA) Hyperpolarized gas MRI (functional imaging) Temperature mapping Cooling pads
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Proposed research projects at the University of Sydney
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Four main research lines
Dose [Gy] 4 8 12 16 20 Hyperpolarized gas MRI for lung perfusion and molecular imaging FAD D() H 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
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I. 3D radiation dosimetry using polymer gel dosimeters
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). Patient / Gel dosimeter MR-scan CT-scan Image date set Treatment-planning & optimization Simulation + localization Conformal radiation treatment
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I. 3D radiation dosimetry using polymer gel dosimeters
Principle: Radiation sensitive hydrogel poured in a humanoid shaped cast is read out after radiation treatment by use of quantitative MRI or optical CT 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] 4 8 12 16 20 Gel fabrication Dose [Gy] R2 [s-1]
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I. 3D radiation dosimetry using polymer gel dosimeters
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: 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
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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. FAD D() H KD() T1 T2 (TEi) MT(f) T1 Water content Protein concentration Membrane permeability Cellular density Cell morphology Interstititial water Macromolecules
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II. Non-invasive microstructure analysis by use of quantitative MRI
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 10 20 5 15 B0 (ppm) Microscopic magnetic field calculations (Maxwell) Random walk simulation R2 dispersion Diffusive dispersion ~ Alveolar size can be determined from R2 (TE) (J. Magn. Reson., 193(2): , 2008) COMPUTATIONAL MODELING SYNTHETIC TEST PHANTOM ANIMAL MODEL HUMAN STUDIES Degree of heterogeneity & complexity Molecular self-diffusion Relaxation Magnetization transfer Perfusion Proton density Oxygen consumption
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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. t B0 M fRF = MHz/T 19F - MRI relaxometry Tumor hypoxia (oxygen tension) 31P – MRS: (Pi)-(PCr) Acidity (pH) Cellular size / Extracellular space Restricted Diffusion: D() Vascular permeability t S DCE-MRI: Ktrans , Cit/Cho Cho / NAA In vivo MR spectra Metabolite concentration
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III. Non-invasive mapping of tumor physiology
by use of quantitative multi-nuclear MRI/MRS and DCE MRI Rationale: (Example) Tumoral oxygen tension (pO2) is a prognostic parameter for cancer progression and for radiation treatment response. healthy cells hypoxic cells dead cells blood vessel Normal blood vessels Tumor blood vessels Tumor neovascularization Carcinogenesis prognosis: Hypoxic tumor cells are dormant. Hypoxia promotes cells that are resistant to apopthosis. Hypoxia activates HIF which plays also a role in angiogenesis. O2 O* Treatment response: Hypoxic cells are more resistant to apopthosis. Hypoxic cells contain less oxygen resulting in less radicalar damage upon irradiation.
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III. Non-invasive mapping of tumor physiology
by use of quantitative multi-nuclear MRI/MRS and DCE MRI Approach: Dedicated test phantoms can be used to simulate the in vivo situation. Gel containing yeast cells Semi-permeable hollow fibers PFC + O2 Fluoroptic oxygen glass fiber sensor pO2 MRI slice 1H MRI images A B C D E F G H I J K pO2 (atm) t (min) Estimated capillary flow rate 50 m/s 100 m/s 0 m/s A-H I J K
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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 pO2 distribution Extravascular extracellular space Radiobiological model incorporating oxygen effect Cell survival upon radiation treatment
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IV. Hyperpolarized gas MRI for lung perfusion
and molecular imaging Rationale: The MR sensitivity can be increased by a factor of by use of hyperpolarization. Sensitivity 1 pM PET In vivo molecular targets 1 nM Sensitivity increase with hyperpolarized MRI SPECT 1 μM MRI 1 mM X-ray 1 μm 10 μm 100 μm 1 mm 1 cm 1 dm Spatial resolution
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IV. Hyperpolarized gas MRI for lung perfusion
and molecular imaging Rationale: Hyperpolarized substances can be injected or inhaled. 3T ) Hyperpolarized substance
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IV. Hyperpolarized gas MRI for lung perfusion and molecular imaging
The spin exchange optical pumping (SEOP) hyperpolarization generator Under construction at the Ghent University 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 NMR unit electromagnet with cache of Faraday (first detection) Rx/Tx cabinet Xe-129 / N2 gas supply and regulator (Vacuum pump)
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IV. Hyperpolarized gas MRI for lung perfusion and molecular imaging
Physiological lung MRI High-res lung imaging Ventilation imaging 3D lung imaging Ventilation/perfusion scans microstructure imaging Motion tagging (Images are from other research groups)
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IV. Hyperpolarized gas MRI for lung perfusion and molecular imaging
Molecular imaging by use of HyperCEST MRI Injection of Xe-129 tracer Saturation RF pulse Breathing hyperpolarized Xe-129 gas Saturation RF pulse Saturation RF pulse CHEMICAL EXCHANGE 200 ppm 100 ppm 100 ppm 50 ppm Schröder et al, Science 314: 446-9, 2006 Chemical shift
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I visited Copenhagen frequently after the war
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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