Quantitative Oxygen Imaging with Electron Paramagnetic/Spin Resonance Oxygen Imaging Why EPR Why EPR Why EPR Why EPR

Quantitative Oxygen Imaging with Electron Paramagnetic/Spin Resonance Oxygen Imaging Why EPR Why EPR Why EPR Why EPR www.phwiki.com

Quantitative Oxygen Imaging with Electron Paramagnetic/Spin Resonance Oxygen Imaging Why EPR Why EPR Why EPR Why EPR

Steigerwald, Julie, Morning Executive Producer has reference to this Academic Journal, PHwiki organized this Journal Quantitative Oxygen Imaging with Electron Paramagnetic/Spin Resonance Oxygen ImagingHoward HalpernWhy EPR Bad News: native diffusible unpaired electrons: RareGood News: rare native electrons mean no background signalBad News: Need to infuse subjects with materials with stable unpaired electronsGood News: Can infuse materials which target pharmacologic compartmentsWhy EPRSpectroscopic Imaging: Specific quantitative sensitivity to Oxygen, Temperature, Viscosity, pH, ThiolEach property of interest is measured with a specifically designed probe.Free Radicals can bedetected as well

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Why EPRSpectroscopic Imaging: Specific quantitative sensitivity to Oxygen, Temperature, Viscosity, pH, ThiolNo water background as long as signal imaging (vs MRI)Why EPRSpectroscopic Imaging: Specific quantitative sensitivity to Oxygen, Temperature, Viscosity, pH, ThiolNo water background as long as signal imaging (vs MRI)Deep sensitivity at lower frequency (vs optical)250 MHz vs 600 THz, 6 orders of magnitude lower7 cm skin depth vs < 1 mmVs typical EPR (0.009T vs 0.33T electromagnet)250 MHz vs 10 GHz, factor of 40 lower7 cm skin depthWhy Electron Paramagnetic (Spin) Resonance ImagingMore sensitive in addition to specific reporter of characteristics of the solvent environment of a paramagnetic reporterThe reporter can be designed to report (mostly) only one characteristic of the environmentE.G.: oxygen concentration, pH, thiol concentrationsWe have chosen to image molecular oxygen. Basic InteractionMagnetic Moment m (let bold indicate vectors)Magnetic Field BEnergy of interaction: E = -µB = -µB cos()Magnetic Moment ~ Classical Orbital DipoleOrbit with diameter r, area a = r2Charge q moves with velocity v; Current is qv/2rMoment µ = aI = r2qv/2r = qvr/2 = qmvr/2mmv×r ~ angular momentum: let mvr “=“ S = q/2m; as long as electron, e = -e/2me (negative as long as e)µB = e S ; S is in units of Key 1/m relationship between µ in addition to mµB (the electron Bohr Magneton) = -9.27 10-24 J/TMagnitude of the Dipole MomentsKey relationship: µ ~ 1/mSource of principle difference between EPR experimentNMR experimentThis is why EPR can be done with cheap electromagnets in addition to magnetic fields ~ 10mT not requiring superconducting magnets Major consequence on image techniqueµelectron=658 µproton (its not quite 1/m);Proton has anomalous magnetic moment due to “non point like” charge distribution (strong interaction effects)mproton= 1836 melectronAnomalous effect multiplies the magnetic moment of the proton by 2.79 so the moment ratio is 658The Damping Term (Redfield)/t=1/i [H(t’)1, (0)]+ 0(1/i)2 dt’[H1(t),[H1(t-t’), (t’)]Each of the H1 has a term in it with H= -µBr in addition to µ ~ q/m/t~ (-) µ2 This is the damping term:~exp(- µ2t with other terms)Thus, state lifetimes, e.g. T2, are inversely proportional to the square of the coupling constant, µ2The state lifetimes, e.g. T2 are proportional to the square of the mass, m2 Consequences of the Damping TermThe coupling of the electron to the magnetic field is 103 times larger than that of a water proton so that the states relax 106 times fasterNo time as long as Fourier Imaging techniquesFor CW we must use Fixed stepped gradients Vary both gradient direction & magnitude (3 angles)2. Back projection reconstruction in 4-D Imaging: Basic StrategyConstraint: Electrons relax 106 times faster than water protonsImage Acquisition: ProjectionReconstruction: BackprojectionProjection Acquisition in EPRSpectral Spatial Object Support ~= Projection DescriptionWith s(Bsw, ) defined as the spectrum we get with gradients imposedMore ProjectionThe integration of fsw is carried out over the hyperplane in 4-space byDefiningwithThe hyperplane becomeswithAnd a Little MoreSo we can write B = Bsw + c tan x So finally it’s a ProjectionwithProjection acquisition in addition to image reconstructionImage reconstruction: backprojections in spectral-spatial spaceResolution: x=B/Gmax THUS THE RESOLUTION OF THE IMAGE PROPORTIONAL TO Beach projection filtered in addition to subsampled;Interpolation of Projections: number of projections x 4 with sinc() interpolation,Enabling as long as fitting Spectral Spatial ObjectAcquisition: Magnetic field sweep w stepped gradients (G)Projections: Angle a: tan(a)=GDL/DHThe Ultimate Object:Spectral spatial imaging Preview: Response of Symmetric Trityl (deuterated) to Oxygen So measuring the spectrum/spectral widthrelaxation rate measures the oxygen. Imaging the spectrum: Oxygen ImageWhy is oxygen importantin cancerKnown Since 1909 but in 1955Thomlinson in addition to Gray showednecrosisviabletissue Steigerwald, Julie KOLD-TV Morning Executive Producer www.phwiki.com

Dramatic differences in survival as long as patients with cervicalcancer treated with radiation depending on mean tumor oxygenation: > or < 10 torrHockel, et al, Ca Res 56 (1996), p 4509 This was thought to be thesource of radiation resistanceHyperbaric oxygen trials (in human trials)Oxygen mimetic radiosensitizers (in animals only due to toxicity)Eppendorf electrode measurements (humans)Intensity Modulated Radiation TherapySculpts radiation dose over distances of 5mmAble to spare normal tissuesBut tumor volumes are homogeneous; no accounting as long as different regions with different sensitivity Biological imaging to enhance targeting of radiation therapy: oxygen imagingIntensity modulated radiation therapy allows sophisticated control over spatial distribution of radiation doseBiological imaging to enhance targeting of radiation therapy: oxygen imagingIntensity modulated radiation therapy allows sophisticated control over spatial distribution of radiation doseBut: some regions may contain hypoxic cellsBiological imaging to enhance targeting of radiation therapy: oxygen imagingHypoxic cells are known to be radioresistant Good agreement!Adjacent tracks in areas of rapid oxygen variationagree with OxyliteNew insight into the oxygen statusof tumors in addition to tissues

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