CCoonnttrraasstt AAggeennttss Altering Tissue...
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Mike Moseley, Ph.D. Mike Moseley, Ph.D. Department of Radiology Stanford University Department of Radiology Stanford University Contrast Agents Contrast Agents Current Concepts Monterey October 2005 Current Concepts Monterey October 2005 Intrinsic tissue contrasts: Intrinsic tissue contrasts: Altering Tissue Contrast Altering Tissue Contrast 1. Nuclei (proton) density - PD 2. Spin lattice Relaxation – T1 3. Susceptibility – T2* Are amenable for pharmacologic perturbation... 1. Nuclei (proton) density - PD 2. Spin lattice Relaxation – T1 3. Susceptibility – T2* Are amenable for pharmacologic perturbation... Magnetic Susceptibility Magnetic Susceptibility MR relaxation enhancement ("relaxivity") is a question of unpaired electrons... MR relaxation enhancement ("relaxivity") is a question of unpaired electrons... Diamagnetic agents no unpaired e- no effect on T1, T2. PD only Paramagnetic agents unpaired e- noninteracting domains Diamagnetic agents no unpaired e- no effect on T1, T2. PD only Paramagnetic agents unpaired e- noninteracting domains Superparamagnetic unpaired e- pools noninteracting domains Superparamagnetic unpaired e- pools noninteracting domains Ferromagnetic unpaired e- oceans strongly interacting domains (>0.035μm) threshold... Ferromagnetic unpaired e- oceans strongly interacting domains (>0.035μm) threshold... 10 10 -1 -1 10 10 +2 +2 10 10 +4 +4 *cm / gauss *cm / gauss 3 3 10 10 0 Oils, PFOB Gd +3 , Fe +3 Fe particle Metal Artifacts… Oils, PFOB Gd +3 , Fe +3 Fe particle Metal Artifacts… T1 - T2*- T1 T2* T1 T2* T1- T2* 1. T1-shortening on T1w images. paramagnetic agents (Gd-DTPA). coated supermagnetic irons (iron particles). 2. T2 (or T2*) shortening on T2*w images. para-/superparamagnetic agents (iron particles). paramagnetic agents (Gd- or Dy-DTPA) 1. T1-shortening on T1w images. paramagnetic agents (Gd-DTPA). coated supermagnetic irons (iron particles). 2. T2 (or T2*) shortening on T2*w images. para-/superparamagnetic agents (iron particles). paramagnetic agents (Gd- or Dy-DTPA) Altering Tissue Contrast Altering Tissue Contrast SI = N(H) [ 1 - e ] e SI = N(H) [ 1 - e ] e -TR/T1 -TR/T1 -TE/T2 -TE/T2 Unpaired electron clouds fluctuate around metal. Create dipole-dipole effects (interactions with proton). Acts as magnetization sink – draws magnetization. Promotes T1 relaxation – shortens T1. Apparent shortening of proton T1- at a given B0 and temperature... Unpaired electron clouds fluctuate around metal. Create dipole-dipole effects (interactions with proton). Acts as magnetization sink – draws magnetization. Promotes T1 relaxation – shortens T1. Apparent shortening of proton T1- at a given B0 and temperature... Unpaired e - and “T1 Relaxivity" Unpaired e - and “T1 Relaxivity" 1/T1 (observed) = 1/ T1 (intrinsic) + R1 [Conc] 1/T1 (observed) = 1/ T1 (intrinsic) + R1 [Conc] ( 200 msec = 1000 msec + 3.8*[0.1mmol/kg] ) ( 200 msec = 1000 msec + 3.8*[0.1mmol/kg] ) *mmol -1 L sec -1 *mmol -1 L sec -1 Gd +3 unpaired electrons T1, T2* Gd +3 unpaired electrons T1, T2* COO– COO– Gd Gd +++ +++ N N N N N N COOH COOH COO– COO– COO– COO– COO– COO– O – NH-CH3 O – NH-CH3 Gd Gd +++ +++ N N N N N N COOH COOH COO– COO– COO– COO– CH3-HN-O CH3-HN-O COO– COO– Gd Gd +++ +++ COO– COO– COO– COO– N N N N N N N N COO– COO– Gd-DTPA: Berlex – Magnevist TM Gd-DTPA: Berlex – Magnevist TM Gd-DTPA-BMA:Nycomed-Amersham – Omniscan TM Gd-DTPA-BMA:Nycomed-Amersham – Omniscan TM Gd-DOTA: Geurbet – DOTAREM TM Gd-DOTA: Geurbet – DOTAREM TM T1- Electron cloud relaxation T2* - Magnetic susceptibility T1- Electron cloud relaxation T2* - Magnetic susceptibility
Transcript of CCoonnttrraasstt AAggeennttss Altering Tissue...
Mike Moseley, Ph.D.Mike Moseley, Ph.D.Department of Radiology
Stanford UniversityDepartment of Radiology
Stanford University
Contrast AgentsContrast Agents
Current ConceptsMonterey
October 2005
Current ConceptsMonterey
October 2005
Intrinsic tissue contrasts:Intrinsic tissue contrasts:
Altering Tissue ContrastAltering Tissue Contrast
1. Nuclei (proton) density - PD2. Spin lattice Relaxation – T13. Susceptibility – T2*
Are amenable for pharmacologicperturbation...
1. Nuclei (proton) density - PD2. Spin lattice Relaxation – T13. Susceptibility – T2*
Are amenable for pharmacologicperturbation...
Magnetic SusceptibilityMagnetic SusceptibilityMR relaxation enhancement ("relaxivity") is a question of
unpaired electrons...MR relaxation enhancement ("relaxivity") is a question of
unpaired electrons...
Diamagnetic agentsno unpaired e-no effect on T1, T2. PD only
Paramagnetic agentsunpaired e-noninteracting domains
Diamagnetic agentsno unpaired e-no effect on T1, T2. PD only
Paramagnetic agentsunpaired e-noninteracting domains
Superparamagneticunpaired e- poolsnoninteracting domains
Superparamagneticunpaired e- poolsnoninteracting domains
Ferromagneticunpaired e- oceansstrongly interacting domains(>0.035µm) threshold...
Ferromagneticunpaired e- oceansstrongly interacting domains(>0.035µm) threshold...
1010-1-1
1010+2+2
1010+4+4
*cm / gauss*cm / gauss33
101000
Oils, PFOB
Gd+3, Fe+3
Fe particle
Metal Artifacts…
Oils, PFOB
Gd+3, Fe+3
Fe particle
Metal Artifacts…
T1 - T2*-
T1 T2*
T1 T2*
T1- T2*
1. T1-shortening on T1w images.paramagnetic agents (Gd-DTPA).coated supermagnetic irons (iron particles).
2. T2 (or T2*) shortening on T2*w images.para-/superparamagnetic agents (iron particles).paramagnetic agents (Gd- or Dy-DTPA)
1. T1-shortening on T1w images.paramagnetic agents (Gd-DTPA).coated supermagnetic irons (iron particles).
2. T2 (or T2*) shortening on T2*w images.para-/superparamagnetic agents (iron particles).paramagnetic agents (Gd- or Dy-DTPA)
Altering Tissue ContrastAltering Tissue ContrastSI = N(H) [ 1 - e ] e SI = N(H) [ 1 - e ] e -TR/T1-TR/T1 -TE/T2-TE/T2
Unpaired electron clouds fluctuate around metal.Create dipole-dipole effects (interactions with proton).Acts as magnetization sink – draws magnetization.Promotes T1 relaxation – shortens T1.
Apparent shortening of proton T1-at a given B0 and temperature...
Unpaired electron clouds fluctuate around metal.Create dipole-dipole effects (interactions with proton).Acts as magnetization sink – draws magnetization.Promotes T1 relaxation – shortens T1.
Apparent shortening of proton T1-at a given B0 and temperature...
Unpaired e- and “T1 Relaxivity"Unpaired e- and “T1 Relaxivity"
1/T1 (observed) = 1/ T1 (intrinsic) + R1 [Conc]1/T1 (observed) = 1/ T1 (intrinsic) + R1 [Conc]( 200 msec = 1000 msec + 3.8*[0.1mmol/kg] )( 200 msec = 1000 msec + 3.8*[0.1mmol/kg] )
*mmol-1 L sec-1*mmol-1 L sec-1
Gd +3 unpairedelectrons T1, T2*Gd +3 unpairedelectrons T1, T2*
COO–COO–GdGd++++++NN
NN
NN
COOHCOOH
COO–COO–
COO–COO–
COO–COO–
O – NH-CH3O – NH-CH3GdGd++++++NN
NN
NN
COOHCOOH
COO–COO–COO–COO–
CH3-HN-OCH3-HN-O
COO–COO–
GdGd++++++
COO–COO–COO–COO–NN
NN
NN
NNCOO–COO–
Gd-DTPA: Berlex – MagnevistTMGd-DTPA: Berlex – MagnevistTM
Gd-DTPA-BMA:Nycomed-Amersham – OmniscanTMGd-DTPA-BMA:Nycomed-Amersham – OmniscanTM
Gd-DOTA: Geurbet – DOTAREMTMGd-DOTA: Geurbet – DOTAREMTM
T1- Electron cloud relaxationT2* - Magnetic susceptibilityT1- Electron cloud relaxationT2* - Magnetic susceptibility
Magnetic moment (# unpaired electrons)Gd has 7 unpaired e-
OxyHb (Fe +2) vs. DeOxyHb (Fe +3) Electron relaxation rate (near that of protons?)
Gd-DTPA vs. Dy-DTPATumbling of the cloud (exposure time to protons)
Gd-DTPA-bindingApproach of water to the unpaired electrons...
MetHb
Magnetic moment (# unpaired electrons)Gd has 7 unpaired e-
OxyHb (Fe +2) vs. DeOxyHb (Fe +3) Electron relaxation rate (near that of protons?)
Gd-DTPA vs. Dy-DTPATumbling of the cloud (exposure time to protons)
Gd-DTPA-bindingApproach of water to the unpaired electrons...
MetHb
1/T1 (observed) = 1/ T1 (intrinsic) + R1 [Conc]1/T1 (observed) = 1/ T1 (intrinsic) + R1 [Conc]( 200 msec = 1000 msec + 0.7[~2mmol/kg] )( 200 msec = 1000 msec + 0.7[~2mmol/kg] )
Unpaired e- and “T1 Relaxivity"Unpaired e- and “T1 Relaxivity"Magnetic moment (# unpaired electrons)
OxyHb vs. DeOxyHbElectron relaxation rate (near that of protons?)
Gd-DTPA vs. Dy-DTPATumbling of the cloud (exposure time to protons)
Gd-DTPA-bindingApproach of water to the unpaired electrons...
MetHb
Magnetic moment (# unpaired electrons)OxyHb vs. DeOxyHb
Electron relaxation rate (near that of protons?)Gd-DTPA vs. Dy-DTPA
Tumbling of the cloud (exposure time to protons)Gd-DTPA-binding
Approach of water to the unpaired electrons...MetHb
Unpaired e- and “T1 Relaxivity"Unpaired e- and “T1 Relaxivity"
Magnetic moment (# unpaired electrons)OxyHb vs. MetHb
Electron relaxation rate (near that of protons?)Gd-DTPA vs. Dy-DTPA
Tumbling of the cloud (exposure time to protons)Gd-DTPA-binding
Approach of water to the unpaired electrons...MetHb
Magnetic moment (# unpaired electrons)OxyHb vs. MetHb
Electron relaxation rate (near that of protons?)Gd-DTPA vs. Dy-DTPA
Tumbling of the cloud (exposure time to protons)Gd-DTPA-binding
Approach of water to the unpaired electrons...MetHb
Unpaired e- and "Relaxivity"Unpaired e- and "Relaxivity"
T1 Relaxivities mmol-1 L sec-1:Gd-DTPA ~ 4 Gd-dimers ~ 10Gd-Dextrans ~ 40MS-325-HSA ~ 45Iron oxides ~ 20
T1 Relaxivities mmol-1 L sec-1:Gd-DTPA ~ 4 Gd-dimers ~ 10Gd-Dextrans ~ 40MS-325-HSA ~ 45Iron oxides ~ 20
Paramagnetics - Blood Pool AgentsParamagnetics - Blood Pool Agents
T1-shortening agents:Affinity to HSA
80-90% labeledR1 ~ 40-50T1/2 ~ 60minutes
T1-shortening agents:Affinity to HSA
80-90% labeledR1 ~ 40-50T1/2 ~ 60minutes
Gd-phostriamine MS-325 -Epix - ScheringGd-phostriamine MS-325 -Epix - Schering
Gd Tr ~ 1010Gd Tr ~ 1010
HSA Tr ~ 108HSA Tr ~ 108
“Conventional” MRI Contrast-generating end
Albumin-targeting end
Rabbit - Thrombus agent (EP-1242) visualizesNon-occlusive arterial thrombus
Pre-Contrast Post-Contrast Blood Pool
Carotid ArteryThrombus
Epix Medical: E. Kent Yucel, Li Zhou, Brigham & Women’s, Boston
Targeted MR Agents:Polymerized NP Vesicles for Detection and Therapy
Targeted MR Agents:Polymerized NP Vesicles for Detection and Therapy
Polydiacetylenecrosslink
TargetingAngiogen ligand
Gd-DTPAligands Drug
Encapsulation
Lipid-based self-assembled system- Plasma life ~ 16 hrs
Vascular targeted gene delivery NP with angiogenesis target
Lipid-based self-assembled system- Plasma life ~ 16 hrs
Vascular targeted gene delivery NP with angiogenesis target
Bernardski, et al. Molecular Imaging Lab,
Stanford
Bernardski, et al. Molecular Imaging Lab,
Stanford
Magnetic moment (# unpaired electrons)OxyHb vs. MetHbElectron relaxation rate (near that of protons?)Gd-DTPA vs. Dy-DTPATumbling of the cloud (exposure time to protons)Gd-DTPA-bindingApproach of water to the unpaired electrons...
MetHb
Magnetic moment (# unpaired electrons)OxyHb vs. MetHbElectron relaxation rate (near that of protons?)Gd-DTPA vs. Dy-DTPATumbling of the cloud (exposure time to protons)Gd-DTPA-bindingApproach of water to the unpaired electrons...
MetHb
Unpaired e- and “T1 Relaxivity"Unpaired e- and “T1 Relaxivity"
Fe(II) Fe(III)Fe(II) Fe(III)OxyHb MetHbOxyHb MetHb
FeFe FeFe
“e-gad”mechanismMeade, et al. Nature 2000
“e-gad”mechanismMeade, et al. Nature 2000
Molecular (Genomic) imaging - Engineered Gd-ligandsMolecular (Genomic) imaging - Engineered Gd-ligandsMR Targeted Agents – “Open for Business”MR Targeted Agents – “Open for Business”
Magnetic moment (# unpaired electrons)OxyHb vs. MetHbElectron relaxation rate (near that of protons?)Gd-DTPA vs. Dy-DTPATumbling of the cloud (exposure time to protons)Gd-DTPA-bindingApproach of water to the unpaired electrons...MetHbConcentration of bolus (CE-MRA)Concentration of agent (GadovistTM)
Magnetic moment (# unpaired electrons)OxyHb vs. MetHbElectron relaxation rate (near that of protons?)Gd-DTPA vs. Dy-DTPATumbling of the cloud (exposure time to protons)Gd-DTPA-bindingApproach of water to the unpaired electrons...MetHbConcentration of bolus (CE-MRA)Concentration of agent (GadovistTM)
Unpaired e- and “T1 Relaxivity"Unpaired e- and “T1 Relaxivity"
Peripheral Run-off CE-MRA with a 1.0 MolarGadolinium Chelate (Gadovist) with
Intraarterial DSA Comparison. M. Gregor, B. Tombach, A. Hentsch, P. Reimer.
www.academicradiology.com
Peripheral Run-off CE-MRA with a 1.0 MolarGadolinium Chelate (Gadovist) with
Intraarterial DSA Comparison. M. Gregor, B. Tombach, A. Hentsch, P. Reimer.
www.academicradiology.com
Concentration of agent (GadovistTM)Concentration of agent (GadovistTM)Unpaired e- and "Relaxivity"Unpaired e- and "Relaxivity"
GadovistTMGadovistTM Gd-DTPAGd-DTPA
R1 = T1 Relaxivities mmol-1 L sec-1:Gd-DTPA (0.5M) ~ 4 Gadovist (1.0M) ~ 8
R1 = T1 Relaxivities mmol-1 L sec-1:Gd-DTPA (0.5M) ~ 4 Gadovist (1.0M) ~ 8
Created by local gradients (of the unpaired electrons).Created by local environment (clots, RBC packing).
Enhanced by proton diffusion through these gradients.Increased spin dephasing = T2* decreased.
Created by local gradients (of the unpaired electrons).Created by local environment (clots, RBC packing).
Enhanced by proton diffusion through these gradients.Increased spin dephasing = T2* decreased.
Unpaired e- and “T2* Relaxivity"Unpaired e- and “T2* Relaxivity"Magnetic susceptibility – T2* Magnetic susceptibility – T2*
Gd
Gd Gd
Gd
Magnetic Susceptibility Affects Tissue Contrast
small gradientacross sample
Observed T2* Observed T2*
M M
gray-white matter tissue
large gradientacross sample
Gd present in brain...a shorter T2*
Gd
Gd Gd
Gd
TETE
HbO2diamagnetic
Low ² χχχχ
HbO2diamagnetic
Low ² χχχχ
Hb4 unpaired electrons -
paramagneticHigh ² χχχχ
Hb4 unpaired electrons -
paramagneticHigh ² χχχχ
FeFe
NN
NN
F8F8
O = OO = O
oxyhemoglobinoxyhemoglobin
HbO2diamagnetic
Low ² χχχχ
HbO2diamagnetic
Low ² χχχχ
deoxygenatesdeoxygenates
oxygenatesoxygenates
FeFe
NN
NN
F8F8
deoxyhemoglobindeoxyhemoglobin
Hb4 unpaired electrons -
paramagneticHigh ² χχχχ
Hb4 unpaired electrons -
paramagneticHigh ² χχχχ
Blood = Ideal MR Contrast Agent? Blood = Ideal MR Contrast Agent? Magnetic moment (# unpaired electrons)
OxyHb vs. deOxyHb - fMRISize and concentration of particle
USPIO (blood pool) vs. SPIO (RES capture)
Magnetic moment (# unpaired electrons)OxyHb vs. deOxyHb - fMRI
Size and concentration of particleUSPIO (blood pool) vs. SPIO (RES capture)
Unpaired e- and “T2* Relaxivity"Unpaired e- and “T2* Relaxivity"
1/T2* (observed) = 1/ T2* (intrinsic) + R2* [Conc]1/T2* (observed) = 1/ T2* (intrinsic) + R2* [Conc]R2* Relaxivity:R2* Relaxivity:
( 100 msec = 1000 msec + 6 [0.1mmol/kg] )( 100 msec = 1000 msec + 6 [0.1mmol/kg] )
T2* Relaxivities (in order): Iron oxidesFeClDyDTPAGdDTPADeOxyHbOxyHb
T2* Relaxivities (in order): Iron oxidesFeClDyDTPAGdDTPADeOxyHbOxyHb
Feridex-enhanced MR “USPIO”Feridex-enhanced MR “USPIO”
Paramagnetics vs. SuperparamagneticsParamagnetics vs. SuperparamagneticsAlterations of T1 and T2Alterations of T1 and T2
Particulates (superparamagnetic irons):Possesses mild T1-shortening at low [Fe].Large T2* effect at higher [Fe].Biodistribution vary depending on size:
Particulates (superparamagnetic irons):Possesses mild T1-shortening at low [Fe].Large T2* effect at higher [Fe].Biodistribution vary depending on size:
>20 nm size Liver (RES) uptake agents20 Oral (gut) agents10-20 Lymph nodes, blood pool4-6 Hepatocytes, targets
>20 nm size Liver (RES) uptake agents20 Oral (gut) agents10-20 Lymph nodes, blood pool4-6 Hepatocytes, targets
Size is the most important aspect of biodistribution.All particles must be < 5 µm to avoid entrapment in lung.Size is the most important aspect of biodistribution.All particles must be < 5 µm to avoid entrapment in lung.
Paramagnetics vs. SuperparamagneticsParamagnetics vs. SuperparamagneticsAlterations of T1 and T2Alterations of T1 and T2
Particulates (superparamagnetic irons):Particulates (superparamagnetic irons):
Size is the most important aspect of biodistribution.All particles must be < 5 µm to avoid entrapment in lung.Size is the most important aspect of biodistribution.All particles must be < 5 µm to avoid entrapment in lung.
Lumiren - > 300nm (- agent)
Abdoscan - 200- 300nm (- agent)
Resovist - 100-200nm (- agent)Sinerem - 40nm particle (-agent)NC-100150- 20nm particle (+agent)
Lumiren - > 300nm (- agent)
Abdoscan - 200- 300nm (- agent)
Resovist - 100-200nm (- agent)Sinerem - 40nm particle (-agent)NC-100150- 20nm particle (+agent)
Paramagnetics vs. SuperparamagneticsParamagnetics vs. SuperparamagneticsFe-Oxide (NC100150 – GE-Amersham)Fe-Oxide (NC100150 – GE-Amersham)
Paramagnetics vs. SuperparamagneticsParamagnetics vs. Superparamagnetics
T1-shortening is a short-range (1/r ) effect...
Represents blood volume effect...Positive enhancement.Effect no larger than T1-differences.Small enhancement in intact BBB.
T1-shortening is a short-range (1/r ) effect...
Represents blood volume effect...Positive enhancement.Effect no larger than T1-differences.Small enhancement in intact BBB.
Alterations of T1 and T2*Alterations of T1 and T2*
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T2*-shortening is a long-range (B0) effect...Local field alterations extend over µm-mm.Pronounced effect in brain.Potent mechanism.Image quality and scan time issues.
T2*-shortening is a long-range (B0) effect...Local field alterations extend over µm-mm.Pronounced effect in brain.Potent mechanism.Image quality and scan time issues.
SISI
[Gd][Gd]00 0.50.5 2 mmol/kg2 mmol/kg
Paramagnetic Contrast on T1, T2*Paramagnetic Contrast on T1, T2*Concentration effectsConcentration effects
T1-shortening effectT1-shortening effect
T2*-shorteningeffect
T2*-shorteningeffect
Paramagnetic Contrast on T2*Paramagnetic Contrast on T2*Intensity and Agent ConcentrationIntensity and Agent Concentration
Bolus Gd-DTPA : T2* ~ 50 msecBolus Gd-DTPA : T2* ~ 50 msec
1/T2* (observed) = 1/ T2 (intrinsic) + R2* [Conc]1/T2* (observed) = 1/ T2 (intrinsic) + R2* [Conc]
( 50 msec = 1000 msec + 6[0.1mmol/kg] )( 50 msec = 1000 msec + 6[0.1mmol/kg] )
capillary bedcapillary bed
200200
sliceslice
secondsseconds
SISI
gray matter (greater rCBV)gray matter (greater rCBV)
white matterwhite matter
120120
140140
160160
180180
-5-5 00 1515 2525 3535 4545 5555 6565
bolusbolus
Contrast Agent FamiliesContrast Agent Families
AngioMARK (MS-325) ScheringNC-100150
Endorem - AMI-225 80-150nm (-)Teslascan – AMI - MnDPDP (+)
Abdoscan - OMP < 300nm (-)Imagent - Alliance – PFOB $200 (-)Lumenhance – MnCl (+ agent)Lumiren - AMI-121 iron oxide > 300nm (-)
Comments
Blood PoolPersistent
Endorem/FeridexTeslascan
Organ SpecifcLiver and lymph
Abdoscan (Amersham)Imagent GILumenHance (Bracco)
Lumirem/ Entera
Oralabdomen and pelvis
Dotarem (Guerbet)Magnevist (Berlex)Omniscan (Amersham)ProHance (Bracco)
ECF
Gd+3-chelates
ApprovedType of AgentContrast Agents and the MarketContrast Agents and the Market
Epix- First true specific agent (+)
NC-100150 - Clariscan 20nm (+)
Eovist-GdEOB-DTPA Schering (+)Resovist- Iron oxide (-) ScheringSinerem family - Iron oxides (-) AMI227 40nm particle
Gadolite– Pharmacyclics (+) GdDendrimer, caged Gd
Gadovist- 1Molar GdDTPA ScheringMultiHance – 5% hepata-activity (+) Bracco
Comments
AngioMARK (MS-325)Sinerem/CombidexMultiHanceNC-100150
Blood PoolPersistent
EovistResovistSinerem/Combidex/Feridex/GastroMark
Organ SpecifcLiver and lymph
Gadolite Oralabdomen and pelvis
GadovistMultihance
ECF
Gd+3-chelates
Not Yet ApprovedType of Agent
HbO2diamagnetic
Low ² χχχχ
HbO2diamagnetic
Low ² χχχχ
Hb4 unpaired electrons -
paramagneticHigh ² χχχχ
Hb4 unpaired electrons -
paramagneticHigh ² χχχχ
FeFe
NN
NNF8F8
O = OO = O
oxyhemoglobinoxyhemoglobin
HbO2diamagnetic
Low ² χχχχ
HbO2diamagnetic
Low ² χχχχ
deoxygenatesdeoxygenates
oxygenatesoxygenates
FeFe
NN
NNF8F8
deoxyhemoglobindeoxyhemoglobin
Hb4 unpaired electrons -
paramagneticHigh ² χχχχ
Hb4 unpaired electrons -
paramagneticHigh ² χχχχ
Blood = Ideal MR Contrast Agent? Blood = Ideal MR Contrast Agent?
Capillary Structure Creates a Local MRGradient - Causes Proton Dephasing... Capillary Structure Creates a Local MRGradient - Causes Proton Dephasing...
Hb:high χχχχHb:
high χχχχHbO2:low χχχχ
HbO2:low χχχχ
blood flowblood flow
Hb:high χχχχHbO2:
low χχχχ
blood flow
...any changes in delivery of HbO2causes changes in image intensity...
...any changes in delivery of HbO2causes changes in image intensity...
Balance of HbO2 to Hb affects T2*.T2* effects extend beyond vascular space.
blood flow
Surplus of HbO2 to Hb leads to a increase in T2*-weighted image intensity...
blood flow
