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Magnetic Resonance Magnetic Resonance Imaging in Imaging in
Characterizing Patterns Characterizing Patterns of Iron Depositionof Iron Deposition
K. K. PallavPallav
KolliKolli, MS4, NUFSOM, MS4, NUFSOMBeth Israel Deaconess Medical CenterBeth Israel Deaconess Medical Center
K. Pallav Kolli, MS4Gillian Lieberman, MD
K. Pallav Kolli, MS4Gillian Lieberman, MD
The interesting case…The interesting case…
GRE T1W out-
of-phase image
GRE T1W in-
phase image
Images from PACS, BIDMC
Normal
Requisition: 47 yearRequisition: 47 year--old woman with elevated old woman with elevated LFTsLFTsOur Patient
K. Pallav Kolli, MS4Gillian Lieberman, MD
The interesting case…The interesting case…
GRE T1W out-
of-phase image
GRE T1W in-
phase image
Images from PACS, BIDMC
NormalRequisition: 47 yearRequisition: 47 year--old woman with elevated old woman with elevated LFTsLFTs
Our Patient↓
signal intensity of liver compared to skeletal muscle
↓
signal intensity of liver compared to skeletal muscle
↑
signal intensity of liver compared to skeletal muscle
↑
signal intensity of liver compared to skeletal muscle
K. Pallav Kolli, MS4Gillian Lieberman, MD
The interesting case…The interesting case…
GRE T1W out-
of-phase image
GRE T1W in-
phase image
Images from PACS, BIDMC
NormalRequisition: 47 yearRequisition: 47 year--old woman with elevated old woman with elevated LFTsLFTs
Our Patient
↓
signal intensity on bottom image compared to top image
↔ signal intensity on bottom image compared to top image
K. Pallav Kolli, MS4Gillian Lieberman, MD
Based on the findings, the radiologists noted iron Based on the findings, the radiologists noted iron deposition in the liver, spleen, bone marrow, and deposition in the liver, spleen, bone marrow, and pancreas.pancreas.
They further characterized the likely etiology of this iron They further characterized the likely etiology of this iron deposition and its clinical implications.deposition and its clinical implications.
How?How?
The MotivationThe Motivation
Images from PACS, BIDMC
K. Pallav Kolli, MS4Gillian Lieberman, MD
ObjectivesObjectives
1.1. Principles of magnetic resonance Principles of magnetic resonance imaging for medical studentsimaging for medical students
2.2. Patterns of iron deposition seen on Patterns of iron deposition seen on MR imagingMR imaging
K. Pallav Kolli, MS4Gillian Lieberman, MD
Principles of MRIPrinciples of MRI““Hydrogen imaging” Hydrogen imaging” →→ H proton as a magnetH proton as a magnet
An electric current flowing in a loop will produce a magnetic field perpendicular to the loop
Similarly, a spinning hydrogen atom proton acts like a tiny magnet
Images from Pooley
RA1
K. Pallav Kolli, MS4Gillian Lieberman, MD
Why Hydrogen?Why Hydrogen?
Any atom with an odd number of protons or Any atom with an odd number of protons or neutrons has a net magnetic moment and neutrons has a net magnetic moment and behaves like a bar magnet. behaves like a bar magnet.
Hydrogen:Hydrogen:1. Is abundant in biologic tissue1. Is abundant in biologic tissue2. Has high sensitivity for its MR signal due to its 2. Has high sensitivity for its MR signal due to its
high resonance frequencyhigh resonance frequency
K. Pallav Kolli, MS4Gillian Lieberman, MD
Tissue Magnetization, MTissue Magnetization, M
A small excess of protons go into the spinA small excess of protons go into the spin--up up alignment, so that the tissue placed under Balignment, so that the tissue placed under Boo has has a small net magnetic field (M) aligned with Ba small net magnetic field (M) aligned with Boo
M
Adapted from Pooley
RA1
K. Pallav Kolli, MS4Gillian Lieberman, MD
PrecessionPrecessionPrecessionPrecession
Frequency of precession (Frequency of precession (LarmorLarmor frequencyfrequency):):
Like a spinning top under a gravitational field, a spinning hydrogen proton under a magnetic field will also wobble, or precess, about its axis
The frequency of that precession is related to an intrinsic property ofthe proton, the gyromagnetic
ratio, and the strength of the applied magnetic field, Bo.
Images from Pooley
RA1
K. Pallav Kolli, MS4Gillian Lieberman, MD
Radiofrequency PulseRadiofrequency Pulse
Magnetic resonanceMagnetic resonanceMagnetic resonance is defined as the Magnetic resonance is defined as the enhanced absorption enhanced absorption of energyof energy that occurs when that occurs when radiofrequency (RF) energy is radiofrequency (RF) energy is applied at the applied at the LarmorLarmor frequencyfrequency to nuclei of atoms within to nuclei of atoms within an external magnetic field an external magnetic field
Absorption of RF energy causes the net magnetization of Absorption of RF energy causes the net magnetization of tissue, M, to rotate away from alignment with Btissue, M, to rotate away from alignment with Boo towards the towards the transverse plane:transverse plane: RF Pulse
M
Adapted from Pooley
RA1
K. Pallav Kolli, MS4Gillian Lieberman, MD
MR SignalMR Signal
MR SignalMR SignalM has been rotated into the transverse plane with the M has been rotated into the transverse plane with the application of RF energy, but it continues to application of RF energy, but it continues to precessprecess at its at its LarmorLarmor frequencyfrequency
After the RF pulse perturbs M, the tissue relaxes back to After the RF pulse perturbs M, the tissue relaxes back to equilibrium. As it does so, it equilibrium. As it does so, it retransmits the energy it retransmits the energy it gained from the RF pulse in the form of the MR signalgained from the RF pulse in the form of the MR signal. . This signal decreases as the tissue relaxes to its equilibrium. This signal decreases as the tissue relaxes to its equilibrium.
K. Pallav Kolli, MS4Gillian Lieberman, MD
The ‘Skinny on MRI’The ‘Skinny on MRI’
The bar magnetThe bar magnet--like features of the proton can be like features of the proton can be exploitedexploited
The external magnetic field (1.5T, 3.0T, etc) sets up a The external magnetic field (1.5T, 3.0T, etc) sets up a condition favorable for energy exchangecondition favorable for energy exchange
We can apply energy with a radiofrequency (RF) pulse We can apply energy with a radiofrequency (RF) pulse and record the energy given off from relaxation as a and record the energy given off from relaxation as a signal intensitysignal intensity
Image Contrast → Differences in Tissue RelaxationImage Contrast → Differences in Tissue Relaxation
K. Pallav Kolli, MS4Gillian Lieberman, MD
Relaxation from a Perturbed StateRelaxation from a Perturbed StateTissue magnetization (M) relaxes to equilibrium (the Tissue magnetization (M) relaxes to equilibrium (the state imposed by the external magnetic field)state imposed by the external magnetic field)
This relaxation occurs as two simultaneous This relaxation occurs as two simultaneous mechanisms:mechanisms:
TT11 relaxationrelaxation (spin(spin--lattice relaxation) lattice relaxation) TT22 relaxationrelaxation (spin(spin--spin relaxation)spin relaxation)
How quickly a given tissue relaxes by each mechanism How quickly a given tissue relaxes by each mechanism is an intrinsic property, i.e. fat relaxes differently than is an intrinsic property, i.e. fat relaxes differently than water…water…
K. Pallav Kolli, MS4Gillian Lieberman, MD
T1 RelaxationT1 RelaxationAfter a 90º RF pulse, M is completely in the transverse After a 90º RF pulse, M is completely in the transverse plane and the longitudinal magnetization is zeroplane and the longitudinal magnetization is zero
The longitudinal magnetization then grows back, The longitudinal magnetization then grows back, known as the known as the TT11 relaxationrelaxation
Image from Pooley
RA1
K. Pallav Kolli, MS4Gillian Lieberman, MD
T1 RelaxationT1 RelaxationThe time it takes for a tissue to regain 63% of its final The time it takes for a tissue to regain 63% of its final value is T1.value is T1.
Each tissue undergoes T1 relaxation at its own rateEach tissue undergoes T1 relaxation at its own rate
Images from Pooley
RA1
K. Pallav Kolli, MS4Gillian Lieberman, MD
T1 Relaxation and Image SequencesT1 Relaxation and Image Sequences
Time to Repetition (TR)Time to Repetition (TR)In imaging sequences, RF pulses are repeated, and the time In imaging sequences, RF pulses are repeated, and the time between RF pulses is designated the between RF pulses is designated the time to repetition (TR)time to repetition (TR)
TR, T1, and EquilibriumTR, T1, and EquilibriumEventually, an equilibrium longitudinal magnetization is reachedEventually, an equilibrium longitudinal magnetization is reachedbetween TR and T1 relaxation. between TR and T1 relaxation. At short At short TRsTRs, tissues with short , tissues with short T1s have increased equilibrium longitudinal magnetization T1s have increased equilibrium longitudinal magnetization compared to tissues with long T1scompared to tissues with long T1s
K. Pallav Kolli, MS4Gillian Lieberman, MD
T1 Weighted ImagesT1 Weighted ImagesDifferences between tissues are accentuated at Differences between tissues are accentuated at short TR times. short TR times.
Therefore, imaging sequences with relatively short Therefore, imaging sequences with relatively short TRsTRs will emphasize T1 contrast. will emphasize T1 contrast. Hence, these are Hence, these are termed T1termed T1--weighted images.weighted images.
TR
Adapted fromPooley
RA1
K. Pallav Kolli, MS4Gillian Lieberman, MD
T1 Relaxation and MR SignalT1 Relaxation and MR SignalMR signal increases with increased longitudinal MR signal increases with increased longitudinal magnetizationmagnetization
Short T1 (fat) Short T1 (fat) ↑ Long. Magnetization ↑ Signal↑ Long. Magnetization ↑ Signal
Long T1 (spleen) ↓ Long. Magnetization ↓ Signal Long T1 (spleen) ↓ Long. Magnetization ↓ Signal
K. Pallav Kolli, MS4Gillian Lieberman, MD
T2 RelaxationT2 Relaxation
During the application of a 90During the application of a 90ºº RF pulse, all the RF pulse, all the protons protons precessprecess synchronously (“in phase”)synchronously (“in phase”)
Immediately following the RF pulse, the protons begin Immediately following the RF pulse, the protons begin to desynchronize, or “to desynchronize, or “dephasedephase””
The main cause of The main cause of dephasingdephasing is spinis spin--spin interactions: spin interactions: the precession frequency of a single proton is related to the precession frequency of a single proton is related to the magnetic field it sees. When two protons come the magnetic field it sees. When two protons come close to each other, they each are affected by Bclose to each other, they each are affected by B00 AND AND the other proton’s magnetic fieldthe other proton’s magnetic field
K. Pallav Kolli, MS4Gillian Lieberman, MD
T2 RelaxationT2 RelaxationDuring the time the two protons are close to each During the time the two protons are close to each other, other, one proton one proton precessesprecesses at a higher frequency at a higher frequency and the other at a slower frequencyand the other at a slower frequency
When the protons move apart, they only see BWhen the protons move apart, they only see Boo and and resume precession at the resume precession at the LarmorLarmor frequencyfrequency
But, because they spent some time spinning at But, because they spent some time spinning at different frequencies, they’re no longer different frequencies, they’re no longer synchronized, or in phasesynchronized, or in phase
K. Pallav Kolli, MS4Gillian Lieberman, MD
T2 RelaxationT2 RelaxationAs time passes, these interactions cause more and more As time passes, these interactions cause more and more protons to be out of phase with each otherprotons to be out of phase with each other
After T2 relaxation, the tissue transverse magnetic field After T2 relaxation, the tissue transverse magnetic field decays as fewer and fewer of the tiny magnets are lined decays as fewer and fewer of the tiny magnets are lined up togetherup together
Image from Pooley
RA1
K. Pallav Kolli, MS4Gillian Lieberman, MD
T2 Relaxation T2 Relaxation ––
A decay processA decay processA tissue’s T2 is the time it takes a tissue to decrease its A tissue’s T2 is the time it takes a tissue to decrease its transverse magnetization to 37% of initial value transverse magnetization to 37% of initial value due to spindue to spin--spin interactionspin interaction
Each tissue undergoes T2 relaxation at its own rateEach tissue undergoes T2 relaxation at its own rate
Images from Pooley
RA1
K. Pallav Kolli, MS4Gillian Lieberman, MD
T2T2--weighted Imagesweighted ImagesTime to EchoTime to Echo
The time between the middle of the RF pulse and when the The time between the middle of the RF pulse and when the MR signal is recorded is designated the MR signal is recorded is designated the time to echo (TE)time to echo (TE)
Greatest difference in tissues’ T2 values:Greatest difference in tissues’ T2 values:
Therefore, Therefore, imaging sequences that have a relatively imaging sequences that have a relatively long TE are T2long TE are T2--weighted imagesweighted images
Image adapted from Pooley
RA1
K. Pallav Kolli, MS4Gillian Lieberman, MD
T2 Relaxation and MR SignalT2 Relaxation and MR SignalMR signal is maximized when transverse MR signal is maximized when transverse magnetization is completely in phasemagnetization is completely in phase
Long T2 (CSF) Long T2 (CSF) ↑ Trans. Magnetization ↑ Signal↑ Trans. Magnetization ↑ Signal
Short T1 (Liver) ↓ Trans. Magnetization ↓ SignalShort T1 (Liver) ↓ Trans. Magnetization ↓ Signal
K. Pallav Kolli, MS4Gillian Lieberman, MD
T2* RelaxationT2* RelaxationDephasingDephasing occurs due to individual protons “seeing” occurs due to individual protons “seeing” different magnetic fieldsdifferent magnetic fields
There are other reasons for individual protons to There are other reasons for individual protons to “see” different magnetic fields from each other:“see” different magnetic fields from each other:
1.1.
External magnetic field (BExternal magnetic field (Boo
) ) inhomogeneitiesinhomogeneities2.2.
Magnetic susceptibility (to be discussed)Magnetic susceptibility (to be discussed)3.3.
Chemical shift effects (for another day’s discussion)Chemical shift effects (for another day’s discussion)
T2*T2* is the time it takes for a tissue’s transverse is the time it takes for a tissue’s transverse magnetization to decrease to 37% of its starting value magnetization to decrease to 37% of its starting value due due to all effects = T2 + additional to all effects = T2 + additional dephasingdephasing
effectseffects
K. Pallav Kolli, MS4Gillian Lieberman, MD
Correcting for T2Correcting for T2**
with Spinwith Spin--EchoEchoSpinSpin--spin spin dephasingdephasing is a random process having to do with protonis a random process having to do with proton--proton interactionsproton interactions
The other causes of T2* The other causes of T2* dephasingdephasing are due to differences in local are due to differences in local magnetic fields that magnetic fields that remain constant over timeremain constant over time
When a 180 RF pulse is applied halfway between the initial RF puWhen a 180 RF pulse is applied halfway between the initial RF pulse lse and the TE, the and the TE, the dephasingdephasing due to fixed due to fixed inhomogeneitiesinhomogeneities becomes becomes rephasingrephasing!!
Images from Pooley
RA1
K. Pallav Kolli, MS4Gillian Lieberman, MD
T2* T2* DephasingDephasing
A pulse sequence = strategy used to create an MR A pulse sequence = strategy used to create an MR imageimage
There are other types of pulse sequences, the discussion There are other types of pulse sequences, the discussion of which is beyond the scope of this presentationof which is beyond the scope of this presentation
It should be noted, though, that It should be noted, though, that GradientGradient--Recalled Recalled Echo (GRE) pulse sequences, often used to Echo (GRE) pulse sequences, often used to decrease imaging time, do not use a refocusing RF decrease imaging time, do not use a refocusing RF pulse and therefore bring out T2*pulse and therefore bring out T2*--weighted weighted featuresfeatures
K. Pallav Kolli, MS4Gillian Lieberman, MD
Putting T1, T2, TR, and TE TogetherPutting T1, T2, TR, and TE Together
T1 and T2 relaxation occur simultaneouslyT1 and T2 relaxation occur simultaneouslyT1 and T2 relaxation properties are specific to tissue T1 and T2 relaxation properties are specific to tissue typetype
T1W images: short TR, short TE (short T1 = bright)T1W images: short TR, short TE (short T1 = bright)
T2W images: long TR, long TE (long T2 = bright)T2W images: long TR, long TE (long T2 = bright)
Mz
TR
T1
Mxy
TE
T2 Relax Fast
Relax Slow
K. Pallav Kolli, MS4Gillian Lieberman, MD
Magnetic SusceptibilityMagnetic Susceptibility
Magnetic susceptibility is the tendency of a substance to Magnetic susceptibility is the tendency of a substance to attract or repel magnetic lines of forceattract or repel magnetic lines of force
Diamagnetic Diamagnetic substances weakly repel magnetic lines of forcesubstances weakly repel magnetic lines of force
Paramagnetic Paramagnetic substances attract magnetic lines of forcesubstances attract magnetic lines of force
SuperparamagneticSuperparamagnetic substances strongly attract magnetic substances strongly attract magnetic lines of forcelines of force
Ferromagnetic Ferromagnetic substances remain permanently magnetized substances remain permanently magnetized after being removed from a magnetic fieldafter being removed from a magnetic field
K. Pallav Kolli, MS4Gillian Lieberman, MD
Variations in magnetic susceptibility create magnetic Variations in magnetic susceptibility create magnetic field field inhomogeneitiesinhomogeneities, which in turn produce , which in turn produce dephasingdephasing and MR signal lossand MR signal loss
This signal loss is most pronounced on images with This signal loss is most pronounced on images with T2*T2*--weighting weighting
GradientGradient--recalled echo images are more sensitive to recalled echo images are more sensitive to magnetic susceptibility than spinmagnetic susceptibility than spin--echo imagesecho images
Magnetic Susceptibility and IronMagnetic Susceptibility and Iron
K. Pallav Kolli, MS4Gillian Lieberman, MD
Iron in tissue Iron in tissue creates strong local magnetic field creates strong local magnetic field inhomogeneitiesinhomogeneities that that ↓↓ MR signalMR signal
In each of the ensuing cases, we will look at the In each of the ensuing cases, we will look at the difference in difference in signal intensitysignal intensity in ironin iron--laden tissues between two images laden tissues between two images created with gradientcreated with gradient--recalled echo (GRE) technique: recalled echo (GRE) technique: T1T1--W W ININ--PHASE (IP) and OUTPHASE (IP) and OUT--OFOF--PHASE (OP) imagesPHASE (OP) images
The IPThe IP--OP sequence has 2 echo times OP sequence has 2 echo times –– the longer the TE, the the longer the TE, the greater time allowed for greater time allowed for dephasingdephasing, hence signal loss., hence signal loss.
Deposition of iron => loss of signal in tissue on IP (longer Deposition of iron => loss of signal in tissue on IP (longer echo) images compared to OP imagesecho) images compared to OP images
Magnetic Susceptibility and IronMagnetic Susceptibility and Iron
K. Pallav Kolli, MS4Gillian Lieberman, MD
The characteristic findings of tissue iron The characteristic findings of tissue iron depositondepositon described in the literature:described in the literature:
1.1.
Decreased signal intensity on T2WI and Decreased signal intensity on T2WI and T2*WI’sT2*WI’s
2.2.
For normal liver, signal intensity should be > For normal liver, signal intensity should be > skeletal muscle on ALL sequencesskeletal muscle on ALL sequences
3.3.
If iron deposition is great enough, decreased If iron deposition is great enough, decreased signal intensity on T1WI’s signal intensity on T1WI’s
Magnetic Susceptibility and IronMagnetic Susceptibility and Iron
K. Pallav Kolli, MS4Gillian Lieberman, MD
ReticuloendothelialReticuloendothelialTransfusion or Transfusion or extravascularextravascular hemolysishemolysis
ParenchymalParenchymalPrimary and secondary Primary and secondary hemochromatosishemochromatosisIntravascular Intravascular hemolysishemolysis
Cirrhosis Cirrhosis SideroticSiderotic nodulesnodules
Patterns of Iron DepositionPatterns of Iron Deposition
K. Pallav Kolli, MS4Gillian Lieberman, MD
Iron MetabolismIron Metabolism
Image from Andrews NC3
K. Pallav Kolli, MS4Gillian Lieberman, MD
ReticuloendothelialReticuloendothelial macrophages in spleen and bone marrow and macrophages in spleen and bone marrow and KupfferKupffer cells of liver scavenge iron from senescent cells of liver scavenge iron from senescent RBCsRBCs
The body has no effective mechanism for losing excess ironThe body has no effective mechanism for losing excess iron
With repeated transfusions or With repeated transfusions or rhabdomyolysisrhabdomyolysis, iron deposits in , iron deposits in the spleen, liver, and bone marrowthe spleen, liver, and bone marrow
Iron deposition limited to the RE system has little clinical Iron deposition limited to the RE system has little clinical significancesignificance
ReticuloendothelialReticuloendothelial
Iron DepositionIron Deposition
K. Pallav Kolli, MS4Gillian Lieberman, MD
ReticuloendothelialReticuloendothelial
Iron DepositionIron Deposition
28 28 yoyo
M with Hodgkin’s M with Hodgkin’s DzDz
s/ps/p
multiple chemotherapy regimens and BM transplantsmultiple chemotherapy regimens and BM transplants
GRE T1W out-
of-phase images
GRE T1W in-
phase images
Images from PACS, BIDMC
K. Pallav Kolli, MS4Gillian Lieberman, MD
ReticuloendothelialReticuloendothelial
Iron DepositionIron Deposition
28 28 yoyo
M with Hodgkin’s M with Hodgkin’s DzDz
s/ps/p
multiple chemotherapy regimens and BM transplantsmultiple chemotherapy regimens and BM transplants
GRE T1W out-
of-phase images
GRE T1W in-
phase images
Images from PACS, BIDMC
↓
signal intensity in liver, spleen, and bone marrow on IP images compared to OP images
K. Pallav Kolli, MS4Gillian Lieberman, MD
When the storage capacity of the RE system is reached, When the storage capacity of the RE system is reached, redistribution of iron to organ parenchyma (cardiac, redistribution of iron to organ parenchyma (cardiac, hepatic, endocrine tissues) is seenhepatic, endocrine tissues) is seen
RE capacity estimated at 10 g iron (~40 units of RE capacity estimated at 10 g iron (~40 units of PRBCsPRBCs))
Organ dysfunction and fibrosis as seen with Organ dysfunction and fibrosis as seen with hemochromatosishemochromatosis can then be seen (to be discussed)can then be seen (to be discussed)
Treatment is phlebotomy (often not clinically tolerated Treatment is phlebotomy (often not clinically tolerated in these patients) or in these patients) or chelationchelation therapytherapy
RE Iron Deposition RE Iron Deposition w/Parenchymalw/Parenchymal RedistributionRedistribution
K. Pallav Kolli, MS4Gillian Lieberman, MD
RE Iron Deposition RE Iron Deposition w/Parenchymalw/Parenchymal RedistributionRedistribution
GRE T1W out-
of-phase images
GRE T1W in-
phase images
47 yo
F with h/o
aplastic
anemia s/p
transfusion > 75 units PRBCs
in 3 yearsImages from PACS, BIDMC
K. Pallav Kolli, MS4Gillian Lieberman, MD
RE Iron Deposition RE Iron Deposition w/Parenchymalw/Parenchymal RedistributionRedistribution
GRE T1W out-
of-phase images
GRE T1W in-
phase images
47 yo
F with h/o
aplastic
anemia s/p
transfusion > 75 units PRBCs
in 3 yearsImages from PACS, BIDMC
↓
signal intensity in liver, spleen, bone marrow, and pancreas on IP images compared to OP images
K. Pallav Kolli, MS4Gillian Lieberman, MD
HemochromatosisHemochromatosis
Intravascular Intravascular hemolysishemolysis
ParenchymalParenchymal
Iron DepositionIron Deposition
K. Pallav Kolli, MS4Gillian Lieberman, MD
AutosomalAutosomal recessive disease wherein 2recessive disease wherein 2--3x normal amount of 3x normal amount of iron is absorbed from GI tractiron is absorbed from GI tract
Iron deposition in liver first, then heart and endocrine organs:Iron deposition in liver first, then heart and endocrine organs:Cirrhosis and Cirrhosis and hepatocellularhepatocellular carcinomacarcinomaCardiomyopathyCardiomyopathyDM, DM, hypopituitarismhypopituitarism, , hypogonadismhypogonadism, , hypoparathyroidismhypoparathyroidismCan also see destructive arthritisCan also see destructive arthritis
Most patients asymptomatic until adulthoodMost patients asymptomatic until adulthood
Primary Primary HemochromatosisHemochromatosis
K. Pallav Kolli, MS4Gillian Lieberman, MD
Primary Primary HemochromatosisHemochromatosisDiagnosisDiagnosis
Biochemical evidence of iron overload (serum, liver Biochemical evidence of iron overload (serum, liver bxbx))Genetic testingGenetic testing
QuantificationQuantificationLiver biopsy remains gold standardLiver biopsy remains gold standard
TreatmentTreatmentPhlebotomy or Phlebotomy or chelatechelate txtx once serum once serum ferritinferritin levels reach a levels reach a designated thresholddesignated thresholdIf treated before organ damage, life expectancy is normal. If treated before organ damage, life expectancy is normal. Endocrine abnormalities and cirrhosis DO NOT resolve.Endocrine abnormalities and cirrhosis DO NOT resolve.
K. Pallav Kolli, MS4Gillian Lieberman, MD
ParenchymalParenchymal
Iron DepositionIron Deposition Primary Primary HemochromatosisHemochromatosis
GRE T1W out-
of-phase image
GRE T1W in-
phase image
41 yo
F with incidentally noted elevated serum ferritin
and transferrin
saturation. Sub-sequent genetic testing provedpositive for C282Y homo-zygosity.
Images from PACS, BIDMC
K. Pallav Kolli, MS4Gillian Lieberman, MD
ParenchymalParenchymal
Iron DepositionIron Deposition Primary Primary HemochromatosisHemochromatosis
GRE T1W out-
of-phase image
GRE T1W in-
phase image
41 yo
F with incidentally noted elevated serum ferritin
and transferrin
saturation. Sub-sequent genetic testing provedpositive for C282Y homo-zygosity.
Images from PACS, BIDMC
↓
signal intensity in liver on IP images compared to OP images
↔ or ↑ signal intensity in bone marrow, pancreas, and spleen on IP images compared to OP images
K. Pallav Kolli, MS4Gillian Lieberman, MD
Primary Primary HemochromatosisHemochromatosis
This patient’s disease has been caught early: This patient’s disease has been caught early: there is only evidence of iron deposition in the there is only evidence of iron deposition in the liver.liver.
This has prognostic significance!This has prognostic significance!
K. Pallav Kolli, MS4Gillian Lieberman, MD
PrecirrhoticPrecirrhotic vs. Cirrhotic Primary vs. Cirrhotic Primary HemochromatosisHemochromatosis((SiegelmanSiegelman et al.)et al.)88
Almost ALL pts with PH and cirrhosis had decreased Almost ALL pts with PH and cirrhosis had decreased signal intensity in the pancreas (10/11)signal intensity in the pancreas (10/11)
ALL pts with PH and without cirrhosis had normal signal ALL pts with PH and without cirrhosis had normal signal intensity in the pancreas (4/4)intensity in the pancreas (4/4)
In ALL pts with cirrhosis not secondary to PH, signal In ALL pts with cirrhosis not secondary to PH, signal intensity in the pancreas was normal (4/4)intensity in the pancreas was normal (4/4)
Primary Primary HemochromatosisHemochromatosis
K. Pallav Kolli, MS4Gillian Lieberman, MD
Secondary Secondary HemochromatosisHemochromatosis
Seen in diseases with ineffective Seen in diseases with ineffective erythropoiesiserythropoiesisThalassemiaThalassemia major, major, sideroblasticsideroblastic anemia, anemia, megaloblasticmegaloblastic anemiaanemia
Spleen and/or bone marrowSpleen and/or bone marrow may or may not may or may not be involved in secondary be involved in secondary hemochromatosishemochromatosis
(muddies the (muddies the
waters of characterizing waters of characterizing parenchymalparenchymal
vs. vs. reticuloendothelialreticuloendothelial iron deposition)iron deposition)
K. Pallav Kolli, MS4Gillian Lieberman, MD
Free hemoglobin binds to Free hemoglobin binds to haptoglobinhaptoglobin and is taken up and is taken up by by hepatocyteshepatocytes
When When haptoglobinhaptoglobin is saturated, free hemoglobin is is saturated, free hemoglobin is filtered by filtered by glomerulusglomerulus and reabsorbed into proximal and reabsorbed into proximal convoluted tubule cellsconvoluted tubule cells
MR: iron deposition in MR: iron deposition in liver +/liver +/-- kidneyskidneys
No known clinical significance of depositionNo known clinical significance of deposition
Intravascular Intravascular HemolysisHemolysis
K. Pallav Kolli, MS4Gillian Lieberman, MD
Common chronic endCommon chronic end--stage liver disease for stage liver disease for variety of hepatic insultsvariety of hepatic insults
Diffuse architectural disorganization with Diffuse architectural disorganization with fibrosis and formation of regenerative nodulesfibrosis and formation of regenerative nodules
MR: preferential atrophy of R lobe with hypertrophy of caudate aMR: preferential atrophy of R lobe with hypertrophy of caudate and nd lateral segments of L lobe, nodular texture, low signallateral segments of L lobe, nodular texture, low signal--intensity nodule, intensity nodule, sequelaesequelae of portal HTNof portal HTN
CirrhosisCirrhosis
K. Pallav Kolli, MS4Gillian Lieberman, MD
Diffuse Diffuse hepatocytehepatocyte iron deposition may be seeniron deposition may be seenMild elevation, seen in up to 50% of cirrhotic livers Mild elevation, seen in up to 50% of cirrhotic livers
SideroticSiderotic regenerating nodulesregenerating nodules~25% of regenerative nodules accumulate iron > ~25% of regenerative nodules accumulate iron >
surrounding parenchymasurrounding parenchymaSomewhat specific for cirrhosisSomewhat specific for cirrhosis
GammaGamma--Gandy bodies (Gandy bodies (sideroticsiderotic nodules) in spleennodules) in spleenPresent in up to 12% of Present in up to 12% of cirrhoticscirrhoticsProvides indirect evidence of portal HTNProvides indirect evidence of portal HTN
Cirrhotic Iron DepositionCirrhotic Iron Deposition
K. Pallav Kolli, MS4Gillian Lieberman, MD
Cirrhotic Iron DepositionCirrhotic Iron Deposition
GRE T1W out-
of-phase image
GRE T1W in-
phase image
51 yo
M with h/o
alcoholic cirrhosis
Images from PACS, BIDMC
K. Pallav Kolli, MS4Gillian Lieberman, MD
Cirrhotic Iron DepositionCirrhotic Iron Deposition
GRE T1W out-
of-phase image
GRE T1W in-
phase image
51 yo
M with h/o
alcoholic cirrhosis
Images from PACS, BIDMC
↓
signal intensity in liver on IP images compared to OP images
↓
signal intensity in regenerative nodules compared to surrounding parenchyma
Gamma-Gandy body in spleen
K. Pallav Kolli, MS4Gillian Lieberman, MD
Future Utility for MRI in Iron Future Utility for MRI in Iron Deposition Deposition
MRI may be useful for more than just MRI may be useful for more than just characterizing the pattern of iron depositioncharacterizing the pattern of iron deposition
Much research currently focuses on using MRI Much research currently focuses on using MRI to quantify the degree of iron depositionto quantify the degree of iron deposition
K. Pallav Kolli, MS4Gillian Lieberman, MD
Serum Serum ferritinferritin stores have poor specificity for stores have poor specificity for body iron storesbody iron stores
Liver biopsy is often used to establish and Liver biopsy is often used to establish and quantify biochemical evidence of iron overloadquantify biochemical evidence of iron overload
MR Quantification of Hepatic Iron MR Quantification of Hepatic Iron Stores? Stores? ((GandonGandon
Y et al)Y et al)99
K. Pallav Kolli, MS4Gillian Lieberman, MD
Algorithm based on ratio of signal intensities of liver to Algorithm based on ratio of signal intensities of liver to skeletal muscle on GRE sequences obtained with 1.5T skeletal muscle on GRE sequences obtained with 1.5T magnetmagnet
89% sensitive in detecting clinically relevant hepatic 89% sensitive in detecting clinically relevant hepatic iron (> 60 µmol/g, normal is < 36 µmol/g) with good iron (> 60 µmol/g, normal is < 36 µmol/g) with good correlation with tissue quantification from liver correlation with tissue quantification from liver bxbx
AdvantagesAdvantagesNoninvasive, eliminates risk of Noninvasive, eliminates risk of bxbx w/inadequate tissue, may w/inadequate tissue, may provide better estimate than biopsy of cirrhotic, provide better estimate than biopsy of cirrhotic, heterogeneous liver, less expensive than heterogeneous liver, less expensive than bxbx
MR Quantification of Hepatic Iron MR Quantification of Hepatic Iron Stores? Stores? ((GandonGandon
Y et al)Y et al)99
K. Pallav Kolli, MS4Gillian Lieberman, MD
Principles of MRIPrinciples of MRIHydrogen imagingHydrogen imagingT1 RelaxationT1 RelaxationT2 and T2T2 and T2** RelaxationRelaxation
MR Characterization of Patterns of Iron DepositionMR Characterization of Patterns of Iron DepositionReticuloendothelialReticuloendothelialParenchymalParenchymalCirrhoticCirrhotic
MR Quantification of Iron DepositionMR Quantification of Iron Deposition
ConclusionsConclusions
K. Pallav Kolli, MS4Gillian Lieberman, MD
Dr. Neil M. Dr. Neil M. RofskyRofsky and Dr. Karen Leeand Dr. Karen LeeDrs. Darren Brennan, Mike Schuster, Marty Drs. Darren Brennan, Mike Schuster, Marty Smith, and Eric SteinSmith, and Eric SteinDr. Gillian Lieberman and Pamela Dr. Gillian Lieberman and Pamela LepkowskiLepkowskiPaul Paul GiganteGigante, Carolynn , Carolynn DeBenedictisDeBenedictis, , SejalSejalPatel, and Patel, and ArghavanArghavan SallesSalles
AcknowledgementsAcknowledgements
K. Pallav Kolli, MS4Gillian Lieberman, MD
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