Imaging the ageing brain: iron accumulation across the ...
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BACKGROUND MRI techniques currently allow in vivo characterization of iron deposits in brain tissue. Understanding the age-related changes in iron content is key to identify abnormal patterns of iron deposition and their connection to pathological changes. Imaging the ageing brain: iron accumulation across the adult lifespan João B. Madureira 1,2 , Carla Guerreiro 1,2 , Filipa Brandão 1,2 , Luísa Biscoito 1 , Sofia Reimão 1,2 1. Departamento de Neurorradiologia, Centro Hospitalar Lisboa Norte, Lisboa, Portugal 2. Clínica Universitária de Imagiologia, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal XIV Congresso Nacional da Sociedade Portuguesa de Neurorradiologia POSTER 18 DOWNLOAD THIS POSTER AT www.neuroradiology.pt FOR MORE INFORMATION João B. Madureira, MD [email protected] REFERENCES 1. Acosta-Cabronero, J., et al. “In Vivo MRI Mapping of Brain Iron Deposition across the Adult Lifespan.” Journal of Neuroscience, vol. 36, no. 2, 2016, pp. 364–374., doi:10.1523/jneurosci.1907-15.2016. 2. Daugherty, Ana M., and Naftali Raz. “Erratum to: Appraising the Role of Iron in Brain Aging and Cognition: Promises and Limitations of MRI Methods.” Neuropsychology Review, vol. 25, no. 3, 2015, pp. 288–288., doi:10.1007/s11065-015-9299-4. 3. Kruer, Michael C., and Nathalie Boddaert. “Neurodegeneration With Brain Iron Accumulation: A Diagnostic Algorithm.” Seminars in Pediatric Neurology, vol. 19, no. 2, 2012, pp. 67–74., doi:10.1016/j.spen.2012.04.001. 4. Stankiewicz, James, et al. “Iron in Chronic Brain Disorders: Imaging and Neurotherapeutic Implications.” Neurotherapeutics, vol. 4, no. 3, 2007, pp. 371–386., doi:10.1016/j.nurt.2007.05.006. 5. www.mriquestions.com/. BRAIN IRON Iron content in brain tissue is critical for key processes such as ATP, neurotransmitter and myelin biosynthesis. However, buildup of unbound iron promotes oxidative stress and inflammation. 1 IRON IMAGING 2 KEY MESSAGES MRI is increasingly sensitive and accurate for brain iron detection, especially with the development of SWI and QSM. There is an exponential number of studies focusing on brain iron and neurodegeneration. However, the value of brain iron as a biomarker still remains to be established. Recognition of normal age brain iron deposition patterns and standardization of iron imaging are crucial to increase the diagnostic value of MRI for neurodegenerative diseases IRON IN BRAIN PATHOLOGY 3,4 Abnormal iron deposits have been linked to inflammation, neurodegeneration and cognitive decline, although the precise mechanisms remain unknown. IRON IN NORMAL AGEING 1,2 MRI measures compound iron and not unbound forms. Ageing associates with increased non-heme iron (mostly ferritin). Heme iron deposits (e.g. haematomas; microbleeds; siderosis) do not take part on healthy ageing. Iron deposition seems to be sex independent. HEME IRON → Iron bound to haemoglobin or myoglobin. ATP synthesis Myelin production Oxidative stress Inflammation NON-HEME IRON → Mostly bound to ferritin (≈90%) or transferrin; also present as UNBOUND IRON (a small fraction, but an important oxidant). Materials that disperse the main field are called diamagnetic. Materials that concentrate the field are called paramagnetic. Adapted from mriquestions.com/. Magnetic susceptibility → property of matter that distorts an applied magnetic field, resulting in field inhomogeneities. Iron imaging is based on the ability to distort the magnetic field (paramagnetism), and is therefore dependent on B 0 . There are several sequences sensitive to brain iron, namely T2*, Relaxometry and Susceptibility-weighted imaging (SWI), that combines magnitude and phase information, increasing the sensitivity for iron detection. Quantitative Susceptibility Mapping (QSM) is a novel technique that allows a more accurate quantification of brain iron content. Iron deposition with ageing has been shown to be spatially selective, with predilection for movement associated circuits. Basal ganglia have the largest iron concentrations. Globus pallidus has the highest concentration, with age independent levels which plateau around the 5 th -6 th decades. IRON DEPOSITION WITH AGE (highest to lowest) 1 MAGNETIC FIELD B 0 DIAMAGNETIC PARAMAGNETIC Calcium | Myelin | Water Gd | Fe 20-40 years 40-60 years 60-80 years >80 years T2 T2* SWI PUTAMEN RED NUCLEUS CAUDATE NUCLEUS SUBSTANTIA NIGRA DENTATE NUCLEUS MAGNITUDE OF INCREASE WITH AGE (highest to lowest) 1 RED NUCLEUS DENTATE NUCLEUS PUTAMEN SUBSTANTIA NIGRA CAUDATE NUCLEUS Female, 27 years PKAN (axial T2) Female, 60 years MSA-P (axial T2*) Male, 39 years Wilson’s Disease (axial T2*) Male, 61 years Huntington’s Disease (axial SWI) Male, 29 years D-2-HGA Aciduria (axial T2*) Female, 44 years Fabry Disease (axial SWI) Abbreviations: D-2-HGA - D-2-hydroxyglutaric; DRPLA - Dentatorubral-pallidoluysian atrophy; MSA-P - Multiple system atrophy, Parkinsonian type; PD – Parkinson’s Disease; PKAN2 - Pantothenate Kinase-Associated Neurodegeneration. Female, 61 years DRPLA (axial T2)
Transcript of Imaging the ageing brain: iron accumulation across the ...
BACKGROUND
MRI techniques currently allow in vivo characterization of iron
deposits in brain tissue. Understanding the age-related
changes in iron content is key to identify abnormal patterns
of iron deposition and their connection to pathological
changes.
Imaging the ageing brain: iron accumulation across the adult lifespanJoão B. Madureira1,2, Carla Guerreiro1,2, Filipa Brandão1,2, Luísa Biscoito1, Sofia Reimão1,2
1. Departamento de Neurorradiologia, Centro Hospitalar Lisboa Norte, Lisboa, Portugal
2. Clínica Universitária de Imagiologia, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal
XIV Congresso Nacional da Sociedade Portuguesa de Neurorradiologia POSTER 18
DOWNLOAD THIS POSTER AT
www.neuroradiology.pt
FOR MORE INFORMATION
João B. Madureira, MD
REFERENCES1. Acosta-Cabronero, J., et al. “In Vivo MRI Mapping of Brain Iron Deposition across the Adult Lifespan.” Journal of Neuroscience, vol. 36, no. 2, 2016, pp. 364–374., doi:10.1523/jneurosci.1907-15.2016.
2. Daugherty, Ana M., and Naftali Raz. “Erratum to: Appraising the Role of Iron in Brain Aging and Cognition: Promises and Limitations of MRI Methods.” Neuropsychology Review, vol. 25, no. 3, 2015, pp. 288–288.,
doi:10.1007/s11065-015-9299-4.
3. Kruer, Michael C., and Nathalie Boddaert. “Neurodegeneration With Brain Iron Accumulation: A Diagnostic Algorithm.” Seminars in Pediatric Neurology, vol. 19, no. 2, 2012, pp. 67–74.,
doi:10.1016/j.spen.2012.04.001.
4. Stankiewicz, James, et al. “Iron in Chronic Brain Disorders: Imaging and Neurotherapeutic Implications.” Neurotherapeutics, vol. 4, no. 3, 2007, pp. 371–386., doi:10.1016/j.nurt.2007.05.006.
5. www.mriquestions.com/.
BRAIN IRON
Iron content in brain tissue is critical for key
processes such as ATP, neurotransmitter and
myelin biosynthesis. However, buildup of
unbound iron promotes oxidative stress and
inflammation.1
IRON IMAGING2
KEY MESSAGES
MRI is increasingly sensitive and accurate for brain iron detection, especially with the development of SWI and QSM.
There is an exponential number of studies focusing on brain iron and neurodegeneration. However, the value of brain iron as a biomarker still remains to be established.
Recognition of normal age brain iron deposition patterns and standardization of iron imaging are crucial to increase the diagnostic value of MRI for neurodegenerative diseases
IRON IN BRAIN PATHOLOGY3,4
Abnormal iron deposits have been linked to inflammation, neurodegeneration and cognitive decline, although the precise mechanisms remain unknown.
IRON IN NORMAL AGEING1,2
MRI measures compound iron and not unbound forms. Ageing associates with increased
non-heme iron (mostly ferritin). Heme iron deposits (e.g. haematomas; microbleeds;
siderosis) do not take part on healthy ageing. Iron deposition seems to be sex independent.
HEME IRON → Iron bound to haemoglobin or myoglobin.
ATP synthesis
Myelin production
Oxidative stress
Inflammation
NON-HEME IRON → Mostly bound to ferritin (≈90%) or transferrin; also present
as UNBOUND IRON (a small fraction, but an important oxidant).
Materials that disperse the main field are called diamagnetic. Materials that
concentrate the field are called paramagnetic. Adapted from mriquestions.com/.
Magnetic susceptibility → property of matter that distorts an applied magnetic field, resulting in field inhomogeneities.
Iron imaging is based on the ability to distort the magnetic field (paramagnetism), and is therefore dependent on B0.
There are several sequences sensitive to brain iron, namely T2*, Relaxometry and Susceptibility-weighted imaging (SWI),
that combines magnitude and phase information, increasing the sensitivity for iron detection. Quantitative Susceptibility
Mapping (QSM) is a novel technique that allows a more accurate quantification of brain iron content.
Iron deposition with ageing has been shown to be spatially selective, with predilection for
movement associated circuits. Basal ganglia have the largest iron concentrations. Globus
pallidus has the highest concentration, with age independent levels which plateau around the
5th-6th decades.
IRON DEPOSITION WITH AGE (highest to lowest)1
MAGNETIC FIELD
B0
DIAMAGNETIC PARAMAGNETIC
Calcium | Myelin | Water Gd | Fe
20-40 years 40-60 years 60-80 years >80 years
T2
T2
*S
WI
PUTAMENRED
NUCLEUS
CAUDATE
NUCLEUS
SUBSTANTIA
NIGRA
DENTATE
NUCLEUS
MAGNITUDE OF INCREASE WITH AGE (highest to lowest)1
RED
NUCLEUS
DENTATE
NUCLEUSPUTAMEN
SUBSTANTIA
NIGRA
CAUDATE
NUCLEUS
Female, 27 years
PKAN
(axial T2)
Female, 60 years
MSA-P
(axial T2*)
Male, 39 yearsWilson’s Disease
(axial T2*)
Male, 61 years
Huntington’s Disease
(axial SWI)
Male, 29 years
D-2-HGA Aciduria
(axial T2*)
Female, 44 years
Fabry Disease
(axial SWI)
Abbreviations: D-2-HGA - D-2-hydroxyglutaric; DRPLA - Dentatorubral-pallidoluysian atrophy; MSA-P - Multiple system atrophy, Parkinsonian type; PD – Parkinson’s Disease; PKAN2 - Pantothenate Kinase-Associated Neurodegeneration.
Female, 61 years
DRPLA
(axial T2)
