Noninvasive measurement of the iron overload in the human body

1
Non-invasive measurement of the iron overload in
the human body
Mauro Marinelli,1,2 Barbara Gianesin,1,2
Antonella Lavagetto,3 Martina Lamagna,3 Eraldo
Oliveri ,1,2 Giuliano Sobrero,2 Laura
Terenzani,3 Gian Luca Forni3 1Physics
Department, University of Genova, Genova Italy
2National Institute of Nuclear Physics (INFN)
Genova 3Centro della Microcitemia e Anemie
Congenite, Ospedali Galliera, Genova, Italy

• SIF 05 Catania, 09/28/2005

2
Problema medico
Patients suffering from Cooleys anemia
(Thalassemia major) need frequent blood
transfusions. Transfused red cell iron
accumulates in tissues and organs with toxic
effects
Assessment of body-iron accumulation is essential
for managing therapy of iron-chelating diseases
characterized by iron overload such as
thalassemia, hereditary hemochromatosis, and
other forms of severe anemia.
The most common method for iron evaluation is the
liver biopsy
"Although chemical analysis of liver biopsy
samples is considered the gold standard for
determining the Liver Iron Concentration
..concern has been raised that variability in
the distribution of liver iron deposition exists
and might lead to errors as high as 200 in
assessing body iron burden by biopsy." Am J
Clinical Phathology 2005 123 146-152
3
Biosusceptometry
The magnetic field flux, threaded with the
pickup, is slightly modified by the diamagnetic
(mainly from water) and paramagnetic (iron)
properties of tissues.
4
Magnetic moments
The magnetization is proportional to the iron
concentration and to the applied magnetic field
5
Curie law
Susceptibilities arise from competition between
the aligning effect of the applied field and
thermal vibrations.
p iron effective magnetic moment (Bohr
magneton) Ferric iron (Fe3) ion p
5.9 Ferritin-Hemosiderin iron p ? 4
The apparatus calibration has been verified by
checking the Curie law with solutions of
hexahydrate ferric chloride (FeCl3?6H2O)
6
Iron contribution
7
SQUID Susceptometer
R. Fisher, E. Eich, R. Engelhardt, H. C.
Heinrich, M. Kessler and P. Nielsen, The
calibration problem in liver iron susceptometry,
in Advances in biomagnetism, S.J. Williamson et
al. , Ed. New York, 1990, pp. 501504.
8
Susc ratti 1
The magnetic field flux, threaded with the pickup
coil, is modified by the apparatus thermal
expansion. It is necessary for temperature
control on the milliKelvin scale to reach the
required sensitivity.
Twelve living rats has been measured with a
smaller prototype susceptometer
Magnet
Pickup
Pickup
9
Susc ratti 2
Marinelli M.1, Gianesin B.1, Avignolo C.2,
Minganti V.3, Parodi S.4   1 Dpt. of Physics,
and National Institute of Nuclear Physics
(INFN) 2 Dpt. of Oncology, Biology and Genetics 3
Dpt. of Chemistry and Pharmaceutical and
Alimentary Technology 4 Department of Oncology,
Biology and Genetics, and National Inst. for Res.
on Canc. of Genoa (IST), University of Genoa,
Genoa, Italy
10
Magnets and shield
(OP)
(IP)
(OM)
(IM)
(OP)
(IP)
11
Biosusceptometer
The magnetic field in this entire region is lower
than 1.9 10-2 T CEI EN 60601-2-3, 1997-02
12
Magnets
 
Inner magnets
Magnet construction
Outer magnets
13
Foto magneti e pick-up
Magnets
Pickup
14
IM-IP OM-OP
15
IM-OP OM-IP
16
Stretcher
We average a few differences between the signals
with the stretcher in and out of the sensitivity
region to account for the changes of the
environment magnetic properties.
This body position is to scan the whole torso.
Simply shifting the body allows measuring the
magnetic signal of other body parts, for instance
the head.
17
Eddy Current Signal
Because of the inductance of the eddy currents
loops within the sample and the solution
resistivity the delay of the eddy currents
relative to the induced electric field is
negligible. This is true also for the eddy
currents induced in the human body.
18

• Variando la concentrazione di
• NaCl in soluzione con 2l acqua deionizzata si
  osserva
• il diamagnetismo del sale sul
• segnale in fase
• le correnti parassite sul
• segnale a 90

19
Phantom
Small holes are evenly distributed on each of the
phantom plastic slices. We poured paramagnetic
powder, equivalent to 3 g of Fe3 and 15 g of
Fe3, inside the holes placed in the phantom
liver region.
Because of 100 nV error the minimum quantity of
detectable iron inside the entire liver region of
the phantom is 130 mg of Fe3 or 270 mg of iron
with an effective magnetic moment of 4 ?B.
20
V010
21
V037
22
P002 V005
Patient P002 and volunteer V005 have similar
anthropometric characteristics
23
P002 therapy
Patient P002 after four months under iron
depletive therapy
24
P029 spleenectomy
Patient P029 before and after the spleenectomy
25
P003 12 phlebotomies
Patient P003 before and after 12 phlebotomies
26
Iron overload
Phantom signals
signal of iron overload difference between the
actual magnetization signal and the signal
estimate of the patient, supposed depleted by the
iron overload.
27
The eddy current signal does not depend on the
iron
In all the patient measurements we never noticed
the iron overload skewness on the eddy current
signal.
The concentration of iron in the tissues as free
aqua ions is not significant. J. F. Schenck, E.
A. Zimmerman, Review Article High-field magnetic
resonance imaging of brain iron birth of a
biomarker?,N.M.R. Biomed, no. 17, pp. 433-445,
2004
28
Eddy current and magnetization signals
The eddy current and magnetization signals of a
person without iron overload have a similar
dependence on the body size.
The estimation of the signal of the patient,
supposed depleted by the iron overload is
strongly based on his eddy curent signal.
29
P029
The expected magnetization signal from the
statistical model using the eddy current signal
and the other patient's data measured before the
spleenectomy
30
P002 Statistical Estimate
31
P003 Statistical Estimate

• Iron overload
• March 7, 2005 10 g
• May 27, 2005 7.5 g

The iron removed by the 12 phlebotomies is 2.7g
32
Measured and calculated magnetization signal of a
few volunteers
33
Errors
34
Correlation with therapy
The measured reduction of the iron overload is
compared with its estimate according with the
therapy.
35
Correlation with serum-ferritin
Correlation of the iron overloads of all 40
patients measured with their blood serum-ferritin
36
Correlation with SQUID
The Liver Iron Concentration (LIC) via SQUID
susceptometry, on a subset of 30 patients, is
compared with the LIC obtained by the
susceptometer data.
37
Referto
38
Calibration
D
C
A
B
A 1 liter B 2 liter C 3 liter D 4 liter