Samir D. Sharma1, Jens-Peter Kühn2, Marie-Luise Kromrey2, Scott B. Reeder1,3, and Diego Hernando1
1Radiology, University of Wisconsin - Madison, Madison, WI, United States, 2Experimental Radiology, Greifswald University, Greifswald, Germany, 3Medical Physics, University of Wisconsin-Madison, Madison, WI, United States
Synopsis
Magnetic
susceptibility is a fundamental property of all tissues. The presence of biomaterials
(e.g. iron, gadolinium) changes the susceptibility of the tissue in a direct
and well-understood manner, allowing quantification of biomaterial concentration. Quantitative
susceptibility mapping (QSM) techniques have been developed, largely to
investigate iron and calcium deposits in the brain. The development and
application of whole-body QSM may enable improved characterization and
quantification of tissue pathophysiology based on a fundamental property of
tissue. Thus, the purpose of this work was to develop and demonstrate the
feasibility of whole-body QSM in healthy subjects and in patients with
suspected iron overload.Purpose
Magnetic
susceptibility is a fundamental property of all tissues
1. The
presence of biomaterials (e.g. iron, gadolinium) changes the susceptibility of
the tissue in a direct and well-understood manner (unlike parameters such as T1
and T2*), allowing quantification of biomaterial concentration based on a fundamental
biophysical property. Thus, measurement of magnetic susceptibility offers a
promising alternative to relaxation-based methods for quantitative MRI. Quantitative
susceptibility mapping (QSM) techniques have been developed
2,3,
largely to investigate iron and calcium deposits in the brain. More recently,
techniques have been developed for QSM of the liver
4, breast
5,
and heart
6. Despite these advances, QSM techniques have focused on
specific organs or anatomy. The development and application of whole-body QSM
may enable improved characterization and quantification of tissue pathophysiology
based on a fundamental property of tissue (i.e. magnetic susceptibility).
Specific applications of this technology would include quantification of iron
concentration throughout the body as well as quantification of contrast agent
concentration in dynamic perfusion imaging and lymph node imaging. Towards this
goal,
the purpose of this work was to develop and demonstrate the feasibility
of a technique for whole-body QSM in healthy subjects and in patients with
suspected iron overload.Methods
Data Acquisition: Experiments were conducted after receiving
informed consent and institutional review board approval. Six participants
(three healthy and three with suspected iron overload) of an ongoing Study of
Health in Pomerania were scanned on a 1.5T system (Siemens Healthcare,
Erlangen, Germany) using a 3D multi-echo, gradient-echo acquisition. Five
overlapping stations were acquired, with the composite acquisition covering the
entire body. Subjects were placed in the supine position, and five phased-array
coils were placed on the head, neck, abdomen, pelvis, and lower extremities. The
spinal array was embedded in the patient table. For each station, acquisition
parameters included: FOV=50x50 cm, matrix size=256x128, slice thickness=5 mm,
number of slices=80, scan plane=coronal, TE1=2.38 ms, ΔTE=2.02 ms, number of
echoes=5. The total scan time=1:45 minutes.
Signal Model: The acquired complex-valued
source images were modeled as a function of the water (ρw) and fat (ρf) components with known
multi-peak fat spectrum (cn), the R2* map, and the B0
field map (ψ),
in the presence of additive white Gaussian noise (Eq. 1).
$$s(TE_n) = (\rho_w+c_n\rho_f)e^{j2\pi \psi TE_n}e^{-R2^*TE_n}+N(0,\sigma^2)$$
QSM Reconstruction:
The source images were processed station-by-station in Matlab (The Mathworks,
Natick, MA). The water and fat images as well as the R2* map and B0 field map were estimated
from the acquired data using a nonlinear least squares fit. The B0 field map was further
processed using a joint background field removal and dipole inversion QSM
technique to generate the magnetic susceptibility map (χ) (Eq. 2).
$$\min_\chi ||(WL\psi -
WLD\chi )||^2_2+\lambda||WCG\chi||^2_2$$
In Eq. 2, W is the data weighting matrix, L is a
Laplacian operator for background field removal, D is the dipole response
kernel, G is the 3D gradient operator, and C denotes both the edge and fat
constraints to regularize the ill-posed inverse problem4. Because QSM yields
estimates of relative susceptibility, the estimated
susceptibility map was shifted such that the subcutaneous adipose tissue was
-8.44 ppm7.
The susceptibility maps from the individual stations were combined using a
smooth weighting function in the overlapping regions, to form the whole-body
susceptibility map. Susceptibility measurements were made in the brain, liver,
vertebral bone marrow, visceral adipose tissue, and leg bone marrow.
Results
Figure
1 shows a mid-coronal slice of the whole-body susceptibility map for one healthy
subject and one patient with iron overload. The patient with iron overload
exhibits higher (i.e. less diamagnetic) magnetic susceptibility in the liver
and vertebral bone marrow, due to the paramagnetic effects of iron (blue
arrows). Susceptibility interfaces between water (e.g. muscle) and fat are
clearly depicted (yellow arrows). Overall, the patients with suspected iron
overload exhibited higher susceptibility in the liver and vertebral bone
marrow, and similar susceptibility in the brain, visceral adipose tissue, and
leg bone marrow as compared to the subjects with no iron overload (Figure 2). Fatty
tissue regions were found to be less diamagnetic than water-based tissues, in
agreement with previous findings
1,7. Liver susceptibility correlated
strongly with liver R2* (Figure 3).
Discussion & Conclusion
We
have developed a technique for whole-body QSM, and demonstrated its feasibility
in healthy subjects and patients with iron overload. Susceptibility differences
between healthy subjects and patients with iron overload were observed in the
liver and vertebral bone marrow, reflecting the presence of iron in these
regions. Ongoing work is focused on further development of this technique and broad
application to a population-based study to clarify the pathophysiology of iron-induced
diseases.
Acknowledgements
The authors acknowledge the support of the NIH (R01DK083380,
R01DK088925, and R01DK100651) and the German Federal Ministry of Education and
Research (01ZZ9603, 01ZZ0103, 01ZZ0403, 01ZZ0701, 03ZIK012), the Ministry of
Cultural Affairs, and the Social Ministry of the Federal State of
Mecklenburg-West Pomerania. We also thank Siemens Healthcare for their support.References
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