WHOLE-BODY QUANTITATIVE SUSCEPTIBILITY MAPPING IN HEALTHY SUBJECTS AND IN PATIENTS WITH IRON OVERLOAD
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 tissues1. 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 developed2,3, largely to investigate iron and calcium deposits in the brain. More recently, techniques have been developed for QSM of the liver4, breast5, and heart6. 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 findings1,7. 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

1Schenck. Med Phys 1996;23:815-850.

2Liu et al. MRM 2011;66:777-783.

3Schweser et al. Neuroimage 2012;62:2083-2100.

4Sharma et al. MRM2015;74:673-683.

5Dimov et al. MRM 2015:73;2100-2110.

6Dibb et al. ISMRM 2014. p 627.

7Szczepaniak MRM 2002;47:607-610.

Figures

Figure 1: Whole-body susceptibility maps for a healthy subject (left) and patient with iron overload (right). The patient with iron overload exhibits a higher (i.e. less diamagnetic) susceptibility in the liver and vertebral bone marrow (blue arrows). Susceptibility interfaces between water (e.g. muscle) and fat are clearly depicted (yellow arrows).

Figure 2: Patients with suspected iron overload exhibited less diamagnetic susceptibility in the liver and vertebral bone marrow than subjects without iron overload. Measurements in the brain, visceral adipose tissue, and leg bone marrow were similar between the two groups.

Figure 3: Liver susceptibility correlates strongly with liver R2*, in six participants (three healthy subjects, and three patients with suspected iron overload).



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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