Original Research High Resolution Magnetic Susceptibility Mapping of the Substantia Nigra in Parkinson’s Disease Ashley K. Lotfipour, MD, 1 Samuel Wharton, MSci, 1 Stefan T. Schwarz, MD, 2 V. Gontu, MRCP, 2 Andreas Scha ¨fer, PhD, 1 Andrew M. Peters, PhD, 1 Richard W. Bowtell, PhD, 1 Dorothee P. Auer, PhD, 2 Penny A. Gowland, PhD, 1 * and Nin P.S. Bajaj, PhD 3 Purpose: To determine if tissue magnetic susceptibility is a more direct marker of tissue iron content than other MR markers of iron. This study presents the first quanti- tative, in vivo measurements of the susceptibility of the substantia nigra in patients with Parkinson’s disease. Materials and Methods: Nine patients and 11 controls were studied at 7 Tesla. Susceptibility maps were created by inverting the filtered phase maps associated with T2* weighted images. Results: On average, patients showed an increase in sus- ceptibility of the pars compacta compared with controls, which correlates with the predicted increase in brain iron in Parkinson’s disease. A rostral–caudal gradient in sus- ceptibility was also observed in controls and patients. Conclusion: Susceptibility mapping may provide a new tool for studying the development of Parkinson’s disease. Key Words: susceptibility; substantia nigra; pars com- pacta; iron; Parkinson’s disease J. Magn. Reson. Imaging 2012;35:48–55. V C 2011 Wiley Periodicals, Inc. PARKINSON’s DISEASE (PD) is a common neurodege- nerative disease that is associated with dopaminergic cell loss in the substantia nigra (SN). In normal aging or Parkinson’s disease, loss of these neurons occurs concurrently with the accumulation of iron, which acts as a nidus for neuronal damage, leading to free radical formation and lipid peroxidation (1). The pars compacta (PC), the medial sub region of the SN, has the greatest concentration of dopaminergic neurons in the SN. There have been several attempts to use MRI to study changes in the SN in PD. Anatomical differen- ces within the borders of the SN have been studied in patients with PD, and an increased latero-medial con- trast gradient has been detected (2,3). Reduced frac- tional anisotropy of water self diffusion, consistent with axonal loss, has also been observed in the SN of PD patients (4–6) and DTI has indicated changes in neuronal connectivity of the SN in patients with PD (3,7). However, most attempts to study PD with MRI have been based on the changes in iron homeostasis in the SN in PD, and the sensitivity of various MRI parame- ters to iron. In the SN there is a relatively inhomoge- neous distribution of iron (8) in the form of ferritin and a heterogeneous distribution of iron within neuro- melanin and hemosiderin, which will cause inhomoge- neities in the magnetic field within a sample. The transverse relaxation rates, R2 and R2*, decrease with increasing iron concentration, due to spin dephasing in the microscopic field inhomogeneities induced in regions of heterogeneous iron distribution. R2 is sensitive to diffusion in the inhomogeneous magnetic field, whereas R2* is also sensitive to static dephasing in the inhomogeneous field. Increased R2 (9–12) and R2* (10) has been observed in the pars compacta of the SN of patients with PD, particularly on the most affected side. However, some studies do not detect this effect, possibly because the value of R2 measured will depend on the echo time interval in multiple spin-echo sequences, or on the echo time regimen explored in single spin echo sequences, due to the effects of diffusion and exchange. It has been proposed that the field dependence of R2 is a direct measure of ferritin, and using this it was suggested that early onset PD patients had an increase in ferri- tin in the SN, whereas the reverse was true for late onset patients (13). Unfortunately, R2 and R2* are affected not only by iron but also by water binding, and so R2 0 (the differ- ence between R2 and R2*) has been proposed as a pa- rameter that is sensitive to field inhomogeneities due to iron without any confounding effects of changes in water binding. Several groups (14–16) found an increase in R2 0 in PD patients compared with healthy 1 Sir Peter Mansfield Magnetic Resonance Centre, School of Physics and Astronomy, Nottingham, UK. 2 Academic Radiology, School of Clinical Sciences, University of Nottingham, Nottingham, UK. 3 Department of Neurology, University Hospital, Nottingham, UK. *Address reprint requests to: P.A.G., Sir Peter Mansfield Magnetic Resonance Centre, School of Physics and Astronomy, University of Nottingham, NG7 2RD, UK. E-mail: penny.gowland@nottingham.ac.uk Received February 4, 2011; Accepted July 21, 2011. DOI 10.1002/jmri.22752 View this article online at wileyonlinelibrary.com. JOURNAL OF MAGNETIC RESONANCE IMAGING 35:48–55 (2012) CME V C 2011 Wiley Periodicals, Inc. 48