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 quantitative, 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 susceptibility 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 susceptibility was also observed in controls and patients. PARKINSON's DISEASE (PD) is a common neurodegenerative 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 differences within the borders of the SN have been studied in patients with PD, and an increased latero-medial contrast gradient has been detected (2,3). Reduced fractional 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 parameters to iron. In the SN there is a relatively inhomogeneous distribution of iron (8) in the form of ferritin and a heterogeneous distribution of iron within neuromelanin and hemosiderin, which will cause inhomogeneities 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 ferritin in the S...