High resolution magnetic susceptibility mapping of the substantia nigra in Parkinson's disease

Abstract

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...

Visualization of nigrosome 1 and its loss in PD

“…15 Mössbauer spectroscopy and colorimetry-based studies found total iron concentration to be unchanged or lower in PD, with a possible increase in non-ferritin-bound iron. 16 In vivo MRI studies tend to suggest iron accumulation in the SN with age 17 and in PD, 18,19 but without distinguishing the form of iron; since it is known that the relaxivity of iron (III) ferric ions is about 10 times greater than that of iron (II), 20 changes in T2* could simply reflect changes in the oxidation state of iron. The lower iron content in the Perl stain of the PD sample found here may be due to the fixation time being longer for the PD sample compared to the HC samples (z2 vs 1 year).…”

Nigrosome 1 Detection at 3T MRI for the Diagnosis of Early-Stage Idiopathic Parkinson Disease: Assessment of Diagnostic Accuracy and Agreement on Imaging Asymmetry and Clinical Laterality

“…2 Recently, a few researchers have tried to visualize the nigrosome 1 area with 7T MR imaging and demonstrated its feasibility as an imaging biomarker for the diagnosis of IPD. [3][4][5][6] The results, however, had a limited clinical utility because of low availability of 7T MR imaging. Hence, several studies have tried to translate nigrosome 1 detection to 3T MR imaging, which is widely available.…”

MR Quantitative Susceptibility Imaging for the Evaluation of Iron Loading in the Brains of Patients with -Thalassemia Major

“…4 Recently, the application of measuring brain iron by use of phase value of MR imaging with SWI 5,6 and quantitative susceptibility mapping (QSM) [7][8][9][10][11][12] has been evaluated for the quantification of iron content in patients with Parkinson disease. 13 QSM is an MR imaging technique that measures the magnetic susceptibility of tissues, such as blood or iron content, through mathematically modeling their induced effects on the phase of signal. Although the derivation of a magnetic susceptibility image from the phase informa-tion obtained from MR imaging is an ill-posed problem, techniques have been established to overcome this by imposing smoothness or sparseness constraints on the susceptibility images.…”