Screening for Early Stages of Nigrostriatal Alteration (I): MR-T2-Relaxation and TCS in Healthy Subjects with Increased Echogenity of the SN

The diagnosis of idiopathic Parkinson's disease (IPD) is primarily based on clinical signs and symptoms. Neuroimaging like magnetic resonance imaging (MRI) is regarded to reveal no consistent abnormalities and is only applied to differentiate IPD from secondary Parkinson syndromes. Recently, we and others demonstrated that transcranial ultrasound examination (TCS) allows one to detect a signal abnormality of the substantia nigra (SN) in most PD patients. Interestingly, the same echo feature can be found in about 8% to 10% of healthy subjects. This actual study aimed to demonstrate the MR-T₂-relaxation to be sensitive regarding changes of SN tissue indicating a nigrostriatal alteration. Seven patients with IPD and 14 healthy controls were included into this study. Patients with IPD were in the early stages of the disease. The healthy subjects were enrolled according to their SN signal intensity on TCS. Seven probands exhibited a distinctly hyperechogenic SN, seven had a normal SN echogenicity. All IPD patients and healthy subjects underwent TCS, ¹⁸F-Dopa PET, and MRI examinations. Informed consent according to the Declaration of Helsinki was obtained from all participants. The study was approved by the local Ethic Committee. The healthy subjects with SN hyperechogenicity exhibited shorter SN T₂-relaxation compared to the healthy participants without this echo feature (Mann-Whitney u-test: p=0.011). SN T₂-relaxion of the IPD patients was once again shorter compared to the controls with SN echogenity (p=2.2×10^-6). However, the IPD patients exhibited slower T₂-relaxation of the white matter compared to controls without (p=0.004) and with (p=0.038) SN echogenity. T₂-relaxation of the white matter did not differ between healthy subjects with and without SN hyperechogenicity (p=0.7). In contrast to this, there was a close correlation of T₂-relaxation of the SN with the decrease of striatal ¹⁸F-Dopa uptake [Spearman-Rho (R): -0.43; p=0.007]. Our findings may open new perspectives for screening for early stages of nigrostriatal alteration and IPD. MRI may serve as an instrument assessing the extent of neuronal degeneration of the SN in subjects identified to exhibit risk markers for IPD. One potentially important risk factor may be increased echogenicity of the SN.