Objective:To explore the pathological mechanism of SN hyperechogenicity by investigating the characteristics of substantia nigra (SN) hyperechogenicity on transcranial sonography (TCS) and serum iron metabolism parameters in the postural instability gait difficulty and tremor dominant subtypes of Parkinson′s disease (PD), and the correlation between them.Methods:A total of 155 PD patients recruited in Parkinson′s Disease Specialty in the Second Affiliated Hospital of Soochow University from January 2019 to December 2021 were divided into postural instability gait difficulty group( n=95) and tremor dominant group( n=60). Meanwhile, 49 healthy gender- and age-matched healthy individuals who sought for physical examination during the same period were included as the control group. All subjects underwent TCS and blood test, and the echo of SN between the postural instability gait difficulty group and tremor dominant group, serum iron metabolism parameters among the three groups were compared. The postural instability gait difficulty group and tremor dominant group were subdivided into with SN hyperechogenicity (SN+ )subgroup and without SN hyperechogenicity (SN-) subgroup respectively according to TCS results, and the differences in serum iron metabolism parameters between the subgroups were further compared. The association between SN hyperechogenicity and serum iron metabolism parameters of the postural instability gait difficulty group and tremor dominant group were further analyzed. Results:The total area of bilateral SN+ , the area of SN+ on the larger side, and the ratio of the total area of SN+ to the midbrain area (S/M) in postural instability gait difficulty group were larger than those in tremor dominant group (all P<0.001). The value of serum ceruloplasmin and transferrin in both postural instability gait difficulty group and tremor dominant group were lower than those in control group (all P<0.001), and compared with tremor dominant group and control group, the postural instability gait difficulty group had lower serum ferritin(all P<0.01). In both postural instability gait difficulty group and tremor dominant group, serum ceruloplasmin in SN+ subgroup was lower than that in SN-subgroup ( P=0.001, 0.032). Moreover, there was a negative correlation between serum transferrin and the area of SN hyperechogenicity in two subgroups(postural instability gait difficulty group: rs=-0.454, P<0.001; tremor dominant group: rs=-0.494, P<0.001). Conclusions:Compared with the tremor dominant patients, the postural instability gait difficulty patients have larger area of SN hyperechogenicity and lower serum ferritin level. The area of SN hyperechogenicity is significantly negatively correlated with serum transferrin level, indicating that the production of this imaging characteristics is related to iron metabolism.