Acute exposure to hypoxia environment can induce a series of symptoms of acute mountain sickness (AMS), hypobaric hypoxia is also often associated with diseases such as such as ischemic stroke and epilepsy. However, the pathophysiologic mechanisms of hypobaric hypoxia remains poorly understood. Previous studies had investigated regional changes of T2 relaxation induced by hypoxia [1,2], an initial increase in T2_,index (which related to the actual T2 relaxation time) in subjects without symptoms of AMS, but an initial decrease in T2_,index in symptomatic subjects was reported. Quantitative susceptibility mapping (QSM) reveals the underlying tissue susceptibility under static magnetic field and has been shown to convey unique information in various applications [3,4]. In this longitudinal study, QSM is applied, for the first time, to investigate the hypobaric induced changes in different cerebral regions. 10 nonsmoking, healthy participants (5 females, age range 24-29) that resides at an altitude of 30-50m with no previous exposure to high altitude were recruited. Ethical approval for this study was granted by the local IRB committee. A total of 4 scans were performed on each of the participant: participants received the first scan at sea level (43m, Beijing) on day 1; they then flew to Lhasa (altitude 3658m), received the second scan within 6 hours of arrival; the third MR scan was performed on day 4 after high-altitude acclimatization; the forth scan was performed after returning to Beijing. MR scans were performed using the model of 3.0T whole body scanner (MR Discovery 750, GE) equipped with an 8-channel head coil. Multi-echo GRE sequence was acquired for QSM with following parameters: FOV = 240 x240 mm, TR = 29.7ms, 12 echoes, first TE = 3.1 ms, echo spacing = 2.2ms, read-out bandwidth = ±62.5 kHz, acquisition matrix = 240x240, slice thickness = 1 mm. Full brain coverage was achieved with a total slice number of 140. The Lake Louise Score (LLS), an AMS selfreport questionnaire, were also recorded during the experiment [3]. The derivation of the QSM was performed using the STI suite toolbox [4]. The selected ROIs including splenium of corpus callosum (SCC), putamen (PU), globus pallidus (GP), caudate nuclei (CN), red nuclei (RN) and substantia nigra (SN) are as shown in Figure 1. These ROIs were selected as their functional properties have been reported to vary sustained hypoxia [2]. A paired two-tailed t-test was used to evaluate whether the means of the hypoxia-induced susceptibility changes in the ROIs were statistically significant (p<0.05).The changes of hypoxia-induced susceptibility in the selected regions of each volunteer are shown in Figure 2. Several observations can be made: the susceptibility in SCC, GP and CN showed a significant change between normoxia and hypoxia exposure within 6h. The susceptibility measured at 4 days hypoxia exposure in all ROIs showed no significant changes compared to normoxia values, except in CN. Also no significant difference before and after the volunteers went to high-altitude was observed in all ROIs. The changes in hypoxia-induced susceptibility were further analyzed by dividing the volunteers into AMS and noAMS groups based on their day one LLS records. Comparing susceptibility between 1day hypoxia and normoxia, measurements in SN and RN behaved largely different for AMS and noAMS group whereas those in other ROIs showed little difference (Fig.3a); comparing susceptibility between 4day hypoxia and normoxia, measurements in most regions showed considerable difference for AMS and noAMS group except CN (Fig. 3b). In this work, QSM was used as a biomarker to track hypoxia induced cerebral functional changes in a longitudinal study. It is well known that the QSM abnormality in deep nuclei regions are closely related to the brain dysfunction, and not only QSM variations were observed with acute exposure to hypopiesia, distinct QMS variations were observed between AMS and noAMS groups. Detailed susceptibility changes and the underlying pathological causes would lead to better understanding of the induction of AMS, and further the general mechanism of hypoxia.