BOLD MRI via T₂* mapping can be sensitive to blood oxygenation and has been used to assess ischemia reperfusion injury where there are large changes in oxygen supply and demand (1). However, the source of signal change in BOLD MRI is not clear, and BOLD MRI can be insensitive and not necessarily reflect changes in oxygenation (2). Identifying the signal source can be critical for accurately characterizing kidney function in health and disease. One MR contrast mechanism called quantitative susceptibility mapping (QSM) is very sensitive to microstructure and chemical composition (3,4). QSM can also resolve strong susceptibility components and identify sources as paramagnetic, such as deoxygenated hemoglobin. In this study, we applied quantitative susceptibility mapping (QSM) to characterize the source of signal change and compared it with BOLD T₂* maps. We used a model of ischemia reperfusion in mouse kidneys and imaged at 1 hr, 1 day, 7 days, and 14 days after injury. QSM was able to identify the source of magnetic susceptibility and detected changes during early stages of ischemia reperfusion recovery.

Male C57Bl/6 mice (14 weeks) were used for ischemia reperfusion (n=6 normal, n=6 ischemia reperfusion). The right kidney was excised while the left renal pedicle was clamped (45 min). No surgery was performed on control animals. Animals were imaged longitudinally at 4 time points after surgical completion (1 hr, 2 days, 7 days, and 14 days). During imaging, animals were anesthetized under isoflurane and breathing freely.

A 3D interleaved multiecho radial sequence at 7T was used (Fig. 1) with the following parameters: views=41548, polar undersampling=4, TR=20 ms, TEs=5.5,10.8,16.1 ms, FA=10°, BW=100 kHz, averages=2, resolution=96×96×96 μm³.

Phase at each echo was calculated from the re-gridded k-space data. The tissue phase was calculated using Laplacian-based unwrapping and V-SHARP background phase removal algorithm (5). Finally, QSM was computed using a two-level reconstruction called STAR-QSM (6). Multiecho QSM images were summed to enhance susceptibility SNR.

BOLD T₂* maps were calculated from the multiecho magnitude images. T₂* and QSM were analyzed at the 4 time points after surgery. ROI measurements (~100-200 pixels) were taken to avoid vessels in the cortex, outer medulla, and inner medulla. A two-tailed t-test was used to determine significance between normal and ischemia reperfusion kidneys at each time point (p<0.05). One-way analysis of variance (ANOVA) was performed to determine significance over time (p<0.05).

BOLD T₂* and QSM are shown in Fig. 2. T₂* and susceptibility values were measured in the cortex, outer medulla, and inner medulla (Fig. 3). In general, T₂* increased in ischemia reperfusion kidneys at later stages of recovery. Specifically, T₂* was greater in injured kidneys compared to normal at day 7 and 14 in both the inner and outer medulla (p<0.05). Susceptibilities were higher at early stages of recovery. The susceptibility source was paramagnetic. Specifically, susceptibilities were more paramagnetic 1 hr after ischemia reperfusion in all three renal regions compared to normal (p<0.05). Susceptibilities were more diamagnetic at day 7 and 14 in the outer medulla of ischemia reperfusion kidneys (p<0.05). Both T₂* and susceptibility values did not change significantly over time in the normal kidneys (ANOVA p>0.05). Susceptibilities in the cortex and inner medulla of ischemia reperfusion kidneys decreased significantly over time (ANOVA p<0.05). T₂* in the outer medulla of ischemia reperfusion kidneys increased significantly over time (ANOVA p<0.05).In the present study, we applied BOLD T₂* and QSM to evaluate kidney injury from ischemia reperfusion. We found that T₂* was higher during the later stages of ischemia reperfusion recovery. Susceptibility difference between ischemia reperfusion and normal kidneys was greatest during the early stages of recovery. More importantly, we identified the source of susceptibility was paramagnetic in injured kidneys. T₂* values can suggest information on oxygen content, however T₂* changes can be affected by a variety of different sources. QSM can offer a more specific identification of the BOLD contributions (7). QSM also offers higher structural detail and can pinpoint local susceptibility changes. Here, the paramagnetic susceptibilities in ischemia reperfusion can be caused by deoxygenated hemoglobin, which is paramagnetic. These results suggest low oxygen content in the kidney. Moreover, susceptibility changes with time were most significant in the cortex and inner medulla, which are areas critical for blood perfusion and areas of high-energy demands for solute transport. QSM can be more sensitive in these renal regions to assess the kidney’s response to injury and detect changes immediately after ischemia reperfusion. In conclusion, QSM can identify the source of signal change in injured kidneys and can complement BOLD MRI to study renal pathophysiology.