Towards Quantitative Renal MR Blood Oximetry by Combined Monitoring of T2*, T2 and Blood Volume Fraction
Andreas Pohlmann1, Karen Arakelyan1,2, Leili Riazy1, Till Huelnhagen1, Stefanie Kox1, Kathleen Cantow2, Sonia Waiczies1, Bert Flemming2, Erdmann Seeliger2, and Thoralf Niendorf1

1Berlin Ultrahigh Field Facility, Max Delbrueck Center for Molecular Medicine, Berlin, Germany, 2Institute of Physiology, Charite Universitaetsmedizin, Berlin, Germany

Synopsis

Acute kidney injuries are often characterized by tissue oxygen hypoxia. T2*-mapping permits probing renal oxygenation but provides a surrogate rather than a quantitative measure of oxygen saturation. The link between pO2 and T2* is influenced by changes in blood volume fraction (BVf). Monitoring BVf in combination with recently developed quantitative BOLD approaches could permit unambiguous interpretation of renal T2*. To test the feasibility of this new approach we monitored renal T2*/T2 during baseline and short periods of venous occlusion. This was performed in the same animal under naïve conditions and again with USPIO to permit estimation of BVf and SO2.

Introduction and Purpose

Acute kidney injuries (AKI) of various origins share one common feature in the initiating chain of events: imbalance between local tissue oxygen delivery and oxygen demand.[1,2] Quantitative parametric MRI (T2* mapping) offers a non-invasive approach to probe renal oxygenation but provides a surrogate rather than a quantitative measure of oxygen saturation. Changes in tissue pO2 and T2* may be closely related, but their link is influenced by various effects, including changes in vascular volume fraction. Previously we reported T2* alterations of renal arterio-venous occlusion were more pronounced than those induced by hypoxia, while arterial occlusion induced a smaller T2* effect than hypoxia.[3,4] This observation might be explained by variations in renal blood volume. The suitability of the intravascular contrast agent (CA) ferumoxytol (ultra small paramagnetic iron oxide, USPIO) for renal blood volume estimation has been demonstrated in mice [5]. Recently quantitative blood oxygenation level-dependent (qBOLD) approaches were developed that intend to map local blood oxygen saturation (SO2), based on MR measurements of T2*, T2, BVf and macroscopic magnetic field distortions (B0 map) [6-9]. We hypothesized that ferumoxytol-based monitoring of renal BVf in combination with qBOLD model analysis is essential for the unambiguous interpretation of renal T2* and ultimately the estimation of SO2. To test the feasibility and establish the importance of this new approach we monitored renal T2*/T2 during baseline and short periods of venous occlusion (VO). In the same animal this was performed under naïve conditions and then again with USPIO. We subsequently estimated BVf and SO2 based on the approach of Christen et al [8].

Methods

Animal model: 6 male Wistar rats were anesthetized (urethane) and kept at 37°C core body temperature during surgery and MRI.[4] For VO a remotely controllable hydraulic occluder was placed around the renal vein. A short-term reversible ischemia was induced by closing the hydraulic occluder for 3 minutes, followed by a reperfusion phase of ~20 minutes. VO was confirmed by time-of-flight MR angiography of the kidney. Subsequently ferumoxytol was injected i.v. at a dose of 4 mg Fe/kg and after a mixing time of 2 minutes the short-term reversible VO was repeated.

MR imaging: in vivo MRI was performed using a 9.4 T animal scanner (Bruker, Germany) in conjunction with birdcage RF resonator and a 4-channel receive RF coil array (Bruker, Germany) customized for rats. Local B0 shimming on a voxel tailored to the kidney was performed first. Parametric T2* mapping used respiratory gated multi gradient echo (MGE) imaging (TR = 50 ms, echoes = 10, first TE = 1.43 ms, echo spacing = 2.14 ms, averages = 4) [4]. A coronal oblique slice across the kidney was acquired with a spatial in plane resolution of (226x445) µm2 and a slice thickness of 1.4 mm.

Quantitative renal MR blood oximetry: We estimated BVf from pre- and post-USPIO MR measurements of T2*. For this, we selected data from matching timepoints in the baseline-occlusion-recovery cycle under naïve conditions and after USPIO administration. BVf and SO2 were then calculated based on the approach of Christen et al [8]. For this feasibility study no B0 mapping was performed, as the effect of macroscopic magnetic field distortions was considered to be constant throughout the experiment. Calculation of absolute values for SO2 would require this information; here we report SO2 in a.u. with the aim to demonstrate that a temporal change can be detected.

Results

USPIO administration decreased cortical and medullary intensity in renal T2*-weighted images (Fig.1). The effect of venous occlusion was substantial without as well as with USPIO. Figure 2 shows maps of renal T2*, BVf and SO2 at baseline, during venous occlusion (VO) and the recovery phase. The reduction in renal T2* during VO could be unraveled into a significant SO2 decrease in cortex and outer medulla combined with a substantial blood volume increase.

Discussion and Conclusion

Our results demonstrate that combined monitoring of T2*, T2 and blood volume fraction is feasible and permits estimation of oxygen saturation of Hb (SO2). This is an important step towards quantitative renal MR blood oximetry, because - as hypothesized and now proven by our data - blood volume fraction may change considerably and confound the interpretation of renal T2* changes as a surrogate of changes in blood oxygenation. BVf may vary e.g. due to changes in renal perfusion pressure, vasoconstriction/-dilation or tubular distension. Unambiguous characterization of renal oxygenation by T2* hence requires multi-parametric MR including BVf. Combining T2*-mapping with USPIO, paralleled by calibration via invasive but quantitative physiological measurements using MR-PHYSIOL [10] might help to gain a better insight into renal oxygenation and hemodynamics.

Acknowledgements

No acknowledgement found.

References

[1] Seeliger, Europ Heart J 2012, 33:2007, [2] Evans, Am J Physiol 2011, 300(4):R931, [3] Arakelyan, Acta Physiol, 2013, 208(2): 202, [4] Pohlmann, PLoS ONE, 2013, 8(2):e57411, [5] Wang, F., Jiang, R. T., Tantawy, M. N., Borza, D. B., Takahashi, K., Gore, J. C., … Quarles, C. C. (2014). Repeatability and sensitivity of high resolution blood volume mapping in mouse kidney disease. Journal of Magnetic Resonance Imaging, 39(4), 866–871. [6] He, X., & Yablonskiy, D. A. (2007). Quantitative BOLD: Mapping of human cerebral deoxygenated blood volume and oxygen extraction fraction: Default state. Magnetic Resonance in Medicine, 57(1), 115–126. [7] Dickson, J. D., Ash, T. W. J., Wiliams, G. B., Sukstanskii, A. L., Ansorge, R. E., & Yablonskiy, D. a. (2011). Quantitative phenomenological model of the BOLD contrast mechanism. Journal of Magnetic Resonance (San Diego, Calif.?: 1997), 212(1), 17–25. [8] Christen, T., Lemasson, B., Pannetier, N., Farion, R., Segebarth, C., Rémy, C., & Barbier, E. L. (2011). Evaluation of a quantitative blood oxygenation level-dependent (qBOLD) approach to map local blood oxygen saturation. NMR in Biomedicine, 24(4), 393–403. [9] Christen, T., Lemasson, B., & Pannetier, N. (2012). Is T2* enough to assess oxygenation? quantitative blood oxygen level–dependent analysis in brain tumor. Radiology, 262(2), 495–502. [10] Pohlmann, Acta Physiol, 2013, 207(4):673.

Figures

T2*-weighted images of a kidney at baseline, during venous occlusion (VO) and in the first minutes of the recovery phase. The strong effect of VO on renal T2* is clearly visible. The same procedure was repeated after i.v. injection of an intravascular contrast agent (USPIO) to estimate blood volume.

Maps of renal T2*, blood volume fraction (BVf) and oxygen saturation of Hb (SO2) at baseline, during venous occlusion (VO) and the recovery phase. The reduction in renal T2* during VO could be unraveled into a SO2 decrease in cortex and outer medulla combined with a substantial blood volume increase.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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