Functional MR imaging of kidney—novel approaches to monitoring renal physiology

Abstract

infusion of hyperpolarized [ 13 C]urea under acute diuretic and antidiuresis conditions and observed upregulation of the urea transporter UT-A1 at the renal inner medulla under antidiuresis. This research reflects progress within the MRI community, and the radiology community in general, from what once was a primarily anatomic discipline to one that provides in vivo dynamic imaging of biological processes that have traditionally been studied in vitro, or analyzed in a very invasive fashion. With the advancement of instrumentation, pulse sequences, comprehension of MR biophysical mechanisms, and novel data analysis methods, MRI is able to provide a dynamic picture of tissue physiology, which includes tissue perfusion, tissue oxygenation, and oxygen metabolism (5, 14), water/solute transportation across cell membranes (4), tissue energetics (6), and more. For instance, based on the sensitivity of the MR signal to the blood oxygenation level (BOLD), the renal BOLD technique can provide a semiquantitative mapping of intrarenal oxygenation (10), thus opening new possibilities to study kidney diseases, particularly those related to tissue hypoxia (9). The quantitative BOLD (qBOLD) technique (5), originally developed for quantification of absolute blood oxygenation in neural applications, has the potential to obtain an absolute quantification of intrarenal oxygenation by separating the effect of blood oxygenation from the rest of hemodynamic parameters affecting renal BOLD signal (3). Since the major portion of kidney oxygen metabolism is used for active transportation of sodium, these BOLD-based techniques enable researchers and clinicians to noninvasively investigate important pathways regulating urine concentration. The intrarenal sodium gradient can also be directly quantified with sodiumMRI in both animal models and human subjects (2, 8). The kinetics of sodium gradient change are site specific and related to the loop diuretic mechanism in both intact and diseased kidneys. Other implementations of in vivo multinuclear magnetic resonance spectroscopy (MRS), including oxygen-17, fluorine19, phosphorus-31, and carbon-13, have been utilized to measure oxygen consumption, phosphate content and energy reserves, substrate selection, and rate of metabolic flux, respectively. However, compared with proton MRI, these multinuclear approaches usually suffer from extremely low intrinsic sensitivity, which results from low magnetogyric ratio, low natural abundance, and low in vivo concentration. At biological temperatures and field strengths that are attainable in a clinical setting, only a