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Urinary Oxygen Tension Measurement in Humans Using Magnetic Resonance Imaging

Rationale and Objectives

Renal medullary hypoxia is frequently implicated in renal dysfunction, and urinary oxygen tension (PO 2 ) in the renal pelvis can be used as a surrogate for the adjacent renal medullary oxygenation. We sought to assess the feasibility of magnetic resonance (MR) quantification of urinary PO 2 in humans.

Materials and Methods

The longitudinal relaxivity (R1) of fluids is linearly related to PO 2 , allowing MR quantification of urinary PO 2 . We imaged urine phantoms with a range of PO 2 using a real-time saturation recovery T2-prepped single-shot fast spin-echo sequence to calibrate urine R1 values to PO 2 . Following institutional review board approval, we imaged the urinary bladders of seven healthy subjects while they were breathing room air and the renal pelvis of nine healthy subjects while they were breathing room air or 100% oxygen via facemask. The renal pelvic urine PO 2 was compared before, during, and after 100% oxygen breathing.

Results

Our phantom study confirmed that urine R1 is linearly related to PO 2 : PO 2 (mm Hg) = (R1 − 0.2253 s −1 )/(2.61 e −4 s −1 /mm Hg). The mean bladder urine PO 2 ranged from 23 to 45 mm Hg among the seven subjects. Successful MR measurements of renal pelvic urine PO 2 were obtained in seven of nine healthy subjects. Following 100% O 2 breathing, the renal pelvic urine PO 2 showed a significant mean increase of 29 mm Hg ( P < .05).

Conclusions

We show that MR quantification of urinary PO 2 is feasible. Noninvasive renal pelvic urine PO 2 determinations could serve as a valuable indirect measure for renal medullary oxygenation, allowing for clinical investigations of the role of renal medullary hypoxia in renal disease.

The oxygen tension in the renal medulla is among the lowest in the human body due to low medullary perfusion and the large amount of oxygen required for sodium reabsorption and urinary concentration ( ). This low oxygen environment places the medulla at risk for ischemic injury, which is associated with numerous common renal diseases, including acute tubular necrosis, diabetic nephropathy, and drug- or contrast-induced nephropathy ( ). Previous studies have shown that measurements of urine oxygen tension (PO 2 ) in the renal pelvis is a sensitive surrogate measure of the oxygenation of the immediately adjacent renal medulla ( ). As urine flows through the tubules of the medullary thick ascending limb into the renal pelvis, the urine PO 2 equilibrates with the medullary PO 2 , which in turn reflects medullary perfusion and oxygen consumption ( ).

Urine PO 2 can change in response to a variety of physiologic and pathologic stimuli. For example, when healthy subjects breathe supplemental oxygen, their urine PO 2 increases, likely due to the increased dissolved oxygen in the blood supplying the medulla ( ). In patients with renal failure and loss of urine-concentrating ability, the urine PO 2 increases and this change is believed to reflect the reduced medullary metabolic function in such patients ( ). Urine PO 2 has also been shown to decrease progressively down the ureter into the bladder due to equilibration with the ureteral wall ( ). Therefore, the renal pelvic urine PO 2 most accurately reflects the renal medullary PO 2 ( ).

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Materials and methods

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MR Imaging

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Figure 1, Schematic diagram of the magnetic resonance sequence used for fluid oxygen tension (PO 2 ) imaging. The ratio of the signal intensity in any voxel (S 1S 2 ) is solely a function of R1. T R1 and T R2 indicate saturation recovery time for two successive acquisitions.

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Phantom Studies

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Human Studies

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Bladder urine

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Renal pelvic urine

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Image Analysis

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Statistical Analysis

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Results

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Figure 2, Plot of longitudinal relaxivity (R1) (1/s) for urine samples at body temperature (37° C) and 1.5 T. The slope (ΔR1/Δ PO 2 ) and intercept [R1(PO 2 = 0)] were used to calibrate the in vivo urine measurements.

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Figure 3, Bladder urine fluid oxygen tension (PO 2 ) measured by magnetic resonance imaging over 10 minutes in seven healthy subjects. The mean bladder urine PO 2 ( filled circles ) ranged from 23 to 45 mm Hg among the seven subjects. The open circles represent individual PO 2 measurements over 10 minutes for each subject. Error bars represent standard deviation.

Figure 4, Bladder urine fluid oxygen tension (PO 2 ) measured by magnetic resonance (MR) imaging versus that measured by oxygen probe in four healthy subjects. Error bars represent standard deviation of the MR imaging measurement over 10 minutes.

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Figure 5, Temporal measurements of renal pelvic urine fluid oxygen tension (PO 2 ) by magnetic resonance imaging in seven healthy subjects with 100% oxygen breathing. (a) Temporal urine PO 2 measurements for individual subjects. (b) Mean temporal urine PO 2 measurements for all seven subjects. Gray background indicates the time period of 100% oxygen breathing (17.5 minutes). BL, average of the two baseline renal pelvic urine PO 2 values while the subjects breathed room air. *Significant changes in urine PO 2 values compared to those obtained at room air ( P < .05). Error bars represent standard deviation of the mean renal pelvic urine PO 2 in the seven subjects.

Figure 6, Maps of renal pelvic urine fluid oxygen tension (PO 2 ) (a) before and (b) after 17.5 minutes of 100% oxygen breathing in a 36-year-old healthy male subject. The mean renal pelvic urine PO 2 increased from 47 to 78 mm Hg.

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Discussion

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