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Assessment of the Renal Corticomedullary 23 Na Gradient Using Isotropic Data Sets

Rationale and Objectives

23 Na magnetic resonance imaging is a promising technique for the noninvasive imaging of renal function. Past investigations of the renal corticomedullary [ 23 Na] gradient have relied on imaging only in the coronal plane and on cumbersome calculations of [ 23 Na], which require the use of external phantoms. The aim of this study is therefore two-fold: to use an isotropic three-dimensional data set to compare coronal measurements of renal [ 23 Na] relative to measurements obtained in planes along the corticomedullary gradients and to investigate cerebrospinal fluid (CSF) 23 Na signal as an internal reference standard, obviating the need for time-intensive [ 23 Na] calculations.

Materials and Methods

Nominal isotropic three-dimensional 23 Na MRI data sets were obtained in 14 healthy volunteers before and after a water load. Images were reconstructed in the coronal plane and in planes angled along the direction of the corticomedullary sodium gradients. [ 23 Na] values and values of the corticomedullary [ 23 Na] gradient were measured by placement of a linear region of interest along corticomedullary gradients in both the coronal/nonangled [ 23 Na non-ang ] and the angled [ 23 Na ang ] image reconstructions. CSF [ 23 Na] was also acquired at multiple levels. Ratios of renal 23 Na and CSF 23 Na signal were calculated to construct a semiquantitative parameter, [ 23 Na CSF ]. Results of water stimulation as measured by [ 23 Na CSF ] and [ 23 Na ang ] were then compared.

Results

Mean values of [ 23 Na ang ] were statistically significantly greater than those of [ 23 Na non-ang ] ( P < .0001), although these values were linearly correlated ( R = 0.553, P < .0001) and exhibited similar extents of decreases in absolute terms ( P = .2) and in terms of the corticomedullary gradient following the water load. CSF [ 23 Na] did not statistically significantly differ at any level after the water load ( P > .5) but tended to increase in the cranial direction ( P < .001). [ 23 Na CSF ] measures demonstrated analogous statistical properties to [ 23 Na ang ] before and after the water load.

Conclusions

Assessment of renal corticomedullary [ 23 Na] gradients using isotropic data sets with image reconstructions along the gradients is likely more accurate than measurements in the coronal plane. Because CSF [ 23 Na] differs based on anatomic levels, such measures are useful as an internal reference only if region of interest placement is consistent. With this caveat in mind, normalization of renal to CSF 23 Na signal provides a feasible, less cumbersome alternative to [ 23 Na] calculations in intraindividual studies.

Recently, the feasibility of in vivo renal 23 Na magnetic resonance (MR) imaging (MRI) has been demonstrated in both animal and human studies . The latter have generally focused on qualitative assessments of normal native and allograft transplant kidneys . The feasibility of assessing the kidneys in physiologic conditions such as water deprivation or water ingestion has likewise been shown with 23 Na MR. To date, all publications in animals and humans have confirmed the presence of a renal corticomedullary [ 23 Na] gradient—more precisely, a normal increase in [ 23 Na] from the cortex to the medulla . Most techniques for the evaluation of this gradient involve placement of a linear region of interest (ROI) from the renal cortex to the medulla followed by pixel-by-pixel assessment of 23 Na signal or 23 Na signal-to-noise ratios. The most technically sophisticated method is the absolute quantification of renal 23 Na concentration from reference phantoms, including a-priori corrections of T1 and T2 effects . Since the introduction of pixel-by-pixel measurements by Maril et al , these assessments have invariably been performed in the coronal plane. However, no study to date has examined the efficacy of this convention, primarily because the nonisotopic spatial resolutions used in human studies (0.3 × 0.3 × 1.5 cm 3 ) do not allow arbitrary selection of an imaging plane for slice reconstruction , and data acquisition in the axial plane would not allow sufficient coverage of the parenchyma within a reasonable scan time. Recently, a technique for 23 Na MRI of the human kidney using isotropic spatial resolutions was described; however, the assessment of the corticomedullary sodium gradients in that trial was still performed in the coronal plane . Because commercially available software allows real-time, post-processing of isotropic three-dimensional (3D) data sets, the corticomedullary gradient can theoretically be assessed along its true anatomic axis in the physiologic direction of the gradient.

To further improve the clinical applicability of 23 Na imaging, other practical considerations much be assessed. For example, quantification of renal 23 Na content appears to serve as a de facto gold standard for measurement, due to the ability to obtain absolute concentration values. However, as described elsewhere, this approach is hampered by technical factors including the need to a priori evaluate relaxation times of reference tubes . One possible solution to simplify this correction is to normalize renal 23 Na signal to that of cerebrospinal fluid (CSF), an internal reference standard, resulting in a nonquantitative parameter referred to hereafter as [ 23 Na CSF ]. However, the assessment and quantification of CSF 23 Na concentration have only been examined, to date, in passing in a work focusing on brain parenchymal tissue . Little is known about 23 Na imaging of the CSF in the lumbar spinal canal—the parameter of interest in calculating the [ 23 Na CSF ].

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Materials and methods

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Image Analysis

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Nonangled Measurements

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Angled Measurements of [ 23 Na ang ]

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Figure 1, (a–c) Three-dimensional orientation of the right kidney for images obtained in a strict coronal plane ( a = sagittal, b = coronal, c = axial). The linear region of interest for measurement of the corticomedullary [ 23 Na non-ang ] gradient is marked with an asterisk in (b) . (d–f) Three-dimensional orientation of the same kidney for images reconstructed along the longitudinal axis of the corticomedullary [ 23 Na ang ]. The corresponding linear region of interest is marked with a double-asterisk in (f) .

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Reference Phantom Measurements for [ 23 Na ang ]

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CSF Measurements

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Figure 2, Comparison between sagittal 23 Na images (a) , 1 H images (c) , and colored, virtually merged images of both (b) .

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Statistical Analysis

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Results

Angled Corticomedullary [ 23 Na ang ] Gradient

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Figure 3, Bland–Altman plot, plotting the ratio of the two methods (standard coronal [ 23 Na non-ang ] and the new angled assessment [ 23 Na ang ]) versus the average of both (in mM). The lines and given numbers on the right side represent the mean of the ratio and the ±1.96 standard deviations of the ratio.

Table 1

Summary Values and Differences of [ 23 Na ang ] and [ 23 Na non-ang ] before and after a Water Load (WL), according to the Distance from the Renal Cortex to the Medullary Pyramid

Distance from the Renal Cortex (in the direction of the medullary pyramid) Before WL After WL Difference before vs. after WL [ 23 Na non-ang ] [ 23 Na ang ] Δ in mM Δ in % [ 23 Na non-ang ] [ 23 Na ang ] Δ in mM Δ in % [ 23 Na non-ang ] Δ in % [ 23 Na ang ] Δ in % 0 mm 59.1 ± 9.3 82.3 ± 20.7 39.4 28.3 45.1 ± 5.3 ∗ 62.7 ± 15.2 38.9 28.0 14.0 −23.7 19.7 −23.9 5 mm 78.5 ± 10.4 101.6 ± 25.4 29.5 22.8 60.2 ± 6.5 ∗ 78.0 ± 19.5 29.5 22.8 18.2 −23.2 23.6 −23.2 10 mm 93.2 ± 11.0 120.0 ± 30.0 28.8 22.3 71.0 ± 8.0 ∗ 93.4 ± 24.2 31.6 24.0 22.1 −23.8 26.5 −22.1 15 mm 99.2 ± 10.7 135.2 ± 34.5 36.3 26.6 75.1 ± 8.9 ∗ 105.9 ± 28.5 40.9 29.0 24.1 −24.3 29.3 −21.7 20 mm 100.7 ± 10.9 145.0 ± 38.0 44.0 30.6 75.2 ± 10.1 ∗ 113.4 ± 31.1 50.8 33.7 25.5 −25.4 31.7 −21.8 25 mm 149.1 ± 39.2 115.6 ± 31.6 33.5 −22.5 Mean 35.6 26.1 38.4 27.5 20.8 −24.1 27.4 −20.0

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Figure 4, Image illustrating the overall mean of [ 23 Na] including all healthy volunteers before and after a water load (WL) in correlation with the distance from the renal cortex in the direction of the medullary pyramid. [ 23 Na] concentrations are given for the standard coronal [ 23 Na non-ang ] and the new angled assessment [ 23 Na ang ].

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CSF as Internal Reference

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Figure 5, Box and whisker plots of mean cerebrospinal fluid (CSF) [ 23 Na] for all volunteers at each evaluated anatomic level. Data shown are the five-number summaries consisting of: the lowest mean 23 Na concentration, the lower quartile (25% percentile), median, upper quartile (75% percentile), and greatest mean 23 Na concentration. The colored asterisks indicate outliers. The brackets at the top mark statistical significant differences ( P < .001). ROI, region of interest.

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Discussion

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