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Evaluation of Renal Oxygenation in Rat by Using R2′ at 3-T Magnetic Resonance

Rationale and Objectives

We sought to initially evaluate the feasibility of R2′ on a 3-T magnetic resonance (MR) scanner for assessment of renal oxygenation changes following administration of furosemide in rats.

Materials and Methods

Eight intact male Wistar rats were involved in experimental group. The experiment was performed at a 3-T MR scanner using a multiple gradient-echo (mGRE) sequence for R2* map and a multiecho fast spin-echo (FSE) sequence for R2 map. R2′ values of cortex and medulla were calculated using the equation R2* = R2 + R2′ . The values of R2 and R2* were measured and R2′ was calculated before and after administration of furosemide, and the changes (delta values) were calculated.

Results

Both R2* and R2 values decreased significantly after administration of furosemide ( P < .001) in both the cortex and medulla. ΔR2* in the medulla was significantly higher than in the cortex ( P < .05). ΔR2 was not significantly different between the cortex and medulla ( P > .05). The baseline R2′ value was 12.13 ± 0.59 1/s in the cortex and 19.52 ± 3.44 1/s in the medulla. R2′ value decreased significantly in the medulla after administration of furosemide ( P < .05), but there was no significant difference in the cortex before and after administration of furosemide ( P > .05).

Conclusion

R2′ may be more appropriate than R2* to indicate the change of oxygenation after administration of furosemide in intact rats at 3-T MR. Further studies are needed for both intact animals and experimental models in comparison with non-MR imaging methods to validate this initial observation.

During the past few years, there has been great interest in the possibility of using magnetic resonance (MR) images to provide an indicator of oxygenation in the kidneys. Blood oxygen level−dependent (BOLD) magnetic resonance imaging (MRI) is a noninvasive method to assess tissue oxygenation, using deoxyhemoglobin as an endogenous contrast agent ( ).

Deoxyhemoglobin is a paramagnetic molecule that generates magnetic moments by its unpaired iron electrons ( ). Increased deoxyhemoglobin speeds up magnetic spin dephasing of blood water protons and decreases signal intensity on T2* (apparent spin-spin relaxation time)-weighted MR images ( ). At 1.5-T MR, the measured parameter of renal BOLD MRI, rate of spin dephasing R2* (1/T2*), is closely related to the tissue content of deoxyhemoglobin, which indicates the oxygen tension (PO 2 ). The PO 2 of capillary blood is believed to be in equilibrium with the surrounding tissue; changes estimated by BOLD MRI may be interpreted as changes in tissue PO 2 ( ). Increased R2* levels imply decreased PO 2 in tissues ( ).

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Materials and methods

Animals

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MR Technique

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R2*=R2+R2′ R

2

*

=

R

2

+

R

2

where R2*, R2, and R2′ were measured in 1/s.

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Statistical Methods

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Results

Baseline Values in Medulla and Cortex

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Table 1

The R2*, R2, and R2′ Values in the Experimental Group

Pre-F Post-F_P_ Value R2* Cortex 26.13 ± 0.71 22.07 ± 2.04 < .001 Medulla 34.79 ± 3.51 28.45 ± 3.48 < .001P value < .001 R2 Cortex 14.00 ± 0.60 11.09 ± 0.65 < .001 Medulla 15.27 ± 0.43 12.41 ± 0.97 < .001P value < .001 R2′ Cortex 12.13 ± 0.59 10.98 ± 1.57 .095 Medulla 19.52 ± 3.44 16.04 ± 3.44 .005P value .001

In the experiment group, the three parameters showed significant values in the medulla compared to in the cortex ( P > .05). R2* and R2 showed significant decreases after administration of furosemide ( P < .001) in the cortex before and after the administration of furosemide. R2′ showed no significant difference ( P > .05). In contrast, all the three parameters showed significant decreases after administration of furosemide ( P < .001 for R2* and R2; P < .05 for R2′) in the medulla. The data in the table are presented as mean ± standard deviation (liters per second).

Pre-F, before the administration of furosemide; Post-F, after the administration of furosemide.

Table 2

The R2*, R2, and R2′ Values in Control Group

Pre-NS Post-NS_P_ Value R2* Cortex 25.00 ± 2.03 25.22 ± 1.13 .836 Medulla 32.58 ± 1.46 32.20 ± 0.91 .667P value .004 R2 Cortex 14.12 ± 0.42 14.00 ± 0.48 .067 Medulla 15.20 ± 0.71 15.20 ± 0.70 .874P value .045 R2′ Cortex 10.88 ± 2.40 11.22 ± 1.60 .748 Medulla 17.37 ± 2.13 17.00 ± 1.17 .671P value .005

In the control group, the three parameters also showed significant values in the medulla compared to the cortex ( P > .05). All the three parameters showed no significant difference before and after administration of NS in both the cortex and medulla. The data in table are presented as mean ± standard deviation (liters per second).

Pre-NS, before the administration of normal sodium; Post-NS, after the administration of normal sodium.

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Influence of Furosemide

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Figure 1, The typical renal R2* maps and the corresponding anatomic templates. Left , baseline R2* map ( A ) and its corresponding anatomic template ( a ). Right , R2* map after administration of furosemide ( B ) and its corresponding anatomic template ( b ). Both the cortex and medulla showed decreased signal intensity on B , but no similar signal intensity changes were found on the anatomic templates (the same window width and widow level).

Figure 2, The typical renal R2 map and the corresponding anatomic templates. Left , baseline R2 map ( A ) and its corresponding anatomic template ( a ). Right , R2 map after administration of furosemide ( B ) and its corresponding anatomic template ( b ). As in Figure 1 , both the cortex and medulla showed decreased signal intensity on B , but no similar signal intensity changes were found on the anatomic templates (the same window width and widow level).

Figure 3, Comparison between the cortex and medulla of ΔR2, ΔR2*, and ΔR2′. There was no significant difference between the cortex and medulla with ΔR2, which indicated that the extent of increase of water content was not significantly different between the cortex and medulla, whereas ΔR2* in the medulla was significantly higher than that in the cortex ( P < .05). That was because ΔR2* contained both ΔR2 and ΔR2′, and the latter was higher in the medulla than in cortex after administration of furosemide. *Significant difference.

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Discussion

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