Multiparametric assessment of renal physiology in healthy volunteers using noninvasive magnetic resonance imaging.

Noninvasive methods of magnetic resonance imaging (MRI) can quantify parameters of kidney function. The main purpose of this study was to determine baseline values of such parameters in healthy volunteers. In 28 healthy volunteers (15 women and 13 men), arterial spin labeling to estimate regional renal perfusion, blood oxygen level-dependent transverse relaxation rate (R2*) to estimate oxygenation, and apparent diffusion coefficient (ADC), true diffusion (D), and longitudinal relaxation time (T1) to estimate tissue properties were determined bilaterally in the cortex and outer and inner medulla. Additionally, phase-contrast MRI was applied in the renal arteries to quantify total renal blood flow. The results demonstrated profound gradients of perfusion, ADC, and D with highest values in the kidney cortex and a decrease towards the inner medulla. R2* and T1 were lowest in kidney cortex and increased towards the inner medulla. Total renal blood flow correlated with body surface area, body mass index, and renal volume. Similar patterns in all investigated parameters were observed in women and men. In conclusion, noninvasive MRI provides useful tools to evaluate intrarenal differences in blood flow, perfusion, diffusion, oxygenation, and structural properties of the kidney tissue. As such, this experimental approach has the potential to advance our present understanding regarding normal physiology and the pathological processes associated with acute and chronic kidney disease.

Assessment of Perfusion and Oxygenation of the Human Renal Cortex and Medulla by Quantitative MRI during Handgrip Exercise.

BACKGROUND: Renal flow abnormalities are believed to play a central role in the pathogenesis of nephropathy and in primary and secondary hypertension, but are difficult to measure in humans. Handgrip exercise is known to reduce renal arterial flow (RAF) by means of increased renal sympathetic nerve activity. METHODS: To monitor medullary and cortical oxygenation under handgrip exercise-reduced perfusion, we used contrast- and radiation-free magnetic resonance imaging (MRI) to measure regional changes in renal perfusion and blood oxygenation in ten healthy normotensive individuals during handgrip exercise. We used phase-contrast MRI to measure RAF, arterial spin labeling to measure perfusion, and both changes in transverse relaxation time (T2*) and dynamic blood oxygenation level-dependent imaging to measure blood oxygenation. RESULTS: Handgrip exercise induced a significant decrease in RAF. In the renal medulla, this was accompanied by an increase of oxygenation (reflected by an increase in T2*) despite a significant drop in medullary perfusion; the renal cortex showed a significant decrease in both perfusion and oxygenation. We also found a significant correlation (R2=0.8) between resting systolic BP and the decrease in RAF during handgrip exercise. CONCLUSIONS: Renal MRI measurements in response to handgrip exercise were consistent with a sympathetically mediated decrease in RAF. In the renal medulla, oxygenation increased despite a reduction in perfusion, which we interpreted as the result of decreased GFR and a subsequently reduced reabsorptive workload. Our results further indicate that the renal flow response's sensitivity to sympathetic activation is correlated with resting BP, even within a normotensive range.

Measurement of renal tissue oxygenation with blood oxygen level-dependent MRI and oxygen transit modeling.

Blood oxygen level-dependent (BOLD) MRI data of kidney, while indicative of tissue oxygenation level (Po2), is in fact influenced by multiple confounding factors, such as R2, perfusion, oxygen permeability, and hematocrit. We aim to explore the feasibility of extracting tissue Po2 from renal BOLD data. A method of two steps was proposed: first, a Monte Carlo simulation to estimate blood oxygen saturation (SHb) from BOLD signals, and second, an oxygen transit model to convert SHb to tissue Po2. The proposed method was calibrated and validated with 20 pigs (12 before and after furosemide injection) in which BOLD-derived tissue Po2 was compared with microprobe-measured values. The method was then applied to nine healthy human subjects (age: 25.7 ± 3.0 yr) in whom BOLD was performed before and after furosemide. For the 12 pigs before furosemide injection, the proposed model estimated renal tissue Po2 with errors of 2.3 ± 5.2 mmHg (5.8 ± 13.4%) in cortex and -0.1 ± 4.5 mmHg (1.7 ± 18.1%) in medulla, compared with microprobe measurements. After injection of furosemide, the estimation errors were 6.9 ± 3.9 mmHg (14.2 ± 8.4%) for cortex and 2.6 ± 4.0 mmHg (7.7 ± 11.5%) for medulla. In the human subjects, BOLD-derived medullary Po2 increased from 16.0 ± 4.9 mmHg (SHb: 31 ± 11%) at baseline to 26.2 ± 3.1 mmHg (SHb: 53 ± 6%) at 5 min after furosemide injection, while cortical Po2 did not change significantly at ∼58 mmHg (SHb: 92 ± 1%). Our proposed method, validated with a porcine model, appears promising for estimating tissue Po2 from renal BOLD MRI data in human subjects.

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)NaCSF]. Results of water stimulation as measured by [(23)NaCSF] 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)NaCSF] 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.

Renal BOLD-MRI and assessment for renal hypoxia.

Renal tissue hypoxia may play a major role in the progression of chronic renal disease. Michaely et al. used blood oxygen level-dependent magnetic resonance imaging to test this hypothesis. They found no relationship between renal oxygenation and stage of chronic kidney disease (CKD). However, renal tissue oxygenation may be related not only to the severity of renal disease but also to its underlying etiology. This added complexity confounds interpretation of data obtained from subjects with CKD due to multiple etiologies.

Assessment of the nitric oxide system in the heart, aorta and kidney of aged Wistar-Kyoto and spontaneously hypertensive rats.

OBJECTIVE: To assess the nitric oxide (NO) system in the cardiovascular and renal systems of old Wistar-Kyoto (WKY) rats and old spontaneously hypertensive rats (SHR) compared with young rats of the same strains. DESIGN AND METHODS: The NO pathway was assessed: (i) in analytical studies measuring the concentration of nitrate in plasma and the activity of NO synthases in the left ventricle, renal cortex and renal medulla; and (ii) in functional studies, in which we measured the blood pressure effects of NO blockade with intravenous N-nitro-L-arginine methyl ester (L-NAME, 0.1 mg/kg) in anaesthetized rats. In addition, we studied NO production in the aorta comparing the force attained by isolated segments exposed to cumulative concentrations of L-NAME (10(-7)-10(-3) mol/l). RESULTS: Plasma nitrate was significantly higher in old rats of both strains. Calcium-dependent NO synthase activity was markedly upregulated in the left ventricle, renal cortex and renal medulla of the old rats, both in hypertensive and normotensive animals. Intravenous L-NAME elicited deeper pressor effects in the old rats of either blood pressure condition. Aortic segments from old WKY rats, but not those from SHR, achieved remarkably stronger tension in response to L-NAME compared with the young counterparts. CONCLUSIONS: These findings suggest that the NO system is upregulated in the cardiovascular system and the kidney in senescence, even in hypertension.

Quantitative assessment of rat kidney function by measuring the clearance of the contrast agent Gd(DOTA) using dynamic MRI.

Magnetic resonance imaging (MRI) has been applied to assess kidney function in normal rats by monitoring the passage of the extracellular contrast agent GdDOTA. High-resolution images have been obtained using either the rapid acquisition with relaxation enhancement (RARE) or the snapshot pulse sequence. The latter was superior in anatomic definition due to the shorter echo delays used. The GdDOTA induced signal enhancements in the various renal structures were theoretically modeled and the results of the regression analysis then used to estimate local tissue concentrations in renal cortex, inner medulla and outer medulla/pelvis. The concentration-time curves in vena cava and renal cortex were similar and distinctly different from the ones in medulla and pelvis. This is reflected in the time-to-peak (TTP) values, which were TTP (blood) = 0.18 +/- 0.03 < TTP (cortex) = 0.26 +/- 0.05 < TTP (outer medulla) = 0.62 +/- 0.03 < TTP (inner medulla/pelvis) = 0.92 +/- 0.16 min. The initial tracer uptake rates depended linearly on the dose of GdDOTA administered, the value of the uptake rate in the cortex being significantly higher than those in the outer and inner medulla, which were identical within error limits. The initial medullar tracer uptake followed a first-order kinetics. The rate constant k(cl) = (dc[medulla]/dt)/c[cortex] = 3.4 +/- 0.5 min(-1) for the transition from cortex (predominantly blood signal) to medulla (predominantly urine) was considered a measure for the renal clearance. Intravenous administration of furosemide at doses 2.5, 5, and 10 mg/kg led to a dose-dependent decrease of k(cl). This reflects the inhibitory effect of the diuretic furosemide on medullary water resorption and thus the dilution of the GdDOTA in urine.

Regional responses within the kidney to ischemia: assessment of adenine nucleotide and catabolite profiles.

UNLABELLED: Renal cortex (C) has predominantly aerobic metabolism, whereas inner medulla (IM) has both aerobic and anaerobic capacities. This study was undertaken (1) to assess how well rat IM anaerobic metabolism maintains this region's ATP content during ischemia; and (2) to determine whether regional variations in adenylate pool/catabolite responses to ischemia exist, obscuring interpretation of cellular energetics in rat studies of acute renal failure (ARF). Adenine nucleotides/catabolites were measured in rat C, IM and outer medulla (OM) after 15 and 45 min of ischemia. After 15 min, all regions showed profound ATP depletion, although the IM maintained slightly higher (by 0.23 mumol/g) absolute ATP levels than C/OM tissues (normal ATP value = 8.7 mumol/g). By 45 min, significant differences in regional ATP levels did not exist. Striking regional catabolite differences were apparent at both 15 and 45 min. Most prominent were: (1) intrarenal purine base/inosine gradients, levels falling approx. 22-50% from C to IM; and (2) preferential OM AMP/IMP/adenosine accumulation. To assess whether more homogeneous results might be found in rabbit kidney, possibly making this animal preferable to rats for studies of renal ischemia, rabbit C, OM and IM adenylate pools were analyzed after 15 min of ischemia. C vs. IM ATP differences were greater (approx. 1.3 mumol/g) and large catabolite concentration differences were still apparent. CONCLUSIONS: (1) anaerobic mechanisms support IM ATP levels during ischemia but, in terms of normal concentrations, the impact is small, particularly in the rat; and (2) marked regional differences in adenylate catabolite levels exist within ischemic kidneys. These need to be recognized when analyzing adenylate pool responses in ischemic ARF.