Oxygen Level-dependent Magnetic Resonance Imaging Research Articles

Compartmental Analysis of Renal BOLD MRI Data

Functional blood oxygenation level-dependent (BOLD) magnetic resonance imaging is a powerful tool to assess renal function, but BOLD analysis using T2* image differentiation of cortex and medulla is laborious and prone to errors. We developed and validated an alternative compartmental analysis method to differentiate renal cortical and medullary BOLD relaxivity index, R2*. This method uses whole-kidney regions of interest (ROI), thus eliminating the need for anatomic cortical and medullary definition. Nine hypertensive patients and 11 domestic pigs, some with renal artery stenosis, were studied using BOLD MRI before and after injection of furosemide, which reduces medullary oxygen consumption. R2* in cortex and medulla estimated before and after furosemide with the compartmental method were compared with those obtained using conventional T2* image selection for ROI (manual ROI method), and a reference method with ROIs obtained using contrast-enhanced computerized tomography images were coregistered for the same kidneys. All 3 methods provided similar cortical R2* values, but the Bland-Altman methods' agreement confidence intervals of the reference and compartmental-derived medullary R2* response in humans and pigs were smaller than those in the manual ROI method. Operator dependency in swine was lower in the compartmental method, and its estimates of variation were almost 1/3 compared with the manual ROI method. The new compartmental method, which is less labor intensive than the conventional method, provides comparable and less variable kidney R2* estimations, especially in renal medulla. This method could be useful for analysis of kidney BOLD data.

Effect of Phosphodiesterase Inhibitor on Diabetic Nephropathy

Effect of Phosphodiesterase Inhibitor on Diabetic Nephropathy

Long-Term Memory Search across the Visual Brain

Signal transmission from the human retina to visual cortex and connectivity of visual brain areas are relatively well understood. How specific visual perceptions transform into corresponding long-term memories remains unknown. Here, I will review recent Blood Oxygenation Level-Dependent functional Magnetic Resonance Imaging (BOLD fMRI) in humans together with molecular biology studies (animal models) aiming to understand how the retinal image gets transformed into so-called visual (retinotropic) maps. The broken object paradigm has been chosen in order to illustrate the complexity of multisensory perception of simple objects subject to visual —rather than semantic— type of memory encoding. The author explores how amygdala projections to the visual cortex affect the memory formation and proposes the choice of experimental techniques needed to explain our massive visual memory capacity. Maintenance of the visual long-term memories is suggested to require recycling of GluR2-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR) and β 2-adrenoreceptors at the postsynaptic membrane, which critically depends on the catalytic activity of the N-ethylmaleimide-sensitive factor (NSF) and protein kinase PKMζ.

Left–right difference in fetal liver oxygenation during hypoxia estimated by BOLD MRI in a fetal sheep model

The purpose of this study was to measure differences in oxygenation between the left and right sides of the fetal liver during varying oxygenation levels. Eight ewes carrying singleton fetuses at gestational age 125 days (term, 145 days) were included in the study. Under anesthesia the ewes were ventilated with gas containing different levels of oxygen, thereby subjecting the fetuses to hyperoxia (mean ± SD maternal arterial partial pressure of oxygen (pO2), 23.2 ± 8.2 kPa) and hypoxia (mean maternal arterial pO2, 7.1 ± 0.5 kPa). Changes in oxygenation within the fetal liver were assessed by blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI). During hyperoxia there was no difference between the BOLD signal in the left and right sides of the fetal liver; mean change in BOLD (ΔBOLD)(hyperox), -0.9 ± 3.7%. During hypoxia, however, the decrease in the BOLD signal was more pronounced in the right side as compared with the left side, thereby creating a significant increase in the left-right difference in the BOLD signal; mean ΔBOLD(hypox), 5.2 ± 2.2% (P = 0.002, paired t-test). The left-right difference was directly proportional to the degree of hypoxia (R2 = 0.86, P = 0.007). To our knowledge, this is the first study demonstrating differences in oxygenation between the left and right sides of the fetal liver during hypoxia, a difference that can be explained by increased ductus venosus shunting. Thus, the BOLD MRI technique is a promising non-invasive tool that might be useful for the future monitoring of the human fetus.

Dynamic Contrast-Enhanced Magnetic Resonance Imaging and Blood Oxygenation Level-Dependent Magnetic Resonance Imaging for the Assessment of Changes in Tumor Biology With Treatment

Functional magnetic resonance imaging (MRI) techniques are rapidly gaining importance as methods of exploring the pathophysiological properties of breast carcinomas. In the neoadjuvant setting where the primary tumor remains in situ, functional MRI is able to noninvasively evaluate microenvironmental features such as blood flow and oxygenation. Dynamic contrast-enhanced MRI provides information on tumor vascularity with evidence suggesting a role in predicting response to neoadjuvant chemotherapy. The spatial heterogeneity of response to anti-angiogenic and vascular disrupting agents can also be depicted. There is preliminary data supporting blood oxygenation level-dependent MRI as a potential marker of tumor oxygenation, with the ability to characterize tissue oxygenation changes with neoadjuvant chemotherapy. Additionally, advanced MR sequences such as diffusion-weighted MRI and MR spectroscopy have the potential to provide information relating to cellularity and metabolism, respectively.

Severely impaired cerebrovascular reserve in patients with cerebral proliferative angiopathy

Cerebral proliferative angiopathy (CPA) has been morphologically distinguished from classically appearing brain arteriovenous malformations (AVMs) by exhibition of functional brain parenchyma that is intermingled with abnormal vascular channels. The presence of oligemia in this intralesional brain tissue may suggest ischemia, which is not detected in classic brain AVMs. The authors hypothesized that patients with CPA would exhibit a greater impairment of cerebrovascular reserve in neuronal tissue surrounding the true nidus compared with those with brain AVMs. Four patients with CPA, 10 patients with brain AVMs and seizures, and 12 young healthy individuals were studied. The 4 patients with CPA underwent blood oxygen level-dependent MR imaging examinations while applying normoxic step changes in end-tidal CO(2) to obtain quantitative cerebrovascular reactivity measurements. Patients with a CPA lesion exhibited severely impaired perilesional cerebrovascular reserve in comparison with patients with brain AVMs and seizures (0.10 ± 0.03 vs 0.16 ± 0.03, respectively; p < 0.05), and young healthy individuals (0.10 ± 0.03 vs 0.21 ± 0.06, respectively; p < 0.01). This study demonstrated severely impaired cerebrovascular reserve in the perilesional brain tissue surrounding the abnormal vessels of patients with CPA. This finding may provide an additional means to distinguish CPA from classic brain AVMs.

BOLD imaging: a potential predictive biomarker of renal functional outcome following revascularization in atheromatous renovascular disease

Stenting of the stenosed renal artery is commonly employed in atheromatous renovascular disease (ARVD) in order to revascularize the affected kidney. However, it is still far from clear which patient subgroups should be revascularized as stenting carries small but significant risks. We have previously demonstrated that the ratio of magnetic resonance-measured renal volume to isotopic single kidney glomerular filtration rate (isoSK-GFR) is higher in kidneys which show functional improvement after revascularization. Blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) does not require contrast administration and is sensitive to changes in tissue concentration of deoxyhaemoglobin. In this study, we test the hypothesis that baseline BOLD R2* map signal and R2*:isoSK-GFR ratio will provide an additional independent predictive biomarker of response to revascularization. Studies were performed in 28 subjects (16 ARVD and 12 controls). All subjects had R2* mapping and isoSK-GFR measured at baseline and at 4-month follow-up. MRI data were collected on a 3 T whole-body MRI scanner using a coronal dual-echo, 2D gradient-echo breath-hold acquisition. Parenchymal regions of interest (ROIs) were drawn on a representative slice through the middle of the kidney. Parametric maps of R2* were generated and mean values of R2* were calculated for every ROI. The ratio of R2*:isoSK-GFR at baseline was significantly greater in kidneys where renal function improved (5.91 ± 6.51) versus stable (1.78 ± 1.11), deteriorated (2.15 ± 1.79) or controls (1.5 ± 0.91), P = 0.003. R2*:isoSK-GFR ratio that was greater than 95% confidence interval of the control kidneys was 66.7% sensitive, but 85.7% specific in predicting a positive renal functional outcome. These pilot data show that BOLD R2* imaging, presumably by detecting intra-renal deoxyhaemoglobin in still viable 'hibernating' parenchyma, coupled with isoSK-GFR may provide an effective predictive biomarker for positive renal functional response to revascularization. R2* imaging is non-invasive, quick to perform and could provide further insight into reversible parenchymal changes in ARVD kidneys.

Investigation of protective effect of hydrogen-rich water against cisplatininduced nephrotoxicity in rats using blood oxygenation level-dependent magnetic resonance imaging

The aim of this study was to assess the mechanism of the protective effect of hydrogen-rich water (HW) against cisplatin (CP)-induced nephrotoxicity in rats using blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI). Apparent transverse relaxation time-weighted images (T2 WI) were acquired in 28 rats. The control group (n = 7) had free access to standard water (SW) and no CP injection. The CP group (n = 7) had free access to SW and was given a CP injection on day 0. The CP+HW group (n = 7) had free access to HW and had a CP injection. The HW group (n = 7) had free access to HW and no CP injection. The apparent transverse relaxation rate (R2) was estimated from T2 WI. In the CP+HW group, the R2 value in the medulla normalized by the value of the day 0 was significantly greater than that in the CP group on days 4 and 7. The creatinine and blood urea nitrogen levels in the CP group were significantly higher than those in the control, CP+HW, and HW groups. BOLD MRI may be useful for demonstrating the change in R2 in CP-induced nephrotoxicity in rats. The changes in the CP+HW group were suspected to be due to a reduction of cytotoxic oxygen radicals.

Peripheral microvascular response to muscle contraction is unaltered by early diabetes but decreases with age

Long-term or untreated diabetes leads to micro- and macrovascular complications. However, there are few tests to evaluate microvascular function. A postcontraction blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) technique was exploited to measure peripheral microvascular function in diabetics and healthy controls matched with respect to age, body mass index, and physical activity. Postcontraction BOLD microvascular response was measured following 1-s maximal isometric ankle dorsiflexion in individuals with diabetes mellitus type I [DMI, n = 15, age 33 ± 3 yr (means ± SE), median diabetes duration = 5.5 yr] and type II (DMII, n = 16, age 45 ± 2 yr, median duration = 2.4 yr); responses were compared with controls (CONI and CONII). Peripheral macrovascular function of the popliteal and tibial arteries was assessed during exercise hyperemia with phase contrast magnetic resonance angiography following repetitive exercise. There were no group differences as a result of diabetes in peripheral microvascular function (peak BOLD response: DMI = 2.04 ± 0.38% vs. CONI = 2.08 ± 0.48%; DMII = 0.93 ± 0.24% vs. CONII = 1.13 ± 0.24%; mean ± SE), but the BOLD response was significantly influenced by age (partial r = -0.384, P = 0.003), supporting its sensitivity as a measure of microvascular function. Eleven individuals had no microvascular BOLD response, including three diabetics with neuropathy and four controls with a family history of diabetes. There were no differences in peripheral macrovascular function between groups when assessing exercise hyperemia or the pulsitility and resistive indexes. Although the BOLD microvascular response was not impaired in early diabetes, these results encourage further investigation of muscle BOLD as it relates to peripheral microvascular health.

Direct fMRI by random spin-lock along the neural field

A theoretical method for direct imaging of neural activity is presented here. It is based on a mechanism of random spin-lock along the magnetic field generated by active neurons. Lock conditions are fulfilled in a rotating frame whose properties are determined by the amplitude and frequency of neural field fluctuations. This technique can be implemented on scanners commonly used for blood oxygen level-dependent functional magnetic resonance imaging.

Neuroanatomical targets of reboxetine and bupropion as revealed by pharmacological magnetic resonance imaging

One of the key targets of psychopharmacology research is to determine the potential sites of action of antidepressants in order to characterise their underlying mechanism of action. Using blood oxygenation level-dependent (BOLD) pharmacological magnetic resonance imaging (phMRI), the neuroanatomical target-sites of reboxetine (a selective noradrenaline reuptake inhibitor) and bupropion (an antidepressant with stimulatory effects on dopamine and potentially on noradrenaline) were mapped. Separate groups of rats were challenged acutely or chronically (daily injections for 14 days) with saline or psychoactive compounds and scanned. Subsequent statistical parametric mapping of the main effects of the drug was performed by identifying changes in the BOLD signal. Acute reboxetine challenge at a low dose (10 mg/kg i.p.) produced positive BOLD responses specifically in the hypothalamus, whereas a larger dose (30 mg/kg i.p.) produced activations in the hypothalamus, anterior hippocampus and prefrontal cortex. Chronic reboxetine (30 mg/kg i.p.) treatment induced increased BOLD responses in the posterior hippocampus and prefrontal cortex, while no significant contrast changes were observed in the hypothalamus and a significant decrease was apparent in the amygdala. In contrast, acute bupropion (15 and 30 mg/kg i.p.) challenge in both doses produced no significant contrast changes in the regions of interest. However, chronic bupropion treatment (30 mg/kg i.p.) produced robust increases in BOLD responses in the hippocampus, amygdala and prefrontal cortex. In summary, this study demonstrates that reboxetine and bupropion evoke a significant increase in BOLD functional activity in specific regions of the brain, including the hypothalamus, hippocampus, prefrontal cortex and amygdala. Furthermore, the study illustrates the potential value of pharmacological MRI in rodents to delineate pharmacologically induced changes in regional brain function.

Renal oxygenation changes during water loading as evaluated by BOLD MRI: Effect of NOS inhibition

To demonstrate a possible role for endogenous release of nitric oxide in determining the response of water loading on intrarenal oxygenation as evaluated by blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI). Twelve Sprague Dawley rats (weight 344.9 ± 40.6 g) were equally divided into two groups, A and B. Water loading was implemented by continuous infusion of hypotonic saline containing glucose (0.25% NaCl, 0.5% glucose). Rats in group A were subject to water loading alone, while group B rats were dosed with N-nitro-L-arginine methyl ester, (L-NAME) (10.0 mg/kg) prior to water loading. T(2) *-weighted images of the kidneys were obtained on a Siemens 3T Verio MRI scanner using a multiple gradient recalled echo (mGRE) sequence. Consistent with previous reports, group A exhibited a significant decrease in medullary R(2) * during water loading (40.64 ± 1.10 s(-1) to 34.68 ± 1.49 s(-1) , P < 0.05). On the other hand, in group B there was no decrease in R(2) * during water loading (48.11 ± 2.38 s(-1) to 51.06 ± 2.18 s(-1) ). The increased prewater loading R(2) * is due to the pretreatment with L-NAME (40.82 ± 3.23 s(-1) to 48.11 ± 2.38 s(-1) , P < 0.05). Our data suggest for the first time a role for endogenous nitric oxide in determining the response of renal medullary oxygenation to water loading.

Quantitative Measurement of Cerebrovascular Reactivity by Blood Oxygen Level-Dependent MR Imaging in Patients with Intracranial Stenosis: Preoperative Cerebrovascular Reactivity Predicts the Effect of Extracranial-Intracranial Bypass Surgery

CVR is a measure of cerebral hemodynamic impairment. A recently validated technique quantifies CVR by using a precise CO(2) vasodilatory stimulus and BOLD MR imaging. Our aim was to determine whether preoperative CO(2) BOLD CVR predicts the hemodynamic effect of ECIC bypass surgery in patients with intracranial steno-occlusive disease. Twenty-five patients undergoing ECIC bypass surgery for treatment of intracranial stenosis or occlusion were recruited. CVR was measured preoperatively and postoperatively and expressed as %ΔBOLD MR signal intensity per mm Hg ΔPetCO(2). Using normative data from healthy subjects, we stratified patients on the basis of preoperative CVR into 3 groups: normal CVR, reduced CVR, and negative (paradoxical) CVR. Wilcoxon 2-sample tests (2-sided, α = 0.05) were used to determine whether the 3 groups differed with respect to change in CVR following bypass surgery. The group with normal preoperative CVR demonstrated no significant change in CVR following bypass surgery (mean, 0.22% ± 0.05% to 0.22% ± 0.01%; P = .881). The group with reduced preoperative CVR demonstrated a significant improvement following bypass surgery (mean, 0.08% ± 0.05% to 0.21 ± 0.08%; P < .001), and the group with paradoxical preoperative CVR demonstrated the greatest improvement (mean change, -0.04% ± 0.03% to 0.27% ± 0.03%; P = .028). Preoperative measurement of CVR by using CO(2) BOLD MR imaging predicts the hemodynamic effect of ECIC bypass in patients with intracranial steno-occlusive disease. The technique is potentially useful for selecting patients for surgical revascularization.

Blood oxygen level‐dependent (BOLD) MRI of diabetic nephropathy: Preliminary experience

To evaluate the blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) findings in kidneys of patients with diabetic nephropathy. BOLD MRI of the kidneys (1.5 T, multigradient-recalled-echo sequence with 12 echoes) was performed in 20 patients with diabetic nephropathy (moderate to severe chronic kidney disease: n = 14; mild chronic kidney disease: n = 6), and seven healthy volunteers. The medullary and cortical R2* values were compared between patients with diabetic nephropathy and healthy volunteers using Student's t-tests. The mean medullary R2* values were lower in patients with diabetic nephropathy compared to healthy volunteers (13.8 ± 2.4 sec(-1) vs. 19.3 ± 1.2 sec(-1), P = 0.0002). The cortical R2* values were not significantly different between the two groups (11.1 ± 0.9 sec(-1) vs. 11.5 ± 0.7 sec(-1), P = 0.7). A multiple logistic regression model using patient age, gender, and degree of chronic kidney disease (none, mild, or moderate to severe) as variables showed that the degree of kidney disease was independently associated with a decrease in medullary R2* values (P = 0.005). The medullary R2* values were lower in patients with diabetic nephropathy compared to healthy volunteers.

Functional magnetic resonance imaging of active and passive hand movement

Objective To assess differences in brain activation between active and passive movement of the right hand using blood oxygen level-dependent functional magnetic resonance imaging （BOLD-fMRI）. Methods Nine healthy adult right handed volunteers were studied. fMRI was performed with active and passive finger-to-finger movement. Results Right hand active and passive movement produced significant activation in the contralateral sensorimotor cortex （ SMC ）, the contralateral premotor cortex （ PMC ）, bilaterally in the supplementary motor area （SMA） and in the ipsilateral cerebellum. The activated brain areas were centered on the contralateral SMC and PMC and located more forward during active movement than during passive movement. The contralateral SMC was the most strongly and the most frequently activated brain area. The contralateral posterior parietal cortex （PPC） was less relevant to the hand movements. Unlike active movement, passivemovement activated more areas in the posterior central gyrus than in the anterior central gyrus. Conclusions Both active and passive movement significantly activate the brain areas which are responsible for hand movement, but there are some differences in the locations of the cortex areas activated and in the incidence activation except in the contralateral SMC. Key words: Functional magnetic resonance imaging; Active movement ; Passive movement ; Sensorimotor cortex; Premotor cortex; Supplementary motor areas

Magnetic resonance imaging of vascular oxygenation changes during hyperoxia and carbogen challenges in the human retina.

To demonstrate blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) of vascular oxygenation changes in normal, unanesthetized human retinas associated with oxygen and carbogen challenge. MRI was performed with a 3-T human scanner and a custom-made surface-coil detector on normal volunteers. BOLD MRI with inversion recovery was used to suppress the vitreous signal. During MRI measurements, volunteers underwent three episodes of air and 100% oxygen or carbogen (5% CO(2) and 95% O(2)) breathing. Eye movement was effectively managed with eye fixation, synchronized blinks, and postprocessing image coregistration. BOLD time-series images were analyzed using the cross-correlation method. Percent changes due to oxygen or carbogen inhalation versus air were tabulated for whole-retina and different regions of the retina. Robust BOLD responses were detected. BOLD MRI percent change from a large region of interest at the posterior pole of the retina was 5.2 ± 1.5% (N = 9 trials from five subjects) for oxygen inhalation and 5.2 ± 1.3% (N = 11 trials from five subjects) for carbogen inhalation. Group-averaged BOLD percent changes were not significantly different between oxygen and carbogen challenges (P > 0.05). The foveal region had greater BOLD response compared with the optic nerve head region for both challenges. BOLD retinal responses to oxygen and carbogen breathing in unanesthetized humans can be reliably imaged at high spatiotemporal resolution. BOLD MRI has the potential to provide a valuable tool to study retinal physiology and pathophysiology, such as how vascular oxygenation at the tissue level is regulated in the normal retina, and how retinal diseases may affect oxygen response.

Determinations of Renal Cortical and Medullary Oxygenation Using Blood Oxygen Level-Dependent Magnetic Resonance Imaging and Selective Diuretics

This study was undertaken to test the hypothesis that blood O2 level-dependent magnetic resonance imaging (BOLD MRI) can detect changes in cortical proximal tubule (PT) and medullary thick ascending limb of Henle (TAL) oxygenation consequent to successive administration of furosemide and acetazolamide (Az). Assessment of PT and TAL function could be useful to monitor renal disease states in vivo. Therefore, the adjunct use of diuretics that inhibit Na reabsorption selectively in PT and TAL, Az and furosemide, respectively, may help discern tubular function by using BOLD MRI to detect changes in tissue oxygenation. BOLD MRI signal R2* (inversely related to oxygenation) and tissue oxygenation with intrarenal O2 probes were measured in pigs that received either furosemide (0.05 mg/kg) or Az (15 mg/kg) alone, Az sequentially after furosemide (n = 6 each, 15-minute intervals), or only saline vehicle (n = 3). R2* decreased in the cortex of Az-treated and medulla of furosemide-treated kidneys, corresponding to an increase in their tissue O2 assessed with probes. However, BOLD MRI also showed decreased cortical R2* following furosemide that was additive to the Az-induced decrease. Az administration, both alone and after furosemide, also decreased renal blood flow (-26% ± 3.5% and -29.2% ± 3%, respectively, P < 0.01). These results suggest that an increase in medullary and cortical tissue O2 elicited by selective diuretics is detectable by BOLD MRI, but may be complicated by hemodynamic effects of the drugs. Therefore, the BOLD MRI signal may reflect functional changes additional to oxygenation, and needs to be interpreted cautiously.

Protective Effect of Hydrogen-rich Water against Gentamicin-induced Nephrotoxicity in Rats using Blood Oxygenation Level-dependent MR Imaging

We assessed intrarenal oxygenation in gentamicin-induced nephrotoxicity (GIN) and the protective effect of hydrogen-rich water (HW) against GIN using blood oxygenation level-dependent magnetic resonance (MR) imaging. We acquired T(2)*-weighted images (T(2)*WI) of 21 rats on Days 0, 2, 4, and 7 using a 1.5-tesla MR imaging system. The rats were divided into 3 groups of seven each: control rats had free access to standard water and no gentamicin (GM) injection; rats designated the GM group had free access to standard water and were injected with GM (80 mg/kg/day) subcutaneously for 7 days; and the third group, designated the GM+HW group, had free access to HW and were injected with GM. R(2)* (=1/T(2)*) was estimated from T(2)*WI. R(2)* values in the cortex were significantly decreased on Days 2, 4, and 7 compared with those on Day 0 in the GM group but not significantly changed in the control and GM+HW groups. R(2)* values in the medulla did not change significantly in any group. Our findings suggested reduced oxygen utility, mainly in the cortex, in gentamicin-induced nephrotoxicity and an ameliorative effect of hydrogen-rich water against GIN.

Evaluation of Renal Hypoxia in Diabetic Mice by BOLD MRI

Renal hypoxia has been proposed to be a pathophysiologic feature of diabetic kidney disease but it has been difficult to demonstrate in vivo, particularly in mouse models of diabetes. The objective of this work was to examine the sensitivity of blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) to assess renal oxygenation in vivo in a mouse model of diabetic kidney disease, the db/db mice. Kidney BOLD MRI studies were performed on a 3.0 T scanner using multiple gradient echo sequence with a custom-designed surface coil to acquire T2*-weighted images. Studies were performed in 10-week-old db/db mice (n = 7) and db/m controls (n = 6). R2* is a measure of the tissue deoxyhemoglobin concentration and higher values of R2* are associated with hypoxia. The db/db mice had higher medullary (43.1 ± 5.1 s⁻¹ vs. 32.3 ± 3.7⁻¹ s, P = 0.001) and cortical R2* (31.7 ± 3.1 s⁻¹ vs. 27.1 ± 4.1 s⁻¹, P = 0.04) values. Using pimonidazole staining as a marker of kidney hypoxia, in kidney sections from 10-week-old db/db mice neither cortex nor medulla had significant differences as compared with 10-week-old db/m mice (cortex: db/db 2.14 ± 0.05 vs. db/m 2.02 ± 0.28, medulla: db/db 2.81 ± 0.08 vs. db/m 2.6 ± 0.08). The db/db mice demonstrated further increased cortical and medullary hypoxia when scanned again at 15 weeks of age. The report shows that renal BOLD MRI is a sensitive method for the in vivo evaluation of renal hypoxia in a mouse model of diabetic kidney disease where progressive renal hypoxia can be documented over time. BOLD MRI may be useful to monitor therapeutic interventions that may improve tissue hypoxia in the diabetic kidney.

Evolution of renal oxygen content measured by BOLD MRI downstream a chronic renal artery stenosis

A decrease in renal oxygen content can be measured non-invasively by the increase of the R2* value derived from blood oxygen level-dependent magnetic resonance imaging (BOLD MRI). The aim of this study was to test if renal hypoxia occurs in kidneys downstream a chronic and unilateral renal artery stenosis. Chronic renal ischaemia was induced in rats using a calibrated clip inserted on the right renal artery. R2* was determined, using a multiple recalled gradient-echo sequence, before and once a week after a clip insertion over 4 weeks, in a group of clipped (n = 8) and sham-operated (n = 7) rats. At baseline, in stenotic kidneys, R2* was higher in the outer stripe of outer medulla (105 ± 4.6) and the outer medulla (99 ± 2.5) than in the cortex (84 ± 2.5; P < 0.002 for comparison with both areas). R2* was unchanged in the cortex, the outer stripe of outer medulla and the outer medulla in stenotic kidneys, sham-operated kidneys and contralateral kidneys during the 4 weeks. Mean blood pressure was higher in rats with clipped kidney than in sham-operated rats from Day 11 and remained increased thereafter. The renal volume increased progressively in sham-operated kidneys and contralateral kidneys, whereas it slightly decreased in stenotic kidneys. Our study shows that after 4 weeks, no renal hypoxia can be detected in the kidney downstream to a renal artery stenosis, suggesting that atrophy could be induced by other factors.