Oxygen Level-dependent Magnetic Resonance Imaging Research Articles

Acute hyperglycemia increases renal tissue oxygenation as measured by BOLD-MRI in healthy overweight volunteers

AimAnimal studies have suggested that acute hyperglycemia induces transient renal hypoxia and kidney damage, yet this has not been tested in humans. Therefore, we assessed in human subjects the effect of acute hyperglycemia on renal tissue oxygenation as measured with blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI). MethodsIn this single center prospective interventional study, healthy overweight subjects were recruited. BOLD-MRI was performed before and immediately after the intravenous administration of 0.15 g/kg of glucose in a 20% solution under standard hydration and fasting conditions. R2* maps were analyzed using the twelve layer concentric objects (TLCO) technique, a semi-automatic procedure which divides the kidney parenchyma in 12 equal layers at increasing depth. R2* is a measure of local desoxyhemoglobin concentrations, with high R2* values corresponding to low oxygenation. ResultsNineteen overweight subjects were enrolled (age 37 ± 10 years, BMI 28.9 ± 3 kg/m2, HbA1c 5.4 ± 0.3%, 57.9% women): 5 were glucose intolerant, none had diabetes. The mean glycemia rose from 4.5 ± 0.3 mmol/l to 9.0 ± 0.9, 8.9 ± 0.7, 7.7 ± 0.6 and 6.8 ± 0.8 mmol/l at respectively 1, 10, 20 and 30 min after IV glucose. Circulating insulin levels quadrupled. The mean R2* values decreased significantly in all kidney layers, irrespective of glucose intolerance. The lower BMI, the larger the decrease in R2*(spearman’s r = 0.41, p = 0.035). ConclusionThese data show that acute hyperglycemia decreases the R2* signal in humans, suggesting an acute increase in renal tissue oxygenation. The precise mechanism of this observation remains unknown, and whether this phenomenon also occurs in patients with diabetes needs additional studies.

The Correlation between Osteoporosis and Blood Circulation Function Based on Magnetic Resonance Imaging.

In order to investigate the relationship between changes in blood circulation and bone mineral density (BMD) loss, the characteristic parameters reflecting the function of tissue oxygen metabolism are obtained by means of blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI), image processing and semi-quantitative analysis. The correlation and variance analysis of the characteristic parameters of different BMD groups are carried out, and the physiological parameters of bone marrow blood perfusion are obtained by dynamic enhanced MRI (DCE-MRI). Multivariate logistic regression analysis is carried out with the physiological parameters of blood oxygen metabolism function and bone marrow blood perfusion as independent variables and BMD as dependent variables. It is found that there are significant differences in oxygen metabolism between individual muscles in different BMD groups and between skeletal muscles of different types of muscle fibers. Age, total volume of bone marrow and oxygen metabolism ability of tibial anterior muscle have significant independent effects on osteoporosis. It shows that the changes of blood circulation in bone marrow and surrounding muscle tissue are indeed one of the causes of osteoporosis.

Effects of short-term continuous positive airway pressure withdrawal on cerebral vascular reactivity measured by blood oxygen level-dependent magnetic resonance imaging in obstructive sleep apnoea: a randomised controlled trial.

Impaired cerebral vascular reactivity (CVR) increases long-term stroke risk. Obstructive sleep apnoea (OSA) is associated with peripheral vascular dysfunction and vascular events. The aim of this trial was to evaluate the effect of continuous positive airway pressure (CPAP) withdrawal on CVR.41 OSA patients (88% male, mean age 57±10 years) were randomised to either subtherapeutic or continuation of therapeutic CPAP. At baseline and after 2 weeks, patients underwent a sleep study and magnetic resonance imaging (MRI). CVR was estimated by quantifying the blood oxygen level-dependent (BOLD) MRI response to breathing stimuli.OSA did recur in the subtherapeutic CPAP group (mean treatment effect apnoea-hypopnoea index +38.0 events·h-1, 95% CI 24.2-52.0; p<0.001) but remained controlled in the therapeutic group. Although there was a significant increase in blood pressure upon CPAP withdrawal (mean treatment effect +9.37 mmHg, 95% CI 1.36-17.39; p=0.023), there was no significant effect of CPAP withdrawal on CVR assessed via BOLD MRI under either hyperoxic or hypercapnic conditions.Short-term CPAP withdrawal did not result in statistically significant changes in CVR as assessed by functional MRI, despite the recurrence of OSA. We thus conclude that, unlike peripheral endothelial function, CVR is not affected by short-term CPAP withdrawal.

Evaluation of Renal Pathophysiological Processes Induced by an Iodinated Contrast Agent in a Diabetic Rabbit Model Using Intravoxel Incoherent Motion and Blood Oxygenation Level-Dependent Magnetic Resonance Imaging.

ObjectiveTo examine the potential of intravoxel incoherent motion (IVIM) and blood oxygen level-dependent (BOLD) magnetic resonance imaging for detecting renal changes after iodinated contrast-induced acute kidney injury (CI-AKI) development in a diabetic rabbit model.Materials and MethodsSixty-two rabbits were randomized into 2 groups: diabetic rabbits with the contrast agent (DCA) and healthy rabbits with the contrast agent (NCA). In each group, 6 rabbits underwent IVIM and BOLD imaging at 1 hour, 1 day, 2 days, 3 days, and 4 days after an iohexol injection while 5 rabbits were selected to undergo blood and histological examinations at these specific time points. Iohexol was administrated at a dose of 2.5 g I/kg of body weight. Further, the apparent transverse relaxation rate (R2*), average pure molecular diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) were calculated.ResultsThe D and f values of the renal cortex (CO) and outer medulla (OM) were significantly decreased compared to baseline values in the 2 groups 1 day after the iohexol injection (p < 0.05). A marked reduction in the D* values for both the CO and OM was also observed after 1 hour in each group (p < 0.05). In the OM, a persistent elevation of the R2* was detected for 4 days in the DCA group (p < 0.05). Histopathological changes were prominent, and the pathological features of CI-AKI aggravated in the DCA group until day 4. The D, f, and R2* values significantly correlated with the histological damage scores, hypoxia-inducible transcription factor-1α expression scores, and serum creatinine levels.ConclusionA combination of IVIM and BOLD imaging may serve as a noninvasive method for detecting and monitoring CI-AKI in the early stages in the diabetic kidney.

Improved White Matter Cerebrovascular Reactivity after Revascularization in Patients with Steno-Occlusive Disease.

One feature that patients with steno-occlusive cerebrovascular disease have in common is the presence of white matter (WM) lesions on MRI. The purpose of this study was to evaluate the effect of direct surgical revascularization on impaired WM cerebrovascular reactivity in patients with steno-occlusive disease. We recruited 35 patients with steno-occlusive disease, Moyamoya disease (n = 24), Moyamoya syndrome (n = 3), atherosclerosis (n = 6), vasculitis (n = 1), and idiopathic stenosis (n = 1), who underwent unilateral brain revascularization using a direct superficial temporal artery-to-MCA bypass (19 women; mean age, 45.8 ± 16.5 years). WM cerebrovascular reactivity was measured preoperatively and postoperatively using blood oxygen level-dependent (BOLD) MR imaging during iso-oxic hypercapnic changes in end-tidal carbon dioxide and was expressed as %Δ BOLD MR signal intensity per millimeter end-tidal partial pressure of CO2. WM cerebrovascular reactivity significantly improved after direct unilateral superficial temporal artery-to-middle cerebral artery (STA-MCA) bypass in the revascularized hemisphere in the MCA territory (mean ± SD, -0.0005 ± 0.053 to 0.053 ± 0.046 %BOLD/mm Hg; P < .0001) and in the anterior cerebral artery territory (mean, 0.0015 ± 0.059 to 0.021 ± 0.052 %BOLD/mm Hg; P = .005). There was no difference in WM cerebrovascular reactivity in the ipsilateral posterior cerebral artery territory nor in the vascular territories of the nonrevascularized hemisphere (P < .05). Cerebral revascularization surgery is an effective treatment for reversing preoperative cerebrovascular reactivity deficits in WM. In addition, direct-STA-MCA bypass may prevent recurrence of preoperative symptoms.

Renal blood oxygenation level-dependent magnetic resonance imaging to measure renal tissue oxygenation: a statement paper and systematic review.

Tissue hypoxia plays a key role in the development and progression of many kidney diseases. Blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) is the most promising imaging technique to monitor renal tissue oxygenation in humans. BOLD-MRI measures renal tissue deoxyhaemoglobin levels voxel by voxel. Increases in its outcome measure R2* (transverse relaxation rate expressed as per second) correspond to higher deoxyhaemoglobin concentrations and suggest lower oxygenation, whereas decreases in R2* indicate higher oxygenation. BOLD-MRI has been validated against micropuncture techniques in animals. Its reproducibility has been demonstrated in humans, provided that physiological and technical conditions are standardized. BOLD-MRI has shown that patients suffering from chronic kidney disease (CKD) or kidneys with severe renal artery stenosis have lower tissue oxygenation than controls. Additionally, CKD patients with the lowest cortical oxygenation have the worst renal outcome. Finally, BOLD-MRI has been used to assess the influence of drugs on renal tissue oxygenation, and may offer the possibility to identify drugs with nephroprotective or nephrotoxic effects at an early stage. Unfortunately, different methods are used to prepare patients, acquire MRI data and analyse the BOLD images. International efforts such as the European Cooperation in Science and Technology (COST) action ‘Magnetic Resonance Imaging Biomarkers for Chronic Kidney Disease’ (PARENCHIMA) are aiming to harmonize this process, to facilitate the introduction of this technique in clinical practice in the near future. This article represents an extensive overview of the studies performed in this field, summarizes the strengths and weaknesses of the technique, provides recommendations about patient preparation, image acquisition and analysis, and suggests clinical applications and future developments.

Breath-Hold Blood Oxygen Level-Dependent MRI: A Tool for the Assessment of Cerebrovascular Reserve in Children with Moyamoya Disease.

There is a critical need for a reliable and clinically feasible imaging technique that can enable prognostication and selection for revascularization surgery in children with Moyamoya disease. Blood oxygen level-dependent MR imaging assessment of cerebrovascular reactivity, using voluntary breath-hold hypercapnic challenge, is one such simple technique. However, its repeatability and reliability in children with Moyamoya disease are unknown. The current study sought to address this limitation. Children with Moyamoya disease underwent dual breath-hold hypercapnic challenge blood oxygen level-dependent MR imaging of cerebrovascular reactivity in the same MR imaging session. Within-day, within-subject repeatability of cerebrovascular reactivity estimates, derived from the blood oxygen level-dependent signal, was computed. Estimates were associated with demographics and intellectual function. Interrater reliability of a qualitative and clinically applicable scoring scheme was assessed. Twenty children (11 males; 12.1 ± 3.3 years) with 30 MR imaging sessions (60 MR imaging scans) were included. Repeatability was "good" on the basis of the intraclass correlation coefficient (0.70 ± 0.19). Agreement of qualitative scores was "substantial" (κ = 0.711), and intrarater reliability of scores was "almost perfect" (κ = 0.83 and 1). Younger participants exhibited lower repeatability (P = .027). Repeatability was not associated with cognitive function (P > .05). However, abnormal cerebrovascular reactivity was associated with slower processing speed (P = .015). Breath-hold hypercapnic challenge blood oxygen level-dependent MR imaging is a repeatable technique for the assessment of cerebrovascular reactivity in children with Moyamoya disease and is reliably interpretable for use in clinical practice. Standardization of such protocols will allow further research into its application for the assessment of ischemic risk in childhood cerebrovascular disease.

Evaluating Renal Fibrosis with R2* Histogram Analysis of the Whole Cortex in a Unilateral Ureteral Obstruction Model

The aim of this study was to use histogram analysis to assess the correlation between blood oxygen-level dependent magnetic resonance imaging (BOLD-MRI) and renal fibrosis induced by unilateral ureteral obstruction (UUO) in an animal model for a long experimental period. The rabbits were randomly divided into a control group (n = 6) and a UUO group (n = 30). The rabbits in the UUO group underwent left ureteral obstruction surgery. BOLD-MRI examinations were performed at 2, 4, 6, and 8 weeks after ligation. After the examinations, nephrectomy was performed for histologic evaluation. Histogram analysis of the left renal cortex (C) R2* values was performed to measure the mean, median, 10th percentile, 90th percentile, skewness, and kurtosis for all kidneys. Masson trichrome staining was used to assess the percentage of fibrotic area. The histogram R2* values of the mean, median, 10th percentile, and 90th percentile at week 2 were all lower than those at baseline. Over the course of UUO progression, there were statistical differences between the histogram R2* values at any other two time points, except between weeks 4 and 6, and weeks 6 and 8. A close correlation was found between the percentage of fibrotic area and R2* values (mean: F = 21.49, p = 0.0001, R2 = 0.49, median: F = 30.07, p < 0.0001, R2 = 0.58, 10th percentile: F = 31.02, p < 0.0001, R2 = 0.59, 90th percentile: F = 24.13, p < 0.0001, R2 = 0.52). BOLD-MRI could reflect the formation and progression of renal fibrosis in a rabbit UUO model; however, the value of BOLD-MRI in the long-term evaluation of fibrosis is limited.

P29. Differential linear and nonlinear brain activation for probabilistic aversive outcomes in pathological gamblers and controls

Objective Functional imaging studies on decision making under uncertain risk of negative (aversive) outcomes are scarce. To get a better understanding of the underlying processes, we tested models of decision making including participants that were gambling regularly despite negative long-term consequences. Primarily, we sought to detect group differences in cortical and subcortical regions involved in decision processes. Also, we wanted to investigate, if current economic decision making models account for observable physiological data. Do we process aversive contingencies of decisions in a linear or a nonlinear manner, or both? Methods We studied 22 pathological and 18 habitual gamblers, as well as 23 control subjects, evaluated by psychologists with a semi-structured interview and self-reported Southern Oaks Gambling Scale. Participants were scanned with blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) and engaged in a card game in which un-ambiguous situations of various risk levels for punishment (unpleasant, but not painful electric shocks) were created. Apart from neural responses to punishment, our paradigm allowed us to measure how neural activity during expectation of a punishment is modulated by the probability to be punished (risk) or the certainty of the outcome (certainty). Results Extending previous work and testing our hypothesis, based on economic studies, we modelled expected outcomes according to the prospect theory. Activations differed spatially when situations were modelled according to risk or certainty. With linearly increasing chances of avoiding punishment we found that the BOLD signal increased in the orbitofrontal cortex, caudate nucleus, precuneus, and the posterior cingulate cortex ( Fig. 1 a). Conversely, with increasing certainty of an outcome (U-shaped from most certain punishment to most certain avoidance), we could demonstrate nonlinear activations in medial superior frontal cortex, anterior cingulate cortex, anterior insula and angular gyrus ( Fig. 1 b). Interestingly, we found no group differences in cerebral activation during the task, which dovetailed with ‘offline’ behavioural analyses of decision making in the same groups. Conclusion Our results support the notion that economic decision making contains both linear and nonlinear cognitive processes largely following contingencies for risk and certainty and provide evidence that these cognitive processes are represented in different sets of brain regions. Correlates of the risk for punishment were found in areas known to be involved in dopaminergic reinforcement learning, while regions known to sub serve decision making, conflict monitoring and punishment show correlation with certainty of the outcome. While differences in reward perception in pathological gamblers are frequently described in the literature, we found no evidence for changes in punishment perception.

Evaluation of Visceral Adipose Tissue Oxygenation by Blood Oxygen Level-Dependent MRI in Zucker Diabetic Fatty Rats.

This study aimed to investigate the feasibility of blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) to evaluate visceral adipose tissue (VAT) oxygenation in Zucker diabetic fatty (ZDF) rats and its associations with systemic metaflammation. Five-week-old ZDF rats and Zucker lean (ZL) rats were fed a high-fat diet (HFD) for 18 weeks. A baseline BOLD-MRI scan of perirenal adipose tissue was performed after 8 weeks of HFD feeding, and then the rats were randomized to receive pioglitazone or a vehicle for the following 10 weeks. At sacrifice, BOLD-MRI scan, Hypoxyprobe-1 injection, and circulating T helper 17 (Th17), regulatory T (Treg) cells, and monocyte subtype flow cytometry analysis were performed. HFD feeding led to a significant increase in VAT BOLD-MRI R2* signals (20.14 ± 0.23 per second vs. 21.53 ± 0.20 per second; P = 0.012), an indicator for decreased oxygenation. R2* signal was significantly correlated with VAT pimonidazole adduct-positive area, insulin resistance, Th17 and Treg cells, CD43 + and CD43+ + monocyte subtypes, and VAT macrophage infiltration. Pioglitazone treatment improved the insulin resistance and was associated with a delayed progression of VAT oxygenation. This work demonstrated the feasibility of BOLD-MRI for detecting the VAT oxygenation status in ZDF rats, and the BOLD-MRI signals were associated with insulin resistance and systemic metaflammation in ZDF rats during the development of obesity.

Update on renal blood oxygenation level–dependent MRI to assess intrarenal oxygenation in chronic kidney disease

Identifying subjects with progressive chronic kidney disease will be important both in clinical practice and in conducting clinical trials. Pruijm etal. (in this issue) demonstrate for the first time that cortical oxygenation as evaluated by blood oxygenation level-dependent magnetic resonance imaging can predict future loss of renal function. These observations provide the necessary stimulus to continue the development of renal blood oxygenation level-dependent magnetic resonance imaging to further improve the sensitivity and specificity to renal oxygenation and hence the predictive power.

Reduced cortical oxygenation predicts a progressive decline of renal function in patients with chronic kidney disease

Renal tissue hypoxia is a final pathway in the development and progression of chronic kidney disease (CKD), but whether renal oxygenation predicts renal function decline in humans has not been proven. Therefore, we performed a prospective study and measured renal tissue oxygenation by blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) in 112 patients with CKD, 47 with hypertension without CKD, and 24 healthy control individuals. Images were analyzed with the twelve-layer concentric objects method that divided the renal parenchyma in 12 layers of equal thickness and reports the mean R2* value of each layer (a high R2* corresponds to low oxygenation), along with the change in R2* between layers called the R2* slope. Serum creatinine values were collected to calculate the yearly change in estimated glomerular function rate (MDRD eGFR). Follow up was three years. The change in eGFR in CKD, hypertensive and control individuals was -2.0, 0.5 and -0.2 ml/min/1.73m2/year, respectively. In multivariable regression analysis adjusted for age, sex, diabetes, RAS-blockers, eGFR, and proteinuria the yearly eGFR change correlated negatively with baseline 24 hour proteinuria and the mean R2* value of the cortical layers, and positively with the R2* slope, but not with the other covariates. Patients with CKD and high outer R2* or a flat R2* slope were three times more likely to develop an adverse renal outcome (renal replacement therapy or over a 30% increase in serum creatinine). Thus, low cortical oxygenation is an independent predictor of renal function decline. This finding should stimulate studies exploring the therapeutic impact of improving renal oxygenation on renal disease progression.

Noninvasive evaluation of renal tissue oxygenation with blood oxygen level-dependent magnetic resonance imaging early after transplantation has a limited predictive value for the delayed graft function.

PurposeThe aim of this study was to evaluate the feasibility of renal oxygenation assessment using blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) in the early period after kidney transplantation and to estimate its prognostic value for delayed graft function.Material and methodsExaminations were performed in 50 subjects: 40 patients within a week after the kidney transplantation and 10 healthy controls, using T2*-weighted sequence. Measurements in transplant patients were correlated to basic laboratory parameters in the early period after transplantation and at follow-up.ResultsExaminations of seven patients (18%) were rejected due to their poor technical quality. Mean R2* values in transplant recipients were lower than in controls (11.6 vs. 15.9 Hz; p = 0.0001). An R2* value of 0.28 Hz was calculated as the minimal detectable change. There was no relation between R2* values and laboratory parameters. However, patients eGFR ≥ 40 ml/min/1.73 m2 presented higher R2* values than recipients eGFR < 40 ml/min/1.73 m2 (12.0 vs. 11.1 Hz; p = 0.0189). In ROC analysis R2* of ≤ 11.7 predicted an early reduced graft function with 0.82 sensitivity and 56% specificity (AUC = 0.708; p = 0.024) but was not useful for delayed graft function prediction (p > 0.7).ConclusionsEvaluation of renal graft oxygenation using BOLD MRI is technically challenging in the early period after transplantation. An R2* value of 0.28 Hz may in practice be considered as the minimal detectable change. The delayed graft function seems not to be dependent on early oxygenation values. Further, large-scale studies are necessary to confirm the latter observation.

Role of Blood Oxygen Level-dependent MRI in Differentiation of Acute Renal Allograft Dysfunction.

Early graft dysfunction after renal transplantation manifests as acute rejection (AR) or acute tubular necrosis (ATN). Blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging is a noninvasive method of assessing tissue oxygenation, which may be useful for predicting acute allograft dysfunction. This was a prospective study involving 40 patients scheduled for renal transplantation from August 2012 to August 2014. In addition, 15 healthy donors were also enrolled in this study. All recipients underwent BOLD MR imaging (MRI) and R2* mapping 10–20 days after transplant, and additionally within 48 h of biopsy if there was any evidence of graft dysfunction. The healthy donors underwent BOLD MRI 1–2 days before surgery. The biopsies were grouped into AR, ATN, and no evidence of AR or ATN. The mean medullary R2*, cortical R2*, corticomedullary gradient, and medullary: cortical R2* ratio were compared between groups using one-way analysis of variance. Spearman's correlation and multinomial linear regression were applied to determine the influence factors of R2* value. Overall, nine patients had graft dysfunction. Six were reported as AR, two as ATN, and one as no evidence of ATN or rejection. The mean medullary and cortical R2* were significantly higher in ATN group compared with AR and normal group, whereas the mean medullary and cortical R2* of AR group were significantly lower than normal group. The corticomedullary gradient of AR group was significantly lower compared with ATN and normal group. Medullary R2*:cortical R2* ratio was significantly lower in AR group compared with normal group. No significant difference was noted between the 15 donors and patients with normal graft function. R2* values on BOLD MRI are significantly decreased in AR allografts and increased in an early stage of ATN allografts, suggesting that BOLD MRI can become a valuable tool for discriminating between AR and ATN.

Science to Practice: Can Functional MR Imaging Be Useful in the Evaluation of Cardiorenal Syndrome?

Functional magnetic resonance (MR) imaging of the kidneys has gained interest recently, especially in the detection of early changes in acute kidney injury or to predict progression of chronic kidney disease (CKD). The application of these methods to cardiorenal syndrome (CRS) is novel. CRS is widely accepted as a complex clinical problem routinely faced by clinicians. In this issue, Chang et al ( 1 ) present their preliminary experience applying blood oxygen level-dependent (BOLD) MR imaging to the kidneys in mice with experimental myocardial infarction. They showed that R2* in the kidney increases after induced myocardial infarction and that the response was higher in animals with larger infarcts and over time. The authors also for the first time correlated the BOLD MR imaging findings against hypoxia-inducible factor-1α (HIF-1α) expression, an independent marker of renal hypoxia. In addition, they showed evidence for renal injury by using a kidney injury marker, kidney injury molecule-1 (KIM-1). The results of their study support the use of renal BOLD MR imaging in subjects with heart failure, in whom the risk of subsequent renal ischemia and/or hypoxia is known to exist. These results, along with those of other recent reports ( 2 ), suggest that functional imaging methods could play a key role in evaluating changes in both the primary and secondary organs involved in complex disease processes such as CRS. Availability of such methods could facilitate translation to the clinic and improve the mechanistic understanding of the complicated and interrelated pathophysiology.

Feasibility of using blood oxygen level-dependent magnetic resonance imaging to evaluate renal fibrosis of ureteral obstruction of rabbits

Objective: To investigate the feasibility of blood oxygen level-dependent MR (MR-BOLD) in assessing renal fibrosis of ureteral obstruction of rabbits. Methods: Forty healthy New Zealand rabbits were randomly divided into control group (n=8) and unilateral ureteral obstruction (UUO) group (n=32). The rabbits in the UUO group were subjected to unilateral ureteral obstruction of the left kidney.Coronal T(2) weighted imaging (T(2)WI) and axial BOLD examinations were performed before operation, 2, 4, 6 and 8 W after operation (each subgroup n=8). After the examinations, nephrectomy was performed for histologic evaluation.The T(2)(*) relaxation rate of the renal cortex (CR(2)(*)) , medulla (MR(2)(*)) and the same level of muscle(R(2)(*)(muscle)) were measured separately.The normalization of the cortex and medulla (sR(2)(*)), and the difference of sR(2)(*) between renal cortex and medulla before and post UUO (ΔsR(2)(*)) were calculated.The differences of sR(2)(*) (sCR(2)(*), sMR(2)(*), sCR(2)(*)(control), sMR(2)(*)(control)) at each time point between control and UUO group were compared by using independent sample t test.The LSD test was used to compare the sR(2)(*) in the control with that in the UUO group.The ΔsCR(2)(*) and ΔsMR(2)(*) values of the subgroups at UUO 2, 4, 6 and 8 W were compared by independent sample t test. Results: The sR(2)(*) values of UUO group were all lower than those of control group (all P<0.05), while sR(2)(*)(control) and sR(2)(*) in UUO group before operation were not significant different (P>0.05). The sCR(2)(*) values of UUO 2, 4, 6 and 8 W were 0.32±0.01, 0.37±0.01, 0.47±0.02 and 0.50±0.03.The sMR(2)(*) values were 0.39±0.02, 0.48±0.02, 0.58±0.04 and 0.65±0.05.There were significant differences of sCR(2)(*)(between) UUO 2 W and 6 W, UUO 2 W and 8 W, UUO 4 W and 6 W, UUO 4 W and 8 W (all P<0.01). There were significant differences of sMR(2)(*)(between) UUO 2 W and 6 W, UUO 2 W and 8 W, UUO 4 W and 8 W (all P<0.01). No significant difference was founded between sCR(2)(*) and sMR(2)(*) at each time point in control group (P>0.05). The ΔsCR(2)(*) values of UUO 2, 4, 6 and 8 W were 0.31±0.02, 0.20±0.02, 0.14±0.20, 0.09±0.04; the ΔsMR(2)(*) values were 0.51±0.05, 0.36±0.04, 0.28±0.05, 0.19±0.05. The ΔsCR(2)(*) values of UUO 2, 4 and 6 W were less than ΔsMR(2)(*) (P<0.05). There was no significant difference between ΔsCR(2)(*) and ΔsMR(2)(*) in UUO 8 W (P>0.05). Conclusions: The R(2)(*) change in medulla resulted from renal fibrosis is more significant than cortex.MR-BOLD can reflect the process of renal fibrosis.It's feasible and of great value to use renal MR-BOLD for the assessment of renal fibrosis induced by unilateral ureteral obstruction.

Impaired cerebrovascular reactivity in obstructive sleep apnea: a case-control study

ObjectiveObstructive sleep apnea (OSA) is an independent risk factor for stroke. Little is known about the cerebrovascular hemodynamic changes during apnea. Hypercapnia occurs in apneas and hypopneas, and a reduced cerebral vasodilatory response to CO2 could compromise the cerebral blood flow (CBF). Therefore, we aimed to evaluate whether the apnea–hypopnea index (AHI) affected the cerebrovascular response to CO2. MethodsA total of 11 patients with OSA were compared to 16 controls. We assessed the cerebrovascular responses with arterial spin labeling (ASL) and blood oxygen level-dependent (BOLD) magnetic resonance imaging during hypercapnia or breath-holding tasks. ResultsThe CBF response to CO2 was impaired with increasing AHI (average CBF: p = 0.018; gray matter: p = 0.038; white matter: p = 0.045), that is, increased OSA severity. When comparing the OSA patients to the control subjects, the OSA patients had a significantly reduced CO2 response of the white matter CBF (p = 0.04). However, the BOLD response to CO2 and the breath-holding task did not show any significant differences between OSA patients and control subjects. ConclusionThe cerebrovascular CO2 reactivity, measured by the CBF, was impaired with increasing AHI, that is, OSA severity. These findings may add to the understanding of the increased stroke risk found in OSA patients.

Peripheral vascular atherosclerosis in a novel PCSK9 gain-of-function mutant Ossabaw miniature pig model

Hypercholesterolemia is a major risk factor for atherosclerosis. Remaining challenges in the management of atherosclerosis necessitate development of animal models that mimic human pathophysiology. We characterized a novel mutant pig model with DNA transposition of D374Y gain-of-function (GOF) cDNA of chimp proprotein convertase subtilisin/kexin type-9 (PCSK9), and tested the hypothesis that it would develop peripheral vascular remodeling and target organ injury in the kidney. Wild-type or PCSK9-GOF Ossabaw miniature pigs fed a standard or atherogenic diet (AD) (n = 7 each) were studied in vivo after 3 and 6 months of diet. Single-kidney hemodynamics and function were studied using multidetector computed tomography and kidney oxygenation by blood oxygen level-dependent magnetic resonance imaging. The renal artery was evaluated by intravascular ultrasound, aortic stiffness by multidetector computed tomography, and kidney stiffness by magnetic resonance elastography. Subsequent ex vivo studies included the renal artery endothelial function and morphology of abdominal aorta, renal, and femoral arteries by histology. Compared with wild type, PCSK9-GOF pigs had elevated cholesterol, triglyceride, and blood pressure levels at 3 and 6 months. Kidney stiffness increased in GOF groups, but aortic stiffness only in GOF-AD. Hypoxia, intrarenal fat deposition, oxidative stress, and fibrosis were observed in both GOF groups, whereas kidney function remained unchanged. Peripheral arteries in GOF groups showed medial thickening and development of atheromatous plaques. Renal endothelial function was impaired only in GOF-AD. Therefore, the PCSK9-GOF mutation induces rapid development of atherosclerosis in peripheral vessels of Ossabaw pigs, which is exacerbated by a high-cholesterol diet. This model may be useful for preclinical studies of atherosclerosis.

Imaging of Chronic Concussion.

Conventional imaging findings in patients with cerebral concussion and chronic traumatic encephalopathy are absent or subtle in the majority of cases. The most common abnormalities include cerebral volume loss, enlargement of the cavum of the septum pellucidum, cerebral microhemorrhages, and white matter signal abnormalities, all of which have poor sensitivity and specificity. Advanced imaging modalities, such as diffusion tensor imaging (DTI), blood oxygen level dependent functional MR Imaging (BOLD fMRI), MR spectroscopy, perfusion imaging, positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetoencephalography detect physiologic abnormalities in symptomatic patients and, although currently in the investigation phase, may become useful in the clinical arena.

Changes in cerebellar functional connectivity and autonomic regulation in cancer patients treated with the Neuro Emotional Technique for traumatic stress symptoms.

A growing number of research studies have implicated the cerebellum in emotional processing and regulation, especially with regard to negative emotional memories. However, there currently are no studies showing functional changes in the cerebellum as a result of treatment for traumatic stress symptoms. The Neuro Emotional Technique (NET) is an intervention designed to help improve symptoms related to traumatic stress using an integrative approach that combines emotional, cognitive, and motor processing, with a particular focus on autonomic nervous system regulation. In this study, we evaluated whether the NET intervention alters functional connectivity in the brain of patients with traumatic stress symptoms associated with a cancer-related event. We hypothesized that the NET intervention would reduce emotional and autonomic reactivity and that this would correlate with connectivity changes between the cerebellum and limbic structures as well as the brain stem. We enrolled patients with a prior cancer diagnosis who experienced distressing cancer-related memories associated with traumatic stress symptoms of at least 6months in duration. Participants were randomized to either the NET intervention or a waitlist control. To evaluate the primary outcome of neurophysiological effects, all participants received resting-state functional blood oxygen level-dependent (BOLD) magnetic resonance imaging (rs-fMRI) before and after the NET intervention. In addition, autonomic reactivity was measured using heart rate response to the traumatic stimulus. Pre/post comparisons were performed between the NET and control groups. The results demonstrated significant changes in the NET group, as compared to the control group, in the functional connectivity between the cerebellum (including the vermis) and the amygdala, parahippocampus, and brain stem. Likewise, participants receiving the NET intervention had significant reductions in autonomic reactivity based on heart rate response to the traumatic stimulus compared to the control group. This study is an initial step towards establishing a neurological signature of treatment effect for the NET intervention. Specifically, functional connectivity between the cerebellum and the amygdala and prefrontal cortex appear to be associated with a reduction in autonomic reactivity in response to distressing cancer-related memories. This study contributes to the understanding of possible mechanisms by which interventions like NET may help reduce emotional distress in cancer patients who suffer from traumatic stress symptoms.