Blood Oxygen Level-dependent MRI Research Articles

High spatial resolution BOLD fMRI using simultaneous multislice excitation with echo-shifting gradient echo at 7 Tesla

We introduce an accelerated gradient echo (GRE) sequence combining simultaneous multislice excitation (SMS) with echo-shifting technique for high spatial resolution blood oxygen level dependent (BOLD) functional MRI (fMRI). The simulation was conducted to optimize scan parameters. To validate the feasibility of the proposed technique, the visual and motor task experiments were performed at 7.0 Tesla (T). The single-shot EPI sequence was also applied in comparison with the proposed technique. The simulation results showed that an optimized flip angle of 9° provided maximal BOLD contrast for our scanning scheme, allowing low power deposition and SMS acceleration factor of 5. Additionally, parallel acquisition imaging with acceleration factor of 2 was utilized, which allowed a total acceleration factor of 10 in volunteer study. The experiment results showed that geometric distortion-free BOLD images with voxel size of 1.0 × 1.0 × 2.5 mm3 were obtained. Significant brain activation was identified in both visual and motor task experiments, which were in accordance with previous investigations. The proposed technique has potential for high spatial resolution fMRI at ultra-high field because of its sufficient BOLD sensitivity as well as improved acquisition speed over conventional GRE-based techniques.

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.

Renal Functional MRI and Its Application.

5 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:863-881.

Hypoxia Detection in Infiltrative Astrocytoma: Ferumoxytol-based Quantitative BOLD MRI with Intraoperative and Histologic Validation.

Purpose To validate ferumoxytol-based quantitative blood oxygenation level-dependent (BOLD) MRI for mapping oxygenation of human infiltrative astrocytomas by using intraoperative measurement of tissue oxygen tension and histologic staining. Materials and Methods Fifteen patients with infiltrative astrocytomas were recruited into this prospective multicenter study between July 2014 and December 2016. Prior to treatment, participants underwent preoperative quantitative BOLD MRI with ferumoxytol to generate tissue oxygen saturation (StO2) maps. Two intratumoral sites were identified, one with low StO2 and one with high StO2. Neuronavigation was used to locate sites intraoperatively for insertion of oxygen-sensing probes to measure local tissue oxygen tension (PtO2). Biopsies from both sites were taken and stained for markers of hypoxia (hypoxia-inducible factor 1α, carbonic anhydrase IX) and neoangiogenesis (vascular endothelial growth factor, endoglin [CD105]). Spearman correlation and nonparametric sign-rank tests were used to analyze data. Results Ten patients with median age of 58.5 years (interquartile range, 25 years; four men and six women) completed the study. Because there is no linear relationship between StO2 and PtO2, the ratios of low to high StO2 versus low to high PtO2 in each patient were compared and a significant correlation was found (r = 0.73; P = .01). Pathologic analyses revealed differences between carbonic anhydrase IX (P = .03) for sites of low StO2 versus high StO2. CD105 displayed a similar trend but was not significant (P = .09). Conclusion Ferumoxytol-based quantitative blood oxygenation level-dependent MRI can potentially be used as a noninvasive surrogate for oxygenation mapping in infiltrative astrocytomas. This technique can potentially be integrated in treatment planning for aggressive targeting of hypoxic areas in tumors.

The value of blood oxygen level dependent (BOLD) imaging in evaluating post-operative renal function outcomes after laparoscopic partial nephrectomy.

To assess the ability of renal blood oxygen level dependent (BOLD) MRI metrics to predict post-operative renal function. We studied 152 patients who underwent laparoscopic partial nephrectomy (LPN) and renal MRI examination including BOLD. Short-term and long-term renal function was evaluated using the glomerular filtration rate (GFR) derived from renal scintigraphy. Renal function decline was assessed as the absolute decline (AD), percentage decline (PD) and optimal renal function preservation (OP). T2* values were analysed in the renal cortex and medulla ipsilateral and contralateral to the tumour. Clinical characteristics and imaging metrics were evaluated using univariate and multivariate linear regression analyses. Risk factors obtained using BOLD metrics (determined by multivariate regression) were then combined and compared with RENAL scores to predict OP. Increasing warm ischaemia time (WIT), resected and ischaemic volume (RAIV), larger tumour size, higher RENAL score and lower preoperative GFR were short-term risk factors for AD, while increasing WIT and lower preoperative GFR were significant for long-term outcomes. Increasing WIT, RAIV, lower T2* value in the cortex and higher T2* value in the medulla on the ipsilateral side were short-term risk factors for PD, while all of the above factors (except WIT and RAIV) were significant for long-term outcomes. The performance of the combination of T2* values in the cortex and medulla on the ipsilateral side to tumour in predicting OP was better than RENAL score (AUC 0.762 vs 0.634, p = 0.013). Renal BOLD-MRI metrics could provide useful information to the clinician in predicting post-operative renal function outcomes. • Renal fMRI metrics may be useful for prediction of renal functional outcomes and merit further study. • Renal fMRI metrics may reflect degree of baseline disease and ability to tolerate warm ischaemia. • Combination of T2* values was better than RENAL score for predicting OP.

Ccl2 deficiency protects against chronic renal injury in murine renovascular hypertension

Inflammation plays an important role in the pathogenesis of renal and cardiovascular disease in renovascular hypertension (RVH). Ccl2 is an important mediator of inflammation, and is induced within 24 hours following surgery to establish RVH in the murine 2 kidney 1 clip model, a time prior to onset of interstitial inflammation, fibrosis, or tubular atrophy. We tested the hypothesis that Ccl2 deficiency protects the stenotic kidney (STK) from development of chronic renal damage in mice with renovascular hypertension due to renal artery stenosis (RAS). RAS surgery was performed on wild type (WT) and Ccl2 knock out (KO) mice; animals were studied for four weeks. Renal blood flow was reduced to similar extent in both WT and Ccl2 KO mice with RVH. Perfusion of the stenotic kidney was significantly reduced in Ccl2 KO mice as assessed by magnetic resonance imaging (MRI). Stenotic kidney volume in WT, but not in Ccl2 KO mice, was significantly reduced following surgery. Cortical hypoxia was observed in the stenotic kidney of Ccl2 KO mice, as assessed by blood oxygen level-dependent MRI (BOLD-MRI). Ccl2 KO mice showed less cortical atrophy than WT RAS mice. Ccl2 deficiency reduced the number of infiltrating mononuclear cells and expression of Ccl5, Ccl7, Ccl8, Ccr2 and Cd206. We conclude that Ccl2 is a critical mediator of chronic renal injury in RVH.

Preeclampsia induced by STOX1 overexpression in mice induces intrauterine growth restriction, abnormal ultrasonography and BOLD MRI signatures.

Preeclampsia is a major hypertensive disease caused by pregnancy, inducing proteinuria and increased blood pressure starting from the second half of pregnancy (early preeclampsia) or near the end of pregnancy (late preeclampsia). Pre-symptomatic diagnosis would allow for therapeutic interventions, such as with low-dose aspirin. Among non-invasive methods to explore organ physiology, Doppler ultrasonography (US) and functional blood oxygenation level-dependent (BOLD) MRI (which do not need radioactive contrast agents such as gadolinium) can be used in pregnant women. In this study, we used US and BOLD MRI to finely characterize the phenotype of preeclampsia induced by the foeto-placental overexpression of the transcription factor storkhead box 1A (STOX1A) in female mice. We could observe late fetal growth restriction consistent with the placental dysfunction revealed by US and the known association between preeclampsia and intra-uterine growth restriction. On US, uterine and umbilical artery as well as heart and kidney parameters were modified in preeclamptic mice. On BOLD MRI, mean T2* values revealed considerable differences between control and preeclamptic placentas, which suggests altered dynamics of oxygen release and ratio of oxyhemoglobin to deoxyhemoglobin in the model. These preliminary pre-clinical results suggest that BOLD MRI could be evaluated as a prognostic/diagnostic tool for preeclampsia.

Modeling hyperoxia-induced BOLD signal dynamics to estimate cerebral blood flow, volume and mean transit time

A new method is proposed for obtaining cerebral perfusion measurements whereby blood oxygen level dependent (BOLD) MRI is used to dynamically monitor hyperoxia-induced changes in the concentration of deoxygenated hemoglobin in the cerebral vasculature. The data is processed using kinetic modeling to yield perfusion metrics, namely: cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). Ten healthy human subjects were continuously imaged with BOLD sequence while a hyperoxic (70% O2) state was interspersed with baseline periods of normoxia. The BOLD time courses were fit with exponential uptake and decay curves and a biophysical model of the BOLD signal was used to estimate oxygen concentration functions. The arterial input function was derived from end-tidal oxygen measurements, and a deconvolution operation between the tissue and arterial concentration functions was used to yield CBF. The venous component of the CBV was calculated from the ratio of the integrals of the estimated tissue and arterial concentration functions. Mean gray and white matter measurements were found to be: 61.6 ± 13.7 and 24.9 ± 4.0 ml 100 g−1 min−1 for CBF; 1.83 ± 0.32 and 1.10 ± 0.19 ml 100 g−1 for venous CBV; and 2.94 ± 0.52 and 3.73 ± 0.60 s for MTT, respectively. We conclude that it is possible to derive CBF, CBV and MTT metrics within expected physiological ranges via analysis of dynamic BOLD fMRI acquired during a period of hyperoxia.

Oxygenation-sensitive cardiovascular magnetic resonance in hypertensive heart disease with left ventricular myocardial hypertrophy and non-left ventricular myocardial hypertrophy: Insight from altered mechanics and cardiac BOLD imaging.

BOLD (blood oxygen level dependent) MRI can detect regional condition of myocardial oxygen supply and demand by means of paramagnetic properties. Noninvasive assessment of myocardial oxygenation by BOLD MRI in hypertensive patients with hypertension (HTN) left ventricular myocardial hypertrophy (LVMH) and HTN non-LVMH and its correlation with myocardial mechanics were performed. Prospective. Twenty patients with HTN LVMH, 21 patients with HTN non-LVMH, and 23 normotensive controls were enrolled. Cine imaging, T2* and T1 mapping sequences were achieved at 3.0T. Dedicated T1 mapping, T2*, and cine imaging analysis were performed by two radiologists using cvi42. One-way analysis of variance, Kruskal-Wallis test, Bland-Altman analysis, Pearson's correlation coefficient, Spearman's rank correlation. T2* values of HTN LVMH group were significantly lower versus the controls (23.78 ± 3.09 versus 30.77 ± 2.71; P < 0.001) and HTN non-LVMH group (23.78 ± 3.09 versus 28.64 ± 4.23; P < 0.001). Left ventricular peak circumferential strain were reduced in HTN LVMH patients compared with other two groups (-11.32 [-15.64, -10.3], -16.78 [-19.35, -15.34], and -19.73 [-20.57, -18.73]; P < 0.05); and longitudinal strain of HTN LVMH patients were lower than other two groups (-11.31 ± 2.91, -15.1 ± 3.06, and -18.85 ± 1.85; P < 0.05); radial strain of HTN LVMH patients were also lower than other two groups (25.03 ± 16, 40.95 ± 17.5 and 47.9 ± 10.23; P < 0.05). Extracellular volume correlated with peak circumferential, longitudinal, and radial strain (spearman rho = 0.6, 0.64, and -0.69; P < 0.05), respectively; T2* negatively correlated with peak circumferential and longitudinal strain (spearman rho = -0.43 and -0.49; P < 0.05), respectively. Patients with lower T2* values had significant decreases in myocardial mechanics (P < 0.05). HTN LVMH patients have both impaired myocardial mechanics and decreased T2* values compared with HTN non-LVMH and normotensive groups. BOLD MRI could provide a feasible assessment modality for detecting altered T2* due to the change of de-oxygenated hemoglobin and hence to the change of signal intensity in oxygenation-sensitive images. 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1297-1306.

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.

Fiber-optic implant for simultaneous fluorescence-based calcium recordings and BOLD fMRI in mice.

Despite the growing popularity of blood oxygen level-dependent (BOLD) functional MRI (fMRI), understanding of its underlying principles is still limited. This protocol describes a technique for simultaneous measurement of neural activity using fluorescent calcium indicators together with the corresponding hemodynamic BOLD fMRI response in the mouse brain. Our early work using small-molecule fluorophores in rats gave encouraging results but was limited to acute measurements using synthetic dyes. Our latest procedure combines fMRI with optical detection of cell-type-specific virally delivered GCaMP6, a genetically encoded calcium indicator (GECI). GCaMP6 fluorescence, which increases upon calcium binding, is collected by a chronically implanted optical fiber, allowing longitudinal studies in mice. The chronic implant, placed horizontally on the skull, has an angulated tip that reflects light into the brain and is connected via fiber optics to a remote optical setup. The technique allows access to the neocortex and does not require adaptations of commercial MRI hardware. The hybrid approach permits fiber-optic calcium recordings with simultaneous artifact-free BOLD fMRI with full brain coverage and 1-s temporal resolution using standard gradient-echo echo-planar imaging (GE-EPI) sequences. The method provides robust, cell-type-specific readouts to link neural activity to BOLD signals, as emonstrated for task-free ('resting-state') conditions and in response to hind-paw stimulation. These results highlight the power of fiber photometry combined with fMRI, which we aim to further advance in this protocol. The approach can be easily adapted to study other molecular processes using suitable fluorescent indicators.

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.

BOLD magnetic resonance imaging in nephrology

Magnetic resonance (MR) imaging, a non-invasive modality that provides anatomic and physiologic information, is increasingly used for diagnosis of pathophysiologic conditions and for understanding renal physiology in humans. Although functional MR imaging methods were pioneered to investigate the brain, they also offer powerful techniques for investigation of other organ systems such as the kidneys. However, imaging the kidneys provides unique challenges due to potential complications from contrast agents. Therefore, development of non-contrast techniques to study kidney anatomy and physiology is important. Blood oxygen level-dependent (BOLD) MR is a non-contrast imaging technique that provides functional information related to renal tissue oxygenation in various pathophysiologic conditions. Here we discuss technical considerations, clinical uses and future directions for use of BOLD MR as well as complementary MR techniques to better understand renal pathophysiology. Our intent is to summarize kidney BOLD MR applications for the clinician rather than focusing on the complex physical challenges that functional MR imaging encompasses; however, we briefly discuss some of those issues.

BOLD MRI to evaluate early development of renal injury in a rat model of diabetes.

ObjectiveTo investigate changes in renal oxygenation levels by blood-oxygenation-level dependent (BOLD)-magnetic resonance imaging (MRI), and to evaluate BOLD-MRI for detecting early diabetic renal injury.MethodsSeventy-five rats, with unilateral nephrectomy, were randomly divided into streptozotocin-induced diabetes mellitus (DM, n = 65) and normal control (NC, n = 10) groups. BOLD-MRI scans were performed at baseline (both groups) and at 3, 7, 14, 21, 28, 35, 42, 49, 56, 63 and 70 days (DM only). Renal cortical (C) and medullary (M) R2* signals were measured and R2* medulla/cortex ratio (MCR) was calculated.ResultsDM-group CR2* and MR2* values were significantly higher than NC values following diabetes induction. R2* values increased gradually and peaked at day 35 (CR2*, 33.95 ± 0.34 s–1; MR2*, 43.79 ± 1.46 s–1), then dropped gradually (CR2*, 33.17 ± 0.69 s–1; MR2*, 41.61 ± 0.95 s–1 at day 70). DM-group MCR rose gradually from 1.12 to 1.32 at day 42, then decreased to 1.25 by day 70.ConclusionsBOLD-MRI can be used to non-invasively evaluate renal hypoxia and early diabetic renal injury in diabetic rats. MCR may be adopted to reflect dynamic changes in renal hypoxia.

Influence of electroencephalograph bionic electrical stimulation on neuronal activities in patients with Alzheimer's disease: A functional magnetic resonance imaging study

PurposeTo investigate the influence of electroencephalograph bionic electrical stimulation on neuronal activity in patients with Alzheimer's disease (AD) using resting-state blood oxygen level dependent functional MRI (BOLD-fMRI) and amplitude of low-frequency fluctuation (ALFF) and fraction ALFF (fALFF) analysis. Methods42 AD patients were divided into two groups in accordance with the randomized double blind principle, every group was 21. Treatment group received electroencephalograph bionic electrical stimulation. Both groups received resting-state BOLD-fMRI scanning before and after treatment and comparing differences in ALFF and fALFF in each group by statistical methods. Correlation analysis was performed between ALFF or fALFF images and neuropsychological tests scale after treatment. ResultsPost-therapy brain regions with higher ALFF included left cerebellum posterior lobe, right cerebellum posterior lobe, left hippocampus/parahippocampus, left posterior cingulated cortex, left dorsolateral prefrontal cortex, right inferior parietal lobule in treatment group. Higher fALFF was observed in the right inferior parietal lobule. In the placebo group lower ALFF was observed in bilateral cerebellum posterior lobe and left posterior cingulated cortex. Alzheimer's Disease Assessment Scale-Cognitive section was closely correlated with ALFF in left cerebellum posterior lobe and right cerebellum posterior lobe. ConclusionThese results indicated improved neuronal activity in some brain areas could be achieved in AD after treatment of electroencephalograph bionic electrical stimulation. The change of BOLD-fMRI signal might provide a potential imaging strategy for studying neural mechanisms of electroencephalograph bionic electrical stimulation for AD.

Blood oxygen level dependent magnetic resonance imaging for detecting pathological patterns in lupus nephritis patients: a preliminary study using a decision tree model

BackgroundPrecise renal histopathological diagnosis will guide therapy strategy in patients with lupus nephritis. Blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) has been applicable noninvasive technique in renal disease. This current study was performed to explore whether BOLD MRI could contribute to diagnose renal pathological pattern.MethodsAdult patients with lupus nephritis renal pathological diagnosis were recruited for this study. Renal biopsy tissues were assessed based on the lupus nephritis ISN/RPS 2003 classification. The Blood oxygen level dependent magnetic resonance imaging (BOLD-MRI) was used to obtain functional magnetic resonance parameter, R2* values. Several functions of R2* values were calculated and used to construct algorithmic models for renal pathological patterns. In addition, the algorithmic models were compared as to their diagnostic capability.ResultsBoth Histopathology and BOLD MRI were used to examine a total of twelve patients. Renal pathological patterns included five classes III (including 3 as class III + V) and seven classes IV (including 4 as class IV + V). Three algorithmic models, including decision tree, line discriminant, and logistic regression, were constructed to distinguish the renal pathological pattern of class III and class IV. The sensitivity of the decision tree model was better than that of the line discriminant model (71.87% vs 59.48%, P < 0.001) and inferior to that of the Logistic regression model (71.87% vs 78.71%, P < 0.001). The specificity of decision tree model was equivalent to that of the line discriminant model (63.87% vs 63.73%, P = 0.939) and higher than that of the logistic regression model (63.87% vs 38.0%, P < 0.001). The Area under the ROC curve (AUROCC) of the decision tree model was greater than that of the line discriminant model (0.765 vs 0.629, P < 0.001) and logistic regression model (0.765 vs 0.662, P < 0.001).ConclusionsBOLD MRI is a useful non-invasive imaging technique for the evaluation of lupus nephritis. Decision tree models constructed using functions of R2* values may facilitate the prediction of renal pathological patterns.

Schizophrenia polygenic risk score predicts mnemonic hippocampal activity.

The use of polygenic risk scores has become a practical translational approach to investigating the complex genetic architecture of schizophrenia, but the link between polygenic risk scores and pathophysiological components of this disorder has been the subject of limited research. We investigated in healthy volunteers whether schizophrenia polygenic risk score predicts hippocampal activity during simple memory encoding, which has been proposed as a risk-associated intermediate phenotype of schizophrenia. We analysed the relationship between polygenic risk scores and hippocampal activity in a discovery sample of 191 unrelated healthy volunteers from the USA and in two independent replication samples of 76 and 137 healthy unrelated participants from Europe and the USA, respectively. Polygenic risk scores for each individual were calculated as the sum of the imputation probability of reference alleles weighted by the natural log of odds ratio from the recent schizophrenia genome-wide association study. We examined hippocampal activity during simple memory encoding of novel visual stimuli assessed using blood oxygen level-dependent functional MRI. Polygenic risk scores were significantly associated with hippocampal activity in the discovery sample [P = 0.016, family-wise error (FWE) corrected within Anatomical Automatic Labeling (AAL) bilateral hippocampal-parahippocampal mask] and in both replication samples (P = 0.033, FWE corrected within AAL right posterior hippocampal-parahippocampal mask in Bari sample, and P = 0.002 uncorrected in the Duke Neurogenetics Study sample). The relationship between polygenic risk scores and hippocampal activity was consistently negative, i.e. lower hippocampal activity in individuals with higher polygenic risk scores, consistent with previous studies reporting decreased hippocampal-parahippocampal activity during declarative memory tasks in patients with schizophrenia and in their healthy siblings. Polygenic risk scores accounted for more than 8% of variance in hippocampal activity during memory encoding in discovery sample. We conclude that polygenic risk scores derived from the most recent schizophrenia genome-wide association study predict significant variability in hippocampal activity during memory encoding in healthy participants. Our findings validate mnemonic hippocampal activity as a genetic risk associated intermediate phenotype of schizophrenia, indicating that the aggregate neurobiological effect of schizophrenia risk alleles converges on this pattern of neural activity.awy004media15749593779001.

Patient-Specific Alterations in CO2 Cerebrovascular Responsiveness in Acute and Sub-Acute Sports-Related Concussion.

Preliminary studies suggest that sports-related concussion (SRC) is associated with alterations in cerebral blood flow (CBF) regulation. Here, we use advanced magnetic resonance imaging (MRI) techniques to measure CBF and cerebrovascular responsiveness (CVR) in individual SRC patients and healthy control subjects. 15 SRC patients (mean age = 16.3, range 14-20 years) and 27 healthy control subjects (mean age = 17.6, range 13-21 years) underwent anatomical MRI, pseudo-continuous arterial spin labeling (pCASL) MRI and model-based prospective end-tidal targeting (MPET) of CO2 during blood oxygenation level-dependent (BOLD) MRI. Group differences in global mean resting CBF were examined. Voxel-by-voxel group and individual differences in regional CVR were examined using statistical parametric mapping (SPM). Leave-one-out receiver operating characteristic curve analysis was used to evaluate the utility of brain MRI CO2 stress testing biomarkers to correctly discriminate between SRC patients and healthy control subjects. All studies were tolerated with no complications. Traumatic structural findings were identified in one SRC patient. No significant group differences in global mean resting CBF were observed. There were no significant differences in the CO2 stimulus and O2 targeting during BOLD MRI. Significant group and patient-specific differences in CVR were observed with SRC patients demonstrating a predominant pattern of increased CVR. Leave-one-out ROC analysis for voxels demonstrating a significant increase in CVR was found to reliably discriminate between SRC patients and healthy control subjects (AUC of 0.879, p = 0.0001). The optimal cutoff for increased CVR declarative for SRC was 1,899 voxels resulting in a sensitivity of 0.867 and a specificity of 0.778 for this specific ROC analysis. There was no correlation between abnormal voxel counts and Postconcussion Symptom Scale scores among SRC patients. Acute and subacute SRCs are associated with alterations in CVR that can be reliably detected by brain MRI CO2 stress testing in individual patients.

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.