Oxygen Level-dependent Magnetic Resonance Imaging Research Articles

A Novel Stress-Diathesis Model to Predict Risk of Post-operative Delirium: Implications for Intra-operative Management.

Introduction: Risk assessment for post-operative delirium (POD) is poorly developed. Improved metrics could greatly facilitate peri-operative care as costs associated with POD are staggering. In this preliminary study, we develop a novel stress-diathesis model based on comprehensive pre-operative psychiatric and neuropsychological testing, a blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) carbon dioxide (CO2) stress test, and high fidelity measures of intra-operative parameters that may interact facilitating POD.Methods: The study was approved by the ethics board at the University of Manitoba and registered at clinicaltrials.gov as NCT02126215. Twelve patients were studied. Pre-operative psychiatric symptom measures and neuropsychological testing preceded MRI featuring a BOLD MRI CO2 stress test whereby BOLD scans were conducted while exposing participants to a rigorously controlled CO2 stimulus. During surgery the patient had hemodynamics and end-tidal gases downloaded at 0.5 hz. Post-operatively, the presence of POD and POD severity was comprehensively assessed using the Confusion Assessment Measure –Severity (CAM-S) scoring instrument on days 0 (surgery) through post-operative day 5, and patients were followed up at least 1 month post-operatively.Results: Six of 12 patients had no evidence of POD (non-POD). Three patients had POD and 3 had clinically significant confusional states (referred as subthreshold POD; ST-POD) (score ≥ 5/19 on the CAM-S). Average severity for delirium was 1.3 in the non-POD group, 3.2 in ST-POD, and 6.1 in POD (F-statistic = 15.4, p < 0.001). Depressive symptoms, and cognitive measures of semantic fluency and executive functioning/processing speed were significantly associated with POD. Second level analysis revealed an increased inverse BOLD responsiveness to CO2 pre-operatively in ST-POD and marked increase in the POD groups when compared to the non-POD group. An association was also noted for the patient population to manifest leucoaraiosis as assessed with advanced neuroimaging techniques. Results provide preliminary support for the interacting of diatheses (vulnerabilities) and intra-operative stressors on the POD phenotype.Conclusions: The stress-diathesis model has the potential to aid in risk assessment for POD. Based on these initial findings, we make some recommendations for intra-operative management for patients at risk of POD.

Blood oxygen level-dependent magnetic resonance imaging for detecting pathological patterns in patients with lupus nephritis: a preliminary study using gray-level co-occurrence matrix analysis.

ObjectiveBlood oxygen level-dependent magnetic resonance imaging (BOLD MRI) is a noninvasive technique useful in patients with renal disease. The current study was performed to determine whether BOLD MRI can contribute to the diagnosis of renal pathological patterns.MethodsBOLD MRI was used to obtain functional magnetic resonance parameter R2* values. Gray-level co-occurrence matrixes (GLCMs) were generated for gray-scale maps. Several GLCM parameters were calculated and used to construct algorithmic models for renal pathological patterns.ResultsHistopathology and BOLD MRI were used to examine 12 patients. Two GLCM parameters, including correlation and energy, revealed differences among four groups of renal pathological patterns. Four Fisher’s linear discriminant formulas were constructed using two variables, including the correlation at 45° and correlation at 90°. A cross-validation test showed that the formulas correctly predicted 28 of 36 samples, and the rate of correct prediction was 77.8%.ConclusionsDifferences in the texture characteristics of BOLD MRI in patients with lupus nephritis may be detected by GLCM analysis. Discriminant formulas constructed using GLCM parameters may facilitate prediction of renal pathological patterns.

Noninvasive Identification of Renal Hypoxia in Experimental Myocardial Infarctions of Different Sizes by Using BOLD MR Imaging in a Mouse Model.

Purpose To test the feasibility of using blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging to measure alterations in renal oxygenation in a mouse model with experimental myocardial infarctions (MIs) of different sizes. Materials and Methods The study was approved by the local animal ethics committee. One hundred eighty-nine male C57BL/6 J mice were randomly subjected to MI surgery (with different locations of left anterior descending coronary artery occlusion) or sham surgery, defined as the exposure of the heart but no ligation. Mice with MI underwent late gadolinium enhancement imaging 1 day after occlusion to confirm infarct size. Mice were sorted into three groups: those with large MI (n = 48), those with small MI (n = 48), and those with sham operation (n = 36). Renal BOLD MR imaging was performed before and 1, 7, 14, 28, and 60 days after MI, and histologic analysis of renal hypoxia-inducible factor-1α (HIF-1α) and kidney injury molecule-1 (KIM-1) was performed to evaluate tissue hypoxia and kidney injury in subgroups imaged at each time point. The relationships between the BOLD R2* and HIF-1α expression and between HIF-1α and KIM-1 expression were assessed. Statistical analyses were performed with one-way analysis of variance or the Kruskal-Wallis test and Spearman correlation test. Results A significant elevation in R2* was detected in the MI groups compared with the sham group in the cortex (P < .001 for large MI vs sham group; P = .007 for small MI vs sham group) and medulla (P < .001 for large MI vs sham group; P = .003 for small MI vs sham group) on day 60, and R2* was higher in the large MI group than in the small MI group (P < .001). Renal HIF-1α expression was increased after MI and showed linear correlation with R2* in the cortex (R2 = 0.56) and medulla (R2 = 0.63). In addition, an increase in renal KIM-1 was observed in the MI groups compared with the sham group on day 60 (sham group, 53.9 × 103 arbitrary units [au] ± 35.2; large MI group, 389.3 × 103 au ± 99.8; and small MI group, 185.8 × 103 au ± 91.9; P < .001 for large MI group vs sham group; P = .037 for small MI group vs sham group), and renal KIM-1 showed a positive correlation with HIF-1α (R2 = 0.68). Conclusion The magnitude of renal hypoxia with MIs of different sizes can be noninvasively measured with BOLD MR imaging, and increased renal hypoxia is a potential risk factor for progressive tubulointerstitial injury in mouse kidneys. © RSNA, 2017 Online supplemental material is available for this article.

Therapy-related longitudinal brain perfusion changes in patients with chronic pelvic pain syndrome.

The imaging method most frequently employed to identify brain areas involved in neuronal processing of nociception and brain pain perception is blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI). Arterial spin labelling (ASL), in contrast, offers advantages when slow varying changes in brain function are investigated. Chronic pelvic pain syndrome (CPPS) is a disorder of, mostly, young males that leads to altered pain perceptions in structures related to the pelvis. We aimed to investigate the potential of ASL to monitor longitudinal cranial blood flow (CBF) changes in patients with CPPS. In a randomised, placebo-controlled, double-blind single centre trial, we investigated treatment effects in CPPS after 12 weeks in patients that underwent sono-electro-magnetic therapy vs placebo. We investigated changes of CBF related to treatment outcome using pseudo-continuous arterial spin labelling (pCASL)-MRI. We observed CBF downregulation in the prefrontal cortex and anterior cingulate cortex and upregulation in the dorsolateral prefrontal cortex in responders. Nonresponders presented with CBF upregulation in the hippocampus. In patients with a history of CPPS of less than 12 months, there were significant correlations between longitudinal CBF changes and the Chronic Prostatitis Symptom Index pain subscore within the joint clusters anterior cingulate cortex and left anterior prefrontal cortex in responders, and the right hippocampus in nonresponders. We demonstrated therapy-related and stimulus-free longitudinal CBF changes in core areas of the pain matrix using ASL. ASL may act as a complementary noninvasive method to functional MRI and single-photon emission computed tomography / positron emission tomography, especially in the longitudinal assessment of pain response in clinical trials.

MR Imaging Measurements of Altered Placental Oxygenation in Pregnancies Complicated by Fetal Growth Restriction.

Purpose To evaluate oxygen-enhanced and blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging parameters in normal pregnancies and those complicated by fetal growth restriction (FGR). Materials and Methods This case-control study was approved by the local research ethics committee. Informed consent was obtained from all subjects. From October 2010 to October 2015, 28 women with uncomplicated pregnancies (individualized birthweight ratio [IBR] >20th percentile and delivery >37 weeks) and 23 with pregnancies complicated by FGR (IBR <5th percentile and abnormal Doppler ultrasonography [US] studies) underwent MR imaging. Differences in placental longitudinal R1 (1/T1) and transverse R2* (1/T2*) were quantified, with subjects breathing either air or oxygen. The difference in R1 (ΔR1) after hyperoxia was converted to change in partial pressure of oxygen (ΔPo2). Data were acquired prospectively, with retrospective interpretation of group differences (unpaired t tests). Diagnostic models were developed by using logistic regression analysis with gestational age as a covariate. Results The mean baseline R1 and R2* for normal pregnancies (R1: 0.59 sec-1, 95% confidence interval [CI]: 0.58 sec-1, 0.60 sec-1; R2*: 17 sec-1, 95% CI: 14 sec-1, 20 sec-1) were significantly different from those of pregnancies complicated by FGR (R1: 0.63 sec-1, 95% CI: 0.62 sec-1, 0.65 sec-1; R2*: 26 sec-1, 95% CI: 22 sec-1, 32 sec-1) (P < .0001). The ΔR1 showed a significant negative association with gestational age (P < .0001) in the combined cohort, with the FGR group having a ΔR1 that was generally 61.5% lower than that in the normal pregnancy group (P = .003). The area under the receiver operating characteristic curve for the differentiation between pregnancy complicated by FGR and normal pregnancy by using ΔPo2, baseline R1, and baseline R2* was 0.91 (95% CI: 0.82, 0.99). Conclusion R1, R2*, and ΔPo2 were significantly different between normal pregnancies and those complicated by severe FGR. MR imaging parameters have the potential to help identify placental dysfunction associated with FGR and may have clinical utility in correctly identifying FGR among fetuses that are small for gestational age. A larger prospective study is needed to assess the incremental benefit beyond that offered by US. © RSNA, 2017.

The effect of imatinib therapy on tumour cycling hypoxia, tissue oxygenation and vascular reactivity

Background: Several biomedical imaging techniques have recently been developed to probe hypoxia in tumours, including oxygen-enhanced (OE) and blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI). These techniques have strong potential for measuring both chronic and transient (cycling) changes in hypoxia, and to assess response to vascular-targeting therapies in the clinic. Methods: In this study, we investigated the use of BOLD and OE-MRI to assess changes in cycling hypoxia, tissue oxygenation and vascular reactivity to hyperoxic gas challenges, in mouse models of colorectal therapy, following treatment with the PDGF-receptor inhibitor, imatinib mesylate (Glivec). Results: Whilst no changes were observed in imaging biomarkers of cycling hypoxia (from BOLD) or chronic hypoxia (from OE-MRI), the BOLD response to carbogen-breathing became significantly more positive in some tumour regions and more negative in other regions, thereby increasing overall heterogeneity. Conclusions: Imatinib did not affect the magnitude of cycling hypoxia or OE-MRI signal, but increased the heterogeneity of the spatial distribution of BOLD MRI changes in response to gas challenges.

A preliminary fMRI study of acupuncture with healthy volunteers

Objective To observe the cortical functioning of healthy volunteers during acupuncture as a way of exploring acupuncture′s neural mechanisms. Methods Twenty healthy volunteers received acupuncture applied to the left hegu and waiguan acupoints while their cortical activity was examined using blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI). Brain activation, especially of the regions related to motor function, were observed and analyzed. Results Acupuncture applied to the left hegu and waiguan acupoints was observed to significantly activate the left middle frontal gyrus and the inferior frontal gyrus, with many activated regions in the left insula and a few in the left cerebellum, the left precentral gyrus, the left postcentral gyrus, the left inferior parietal lobule, the left medial frontal gyrus, the left precuneus, the left anterior cingulate gyrus and the left claustrum. The right side of the brain was excited mainly in the right middle frontal gyrus and the right medial frontal gyrus. The right inferior parietal lobule and the right precentral gyrus were also activated to some extent. There was slight activation of the right middle temporal gyrus, the right superior temporal gyrus, the right insula, the right inferior frontal gyrus and the right postcentral gyrus. The negatively activated regions were mainly located on both sides of the limbic lobe, including the hippocampus, the parahippocampal gyrus and the cingulate gyrus. The left superior temporal gyrus, the left middle temporal gyrus and the right middle frontal gyrus also had small negative activation zones. Conclusions In brain regions associated with motor function, in addition to partial activation of the contralateral primary sensorimotor area, acupuncture at these two points clearly generates bilateral activation of secondary motor areas with some activation in the ipsilateral cerebellum. This may serve as a neuropathological basis for acupuncture treatment of motor dysfunction. BOLD-fMRI imaging displays the neural effects of acupuncture in an intuitive way. It can be a useful technique for further study of the neural effects of acupuncture on pathological conditions. Key words: Acupuncture; Hegu; Waiguan; Functional magnetic resonance imaging

Eccentric Exercise And Microvascular Function

Exercise involving eccentric contractions results in reduced muscle function. Blood oxygen level dependent (BOLD) MR imaging has demonstrated slowed microvascular reactivity in eccentrically exercised tibialis anterior (TA) muscle. While the mechanism is unclear, exercise-induced inflammation and oxidative stress may reduce nitric oxide (NO) bioavailability, and consequently slow microvascular reactivity. PURPOSE: To test the hypotheses that ingestion of dietary nitrate or antioxidants preserve microvascular reactivity following eccentric exercise. METHODS: Thirty young men and women were randomized into three groups, who ingested a single dose of: i) beetroot juice (BR, 8.4mmol NO3-), ii) antioxidants (AO, Vitamin C and E, alpha-lipoic acid), or iii) placebo (PLA, fruit juice) at 46 hours after an exercise protocol. The protocol consisted of eccentric contractions of the TA in one leg, while the contralateral leg served as control. At baseline, and 48h after eccentric exercise, participants were positioned in a 3T magnet, and BOLD images were acquired bilaterally in TA muscle during i) brief maximal contractions (MVC), and ii) cuff occlusion (5 min, 260mmHg) to monitor the hyperemic responses. The time-to-peak (TTP, s) of the hyperemic response was used as an index of microvascular reactivity. Data were analyzed using mixed model, three-way (Leg, Group, Session (0h, 48h)) repeated measures ANOVA. RESULTS: The ANOVA revealed leg-by-session interactions for TTP following brief MVCs and cuff occlusion (P < 0.001), with no main or interaction effects of group. Specifically, 48h after eccentric exercise, TTP (MVC) was prolonged in all groups compared with baseline (BR: 8.6±1.0 vs.10.9±1.0 s; AO: 8.4±0.4 vs.10.1±0.4 s, PLA: 9.0±0.9 vs.11.0±0.8 s), with no changes in control leg. Similarly, 48h after eccentric exercise, TTP (cuff) was prolonged in all groups compared with baseline (BR: 45.5±4.7 vs.68.6±7.7 s; AO: 36.8±5.7 vs.54.5±8.5 s, PLA: 42.1±6.4 vs.68.1±7.1 s), with no changes in control leg. CONCLUSION: Ingestion of BR and AO do not preserve microvascular reactivity after eccentric exercise, indicating that elevated oxidative stress and lower NO bioavailability do not contribute to altered microvascular function after eccentric exercise. Supported by Danish Ministry of Culture grant.

The metabolic syndrome induces early changes in the swine renal medullary mitochondria

The metabolic syndrome (MetS) is associated with nutrient surplus and kidney hyperfiltration, accelerating chronic renal failure. Mitochondria can be overwhelmed by substrate excess, leading to inefficient energy production and thereby tissue hypoxia. Mitochondrial dysfunction is emerging as an important determinant of renal damage, but whether it contributes to MetS-induced renal injury remains unknown. We hypothesized that early MetS induces kidney mitochondrial abnormalities and dysfunction, which would be notable in the vulnerable renal medulla. Pigs were studied after 16weeks of diet-induced MetS, MetS treated for the last 4weeks with the mitochondria-targeted peptide elamipretide (0.1mg/kg SC q.d), and Lean controls (n=7 each). Single-kidney renal blood flow, glomerular filtration rate, and oxygenation were measured in-vivo, whereas cortical and medullary mitochondrial structure and function and renal injurious pathways were studied ex-vivo. Blood pressure was slightly elevated in MetS pigs, and their renal blood flow and glomerular filtration rate were elevated. Blood oxygen level-dependent magnetic resonance imaging demonstrated that this was associated with medullary hypoxia, whereas cortical oxygenation remained intact. MetS decreased renal content of the inner mitochondrial membrane cardiolipin, particularly the tetra-linoleoyl (C18:2) cardiolipin species, and altered mitochondrial morphology and function, particularly in the medullary thick ascending limb. MetS also increased renal cytochrome-c-induced apoptosis, oxidative stress, and tubular injury. Chronic mitoprotection restored mitochondrial structure, ATP synthesis, and antioxidant defenses and decreased mitochondrial oxidative stress, medullary hypoxia, and renal injury. These findings implicate medullary mitochondrial damage in renal injury in experimental MetS, and position the mitochondria as a therapeutic target.

Application of BOLD MRI and DTI for the evaluation of renal effect related to viscosity of iodinated contrast agent in a rat model.

To evaluate the effects of viscosity of contrast agent (CA) on intrarenal oxygenation and diffusion as measured by blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) in a rat model. Radiocontrast iodixanol formulated in three viscosities were designated 270, 320, and 350 (mg iodine/mL). Sixty-three male Wistar rats were divided into four groups. Saline and iodixanol (4 g iodine/kg) were administered. MR images were acquired on a 3.0T scanner at baseline and at 1 hour, 24 hours, 48 hours, and 72 hours postinjection of solutions. BOLD-MRI was performed with a multiple gradient-recalled-echo sequence. The changes in R2*, apparent diffusion coefficient (ADC), fractional anisotropy (FA), histology, and hypoxia-inducible factor-1α (HIF-1α) immunoexpression were evaluated. The R2*, ADC, and FA values were normalized to baseline to calculate ΔR2*, ΔADC, and ΔFA. Compared with baseline levels, distinct elevation of ΔR2* (P < 0.05) and obvious decrease in ΔADC (P < 0.01) and ΔFA (P < 0.05) were observed in all the anatomical compartments at 1 hour after administration of CA. The absolute values in ΔR2*, ΔADC, and ΔFA increased with increases in CA viscosity, and differed significantly between the CA groups in renal cortex (CO), outer stripe of outer medulla (OSOM), and inner stripe of outer medulla (ISOM) (all P < 0.05). A significant positive correlation was observed between ΔR2* and HIF-1α expression (P < 0.001, r = 0.75). Significant negative correlations were observed between ΔADC, ΔFA, and pathologies in CO, OSOM, ISOM (all P < 0.001, r = -0.68-0.87; all P < 0.001, r = -0.60-0.66). The effect of CA viscosity on intrarenal oxygenation and diffusion was viscosity-dependent, and was identified using BOLD-MRI and DTI. 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1320-1331.

Scalp cluster acupuncture combined with constraint-induced movement therapy improves functional recovery after ischemic stroke

Objective To compare the effect of clustered acupuncture of the scalp combined with constraint-induced movement therapy (CIMT) with that of conventional acupuncture of the body points plus conventional rehabilitation intervention after cerebral infarction using blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI). Methods Thirty acute cerebral infarction patients with hemiplegia were equally divided into two groups at random. The test group received the clustered acupuncture of the scalp combined with CIMT, while the control group received the body point acupuncture plus conventional rehabilitation intervention. Before and after two weeks of treatment, blood oxygenation level-dependent functional magnetic resonance imaging at 3.0 T was performed during a passive digital opposition movement. The volume and intensity of the activated areas were compared. Fugl-Meyer assessment (FMA) was carried out as well. Results The most pronounced activation appeared in the contralateral somatosensory motor cortex for both groups. There was no significant difference in average FMA scores between the two groups before the treatment, but after the treatment the averages were significantly different. An increase in activated volume and intensity in the contralateral SMC was observed in both groups after the treatment, but the test group showed a much larger change in both activated volume and intensity. Conclusion The clustered acupuncture of the scalp combined with CIMT can achieve a more significant improvement in functional recovery after acute cerebral infarction than conventional acupuncture of the body points plus conventional rehabilitation intervention. Such combined therapy is worthy of application in clinical practice. Key words: Scalp; Acupuncture; Constraint-induced movement therapy; Functional MRI; Cerebral infarction

Renal Hypoxia in CKD; Pathophysiology and Detecting Methods.

Chronic kidney disease (CKD) is a major public health problem. Accumulating evidence suggests that CKD aggravates renal hypoxia, and in turn, renal hypoxia accelerates CKD progression. To eliminate this vicious cycle, hypoxia-related therapies, such as hypoxia-inducible factor (HIF) activation (prolyl hydroxylase domain inhibition) or NF-E2-related factor 2 activation, are currently under investigation. Clinical studies have revealed heterogeneity in renal oxygenation; therefore, the detection of patients with more hypoxic kidneys can be used to identify likely responders to hypoxia-oriented therapies. In this review, we provide a detailed description of current hypoxia detection methods. HIF degradation correlates with the intracellular oxygen concentration; thus, methods that can detect intracellular oxygen tension changes are desirable. The use of a microelectrode is a classical technique that is superior in quantitative performance; however, its high invasiveness and the fact that it reflects the extracellular oxygen tension are disadvantages. Pimonidazole protein adduct immunohistochemistry and HIF activation detection reflect intracellular oxygen tension, but these techniques yield qualitative data. Blood oxygen level-dependent magnetic resonance imaging has the advantage of low invasiveness, high quantitative performance, and application in clinical use, but its biggest disadvantage is that it measures only deoxyhemoglobin concentrations. Phosphorescence lifetime measurement is a relatively novel in vivo oxygen sensing technique that has the advantage of being quantitative; however, it has several disadvantages, such as toxicity of the phosphorescent dye and the inability to assess deeper tissues. Understanding the advantages and disadvantages of these hypoxia detection methods will help researchers precisely assess renal hypoxia and develop new therapeutics against renal hypoxia-associated CKD.

Risk assessment of aggressive behavior in Chinese patients with schizophrenia by fMRI and COMT gene.

BackgroundBlood–oxygen-level dependent functional magnetic resonance imaging (BOLD-fMRI) maps cerebral activity by the hemodynamic response. Catechol-O-methyltransferase (COMT) gene is involved in the metabolism of dopamine. It is reported that both of these can be used to assess the aggression risk in patients with schizophrenia. However, these methods to assess the aggression risk patients with schizophrenia have not been established in China. Therefore, we deliver here a systematic review and meta-analysis based on the studies dealing with Chinese patients.MethodNine fMRI studies and 12 gene studies were included. The data of each study were extracted and summarized. Odds ratios with 95% confidence intervals were estimated on allele, dominant, and recessive models. Publication bias was evaluated by Begg’s funnel plot.ResultsPositive BOLD-fMRI values in the lower central neural system (CNS) and negative values in the high-level CNS were observed in the patients with aggression risk. A strong association was derived from the recessive gene model of COMT polymorphism rs4680 and risk in aggression behavior (odds ratio =2.10). No significant publication bias was identified.ConclusionAggression behavior in patients with schizophrenia can be indicated by positive BOLD-fMRI values in the lower CNS and negative values in the high-level CNS and by a recessive gene model in COMT polymorphism rs4680. A combined test of fMRI and COMT gene could increase the predictive value.

Functional MRI of human pancreas using BOLD contrast: Responses following glucose ingestion.

To evaluate the response of the pancreas to glucose ingestion in healthy volunteers by blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI). This study was approved by the local Ethics Committee, and informed consent was obtained from all subjects. A multiple gradient recalled echo (mGRE) sequence was performed on a 3.0T MR scanner in 12 healthy volunteers before and after glucose or water ingestion. Pancreatic T2* values were calculated from it at each timepoint, and changes following stimulation were analyzed using summary measures. The valley values and times were compared between the glucose and water ingestion by paired samples t-test. The repeatability of the pancreatic T2* measurements was assessed by calculating the intraclass correlation coefficient (ICC) and coefficient of variation (CV). Pancreatic T2* measurements showed good repeatability (all ICC >0.75). CV for the six baseline acquisitions was 2.74 ± 0.97%, indicating a 5.37% measurement error. A transient but significant decrease (-6.88 ± 1.01%, P value, 0.0005-0.0467) in the pancreatic T2* values was observed within 5 minutes after glucose ingestion, rather than water consumption. Compared to water, glucose ingestion induced earlier (valley times: 3.46 ± 3.22 vs. 7.75 ± 4.09 min, P = 0.0006) and remarkable pancreatic T2* decrease (valley values: -15.33 ± 5.90% vs. -6.88 ± 3.11%, P = 0.0006). BOLD MRI enabled noninvasive quantification of pancreatic T2* changes during glucose stimulation. Glucose ingestion resulted in a rapid and significant pancreatic T2* decrease in healthy young volunteers. 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:831-836.

Cerebrovascular Reactivity and Intellectual Outcome in Childhood Stroke With Transient Cerebral Arteriopathy

BackgroundHypercapnic-challenge blood oxygen level–dependent magnetic resonance imaging cerebrovascular reactivity (CVR), measures the regional perfusion response to altered carbon dioxide. CVR correlates with the tissue-level microvascular dysfunction and ischemic risk. Among children with arterial ischemic stroke, transient cerebral arteriopathy (TCA) is a frequent, nonprogressive unilateral intracranial arteriopathy, which typically results in basal ganglia infarction and chronic cerebral artery stenosis. Therefore TCA provides a model for studying the consequences of chronic nonprogressive stenosis using CVR and intellectual outcome. We hypothesized that children with TCA and chronic nonprogressive intracranial artery stenosis have impaired CVR distal to the stenosis and associated cognitive impairment. MethodsWe studied children with a prior diagnosis of TCA as defined by infarction limited to the basal ganglia, internal capsule, or both; and significant (greater than 50% diameter) residual stenosis of the supraclinoid internal carotid artery, its proximal branches or both. All children had CVR, intellectual function, and infarct volumes quantified. ResultsWe performed CVR studies in five children at mean 8.96 years (3.33 to 14.58 years) poststroke. Impaired CVR was limited to the infarct zone and adjacent white matter in most children. Intellectual function was broadly average in all but one subject. ConclusionsIn children with typical TCA, ipsilateral cortical CVR and intellectual function seem to be preserved despite persistent arterial stenosis in the majority. These findings suggest that chronic revascularization strategies in these children may not be indicated and require further exploration in a larger cohort of children.

Blood Oxygenation Level-Dependent MRI to Assess Renal Oxygenation in Renal Diseases: Progresses and Challenges.

BOLD-MRI (blood oxygenation-level dependent magnetic resonance imaging) allows non-invasive measurement of renal tissue oxygenation in humans, without the need for contrast products. BOLD-MRI uses the fact that magnetic properties of hemoglobin depend of its oxygenated state:: the higher local deoxyhemoglobin, the higher the so called apparent relaxation rate R2* (sec−1), and the lower local tissue oxygen content. Several factors other than deoxyhemoglobin (such as hydration status, dietary sodium intake, and susceptibility effects) influence the BOLD signal, and need to be taken into account when interpreting results. The last 5 years have witnessed important improvements in the standardization of these factors, and the appearance of new, highly reproducible analysis techniques of BOLD-images, that are reviewed in this article. Using these new BOLD-MRI analysis techniques, it has recently been shown that persons suffering from chronic kidney diseases (CKD) have lower cortical oxygenation than normotensive controls, thus confirming the chronic hypoxia hypothesis. The acute alterations in R2* after the administration of furosemide are smaller in CKD, and represent an estimate of the oxygen-dependent tubular transport of sodium. BOLD-MRI-alone or in combination with other functional MRI methods- can be used to monitor the renal effects of drugs, and is increasingly used in the preclinical setting. The near future will tell whether or not BOLD-MRI represents a new tool to predict renal function decline an adverse renal outcome.

Detection of Acute Tubular Necrosis Using Blood Oxygenation Level-Dependent (BOLD) MRI

Background/Aims: To date, there is no imaging technique to assess tubular function in vivo. Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI) measures tissue oxygenation based on the transverse relaxation rate (R2*). The present study investigates whether BOLD MRI can assess tubular function using a tubule-specific pharmacological maneuver. Methods: Cross sectional study with 28 participants including 9 subjects with ATN-induced acute kidney injury (AKI), 9 healthy controls, and 10 subjects with nephron sparing tumor resection (NSS) with clamping of the renal artery serving as a model of ischemia/reperfusion (I/R)-induced subclinical ATN (median clamping time 15 min, no significant decrease of eGFR, p=0.14). BOLD MRI was performed before and 5, 7, and 10 min after intravenous administration of 40 mg furosemide. Results: Urinary neutrophil gelatinase-associated lipocalin was significantly higher in ATN-induced AKI and NSS subjects than in healthy controls (p=0.03 and p=0.01, respectively). Before administration of furosemide, absolute medullary R2*, cortical R2*, and medullary/cortical R2* ratio did not significantly differ between ATN-induced AKI vs. healthy controls and between NSS-I/R vs. contralateral healthy kidneys (p>0.05 each). Furosemide led to a significant decrease in the medullary and cortical R2* of healthy subjects and NSS contralateral kidneys (p<0.05 each), whereas there was no significant change of R2* in ATN-induced AKI and the NSS-I/R kidneys (p>0.05 each). Conclusion: BOLD-MRI is able to detect even mild tubular injury but necessitates a tubule-specific pharmacological maneuver, e.g. blocking the Na⁺-K⁺-2Cl^- transporter by furosemide.

Cerebral blood flow and vasoreactivity in aging: an arterial spin labeling study.

Regional cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) in young and elderly participants were assessed using pulsed arterial spin labeling (ASL) and blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) techniques in combination with inhalation of CO2. Pulsed ASL and BOLD-MRI were acquired in seventeen asymptomatic volunteers (10 young adults, age: 30±7 years; 7 elderly adults, age: 64±8 years) with no history of diabetes, hypertension, and neurological diseases. Data from one elderly participant was excluded due to the incorrigible head motion. Average baseline CBF in gray matter was significantly reduced in elderly (46±9 mL·100 g-1·min-1) compared to young adults (57±8 mL·100 g-1·min-1; P=0.02). Decreased pulsed ASL-CVR and BOLD-CVR in gray matter were also observed in elderly (2.12±1.30 and 0.13±0.06 %/mmHg, respectively) compared to young adults (3.28±1.43 and 0.28±0.11 %/mmHg, respectively; P<0.05), suggesting some degree of vascular impairment with aging. Moreover, age-related decrease in baseline CBF was observed in different brain regions (inferior, middle and superior frontal gyri; precentral and postcentral gyri; superior temporal gyrus; cingulate gyri; insula, putamen, caudate, and supramarginal gyrus). In conclusion, CBF and CVR were successfully investigated using a protocol that causes minimal or no discomfort for the participants. Age-related decreases in baseline CBF and CVR were observed in the cerebral cortex, which may be related to the vulnerability for neurological disorders in aging.

Clinical application of intraoperative MRI navigation in microsurgical resection of cerebral arteriovenous malformations located near the main functional areas

Objective To evaluate the efficacy and safety of intraoperative MRI navigation in the microsurgical treatment of arteriovenous malformations (AVM) located near the main functional areas of brain. Methods A total of 53 patients with AVM in the adjacent functional areas were treated by microsurgical operation with intraoperative MRI navigation and electrophysiological monitoring. Blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) and diffusion tensor imaging (DTI) examinations were performed before and during operation. We fused BOLD-fMRI and DTI images to form three-dimensional images containing lesions, important functional areas and pyramidal tract so as to study the relationship between them and their changes before and after operation. Results The diameter of malformations in 53 patients was 2-7 cm, on average of (3.41 ± 0.85) cm. There were 6 patients involved in sensory areas, 7 patients in motor areas, 10 patients in pyramidal tract, 14 patients in language areas, 2 patients in visual cortex, 9 patients in optic radiation, 2 patients in basal ganglia and 3 patients in brain stem. Gross total resection was achieved in 49 patients while full functionality was retained. The other 4 patients with intraoperative MRI navigation were found that malformations and functional areas were closely related, so the lesions were partially resected. There were 8 patients with new-onset postoperative neurological dysfunction, among whom one case was found bilateral visual field defects, 3 patients' muscle tone was lower than before, one case of facial paralysis, 2 cases of aphasia, one with decreased muscle tone and motor aphasia. Follow-up period varied from 3 to 60 months [median 19.37 (6.00, 30.00) months], and 2 cases died (one died of respiratory failure after one year, and the other was agnogenic). Glasgow Outcome Scale (GOS) score was 5 in 45 cases (84.91%), 4 in 3 cases (5.66%), 3 in 2 cases (3.77%), 2 in one case (1.89%) and one in 2 cases (3.77%). Conclusions With the application of intraoperative MRI navigation and electrophysiological monitoring, it may be appropriate to expand the surgical indications of AVM located near the main functional areas of brain. DOI: 10.3969/j.issn.1672-6731.2016.12.006

Impact of physiological noise correction on detecting blood oxygenation level-dependent contrast in the breast

Physiological fluctuations are expected to be a dominant source of noise in blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) experiments to assess tumour oxygenation and angiogenesis. This work investigates the impact of various physiological noise regressors: retrospective image correction (RETROICOR), heart rate (HR) and respiratory volume per unit time (RVT), on signal variance and the detection of BOLD contrast in the breast in response to a modulated respiratory stimulus. BOLD MRI was performed at 3 T in ten volunteers at rest and during cycles of oxygen and carbogen gas breathing. RETROICOR was optimized using F-tests to determine which cardiac and respiratory phase terms accounted for a significant amount of signal variance. A nested regression analysis was performed to assess the effect of RETROICOR, HR and RVT on the model fit residuals, temporal signal-to-noise ratio, and BOLD activation parameters. The optimized RETROICOR model accounted for the largest amount of signal variance ( = 3.3 ± 2.1%) and improved the detection of BOLD activation (P = 0.002). Inclusion of HR and RVT regressors explained additional signal variance, but had a negative impact on activation parameter estimation (P < 0.001). Fluctuations in HR and RVT appeared to be correlated with the stimulus and may contribute to apparent BOLD signal reactivity.