Blood Oxygen Level-dependent MR Research Articles

Pathological Factors Affecting the R2* Values of the Kidney in Blood Oxygenation Level-dependent MR Imaging: A Retrospective Study.

Despite the usefulness of blood oxygenation level-dependent (BOLD) MRI in assessing glomerulonephritis activity, its relationship with histological findings remains unclear. Because glomerulonephritis presents multiple complex injury patterns, analysis of each pattern is essential. We aimed to elucidate the relationship between the histological findings of the kidney and BOLD MRI findings in mesangial proliferative glomerulonephritis. Children under 16 years of age diagnosed with mesangial proliferative glomerulonephritis by kidney biopsy at our university hospital between January 2013 and September 2022 were included in this study. Cortical and medullary spin relaxation rate (R2*) values were measured using BOLD MRI at 3T within two weeks before and after the kidney biopsy. The R2* values, including the fluctuations with low-dose oxygen administration, were retrospectively examined in relation to the cortical (mesangial proliferation, endothelial cell proliferation, crescent, sclerosis, and fibrosis) and medullary findings (fibrosis). Sixteen times kidney biopsies were performed for glomerulonephritis during the study period, and one patient was excluded because of comorbidities; the remaining 14 patients included six boys with a mean age of 11.9 ± 3.5 years at the BOLD examination. None of the patients had medullary fibrosis. Among the kidney tissue parameters, only sclerosis showed a significant correlation with R2* values: medulla with R2* values under atmospheric pressure (r = 0.53, P < 0.05) and cortex with the rate of change in R2* values with low-dose oxygen administration (r = -0.57, P < 0.03). In the multiple regression analysis, only sclerosis was an independent contributor to the change in R2* values with oxygen administration in the cortex (regression coefficient -0.109, P < 0.05). Since the R2* values reflect histological changes in the kidney, BOLD MRI may facilitate the evaluation of mesangial proliferative glomerulonephritis, potentially reducing the patient burden.

Perfusion MRI Techniques: Beyond DSC

The use of brain hemodynamics is important in the assessment of numerous pathophysiologic conditions. The measurement of perfusion or delivery of blood to tissues by MR imaging is essential for neuroradiologists to understand and appropriately apply to clinical practice. Several different approaches are used. DSC and dynamic contrast-enhanced MR imaging study the signal change (according to T2* and T1, respectively) induced by an exogenous contrast agent, allowing the measurement of CBF, CBV, and time-related parameters. Blood oxygen level‐dependent (BOLD) MR imaging measures the T2* signal changes induced by the paramagnetic molecule deoxyhemoglobin. BOLD MR imaging provides complex measurements because the signal varies not only with changes in CBF but also with several other parameters such as tissular oxygen uptake and brain activation. Arterial spin-labeling MR imaging is a technique relying on labeled endogenous water as a tracer. By measuring the signal difference between 2 sets of acquisitions (labeling and control), arterial spin-labeling MR imaging calculates cerebral perfusion in a quantitative manner. This article aims to review the fundamentals of perfusion MR imaging techniques essential to any neuroradiology practice along with their advantages, disadvantages, and applications to research and clinical care.Learning Objective: To review DSC MR imaging and alternative MR imaging perfusion techniques, focusing on methodology, advancements, and applications essential for the neuroradiologist to understand and clinically use these techniques

Brain Stress Test for Assessing Risk for Hemodynamic Stroke.

In patients with intracranial steno-occlusive disease (SOD), the risk of hemodynamic stroke depends on the poststenotic vasodilatory reserve. Cerebrovascular reactivity (CVR) is a test for vasodilatory reserve. We tested for vasodilatory reserve by using PETCO2 as the stressor, and Blood Oxygen Level Dependent (BOLD) MRI as a surrogate of blood flow. We correlate the CVR to the incidence of stroke after a 1-year follow-up in patients with symptomatic intracranial SOD. In this retrospective study, 100 consecutive patients with symptomatic intracranial SOD that had undergone CVR testing were identified. CVR was measured as % BOLD MR signal intensity/mmHg PETCO2. All patients with normal CVR were treated with optimal medical therapy; those with abnormal CVR were offered revascularization where feasible. We determined the incidence of stroke at 1 year. 83 patients were included in the study. CVR was normal in 14 patients and impaired in 69 patients ipsilateral to the lesion. Of these, 53 underwent surgical revascularization. CVR and symptoms improved in 86% of the latter. The overall incidence of stroke was 4.8 % (4/83). All strokes occurred in patients with impaired CVR (4/69; 2/53 in the surgical group, all in the nonrevascularized hemisphere), and none in patients with normal CVR (0/14). Our study confirms that CO2-BOLD MRI CVR can be used as a brain stress test for the assessment of cerebrovascular reserve. Impaired CVR is associated with a higher incidence of stroke and normal CVR despite significant stenosis is associated with a low risk for stroke.

Cyclic changes in T2* relaxometry of human uterus during the menstrual cycle using BOLD MR imaging

PurposeTo evaluate dynamic changes of T2* values within the endometrium, junctional zone and myometrium during the menstrual cycle using blood oxygen level-dependent (BOLD) magnetic resonance imaging. MethodVolunteers underwent MRI scans on menstrual phase, ovulatory phase and luteal phase, including T2-weighted imaging and BOLD MR imaging. Multi-gradient-recalled echo (MGRE) sequence was used to obtain BOLD MR images. T2* values of different uterine layers, including endometrium, junctional zone and myometrium, on sagittal images were analyzed quantitatively. ResultsTwenty-four subjects calculated T2* values successfully. The T2* values of each zonal structure during menstruation were significantly lower than those during ovulatory phase (P < 0.05) and luteal phase (P < 0.001). The T2* value of junctional zone was significantly lower than that of the myometrium over all three menstrual phases (P = 0.000, menstrual; P = 0.000, ovulatory; P = 0.001, luteal). The mean T2* value in endometrium during the ovulatory phase was the highest of the uterine zones over menstrual cycle. During menstrual phase, there was no statistical difference between endometrium and junctional zone (P > 0.05). Conversely, the comparison of the T2* values between endometrium and myometrium, junctional zone and myometrium both showed significant difference (P = 0.000). The mean T2* values within endometrium during ovulatory phase and luteal phase were significantly higher than those within junctional zone and myometrium (P < 0.05). ConclusionsCyclic changes of T2* values in each zonal structure of the uterus were revealed during the menstrual cycle by means of BOLD technique, which may be potentially beneficial in investigating dysmenorrhea, guiding assisted reproductive technologies and monitoring hypoxia in gynecological tumors.

Impaired Neurovascular Function Underlies Poor Neurocognitive Outcomes and Is Associated with Nitric Oxide Bioavailability in Congenital Heart Disease.

We use a non-invasive MRI proxy of neurovascular function (pnvf) to assess the ability of the vasculature to supply baseline metabolic demand, to compare pediatric and young adult congenital heart disease (CHD) patients to normal referents and relate the proxy to neurocognitive outcomes and nitric oxide bioavailability. In a prospective single-center study, resting-state blood-oxygen-level-dependent (BOLD) and arterial spin labeling (ASL) MRI scans were successfully obtained from 24 CHD patients (age = 15.4 ± 4.06 years) and 63 normal referents (age = 14.1 ± 3.49) years. Pnvf was computed on a voxelwise basis as the negative of the ratio of functional connectivity strength (FCS) estimated from the resting-state BOLD acquisition to regional cerebral blood flow (rCBF) as estimated from the ASL acquisition. Pnvf was used to predict end-tidal CO2 (PETCO2) levels and compared to those estimated from the BOLD data. Nitric oxide availability was obtained via nasal measurements (nNO). Pnvf was compared on a voxelwise basis between CHD patients and normal referents and correlated with nitric oxide availability and neurocognitive outcomes as assessed via the NIH Toolbox. Pnvf was shown as highly predictive of PETCO2 using theoretical modeling. Pnvf was found to be significantly reduced in CHD patients in default mode network (DMN, comprising the ventromedial prefrontal cortex and posterior cingulate/precuneus), salience network (SN, comprising the insula and dorsal anterior cingulate), and central executive network (CEN, comprising posterior parietal and dorsolateral prefrontal cortex) regions with similar findings noted in single cardiac ventricle patients. Positive correlations of Pnvf in these brain regions, as well as the hippocampus, were found with neurocognitive outcomes. Similarly, positive correlations between Pnvf and nitric oxide availability were found in frontal DMN and CEN regions, with particularly strong correlations in subcortical regions (putamen). Reduced Pnvf in CHD patients was found to be mediated by nNO. Mediation analyses further supported that reduced Pnvf in these regions underlies worse neurocognitive outcome in CHD patients and is associated with nitric oxide bioavailability. Impaired neuro-vascular function, which may be non-invasively estimated via combined arterial-spin label and BOLD MR imaging, is a nitric oxide bioavailability dependent factor implicated in adverse neurocognitive outcomes in pediatric and young adult CHD.

Dynamic changes of hepatic microenvironment related to graft function in donation after cardiac death liver transplantation

PurposeThe study aimed to evaluate dynamic changes in the liver microenvironment at 3 weeks, 3 months, and 6 months following donation after cardiac death liver transplantation (DCDLT) using multiparametric MRI, and further explore the correlation between the hepatic microenvironment and liver function after DCDLT. MethodsTwenty-seven patients after DCDLT (the LT group) at times of 3 weeks (LT-3W), 3 months (LT-3M), and 6 months (LT-6M) and 20 normal volunteers (the N group) underwent intravoxel incoherent motion (IVIM), diffusion tensor imaging (DTI), and blood oxygen level-dependent (BOLD) MR scanning. One-way repeated-measures ANOVA was used to compare MR parameters and liver volume (LV)/estimated standard liver volume (ESLV) at three follow-up times in the LT group. An independent sample t-test was used to compare MR parameters and LV/ESLV between each time of the LT group and the N group. Pearson and Spearman correlation analyses were employed to assess the correlation between MR parameters and liver blood indicators, LV/ESLV after DCDLT. ResultsAfter DCDLT, true diffusion coefficient (Dslow), pseudo diffusion coefficient (Dfast), perfusion fraction (PF), and apparent diffusion coefficient (ADC) values were increased, and fractional anisotropy (FA) and R2* values were decreased. Dfast values in the LT-3M and LT-6M were significantly higher than in the LT-3W. Compared to the LT-3W, PF and ADC values were significantly increased and R2* values were significantly decreased in the LT-6M (all P < 0.05). All MR parameters in the LT-3W were significantly different from the N group, and Dfast and ADC values in the LT-6M remained significantly higher than in the N group (all P < 0.05). In the LT group, Dslow, Dfast, PF, and ADC values were correlated with liver blood indicators and LV/ESLV (|r| = 0.364–0.561, all P < 0.05). ConclusionAfter DCDLT, the hepatic microenvironment showed an improving trend, which was correlated to the liver function. Except for the microcirculatory perfusion, the hepatic microenvironment was close to normality at six months.

Detection of renal hypoxia configuration in patients with lupus nephritis: a primary study using blood oxygen level-dependent MR imaging.

Renal microstructure and function are closely associated with oxygenation homeostasis. Analyzing renal blood oxygen level‒dependent (BOLD) magnetic resonance imaging (MRI) examination results will provide information on the biological status of the kidneys. The current study was performed to explore the hypoxia mode of the entire renal parenchyma in patients with lupus nephritis (LN). A total of 23 adult patients with LN and 18 healthy volunteers were recruited. R2* values were acquired using BOLD MRI analysis. The narrow rectangular region of interest was used to explore the hypoxia configuration in entire depths of renal parenchyma. Acquired sequential R2* data were fitted using four categories of mathematic functions. The tendency of R2* data in both patients with LN and healthy volunteers was also compared using repeated-measures analysis of variance. R2* data from the superficial cortex to deep medulla displayed two patterns called a sharp uptrend style and a flat uptrend style. After sequential R2* data were fitted individually with the use of four mathematic formulas, the multiple-compartment Gaussian function showed the highest goodness of fit. Compared with two categories of R2* value styles, the R2* tendency of entire parenchyma in patients with LN was different from that in healthy volunteers. Deep renal medullary oxygenation was not always overtly lower than oxygenation in the superficial renal cortical zone. The manifestation of renal parenchyma oxygenation could be described using a Gaussian function model. Deoxygenation tolerance was damaged in patients with LN.

Management of renovascular hypertension.

Renovascular occlusive disease remains a common cause of resistant and rapidly progressive hypertension. The present review summarizes current practice regarding management of renovascular hypertension (RVH). Current data using blood oxygen level dependent MR emphasize the tolerance of the kidney to moderate reductions in blood flow and the efficacy of antihypertensive drug therapy for many individuals. Prospective trials have failed to identify benefits of revascularization for moderate disease, either regarding blood pressure or renal function. Antihypertensive drug therapy including renin-angiotensin system blockade is central to management of RVH. Recent and ongoing observational studies report important improvements after revascularization regarding blood pressure, management of refractory or 'flash' pulmonary edema, and survival in specific 'high risk' clinical populations not included in randomized trials. Research directions underscore the role of adjunctive measures, including mitochondrial protection, therapeutic angiogenesis, and cell-based regenerative repair to protect kidney function in RVH. Clinicians should recognize the potential for disease progression to threaten renal function with severe and prolonged renal ischemia. Improved patient selection for true resistant hypertension with RVH and 'high-risk' clinical manifestations is critical to identify those likely to benefit from renal revascularization.

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.

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.

Changes in Gray Matter Density, Regional Homogeneity, and Functional Connectivity in Methamphetamine-Associated Psychosis: A Resting-State Functional Magnetic Resonance Imaging (fMRI) Study.

BackgroundUsing regional homogeneity (ReHo) blood oxygen level-dependent functional MR (BOLD-fMRI), we investigated the structural and functional alterations of brain regions among patients with methamphetamine-associated psychosis (MAP).Material/MethodsThis retrospective study included 17 MAP patients, 16 schizophrenia (SCZ) patients, and 18 healthy controls. Informed consent was obtained from all patients before the clinical assessment, the severity of clinical symptoms was evaluated prior to the fMRI scanning, and then images were acquired and preprocessed after each participant received 6-min fRMI scanning. The participants all underwent BOLD-fMRI scanning. Voxel-based morphometry was used to measure gray matter density (GMD). Resting-state fMRI (rs-fMRI) was conducted to analyze functional MR, ReHo, and functional connectivity (FC).ResultsGMD analysis results suggest that MAP patients, SCZ patients, and healthy volunteers show different GMDs within different brain regions. Similarly, the ReHo analysis results suggest that MAP patients, SCZ patients, and healthy volunteers have different GMDs within different brain regions. Negative correlations were found between ReHo- and the PANSS-positive scores within the left orbital interior frontal gyrus (L-orb-IFG) of MAP patients. ReHo- and PANSS-negative scores of R-SFG were negatively correlated among SCZ patients. The abnormal FC of R-MFG showed a negative correlation with the PANSS score among MAP patients.ConclusionsThe abnormalities in brain structure and FC were associated with the development of MAP.

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.

Unsupervised Myocardial Segmentation for Cardiac BOLD.

A fully automated 2-D+time myocardial segmentation framework is proposed for cardiac magnetic resonance (CMR) blood-oxygen-level-dependent (BOLD) data sets. Ischemia detection with CINE BOLD CMR relies on spatio-temporal patterns in myocardial intensity, but these patterns also trouble supervised segmentation methods, the de facto standard for myocardial segmentation in cine MRI. Segmentation errors severely undermine the accurate extraction of these patterns. In this paper, we build a joint motion and appearance method that relies on dictionary learning to find a suitable subspace. Our method is based on variational pre-processing and spatial regularization using Markov random fields, to further improve performance. The superiority of the proposed segmentation technique is demonstrated on a data set containing cardiac phase-resolved BOLD MR and standard CINE MR image sequences acquired in baseline and ischemic condition across ten canine subjects. Our unsupervised approach outperforms even supervised state-of-the-art segmentation techniques by at least 10% when using Dice to measure accuracy on BOLD data and performs at par for standard CINE MR. Furthermore, a novel segmental analysis method attuned for BOLD time series is utilized to demonstrate the effectiveness of the proposed method in preserving key BOLD patterns.

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.

Evaluation of Usage fMRI in Alzheimer’s Disease Diagnose

: Background: Alzheimer’s disease (AD) is a state where neurons within the brain stop functioning, lose connection with other neurons and die. It’s the most common cause of dementia, a loss of brain function that can harmfully impact memory, thinking, language, judgment and behavior. Alzheimer’s is irreversible and progressive. Although the cause of Alzheimer’s disease is unknown, scientists believe that a build-up of beta-amyloid plaques and neurofibrillary tangles in the brain are associated with the disease. Medications that slow the progression of the disease and manage symptoms are available, but there is no cure for Alzheimer’s disease. Current diagnosis of AD is through clinical, neuropsychological, and neuroimaging assessments. Functional MRI (fMRI) measures brain activity during a cognitive, sensory, or motor task or at rest by measuring changes in blood oxygen level dependent (BOLD) MR signal. Objectives: In this paper, we evaluate application of fMRI to detect AD. Methods: The papers were searched in PubMed, Medline and Scopus databases with the relevant key words such as fMRI, Alzheimer disease and early detection. Results: BOLD fMRI is considered to reflect the joined synaptic activity of neurons through MRI signal changes because of alterations in blood flow, blood volume, and the blood oxyhemoglobin/deoxyhemoglobin ratio. In patients with clinically diagnosed AD, the outcomes of fMRI have been quite consistent, showing reduced hippocampal activity during the encoding of new data. Several studies have reported increased prefrontal cortical activity in AD patients, suggesting that other networks may increase activity as an attempted compensatory mechanism during hippocampal failure. In particular, the event-related fMRI studies have found that hyperactivity was observed, which suggested that hyperactivity might represent a compensatory mechanism in the setting of early AD pathology. Also, fMRI of default mode network (DMN) brain activity during resting is lately achievement attention as a potential noninvasive biomarker to diagnose initial AD. Conclusions: Both task-related and resting fMRI techniques have the potential to detect early brain dysfunction related to AD. However, the use of fMRI in AD populations thus far has been limited to a relatively small number of research groups.

The Effects of Acetazolamide on the Evaluation of Cerebral Hemodynamics and Functional Connectivity Using Blood Oxygen Level-Dependent MR Imaging in Patients with Chronic Steno-Occlusive Disease of the Anterior Circulation.

Measuring cerebrovascular reactivity with the use of vasodilatory stimuli, such as acetazolamide, is useful for chronic cerebrovascular steno-occlusive disease. The purpose of this study was to evaluate the effects of acetazolamide on the assessment of hemodynamic impairment and functional connectivity by using noninvasive resting-state blood oxygen level-dependent MR imaging. A 20-minute resting-state blood oxygen level-dependent MR imaging scan was acquired with infusion of acetazolamide starting at 5 minutes after scan initiation. A recently developed temporal-shift analysis technique was applied on blood oxygen level-dependent MR imaging data before and after acetazolamide infusion to identify regions with hemodynamic impairment, and the results were compared by using contrast agent-based DSC perfusion imaging as the reference standard. Functional connectivity was compared with and without correction on the signal by using information from temporal-shift analysis, before and after acetazolamide infusion. Visually, temporal-shift analysis of blood oxygen level-dependent MR imaging data identified regions with compromised hemodynamics as defined by DSC, though performance deteriorated in patients with bilateral disease. The Dice similarity coefficient between temporal-shift and DSC maps was higher before (0.487 ± 0.150 by using the superior sagittal sinus signal as a reference for temporal-shift analysis) compared with after acetazolamide administration (0.384 ± 0.107) (P = .006, repeated-measures ANOVA). Functional connectivity analysis with temporal-shift correction identified brain network nodes that were otherwise missed. The accuracy of functional connectivity assessment decreased after acetazolamide administration (P = .015 for default mode network, repeated-measures ANOVA). Temporal-shift analysis of blood oxygen level-dependent MR imaging can identify brain regions with hemodynamic compromise in relation to DSC among patients with chronic cerebrovascular disease. The use of acetazolamide reduces the accuracy of temporal-shift analysis and network connectivity evaluation.

Stimulation-induced transient changes in neuronal activity, blood flow and N-acetylaspartate content in rat prefrontal cortex: a chemogenetic fMRS-BOLD study.

Brain activation studies in humans have shown the dynamic nature of neuronal N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) based on changes in their MRS signals in response to stimulation. These studies demonstrated that upon visual stimulation there was a focal increase in cerebral blood flow (CBF) and a decrease in NAA or in the total of NAA and NAAG signals in the visual cortex, and that these changes were reversed upon cessation of stimulation. In the present study we have developed an animal model in order to explore the relationships between brain stimulation, neuronal activity, CBF and NAA. We use "designer receptor exclusively activated by designer drugs" (DREADDs) technology for site-specific neural activation, a local field potential electrophysiological method for measurement of changes in the rate of neuronal activity, functional MRS for measurement of changes in NAA and a blood oxygenation level-dependent (BOLD) MR technique for evaluating changes in CBF. We show that stimulation of the rat prefrontal cortex using DREADDs results in the following: (i) an increase in level of neuronal activity; (ii) an increase in BOLD and (iii) a decrease in the NAA signal. These findings show for the first time the tightly coupled relationships between stimulation, neuron activity, CBF and NAA dynamics in brain, and also provide the first demonstration of the novel inverse stimulation-NAA phenomenon in an animal model.

Modulation of renal oxygenation and perfusion in rat kidney monitored by quantitative diffusion and blood oxygen level dependent magnetic resonance imaging on a clinical 1.5T platform.

BackgroundTo investigate the combined use of intravoxel incoherent motion (IVIM) diffusion-weighted (DW) and blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) to assess rat renal function using a 1.5T clinical platform.MethodsMultiple b-value DW and BOLD MR images were acquired from adult rats using a parallel clinical coil arrangement, enabling quantitation of the apparent diffusion coefficient (ADC), IVIM-derived diffusion coefficient (D), pseudodiffusion coefficient (D*) and perfusion fraction (f), and the transverse relaxation time T2*, for whole kidney, renal cortex, and medulla. Following the acquisition of two baseline datasets to assess measurement repeatability, images were acquired following i.v. administration of hydralazine, furosemide, or angiotensin II for up to 40 min.ResultsExcellent repeatability (CoV <10 %) was observed for ADC, D, f and T2* measured over the whole kidney. Hydralazine induced a marked and significant (p < 0.05) reduction in whole kidney ADC, D, and T2*, and a significant (p < 0.05) increase in D* and f. Furosemide significantly (p < 0.05) increased whole kidney ADC, D, and T2*. A more variable response to angiotensin II was determined, with a significant (p < 0.05) increase in medulla D* and significant (p < 0.05) reduction in whole kidney T2* established.ConclusionsMultiparametric MRI, incorporating quantitation of IVIM DWI and BOLD biomarkers and performed on a clinical platform, can be used to monitor the acute effects of vascular and tubular modulating drugs on rat kidney function in vivo. Clinical adoption of such functional imaging biomarkers can potentially inform on treatment effects in patients with renal dysfunction.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-016-0356-x) contains supplementary material, which is available to authorized users.

Vascular Dysfunction in Leukoaraiosis.

The pathogenesis of leukoaraiosis has long been debated. This work addresses a less well-studied mechanism, cerebrovascular reactivity, which could play a leading role in the pathogenesis of this disease. Our aim was to evaluate blood flow dysregulation and its relation to leukoaraiosis. Cerebrovascular reactivity, the change in the blood oxygen level-dependent 3T MR imaging signal in response to a consistently applied step change in the arterial partial pressure of carbon dioxide, was measured in white matter hyperintensities and their contralateral spatially homologous normal-appearing white matter in 75 older subjects (age range, 50-91 years; 40 men) with leukoaraiosis. Additional quantitative evaluation of regions of leukoaraiosis was performed by using diffusion (n = 75), quantitative T2 (n = 54), and DSC perfusion MRI metrics (n = 25). When we compared white matter hyperintensities with contralateral normal-appearing white matter, cerebrovascular reactivity was lower by a mean of 61.2% ± 22.6%, fractional anisotropy was lower by 44.9 % ± 6.9%, and CBF was lower by 10.9% ± 11.9%. T2 was higher by 61.7% ± 13.5%, mean diffusivity was higher by 59.0% ± 11.7%, time-to-maximum was higher by 44.4% ± 30.4%, and TTP was higher by 6.8% ± 5.8% (all P < .01). Cerebral blood volume was lower in white matter hyperintensities compared with contralateral normal-appearing white matter by 10.2% ± 15.0% (P = .03). Not only were resting blood flow metrics abnormal in leukoaraiosis but there is also evidence of reduced cerebrovascular reactivity in these areas. Studies have shown that reduced cerebrovascular reactivity is more sensitive than resting blood flow parameters for assessing vascular insufficiency. Future work is needed to examine the sensitivity of resting-versus-dynamic blood flow measures for investigating the pathogenesis of leukoaraiosis.

Interrogating the Functional Correlates of Collateralization in Patients with Intracranial Stenosis Using Multimodal Hemodynamic Imaging.

The importance of collateralization for maintaining adequate cerebral perfusion is increasingly recognized. However, measuring collateral flow noninvasively has proved elusive. The aim of this study was to assess correlations among baseline perfusion and arterial transit time artifacts, cerebrovascular reactivity, and the presence of collateral vessels on digital subtraction angiography. The relationship between the presence of collateral vessels on arterial spin-labeling MR imaging and DSA was compared with blood oxygen level-dependent MR imaging measures of hypercapnic cerebrovascular reactivity in patients with symptomatic intracranial stenosis (n = 18). DSA maps were reviewed by a neuroradiologist and assigned the following scores: 1, collaterals to the periphery of the ischemic site; 2, complete irrigation of the ischemic bed via collateral flow; and 3, normal antegrade flow. Arterial spin-labeling maps were scored according to the following: 0, low signal; 1, moderate signal with arterial transit artifacts; 2, high signal with arterial transit artifacts; and 3, normal signal. In regions with normal-to-high signal on arterial spin-labeling, collateral vessel presence on DSA strongly correlated with declines in cerebrovascular reactivity (as measured on blood oxygen level-dependent MR imaging, P < .001), most notably in patients with nonatherosclerotic disease. There was a trend toward increasing cerebrovascular reactivity with increases in the degree of collateralization on DSA (P = .082). Collateral vessels may have fundamentally different vasoreactivity properties from healthy vessels, a finding that is observed most prominently in nonatherosclerotic disease and, to a lesser extent, in atherosclerotic disease.