Blood Oxygen Level-dependent MRI Research Articles

Improving temporal resolution in fMRI using a 3D spiral acquisition and low rank plus sparse (L+S) reconstruction

Rapid whole-brain dynamic Magnetic Resonance Imaging (MRI) is of particular interest in Blood Oxygen Level Dependent (BOLD) functional MRI (fMRI). Faster acquisitions with higher temporal sampling of the BOLD time-course provide several advantages including increased sensitivity in detecting functional activation, the possibility of filtering out physiological noise for improving temporal SNR, and freezing out head motion. Generally, faster acquisitions require undersampling of the data which results in aliasing artifacts in the object domain. A recently developed low-rank (L) plus sparse (S) matrix decomposition model (L+S) is one of the methods that has been introduced to reconstruct images from undersampled dynamic MRI data. The L+S approach assumes that the dynamic MRI data, represented as a space-time matrix M, is a linear superposition of L and S components, where L represents highly spatially and temporally correlated elements, such as the image background, while S captures dynamic information that is sparse in an appropriate transform domain. This suggests that L+S might be suited for undersampled task or slow event-related fMRI acquisitions because the periodic nature of the BOLD signal is sparse in the temporal Fourier transform domain and slowly varying low-rank brain background signals, such as physiological noise and drift, will be predominantly low-rank. In this work, as a proof of concept, we exploit the L+S method for accelerating block-design fMRI using a 3D stack of spirals (SoS) acquisition where undersampling is performed in the kz−t domain. We examined the feasibility of the L+S method to accurately separate temporally correlated brain background information in the L component while capturing periodic BOLD signals in the S component. We present results acquired in control human volunteers at 3T for both retrospective and prospectively acquired fMRI data for a visual activation block-design task. We show that a SoS fMRI acquisition with an acceleration of four and L+S reconstruction can achieve a brain coverage of 40 slices at 2mm isotropic resolution and 64 x 64 matrix size every 500ms.

Investigating the Blood Oxygenation Level-Dependent Functional MRI Response to a Verbal Fluency Task in Early Stroke before and after Hemodynamic Scaling.

Blood oxygenation level-dependent (BOLD) functional MRI (fMRI) has been extensively used as a marker of brain dysfunction and subsequent recovery following stroke. However, growing evidence suggests that straightforward interpretation of BOLD fMRI changes with aging and disease is challenging. In this study, we investigated the effect of calibrating task fMRI data by applying a hemodynamic calibration method using the resting-state fluctuation amplitude (RSFA). Task fMRI responses were obtained during a covert verbal fluency task in a group of early stage stroke patients and matched healthy normal controls. Fifteen acute left hemisphere stroke patients (less than 7 days from stroke; aged 44-84 years, average ~64 years) and 21 healthy controls (aged 55-77 years, average ~61 years) were prospectively studied. All subjects completed a 3-min covert verbal fluency task, and a 10-min eyes-closed resting-state fMRI scan, from which the calibration factor (RSFA) was computed. A behavioral measure on the verbal fluency task was also collected outside the scanner. Whole brain activation volumes and region-of-interest (ROI)-wise percent signal change and activation volumes before and after calibration were computed. Between-group differences in whole brain activation volumes, although statistically significant before calibration failed to be significant after calibration. There were significant within-group differences before and after calibration with RSFA. Statistically significant between-group differences on ROI-wise measures before calibration also significantly reduced after calibration. Exploratory brain-behavior correlations revealed a similar pattern: significant correlations before calibration failed to survive after calibration. BOLD fMRI changes with aging and disease is confounded by changes in neurofunctional coupling leading to challenges in the straightforward interpretation of task fMRI results. Application of the hemodynamic calibration using the RSFA technique in the current study appeared to mitigate any differences between stroke and age-matched healthy controls. Our study indicates that estimating neural activity after applying hemodynamic scaling is important for studies of aging and for studies tracking post-stroke changes. We recommend that further investigation of hemodynamic calibration with RSFA in healthy subjects and in stroke in larger samples is necessary.

In Vivo Quantification of Placental Insufficiency by BOLD MRI: A Human Study

Fetal health is critically dependent on placental function, especially placental transport of oxygen from mother to fetus. When fetal growth is compromised, placental insufficiency must be distinguished from modest genetic growth potential. If placental insufficiency is present, the physician must trade off the risk of prolonged fetal exposure to placental insufficiency against the risks of preterm delivery. Current ultrasound methods to evaluate the placenta are indirect and insensitive. We propose to use Blood-Oxygenation-Level-Dependent (BOLD) MRI with maternal hyperoxia to quantitatively assess mismatch in placental function in seven monozygotic twin pairs naturally matched for genetic growth potential. In-utero BOLD MRI time series were acquired at 29 to 34 weeks gestational age. Maps of oxygen Time-To-Plateau (TTP) were obtained in the placentas by voxel-wise fitting of the time series. Fetal brain and liver volumes were measured based on structural MR images. After delivery, birth weights were obtained and placental pathological evaluations were performed. Mean placental TTP negatively correlated with fetal liver and brain volumes at the time of MRI as well as with birth weights. Mean placental TTP positively correlated with placental pathology. This study demonstrates the potential of BOLD MRI with maternal hyperoxia to quantify regional placental function in vivo.

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.

Bilateral arm training and cortical reorganization in cerebral infarction: A functional MRI study

Objective To study the effect of bilateral arm training on cortical reorganization in cerebral infarction patients using blood oxygen level-dependent functional MRI (BOLD-fMRI). Methods Fourteen cerebral infarction subjects with moderate to severe upper limb impairment participated in this randomized and single-blinded training study. Subjects in the bilateral arm training group (n=7) practiced bilateral symmetrical or opposite activities, while the control group (n=7) performed conventional, mainly unilateral, arm training. Those in both groups received fMRI scans before and after the training with passive elbow movement as the task in the imaging. Results Both groups had significant improvements in their average scores on the Fugl-Meyer upper extremity assessment and in their modified Barthel index scores after the treatment, and there were no significant differences between the two groups. Brain activation had increased in both groups after the treatment, especially in the bilateral training group. After the treatment, the first motor area (M1), the first somatosensory area and the supplementary motor area on both sides were activated in the bilateral training group. Moreover, for patients in the bilateral training group with injuries of moderate severity, the M1 of the opposite side tended to be activated, while for those more severely injured the same side had a tendency to be activated. Conclusion Convalescing subcortical infarction patients with moderate to severe upper limb impairment benefit from bilateral arm training in terms of motor activity and performing activities in daily life. It may be related to the normalization of inhibition between the hemispheres of the bilateral cerebral cortex and the reconnection of ipsilateral corticospinal pathways. Key words: Cerebral infarction; Bilateral arm training; Neural plasticity; Magnetic resonance imaging

Blood Oxygenation Level-Dependent Functional MRI of Early Evidences of Brain Plasticity after Hemodialysis Session by Helixone Membrane of Patients with Indices of Adrenal Deficiency

Background: Various alterations of hypothalamic-pituitary-adrenal axis function have been described in patients with chronic renal failure. Nevertheless, controversial evidences were stated about the association between adrenal function deficiency (AD) and hemodialysis (HD). Purpose: The goal of this paper was to estimate indirect indices of the adrenal gland dysfunction which is potentially influenced by oxidative stress (OS) that still generates brain plasticity and reorganization of the functional control.Methods: Two male patients undergoing HD by the synthetic Helixone membrane for more than 6 months at the HD Center of the University Hospital of Fez, Fez, Morocco, were recruited. They underwent identical assessment immediately before and after the full HD session; this consisted of a blood ionogram revealing rates of sodium and calcium, and brain blood oxygenation level-dependent functional MRI (BOLD-fMRI) using a motor paradigm in block design. Results: The blood ionogram revealed hypercalcemia and hyponatremia in both patients. Both biological assessment and BOLD-fMRI study results revealed a high level of OS that induced activation of a significantly large brain volume area suggesting the occurrence of possible brain plasticity and functional control reorganization induced by free radicals and enhanced by AD. Conclusion: The occurrence of brain plasticity and functional control reorganization was demonstrated in both patients studied who were undergoing HD by BOLD-fMRI with a notable sensitivity; this plasticity is induced by elevated OS occasioned by HD technique itself and probably amplified by AD. Similar results were found in a previous study performed on the same patients undergoing HD by a polysulfone membrane.

Mapping of the brain hemodynamic responses to sensorimotor stimulation in a rodent model: A BOLD fMRI study.

Blood Oxygenation Level Dependent functional MRI (BOLD fMRI) during electrical paw stimulation has been widely used in studies aimed at the understanding of the somatosensory network in rats. However, despite the well-established anatomical connections between cortical and subcortical structures of the sensorimotor system, most of these functional studies have been concentrated on the cortical effects of sensory electrical stimulation. BOLD fMRI study of the integration of a sensorimotor input across the sensorimotor network requires an appropriate methodology to elicit functional activation in cortical and subcortical areas owing to the regional differences in both neuronal and vascular architectures between these brain regions. Here, using a combination of low level anesthesia, long pulse duration of the electrical stimulation along with improved spatial and temporal signal to noise ratios, we provide a functional description of the main cortical and subcortical structures of the sensorimotor rat brain. With this calibrated fMRI protocol, unilateral non-noxious sensorimotor electrical hindpaw stimulation resulted in robust positive activations in the contralateral sensorimotor cortex and bilaterally in the sensorimotor thalamus nuclei, whereas negative activations were observed bilaterally in the dorsolateral caudate-putamen. These results demonstrate that, once the experimental setup allowing necessary spatial and temporal signal to noise ratios is reached, hemodynamic changes related to neuronal activity, as preserved by the combination of a soft anesthesia with a soft muscle relaxation, can be measured within the sensorimotor network. Moreover, the observed responses suggest that increasing pulse duration of the electrical stimulus adds a proprioceptive component to the sensory input that activates sensorimotor network in the brain, and that these activation patterns are similar to those induced by digits paw’s movements. These findings may find application in fMRI studies of sensorimotor disorders within cortico-basal network in rodents.

Water diffusion closely reveals neural activity status in rat brain loci affected by anesthesia.

Diffusion functional MRI (DfMRI) reveals neuronal activation even when neurovascular coupling is abolished, contrary to blood oxygenation level—dependent (BOLD) functional MRI (fMRI). Here, we show that the water apparent diffusion coefficient (ADC) derived from DfMRI increased in specific rat brain regions under anesthetic conditions, reflecting the decreased neuronal activity observed with local field potentials (LFPs), especially in regions involved in wakefulness. In contrast, BOLD signals showed nonspecific changes, reflecting systemic effects of the anesthesia on overall brain hemodynamics status. Electrical stimulation of the central medial thalamus nucleus (CM) exhibiting this anesthesia-induced ADC increase led the animals to transiently wake up. Infusion in the CM of furosemide, a specific neuronal swelling blocker, led the ADC to increase further locally, although LFP activity remained unchanged, and increased the current threshold awakening the animals under CM electrical stimulation. Oppositely, induction of cell swelling in the CM through infusion of a hypotonic solution (−80 milliosmole [mOsm] artificial cerebrospinal fluid [aCSF]) led to a local ADC decrease and a lower current threshold to wake up the animals. Strikingly, the local ADC changes produced by blocking or enhancing cell swelling in the CM were also mirrored remotely in areas functionally connected to the CM, such as the cingulate and somatosensory cortex. Together, those results strongly suggest that neuronal swelling is a significant mechanism underlying DfMRI.

Resting-State BOLD MRI for Perfusion and Ischemia.

Advanced imaging techniques including computed tomography (CT) angiography, CT perfusion, magnetic resonance (MR) angiography, MR with diffusion- and perfusion-weighted imaging, and, more recently, resting-state BOLD (Blood Oxygen Level Dependent) functional MRI (rs-fMRI) are increasingly used to evaluate patients with acute ischemic stroke. Advanced imaging allows for identification of patients with ischemic stroke and determination of the size of infarcted and potentially salvageable tissue, all of which yield crucial information for proper stroke management. The addition of rs-fMRI for ischemia adds information at the microvascular level, thereby improving the understanding of pathophysiologic mechanisms of impaired cerebral perfusion and tissue oxygenation beyond the known concepts at the macrovascular level. As such, it may further delineate functional and dysfunctional neuronal networks, guide stroke interventions, and improve prognosis and monitoring of patient outcomes.

Tumor physiological changes during hypofractionated stereotactic body radiation therapy assessed using multi-parametric magnetic resonance imaging.

Radiation therapy is a primary treatment for non-resectable lung cancer and hypoxia is thought to influence tumor response. Hypoxia is expected to be particularly relevant to the evolving new radiation treatment scheme of hypofractionated stereotactic body radiation therapy (SBRT). As such, we sought to develop non-invasive tools to assess tumor pathophysiology and response to irradiation. We applied blood oxygen level dependent (BOLD) and tissue oxygen level dependent (TOLD) MRI, together with dynamic contrast enhanced (DCE) MRI to explore the longitudinal effects of SBRT on tumor oxygenation and vascular perfusion using A549 human lung cancer xenografts in a subcutaneous rat model. Intra-tumor heterogeneity was seen on multi-parametric maps, especially in BOLD, T2* and DCE. At baseline, most tumors showed a positive BOLD signal response (%ΔSI) and increased T2* in response to oxygen breathing challenge, indicating increased vascular oxygenation. Control tumors showed similar response 24 hours and 1 week later. Twenty-four hours after a single dose of 12 Gy, the irradiated tumors showed a significantly decreased T2* (-2.9±4.2 ms) and further decrease was observed (-4.0±6.0 ms) after 1 week, suggesting impaired vascular oxygenation. DCE revealed tumor heterogeneity, but showed minimal changes following irradiation. Rats were cured of the primary tumors by 3×12 Gy, providing long term survival, though with ultimate metastatic recurrence.

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.

Studying brain microstructure with magnetic susceptibility contrast at high-field

A rapidly developing application of high field MRI is the study of brain anatomy and function with contrast based on the magnetic susceptibility of tissues. To study the subtle variations in susceptibility contrast between tissues and with changes in brain activity, dedicated scan techniques such as susceptibility-weighted MRI and blood-oxygen level dependent functional MRI have been developed. Particularly strong susceptibility contrast has been observed with systems that operate at 7T and above, and their recent widespread use has led to an improved understanding of contributing sources and mechanisms. To interpret magnetic susceptibility contrast, analysis approaches have been developed with the goal of extracting measures that report on local tissue magnetic susceptibility, a physical quantity that, under certain conditions, allows estimation of blood oxygenation, local tissue iron content, and quantification of its changes with disease.Interestingly, high field studies have also brought to light that not only the makeup of tissues affects MRI susceptibility contrast, but that also a tissue's sub-voxel structure at scales all the way down to the molecular level plays an important role as well. In this review, various ways will be discussed by which sub-voxel structure can affect the MRI signal in general, and magnetic susceptibility in particular, sometimes in a complex fashion. In the light of this complexity, it appears likely that accurate, brain-wide quantification of iron will require the combination of multiple contrasts that may include diffusion and magnetization transfer information with susceptibility-weighted contrast. On the other hand, this complexity also offers opportunities to use magnetic susceptibility contrast to inform about specific microstructural aspects of brain tissue. Details and several examples will be presented in this review.

Spatiotemporal alignment of in utero BOLD-MRI series.

To present a method for spatiotemporal alignment of in-utero magnetic resonance imaging (MRI) time series acquired during maternal hyperoxia for enabling improved quantitative tracking of blood oxygen level-dependent (BOLD) signal changes that characterize oxygen transport through the placenta to fetal organs. The proposed pipeline for spatiotemporal alignment of images acquired with a single-shot gradient echo echo-planar imaging includes 1) signal nonuniformity correction, 2) intravolume motion correction based on nonrigid registration, 3) correction of motion and nonrigid deformations across volumes, and 4) detection of the outlier volumes to be discarded from subsequent analysis. BOLD MRI time series collected from 10 pregnant women during 3T scans were analyzed using this pipeline. To assess pipeline performance, signal fluctuations between consecutive timepoints were examined. In addition, volume overlap and distance between manual region of interest (ROI) delineations in a subset of frames and the delineations obtained through propagation of the ROIs from the reference frame were used to quantify alignment accuracy. A previously demonstrated rigid registration approach was used for comparison. The proposed pipeline improved anatomical alignment of placenta and fetal organs over the state-of-the-art rigid motion correction methods. In particular, unexpected temporal signal fluctuations during the first normoxia period were significantly decreased (P < 0.01) and volume overlap and distance between region boundaries measures were significantly improved (P < 0.01). The proposed approach to align MRI time series enables more accurate quantitative studies of placental function by improving spatiotemporal alignment across placenta and fetal organs. 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:403-412.

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.

Advances in MR angiography with 7T MRI: From microvascular imaging to functional angiography

Over the past few decades, vascular flow-dependent imaging techniques have proven to be effective for the visualization of large vessel diseases. However, these approaches are unlikely to be efficacious for small vessels because the affected small vessels cannot always be visualized directly, owing to a lack of detection sensitivity. Recently, many researchers have introduced state-of-the-art imaging techniques to visualize cerebral microvessels using ultra-high-field (UHF) magnetic resonance angiography (MRA). They have demonstrated the superiority of UHF MRA, especially for visualization of the microvasculature compared with clinical MRA images using 1.5T or 3T magnetic resonance imaging (MRI). Thus, UHF MRA may become an important investigative tool for research, facilitating examinations of vascular mechanisms for small vessel diseases and contributing to the early detection of cerebrovascular diseases in clinics. Furthermore, new imaging methods for visualizing vascular dynamics or flow effects may help investigate brain functions, especially in conjunction with blood oxygenation level-dependent contrast functional MRI modalities, as well as situations in which small vessel abnormalities are clinically important. The present article reviews recent technological advances in UHF MRA, especially 7T MRA, and discusses the potential benefits and future directions of UHF MRA.

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.

Detection of Renal Hypoxia in Lupus Nephritis Using Blood Oxygen Level-Dependent MR Imaging: A Multiple Correspondence Analysis

Background/Aims: Nephrologists have pursued ideal, dynamic and noninvasive methods for assessing renal function and disease progression. Blood oxygen level dependent (BOLD) imaging is a useful technique for assessing renal disease. This current study was performed to explore the correlation between the hypoxia iconographical index and renal pathological features in lupus nephritis. Methods: Adult patients with lupus nephritis (LN) and healthy volunteers were recruited for this study. Renal biopsy tissues were characterized based on the LNISN/RPS 2003 classification. R2* values of functional magnetic resonance parameters were acquired using the BOLD technique. The data characteristics of R2* values of different pathological patterns were calculated. Multiple correspondence analysis (MCA) was performed to explore the correlation between R2* values and clinical or pathological features. Results: A total of twenty-three patients and eighteen healthy volunteers were examined with BOLD MRI. Renal pathological patterns included five class III (including 3 class III+V), eight class IV (including 4 class IV+V) and five class IV. The mean renal R2* values in LN patients were higher than those in healthy volunteers. R2* values in class V patients were higher than those in class IV and class III. The MCA showed that higher R2* values were associated with pathological features in class V patients. Conclusions: The extent of renal hypoxia in patients with LN was more serious compared with the healthy volunteers. Differentiated mechanisms of renal oxygenation are possibly involved in proliferative and non-proliferative LN patients. R2* values may be linked with multiple clinical and pathological indexes.

Compensatory changes in energy balance during dapagliflozin treatment in type 2 diabetes mellitus: a randomised double-blind, placebo-controlled, cross-over trial (ENERGIZE)—study protocol

IntroductionSodium glucose cotransporter 2 (SGLT2) inhibitors are effective blood-glucose-lowering medications with beneficial effects on body weight in patients with type 2 diabetes mellitus (T2DM). However, observed weight loss is less...

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.