Blood Oxygenation Level Dependent Effect Research Articles

Neural responses to facial emotions and subsequent clinical outcomes in difficult-to-treat depression.

Amygdala and dorsal anterior cingulate cortex responses to facial emotions have shown promise in predicting treatment response in medication-free major depressive disorder (MDD). Here, we examined their role in the pathophysiology of clinical outcomes in more chronic, difficult-to-treat forms of MDD. Forty-five people with current MDD who had not responded to ⩾2 serotonergic antidepressants (n = 42, meeting pre-defined fMRI minimum quality thresholds) were enrolled and followed up over four months of standard primary care. Prior to medication review, subliminal facial emotion fMRI was used to extract blood-oxygen level-dependent effects for sad v. happy faces from two pre-registered a priori defined regions: bilateral amygdala and dorsal/pregenual anterior cingulate cortex. Clinical outcome was the percentage change on the self-reported Quick Inventory of Depressive Symptomatology (16-item). We corroborated our pre-registered hypothesis (NCT04342299) that lower bilateral amygdala activation for sad v. happy faces predicted favorable clinical outcomes (rs[38] = 0.40, p = 0.01). In contrast, there was no effect for dorsal/pregenual anterior cingulate cortex activation (rs[38] = 0.18, p = 0.29), nor when using voxel-based whole-brain analyses (voxel-based Family-Wise Error-corrected p < 0.05). Predictive effects were mainly driven by the right amygdala whose response to happy faces was reduced in patients with higher anxiety levels. We confirmed the prediction that a lower amygdala response to negative v. positive facial expressions might be an adaptive neural signature, which predicts subsequent symptom improvement also in difficult-to-treat MDD. Anxiety reduced adaptive amygdala responses.

Changes in white matter functional networks across late adulthood.

The aging brain is characterized by decreases in not only neuronal density but also reductions in myelinated white matter (WM) fibers that provide the essential foundation for communication between cortical regions. Age-related degeneration of WM has been previously characterized by histopathology as well as T2 FLAIR and diffusion MRI. Recent studies have consistently shown that BOLD (blood oxygenation level dependent) effects in WM are robustly detectable, are modulated by neural activities, and thus represent a complementary window into the functional organization of the brain. However, there have been no previous systematic studies of whether or how WM BOLD signals vary with normal aging. We therefore performed a comprehensive quantification of WM BOLD signals across scales to evaluate their potential as indicators of functional changes that arise with aging. By using spatial independent component analysis (ICA) of BOLD signals acquired in a resting state, WM voxels were grouped into spatially distinct functional units. The functional connectivities (FCs) within and among those units were measured and their relationships with aging were assessed. On a larger spatial scale, a graph was reconstructed based on the pair-wise connectivities among units, modeling the WM as a complex network and producing a set of graph-theoretical metrics. The spectral powers that reflect the intensities of BOLD signals were found to be significantly affected by aging across more than half of the WM units. The functional connectivities (FCs) within and among those units were found to decrease significantly with aging. We observed a widespread reduction of graph-theoretical metrics, suggesting a decrease in the ability to exchange information between remote WM regions with aging. Our findings converge to support the notion that WM BOLD signals in specific regions, and their interactions with other regions, have the potential to serve as imaging markers of aging.

Spectral peak areas do not vary according to spectral averaging scheme used in functional MRS experiments at 3 T with interleaved visual stimulation

Abstract Brain response to visual stimulation can be probed quantitatively using functional magnetic resonance spectroscopy (fMRS), which relies on the blood oxygenation level dependent (BOLD) contrast mechanism. BOLD effect in fMRS is associated with changes in the areas, widths, and heights of the MR spectra. This study investigated the effect of spectral averaging scheme (NEX value) on BOLD changes in the spectra. Using a visual stimulus at 8 Hz in single and interleaved stimulation paradigms, the BOLD effects in spectra acquired from the occipital brain region of three healthy volunteers (mean age ± SD = 32.7 ± 3.5 years) were compared for two fMRS data sets acquired with two NEX values (“2” and “8”) available on a 3 T MR scanner. BOLD signal changes were estimated as percentage changes in spectral areas, heights, and widths of six cerebral metabolites and water using the SAGE software package (version 7). There was a general trend of lower BOLD effects with NEX = 8 in both stimulation paradigms. In the single stimulation paradigm, NEX = 8 was associated with significantly lower N-acetyl aspartate (NAA) spectral height (p = 0.03), creatine (p = 0.04) and choline (p = 0.02) spectral widths, and NAA (p = 0.03), water (p &lt; 0.01), and glutamate (p = 0.02) spectral areas. In the interleaved stimulation paradigm, NEX = 8 was associated with significantly lower glutamate spectral height (p = 0.02), water (p = 0.03), and glutamine (p = 0.03) spectral widths, but there was no significant difference in all spectral areas between the two NEX values. Even though the two NEX values offered some differences in observable BOLD effects, their spectral areas were not significantly different in the interleaved visual stimulation experiments.

Virtual reality-induced motor function of the upper extremity and brain activation in stroke: study protocol for a randomized controlled trial.

The benefits of virtual reality (VR)-based rehabilitation were reported in patients after stroke, but there is insufficient evidence about how VR promotes brain activation in the central nervous system. Hence, we designed this study to explore the effects of VR-based intervention on upper extremity motor function and associated brain activation in stroke patients. In this single-center, randomized, parallel-group clinical trial with a blinded assessment of outcomes, a total of 78 stroke patients will be assigned randomly to either the VR group or the control group. All stroke patients who have upper extremity motor deficits will be tested with functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and clinical evaluation. Clinical assessment and fMRI will be performed three times on each subject. The primary outcome is the change in performance on the Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE). Secondary outcomes are functional independence measure (FIM), Barthel Index (BI), grip strength, and changes in the blood oxygenation level-dependent (BOLD) effect in the ipsilesional and contralesional primary motor cortex (M1) on the left and right hemispheres assessed with resting-state fMRI (rs-fMRI), task-state fMRI (ts-fMRI), and changes in EEG at the baseline and weeks 4 and 8. This study aims to provide high-quality evidence for the relationship between upper extremity motor function and brain activation in stroke. In addition, this is the first multimodal neuroimaging study that explores the evidence for neuroplasticity and associated upper motor function recovery after VR in stroke patients. Chinese Clinical Trial Registry, identifier: ChiCTR2200063425.

Neuronal nitric oxide synthase positive neurons in the human corpus callosum: a possible link with the callosal blood-oxygen-level dependent (BOLD) effect.

Brain functions have been investigated in the past decades via the blood-oxygen-level dependent (BOLD) effect using functional magnetic resonance imaging. One hypothesis explaining the BOLD effect involves the Nitric Oxide (NO) gaseous neurotransmitter, possibly released also by cells in the corpus callosum (CC). The eventual presence of NO releasing neurons and/or glial cells in the CC can be assessed by immunohistochemistry. Serial sections both from paraffin-embedded and frozen samples of CC obtained from adult human brains autopsy were studied with immunohistochemistry and immunofluorescence analysis, using an antibody against the neuronal isoform of Nitric Oxide Synthase (nNOS), the enzyme synthetizing the NO. The staining revealed the presence of many nNOS-immunopositive cells in the CC, shown to be neurons with immunofluorescence. Neuronal NOS-positive neurons presented different morphologies, were more numerous 4mm apart from the midline, and displayed a peak in the body of the CC. In some cases, they were located at the upper boundary of the CC, more densely packed in the proximity of the callosal arterioles. The significant presence of nNOS-immunopositive neurons within the commissure suggests their probable role in the CC neurovascular regulation in the adult brain and could explain the BOLD effect detected in human CC.

Review of the Research Progress of Human Brain Oxygen Extraction Fraction by Magnetic Resonance Imaging.

In recent years, the incidence of cerebrovascular diseases (CVD) is increasing, which seriously endangers human health. The study on hemodynamics of cerebrovascular disease can help us to understand, prevent, and treat the disease. As one of the important parameters of human cerebral hemodynamics and tissue metabolism, OEF (oxygen extraction fraction) is of great value in central nervous system diseases. The use of BOLD (blood oxygen level dependent) effect offers the possibility to study cerebral hemodynamic and metabolic characteristics by MRI (magnetic resonance imaging) measurements. Therefore, this paper reviews the hemodynamic parameters of brain tissue, discusses the principles and methods of quantitative BOLD-based MRI measurements of OEF, and discusses the advantages and disadvantages of each method.

Alterations in brain activation patterns in women with functional defecatory disorder: A novel fMRI rectal balloon expulsion study.

Functional defecatory disorders (FDD) are common among women. Despite the extensive research on peripheral mechanisms involved in FDD, the central-neural contribution to its pathophysiology remains poorly understood. We aimed to delineate specific supra-spinal regions involved in defecation and examine whether their activity, as measured by blood-oxygen-level-dependent (BOLD) signals, is different in FDD. We performed functional MRI (fMRI) with concurrent rectal manometry in 15 controls and 18 females with ROME III diagnosis of FDD. A block design was used and brain activation maps based on BOLD effect employing the generalized linear model were calculated for each subject. Statistical significance between groups was assessed by a Student t-test with cluster-based multiple comparisons correction (corrected p<0.01). Simulated defecation was associated with activation of regions of primary and supplementary motor (SMA) and somatosensory cortices, homeostatic afferent (thalamus, mid-cingulate cortex, and insula), and emotional arousal networks (hippocampus and prefrontal cortex), occipital and cerebellum along with deactivation of right anterior cingulate cortex (ACC) in controls. Women with FDD had fewer regions engaged in defecation and BOLD activation was much decreased is areas related to executive-cognitive function (insula, parietal, and prefrontal cortices). Patients unlike controls showed activation in right ACC and otherwise had similar brain activation patterns during anal squeeze. Our results provide evidence that distinct differences exist in supra-spinal control of defecation in key regions of motivational-affective regulation and executive-cognitive function, in patients with FDD as compared to controls.

Non-Linear Frequency Dependence of Neurovascular Coupling in the Cerebellar Cortex Implies Vasodilation-Vasoconstriction Competition.

Neurovascular coupling (NVC) is the process associating local cerebral blood flow (CBF) to neuronal activity (NA). Although NVC provides the basis for the blood oxygen level dependent (BOLD) effect used in functional MRI (fMRI), the relationship between NVC and NA is still unclear. Since recent studies reported cerebellar non-linearities in BOLD signals during motor tasks execution, we investigated the NVC/NA relationship using a range of input frequencies in acute mouse cerebellar slices of vermis and hemisphere. The capillary diameter increased in response to mossy fiber activation in the 6–300 Hz range, with a marked inflection around 50 Hz (vermis) and 100 Hz (hemisphere). The corresponding NA was recorded using high-density multi-electrode arrays and correlated to capillary dynamics through a computational model dissecting the main components of granular layer activity. Here, NVC is known to involve a balance between the NMDAR-NO pathway driving vasodilation and the mGluRs-20HETE pathway driving vasoconstriction. Simulations showed that the NMDAR-mediated component of NA was sufficient to explain the time course of the capillary dilation but not its non-linear frequency dependence, suggesting that the mGluRs-20HETE pathway plays a role at intermediate frequencies. These parallel control pathways imply a vasodilation–vasoconstriction competition hypothesis that could adapt local hemodynamics at the microscale bearing implications for fMRI signals interpretation.

The behaviour of T2* and T2 relaxation time in extrinsic foot muscles under continuous exercise: A prospective analysis during extended running.

ObjectivesPrevious studies on T2* and T2 relaxation time of the muscles have shown that exercise leads to an initial increase, presumably representing different intramuscular physiological processes such as increase in intracellular volume or blood oxygenation level dependent effects with a subsequent decrease after cessation of exercise. Their behaviour during prolonged exercise is still unknown but could provide important information for example about the pathophysiology of overuse injuries. The aim of this study was to evaluate the temporal course of T2* and T2 relaxation time in extrinsic foot muscles during prolonged exercise and determine the optimal mapping technique.MethodsTen participants had to run a total of 75 minutes at their individual highest possible running speed, with interleaved MR scans at baseline and after 2.5, 5, 10, 15, 45 and 75 minutes. The examined extrinsic foot muscles were manually segmented, and relaxation time were analysed regarding its respective time course.ResultsT2* and T2 relaxation time showed an initial increase, followed by a plateau phase between 2.5 and 15 minutes and a subsequent decrease. For the T2* relaxation time, this pattern was also apparent, but less pronounced, with more muscles not reaching significance (p<0.05) when comparing different time points.ConclusionsT2* and T2 relaxation time showed a similar course with an initial rapid increase, a plateau phase and a subsequent decrease under prolonged exercise. Moderate but long-term muscular activity appears to have a weaker effect on T2* relaxation time than on T2 relaxation time.

Effects of Repetitive Peripheral Sensory Stimulation in the Subacute and Chronic Phases After Stroke: Study Protocol for a Pilot Randomized Trial.

BackgroundRepetitive peripheral nerve sensory stimulation (RPSS) is a potential add-on intervention to motor training for rehabilitation of upper limb paresis after stroke. Benefits of RPSS were reported in subjects in the chronic phase after stroke, but there is limited information about the effects of this intervention within the 1st weeks or months. The primary goal of this study is to compare, in a head-to-head proof-of-principle study, the impact of a single session of suprasensory vs. subsensory RPSS on the upper limb motor performance and learning in subjects at different phases after stroke subacute and chronic phases and mild upper limb motor impairments after stroke. In addition, we examine the effects of RPSS on brain perfusion, functional imaging activation, and γ-aminobutyric acid (GABA) levels. Subjects with mild upper limb motor impairments will be tested with MRI and clinical assessment either at an early (7 days to 3 months post-stroke) or at a chronic (>6 months) stage after stroke.MethodsIn this multicenter, randomized, parallel-group, proof-of-principle clinical trial with blinded assessment of outcomes, we compare the effects of one session of suprasensory or subsensory RPSS in patients with ischemic or hemorrhagic stroke and upper limb paresis. Clinical assessment and MRI will be performed only once in each subject (either at an early or at a chronic stage). The primary outcome is the change in performance in the Jebsen–Taylor test. Secondary outcomes: hand strength, cerebral blood flow assessed with arterial spin labeling, changes in the blood oxygenation level-dependent (BOLD) effect in ipsilesional and contralesional primary motor cortex (M1) on the left and the right hemispheres assessed with functional MRI (fMRI) during a finger-tapping task performed with the paretic hand, and changes in GABA levels in ipsilesional and contralesional M1 evaluated with spectroscopy. The changes in outcomes will be compared in four groups: suprasensory, early; subsensory, early; suprasensory, chronic; and subsensory, chronic.DiscussionThe results of this study are relevant to inform future clinical trials to tailor RPSS to patients more likely to benefit from this intervention.Trial RegistrationNCT03956407.

Amygdalar functional connectivity during resting and evoked pain in youth with functional abdominal pain disorders.

Pediatric functional abdominal pain disorders (FAPD) are highly prevalent, difficult to diagnose, and challenging to treat. The brain systems supporting FAPD remain poorly understood. This investigation examined the neuromechanisms of FAPD during a well-tolerated visceral pain induction task, the water load symptom provocation task (WL-SPT). Youth between the ages of 11 and 17 years participated. Functional connectivity (FC) was examined through the blood oxygenation level-dependent effect using the left and right amygdala (AMY) as seed regions. Relationships of the time courses within these seeds with voxels across the whole brain were evaluated. Arterial spin labeling was used to assess regional brain activation by examining cerebral blood flow. Increased FC between the left AMY with regions associated with nociceptive processing (eg, thalamus) and right AMY FC changes with areas associated with cognitive functioning (dorsolateral prefrontal cortex) and the default mode network (DMN; parietal lobe) were observed in youth with FAPD after the WL-SPT. These changes were related to changes in pain unpleasantness. Amygdala FC changes post-WL-SPT were also related to changes in pain intensity. Amygdala FC with the DMN in youth with FAPD also differed from healthy controls. Global cerebral blood flow changes were also noted between FAPD and healthy controls, but no significant differences in grey matter were detected either between groups or during the WL-SPT in youth with FAPD. Findings confirm youth with FAPD undergo changes in brain systems that could support the development of biomarkers to enhance understanding of the mechanisms of pain and treatment response.

3 T: the good, the bad and the ugly.

It is around 20 years since the first commercial 3 T MRI systems became available. The theoretical promise of twice the signal-to-noise ratio of a 1.5 T system together with a greater sensitivity to magnetic susceptibility-related contrast mechanisms, such as the blood oxygen level dependent effect that is the basis for functional MRI, drove the initial market in neuroradiology. However, the limitations of the increased field strength soon became apparent, including the increased radiofrequency power deposition, tissue-dependent changes in relaxation times, increased artifacts, and greater safety concerns. Many of these issues are dependent upon MR physics and workarounds have had to be developed to try and mitigate their effects. This article reviews the underlying principles of the good, the bad and the ugly aspects of 3 T, discusses some of the methods used to improve image quality and explains the remaining challenges and concerns.

Distinct Neurophysiological Correlates of the fMRI BOLD Signal in the Hippocampus and Neocortex.

Functional magnetic resonance imaging (fMRI) is among the foremost methods for mapping human brain function but provides only an indirect measure of underlying neural activity. Recent findings suggest that the neurophysiological correlates of the fMRI blood oxygenation level-dependent (BOLD) signal might be regionally specific. We examined the neurophysiological correlates of the fMRI BOLD signal in the hippocampus and neocortex, where differences in neural architecture might result in a different relationship between the respective signals. Fifteen human neurosurgical patients (10 female, 5 male) implanted with depth electrodes performed a verbal free recall task while electrophysiological activity was recorded simultaneously from hippocampal and neocortical sites. The same patients subsequently performed a similar version of the task during a later fMRI session. Subsequent memory effects (SMEs) were computed for both imaging modalities as patterns of encoding-related brain activity predictive of later free recall. Linear mixed-effects modeling revealed that the relationship between BOLD and gamma-band SMEs was moderated by the lobar location of the recording site. BOLD and high gamma (70-150 Hz) SMEs positively covaried across much of the neocortex. This relationship was reversed in the hippocampus, where a negative correlation between BOLD and high gamma SMEs was evident. We also observed a negative relationship between BOLD and low gamma (30-70 Hz) SMEs in the medial temporal lobe more broadly. These results suggest that the neurophysiological correlates of the BOLD signal in the hippocampus differ from those observed in the neocortex.SIGNIFICANCE STATEMENT The BOLD signal forms the basis of fMRI but provides only an indirect measure of neural activity. Task-related modulation of BOLD signals are typically equated with changes in gamma-band activity; however, relevant empirical evidence comes largely from the neocortex. We examined neurophysiological correlates of the BOLD signal in the hippocampus, where the differing neural architecture might result in a different relationship between the respective signals. We identified a positive relationship between encoding-related changes in BOLD and gamma-band activity in the frontal and parietal cortices. This effect was reversed in the hippocampus, where BOLD and gamma-band effects negatively covaried. These results suggest regional variability in the transfer function between neural activity and the BOLD signal in the hippocampus and neocortex.

The blood oxygen level dependent (BOLD) effect of in-vitro myoglobin and hemoglobin

The presence of deoxygenated hemoglobin (Hb) results in a drop in T2 and T2* in magnetic resonance imaging (MRI), known as the blood oxygenation level-dependent (BOLD-)effect. The purpose of this study was to investigate if deoxygenated myoglobin (Mb) exerts a BOLD-like effect. Equine Met-Mb powder was dissolved and converted to oxygenated Mb. T1, T2, T2*-maps and BOLD-bSSFP images at 3Tesla were used to scan 22 Mb samples and 12 Hb samples at room air, deoxygenation, reoxygenation and after chemical reduction. In Mb, T2 and T2* mapping showed a significant decrease after deoxygenation (− 25% and − 12%, p < 0.01), increase after subsequent reoxygenation (+ 17% and 0% vs. room air, p < 0.01), and finally a decrease in T2 after chemical reduction (− 28%, p < 0.01). An opposite trend was observed with T1 for each stage, while chemical reduction reduced BOLD-bSSFP signal (− 3%, p < 0.01). Similar deflections were seen at oxygenation changes in Hb. The T1 changes suggests that the oxygen content has been changed in the specimen. The shortening of transverse relaxation times in T2 and T2*-mapping after deoxygenation in Mb specimens are highly indicative of a BOLD-like effect.

Simultaneous Measurement of the BOLD Effect and Metabolic Changes in Response to Visual Stimulation Using the MEGA-PRESS Sequence at 3 T.

The blood oxygen level dependent (BOLD) effect that provides the contrast in functional magnetic resonance imaging (fMRI) has been demonstrated to affect the linewidth of spectral peaks as measured with magnetic resonance spectroscopy (MRS) and through this, may be used as an indirect measure of cerebral blood flow related to neural activity. By acquiring MR-spectra interleaved with frames without water suppression, it may be possible to image the BOLD effect and associated metabolic changes simultaneously through changes in the linewidth of the unsuppressed water peak. The purpose of this study was to implement this approach with the MEGA-PRESS sequence, widely considered to be the standard sequence for quantitative measurement of GABA at field strengths of 3 T and lower, to observe how changes in both glutamate (measured as Glx) and GABA levels may relate to changes due to the BOLD effect. MR-spectra and fMRI were acquired from the occipital cortex (OCC) of 20 healthy participants whilst undergoing intrascanner visual stimulation in the form of a red and black radial checkerboard, alternating at 8 Hz, in 90 s blocks comprising 30 s of visual stimulation followed by 60 s of rest. Results show very strong agreement between the changes in the linewidth of the unsuppressed water signal and the canonical haemodynamic response function as well as a strong, negative, but not statistically significant, correlation with the Glx signal as measured from the OFF spectra in MEGA-PRESS pairs. Findings from this experiment suggest that the unsuppressed water signal provides a reliable measure of the BOLD effect and that correlations with associated changes in GABA and Glx levels may also be measured. However, discrepancies between metabolite levels as measured from the difference and OFF spectra raise questions regarding the reliability of the respective methods.

Research on BOLD-fMRI Data Denoising Based on Bayesian Estimation and Adaptive Wavelet Threshold.

The acquisition of functional magnetic resonance imaging (fMRI) images of blood oxygen level-dependent (BOLD) effect and the signals to be analyzed is based on weak changes in the magnetic field caused by small changes in blood oxygen physiological levels, which are weak signals and complex in noise. In order to model and analyze the pathological and hemodynamic parameters of BOLD-fMRI images effectively, it is urgent to use effective signal analysis techniques to reduce the interference of noise and artifacts. In this paper, the noise characteristics of functional magnetic resonance imaging and the traditional signal denoising methods are analyzed. The Bayesian decision criterion takes into account the probability of the total occurrence of all kinds of references and the loss caused by misjudgment and has strong discriminability. So, an improved adaptive wavelet threshold denoising method based on Bayesian estimation is proposed. By using the correlation characteristics of multiscale wavelet coefficients, the corresponding wavelet components of useful signals and noises are processed differently; while retaining useful frequency information, the noise is weakened to the greatest extent. The new adaptive threshold wavelet denoising method based on Bayesian estimation is applied to the actual experiment, and the results of OEF (oxygen extraction fraction) are optimized. A series of simulation experiments are carried out to verify the effectiveness of the proposed method.

Magnetic resonance imaging simulation with spin-lock preparations to detect tiny oscillatory magnetic fields

Spin-lock preparation was studied to detect tiny oscillatory magnetic fields such as a neural magnetic field without the blood oxygen level-dependent effect. This approach is a direct measurement and independent of static magnetic field strength. Accordingly, it is anticipated as a feasible functional magnetic resonance imaging (fMRI) in low and ultra-low-field MRI. Several reports have been published on spin-lock preparation but reports on imaging simulation are rare. Research in this area can assist in investigating magnetic resonance signal changes and, accordingly, can help to develop new spin-lock methods. In this study, we propose an imaging simulation method with an analytical solution using the Bloch equation. To demonstrate the feasibility of our proposed method, we compared simulated images with experimental results in which the number of sub-voxels and the amplitude and phase of the target oscillatory magnetic fields varied. In addition, we also applied graphics processing unit parallel computing and investigated the feasibility of avoiding an impracticable calculation time by doing so.

Experimental Protocol for MRI Mapping of the Blood Oxygenation-Sensitive Parameters T2* and T2 in the Kidney.

Renal hypoxia is generally accepted as a key pathophysiologic event in acute kidney injury of various origins, and has also been suggested to play a role in the development of chronic kidney disease. Here we describe a step-by-step experimental protocol for indirect monitoring of renal blood oxygenation in rodents via the deoxyhemoglobin sensitive MR parameters T2* and T2-a contrast mechanism known as the blood oxygenation level dependent (BOLD) effect. Since an absolute quantification of renal oxygenation from T2*/T2 remains challenging, the effects of controlled and standardized variations in the fraction of inspired oxygen are used for bench marking. This MRI method may be useful for investigating renal blood oxygenation of small rodents in vivo under various experimental (patho)physiological conditions.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This experimental protocol chapter is complemented by two separate chapters describing the basic concept and data analysis.

Assessment of BOLD response in the fetal lung.

Assessment of lung development and maturity is of utmost importance in prenatal counseling. Blood oxygen level-dependent (BOLD) effect MRI was developed for functional evaluations of organs. To date, no data are available in fetal lungs and nothing is known about the existence of a BOLD effect in the lungs. The aim of our study was to evaluate if a BOLD response could be detected in fetal lungs. From January 2014 to December 2016, 38 healthy pregnant women were prospectively enrolled. After a routine scan on a 1.5-T MRI device (normoxic period), maternal hyperoxia was induced for 5 min before the BOLD sequence (hyperoxic period). R2* was evaluated by fitting average intensity of the signal, both for normoxic (norm) and hyperoxic (hyper) periods. A significant BOLD response was observed after maternal hyperoxia in the lungs with a mean R2* decrease of 12.1 ± 2.5% (p < 0.001), in line with the placenta response with a mean R2* decrease of 19.2 ± 5.9% (p < 0.0001), confirming appropriate oxygen uptake. Conversely, no significant BOLD effect was observed for the brain nor the liver with a mean ∆R2* of 3.6 ± 3.1% (p = 0.64) and 2.8 ± 3.7% (p = 0.23). This study shows for the first time in human that a BOLD response can be observed in the normal fetal lung despite its prenatal "non-functional status." If confirmed in congenital lung and chest malformations, this property could be used in addition to the lung volume for a better prediction of postnatal respiratory status. • Blood oxygen level-dependent (BOLD) effect MRI was developed for functional evaluations of organs and could have interesting implications for the fetal organs. • Assessment of lung development is of utmost importance in prenatal counseling, but to date no data are available in fetal lungs. • BOLD response can be observed in the normal fetal lung opening the way to studies on fetus with pathological lungs.

A case of refractory generalized atonic seizure and hemifacial spasm with the possible causative pontocerebellar lesion

The patient was a 35-year-old woman. At the age of 1, she had undergone resection and radiation therapy for neoplastic lesions in the pons. She had a history of gelastic seizures when she was in elementary school, and brief lapses of the neck and truncal muscular tone and convulsions on the left face occurred at the age of 23. After a generalized sharp wave in the ictal electroencephalogram and electromyogram recording, left orbicularis oris muscle contraction was observed followed by sudden cervical extensor atonia. Seizure propagation was noted in the cerebral cortex, left facial nerve nucleus, and brainstem reticular formation. In a simultaneous electroencephalography with functional MRI, the blood oxygen level-dependent effect related to generalized sharp waves was observed in the vicinity of brainstem lesions in addition to a decrease in bilateral frontal and parietal lobes signals, as detected in generalized seizures. These findings suggest that the lesion could be a part of the epilepsy network. Although most epileptic seizures are derived from the cerebral cortex, it is important to note that brainstem lesions are involved in seizures in the patient presented in this study.