The effect of dairy products on liver fat and metabolic risk markers in males with abdominal obesity - a four-arm randomized controlled trial.

BACKGROUND & AIMS: In recent years, epidemiological studies have reported links between the consumption of fermented dairy products, such as yogurt, and health; however, evidence from human intervention trials is scarce and inconsistent. We aimed to investigate the effect of consumption of four different types of dairy products (two fermented and two non-fermented) on liver fat (primary outcome) and metabolic risk markers in males with abdominal obesity. METHODS: In this parallel randomized controlled trial with four arms, 100 males aged 30-70 years, with body mass index 28.0-45.0 kg/m2, and waist circumference ≥102 cm underwent a 16-weeks intervention where they were instructed to consume 400 g/day of either milk, yogurt, heat-treated yogurt, or acidified milk as part of their habitual diet. Liver fat was measured by magnetic resonance imaging. RESULTS: In the complete case analyses (n = 80), no effects of the intervention or differences between groups were detected in anthropometry or body composition including liver fat. Moreover, no effects were detected in inflammatory markers. Main effects of time were detected in blood pressure (decrease; P < 0.001), insulin (decrease; P < 0.001), C-peptide (decrease; P = 0.040), homeostatic model assessment for insulin resistance (decrease; P < 0.001), total cholesterol (decrease; P = 0.016), low-density lipoprotein (decrease; P = 0.033), high-density lipoprotein (decrease; P = 0.006), and alanine transaminase (decrease; P = 0.019). Interactions between group and time failed to reach significance. CONCLUSIONS: In conclusion, findings from our study do not confirm that fermented yogurt products are superior in reducing liver fat or improving metabolic risk markers compared to non-fermented milk products. In fact, all intervention products (both fermented yogurt products and non-fermented milk products) did not affect liver fat and caused largely similar modest favorable changes in some metabolic risk markers. The study was registered at www. CLINICALTRIALS: gov (# NCT04755530).

Add-On MEmaNtine to Dopamine Antagonism to Improve Negative Symptoms at First Psychosis- the AMEND Trial Protocol.

Background: Antipsychotic drugs are primarily efficacious in treating positive symptoms by blocking the dopamine D2 receptor, but they fail to substantially improve negative symptoms and cognitive deficits. The limited efficacy may be attributed to the fact that the pathophysiology of psychosis involves multiple neurotransmitter systems. In patients with chronic schizophrenia, memantine, a non-competitive glutamatergic NMDA receptor antagonist, shows promise for ameliorating negative symptoms and improving cognition. Yet, it is unknown how memantine modulates glutamate levels, and memantine has not been investigated in patients with first-episode psychosis. Aims: This investigator-initiated double-blinded randomized controlled trial is designed to (1) test the clinical effects on negative symptoms of add-on memantine to antipsychotic medication, and (2) neurobiologically characterize the responders to add-on memantine. Materials and Equipment: Antipsychotic-naïve patients with first-episode psychosis will be randomized to 12 weeks treatment with [amisulpride + memantine] or [amisulpride + placebo]. We aim for a minimum of 18 patients in each treatment arm to complete the trial. Brain mapping will be performed before and after 12 weeks focusing on glutamate and neuromelanin in predefined regions. Regional glutamate levels will be probed with proton magnetic resonance spectroscopy (MRS), while neuromelanin signal will be mapped with neuromelanin-sensitive magnetic resonance imaging (MRI). We will also perform structural and diffusion weighted, whole-brain MRI. MRS and MRI will be performed at an ultra-high field strength (7 Tesla). Alongside, participants undergo clinical and neuropsychological assessments. Twenty matched healthy controls will undergo similar baseline- and 12-week examinations, but without receiving treatment. Outcome Measures: The primary endpoint is negative symptom severity. Secondary outcomes comprise: (i) clinical endpoints related to cognition, psychotic symptoms, side effects, and (ii) neurobiological endpoints related to regional glutamate- and neuromelanin levels, and structural brain changes. Anticipated Results: We hypothesize that add-on memantine to amisulpride will be superior to amisulpride monotherapy in reducing negative symptoms, and that this effect will correlate with thalamic glutamate levels. Moreover, we anticipate that add-on memantine will restore regional white matter integrity and improve cognitive functioning. Perspectives: By combining two licensed, off-patent drugs, AMEND aims to optimize treatment of psychosis while investigating the memantine response. Alongside, AMEND will provide neurobiological insights to effects of dual receptor modulation, which may enable future stratification of patients with first-episode psychosis before initial antipsychotic treatment. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT04789915].

Locus Coeruleus Shows a Spatial Pattern of Structural Disintegration in Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) causes a loss of neuromelanin-positive, noradrenergic neurons in the locus coeruleus (LC), which has been implicated in nonmotor dysfunction. OBJECTIVES: We used "neuromelanin sensitive" magnetic resonance imaging (MRI) to localize structural disintegration in the LC and its association with nonmotor dysfunction in PD. METHODS: A total of 42 patients with PD and 24 age-matched healthy volunteers underwent magnetization transfer weighted (MTw) MRI of the LC. The contrast-to-noise ratio of the MTw signal (CNRMTw ) was used as an index of structural LC integrity. We performed slicewise and voxelwise analyses to map spatial patterns of structural disintegration, complemented by principal component analysis (PCA). We also tested for correlations between regional CNRMTw and severity of nonmotor symptoms. RESULTS: Mean CNRMTw of the right LC was reduced in patients relative to controls. Voxelwise and slicewise analyses showed that the attenuation of CNRMTw was confined to the right mid-caudal LC and linked regional CNRMTw to nonmotor symptoms. CNRMTw attenuation in the left mid-caudal LC was associated with the orthostatic drop in systolic blood pressure, whereas CNRMTw attenuation in the caudal most portion of right LC correlated with apathy ratings. PCA identified a bilateral component that was more weakly expressed in patients. This component was characterized by a gradient in CNRMTw along the rostro-caudal and dorso-ventral axes of the nucleus. The individual expression score of this component reflected the overall severity of nonmotor symptoms. CONCLUSION: A spatially heterogeneous disintegration of LC in PD may determine the individual expression of specific nonmotor symptoms such as orthostatic dysregulation or apathy. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

Comparative Analysis of Blood T2 Values Measured by T2 -TRIR and TRUST.

BACKGROUND: Venous blood oxygenation (Yv), which can be derived from venous blood T2 (T2 b), combined with oxygen-extraction fraction (OEF) and cerebral metabolic rate of oxygen, is considered indicative for tissue viability and brain functioning and frequently assessed in patients with sickle cell disease. Recently, T2 -Prepared-Blood-Relaxation-Imaging-with-Inversion-Recovery (T2 -TRIR) was introduced allowing for simultaneous measurements of blood T2 and T1 (T1 b), potentially improving Yv estimation by overcoming the need to estimate hematocrit. PURPOSE: To optimize and compare T2 -TRIR with T2 -relaxation-under-spin-tagging (TRUST) sequence. STUDY TYPE: Prospective. POPULATION: A total of 12 healthy volunteers (six female, 27 ± 3 years old) and 7 patients with sickle cell disease (five female, 32 ± 12 years old). FIELD STRENGTH/SEQUENCE: 3 T; turbo field echo planar imaging (TFEPI), echo planar imaging (EPI), and fast field echo (FFE). ASSESSMENT: T2 b, Yv, and OEF from TRUST and T2 -TRIR were compared and T2 -TRIR-derived T1 b was assessed. Within- and between-session repeatability was quantified in the controls, whereas sensitivity to hemodynamic changes after acetazolamide (ACZ) administration was assessed in the patients. STATISTICAL TESTS: Shapiro-Wilk, one-sample and paired-sample t-test, repeated measures ANOVA, mixed linear model, Bland-Altman analysis and correlation analysis. Sidak multiple-comparison correction was performed. Significance level was 0.05. RESULTS: In controls, T2 b from T2 -TRIR (70 ± 11 msec) was higher compared to TRUST (60 ± 8 msec). In patients, T2 b values were lower pre- compared to post-ACZ administration (TRUST: 80 ± 15 msec and 106 ± 23 msec and T2 -TRIR: 95 ± 21 msec and 125 ± 36 msec). Consequently, Yv and OEF were lower and higher pre- compared to post-ACZ administration (TRUST Yv: 68% ± 7% and 77% ± 8%, T2 -TRIR Yv: 74% ± 8% and 80% ± 6%, TRUST OEF: 30% ± 7% and 21% ± 8%, and T2 -TRIR OEF: 25% ± 8% and 18% ± 6%). DATA CONCLUSION: TRUST and T2 -TRIR are reproducible, but T2 -TRIR-derived T2 b values are significantly higher compared to TRUST, resulting in higher Yv and lower OEF estimates. This bias might be considered when evaluating cerebral oxygen homeostasis. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Feasibility of Glutamate and GABA Detection in Pons and Thalamus at 3T and 7T by Proton Magnetic Resonance Spectroscopy.

Glutamate detection in pons and thalamus using proton magnetic resonance spectroscopy (1H-MRS) after an intervention is of interest for studying various brain disorders. However, 1H-MRS in these brain regions is challenging and time-consuming, especially in longitudinal study designs. 1H-MRS of more cortical structures at the ultrahigh magnetic field strength of 7T yields an improved spectral output, including separation of the glutamate signal from the glutamine signal, in a shorter and more feasible scan time, as compared to conventional clinical field strengths. For this purpose, we compared the feasibility of 1H-MRS at 3T and 7T in pons and thalamus by applying a longitudinal study design of repeated measures on same day and three separate days at both field strength in five healthy participants. Total 1H-MRS acquisition time was reduced by a factor 3.75 for pons and by a factor 3 for thalamus at 7T as compared to 3T. We found higher spectral signal-to-noise ratio (SNR) (p < 0.001), lower linewidth (p = 0.001) and lower Cramér-Rao lower bounds (CRLB) (p < 0.001) for the combined glutamate and glutamine signal (Glx) in thalamus at 7T as compared to 3T. In pons, CRLB of Glx and SNR were lower at 7T (p = 0.002 and p = 0.006), with no differences in linewidth compared to 3T. Mean within-subject variability of Glx concentration estimates was lower at 7T compared to 3T for both pons and thalamus. At 7T, it was possible to assess glutamate and γ-aminobutyric acid (GABA) simultaneously in pons and thalamus. In conclusion, 1H-MRS at 7T resulted in improved spectral quality while allowing shorter scan times than at 3T as well as estimation of the pure glutamate signal in pons and thalamus. This opens up the opportunity for multimodal study designs and multiregional subcortical 1H-MRS research. Glutamate and GABA measurement at 7T in pons and thalamus is advantageous for future investigations of excitatory-inhibitory mechanisms in brain disorders.

MR spectroscopy using static higher order shimming with dynamic linear terms (HOS-DLT) for improved water suppression, interleaved MRS-fMRI, and navigator-based motion correction at 7T.

PURPOSE: To interleave global and local higher order shimming for single voxel MRS. Single voxel MR spectroscopy requires optimization of the B0 field homogeneity in the region of the voxel to obtain a narrow linewidth and provide high data quality. However, the optimization of local higher order fields on a localized MRS voxel typically leads to large field offsets outside that volume. This compromises interleaved MR sequence elements that benefit from global field homogeneity such as water suppression, interleaved MRS-fMRI, and MR motion correction. METHODS: A shimming algorithm was developed to optimize the MRS voxel homogeneity and the whole brain homogeneity for interleaved sequence elements, using static higher order shims and dynamic linear terms (HOS-DLT). Shimming performance was evaluated using 6 brain regions and 10 subjects. Furthermore, the benefits of HOS-DLT was demonstrated for water suppression, MRS-fMRI, and motion corrected MRS using fat-navigators. RESULTS: The HOS-DLT algorithm was shown to improve the whole brain homogeneity compared to an MRS voxel-based shim, without compromising the MRS voxel homogeneity. Improved water suppression over the brain, reduced image distortions in MRS-fMRI, and improved quality of motion navigators were demonstrated using the HOS-DLT method. CONCLUSION: HOS-DLT shimming allowed for both local and global field homogeneity, providing excellent MR spectroscopy data quality, as well as good field homogeneity for interleaved sequence elements, even without the need for dynamic higher order shimming capabilities.

Cortical microinfarcts in memory clinic patients are associated with reduced cerebral perfusion.

Cerebral cortical microinfarcts (CMIs) are small ischemic lesions associated with cognitive impairment and dementia. CMIs are frequently observed in cortical watershed areas suggesting that hypoperfusion contributes to their development. We investigated if presence of CMIs was related to a decrease in cerebral perfusion, globally or specifically in cortex surrounding CMIs. In 181 memory clinic patients (mean age 72 ± 9 years, 51% male), CMI presence was rated on 3-T magnetic resonance imaging (MRI). Cerebral perfusion was assessed from cortical gray matter of the anterior circulation using pseudo-continuous arterial spin labeling parameters cerebral blood flow (CBF) (perfusion in mL blood/100 g tissue/min) and spatial coefficient of variation (CoV) (reflecting arterial transit time (ATT)). Patients with CMIs had a 12% lower CBF (beta = -.20) and 22% higher spatial CoV (beta = .20) (both p < .05) without a specific regional pattern on voxel-based CBF analysis. CBF in a 2 cm region-of-interest around the CMIs did not differ from CBF in a reference zone in the contralateral hemisphere. These findings show that CMIs in memory clinic patients are primarily related to global reductions in cerebral perfusion, thus shedding new light on the etiology of vascular brain injury in dementia.

Quantification of cerebral perfusion and cerebrovascular reserve using Turbo-QUASAR arterial spin labeling MRI.

PURPOSE: To compare cerebral blood flow (CBF) and cerebrovascular reserve (CVR) quantification from Turbo-QUASAR (quantitative signal targeting with alternating radiofrequency labeling of arterial regions) arterial spin labeling (ASL) and single post-labeling delay pseudo-continuous ASL (PCASL). METHODS: A model-based method was developed to quantify CBF and arterial transit time (ATT) from Turbo-QUASAR, including a correction for magnetization transfer effects caused by the repeated labeling pulses. Simulations were performed to assess the accuracy of the model-based method. Data from an in vivo experiment conducted on a healthy cohort were retrospectively analyzed to compare the CBF and CVR (induced by acetazolamide) measurement from Turbo-QUASAR and PCASL on the basis of global and regional differences. The quality of the two ASL data sets was examined using the coefficient of variation (CoV). RESULTS: The model-based method for Turbo-QUASAR was accurate for CBF estimation (relative error was 8% for signal-to-noise ratio = 5) in simulations if the bolus duration was known. In the in vivo experiment, the mean global CVR estimated by Turbo-QUASAR and PCASL was between 63% and 64% and not significantly different. Although global CBF values of the two ASL techniques were not significantly different, regional CBF differences were found in deep gray matter in both pre- and postacetazolamide conditions. The CoV of Turbo-QUASAR data was significantly higher than PCASL. CONCLUSION: Both ASL techniques were effective for quantifying CBF and CVR, despite the regional differences observed. Although CBF estimated from Turbo-QUASAR demonstrated a higher variability than PCASL, Turbo-QUASAR offers the advantage of being able to measure and control for variation in ATT.

Gamma-aminobutyric acid edited echo-planar spectroscopic imaging (EPSI) with MEGA-sLASER at 7T.

PURPOSE: For rapid spatial mapping of gamma-aminobutyric acid (GABA) at the increased sensitivity and spectral separation for ultra-high magnetic field strength (7 tesla [T]), an accelerated edited magnetic resonance spectroscopic imaging technique was developed and optimized for the human brain at 7 T. METHODS: A MEGA-sLASER sequence was used for GABA editing and volume selection to maximize editing efficiency and minimize chemical shift displacement errors. To accommodate the high bandwidth requirements at 7 T, a single-shot echo planar readout was used for rapid simultaneous encoding of the temporal dimension and 1 spatial. B0 and B1 field aspects specific for 7 T were studied together with correction procedures, and feasibility of the EPSI MEGA-sLASER technique was tested in vivo in 5 healthy subjects. RESULTS: Localized edited spectra could be measured in all subjects giving spatial GABA signal distributions over a central brain region, having 45- to 50-Hz spatial intervoxel B0 field variations and up to 30% B1 field deviations. MEGA editing was found unaffected by the B0 inhomogeneities for the optimized sequence. The correction procedures reduced effects of intervoxel B0 inhomogeneities, corrected for spatial editing efficiency variations, and compensated for GABA resonance phase and frequency shifts from subtle motion and acquisition instabilities. The optimized oscillating echo-planar gradient scheme permitted full spectral acquisition at 7 T and exhibited minimal spectral-spatial ghosting effects for the selected brain region. CONCLUSION: The EPSI MEGA-sLASER technique was shown to provide time-efficient mapping of regional variations in cerebral GABA in a central volume of interest with spatial B1 and B0 field variations typical for 7 T.

The effect of physical exercise on cerebral blood flow in Alzheimer's disease.

In recent years there has been an increasing focus on the relation between cerebrovascular health, physical exercise and Alzheimer's disease. The aim of the current study was to determine the effect of moderate-to-high-intensity aerobic exercise on cerebral blood flow in patients with mild to moderate Alzheimer's disease. Fifty-one patients were randomized to either usual care or moderate-to-high intensity aerobic exercise for 16 weeks. Exercise had no consistent effect on whole brain or regional cerebral blood flow. Sixteen weeks of exercise are, therefore, not sufficient to produce a consistent increase in cerebral blood flow in a relatively small sample of Alzheimer's patients.

Effect sizes of BOLD CVR, resting-state signal fluctuations and time delay measures for the assessment of hemodynamic impairment in carotid occlusion patients.

BACKGROUND AND PURPOSE: The BOLD signal amplitude as a response to a hypercapnia stimulus is commonly used to assess cerebrovascular reserve. Despite recent advances, the implementation remains cumbersome and alternative ways to assess hemodynamic impairment are desirable. Resting-state BOLD signal fluctuations (rsBOLD) have been proposed however data on its sensitivity and dependence on baseline venous cerebral blood volume (vCBV) is limited. The primary aim of this study was to compare the effect sizes of resting-state and hypercapnia induced BOLD signal changes in the detection of hemodynamic impairment. The second aim of the study was to assess the dependence of BOLD signal variability on vCBV. MATERIALS AND METHODS: Fifteen patients with internal carotid artery occlusive disease and 15 matched healthy controls were included in this study. The BOLD signal was derived from a dual-echo gradient-echo echo-planar sequence during hypercapnia (HC) and hyperoxia (HO) gas modulations. BOLD (fractional) amplitude of low frequency fluctuations ((f)ALFF) was compared to HC-BOLD, BOLD response delays derived from time delay analysis and ΔBOLD in response to progressively increasing HC. Effect sizes (i.e. the standard mean difference between patients and controls) were calculated. HO-BOLD was used to estimate vCBV, and its contribution to the variability in rsBOLD signal was evaluated. RESULTS: The effect sizes of ALFF and fALFF (0.61 and 0.72) were lower than the effect sizes related to hypercapnia-based hemodynamic assessment analysis; 1.62, 1.56 and 0.90 for HC-BOLD, BOLD response delays and ΔBOLD in response to progressively increasing HC. A moderate relation was found between (f)ALFF and HC-BOLD in controls (R2 of 0.61 and 0.42), but this relation decreased in patients (R2 of 0.33 and 0.15). (f)ALFF did not differ between patients and controls whereas HC-BOLD did (p < 0.005). The ΔBOLD response to progressively increasing HC was significantly different in between patients and controls for ΔEtCO2 values ≥ 2 mmHg (at +2  mmHg F(1, 18) = 5.85, p = 0.026). Up to 31% and 53% of the variance in the ALFF and HC-BOLD spatial distribution could be explained by HO-BOLD. CONCLUSION: ALFF and fALFF demonstrated a moderate effect size to detect hemodynamic impairment whereas the effect size was large for methods employing a hypercapnia-based vascular stress stimulus. Based on our analysis of BOLD signal change as a response to a progressively increasing hypercapnia stimulus we can argue that a hypercapnia stimulus of at least 2 mmHg above baseline EtCO2 is necessary to evaluate hemodynamic impairment. We also demonstrated that a substantial amount of information imbedded in the rsBOLD and HC-BOLD was explained by HO-BOLD. HO-BOLD can serve as a proxy for vCBV and this thus indicates that one should be careful when adopting these techniques in disease cases with compromised CBV.

Fast CSF MRI for brain segmentation; Cross-validation by comparison with 3D T1-based brain segmentation methods.

OBJECTIVE: In previous work we have developed a fast sequence that focusses on cerebrospinal fluid (CSF) based on the long T2 of CSF. By processing the data obtained with this CSF MRI sequence, brain parenchymal volume (BPV) and intracranial volume (ICV) can be automatically obtained. The aim of this study was to assess the precision of the BPV and ICV measurements of the CSF MRI sequence and to validate the CSF MRI sequence by comparison with 3D T1-based brain segmentation methods. MATERIALS AND METHODS: Ten healthy volunteers (2 females; median age 28 years) were scanned (3T MRI) twice with repositioning in between. The scan protocol consisted of a low resolution (LR) CSF sequence (0:57min), a high resolution (HR) CSF sequence (3:21min) and a 3D T1-weighted sequence (6:47min). Data of the HR 3D-T1-weighted images were downsampled to obtain LR T1-weighted images (reconstructed imaging time: 1:59 min). Data of the CSF MRI sequences was automatically segmented using in-house software. The 3D T1-weighted images were segmented using FSL (5.0), SPM12 and FreeSurfer (5.3.0). RESULTS: The mean absolute differences for BPV and ICV between the first and second scan for CSF LR (BPV/ICV: 12±9/7±4cc) and CSF HR (5±5/4±2cc) were comparable to FSL HR (9±11/19±23cc), FSL LR (7±4, 6±5cc), FreeSurfer HR (5±3/14±8cc), FreeSurfer LR (9±8, 12±10cc), and SPM HR (5±3/4±7cc), and SPM LR (5±4, 5±3cc). The correlation between the measured volumes of the CSF sequences and that measured by FSL, FreeSurfer and SPM HR and LR was very good (all Pearson's correlation coefficients >0.83, R2 .67-.97). The results from the downsampled data and the high-resolution data were similar. CONCLUSION: Both CSF MRI sequences have a precision comparable to, and a very good correlation with established 3D T1-based automated segmentations methods for the segmentation of BPV and ICV. However, the short imaging time of the fast CSF MRI sequence is superior to the 3D T1 sequence on which segmentation with established methods is performed.

Relationship between haemodynamic impairment and collateral blood flow in carotid artery disease.

Collateral blood flow plays a pivotal role in steno-occlusive internal carotid artery (ICA) disease to prevent irreversible ischaemic damage. Our aim was to investigate the effect of carotid artery disease upon cerebral perfusion and cerebrovascular reactivity and whether haemodynamic impairment is influenced at brain tissue level by the existence of primary and/or secondary collateral. Eighty-eight patients with steno-occlusive ICA disease and 29 healthy controls underwent MR examination. The presence of collaterals was determined with time-of-flight, two-dimensional phase contrast MRA and territorial arterial spin labeling (ASL) imaging. Cerebral blood flow and cerebrovascular reactivity were assessed with ASL before and after acetazolamide. Cerebral haemodynamics were normal in asymptomatic ICA stenosis patients, as opposed to patients with ICA occlusion, in whom the haemodynamics in both hemispheres were compromised. Haemodynamic impairment in the affected brain region was always present in symptomatic patients. The degree of collateral blood flow was inversely correlated with haemodynamic impairment. Recruitment of secondary collaterals only occurred in symptomatic ICA occlusion patients. In conclusion, both CBF and cerebrovascular reactivity were found to be reduced in symptomatic patients with steno-occlusive ICA disease. The presence of collateral flow is associated with further haemodynamic impairment. Recruitment of secondary collaterals is associated with severe haemodynamic impairment.

T 2 mapping of cerebrospinal fluid: 3 T versus 7 T.

OBJECT: Cerebrospinal fluid (CSF) T 2 mapping can potentially be used to investigate CSF composition. A previously proposed CSF T 2-mapping method reported a T 2 difference between peripheral and ventricular CSF, and suggested that this reflected different CSF compositions. We studied the performance of this method at 7 T and evaluated the influence of partial volume and B 1 and B 0 inhomogeneity. MATERIALS AND METHODS: T 2-preparation-based CSF T 2-mapping was performed in seven healthy volunteers at 7 and 3 T, and was compared with a single echo spin-echo sequence with various echo times. The influence of partial volume was assessed by our analyzing the longest echo times only. B 1 and B 0 maps were acquired. B 1 and B 0 dependency of the sequences was tested with a phantom. RESULTS: T 2,CSF was shorter at 7 T compared with 3 T. At 3 T, but not at 7 T, peripheral T 2,CSF was significantly shorter than ventricular T 2,CSF. Partial volume contributed to this T 2 difference, but could not fully explain it. B 1 and B 0 inhomogeneity had only a very limited effect. T 2,CSF did not depend on the voxel size, probably because of the used method to select of the regions of interest. CONCLUSION: CSF T 2 mapping is feasible at 7 T. The shorter peripheral T 2,CSF is likely a combined effect of partial volume and CSF composition.

Brain oxygen saturation assessment in neonates using T2-prepared blood imaging of oxygen saturation and near-infrared spectroscopy.

Although near-infrared spectroscopy is increasingly being used to monitor cerebral oxygenation in neonates, it has a limited penetration depth. The T2-prepared Blood Imaging of Oxygen Saturation (T2-BIOS) magnetic resonance sequence provides an oxygen saturation estimate on a voxel-by-voxel basis, without needing a respiratory calibration experiment. In 15 neonates, oxygen saturation measured by T2-prepared blood imaging of oxygen saturation and near-infrared spectroscopy were compared. In addition, these measures were compared to cerebral blood flow and venous oxygen saturation in the sagittal sinus. A strong linear relation was found between the oxygen saturation measured by magnetic resonance imaging and the oxygen saturation measured by near-infrared spectroscopy ( R2 = 0.64, p < 0.001). Strong linear correlations were found between near-infrared spectroscopy oxygen saturation, and magnetic resonance imaging measures of frontal cerebral blood flow, whole brain cerebral blood flow and venous oxygen saturation in the sagittal sinus ( R2 = 0.71, 0.50, 0.65; p < 0.01). The oxygen saturation obtained by T2-prepared blood imaging of oxygen saturation correlated with venous oxygen saturation in the sagittal sinus ( R2 = 0.49, p = 0.023), but no significant correlations could be demonstrated with frontal and whole brain cerebral blood flow. These results suggest that measuring oxygen saturation by T2-prepared blood imaging of oxygen saturation is feasible, even in neonates. Strong correlations between the various methods work as a cross validation for near-infrared spectroscopy and T2-prepared blood imaging of oxygen saturation, confirming the validity of using of these techniques for determining cerebral oxygenation.

Insight into the labeling mechanism of acceleration selective arterial spin labeling.

OBJECTIVES: Acceleration selective arterial spin labeling (AccASL) is a spatially non-selective labeling technique, used in traditional ASL methods, which labels spins based on their flow acceleration rather than spatial localization. The exact origin of the AccASL signal within the vasculature is not completely understood. To obtain more insight into this, the acceleration selective module was performed followed by a velocity selective module, which is used in velocity selective arterial spin labeling (VS-ASL). MATERIALS AND METHODS: Nine healthy volunteers were scanned with various combinations of the control and label conditions in both the acceleration and velocity selective module. The cut-off acceleration (0.59 m/s2) or velocity (2 cm/s) was kept constant in one module, while it was varied over a large range in the other module. With the right subtractions this resulted in AccASL, VS-ASL, combined AccASL and VS-ASL signal, and signal from one module with crushing from the other. RESULTS: The label created with AccASL has an overlap of approximately 50% in the vascular region with VS-ASL, but also originates from smaller vessels closer to the capillaries. CONCLUSION: AccASL is able to label spins both in the macro- and meso-vasculature, as well as in the microvasculature.

Magnetic resonance imaging based noninvasive measurements of brain hemodynamics in neonates: a review.

Perinatal disturbances of brain hemodynamics can have a detrimental effect on the brain's parenchyma with consequently adverse neurodevelopmental outcome. Noninvasive, reliable tools to evaluate the neonate's brain hemodynamics are scarce. Advances in magnetic resonance imaging have provided new methods to noninvasively assess brain hemodynamics. More recently these methods have made their transition to the neonatal population. The aim of this review is twofold. Firstly, to describe these newly available noninvasive methods to investigate brain hemodynamics in neonates. Secondly, to discuss the results that were obtained with these techniques, identifying both potential clinical applications as well as gaps of knowledge.

The BOLD cerebrovascular reactivity response to progressive hypercapnia in young and elderly.

Blood Oxygenation Level Dependent (BOLD) imaging in combination with vasoactive stimuli can be used to probe cerebrovascular reactivity (CVR). Characterizing the healthy, age-related changes in the BOLD-CVR response can provide a reference point from which to distinguish abnormal CVR from the otherwise normal effects of ageing. Using a computer controlled gas delivery system, we examine differences in BOLD-CVR response to progressive hypercapnia between 16 young (28±3years, 9 female) and 30 elderly subjects (66±4years, 13 female). Furthermore, we incorporate baseline T2* information to broaden our interpretation of the BOLD-CVR response. Significant age-related differences were observed. Grey matter CVR at 7mmHg above resting PetCO2 was lower amongst elderly (0.19±0.06%ΔBOLD/mmHg) as compared to young subjects (0.26±0.07%ΔBOLD/mmHg). White matter CVR at 7mmHg above baseline PetCO2 showed no significant difference between young (0.04±0.02%ΔBOLD/mmHg) and elderly subjects (0.05±0.03%ΔBOLD/mmHg). We saw no significant differences in the BOLD signal response to progressive hypercapnia between male and female subjects in either grey or white matter. The observed differences in the healthy BOLD-CVR response could be explained by age-related changes in vascular mechanical properties.

T2-prepared velocity selective labelling: A novel idea for full-brain mapping of oxygen saturation.

BACKGROUND AND AIM: Disturbances in cerebral oxygenation saturation (SO2) have been linked to adverse outcome in adults, children, and neonates. In intensive care, the cerebral SO2 is increasingly being monitored by Near-InfraRed Spectroscopy (NIRS). Unfortunately NIRS has a limited penetration depth. The "modified T2-prepared Blood Imaging of Oxygen Saturation" (T2-BIOS) MR sequence provides a step towards full brain SO2 measurement. MATERIALS AND METHODS: Tissue SO2, and venous SO2 (SvO2) were obtained simultaneously by T2-BIOS during a respiratory challenge in ten healthy volunteers. These two measures were compared to SO2 that was obtained by a single probe MR-compatible NIRS setup, and to cerebral blood flow and venous SO2 that were obtained by arterial spin labelling and T2-TRIR, respectively. RESULTS: SO2-T2-BIOS and SO2-NIRS had a mean bias of -4.0% (95% CI -21.3% to 13.3%). SvO2-T2-BIOS correlated with SO2-NIRS (R2=0.41, p=0.002) and SvO2-T2-TRIR (R2=0.87, p=0.002). In addition, SO2-NIRS correlated with SvO2-T2-TRIR (R2=0.85, p=0.003) Frontal cerebral blood flow correlated with SO2-T2-BIOS (R2=0.21, p=0.04), but was not significant in relation to SO2-NIRS. DISCUSSION/CONCLUSION: Full brain SO2 assessment by any technique may help validating NIRS and may prove useful in guiding the clinical management of patient populations with cerebral injury following hypoxic-ischaemic events. The agreement between NIRS and T2-BIOS provides confidence in measuring cerebral SO2 by either technique. As it stands now, the T2-BIOS represents a novel idea and future work will focus on improvements to make it a reliable tool for SO2 assessment.

Arterial Spin Labeling and Blood Oxygen Level-Dependent MRI Cerebrovascular Reactivity in Cerebrovascular Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: The cerebrovascular reactivity (CVR) results of blood oxygen level-dependent (BOLD) and arterial spin labeling (ASL) MRI studies performed in patients with cerebrovascular disease (steno-occlusive vascular disease or stroke) were systematically reviewed. SUMMARY: Thirty-one articles were included. Twenty-three (74.2%) studies used BOLD MRI to evaluate the CVR, 4 (12.9%) studies used ASL MRI and 4 (12.9%) studies used both BOLD and ASL MRI. Thirteen studies (3 significant) found a lower BOLD CVR, 2 studies found a similar CVR and 3 studies found a higher CVR in the ipsilateral compared to the contralateral hemisphere. Nine (5 significant) out of 10 studies found a lower BOLD CVR in the ipsilateral hemispheres of patients compared to controls. Six studies (2 significant) found a lower ASL CVR in the ipsilateral compared to the contralateral hemispheres. Three out of 5 studies found a significant lower ASL CVR in the ipsilateral hemispheres of patients compared to controls. KEY MESSAGES: This review brings support for a reduced BOLD and ASL CVR in the ipsilateral hemisphere of patients with cerebrovascular disease. We suggest that future studies will be performed in a uniform way so reference values can be established and could be used to guide treatment decisions in patients with cerebrovascular disease.