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.

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.

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.

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.

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.

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.

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.

Feasibility of measuring thermoregulation during RF heating of the human calf muscle using MR based methods.

PURPOSE: One of the main safety concerns in MR is heating of the subject due to radiofrequency (RF) exposure. Recently was shown that local peak temperatures can reach dangerous values and the most prominent parameter for accurate temperature estimations is thermoregulation. Therefore, the goal of this research is testing the feasibility of measuring thermoregulation in vivo using MR methods. THEORY AND METHODS: The calves of 13 volunteers were scanned at 3 tesla. A Proton Resonance Frequency Shift method was used for temperature measurement. Arterial Spin Labeling and phase contrast scans were used for perfusion and flow measurements respectively. The calves were monitored during extreme RF exposure (20 W/kg, 16 min) and after physical exercise. RESULTS: Temperature increases due to RF absorption (range of the 90th percentile of all volunteers: 1.1-2.5°C) matched with the reference skin temperature changes. Increases in perfusion and flow were defined on the whole leg and normalized to baseline. Perfusion showed a significant increase due to RF heating (ratio compared with baseline: 1.28 ± 0.37; P < 0.05), the influence of exercise was much greater, however (2.97 ± 2.45, P < 0.01). CONCLUSION: This study represents a first exploration of measuring thermoregulation, which will become essential when new safety guidelines are based on thermal dose.

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.

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.

Neuronal activation induced BOLD and CBF responses upon acetazolamide administration in patients with steno-occlusive artery disease.

Blood-oxygenation-level-dependent (BOLD) MRI is widely used for inferring neuronal activation and is becoming increasingly popular for assessing cerebrovascular reactivity (CVR) when combined with a vasoactive stimulus. The BOLD signal contains changes in cerebral blood flow (CBF) and thus information regarding neurovascular coupling and CVR. The BOLD signal, however, is also modulated by changes in cerebral blood volume (CBV) and cerebral metabolic rate of oxygen (CMRO2), as well as changes in the physiological baseline state. Here, we measured BOLD and CBF responses upon neuronal (visual) activation, before and after a vasodilatory challenge (acetazolamide, ACZ) in patients with vertebrobasilar steno-occlusive disease. After ACZ, the neuronal activation induced BOLD response was reduced or even negative (3 out of 8 subjects), whereas the CBF response remained similar. We show that BOLD alone cannot correctly assess the neuronal activation and underlying neurovascular coupling. The generally assumed positive relationship between BOLD and CBF responses may be severely compromised under changes in the physiological baseline state. Accompanying CBF measurements contain crucial information, and simulations suggest an altered flow-metabolism coupling in these patients.

Compensating for magnetic field inhomogeneity in multigradient-echo-based MR thermometry.

PURPOSE: MR thermometry (MRT) is a noninvasive method for measuring temperature that can potentially be used for radio frequency (RF) safety monitoring. This application requires measuring absolute temperature. In this study, a multigradient-echo (mGE) MRT sequence was used for that purpose. A drawback of this sequence, however, is that its accuracy is affected by background gradients. In this article, we present a method to minimize this effect and to improve absolute temperature measurements using MRI. THEORY: By determining background gradients using a B0 map or by combining data acquired with two opposing readout directions, the error can be removed in a homogenous phantom, thus improving temperature maps. METHODS: All scans were performed on a 3T system using ethylene glycol-filled phantoms. Background gradients were varied, and one phantom was uniformly heated to validate both compensation approaches. Independent temperature recordings were made with optical probes. RESULTS: Errors correlated closely to the background gradients in all experiments. Temperature distributions showed a much smaller standard deviation when the corrections were applied (0.21°C vs. 0.45°C) and correlated well with thermo-optical probes. CONCLUSION: The corrections offer the possibility to measure RF heating in phantoms more precisely. This allows mGE MRT to become a valuable tool in RF safety assessment.

Cerebral blood flow measurements in infants using look-locker arterial spin labeling.

PURPOSE: To measure cerebral blood flow (CBF) using Look-Locker arterial spin labeling (ASL) in children under 1 year of age and to investigate the advantages of using subject-specific estimates of ASL model parameters in this population. MATERIALS AND METHODS: Of 12 scanned infants, we successfully acquired CBF maps in 7 (postmenstrual age: 32 to 78 weeks) using a Look-Locker ASL scheme and both adult literature-derived and subject-specific model parameters. ASL global CBF measurements were compared with independent global CBF measurements obtained in the same scanning session using phase-contrast angiography. RESULTS: Measured global CBF values ranged from 24 to 56 mL/100g/min in the scanned infants, increasing significantly with postmenstrual age (ρSpearman = 0.89, P-value = 0.01). Using subject-specific model parameters yielded CBF estimates in significantly better agreement with phase-contrast angiography values (P-value: 0.80) than when standard adult parameters were used (P-value: 0.04). CONCLUSION: Look-Locker ASL can be used to measure CBF in infants and its accuracy is improved with the use of infant-specific auxiliary parameters, particularly blood and tissue T1 , which were much more variable in the imaged infants in than adults.

Arterial and portal venous liver perfusion using selective spin labelling MRI.

PURPOSE: To investigate the feasibility of selective arterial and portal venous liver perfusion imaging with spin labelling (SL) MRI, allowing separate labelling of each blood supply. METHODS: The portal venous perfusion was assessed with a pulsed EPISTAR technique and the arterial perfusion with a pseudo-continuous sequence. To explore precision and reproducibility, portal venous and arterial perfusion were separately quantified in 12 healthy volunteers pre- and postprandially (before and after meal intake). In a subgroup of 6 volunteers, the accuracy of the absolute portal perfusion and its relative postprandial change were compared with MRI flow measurements of the portal vein. RESULTS: The portal venous perfusion significantly increased from 63 ± 22 ml/100g/min preprandially to 132 ± 42 ml/100g/min postprandially. The arterial perfusion was lower with 35 ± 22 preprandially and 22 ± 30 ml/100g/min postprandially. The pre- and postprandial portal perfusion using SL correlated well with flow-based perfusion (r(2) = 0.71). Moreover, postprandial perfusion change correlated well between SL- and flow-based quantification (r(2) = 0.77). The SL results are in range with literature values. CONCLUSION: Selective spin labelling MRI of the portal venous and arterial blood supply successfully quantified liver perfusion. This non-invasive technique provides specific arterial and portal venous perfusion imaging and could benefit clinical settings where contrast agents are contraindicated. KEY POINTS: • Perfusion imaging of the liver by Spin Labelling MRI is feasible • Selective Spin Labelling MRI assessed portal venous and arterial liver perfusion separately • Spin Labelling based portal venous liver perfusion showed significant postprandial increase • Spin Labelling based portal perfusion correlated well with phase-contrast based portal perfusion • This non-invasive technique could benefit settings where contrast agents are contraindicated.

Arterial spin-labelling perfusion MRI and outcome in neonates with hypoxic-ischemic encephalopathy.

PURPOSE: Hyperperfusion may be related to outcome in neonates with hypoxic-ischemic encephalopathy (HIE). The purpose of this study was to evaluate whether arterial spin labelling (ASL) perfusion is associated with outcome in neonates with HIE and to compare the predictive value of ASL MRI to known MRI predictive markers. METHODS: Twenty-eight neonates diagnosed with HIE and assessed with MR imaging (conventional MRI, diffusion-weighted MRI, MR spectroscopy [MRS], and ASL MRI) were included. Perfusion in the basal ganglia and thalami was measured. Outcome at 9 or 18 months of age was scored as either adverse (death or cerebral palsy) or favourable. RESULTS: The median (range) perfusion in the basal ganglia and thalami (BGT) was 63 (28-108) ml/100 g/min in the neonates with adverse outcome and 28 (12-51) ml/100 g/min in the infants with favourable outcome (p < 0.01). The area-under-the-curve was 0.92 for ASL MRI, 0.97 for MRI score, 0.96 for Lac/NAA and 0.92 for ADC in the BGT. The combination of Lac/NAA and ASL MRI results was the best predictor of outcome (r(2) = 0.86, p < 0.001). CONCLUSION: Higher ASL perfusion values in neonates with HIE are associated with a worse neurodevelopmental outcome. A combination of the MRS and ASL MRI information is the best predictor of outcome. KEY POINTS: • Arterial spin labelling MRI can predict outcome in neonates with hypoxic-ischemic encephalopathy • Basal ganglia and thalami perfusion is higher in neonates with adverse outcome • Arterial spin labelling complements known MRI parameters in the prediction of outcome • The combined information of ASL and MRS measurements is the best predictor of outcome.

Chronic pain: lost inhibition?

Human brain imaging has revealed that acute pain results from activation of a network of brain regions, including the somatosensory, insular, prefrontal, and cingulate cortices. In contrast, many investigations report little or no alteration in brain activity associated with chronic pain, particularly neuropathic pain. It has been hypothesized that neuropathic pain results from misinterpretation of thalamocortical activity, and recent evidence has revealed altered thalamocortical rhythm in individuals with neuropathic pain. Indeed, it was suggested nearly four decades ago that neuropathic pain may be maintained by a discrete central generator, possibly within the thalamus. In this investigation, we used multiple brain imaging techniques to explore central changes in subjects with neuropathic pain of the trigeminal nerve resulting in most cases (20 of 23) from a surgical event. Individuals with chronic neuropathic pain displayed significant somatosensory thalamus volume loss (voxel-based morphometry) which was associated with decreased thalamic reticular nucleus and primary somatosensory cortex activity (quantitative arterial spin labeling). Furthermore, thalamic inhibitory neurotransmitter content was significantly reduced (magnetic resonance spectroscopy), which was significantly correlated to the degree of functional connectivity between the somatosensory thalamus and cortical regions including the primary and secondary somatosensory cortices, anterior insula, and cerebellar cortex. These data suggest that chronic neuropathic pain is associated with altered thalamic anatomy and activity, which may result in disturbed thalamocortical circuits. This disturbed thalamocortical activity may result in the constant perception of pain.

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).