Contrast-agent-free state-of-the-art MRI on cerebral small vessel disease-part 1. ASL, IVIM, and CVR.

Cerebral small vessel disease (cSVD), a common cause of stroke and dementia, is traditionally considered the small vessel equivalent of large artery occlusion or rupture that leads to cortical and subcortical brain damage. Microvessel endothelial dysfunction can also contribute to it. Brain imaging, including MRI, is useful to show the presence of lesions of several types, although the association between conventional MRI measures and clinical features of cSVD is not always concordant. We assessed the additional contribution of contrast-agent-free, state-of-the-art MRI techniques such as arterial spin labeling (ASL), diffusion tensor imaging, functional MRI, and intravoxel incoherent motion (IVIM) applied to cSVD in the existing literature. We performed a review following the PICO Worksheet and Search Strategy, including original papers in English, published between 2000 and 2022. For each MRI method, we extracted information about their contributions, in addition to those established with traditional MRI methods and related information about the origins, pathology, markers, and clinical outcomes in cSVD. This paper presents the first part of the review, which includes 37 studies focusing on ASL, IVIM, and cerebrovascular reactivity (CVR) measures. In general, they have shown that, in addition to white matter hyperintensities, alterations in other neuroimaging parameters such as blood flow and CVR also indicate the presence of cSVD. Such quantitative parameters were also related to cSVD risk factors. Therefore, they are promising, noninvasive tools to explore questions that have not yet been clarified about this clinical condition. However, protocol standardization is essential to increase their clinical use.

Relationships Between Regional Cerebral Blood Flow and Neurocognitive Outcomes in Children and Adolescents With Congenital Heart Disease.

To identify regional cerebral blood flow (rCBF) alterations in children and adolescents with congenital heart disease (CHD) in relation to neurocognitive outcomes using a nonbiased data-driven approach. This is a prospective, observational study of children and adolescents with CHD without brain injury and healthy controls using pseudo-continuous arterial spin labeling (pCASL) MRI. Quantitative rCBF was compared between participants with CHD and healthy controls using a voxelwise data-driven method. Mediation analysis was then performed on a voxelwise basis, with the grouping variable as the independent variable, neurocognitive outcomes (from the NIH Toolbox Cognitive Battery) as the dependent variables, and rCBF as the mediator. After motion correction, a total of 80 studies were analyzable (27 for patients with CHD, 53 for controls). We found steeper age-related decline in rCBF among those with CHD compared to normal controls in the insula/ventromedial prefrontal regions (salience network) and the dorsal anterior cingulate and precuneus/posterior cingulate (default mode network), and posterior parietal/dorsolateral prefrontal (central executive network) (FWE-corrected P< 0.05). The reduced rCBF in the default mode/salience network was found to mediate poorer performance on an index of crystallized cognition from the NIH Toolbox Cognitive Battery in those with CHD compared to controls. In contrast, reduced rCBF in the central executive network/salience network mediated reduced deficits in fluid cognition among patients with CHD compared to controls. Regional cerebral blood flow alterations mediate domain-specific differences in cognitive performance in children and adolescents with CHD compared to healthy controls, independent of injury, and are likely related to brain and cognitive reserve mechanisms. Further research is needed to evaluate the potential of interventions in CHD targeting regional cerebral blood flow across lifespan.

Contrast optimization in arterial spin labeling with multiple post-labeling delays for cerebrovascular assessment.

OBJECTIVE: Improving the readout for arterial spin labeling with multiple post-labeling delays (multi-PLD ASL) through a flip angle (FA) sweep towards increasing contrast-to-noise ratio for long PLD images. METHODS: Images were acquired from 20 healthy subjects and 14 patients with severe, asymptomatic carotid artery stenosis (ACAS) in a 3T MRI scanner. Multi-PLD ASL images with conventional and proposed (FA sweep) readouts were acquired. For patients, magnetic resonance angiography was used to validate the multi-PLD ASL results. Perfusion values were calculated for brain regions irrigated by the main cerebral arteries and compared by analysis of variance. RESULTS: For healthy subjects, better contrast was obtained for long PLDs when using the proposed multi-PLD method compared to the conventional. For both methods, no hemispheric difference of perfusion was observed. For patients, the proposed method facilitated the observation of delayed tissue perfusion, which was not visible for long PLD using the conventional multi-PLD ASL. CONCLUSION: We successfully assessed brain perfusion of patients with asymptomatic CAS using multi-PLD ASL with FA sweep. We were able to show subtle individual differences. Moreover, prolonged arterial transit time in patients was observed, although they were considered asymptomatic, suggesting that it may not be an adequate term to characterize them.

Effects of global signal regression and subtraction methods on resting-state functional connectivity using arterial spin labeling data.

BACKGROUND: Arterial spin labeling (ASL) is an established magnetic resonance imaging (MRI) technique that is finding broader applications in functional studies of the healthy and diseased brain. To promote improvement in cerebral blood flow (CBF) signal specificity, many algorithms and imaging procedures, such as subtraction methods, were proposed to eliminate or, at least, minimize noise sources. Therefore, this study addressed the main considerations of how CBF functional connectivity (FC) is changed, regarding resting brain network (RBN) identification and correlations between regions of interest (ROI), by different subtraction methods and removal of residual motion artifacts and global signal fluctuations (RMAGSF). METHODS: Twenty young healthy participants (13 M/7F, mean age = 25 ±â€¯3 years) underwent an MRI protocol with a pseudo-continuous ASL (pCASL) sequence. Perfusion-based images were obtained using simple, sinc and running subtraction. RMAGSF removal was applied to all CBF time series. Independent Component Analysis (ICA) was used for RBN identification, while Pearson' correlation was performed for ROI-based FC analysis. RESULTS: Temporal signal-to-noise ratio (tSNR) was higher in CBF maps obtained by sinc subtraction, although RMAGSF removal had a significant effect on maps obtained with simple and running subtractions. Neither the subtraction method nor the RMAGSF removal directly affected the identification of RBNs. However, the number of correlated and anti-correlated voxels varied for different subtraction and filtering methods. In an ROI-to-ROI level, changes were prominent in FC values and their statistical significance. CONCLUSIONS: Our study showed that both RMAGSF filtering and subtraction method might influence resting-state FC results, especially in an ROI level, consequently affecting FC analysis and its interpretation. Taking our results and the whole discussion together, we understand that for an exploratory assessment of the brain, one could avoid removing RMAGSF to not bias FC measures, but could use sinc subtraction to minimize low-frequency contamination. However, CBF signal specificity and frequency range for filtering purposes still need to be assessed in future studies.

Altered Cerebral Perfusion in Infants Born Preterm Compared with Infants Born Full Term.

OBJECTIVES: To compare regional cerebral cortical blood flow (CBF) in infants born very preterm at term-equivalent age (TEA) and healthy newborns born full term and to examine the impact of clinical risk factors on CBF in the cohort born preterm. STUDY DESIGN: This prospective, cross-sectional study included infants born very preterm (gestational age at birth <32 weeks; birth weight <1500 g) and healthy infants born full term. Using noninvasive 3T arterial spin labeling magnetic resonance imaging, we quantified regional CBF in the cerebral cortex: sensorimotor/auditory/visual cortex, superior medial/dorsolateral prefrontal cortex, anterior cingulate cortex (ACC)/posterior cingulate cortex, insula, and lateral posterior parietal cortex, as well as in the brainstem, and deep gray matter. Analyses were performed controlling for sex, gestational age, and age at magnetic resonance imaging. RESULTS: We studied 202 infants: 98 born preterm and 104 born full term at TEA. Infants born preterm demonstrated greater global CBF (ß = 9.03; P < .0001) and greater absolute regional CBF in all brain regions except the insula. Relative CBF in the insula, ACC and auditory cortex were decreased significantly in infants born preterm compared with their peers born at full term (P < .0001; P = .026; P = .036, respectively). In addition, the presence of parenchymal brain injury correlated with lower global and regional CBF (insula, ACC, sensorimotor, auditory, and visual cortices) whereas the need for cardiac vasopressor support correlated with lower regional CBF in the insula and visual cortex. CONCLUSIONS: Altered regional cortical CBF in infants born very preterm at TEA may reflect early brain dysmaturation despite the absence of cerebral cortical injury. Furthermore, specific cerebral cortical areas may be vulnerable to early hemodynamic instability and parenchymal brain injury.

Cerebral blood flow and vasoreactivity in aging: an arterial spin labeling study

Regional cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) in young and elderly participants were assessed using pulsed arterial spin labeling (ASL) and blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) techniques in combination with inhalation of CO2. Pulsed ASL and BOLD-MRI were acquired in seventeen asymptomatic volunteers (10 young adults, age: 30±7 years; 7 elderly adults, age: 64±8 years) with no history of diabetes, hypertension, and neurological diseases. Data from one elderly participant was excluded due to the incorrigible head motion. Average baseline CBF in gray matter was significantly reduced in elderly (46±9 mL·100 g-1·min-1) compared to young adults (57±8 mL·100 g-1·min-1; P=0.02). Decreased pulsed ASL-CVR and BOLD-CVR in gray matter were also observed in elderly (2.12±1.30 and 0.13±0.06 %/mmHg, respectively) compared to young adults (3.28±1.43 and 0.28±0.11 %/mmHg, respectively; P<0.05), suggesting some degree of vascular impairment with aging. Moreover, age-related decrease in baseline CBF was observed in different brain regions (inferior, middle and superior frontal gyri; precentral and postcentral gyri; superior temporal gyrus; cingulate gyri; insula, putamen, caudate, and supramarginal gyrus). In conclusion, CBF and CVR were successfully investigated using a protocol that causes minimal or no discomfort for the participants. Age-related decreases in baseline CBF and CVR were observed in the cerebral cortex, which may be related to the vulnerability for neurological disorders in aging.

Arterial spin labeling in patients with schizophrenia: a systematic review

Abstract Background: Neuroimaging studies are an invaluable source of information about the physiopathology of schizophrenia. Arterial spin labeling (ASL) is a new magnetic resonance technique (MRI) that is able to effectively evaluate brain function without the use of radiation. Objective: To make a systematic review of studies using ASL to compare resting-state regional cerebral blood flow (rCBF) patterns in patients with schizophrenia and healthy controls. Methods: Original articles were searched for on PubMed, Scopus, Web of Science and PsycINFO electronic databases. The search terms used were 'arterial', 'spin', 'labeling', and 'schizophrenia'. Only studies comparing resting-state rCBF were included, a qualitative synthesis was then performed. Results: Ten articles were included in the review among a total of 22. Decreased rCBF in schizophrenia patients was described in the anterior cingulate, cuneus, fusiform gyrus, frontal lobe, left middle frontal gyrus, inferior frontal gyrus, lingual gyrus, middle occipital gyrus, and parietal lobe. The putamen was the only region with increased rCBF in schizophrenia. Discussion: The evidence of the studies reviewed lends support to the concept of hipofrontality in schizophrenia. rCBF alterations were found in regions classically associated with schizophrenia. ASL seems to be valid, and reliable tool to assess schizophrenia.

The two sides of a lipid-protein story.

Protein-membrane interactions play essential roles in a variety of cell functions such as signaling, membrane trafficking, and transport. Membrane-recruited cytosolic proteins that interact transiently and interfacially with lipid bilayers perform several of those functions. Experimental techniques capable of probing changes on the structural dynamics of this weak association are surprisingly limited. Among such techniques, electron spin resonance (ESR) has the enormous advantage of providing valuable local information from both membrane and protein perspectives by using intrinsic paramagnetic probes in metalloproteins or by attaching nitroxide spin labels to proteins and lipids. In this review, we discuss the power of ESR to unravel relevant structural and functional details of lipid-peripheral membrane protein interactions with special emphasis on local changes of specific regions of the protein and/or the lipids. First, we show how ESR can be used to investigate the direct interaction between a protein and a particular lipid, illustrating the case of lipid binding into a hydrophobic pocket of chlorocatechol 1,2-dioxygenase, a non-heme iron enzyme responsible for catabolism of aromatic compounds that are industrially released in the environment. In the second case, we show the effects of GPI-anchored tissue-nonspecific alkaline phosphatase, a protein that plays a crucial role in skeletal mineralization, and on the ordering and dynamics of lipid acyl chains. Then, switching to the protein perspective, we analyze the interaction with model membranes of the brain fatty acid binding protein, the major actor in the reversible binding and transport of hydrophobic ligands such as long-chain, saturated, or unsaturated fatty acids. Finally, we conclude by discussing how both lipid and protein views can be associated to address a common question regarding the molecular mechanism by which dihydroorotate dehydrogenase, an essential enzyme for the de novo synthesis of pyrimidine nucleotides, and how it fishes out membrane-embedded quinones to perform its function.

Angiografía no contrastada con Arterial Spin Labeling / Non-contrast angioresonance with Arterial Spin Labeling

Introducción: La angiografía por resonancia magnética no contrastada realizada con "Arterial Spin Labeling" (ARM ASL) es un método diseñado para marcar los espines sanguíneos y así crear un contraste endógeno adecuado para evaluar territorios vasculares selectivamente sin la necesidad de aplicar medio de contraste intravenoso (compuestos de Gadolinio). Metodología: Se realizó un estudio descriptivo de una serie de casos, donde se describen los detalles técnicos y los resultados de la aplicación de la ARM ASL en equipos de 1.5 y 3 Tesla en voluntarios sanos. Resultados: Se observaron dos casos: Para la técnica angiográfica del primer caso (ASL "Flow-in") se usó un resonador de 3T, sincronización cardiaca, una secuencia b-SSFP 3D y un pre-pulso de inversión, este último para saturar los tejidos estáticos. El volumen de examen se ubicó en el plano axial teniendo la precaución de cubrir la anatomía vascular renal, lo cual se logra en la mayoría de los casos con 60 a 70 cortes de 2 mm solapados en 50 porciento, voxel de 2x1x1 mm y campo de visión (FOV) de 250x100 mm. El protocolo del segundo caso fue obtenido en un equipo de 1.5T, sin sincronización cardiaca, con un navegador respiratorio dia fragmático y con una secuencia coronal Turbo SE 3D después de aplicar dos pre-pulsos de marcación sanguínea, el primero similar al del caso anterior y el segundo, o pulso selectivo, para marcar el flujo del vaso de interés. Con este método (ASL "Flow-Out") sólo la sangre marcada emite señal. Conclusión: Las técnicas de angiografía b-SSFP 3D y Turbo SE 3D no contrastadas con pre-pulsos de ASL en 1.5 y 3T son alternativas disponibles y, por lo tanto, pueden considerarse como complemento a otros métodos de angiografía por resonancia magnética al momento de evaluar la patología vascular.

Introduction: Non-contrast magnetic resonance angiography using "Arterial Spin Labeling" (MRA ASL) is a technique designed to label blood spins and therefore create an endogenous contrast suitable for selectively evaluating vascular territories without intravenous contrast (Gadolinium compounds). Methodology: Technical details and results of the implementación of the MRA ASL using 1.5 and 3.0 Tesla systems in healthy volunteers is described. Results: Two cases were observed: for the angiographic technique of the first case (ASL "Flow-in") in a 3.0 T unit, cardiac synchronization (cardiac gating), a 3D b-SSFP sequence, and an inversion pre-pulse was used, the latter to saturate the static tissues. The examination volume was located in the axial plane taking care to cover the renal vascular anatomy, which is achieved in most cases with 60 to 70 2 mm slices overlapped in 50%, voxel of 2x1x1 mm and a field of vision (FOV) of 250 x100 mm. The protocol for the second case was obtained on a 1.5 T system, without cardiac gating, with a diaphragmatic respiratory navigator and a 3D Turbo SE coronal sequence after applying two pre-pulse blood saturation bands, the first similar to the previous case and the second, or selective pulse, to label the flow of the vessel of interest. With this method (ASL "Flow-Out") only the labeled blood emits a signal. Discussion: 3D b-SSFP and 3D Turbo SE non-contrast angiography techniques with ASL pre-pulses in 1.5 and 3T are available alternatives and, therefore, can be considered as a complement to other methods of magnetic resonance angiography when assessing vascular pathology.