MRI-­based quantification of cerebral oxygen extraction and oxygen metabolism using the relationship between phase shift and magnetic susceptibility

Introduction: The main purpose of this study was to extract global values of oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) in healthy volunteers, using magnetic resonance imaging (MRI) phase maps. The repeatability of the method was evaluated, and the age dependences of OEF and CMRO2 were analyzed. Material and methods: Phase data were acquired using a 3T MRI scanner with an 8- channel head coil, and a total of 20 volunteers (10 male, 10 female, age 25-84 years) participated. Magnitude and phase data were acquired from each subject, on two different occasions separated by 7-20 days, using a 3D double gradient echo pulse sequence. The difference in magnetic susceptibility between venous blood and surrounding tissue was obtained for the superior sagittal sinus (SSS) and the vein of Galen, using MRI phase data, and estimates of OEF and CMRO2 were subsequently calculated. Results: OEF estimates were 0.40 0.11 for vein of Galen and 0.31 0.08 for the SSS, and CMRO2 was 159.8 and 116.7 27.5 for the vein of Galen and the SSS, respectively. The method showed promising repeatability, with intraclass correlation coefficients (ICCs) of 0.95 and 0.82 for OEF measured in the vein of Galen and the SSS, respectively, and similar repeatability for CMRO2. The estimates showed, however, relatively large spread between volunteers, with coefficients of variation (CoVs) of 0.25 and 0.26 for OEF measured in the vein of Galen and the SSS, respectively, and similar CoVs for CMRO2. Finally, CMRO2 showed the anticipated relationship with age. Conclusion: Population mean values of OEF and CMRO2 were in good agreement with literature values, and the method delivered high repeatability, indicating stable measurements. The spread between different volunteers, however, was somewhat larger than expected. This may suggest that the method is sensitive towards measuring in different anatomical locations between volunteers.Magnetkameran används vanligen för att generera anatomiska bilder som används vid diagnostik av olika sjukdomstillstånd. Normala anatomiska bilder avspeglar magnetresonanssignalens (MR-signalens) magnitud, vilket är signalvektorns längd. Denna är proportionell mot bl.a. antalet vätekärnor i varje volymselement. Ett annat sätt att använda MR-signalen är att skapa en bild av signalvektorns fasvinkel, vilken är relaterad till hur snabbt vätekärnornas magnetiska moment roterar (precesserar) kring det externa magnetfältet i magnetkameran. Precessionsfrekvensen är proportionell mot det lokala magnetfältet i objektet och fasbilder kan därmed användas som kartor över hur magnetfältet varierar över objektet. Den magnetiska susceptibiliteten är ett mått på ett materials förmåga att bli magnetisterat av ett yttre magnetiskt fält, och denna egenskap varierar mellan syrerikt och syrefattigt blod. Följaktligen kommer arteriellt och venöst blod att ge upphov till olika lokala magnetfält och därmed ge olika fasskift. Syrefattigt blod innehåller deoxyhemoglobin, vilket är en molekyl som innehåller oparade elektroner. Ämnen med oparade elektroner kallas paramagnetiska och förstärker ett eventuellt externt magnetfält eftersom de oparade elektronerna beter sig som små magneter. Detta innebär att det lokala magnetfältet inuti en ven blir något högre än det externa magnetfältet. Syrerikt blod är, i likhet med normal vävnad, däremot svagt diamagnetiskt, vilket innebär att det skapas ett svagt motriktat magnetfält i dessa miljöer, som gör att det lokala magnetfältet blir lägre än det externa magnetfältet. Skillnaden i magnetfält mellan venöst blod och kringliggande vävnad kommer att bero på skillnaden i magnetisk susceptibilitet, vilket i sin tur beror på hur mycket syre det finns i det venösa blodet. Sjunker syrehalten i det venösa blodet så ökar det lokala magnetfältet. Detta gör att protonernas precessionsfrekvens ökar, vilket resulterar i en större fasvinkel under en given mättid. Genom att jämföra fasen i venöst blod med fasen i omkringliggande vävnad är det möjligt att beräkna motsvarande skillnad i magnetisk susceptibilitet. Från skillnaden i magnetisk susceptibilitet mellan venöst blod och omkringliggande vävnad kan sedan det venösa blodets syresättning beräknas. Om genomblödningen (perfusionen) i hjärnan är känd så är det möjligt att gå vidare med att, utifrån den venösa syresättningen, beräkna hjärnans syreförbrukning (s.k. syremetabolism). Om den venösa syrehalten mäts i ett kärl som dränerar hela hjärnan erhålls den globala metabolismen, d.v.s ett mått på hur mycket syre hela hjärnan förbrukar. Detta kan ge viktig klinisk information, eftersom metabolismen av syre är kopplad till vissa sjukdomstillstånd (t.ex. stroke och metaboliska sjukdomar) och hjärnans allmänna hälsa. Det finns andra metoder för att ta reda på den venösa syresättningen, men de är ofta invasiva eller innebär exponering för joniserande strålning, och det är därför önskvärt att kunna bedöma den venösa syresättningen med hjälp av MRavbildning. Den fasbaserade MR-metod som beskrivits ovan har, i denna studie, utvärderats med avseende på hur väl mätningarna kan upprepas, och absolutvärdena har jämförts med värden från andra studier. Metoden visade att mätningarna gav liknande resultat vid upprepade mätningar och absolutvärdena stämde väl överens med andra undersökningsmetoder, men relativt stor spridning observerades

Efficient Brain Age Prediction from 3D MRI Volumes Using 2D Projections

Using 3D CNNs on high-resolution medical volumes is very computationally demanding, especially for large datasets like UK Biobank, which aims to scan 100,000 subjects. Here, we demonstrate that using 2D CNNs on a few 2D projections (representing mean and standard deviation across axial, sagittal and coronal slices) of 3D volumes leads to reasonable test accuracy (mean absolute error of about 3.5 years) when predicting age from brain volumes. Using our approach, one training epoch with 20,324 subjects takes 20–50 s using a single GPU, which is two orders of magnitude faster than a small 3D CNN. This speedup is explained by the fact that 3D brain volumes contain a lot of redundant information, which can be efficiently compressed using 2D projections. These results are important for researchers who do not have access to expensive GPU hardware for 3D CNNs.publishedVersio

Efficient brain age prediction from 3D MRI volumes using 2D projections

Using 3D CNNs on high resolution medical volumes is very computationally demanding, especially for large datasets like the UK Biobank which aims to scan 100,000 subjects. Here we demonstrate that using 2D CNNs on a few 2D projections (representing mean and standard deviation across axial, sagittal and coronal slices) of the 3D volumes leads to reasonable test accuracy when predicting the age from brain volumes. Using our approach, one training epoch with 20,324 subjects takes 20 - 50 seconds using a single GPU, which two orders of magnitude faster compared to a small 3D CNN. These results are important for researchers who do not have access to expensive GPU hardware for 3D CNNs

Genetic Variants For Head Size Share Genes and Pathways With Cancer

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer

Assessment of MRI contrast agent concentration by quantitative susceptibility mapping (QSM) : application to estimation of cerebral blood volume during steady state

Objective: One major issue in dynamic susceptibility contrast MRI (DSC-MRI) is to accurately determine contrast agent (CA) concentration, since T2* relaxivity in vivo is generally unknown and varies between blood and tissue. In this study, quantitative susceptibility mapping (QSM) was used for quantification of CA concentration. Materials and methods: A DSC-MRI protocol, including phase data acquisition, was applied to 20 healthy volunteers in a test–retest study. By selecting a CSF reference region of interest (ROI), the values of all QSM images were shifted to show no CA-induced change in CSF. CA concentration and cerebral blood volume (CBV) were estimated using shifted QSM data. CSF reference ROI optimization was evaluated by investigation of CBV repeatability. The CBV age dependence was analysed and tissue T2* relaxivity was estimated. Results: The best repeatability of CBV, using an optimal CSF reference ROI, showed test-versus-retest correlations of r = 0.81 and r = 0.91 for white and grey matter, respectively. A slight CBV decrease with age was observed, and the estimated in vivo T2* relaxivity was 85 mM−1s−1. Conclusion: Provided that a carefully selected CSF reference ROI is used to shift QSM image values, susceptibility information can be used to estimate concentration of contrast agent and to calculate CBV

Prediction and action in cortical pain processing

Predicting that a stimulus is painful facilitates action to avoid harm. But how distinct are the neural processes underlying the prediction of upcoming painful events vis-a-vis those taking action to avoid them? Here, we investigated brain activity as a function of current and predicted painful or nonpainful thermal stimulation, as well as the ability of voluntary action to affect the duration of upcoming stimulation. Participants performed a task which involved the administration of a painful or nonpainful stimulus (S1), which predicted an immediately subsequent very painful or nonpainful stimulus (S2). Pressing a response button within a specified time window during S1 either reduced or did not reduce the duration of the upcoming stimulation. Predicted pain increased activation in several regions, including anterior cingulate cortex (ACC), midcingulate cortex (MCC), and insula; however, activation in ACC and MCC depended on whether a meaningful action was performed, with MCC activation showing a direct relationship with motor output. Insulas responses for predicted pain were also modulated by potential action consequences, albeit without a direct relationship with motor output. These findings suggest that cortical pain processing is not specifically tied to the sensory stimulus, but instead, depends on the consequences of that stimulus for sensorimotor control of behavior.Funding Agencies|Swedish Research CouncilSwedish Research CouncilEuropean Commission [FYF-2013-687]</p

The salience of self, not social pain, is encoded by dorsal anterior cingulate and insula

The human neural correlates of social rejection have attracted significant research interest, but remain subject to vigorous debate. Specifically, it has been proposed that a matrix of brain regions overlapping with the classical pain matrix, and including the dorsal anterior cingulate cortex (dACC) and the anterior insular cortex (AI) is critical for processing of social rejection. The present study expands on this conceptualization, by showing that these areas are involved in processing of self-relevant social evaluation, irrespective of valence. Forty healthy adolescents (N = 20 females) were tested in a magnetic resonance imaging (MRI) scanner. We used a novel paradigm that balanced participants experience of rejection and acceptance. In addition, the paradigm also controlled for whether the social judgment was towards the participants or towards other fictitious players. By creating a "self" and "other" distinction, we show that right AI and dACC are involved in processing the salience of being judged by others, irrespective of the quality of this judgment. This finding supports the idea that these regions are not specific to social rejection or even to pain or metaphorically painful experiences, but activate to self-relevant, highly salient information.Funding Agencies|Swedish Research Council [538-2013-7434]; ALF Grants, Region Ostergotland [LIO-535931]</p

Human endogenous oxytocin and its neural correlates show adaptive responses to social touch based on recent social context

Both oxytocin (OT) and touch are key mediators of social attachment. In rodents, tactile stimulation elicits the endogenous release of OT, potentially facilitating attachment and other forms of prosocial behavior, yet the relationship between endogenous OT and neural modulation remains unexplored in humans. Using a serial sampling of plasma hormone levels during functional neuroimaging across two successive social interactions, we show that contextual circumstances of social touch influence not only current hormonal and brain responses but also later responses. Namely, touch from a male to his female romantic partner enhanced her subsequent OT release for touch from an unfamiliar stranger, yet females’ OT responses to partner touch were dampened following stranger touch. Hypothalamus and dorsal raphe activation reflected plasma OT changes during the initial social interaction. In the subsequent interaction, precuneus and parietal-temporal cortex pathways tracked time- and context-dependent variables in an OT-dependent manner. This OT-dependent cortical modulation included a region of the medial prefrontal cortex that also covaried with plasma cortisol, suggesting an influence on stress responses. These findings demonstrate that modulation between hormones and the brain during human social interactions can flexibly adapt to features of social context over time

Deactivation of default mode network during touch

Interpersonal touch possesses a strong affective component, which immediately evokes attention. The neural processing of such touch is moderated by specialized C-tactile nerve fibers in the periphery and results in central activation of somatosensory areas as well as regions involved in social processing, such as the superior temporal gyrus (STG). In the present functional neuroimaging investigation, we tested the hypothesis that the attention grasping effect of interpersonal touch as compared to impersonal touch is reflected in a more-pronounced deactivation of the default mode network (DMN). Using functional magnetic resonance imaging, we investigated the neural processing of interpersonal relative to impersonal touch conditions that were furthermore modulated by stroking velocity in order to target c-tactile nerve fibers to a different extent. A sample of 30 healthy participants (19 women, mean age 40.5 years) was investigated. In the impersonal touch, participants were stroked with a brush on the forearm. In the interpersonal touch condition, the experimenter performed the stroking with the palm of his hand. Interpersonal touch was rated as more pleasant and intense than impersonal touch and led to a stronger blood oxygen level dependent (BOLD) signal increase in the somatosensory cortex SII extending to the superior temporal cortex. Over all touch conditions, this activation was coupled in time to the deactivation of prominent nodes of the DMN. Although deactivation of the DMN was most pronounced for interpersonal touch conditions, the direct comparison did not show significant differences in DMN deactivation between interpersonal and impersonal touch or between different stroking velocities. We therefore conclude that all applied touch conditions deactivate the DMN and the strong connection to areas which code the contextual and social characteristics of affective touch may explain the attention grasping effect of touch.Funding Agencies|Graduate Academy of TU Dresden; German Academic Exchange Service within the frame of the IPID4all program; Excellence Initiative by the German Federal Government; Excellence Initiative by the German State Government</p