Diffusion Tensor Imaging as a Diagnostic and Research Tool: A Study on Preterm Infants

Diffusion tensor imaging (DTI) is an advanced magnetic resonance imaging (MRI) technique. DTI is based on free thermal motion (diffusion) of water molecules. The properties of diffusion can be represented using parameters such as fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity, which are calculated from DTI data. These parameters can be used to study the microstructure in fibrous structure such as brain white matter. The aim of this study was to investigate the reproducibility of region-of-interest (ROI) analysis and determine associations between white matter integrity and antenatal and early postnatal growth at term age using DTI. Antenatal growth was studied using both the ROI and tract-based spatial statistics (TBSS) method and postnatal growth using only the TBSS method. The infants included to this study were born below 32 gestational weeks or birth weight less than 1,501 g and imaged with a 1.5 T MRI system at term age. Total number of 132 infants met the inclusion criteria between June 2004 and December 2006. Due to exclusion criteria, a total of 76 preterm infants (ROI) and 36 preterm infants (TBSS) were accepted to this study. The ROI analysis was quite reproducible at term age. Reproducibility varied between white matter structures and diffusion parameters. Normal antenatal growth was positively associated with white matter maturation at term age. The ROI analysis showed associations only in the corpus callosum. Whereas, TBSS revealed associations in several brain white matter areas. Infants with normal antenatal growth showed more mature white matter compared to small for gestational age infants. The gestational age at birth had no significant association with white matter maturation at term age. It was observed that good early postnatal growth associated negatively with white matter maturation at term age. Growth-restricted infants seemed to have delayed brain maturation that was not fully compensated at term, despite catchup growth.Diffuusiotensorikuvaus diagnostisena ja tutkimustyökaluna keskostutkimuksessa Diffuusiotensorikuvaus (DTI) on magneettikuvauksen erikoistekniikka. DTI perustuu veden vapaaseen lämpöliikkeeseen (diffuusioon). Diffuusion ominaisuuksia voidaan esittää DTI-datasta laskettavien parametrien avulla. Tällaisia parametreja ovat esimerkiksi fraktionaalinen anisotropia, keskimääräinen diffusiviteetti, aksiaalinen ja radiaalinen diffusiviteetti. Näitä parametrejä voidaan käyttää säikeisten rakenteiden esimerkiksi aivojen valkoisen aineen tutkimiseen. Tässä tutkimuksessa selvitettiin keskosten aivojen diffuusiotensorikuvista tehtyjen mielenkiintoalueisiin (ROI) perustuvien mittausten toistettavuutta sekä tutkittiin valkoisen aineen kypsyyden ja raskauden aikaisen sekä varhaisen postnataalisen kasvun välistä yhteyttä. Raskauden aikaisen kasvun vaikutusta tutkittiin käyttäen sekä ROI- että TBSS-tekniikoita. Postnataalista kasvua tarkasteltiin ainoastaan TBSS-tekniikalla. Tähän tutkimukseen otettiin mukaan keskoset, jotka syntyivät ennen 32 raskausviikkoa tai joiden syntymäpaino oli alle 1,501 g sekä MRI kuvaus oli tehty lasketunajan kohdalla. Tutkimukseen hyväksyttiin kesäkuun 2004 ja joulukuun 2006 välillä 132 keskosta. Poissulkukriteerien takia 76 keskosta (ROI) ja 36 (TBSS) hyväksyttiin tähän tutkimukseen. ROI-analyysi osoittautui melko toistettavaksi lasketun ajan iässä. Toistettavuus vaihteli sekä valkoisen aineen rakenteiden että diffuusioparametrien välillä. Normaali raskauden aikainen kasvu liittyi hyvään valkoisen aineen kehitykseen lasketunajan kohdalla. ROI-tekniikalla yhteys havaittiin corpus callosumin alueella. TBSS-menetelmä puolestaan näytti yhteyden usealla eri valkoisen aineen alueella. Syntymähetken gestaatioiällä ei havaittu yhteyttä valkoisen aineen kehitysasteeseen lasketun ajan kohdalla. Hyvän varhaisen vaiheen postnataalisen kasvun havaittiin liittyvän heikompaan valkoisen aineen kehitysasteeseen lasketunajan kohdalla. Saavutuskasvu ei ollut korjannut raskauden aikaisen kasvuhäiriön vaikutusta aivojen kypsyyteen laskettuun aikaan mennessä.Siirretty Doriast

Recent advances in diffusion neuroimaging: applications in the developing preterm brain

Measures obtained from diffusion-weighted imaging provide objective indices of white matter development and injury in the developing preterm brain. To date, diffusion tensor imaging (DTI) has been used widely, highlighting differences in fractional anisotropy (FA) and mean diffusivity (MD) between preterm infants at term and healthy term controls; altered white matter development associated with a number of perinatal risk factors; and correlations between FA values in the white matter in the neonatal period and subsequent neurodevelopmental outcome. Recent developments, including neurite orientation dispersion and density imaging (NODDI) and fixel-based analysis (FBA), enable white matter microstructure to be assessed in detail. Constrained spherical deconvolution (CSD) enables multiple fibre populations in an imaging voxel to be resolved and allows delineation of fibres that traverse regions of fibre-crossings, such as the arcuate fasciculus and cerebellar-cortical pathways. This review summarises DTI findings in the preterm brain and discusses initial findings in this population using CSD, NODDI, and FBA

A tract-specific approach to assessing white matter in preterm infants.

Diffusion-weighted imaging (DWI) is becoming an increasingly important tool for studying brain development. DWI analyses relying on manually-drawn regions of interest and tractography using manually-placed waypoints are considered to provide the most accurate characterisation of the underlying brain structure. However, these methods are labour-intensive and become impractical for studies with large cohorts and numerous white matter (WM) tracts. Tract-specific analysis (TSA) is an alternative WM analysis method applicable to large-scale studies that offers potential benefits. TSA produces a skeleton representation of WM tracts and projects the group's diffusion data onto the skeleton for statistical analysis. In this work we evaluate the performance of TSA in analysing preterm infant data against results obtained from native space tractography and tract-based spatial statistics. We evaluate TSA's registration accuracy of WM tracts and assess the agreement between native space data and template space data projected onto WM skeletons, in 12 tracts across 48 preterm neonates. We show that TSA registration provides better WM tract alignment than a previous protocol optimised for neonatal spatial normalisation, and that TSA projects FA values that match well with values derived from native space tractography. We apply TSA for the first time to a preterm neonatal population to study the effects of age at scan on WM tracts around term equivalent age. We demonstrate the effects of age at scan on DTI metrics in commissural, projection and association fibres. We demonstrate the potential of TSA for WM analysis and its suitability for infant studies involving multiple tracts

Mapping White Matter Microstructure in the One Month Human Brain

White matter microstructure, essential for efficient and coordinated transmission of neural communications, undergoes pronounced development during the first years of life, while deviations to this neurodevelopmental trajectory likely result in alterations of brain connectivity relevant to behavior. Hence, systematic evaluation of white matter microstructure in the normative brain is critical for a neuroscientific approach to both typical and atypical early behavioral development. However, few studies have examined the infant brain in detail, particularly in infants under 3 months of age. Here, we utilize quantitative techniques of diffusion tensor imaging and neurite orientation dispersion and density imaging to investigate neonatal white matter microstructure in 104 infants. An optimized multiple b-value diffusion protocol was developed to allow for successful acquisition during non-sedated sleep. Associations between white matter microstructure measures and gestation corrected age, regional asymmetries, infant sex, as well as newborn growth measures were assessed. Results highlight changes of white matter microstructure during the earliest periods of development and demonstrate differential timing of developing regions and regional asymmetries. Our results contribute to a growing body of research investigating the neurobiological changes associated with neurodevelopment and suggest that characteristics of white matter microstructure are already underway in the weeks immediately following birth

Diffusion-weighted and functional magnetic resonance imaging of the brain in preterm and term-born adolescents

Magnetic resonance imaging (MRI) is widely used in clinical and research settings in the adolescent population. Technical development has allowed the use of fine-grained methods to assess both the structural and functional properties of the brain. However, the specific technical limitations and improvements are mostly studied in phantom or adult studies, which may have an impact on their reliability as research tools when studying the younger population. Very preterm (VPT) birth is associated with several neurodevelopmental impairments. The present MRI tools provide opportunities to study brain maturation in detail. This thesis is a part of the multidisciplinary longitudinal follow-up study on the development and functioning of very low birth weight infants from infancy to school age (PIPARI). The follow-up cohort consists of infants born VPT (birth weight ≤1500 g and/or gestational age <32 weeks) in Turku University Hospital in 2001–2006 and term-born controls born in 2001–2004 in the same hospital. This thesis includes only children born VPT in 2004–2006 and controls born between 2003–2004 due to an upgrade of the MRI scanner during the recruitment. In Study I, the diffusion-weighted imaging (DWI) metrics at term-equivalent age were compared to the motor outcome at 11 years of age in children born VPT. Study II assessed the effect of the susceptibility correction to the DWI metrics in a healthy adolescent population. In Study III, temporal fluctuation of the resting state brain functioning was compared between 13-year-old adolescents born VPT and at term. The main prematurity-related findings of this thesis were that the DWI metrics of the corpus callosum, left corona radiata and right optic radiation at term are associated with later motor outcome in children born VPT and that adolescents born VPT show a decrease in active time, fluidity and range in brain activation during rest. These findings may reflect the adjustments in brain microstructure and function caused by the VPT birth. Fine-grained MRI methods are reliable tools for studying the mechanisms behind the clinical phenotypes of adolescents when technical limitations and age-appropriate analysis adjustments are considered.Diffuusiopainotteisen ja toiminnallisen aivojen magneettikuvantamisen käyttö nuoruusiässä entisillä pikkukeskosilla ja täysiaikaisilla verrokeilla Magneettikuvaus (MRI) on laajassa kliinisessä ja tieteellisessä käytössä lapsia ja nuoria tutkittaessa. Tekninen kehitys mahdollistaa yhä hienojakoisempia aivojen tutkimuksia. MRI:n teknisiä korjauksia on tutkittu pääosin mallintamalla tai aikuisilla, mikä voi heikentää luotettavuutta alaikäisillä. Hyvin ennenaikaisesti syntyvillä lapsilla neurologisen kehityksen poikkeavuuksien riski on täysiaikaisena syntyviä suurempi. Poikkeavuudet voivat liittyä aivojen kehityksen muutoksiin, joita nykyisillä tekniikoilla voidaan tutkia aiempaa yksityiskohtaisemmin. Väitöskirja on osa PIPARI-tutkimusta (Pienipainoisten riskilasten käyttäytyminen ja toimintakyky imeväisiästä kouluikään). Seurantakohortti koostuu pikkukeskosina (syntymäpaino ≤1500 g ja/tai raskauden kesto <32 viikkoa) Tyksissä vuosina 2001–2006 syntyneistä lapsista sekä täysiaikaisena 2001–2004 syntyneistä verrokeista. MRI-laitteiston päivityksestä johtuen osatyöt käsittelevät pikkukeskosina vuosina 2004–2006 ja verrokkeina vuosina 2003–2004 syntyneitä. Ensimmäisessä osatyössä verrattiin aivojen diffuusiokuvantamistuloksia entisten pikkukeskosten motoriseen toimintakykyyn 11-vuotiaana. Toinen osatyö käsitteli suskeptibiliteettikorjauksen vaikutusta aivojen diffuusiokuvantamisen mittaustuloksiin. Kolmannessa osatyössä vertailtiin 13-vuotiaiden entisten pikkukeskosten ja verrokkien aivojen aktiivisuuden vaihtelua lepotilassa toiminnallisen MRI-kuvauksen aikana. Tämän väitöskirjan keskosuuteen liittyvät päätulokset olivat lasketun syntymäajan corpus callosumin, vasemman corona radiatan ja oikean optisen radaston diffuusiomittaustulosten yhteys motoriseen kehitykseen 11-vuotiaana sekä pikkukeskosina syntyneillä havaittu aivojen vähäisempi aktiivinen aika ja alentunut aktiivisuuden vaihtelun joustavuus 13-vuotiaana. Nämä löydökset saattavat olla seurausta varhaiseen syntymään liittyvistä aivojen mikrorakenteen ja toiminnan muutoksista. Hienojakoiset MRI-menetelmät vaikuttavat olevan luotettavia nuorisoikäisiä tutkittaessa, kunhan tekniset rajoitteet ja ikäsovitukset huomioidaan

Reduced apparent fiber density in the white matter of premature-born adults

Premature-born adults exhibit lasting white matter alterations as demonstrated by widespread reduction in fractional anisotropy (FA) based on diffusion-weighted imaging (DWI). FA reduction, however, is non-specific for microscopic underpinnings such as aberrant myelination or fiber density (FD). Using recent advances in DWI, we tested the hypothesis of reduced FD in premature-born adults and investigated its link with the degree of prematurity and cognition. 73 premature- and 89 mature-born adults aged 25–27 years underwent single-shell DWI, from which a FD measure was derived using convex optimization modeling for microstructure informed tractography (COMMIT). Premature-born adults exhibited lower FD in numerous tracts including the corpus callosum and corona radiata compared to mature-born adults. These FD alterations were associated with both the degree of prematurity, as assessed via gestational age and birth weight, as well as with reduced cognition as measured by full-scale IQ. Finally, lower FD overlapped with lower FA, suggesting lower FD underlie unspecific FA reductions. Results provide evidence that premature birth leads to lower FD in adulthood which links with lower full-scale IQ. Data suggest that lower FD partly underpins FA reductions of premature birth but that other processes such as hypomyelination might also take place

MR connectomics: a conceptual framework for studying the developing brain

The combination of advanced neuroimaging techniques and major developments in complex network science, have given birth to a new framework for studying the brain: “connectomics.” This framework provides the ability to describe and study the brain as a dynamic network and to explore how the coordination and integration of information processing may occur. In recent years this framework has been used to investigate the developing brain and has shed light on many dynamic changes occurring from infancy through adulthood. The aim of this article is to review this work and to discuss what we have learned from it. We will also use this body of work to highlight key technical aspects that are necessary in general for successful connectome analysis using today's advanced neuroimaging techniques. We look to identify current limitations of such approaches, what can be improved, and how these points generalize to other topics in connectome research