Diffusion tensor imaging of normal and injured developing human brain-a technical review

“DTI has potential importance for the paediatric populatio”

“DTI uses the uneven water diffusion along Change in frontal-striatal circuits is the most likely signif- axons to measure white matter tissue integrity (LeBihan icant cause of reduced executive function in nonde- et al., 2001; Neil et al., 2002).”

“Neil et al. [ 27 ] found dramatic and generalized changes in water apparent diffusion coefficients and diffusion anisotropy.”

“DT MRI (DTI) has also appeared as a promising tool for monitoring brain maturation and development (10,11), and especially the myelination process, as well Anatomical and Functional Neuroimaging Laboratory, Service Hospitalier Frédéric Joliot, Commissariat à l’Energie Atomique, Orsay, France.”

“In particular, several MRI techniques available on clinical scanners (section ‘Structural MRI techniques and developmental specificities’) enable to investigate and follow longitudinally the brain development and plasticity of healthy and at-risk children (Barkovich, 2000; Paus et al., 2001; Neil et al., 2002; Prayer…”

“…Ben Bashat et al., 2005; Bonekamp et al., 2007; Eluvathingal et al., 2007; Giorgio et al., 2008; Klingberg et al., 1999; Mukherjee et al., 2001; Neil et al., 1998, 2002; Schmithorst et al., 2002; Snook et al., 2005; Suzuki et al., 2003], suggesting that DTI is indeed sensitive to maturation of…”

“It has been used increasingly to study a host of brain conditions including white matter diseases, neuropsychiatric conditions, ischemic syndromes, neurodevelopment, and aging (Horsfield and Jones, 2002; Lim and Helpern, 2002; Moseley, 2002; Neil et al., 2002; Sotak, 2002).”

“There has been great interest in using diffusion anisotropy as a marker for white matter tract integrity, for example for disease diagnosis, tracking disease progression, finding disease subcategories, studying normal development or aging and as complementary information to functional magnetic resonance imaging (FMRI)…”

“Rapid decreases in diffusivity during infancy may also reflect, in part, decreasing water content (Neil et al., 2002).”

“DTI has clearly an important potential for the pediatric population (Neil et al., 2002).”

“High quality DTI data from pediatric brains are becoming more and more abundant (Huppi and Inder, 2001; Neil et al., 2002 ).”

“It has been postulated that injuries of specific white matter tracts in cerebral palsy are due to an incomplete state of development of the vascular supply to the cerebral white matter and the maturation-dependent vulnerability of the oligodendroglia precursor cells (the timing of insults and actively growing of axons…”

“1, for reviews, Beaulieu et al., 2002; Neil et al., 2002].”

“…based on relaxation parameters, this technology has superior contrast to delineate the anatomy of premyelinated brains (Hüppi et al., 1998, 2001; Neil et al., 1998, 2002; McKinstry et al., 2002; Miller et al., 2002b; Mukherjee et al., 2002; Zhang et al., 2003; Maas et al., 2004; Partridge et…”

“DTI has been applied to better understand neurodevelopment in several studies from neonates up to the 8th decade of life (Moseley, 2002; Neil et al., 2002).”

“This technique was found to be more sensitive than other imaging methods to diffuse axonal injury following TBI ( Neil, Miller, Mukherjee, & Huppi, 2002 ; Rugg-Gunn, Symms, Barker, Greenwood, & Duncan, 2001 ).”

“…proliferation, whereas the increase in FA might rather reflect changes which accompany the ''premyelinating state'', the last stage of ''true'' myelination with wrapping of the myelin sheath around the axons and the increasing organization and compacity of the bundles (Neil et al., 2002).”

“Although less common, severe selective involvement of subcortical white matter has been documented (Neil et al., 2002; Vermeulen et al., 2003).”

“DWI, T1 and T2 imaging), which assess mainly hemorrhage and edema (Arfanakis et al., 2002; Gupta et al., 2005; Neil et al., 2002; Pierpaoli et al., 1996; RuggGunn et al., 2001; Wieshmann et al., 1999).”

“The tightly organized white-matter tracts restrict the diffusion of water, producing anisotropic diffusion, whereas water diffusion in the grey matter tends to be less restricted [33,34].”

“In the noninjured developing brain, diffusion anisotropy in white matter, as measured by DTI, is a function of a number of factors including axon structure, axon packing, tissue water content, and myelin, among others (Neil et al., 2002).”

“Estimation of white matter using imaging techniques is more accurately performed through diffusion tensor imaging (DTI) ((Engelbrecht et al., 2002; Mukherjee and McKinstry, 2006; Neil et al., 2002).”

“In the present study, K // and λ // in WM were observed to increase concurrently. known that there are premyelination modifications in WM that affect the diffusion properties, hence the FA in WM is higher in early postnatal stage (Huppi and Dubois, 2006; Neil et al., 2002).”

“Especially in neuroimaging, DWI offers the possibility of detecting injuries earlier than they can be detected with conventional imaging methods [15].”

“DTI has been used in the study of neurodevelopment ( Neil et al., 2002 ) and shows more widespread white matter changes with age than previous T1-weighted studies (Paus et al., 1999; Thompson et al., 2000).”

“With the advent of DTI, a technique based on the measurement of water molecular diffusion, the architecture of human WM tracts can be more thoroughly scrutinized in vivo (Engelbrecht et al., 2002; Mukherjee and McKinstry, 2006; Mukherjee et al., 2002; Neil et al., 2002; Neil et al., 1998).”

“Also, fractional anisotropy of white matter tracts increases with age during childhood and adolescence (Barnea-Goraly et al., 2005; Neil et al., 2002; Snook et al., 2005).”

“Diffusion tensor imaging, a nuclear magnetic resonance modality, uses the variability in water diffusion in different directions to map white matter pathways based on structural tissue organization.(84) Diffusion tensor imaging is the only noninvasive method for mapping white matter fiber tract trajectories in the hum…”

“This technique has been widely applied for the evaluation of CNS development and pathology (Bammer et al., 2000; Lim and Helpern, 2002; Moseley, 2002; Neil et al., 2002).”

“The quantitative diffusion information generated by DTI further allows white matter injury to be assessed in various neurodegenerative disorders (8,9).”

“Neil and colleagues [89] have previously pointed out the technical challenges that hinder the application of DTI tractography to the pediatric”

“It is more sensitive than conventional magnetic resonance imaging for detecting subtle abnormalities (32-38).”

“These measurements are possible indicators of axonal organization and degree of myelination (Hüppi et al., 1998, Neil et al., 1998, Beaulieu, 2002, Neil et al., 2002, Song et al., 2002).”

“…2002; Song et al., 2005) and the subsequent increase of FA observed during childhood and adolescence, while the decreasing λ// that contributes to decreasing MD could be caused by reduced brain water content or increased prevalence of isotropicmembranes (Neil et al., 2002; Song et al., 2003).”

“structed by tractography in the infant brain, even before maturation of these tracts is complete [70] (Figure I). Because arrangement, density and myelination of the fibers vary with age at different rates across bundles, maturation can be mapped in vivo through the monitoring of diffusion parameters [ 71 ].”

“…changes could be attributed to reduced axonal density and/or myelination of these long tracts as suggested by diffusion tensor imaging studies of brain development in normal children (Huppi et al., 1998; Neil et al., 2002) and subjects with 22qDS (Barnea-Goraly et al., 2003; Simon et al., 2005).”

“[3] For sinusoidal undulation, the solution to Equation [2] is given by:”

“…to the pattern of findings identified in several association and commissural pathways in typically developing children and adolescents (Alexander et al., 2007; Ashtari et al., 2005; Eluvathingal et al., 2007; Nagy et al., 2004; Neil et al., 2002; Olesen et al., 2003; Schmithorst et al., 2002).”

“We observed in rats a decrease in MD with age similar to that in neonates and children (Neil et al., 2002; Huppi and Dubois, 2006).”

“FA reflects aspects of axonal integrity and organization that are not related to myelin (Beaulieu, 2002; Neil et al., 2002; Wozniak and Lim, 2006), and myelin is not necessary for fibers to have significant diffusion anisotropy (Beaulieu and Allen, 1994; Prayer et al.”

“DTI has been well studied in normal brain development(16-18) and has been shown to improve detection of lesions in the first years of life.(19-21) Results have provided further understanding of pathogenesis and treatment in a range of neurologic disorders by providing visualization of specific white matter fiber tract…”

“N IH -PA Author M anuscript N IH -PA Author M anuscript N IH -PA Author M anuscript Diffusion tensor imaging (DTI; Basser 1995) affords an opportunity to detect subtle abnormalities in directionally organized tissues such as white matter.”

“Diffusion-tensor imaging is an MR imaging technique that is sensitized to the diffusive properties of water molecules (13) and offers the possibility of detecting brain injuries earlier than they can be detected with conventional imaging methods (14).”

“Although little has been reported on the correlation of FA changes and MD changes, they are independent of one another, and a change in one is not always accompanied by an opposite change in the other [37, 71, 90].”

“…to investigate potential WM deficits as DT-MRI may be better able to detect pathology in normal appearing WM tissue while conventional MRI is able to ascertain independently occurring WM volumetric changes (Makki et al., 2007; Neil et al., 2002; Rugg-Gunn et al., 2001; Sundram et al., 2010).”

“On the contrary, DWI and DTI parameters have been applied in CC studies and have demonstrated much greater sensitivity in revealing the WM degeneration in AD than conventional MRI imaging techniques [68,71, 77].”

“Diffusion tensor imaging (DTI) has recently emerged as a sensitive, noninvasive tool for assessing white matter abnormalities in the central nervous system (5,6).”

“, demyelination) are reflected in lower FA and higher MD (Neil et al., 2002).”

“Previous studies have demonstrated correlations between age and increases in fractional anisotropy (FA) and decreases in mean ( D ), transverse ( ), and longitudinal ( //) diffusivities (for a review, see Neil et al., 2002; Partridge et al., 2004).”

“As the brain develops there are many changes seen in the grey and white matter that are associated with the changing microstructures of the tissues that coincide with process of myelination, synaptogenesis and dendritc arborization (Neil et al. 2002).”

“DTI provides noninvasive measures of microstructural WM integrity by measuring molecular diffusion and is highly sensitive in detecting axonal injury.(11,12) DTI has been used in Received January 17, 2011; accepted after revision May 1.”

“Therefore, the myelination process is only described indirectly and the exact relations between the decrease in ADCav and increase in RA and FA due to brain maturation are not yet completely understood [7, 12, 13].”

“Abnormal brain development or acquired brain damage typically contributes to lower FA and higher MD values in affected white matter compared with normal white matter (Neil et al. 2002).”

“For example, the mapping of the spatial organization of white matter in fiber bundles with DTI (Mori and Van Zijl, 2002), revealed that arrangement, density, and myelination of the fibers change with age and at different rates across bundles (Neil et al., 2002; Dubois et al., 2006).”

“, 2008) and cannot be observed macroscopically with the structural MRI technique (Neil et al., 2002; Sundgren et al., 2004; Sun et al., 2005).”

“Keywords: brain development, cortex, diffusion tensor imaging, hypoxia--ischemia, rat”

“More recently, WM changes have been investigated using diffusion tensor imaging (DTI), a magnetic resonance imaging (MRI) technique that provides information about WM integrity through measurements of water diffusion and its directional dependence.(13,14) Several DTI studies, as well as related MRI measurements of tra…”

“Thus, DW-MRI can be used to characterize the ultrastructural properties and integrity of tissues [7].”

“DTI parameters reflect restriction of water movement in tissue (Drobyshevsky et al., 2005; Huppi et al., 1998; Le Bihan, 2003; Neil et al., 2002): Fractional anisotropy (FA) is a composite measure of the extent of tissue directionality (Pierpaoli and Basser, 1996).”

“DTI measures the molecular motion of water in the brain tissue and is a non-invasive way of studying tissue organization with regard to both brain development and injury (10).”

“However, the material properties of the brain might change significantly during postnatal development or maturation due to alterations in water content and myelination of fiber tracts (Larvaron et al. 2007; Neil et al. 2002).”

“DTI measures the rate and directionality of water diffusion within specifi c anatomic regions of interest and there is some evidence that DTI is more sensitive to structural brain abnormalities compared to traditional MRI morphometry (Neil et al 2002).”

“After the second year of life, the myelination can be regarded as completed [Mukherjee et al., 2002; Neil et al., 2002].”

“DTI offers the unique opportunity to assess in vivo the integrity of fiber tracts and cortical connections, especially in patients with brain lesions (Gauvain et al., 2001; Huppi et al., 1998, 2001; Mori et al., 2002; Neil et al., 2002).”

“Age-related changes in RTOP likely reflect aggregate water restriction from developmental factors like myelination and axonal packing (Aung et al., 2013; Beaulieu, 2002; Feldman et al., 2010; Neil et al., 2002), as RTOP is equally sensitive to water movement in all directions in all voxels.”