Analiza mikrostrukture prolaznih fetalnih zona i segmenata bijele tvari ljudskoga mozga histološkim metodama i magnetskom rezonancijom [Microstructural analysis of transient fetal zones and white matter segments of human brain using histological methods and magnetic resonance imaging]

The development of human brain axonal pathways is a complex process where transitional fetal zones and white matter segments play an important role due to the various spatio-temporal frames of intense growth and the consequent specific sensitivity to the harmful factors during development. The aim of this thesis was to define the microstructural changes of the white matter segments, for the purpose of better correlation of MRI with clinical parameters in neurodevelopmental disorders. This study included postmortem brains (fetal/early postnatal period) treated with histological, immunohistochemical and MRI in vitro methods (40 samples in total). In vivo MR images were used in qualitative (12 fetuses in utero, 49 premature infants) and FA-ADC analysis at the (corrected) term-age (7 newborns, 52 premature infants) and at the second year of life (31 subjects). The histological/MRI analysis of the prenatal/perinatal development of the white matter segments reveals maturational specificity of the second white matter segment, especially the differences between premature and full term infants. The FA and ADC values follow the histological development of the segments, pointing to their differentiation in radial direction, from cerebral ventricles to pial surface, distinguishing groups of neonates between themselves and in comparison with the control group at the corrected term-age, with the tendency of reducing the differences towards the second year of life. Groups with and without perinatal lesions visible on structural MRI differ in the ADC values in the second year of life The most complex system of commissural, projection and associative fibers is present in the sagittal strata, characterized by particular MR signal intensity changes, which makes it the potential biomarker of perinatal neurorisk. Knowledge of histological/MRI development of the white matter segments has potential for application during routine brain imaging analysis

Interactive histogenesis of axonal strata and proliferative zones in the human fetal cerebral wall

Development of the cerebral wall is characterized by partially overlapping histogenetic events. However, little is known with regards to when, where, and how growing axonal pathways interact with progenitor cell lineages in the proliferative zones of the human fetal cerebrum. We analyzed the developmental continuity and spatial distribution of the axonal sagittal strata (SS) and their relationship with proliferative zones in a series of human brains (8-40 post-conceptional weeks; PCW) by comparing histological, histochemical, and immunocytochemical data with magnetic resonance imaging (MRI). Between 8.5 and 11 PCW, thalamocortical fibers from the intermediate zone (IZ) were initially dispersed throughout the subventricular zone (SVZ), while sizeable axonal "invasion" occurred between 12.5 and 15 PCW followed by callosal fibers which "delaminated" the ventricular zone-inner SVZ from the outer SVZ (OSVZ). During midgestation, the SS extensively invaded the OSVZ, separating cell bands, and a new multilaminar axonal-cellular compartment (MACC) was formed. Preterm period reveals increased complexity of the MACC in terms of glial architecture and the thinning of proliferative bands. The addition of associative fibers and the formation of the centrum semiovale separated the SS from the subplate. In vivo MRI of the occipital SS indicates a "triplet" structure of alternating hypointense and hyperintense bands. Our results highlighted the developmental continuity of sagittally oriented "corridors" of projection, commissural and associative fibers, and histogenetic interaction with progenitors, neurons, and glia. Histogenetical changes in the MACC, and consequently, delineation of the SS on MRI, may serve as a relevant indicator of white matter microstructural integrity in the developing brain

Microstructural analysis of transient fetal zones and white matter segments of human brain using histological methods and magnetic resonance imaging

Razvoj aksonskih puteva ljudskog mozga složen je proces gdje podjela na prolazne fetalne zone i segmente bijele tvari ima važnu ulogu zbog različitih vremensko-prostornih okvira intenzivnog rasta i posljedične specifične osjetljivosti na štetne čimbenike tijekom razvoja. Cilj rada je definiranje mikrostrukturalnih promjena segmenata bijele tvari, u svrhu jasnije korelacije MR-a i kliničkih parametara u nerorazvojnim poremećajima. Istraživanje uključuje postmortem mozgove (fetalno/rano postnatalno razdoblje) obrađene histološkim, imunohistokemijskim i in vitro MR metodama (ukupno 40 uzoraka), te ispitanike čiji su in vivo MR slikovni prikazi korišteni u kvalitativnoj (12 fetusa in utero, 49 nedonoščadi) i FA-ADC analizi u (korigiranoj) terminskoj dobi (7 novorođenčadi, 52 nedonoščadi) i drugoj godini života (31 ispitanik). Histološka/MR analiza prenatalnog/perinatalnog razvoja segmenata bijele tvari otkriva specifičnosti maturacije segmenta II bijele tvari, posebice različitosti između nedonoščadi i terminske novorođenčadi. FA i ADC vrijednosti prate histološki razvoj segmenata, ističući diferencijaciju razvoja segmenata bijele tvari u radijalnom smjeru od moždanih komora prema pijalnoj površini, razlikujući se između nedonoščadi međusobno i u odnosu na kontrolnu skupinu u terminskoj dobi, s tendencijom smanjivanja razlika u drugoj godini života. ADC vrijednosti u drugoj godini života razlikuju skupine s/bez perinatalnih lezija vidljivih na strukturnom MR-u. Najsloženiji sustav komisuralnih, projekcijskih i asocijativnih vlakana prisutan je u sagittal strata, što ga, uz specifične promjene intenziteta MR-signala, čini potencijalnim biomarkerom neurorizika. Poznavanje histološkog/MR razvoja segmenata bijele tvari ima potencijalnu primjenu tijekom rutinske analize mozga nedonoščeta.The development of human brain axonal pathways is a complex process where transitional fetal zones and white matter segments play an important role due to the various spatio-temporal frames of intense growth and the consequent specific sensitivity to the harmful factors during development. The aim of this thesis was to define the microstructural changes of the white matter segments, for the purpose of better correlation of MRI with clinical parameters in neurodevelopmental disorders. This study included postmortem brains (fetal/early postnatal period) treated with histological, immunohistochemical and MRI in vitro methods (40 samples in total). In vivo MR images were used in qualitative (12 fetuses in utero, 49 premature infants) and FA-ADC analysis at the (corrected) term-age (7 newborns, 52 premature infants) and at the second year of life (31 subjects). The histological/MRI analysis of the prenatal/perinatal development of the white matter segments reveals maturational specificity of the second white matter segment, especially the differences between premature and full term infants. The FA and ADC values follow the histological development of the segments, pointing to their differentiation in radial direction, from cerebral ventricles to pial surface, distinguishing groups of neonates between themselves and in comparison with the control group at the corrected term-age, with the tendency of reducing the differences towards the second year of life. Groups with and without perinatal lesions visible on structural MRI differ in the ADC values in the second year of life The most complex system of commissural, projection and associative fibers is present in the sagittal strata, characterized by particular MR signal intensity changes, which makes it the potential biomarker of perinatal neurorisk. Knowledge of histological/MRI development of the white matter segments has potential for application during routine brain imaging analysis

Microstructural analysis of transient fetal zones and white matter segments of human brain using histological methods and magnetic resonance imaging

Razvoj aksonskih puteva ljudskog mozga složen je proces gdje podjela na prolazne fetalne zone i segmente bijele tvari ima važnu ulogu zbog različitih vremensko-prostornih okvira intenzivnog rasta i posljedične specifične osjetljivosti na štetne čimbenike tijekom razvoja. Cilj rada je definiranje mikrostrukturalnih promjena segmenata bijele tvari, u svrhu jasnije korelacije MR-a i kliničkih parametara u nerorazvojnim poremećajima. Istraživanje uključuje postmortem mozgove (fetalno/rano postnatalno razdoblje) obrađene histološkim, imunohistokemijskim i in vitro MR metodama (ukupno 40 uzoraka), te ispitanike čiji su in vivo MR slikovni prikazi korišteni u kvalitativnoj (12 fetusa in utero, 49 nedonoščadi) i FA-ADC analizi u (korigiranoj) terminskoj dobi (7 novorođenčadi, 52 nedonoščadi) i drugoj godini života (31 ispitanik). Histološka/MR analiza prenatalnog/perinatalnog razvoja segmenata bijele tvari otkriva specifičnosti maturacije segmenta II bijele tvari, posebice različitosti između nedonoščadi i terminske novorođenčadi. FA i ADC vrijednosti prate histološki razvoj segmenata, ističući diferencijaciju razvoja segmenata bijele tvari u radijalnom smjeru od moždanih komora prema pijalnoj površini, razlikujući se između nedonoščadi međusobno i u odnosu na kontrolnu skupinu u terminskoj dobi, s tendencijom smanjivanja razlika u drugoj godini života. ADC vrijednosti u drugoj godini života razlikuju skupine s/bez perinatalnih lezija vidljivih na strukturnom MR-u. Najsloženiji sustav komisuralnih, projekcijskih i asocijativnih vlakana prisutan je u sagittal strata, što ga, uz specifične promjene intenziteta MR-signala, čini potencijalnim biomarkerom neurorizika. Poznavanje histološkog/MR razvoja segmenata bijele tvari ima potencijalnu primjenu tijekom rutinske analize mozga nedonoščeta.The development of human brain axonal pathways is a complex process where transitional fetal zones and white matter segments play an important role due to the various spatio-temporal frames of intense growth and the consequent specific sensitivity to the harmful factors during development. The aim of this thesis was to define the microstructural changes of the white matter segments, for the purpose of better correlation of MRI with clinical parameters in neurodevelopmental disorders. This study included postmortem brains (fetal/early postnatal period) treated with histological, immunohistochemical and MRI in vitro methods (40 samples in total). In vivo MR images were used in qualitative (12 fetuses in utero, 49 premature infants) and FA-ADC analysis at the (corrected) term-age (7 newborns, 52 premature infants) and at the second year of life (31 subjects). The histological/MRI analysis of the prenatal/perinatal development of the white matter segments reveals maturational specificity of the second white matter segment, especially the differences between premature and full term infants. The FA and ADC values follow the histological development of the segments, pointing to their differentiation in radial direction, from cerebral ventricles to pial surface, distinguishing groups of neonates between themselves and in comparison with the control group at the corrected term-age, with the tendency of reducing the differences towards the second year of life. Groups with and without perinatal lesions visible on structural MRI differ in the ADC values in the second year of life The most complex system of commissural, projection and associative fibers is present in the sagittal strata, characterized by particular MR signal intensity changes, which makes it the potential biomarker of perinatal neurorisk. Knowledge of histological/MRI development of the white matter segments has potential for application during routine brain imaging analysis

Microstructural analysis of transient fetal zones and white matter segments of human brain using histological methods and magnetic resonance imaging

Razvoj aksonskih puteva ljudskog mozga složen je proces gdje podjela na prolazne fetalne zone i segmente bijele tvari ima važnu ulogu zbog različitih vremensko-prostornih okvira intenzivnog rasta i posljedične specifične osjetljivosti na štetne čimbenike tijekom razvoja. Cilj rada je definiranje mikrostrukturalnih promjena segmenata bijele tvari, u svrhu jasnije korelacije MR-a i kliničkih parametara u nerorazvojnim poremećajima. Istraživanje uključuje postmortem mozgove (fetalno/rano postnatalno razdoblje) obrađene histološkim, imunohistokemijskim i in vitro MR metodama (ukupno 40 uzoraka), te ispitanike čiji su in vivo MR slikovni prikazi korišteni u kvalitativnoj (12 fetusa in utero, 49 nedonoščadi) i FA-ADC analizi u (korigiranoj) terminskoj dobi (7 novorođenčadi, 52 nedonoščadi) i drugoj godini života (31 ispitanik). Histološka/MR analiza prenatalnog/perinatalnog razvoja segmenata bijele tvari otkriva specifičnosti maturacije segmenta II bijele tvari, posebice različitosti između nedonoščadi i terminske novorođenčadi. FA i ADC vrijednosti prate histološki razvoj segmenata, ističući diferencijaciju razvoja segmenata bijele tvari u radijalnom smjeru od moždanih komora prema pijalnoj površini, razlikujući se između nedonoščadi međusobno i u odnosu na kontrolnu skupinu u terminskoj dobi, s tendencijom smanjivanja razlika u drugoj godini života. ADC vrijednosti u drugoj godini života razlikuju skupine s/bez perinatalnih lezija vidljivih na strukturnom MR-u. Najsloženiji sustav komisuralnih, projekcijskih i asocijativnih vlakana prisutan je u sagittal strata, što ga, uz specifične promjene intenziteta MR-signala, čini potencijalnim biomarkerom neurorizika. Poznavanje histološkog/MR razvoja segmenata bijele tvari ima potencijalnu primjenu tijekom rutinske analize mozga nedonoščeta.The development of human brain axonal pathways is a complex process where transitional fetal zones and white matter segments play an important role due to the various spatio-temporal frames of intense growth and the consequent specific sensitivity to the harmful factors during development. The aim of this thesis was to define the microstructural changes of the white matter segments, for the purpose of better correlation of MRI with clinical parameters in neurodevelopmental disorders. This study included postmortem brains (fetal/early postnatal period) treated with histological, immunohistochemical and MRI in vitro methods (40 samples in total). In vivo MR images were used in qualitative (12 fetuses in utero, 49 premature infants) and FA-ADC analysis at the (corrected) term-age (7 newborns, 52 premature infants) and at the second year of life (31 subjects). The histological/MRI analysis of the prenatal/perinatal development of the white matter segments reveals maturational specificity of the second white matter segment, especially the differences between premature and full term infants. The FA and ADC values follow the histological development of the segments, pointing to their differentiation in radial direction, from cerebral ventricles to pial surface, distinguishing groups of neonates between themselves and in comparison with the control group at the corrected term-age, with the tendency of reducing the differences towards the second year of life. Groups with and without perinatal lesions visible on structural MRI differ in the ADC values in the second year of life The most complex system of commissural, projection and associative fibers is present in the sagittal strata, characterized by particular MR signal intensity changes, which makes it the potential biomarker of perinatal neurorisk. Knowledge of histological/MRI development of the white matter segments has potential for application during routine brain imaging analysis

Transient structural MRI patterns correlate with the motor functions in preterm infants

Aim: To explore the relationships between transient structural brain patterns on MRI at preterm and at term-equivalent age (TEA) as a predictor of general movements (GMs) and motor development at 1-year corrected age (CA) in very preterm infants. ----- Methods: In this prospective study, 30 very preterm infants (median = 28wks; 16 males) had structural magnetic resonance imaging (MRI) at preterm (median = 31wks + 6d) and at TEA (median = 40wks) and neuromotor assessments. The quality of GMs was assessed by Prechtl's general movements assessment and a detailed analysis of the motor repertoire was performed by calculating a motor optimality score (MOS), both at term age and at 3 months post-term. Motor development at 1-year CA was evaluated with the Infant Motor Profile (IMP). Associations between qualitative MRI findings and neuromotor scores were investigated. ----- Results: Abnormal GMs and low motor performance at 1-year CA were associated with the poor visibility of transient structural pattern, that is with sagittal strata. ----- Interpretation: Transient structural MRI pattern, sagittal strata, at preterm age is related to the quality of GMs and later motor development in preterm infants. This transient fetal brain compartment may be considered as a component of neurobiological basis for early neuromotor behavior, as expressed by GMs

Linking integrity of visual pathways trajectories to visual behavior deficit in very preterm infants

Low-risk premature infants often develop visual deficits, even in the absence of ophthalmological complications and high-graded brain injury. These complications can be explained by the nature of subtle perinatal lesions and alterations of brain growth due to the prematurity. Subtle brain injuries and vulnerability of axonal pathways can be observed in spatiotemporal context of the white matter segments. The aim of this study was to examine the link between MRI quantitative (brain metrics data) and qualitative features (visibility of 2nd white matter segment - sagittal strata and periventricular crossroads C1-C6) and visual behavior in preterm neonates at term-equivalent age. Seventy-one very preterm infants without high-graded brain injury on MRI and no ocular pathologies were studies. The infants received MRI scans at term-equivalent age. MRI scans were analyzed using (a) simple brain metrics and (b) scoring the visibility of transient structural patterns (sagittal strata and periventricular crossroads). At the median age of 41+5 PMA weeks infants completed the Neonatal Visual Assessment. Results indicated that visibility of temporal crossroad area C6 and frontal and occipital sagittal strata was positively correlated with visual tracking skills in neonatal period. Furthermore, the visibility of frontal and occipital sagittal strata were strong predictors of total Neonatal Visual Assessment score. The findings confirmed that sagittal strata and periventricular crossroads prominence is a valuable additional marker in perinatal neuroimaging at term-equivalent age. Thus, alteration in MRI appearance of temporal crossroad and sagittal strata may be useful in predicting of visual behavior for very premature born infants