In this study, we aimed to identify major fiber pathways and their spatiotemporal relationships w... more In this study, we aimed to identify major fiber pathways and their spatiotemporal relationships within transient fetal zones in the human fetal brain by comparing postmortem high-angular resolution diffusion MR imaging (HARDI) in combination with deterministic streamline tractography and histology. Diffusion weighted imaging was performed on postmortem human fetal brains [N = 9, age = 18-34 post-conceptual weeks (PCW)] that were grossly normal with no pathologic abnormalities. After HARDI was performed, the fibers were reconstructed using Q-ball algorithm and deterministic streamline tractography. The position of major fiber pathways within transient fetal zones was identified both on diffusion weighted images and on histological sections. Our major findings include: (1) the development of massive projection fibers by 18 PCW, as compared to most association fibers (with the exception of limbic fibers) which have only begun to emerge, (2) the characteristic laminar distribution and sagittal plane geometry of reconstructed fibers throughout development, (3) the protracted prenatal development shown of the corpus collosum and its' associated fibers, as well as the association fibers, and (4) the predomination of radial coherence in the telencephalon (i.e., majority of streamlines in the telencephalic wall were radially oriented) during early prenatal period (24 PCW). In conclusion, correlation between histology and HARDI (in combination with Q-ball reconstruction and deterministic streamline tractography) allowed us to detect sequential development of fiber systems (projection, callosal, and association), their spatial relations with transient fetal zones, and their geometric properties.
Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery, 2017
The purpose of the study was to estimate the size and bone thickness at the margin of the foramen... more The purpose of the study was to estimate the size and bone thickness at the margin of the foramen magnum in a pediatric population. Sixty occipital bone specimens from the collection of macerated skulls at the Department of Anatomy, University of Zagreb, were examined and measured using a vernier scale/caliper. For the purpose of analysis, specimens were divided into two age groups: 1-6 years and 7-18 years of age (before and after the fusion of ossification centers in the occipital bone). We measured the following: antero-posterior and transverse diameters of the foramen magnum, bone thicknesses at the basion, opisthion, two paramedial points on the anterior and posterior margins, and at the occipito-squamous junction. Data presented in this study show that diameters of the foramen magnum increase with age, whereas bone thickness shows variable behavior depending on the measured area. Increases in diameters in specimens from the younger age group and their absence in specimens from...
Previous studies have demonstrated that in primates, cortical GABAergic neurons (cxGABAn) are fir... more Previous studies have demonstrated that in primates, cortical GABAergic neurons (cxGABAn) are first generated exclusively by the ganglionic eminence (GE), resembling spatial pattern in origin of cxGABAn in rodents. Then, during the second trimester of gestation cxGABAn are massively produced in the newly evolved outer subventricular zone of the pallium. This massive production of cxGABAn by pallium progenitors reported in primates could be an evolutionary answer to provide cxGABAn to a complex and expanded cortex. How the GE contribute to cxGABAn production during this second trimester of gestation remains to be established. For this purpose we investigate the development of the primate GE during the stage when pallial production of cxGABAn occurs. Our data indicate that there is no decrease in the proliferative capability of the GE up to midgestation both in human and monkey when cxGABAn are generated in the pallium. In the rhesus monkey no decrease was observed in a stream of GAD6...
The cerebral wall of the human fetal brain is composed of transient cellular compartments, which ... more The cerebral wall of the human fetal brain is composed of transient cellular compartments, which show characteristic spatiotemporal relationships with intensity of major neurogenic events (cell proliferation, migration, axonal growth, dendritic differentiation, synaptogenesis, cell death, and myelination). The aim of the present study was to obtain new quantitative data describing volume, surface area, and thickness of transient compartments in the human fetal cerebrum. Forty-four postmortem fetal brains aged 13-40 postconceptional weeks (PCW) were included in this study. High-resolution T1 weighted MR images were acquired on 19 fetal brain hemispheres. MR images were processed using in-house software (MNI-ACE toolbox). Delineation of fetal compartments was performed semi-automatically by co-registration of MRI with histological sections of the same brains, or with the age-matched brains from Zagreb Neuroembryological Collection. Growth trajectories of transient fetal compartments were reconstructed. The composition of telencephalic wall was quantitatively assessed. Between 13 and 25 PCW, when the intensity of neuronal proliferation decreases drastically, the relative volume of proliferative (ventricular and subventricular) compartments showed pronounced decline. In contrast, synapse- and extracellular matrix-rich subplate compartment continued to grow during the first two trimesters, occupying up to 45% of telencephalon and reaching its maximum volume and thickness around 30 PCW. This developmental maximum coincides with a period of intensive growth of long cortico-cortical fibers, which enter and wait in subplate before approaching the cortical plate. Although we did not find significant age related changes in mean thickness of the cortical plate, the volume, gyrification index, and surface area of the cortical plate continued to exponentially grow during the last phases of prenatal development. This cortical expansion coincides developmentally with the transformation of embryonic cortical columns, dendritic differentiation, and ingrowth of axons. These results provide a quantitative description of transient human fetal brain compartments observable with MRI. Moreover, they will improve understanding of structural-functional relationships during brain development, will enable correlation between in vitro/in vivo imaging and fine structural histological studies, and will serve as a reference for study of perinatal brain injuries.
This retrospective study was designed to evaluate whether patients with hydrocephalus associated ... more This retrospective study was designed to evaluate whether patients with hydrocephalus associated with central nervous system (CNS) anomalies, compared with patients with hydrocephalus and absent CNS anomalies, present with significantly higher rate of postoperative complications, including more serious clinical presentation, increased life threat, and higher postoperative or late mortality rate. We performed a retrospective study using medical records of 100 patients of pediatric and adolescent age (0-18 years) between 2004 and 2010 treated with operative cerebrospinal fluid (CSF) shunt placement. In both groups of patients, there were 43 postoperative complications, including 12 mechanical obstructions of the CSF drainage systems, 13 disconnections, 11 dislocations of proximal catheter, 6 inflammatory complications (meningitis), and 1 latex allergy. Patients with hydrocephalus associated with CNS anomalies were presented with statistically higher rate of postoperative complications (U = 303.5, z = -3.27, p = 0.001), higher number of operations, at least one complication more per patient, more complicated clinical course, higher life threat, and higher late mortality rate. After installing the CSF drain system, children and adolescents with hydrocephalus associated with anomalies of the CNS require regular and careful follow-up.
Previous studies have demonstrated that in primates, cortical GABAergic neurons (cxGABAn) are fir... more Previous studies have demonstrated that in primates, cortical GABAergic neurons (cxGABAn) are first generated exclusively by the ganglionic eminence (GE), resembling spatial pattern in origin of cxGABAn in rodents. Then, during the second trimester of gestation cxGABAn are massively produced in the newly evolved outer subventricular zone of the pallium. This massive production of cxGABAn by pallium progenitors reported in primates could be an evolutionary answer to provide cxGABAn to a complex and expanded cortex. How the GE contribute to cxGABAn production during this second trimester of gestation remains to be established. For this purpose we investigate the development of the primate GE during the stage when pallial production of cxGABAn occurs. Our data indicate that there is no decrease in the proliferative capability of the GE up to midgestation both in human and monkey when cxGABAn are generated in the pallium. In the rhesus monkey no decrease was observed in a stream of GAD6...
In this study, we aimed to identify major fiber pathways and their spatiotemporal relationships w... more In this study, we aimed to identify major fiber pathways and their spatiotemporal relationships within transient fetal zones in the human fetal brain by comparing postmortem high-angular resolution diffusion MR imaging (HARDI) in combination with deterministic streamline tractography and histology. Diffusion weighted imaging was performed on postmortem human fetal brains [N = 9, age = 18-34 post-conceptual weeks (PCW)] that were grossly normal with no pathologic abnormalities. After HARDI was performed, the fibers were reconstructed using Q-ball algorithm and deterministic streamline tractography. The position of major fiber pathways within transient fetal zones was identified both on diffusion weighted images and on histological sections. Our major findings include: (1) the development of massive projection fibers by 18 PCW, as compared to most association fibers (with the exception of limbic fibers) which have only begun to emerge, (2) the characteristic laminar distribution and sagittal plane geometry of reconstructed fibers throughout development, (3) the protracted prenatal development shown of the corpus collosum and its' associated fibers, as well as the association fibers, and (4) the predomination of radial coherence in the telencephalon (i.e., majority of streamlines in the telencephalic wall were radially oriented) during early prenatal period (24 PCW). In conclusion, correlation between histology and HARDI (in combination with Q-ball reconstruction and deterministic streamline tractography) allowed us to detect sequential development of fiber systems (projection, callosal, and association), their spatial relations with transient fetal zones, and their geometric properties.
Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery, 2017
The purpose of the study was to estimate the size and bone thickness at the margin of the foramen... more The purpose of the study was to estimate the size and bone thickness at the margin of the foramen magnum in a pediatric population. Sixty occipital bone specimens from the collection of macerated skulls at the Department of Anatomy, University of Zagreb, were examined and measured using a vernier scale/caliper. For the purpose of analysis, specimens were divided into two age groups: 1-6 years and 7-18 years of age (before and after the fusion of ossification centers in the occipital bone). We measured the following: antero-posterior and transverse diameters of the foramen magnum, bone thicknesses at the basion, opisthion, two paramedial points on the anterior and posterior margins, and at the occipito-squamous junction. Data presented in this study show that diameters of the foramen magnum increase with age, whereas bone thickness shows variable behavior depending on the measured area. Increases in diameters in specimens from the younger age group and their absence in specimens from...
Previous studies have demonstrated that in primates, cortical GABAergic neurons (cxGABAn) are fir... more Previous studies have demonstrated that in primates, cortical GABAergic neurons (cxGABAn) are first generated exclusively by the ganglionic eminence (GE), resembling spatial pattern in origin of cxGABAn in rodents. Then, during the second trimester of gestation cxGABAn are massively produced in the newly evolved outer subventricular zone of the pallium. This massive production of cxGABAn by pallium progenitors reported in primates could be an evolutionary answer to provide cxGABAn to a complex and expanded cortex. How the GE contribute to cxGABAn production during this second trimester of gestation remains to be established. For this purpose we investigate the development of the primate GE during the stage when pallial production of cxGABAn occurs. Our data indicate that there is no decrease in the proliferative capability of the GE up to midgestation both in human and monkey when cxGABAn are generated in the pallium. In the rhesus monkey no decrease was observed in a stream of GAD6...
The cerebral wall of the human fetal brain is composed of transient cellular compartments, which ... more The cerebral wall of the human fetal brain is composed of transient cellular compartments, which show characteristic spatiotemporal relationships with intensity of major neurogenic events (cell proliferation, migration, axonal growth, dendritic differentiation, synaptogenesis, cell death, and myelination). The aim of the present study was to obtain new quantitative data describing volume, surface area, and thickness of transient compartments in the human fetal cerebrum. Forty-four postmortem fetal brains aged 13-40 postconceptional weeks (PCW) were included in this study. High-resolution T1 weighted MR images were acquired on 19 fetal brain hemispheres. MR images were processed using in-house software (MNI-ACE toolbox). Delineation of fetal compartments was performed semi-automatically by co-registration of MRI with histological sections of the same brains, or with the age-matched brains from Zagreb Neuroembryological Collection. Growth trajectories of transient fetal compartments were reconstructed. The composition of telencephalic wall was quantitatively assessed. Between 13 and 25 PCW, when the intensity of neuronal proliferation decreases drastically, the relative volume of proliferative (ventricular and subventricular) compartments showed pronounced decline. In contrast, synapse- and extracellular matrix-rich subplate compartment continued to grow during the first two trimesters, occupying up to 45% of telencephalon and reaching its maximum volume and thickness around 30 PCW. This developmental maximum coincides with a period of intensive growth of long cortico-cortical fibers, which enter and wait in subplate before approaching the cortical plate. Although we did not find significant age related changes in mean thickness of the cortical plate, the volume, gyrification index, and surface area of the cortical plate continued to exponentially grow during the last phases of prenatal development. This cortical expansion coincides developmentally with the transformation of embryonic cortical columns, dendritic differentiation, and ingrowth of axons. These results provide a quantitative description of transient human fetal brain compartments observable with MRI. Moreover, they will improve understanding of structural-functional relationships during brain development, will enable correlation between in vitro/in vivo imaging and fine structural histological studies, and will serve as a reference for study of perinatal brain injuries.
This retrospective study was designed to evaluate whether patients with hydrocephalus associated ... more This retrospective study was designed to evaluate whether patients with hydrocephalus associated with central nervous system (CNS) anomalies, compared with patients with hydrocephalus and absent CNS anomalies, present with significantly higher rate of postoperative complications, including more serious clinical presentation, increased life threat, and higher postoperative or late mortality rate. We performed a retrospective study using medical records of 100 patients of pediatric and adolescent age (0-18 years) between 2004 and 2010 treated with operative cerebrospinal fluid (CSF) shunt placement. In both groups of patients, there were 43 postoperative complications, including 12 mechanical obstructions of the CSF drainage systems, 13 disconnections, 11 dislocations of proximal catheter, 6 inflammatory complications (meningitis), and 1 latex allergy. Patients with hydrocephalus associated with CNS anomalies were presented with statistically higher rate of postoperative complications (U = 303.5, z = -3.27, p = 0.001), higher number of operations, at least one complication more per patient, more complicated clinical course, higher life threat, and higher late mortality rate. After installing the CSF drain system, children and adolescents with hydrocephalus associated with anomalies of the CNS require regular and careful follow-up.
Previous studies have demonstrated that in primates, cortical GABAergic neurons (cxGABAn) are fir... more Previous studies have demonstrated that in primates, cortical GABAergic neurons (cxGABAn) are first generated exclusively by the ganglionic eminence (GE), resembling spatial pattern in origin of cxGABAn in rodents. Then, during the second trimester of gestation cxGABAn are massively produced in the newly evolved outer subventricular zone of the pallium. This massive production of cxGABAn by pallium progenitors reported in primates could be an evolutionary answer to provide cxGABAn to a complex and expanded cortex. How the GE contribute to cxGABAn production during this second trimester of gestation remains to be established. For this purpose we investigate the development of the primate GE during the stage when pallial production of cxGABAn occurs. Our data indicate that there is no decrease in the proliferative capability of the GE up to midgestation both in human and monkey when cxGABAn are generated in the pallium. In the rhesus monkey no decrease was observed in a stream of GAD6...
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Papers by Marina Raguz