Publications by authors named "Gerlinde M Gruber"

13 Publications

  • Page 1 of 1

Comparison of the Visibility of Fetal Tooth Buds on 1.5 and 3 Tesla MRI.

J Clin Med 2020 Oct 26;9(11). Epub 2020 Oct 26.

Department of Cranio-Maxillofacial Surgery, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland.

Dental anomalies coincide with genetic disorders, and prenatal identification may contribute to a more accurate diagnosis. The aim of this study was to assess whether fetal Magnet Resonance Imaging (MRI) is suitable to visualize and investigate intrauterine dental development in the upper jaw, and to compare the quality of visibility of tooth buds between 1.5 Tesla (T) and 3T images. MR images of fetuses Gestational Week (GW) 26.71 ± 4.97 from 286 pregnant women with diagnoses unrelated to dental anomalies were assessed by three raters. We compared the visibility between groups and field strengths in five gestational age groups, using chi square and Fisher's exact tests. All ten primary tooth buds were identifiable in 5.4% at GW 18-21, in 75.5% at GW 26-29, and in 90.6% at GW 34+. Before GW 30, more tooth buds were identifiable on 3T images than on 1.5T images. Statistical significance was only reached for identification of incisors ( = 0.047). Therefore, 1.5T and 3T images are viable to visualize tooth buds, particularly after GW 25, and their analysis may serve as diagnostic criterion. MRI tooth bud data might have an impact on various fields of research, such as the maldevelopment of teeth and their causes. Analyzing tooth buds as an additional diagnostic criterion is not time consuming, and could lead to an improvement of syndrome diagnosis.
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http://dx.doi.org/10.3390/jcm9113424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693030PMC
October 2020

Developmental dynamics of the periventricular parietal crossroads of growing cortical pathways in the fetal brain - In vivo fetal MRI with histological correlation.

Neuroimage 2020 04 21;210:116553. Epub 2020 Jan 21.

Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria. Electronic address:

The periventricular crossroads have been described as transient structures of the fetal brain where major systems of developing fibers intersect. The triangular parietal crossroad constitutes one major crossroad region. By combining in vivo and post-mortem fetal MRI with histological and immunohistochemical methods, we aimed to characterize these structures. Data from 529 in vivo and 66 post-mortem MRI examinations of fetal brains between gestational weeks (GW) 18-39 were retrospectively reviewed. In each fetus, the area adjacent to the trigone of the lateral ventricles at the exit of the posterior limb of the internal capsule (PLIC) was assessed with respect to signal intensity, size, and shape on T2-weighted images. In addition, by using in vivo diffusion tensor imaging (DTI), the main fiber pathways that intersect in these areas were identified. In order to explain the in vivo features of the parietal crossroads (signal intensity and developmental profile), we analyzed 23 post-mortem fetal human brains, between 16 and ​40 GW of age, processed by histological and immunohistochemical methods. The parietal crossroads were triangular-shaped areas with the base in the continuity of the PLIC, adjacent to the germinal matrix and the trigone of the lateral ventricles, with the tip pointing toward the subplate. These areas appeared hyperintense to the subplate, and corresponded to a convergence zone of the developing external capsule, the PLIC, and the fronto-occipital association fibers. They were best detected between GW 25-26, and, at term, they became isointense to the adjacent structures. The immunohistochemical results showed a distinct cellular, fibrillar, and extracellular matrix arrangement in the parietal crossroads, depending on the stage of development, which influenced the MRI features. The parietal crossroads are transient, but important structures in white matter maturation and their damage may be indicative of a poor prognosis for a fetus with regard to neurological development. In addition, impairment of this region may explain the complex neurodevelopmental deficits in preterm infants with periventricular hypoxic/ischemic or inflammatory lesions.
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http://dx.doi.org/10.1016/j.neuroimage.2020.116553DOI Listing
April 2020

Newly formed and remodeled human bone exhibits differences in the mineralization process.

Acta Biomater 2020 03 9;104:221-230. Epub 2020 Jan 9.

Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, D-14424 Potsdam, Germany.

During human skeletal growth, bone is formed via different processes. Two of them are: new bone formation by depositing bone at the periosteal (outer) surface and bone remodeling corresponding to a local renewal of tissue. Since in remodeling formation is preceded by resorption, we hypothesize that modeling and remodeling could require radically different transport paths for ionic precursors of mineralization. While remodeling may recycle locally resorbed mineral, modeling implies the transport over large distances to the site of bone apposition. Therefore, we searched for potential differences of size, arrangement and chemical composition of mineral particles just below surfaces of modeling and remodeling sites in femur midshaft cross-sections from healthy children. These bone sites were mapped using scanning synchrotron X-ray scattering, Raman microspectroscopy, energy dispersive X-ray analysis and quantitative backscattered electron microscopy. The results show clear differences in mineral particle size and composition between the sites, which cannot be explained by a change in the rate of mineral apposition or accumulation. At periosteal modeling sites, mineral crystals are distinctly larger, display higher crystallinity and exhibit a lower calcium to phosphorus ratio and elevated Na and Mg content. The latter may originate from Mg used for phase stabilization of mineral precursors and therefore indicate different time periods for mineral transport. We conclude that the mineralization process is distinctively different between modeling and remodeling sites due to varying requirements for the transport distance and, therefore, the stability of non-crystalline ionic precursors, resulting in distinct compositions of the deposited mineral phase. STATEMENT OF SIGNIFICANCE: In growing children new bone is formed either due to apposition of bone tissue e.g. at the outer ridge of long bones to allow growth in thickness (bone modeling), or in cavities inside the mineralized matrix when replacing tissue (bone remodeling). We demonstrate that mineral crystal shape and composition are not the same between these two sites, which is indicative of differences in mineralization precursors. We suggest that this may be due to a longer mineral transport distance to sites of new bone formation as compared to remodeling where mineral can be locally recycled.
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http://dx.doi.org/10.1016/j.actbio.2020.01.004DOI Listing
March 2020

Echo-planar FLAIR Sequence Improves Subplate Visualization in Fetal MRI of the Brain.

Radiology 2019 07 14;292(1):159-169. Epub 2019 May 14.

From the Department of Image Guided Therapy, University Clinic for Neuroradiology and Musculoskeletal Radiology, Medical University of Vienna, Waehringer Guertel 18-20, Leistelle 6F, 1090 Vienna, Austria (M.C.D., D.P., F.S., M.W., G.K.); Center for Anatomy and Cell Biology, Division of Systematic Anatomy, Medical University of Vienna, Vienna, Austria (G.M.G., P.C.B.); and University Clinic for Gynecology and Obstetrics, Medical University of Vienna, Vienna, Austria (D.B.).

Background The cortical plate (future cortex) is readily identifiable in utero at MRI. However, MRI evaluation of the remaining brain layers is limited by the poor T2 contrast between the subplate and the underlying intermediate zone (IZ). Purpose To compare the delineation of fetal brain lamination between T2-weighted single-shot fast spin-echo (SSFSE) and echo-planar imaging (EPI) fluid-attenuated inversion recovery (FLAIR) images, and to quantify differences in the depiction of brain layering between the two sequences. Materials and Methods Consecutive fetal brain MRI examinations performed between January 2014 and March 2018 with T2-weighted SSFSE and EPI-FLAIR images were reviewed. Two neuroradiologists evaluated the visibility of brain layers by using a three-point grading system, and findings were compared by using the sign test. One rater performed region-of-interest analysis in the cortical plate (CP), subplate (gyral crest and sulcal bottom), and IZ. Signal intensity (SI) ratios between adjacent brain compartments were calculated and compared by using the paired test. Reader agreement was assessed by using weighted κ values. Results A total of 259 MRI examinations (mean gestational age [GA], 26.9 weeks ± 5.6) were included in the qualitative analysis, and 72 MRI examinations (mean GA, 27.4 weeks ± 5.5) were included in the quantitative analysis. Subplate identification on EPI-FLAIR images was superior to that on T2-weighted SSFSE images (subplate visualization [complete + partial]: frontal lobe, = 243 vs = 117; temporal lobe, = 244 vs = 137; parietal lobe = 240 vs = 93; and occipital lobe, = 241 vs = 97, respectively; < .001), with higher interrater reliability (κ = 0.91-0.95 for EPI-FLAIR images and 0.80-0.87 for T2-weighted SSFSE images). SI ratios between the IZ and subplate were significantly higher on EPI-FLAIR images in all lobes (EPI-FLAIR images: 1.6-2.1; T2-weighted SSFSE images:1.2-1.2; < .001). Subplate-to-CP ratios were not statistically significant between the two sequences (EPI-FLAIR:1.8-2.4; T2-weighted SSFSE: 2.0-2.2; < .001). Conclusion The echo-planar fluid-attenuated inversion recovery sequence improves visualization of fetal brain lamination compared with the T2-weighted single-shot fast spin-echo sequence, as established by quantitative and qualitative methods. © RSNA, 2019 See also the editorial by Rossi in this issue.
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http://dx.doi.org/10.1148/radiol.2019181976DOI Listing
July 2019

High-Resolution Ultrasound Visualization of Pacinian Corpuscles.

Ultrasound Med Biol 2018 12 14;44(12):2596-2601. Epub 2018 Sep 14.

PUC Private Ultrasound Center, Vienna, Austria.

The aim of this study was to evaluate the possibility of visualizing Pacinian corpuscles in the palm of the hand with high-resolution ultrasound (HRUS). In this prospective study, HRUS with a high-frequency probe (22 MHz) was used. The palms of two fresh cadaveric hands were screened for potential Pacinian corpuscles. Still ultrasound images and dynamic video sequences were obtained. In five regions with large amounts of suspected Pacinian corpuscles, tissue blocks were excised and histologically processed, and corresponding slices were compared with ultrasound images. Further, the transverse diameters of five Pacinian corpuscles, at the level of the metacarpal heads in the palm, were assessed on both sides (in total 100) in healthy volunteers. On ultrasound, Pacinian corpuscles presented as echolucent dots in the subcutis, adjacent to digital nerves and vessels and located 2-3 mm beneath the surface. On histologic sections, these echolucent dots corresponded to Pacinian corpuscles with respect to their position and topographic relationships. The mean transverse diameter for all volunteers was 1.40 ± 0.23 mm (range: 0.8-2.2 mm). This study confirms the ability to reliably visualize Pacinian corpuscles with HRUS, which contributes to our basic understanding of ultrasonographically visible subcutaneous structures and may enhance the diagnosis of pathologies related to Pacinian corpuscles.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2018.08.001DOI Listing
December 2018

How accurate are prenatal tractography results? A postnatal in vivo follow-up study using diffusion tensor imaging.

Pediatr Radiol 2018 04 17;48(4):486-498. Epub 2018 Mar 17.

Department of Biomedical Imaging and Image-guided Therapy,, Medical University of Vienna,, Währinger Gürtel 18-20, 1090, Vienna, Austria.

Prenatal detection of abnormal white matter tracts might serve as a structural marker for altered neurodevelopment. As a result of many technical and patient-related challenges, the accuracy of prenatal tractography remains unknown. We hypothesized that characteristics of prenatal tractography of the corpus callosum and corticospinal tracts derived from fetal diffusion tensor imaging (DTI) data are accurate and predictive of the integrity of these tracts postnatally. We compared callosal and corticospinal tracts of 12 subjects with paired prenatal (age: 23-35 gestational weeks) and postnatal (age: 1 day to 2 years) DTI examinations (b values of 0 s/mm and 700 s/mm, 16 gradient encoding directions) using deterministic tractography. Evaluation for the presence of callosal segments and corticospinal tracts showed moderate degrees of accuracy (67-75%) for the four segments of the corpus callosum and moderate to high degrees of accuracy (75-92%) for the corticospinal tracts. Positive predictive values for segments of the corpus callosum ranged from 50% to 100% and for the corticospinal tracts, 89% to 100%. Negative predictive values for segments of the corpus callosum ranged from 25% to 80% and for the corticospinal tracts, 33% to 50%. The results suggest that when the tracts are not well characterized on the fetal MR, predictions about the postnatal tracts are difficult to make. However, accounting for brain maturation, prenatal visualization of the main projection and commissural tracts can be clinically used as an important predictive tool in the context of image interpretation for the assessment of fetal brain malformations.
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http://dx.doi.org/10.1007/s00247-017-3982-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5857276PMC
April 2018

Coalignment of osteocyte canaliculi and collagen fibers in human osteonal bone.

J Struct Biol 2017 09 1;199(3):177-186. Epub 2017 Aug 1.

Max Planck Institute of Colloids and Interfaces, Department of Biomaterials, D-14424 Potsdam, Germany. Electronic address:

During bone formation osteocytes get connected with each other via a dense network of canaliculi within the mineralized bone matrix. Important functions attributed to the osteocyte network include the control of bone remodeling and a contribution to mineral homeostasis. To detect structural clues of the formation and functionality of the network, this study analyzes the structure and orientation of the osteocyte lacuno-canalicular network (OLCN), specifically in relation to the concentric bone lamellae within human osteons. The network structure within 49 osteons from four samples of cortical bone from the femoral midshaft of middle-aged healthy women was determined by a combination of rhodamine staining and confocal laser scanning microscopy followed by computational image analysis. A quantitative evaluation showed that 64±1% of the canalicular length has an angle smaller than 30° to the direction towards the osteon center, while the lateral network - defined by an orientation angle larger than 60° - comprises 16±1%. With the same spatial periodicity as the bone lamellae, both radial and lateral network show variations in the network density and order. However, only the preferred orientation of the lateral network twists when crossing a lamella. This twist agrees with the preferred orientation of the fibrous collagen matrix. The chirality of the twist was found to be individual-specific. The coalignment between network and matrix extends to the orientation of the elongated osteocyte lacunae. The intimate link between OLCN and collagen matrix implies an interplay between osteocyte processes and the arrangement of the surrounding collagen fibers during osteoid formation.
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http://dx.doi.org/10.1016/j.jsb.2017.07.004DOI Listing
September 2017

Spatial heterogeneity in the canalicular density of the osteocyte network in human osteons.

Bone Rep 2017 Jun 15;6:101-108. Epub 2017 Mar 15.

Max Planck Institute of Colloids and Interfaces, Department of Biomaterials, D-14424 Potsdam, Germany.

Osteocytes interconnect with each other forming an intricate cell network within the mineralized bone matrix. One important function of the osteocyte network is the mechano-regulation of bone remodeling, where a possible mechanism includes the fluid flow through the porosity housing the cell network - the osteocyte lacuno-canalicular network (OLCN). In our study the OLCN in human osteons was three-dimensionally imaged with the aim to obtain a quantitative description of the canalicular density and spatial variations of this quantity within osteons. The topology of the OLCN was determined by first staining the bone samples with rhodamine, then imaging the OLCN with confocal laser scanning microscopy and finally using image analysis to obtain a skeletonized version of the network for further analysis. In total 49 osteons were studied from the femoral cortical bone of four different middle-aged healthy women. The mean canalicular density given as length of the canaliculi in a unit volume was 0.074 ± 0.015 μm/μm (corresponding to 74 km/cm). No correlation was found between the canalicular density and neither the size of the osteon nor the volume fraction occupied by osteocyte lacunae. Within osteons the canalicular density varied substantially with larger regions without any network. On average the canalicular density decreases when moving from the Haversian canal outwards towards the cement line. We hypothesize that a decrease in accessible canaliculi with tissue age as a result of micropetrosis can reduce the local mechanosensitivity of the bone. Systematic future studies on age- and disease-related changes on the topology of the OLCN have to demonstrate the diagnostic potential of the presented characterization method.
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http://dx.doi.org/10.1016/j.bonr.2017.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5369863PMC
June 2017

Fetal MRI at 3T-ready for routine use?

Br J Radiol 2017 Jan 21;90(1069):20160362. Epub 2016 Oct 21.

1 Division of Neuro- and Musculoskeletal Radiology, Department of Radiology, Medical University of Vienna, Vienna, Austria.

Fetal MR now plays an important role in the clinical work-up of pregnant females. It is performed mainly at 1.5 T. However, the desire to obtain a more precise fetal depiction or the fact that some institutions have access only to a 3.0 T scanner has resulted in a growing interest in performing fetal MR at 3.0 T. The aim of this article was to provide a reference for the use of 3.0 T MRI as a prenatal diagnostic method.
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http://dx.doi.org/10.1259/bjr.20160362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605013PMC
January 2017

Validation of In utero Tractography of Human Fetal Commissural and Internal Capsule Fibers with Histological Structure Tensor Analysis.

Front Neuroanat 2015 24;9:164. Epub 2015 Dec 24.

Division of Neuroradiology and Musculoskeletal Radiology, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna Vienna, Austria.

Diffusion tensor imaging (DTI) and tractography offer the unique possibility to visualize the developing white matter macroanatomy of the human fetal brain in vivo and in utero and are currently under investigation for their potential use in the diagnosis of developmental pathologies of the human central nervous system. However, in order to establish in utero DTI as a clinical imaging tool, an independent comparison between macroscopic imaging and microscopic histology data in the same subject is needed. The present study aimed to cross-validate normal as well as abnormal in utero tractography results of commissural and internal capsule fibers in human fetal brains using postmortem histological structure tensor (ST) analysis. In utero tractography findings from two structurally unremarkable and five abnormal fetal brains were compared to the results of postmortem ST analysis applied to digitalized whole hemisphere sections of the same subjects. An approach to perform ST-based deterministic tractography in histological sections was implemented to overcome limitations in correlating in utero tractography to postmortem histology data. ST analysis and histology-based tractography of fetal brain sections enabled the direct assessment of the anisotropic organization and main fiber orientation of fetal telencephalic layers on a micro- and macroscopic scale, and validated in utero tractography results of corpus callosum and internal capsule fiber tracts. Cross-validation of abnormal in utero tractography results could be achieved in four subjects with agenesis of the corpus callosum (ACC) and in two cases with malformations of internal capsule fibers. In addition, potential limitations of current DTI-based in utero tractography could be demonstrated in several brain regions. Combining the three-dimensional nature of DTI-based in utero tractography with the microscopic resolution provided by histological ST analysis may ultimately facilitate a more complete morphologic characterization of axon guidance disorders at prenatal stages of human brain development.
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http://dx.doi.org/10.3389/fnana.2015.00164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4689804PMC
January 2016

High-resolution ultrasound of the posterior femoral cutaneous nerve: visualization and initial experience with patients.

Skeletal Radiol 2015 Oct 24;44(10):1421-6. Epub 2015 Jun 24.

Department of Radiology, KFJ Hospital, Vienna, Austria,

Objective: The posterior femoral cutaneous nerve (PFCN) is a sensory nerve originating from the sacral plexus. PFCN neuropathy leads to pain within the inferior gluteal region and the posterior aspect of the thigh. As electrophysiological assessment is challenging, diagnosis of PFCN neuropathy has been, thus far, primarily based on clinical findings, which can result in misdiagnosis. Therefore, alternative confirmatory assessments such as an imaging modality that could aid in the diagnosis of PFCN neuropathy would be desirable. The purpose of this study was to determine the feasibility of visualization of the PFCN with high-resolution ultrasound (HRUS) and to test this technique in our clinical routine.

Materials And Methods: The study consisted of two parts. In the first part, HRUS-guided perineural ink injections along the course of the PFCN were performed at the posterior aspect of the thigh in 26 lower limbs of 14 fresh non-embalmed cadavers. Subsequent dissection confirmed correct identification of the nerve. In the second part, patients with a suspected PFCN neuropathy were examined and a selective HRUS-guided nerve block was performed to verify the suspected diagnosis.

Results: The PFCN was correctly identified with HRUS in 96.2% (25/26) of cadavers. Further, six patients with a suspected lesion of the PFCN were examined, and the diagnosis was proven by successful HRUS-guided block in all cases.

Conclusion: We confirmed the reliable visualization of the PFCN using HRUS. This offers a new technique for the assessment of the PFCN, which could also be demonstrated with the case series presented.
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http://dx.doi.org/10.1007/s00256-015-2177-6DOI Listing
October 2015

Fetal MRI detects early alterations of brain development in Tetralogy of Fallot.

Am J Obstet Gynecol 2015 Sep 23;213(3):392.e1-7. Epub 2015 May 23.

Division of Neuro- and Musculoskeletal Radiology, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria. Electronic address:

Objective: Prenatal imaging has identified alterations of brain growth in fetuses with congenital heart disease. However, little is known about the timing of altered brain development and its occurrence in specific congenital heart disease subgroups. This magnetic resonance imaging study aimed to identify early (median, 25 gestational weeks [GW]) changes in fetal total brain (TBV), gray matter (GMV), and subcortical brain (SBV) volumes in Tetralogy of Fallot (TOF) cases in utero.

Study Design: Fetal magnetic resonance imaging (1.5 Tesla) was performed in 24 fetuses who were diagnosed with TOF and 24 normal age-matched control fetuses (20-34 GW). TBV, GMV, SBV, intracranial cavity, cerebellar, ventricular, and external cerebrospinal fluid volumes were quantified by manual segmentation based on coronal T2-weighted sequences. Mixed model analyses of variance and t-tests were conducted to compare cases and control fetuses.

Results: TBV was significantly lower (P < .001) in early (<25 GW) and late TOF cases. Both GMV (P = .003) and SBV (P = .001) were affected. The GMV-to-SBV ratio declined in fetuses with TOF (P = .026). Compared with normal fetuses, ventricular volume was increased (P = .0048). External cerebrospinal fluid was enlarged in relation to head size (P < .001). Intracranial cavity volume (P = .314) and cerebellar volume (P = .074) were not significantly reduced in fetuses with TOF.

Conclusion: TOF is associated with smaller volumes of gray and white matter and enlarged cerebrospinal fluid spaces. These changes are present at ≤25 GW and indicate altered fetal brain growth in this pathophysiologic entity during early stages of human brain development.
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http://dx.doi.org/10.1016/j.ajog.2015.05.046DOI Listing
September 2015

Fetal functional imaging portrays heterogeneous development of emerging human brain networks.

Front Hum Neurosci 2014 22;8:852. Epub 2014 Oct 22.

Computational Imaging Research Lab, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna Vienna, Austria ; Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology Cambridge, MA, USA.

The functional connectivity architecture of the adult human brain enables complex cognitive processes, and exhibits a remarkably complex structure shared across individuals. We are only beginning to understand its heterogeneous structure, ranging from a strongly hierarchical organization in sensorimotor areas to widely distributed networks in areas such as the parieto-frontal cortex. Our study relied on the functional magnetic resonance imaging (fMRI) data of 32 fetuses with no detectable morphological abnormalities. After adapting functional magnetic resonance acquisition, motion correction, and nuisance signal reduction procedures of resting-state functional data analysis to fetuses, we extracted neural activity information for major cortical and subcortical structures. Resting fMRI networks were observed for increasing regional functional connectivity from 21st to 38th gestational weeks (GWs) with a network-based statistical inference approach. The overall connectivity network, short range, and interhemispheric connections showed sigmoid expansion curve peaking at the 26-29 GW. In contrast, long-range connections exhibited linear increase with no periods of peaking development. Region-specific increase of functional signal synchrony followed a sequence of occipital (peak: 24.8 GW), temporal (peak: 26 GW), frontal (peak: 26.4 GW), and parietal expansion (peak: 27.5 GW). We successfully adapted functional neuroimaging and image post-processing approaches to correlate macroscopical scale activations in the fetal brain with gestational age. This in vivo study reflects the fact that the mid-fetal period hosts events that cause the architecture of the brain circuitry to mature, which presumably manifests in increasing strength of intra- and interhemispheric functional macro connectivity.
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http://dx.doi.org/10.3389/fnhum.2014.00852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4205819PMC
November 2014