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In this study we compare temporal lobe (TL) signal intensity (SI) profiles, along with the average thicknesses of the transient zones obtained from postmortem MRI (pMRI) scans and corresponding histological slices, to the frontal lobe (FL) SI and zone thicknesses, in normal fetal brains. The purpose was to assess the synchronization of the corticogenetic processes in different brain lobes. Nine postmortem human fetal brains without cerebral pathologies, from 19 to 24 weeks of gestation (GW) were analyzed on T2-weighted 3T pMRI, at the coronal level of the thalamus and basal ganglia. The SI profiles of the transient zones in the TL correlate well spatially and temporally to the signal intensity profile of the FL. During the examined period, in the TL, the intermediate and subventricular zone are about the size of the subplate zone (SP), while the superficial SP demonstrates the highest signal intensity. The correlation of the SI profiles and the distributions of the transient zones in the two brain lobes, indicates a time-aligned histogenesis during this narrow time window. The 3TpMRI enables an assessment of the regularity of lamination patterns in the fetal telencephalic wall, upon comparative evaluation of sizes of the transient developmental zones and the SI profiles of different cortical regions. A knowledge of normal vs. abnormal transient lamination patterns and the SI profiles is a prerequisite for further advancement of the MR diagnostic tools needed for early detection of developmental brain pathologies prenatally, especially mild white matter injuries such as lesions of TL due to prenatal cytomegalovirus infections, or cortical malformations.

To uncover the ontogenesis of the human indusium griseum (IG), 28 post-mortem fetal human brains, 12–40 postconceptional weeks (PCW) of age, and 4 adult brains were analyzed immunohistochemically and compared with post-mortem magnetic resonance imaging (MRI) of 28 fetal brains (14–41 PCW). The morphogenesis of the IG occurred between 12 and 15 PCW, transforming the bilateral IG primordia into a ribbon-like cortical lamina. The histogenetic transition of sub-laminated zones into the three-layered cortical organization occurred between 15 and 35 PCW, concomitantly with rapid cell differentiation that occurred from 18 to 28 PCW and the elaboration of neuronal connectivity during the entire second half of gestation. The increasing number of total cells and neurons in the IG at 25 and 35 PCW confirmed its continued differentiation throughout this period. High-field 3.0 T post-mortem MRI enabled visualization of the IG at the mid-fetal stage using T2-weighted sequences. In conclusion, the IG had a distinct histogenetic differentiation pattern than that of the neighboring intralimbic areas of the same ontogenetic origin, and did not show any signs of regression during the fetal period or postnatally, implying a functional role of the IG in the adult brain, which is yet to be disclosed.

The purpose of the study was to investigate the interrelation of the signal intensities and thicknesses of the transient developmental zones in the cingulate and neocortical telencephalic wall, using T2-weighted 3 T-magnetic resonance imaging (MRI) and histological scans from the same brain hemisphere. The study encompassed 24 postmortem fetal brains (15–35 postconceptional weeks, PCW). The measurements were performed using Fiji and NDP.view2. We found that T2w MR signal-intensity curves show a specific regional and developmental stage profile already at 15 PCW. The MRI-histological correlation reveals that the subventricular-intermediate zone (SVZ-IZ) contributes the most to the regional differences in the MRI-profile and zone thicknesses, growing by a factor of 2.01 in the cingulate, and 1.78 in the neocortical wall. The interrelations of zone or wall thicknesses, obtained by both methods, disclose a different rate and extent of shrinkage per region (highest in neocortical subplate and SVZ-IZ) and stage (highest in the early second half of fetal development), distorting the zones’ proportion in histological sections. This intrasubject, slice-matched, 3 T correlative MRI-histological study provides important information about regional development of the cortical wall, critical for the design of MRI criteria for prenatal brain monitoring and early detection of cortical or other brain pathologies in human fetuses.

The choroid plexus (ChP) secretes cerebrospinal fluid and is critical for the development and function of the brain. In the telencephalon, the ChP epithelium (ChPe) arises from the Wnt-expressing cortical hem. Embryonic mouse and human ChPe both express nuclear β-CATENIN, a canonical Wnt signaling pathway effector, indicating that this pathway is active during ChPe development. Point mutations in human β-CATENIN result in the constitutive activation of canonical Wnt signaling. In a mouse model that recapitulates this perturbation, we report a loss of ChPe identity and an apparent transformation of the ChPe to a neuronal identity. Aspects of this phenomenon are recapitulated in human embryonic stem cell (hESC)-derived organoids. The ChPe is also disrupted when β-Catenin is conditionally inactivated in the mouse. Together, our results indicate that canonical Wnt signaling is required in a precise and regulated manner for normal ChPe development in the mammalian brain.

Background There is a need for highly sensitive and specific tests and biomarkers that would allow preclinical diagnosis of mild cognitive impairment (MCI) and Alzheimer's disease (AD), which would also enable timely intervention. New method We have developed a new system (ALZENTIA) to help detect early MCI, mainly caused by AD. The system is based on a hidden-goal task (HGT) in which the human subject has to find a target that is not visible; as such, the navigation is based on a previously memorized target position, in relation to the starting position (egocentric variant) and/or other navigational landmarks (allocentric variant of the task). We present our preliminary results obtained in 33 patients with MCI and 91 healthy controls (HC). Results and comparison with existing methods Between-group differences in the average error measured in allocentric, egocentric, and combined allocentric-egocentric subtests were statistically significant in MCI compared to HC. The high negative predictive values suggested high discriminative capacity and diagnostic potential for the HGT test as a tool to detect subjects in healthy population who will progress to MCI. Considering the low sensitivity of the Mini-Mental Status Examination and Montreal Cognitive Assessment tests, we believe that HGT can improve early identification of MCI patients who will progress to AD. Conclusion The HGT carried out with the ALZENTIA system proved to be a reliable screening test to identify individuals with MCI from an aging cohort.

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.