Developmental Differences Between the Limbic and Neocortical Telencephalic Wall: An Intrasubject Slice-Matched 3 T MRI-Histological Correlative Study in Humans.

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.

Intact in vivo visualization of telencephalic microvasculature in medaka using optical coherence tomography.

To date, various human disease models in small fish-such as medaka (Oryzias lapties)-have been developed for medical and pharmacological studies. Although genetic and environmental homogeneities exist, disease progressions can show large individual differences in animal models. In this study, we established an intact in vivo angiographic approach and explored vascular networks in the telencephalon of wild-type adult medaka using the spectral-domain optical coherence tomography. Our approach, which required neither surgical operations nor labeling agents, allowed to visualize blood vessels in medaka telencephala as small as about 8 µm, that is, almost the size of the blood cells of medaka. Besides, we could show the three-dimensional microvascular distribution in the medaka telencephalon. Therefore, the intact in vivo imaging via optical coherence tomography can be used to perform follow-up studies on cerebrovascular alterations in metabolic syndrome and their associations with neurodegenerative disease models in medaka.

Volumetric analysis and morphological assessment of the ascending olfactory pathway in an elasmobranch and a teleost using diceCT.

The size (volume or mass) of the olfactory bulbs in relation to the whole brain has been used as a neuroanatomical proxy for olfactory capability in a range of vertebrates, including fishes. Here, we use diffusible iodine-based contrast-enhanced computed tomography (diceCT) to test the value of this novel bioimaging technique for generating accurate measurements of the relative volume of the main olfactory brain areas (olfactory bulbs, peduncles, and telencephalon) and to describe the morphological organisation of the ascending olfactory pathway in model fish species from two taxa, the brownbanded bamboo shark Chiloscyllium punctatum and the common goldfish Carassius auratus. We also describe the arrangement of primary projections to the olfactory bulb and secondary projections to the telencephalon in both species. Our results identified substantially larger olfactory bulbs and telencephalon in C. punctatum compared to C. auratus (comprising approximately 5.2% vs. 1.8%, and 51.8% vs. 11.8% of the total brain volume, respectively), reflecting differences between taxa, but also possibly in the role of olfaction in the sensory ecology of these species. We identified segregated primary projections to the bulbs, associated with a compartmentalised olfactory bulb in C. punctatum, which supports previous findings in elasmobranch fishes. DiceCT imaging has been crucial for visualising differences in the morphological organisation of the olfactory system of both model species. We consider comparative neuroanatomical studies between representative species of both elasmobranch and teleost fish groups are fundamental to further our understanding of the evolution of the olfactory system in early vertebrates and the neural basis of olfactory abilities.

Deep three-photon imaging of the brain in intact adult zebrafish.

Behaviors emerge from activity throughout the brain, but noninvasive optical access in adult vertebrate brains is limited. We show that three-photon (3P) imaging through the head of intact adult zebrafish allows structural and functional imaging at cellular resolution throughout the telencephalon and deep into the cerebellum and optic tectum. With 3P imaging, considerable portions of the brain become noninvasively accessible from embryo to sexually mature adult in a vertebrate model.

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

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 â€‹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.

Image analysis of neural stem cell division patterns in the zebrafish brain.

Proliferating stem cells in the adult body are the source of constant regeneration. In the brain, neural stem cells (NSCs) divide to maintain the stem cell population and generate neural progenitor cells that eventually replenish mature neurons and glial cells. How much spatial coordination of NSC division and differentiation is present in a functional brain is an open question. To quantify the patterns of stem cell divisions, one has to (i) identify the pool of NSCs that have the ability to divide, (ii) determine NSCs that divide within a given time window, and (iii) analyze the degree of spatial coordination. Here, we present a bioimage informatics pipeline that automatically identifies GFP expressing NSCs in three-dimensional image stacks of zebrafish brain from whole-mount preparations. We exploit the fact that NSCs in the zebrafish hemispheres are located on a two-dimensional surface and identify between 1,500 and 2,500 NSCs in six brain hemispheres. We then determine the position of dividing NSCs in the hemisphere by EdU incorporation into cells undergoing S-phase and calculate all pairwise NSC distances with three alternative metrics. Finally, we fit a probabilistic model to the observed spatial patterns that accounts for the non-homogeneous distribution of NSCs. We find a weak positive coordination between dividing NSCs irrespective of the metric and conclude that neither strong inhibitory nor strong attractive signals drive NSC divisions in the adult zebrafish brain. © 2017 International Society for Advancement of Cytometry.

Telencephalic Flexure and Malformations of the Lateral Cerebral (Sylvian) Fissure.

After sagittal division of the prosencephalon at 4.5 weeks of gestation, the early fetal cerebral hemisphere bends or rotates posteroventrally from seven weeks of gestation. The posterior pole of the telencephalon thus becomes not the occipital but the temporal lobe as the telencephalic flexure forms the operculum and finally the lateral cerebral or Sylvian fissure. The ventral part is infolded to become the insula. The frontal and temporal lips of the Sylvian fissure, as well as the insula, all derive from the ventral margin of the primitive telencephalon, hence may be influenced by genetic mutations with a ventrodorsal gradient of expression. The telencephalic flexure also contributes to a shift of the hippocampus from a dorsal to a ventral position, the early rostral pole of the hippocampus becoming caudal and dorsal becoming ventral. The occipital horn is the most recent recess of the lateral ventricle, hence most vulnerable to anatomic variations that affect the calcarine fissure. Many major malformations include lack of telencephalic flexure (holoprosencephaly, extreme micrencephaly) or dysplastic Sylvian fissure (lissencephalies, hemimegalencephaly, schizencephaly). Although fissures and sulci are genetically programmed, mechanical forces of growth and volume expansion are proposed to be mainly extrinsic (including ventricles) for fissures and intrinsic for sulci. In fetal hydrocephalus, the telencephalic flexure is less affected because ventricular dilatation occurs later in gestation. Flexures can be detected prenatally by ultrasound and fetal magnetic resonance imaging and should be described neuropathologically in cerebral malformations.

Ultrasonographic study of deep portion of diencephalo-telencephalic vesicle for the determination of gestational age of the canine foetus.

The aim of this study was to evaluate the accuracy of ultrasonographic measurement of the deep portion of diencephalo-telencephalic vesicle (DPTV) in the prediction of delivery date in different size bitches. The effects of litter size and foetal sex ratio on the accuracy were also investigated. For this purpose, the growth curve of DPTV was derived in large size dogs (26-40 kg) and the results of the accuracy of the prediction were compared with those obtained in small (< or =10 kg) and medium (11-25 kg) size dogs by the application of the equations derived from the growth curve previously described. Ultrasonographic examinations were performed once a week during the second half of pregnancy in seven large size bitches (26-40 kg body weight). A linear regression model was adopted to analyse the relationship between the DPTV mean values and the days remaining to parturition. The results of regression analysis indicated that DPTV measurement in large size dogs is significantly and linearly related to the gestational age. Ultrasonographic measurements of DPTV were also performed during pregnancy in different size bitches with unknown breeding dates. Although the results indicated a similar accuracy of the prediction of the date of parturition in the different sizes of bitches, a higher accuracy was obtained in normal and large litter size compared with small litters. Foetal sex ratio did not affect the accuracy. In conclusion, this study demonstrated that the accuracy of the prediction of parturition day obtained by ultrasonographic evaluation of DPTV growth is reliable when specific formulae for different size dogs are applied. It should be noted that although foetal sex ratio does not affect the accuracy, the prediction could be less accurate when a small litter is present.

[A 48-year-old woman's survival from a massive verapamil overdose]. / Overlevelse efter massiv verapamiloverdosis hos en 48-årig kvinde.

We present a case report of survival from a massive verapamil overdose. The patient, a 48-year-old female, was admitted 12 hours after suicidal ingestion of 10.08 grams of Isoptin Retard, a sustained release calcium channel blocker. On admittance, the patient had altered mental status, was hypotensive, and ECG showed bradycardia with nodal rhythm. The patient was treated with activated charcoal, colloids, crystalloids, norepinephrine, isoprenalin and epinephrine infusion, high dose glucose-insulin infusion and calcium. The patient was discharged for rehabilitation after two weeks.

Disseminated necrotizing leukoencephalopathy following low-dose oral methotrexate.

Leukoencephalopathy is a recognized complication with intrathecal or intravenous methotrexate (MTX). We report a 59-year-old lady who developed MTX leukoencephalopathy with long-term low-dose oral MTX. She developed posterior leukoencephalopathy (PLE) that initially was reversible on discontinuation of oral MTX. Four months later, she developed disseminated necrotizing leukoencephalopathy (DNL), and was left with devastating neurological deficits. The sequential conventional magnetic resonance imaging (MRI), diffusion weighted imaging (DWI), MR perfusion (MRP) and MR spectroscopic (MRS) changes are highlighted in this report. MRP and MRS showed more wide spread abnormalities than DWI. Stereotactic biopsy from the lesion revealed demyelination with macrophagic infiltration, pericapillary lymphomononuclear aggregation, fibrinoid changes in the capillaries and neovascularization. Of the two cases of PLE with oral MTX reported in literature, one reversed clinically and radiologically with the discontinuation of MTX. To the best of our knowledge, this is the first reported case of DNL following oral MTX in the world literature.

Fatal cerebral lymphomatoid granulomatosis in an HIV-1-infected patient.

Lymphomatoid granulomatosis (LYG) is a rare systematic lymphoproliferative disorder of uncertain etiology. We present a rare case of isolated cerebral LYG developing in an HIV-1-infected patient after initiation of highly active antiretroviral therapy (HAART).

Acquired stuttering in a patient with Wernicke's aphasia.

We report a patient with aphasia caused by cerebral infarction in the left temporal, parietal and occipital lobes that was complicated by acquired stuttering (AS), which is an unusual association. Our findings indicated that Wernicke's area might be involved in the development of AS.

Metastatic adenocarcinoma mimicking 'target sign' of cerebral tuberculosis.

We present a 74-year-old male ex-smoker presenting with a 6-week history of personality change, confusion and headache. Magnetic resonance imaging revealed multiple supratentorial and infratentorial parenchymal masses, predominately in the frontal and parietal lobe white matter. A thin enhancing halo was demonstrated with central low signal intensity on T(1)-and T(2)-weighted imaging compatible with calcification. A tiny extra-axial lesion was also noted near the right cerebellopontine angle. Computed tomography (CT) scan confirmed the finding of a 'target' lesion with a central core of calcification and a ring of enhancement. The 'target sign' of intracerebral tuberculomata was first described in 1979 and reported to be pathognomic for this diagnosis in 1988. However, cerebral tuberculosis was considered unlikely clinically because the patient had recently completed a 12-month course of therapy for Mycobacterium avium complex respiratory infection with agents also active against Mycobacterium tuberculosis. He was afebrile and blood tests did not support an inflammatory process. Subsequent histopathology demonstrated metastatic papillary adenocarcinoma and immunohistochemical studies revealed the origin to be that of primary lung carcinoma. A spiculated pulmonary nodule was seen on CT scan but previous bronchoscopy failed to demonstrate malignant cells. In summary, the 'target sign' is a non-specific radiologic finding but most commonly indicates cerebral tuberculoma or metastatic adenocarcinoma in the appropriate clinical context.

Enhanced perfusion in eyes and cerebral perfusion defects in a patient with Fragile X Syndrome.

Fragile X syndrome (FXS) is known as the most common form of inherited mental retardation. In our study, brain perfusion single photon emission computed tomography (SPECT) was performed in a 6 year-old boy diagnosed with FXS. Diffuse bilateral uptake of Technetium-99m hexamethyl propylene amine oxime (99mTc-HMPAO) was noted in his orbits, as well as cortical perfusion defects (hypoperfusion in the right parietal and the left temporal lobe). Ophthalmologic examination showed no pathological findings. Magnetic resonance imaging (MRI) revealed no abnormality in the orbital structures, although hypoplasia of cerebellum and vermis was visualized. Since the patient was crying during the injection, the increased blood flow or the increased metabolism of the eyes and/or ocular muscles may be responsible for this orbital finding. Alternatively, the enhanced uptake of HMPAO in the orbits may reflect the pathology associated with FXS, because patients with FXS might have visual-motor abnormalities. To the best of our knowledge, there has been no report documenting such an orbital uptake of HMPAO. Moreover, the visualization of decreased cerebral perfusion, with the normal findings of MRI, indicates that brain SPECT imaging with HMPAO is helpful for detecting brain abnormalities in children with FXS.

Combined direct anastomosis and encephaloduroarteriogaleosynangiosis using inverted superficial temporal artery-galeal flap and superficial temporal artery-galeal pedicle in adult moyamoya disease.

BACKGROUND: We evaluated the efficacy of combined STA-MCA anastomosis and EDAGS using inverted STAGF and STAGP for the treatment of adult MMD. METHODS: This study included 8 patients with nonhemorrhagic MMD. There were 6 women and 2 men who were between 23 and 62 years old (mean = 37.8 years) in the sample. The combined surgery was performed on 12 sides in the 8 patients. The surgical results were assessed for clinical outcome, angiographic revascularization, and hemodynamic change on HMPAO brain SPECT. The follow-up period ranged from 6 to 62 months (mean = 27 months). RESULTS: Clinical symptoms and signs were improved or stabilized, and the extent of revascularization evident on external carotid angiograms was excellent in all 8 patients. The CBF on HMPAO SPECT also improved in all 12 sides that were operated on with the combined surgery, except for the preexisting infarcted area, on the basal as well as Diamox stimulation studies. One patient had a transient speech disturbance after surgery, and another patient had delayed wound healing. CONCLUSIONS: The combined STA-MCA anastomosis and EDAGS using inverted STAGF/P seems to be one of the most effective surgical modalities for the treatment of nonhemorrhagic MMD in adults.

Oscillatory cerebral hemodynamics--the macro- vs. microvascular level.

The phase shift between oscillations of blood pressure (BP) and Doppler middle cerebral artery flow velocity (MCAFV) reflects continuous cerebral autoregulatory action. It is not known whether a similar phase shift exists for cortical hemodynamics ('microvascular level') assessed by near infrared spectroscopy (NIRS) and what the effects are of pathological conditions. This study investigates the phase relations between oscillations of BP, MCAFV and NIRS parameters in 38 healthy older adults and 28 patients with unilateral severe obstructive carotid disease. BP was recorded noninvasively by finger plethysmography. Stable 0.1 Hz oscillations of all hemodynamic parameters were induced by regular breathing at a rate of 6/min. Basic results were that: (1) BP-induced cortical microvascular oscillations (NIRS) follow those of macrovascular oscillations (MCAFV) with a phase of 80-90 degrees (corresponding to 2-2.5 s at 0.1 Hz), most likely reflecting a transit time phenomenon; (2) oxy- and deoxyhemoglobin thereby oscillate in counterphase; (3) hemodynamic compromise in carotid obstruction leads to (a) delayed NIRS oscillations in comparison to BP which are highly correlated to a shorter phase lead of MCAFV against BP and (b) a decoupling of the oxy-/deoxyhemoglobin counterphase to 240 degrees . Cortical hemodynamic responses to BP oscillations follow specific phase relationships due to cerebral autoregulatory action and circulatory transit times. With hemodynamic impairment, as in unilateral carotid obstruction, these phases are significantly changed reflecting disturbed autoregulation.

Comparison of regional cerebral blood flow in two subsets of subcortical ischemic vascular dementia: statistical parametric mapping analysis of SPECT.

BACKGROUND: The brain imaging criteria for subcortical ischemic vascular dementia (SIVD), as proposed by Erkinjuntti, incorporated two clinical entities, the lacunar state and Binswanger's disease. However it has not been proven whether these two subtypes of SIVD have common pathophysiological features. This study investigated the changes of regional cerebral blood flow (CBF) in the two subsets of SIVD to establish whether these two subtypes could be incorporated into the same group for the purpose of conducting clinical trials. METHODS: Twelve SIVD patients with predominant white matter lesions, 13 patients with predominant lacunar infarctions and 17 controls were evaluated. Single photon emission computed tomography (SPECT) was performed to measure the regional CBF, and statistical parametric mapping (SPM) was applied to the analysis of the SPECT data. RESULTS: The normalized CBF (nCBF) in the bilateral thalami, the anterior cingulate gyri, the superior temporal gyri, the caudate heads and the left parahippocampal gyrus was significantly decreased in the SIVD patients compared to the controls. This pattern of nCBF reduction was same in both the two subtypes of SIVD patients. CONCLUSION: Our study suggests that the two subsets of SIVD may have a common nCBF abnormality, and Erkinjuntti's criteria offer a solution for researchers to identify the more homogeneous group of vascular dementia patients.