Gregor Kasprian

In utero tractography of fetal white matter development.

Diffusion tensor imaging (DTI) and tractography are noninvasive tools that enable the study of three-dimensional diffusion characteristics and their molecular, cellular, and microstructural correlates in the human brain. To date, these techniques have mainly been limited to postnatal MR studies of premature infants and newborns. The primary aim of this cross-sectional study was to assess the potential of in utero DTI and tractography to visualize the main projection and commissural pathways in 40 living, non-sedated human fetuses between 18 and 37 gestational weeks (GW) of age, with no structural brain pathologies. During a mean time of 1 min and 49 s, an axial, single-shot, echo planar DT sequence, with 32 diffusion gradient encoding directions and a reconstructed voxel size of 1.44 mm/1.45 mm/4.5 mm, was acquired. Most (90%) of the fetuses were imaged in the cephalic presentation. In 40% of examined fetuses, DTI measurements were robust enough to successfully calculate and visualize bilateral, craniocaudally oriented (mainly sensorimotor), and callosal trajectories in utero. Furthermore, fiber lengths, ADC, FA, and eigenvalues (lambda(1), lambda(2) and lambda(3)) were determined at different anatomically defined areas. FA values and the axial eigenvalue (lambda(1)) showed a characteristic distribution, with the highest values for the splenium, followed by the genu, the right, and the left posterior limb of the internal capsule. The right-sided sensorimotor trajectories were found to be significantly longer than on the left side (p=0.007), reflecting higher right-sided lambda(1) values (14 cases vs. 9 cases). Based on the good correlation of these initial in utero tractography results with prior documented postmortem and ex utero DTI data, this new imaging technique promises new insights into the normal and pathological development of the unborn child.

The Prenatal Origin of Hemispheric Asymmetry: An In Utero Neuroimaging Study

Anatomical and functional hemispheric lateralization originates from differential gene expression and leads to asymmetric structural brain development, which initially appears in the perisylvian regions by 26 gestational weeks (GWs). In this in vivo neuroimaging study, we demonstrated a predominant pattern of temporal lobe (TL) asymmetry in a large cohort of human fetuses between 18 and 37 GWs. Over two-thirds of fetuses showed a larger, left-sided TL, combined with the earlier appearance of the right superior temporal sulcus by 23 GWs (vs. 25 GWs on the left side), which was also deeper than its left counterpart in the majority of cases (94.2%). Shape analysis detected highly significant differences in the contour of the right and left TLs by 20 GWs. Thus, fetal hemispheric asymmetry can be detected in utero, opening new diagnostic possibilities for the assessment of diseases that are believed to be linked to atypical hemispheric lateralization.

Watching the fetal brain at 'rest'.

Functional magnetic resonance imaging (fMRI) has allowed insights into the spatiotemporal distribution of human brain networks. According to the neurophysiological property of the fetal brain to generate spontaneous activity, we aimed to determine the feasibility of investigating the maturation of intrinsic networks, beginning at gestational week 20 in healthy human fetuses by combining resting‐state fMRI and an analytical approach, independent component analysis (ICA).

3T MR tomography of the brachial plexus: structural and microstructural evaluation.

Magnetic resonance (MR) neurography comprises an evolving group of techniques with the potential to allow optimal noninvasive evaluation of many abnormalities of the brachial plexus. MR neurography is clinically useful in the evaluation of suspected brachial plexus traumatic injuries, intrinsic and extrinsic tumors, and post-radiogenic inflammation, and can be particularly beneficial in pediatric patients with obstetric trauma to the brachial plexus. The most common MR neurographic techniques for displaying the brachial plexus can be divided into two categories: structural MR neurography; and microstructural MR neurography. Structural MR neurography uses mainly the STIR sequence to image the nerves of the brachial plexus, can be performed in 2D or 3D mode, and the 2D sequence can be repeated in different planes. Microstructural MR neurography depends on the diffusion tensor imaging that provides quantitative information about the degree and direction of water diffusion within the nerves of the brachial plexus, as well as on tractography to visualize the white matter tracts and to characterize their integrity. The successful evaluation of the brachial plexus requires the implementation of appropriate techniques and familiarity with the pathologies that might involve the brachial plexus.

Placental Pathologies in Fetal MRI with Pathohistological Correlation

INTRODUCTION The purpose of this study was to evaluate whether currently available fetal Magnetic Resonance Imaging (MRI/MR) techniques are sufficient for the assessment of placental pathologies. We hypothesized that placental pathologies as detected and evaluated by MRI, would correlate with histological findings. PATIENTS AND METHODS In a retrospective study, 45 singleton pregnancies from 19 to 35 gestational weeks, with placental pathologies on MR scans, were included. MRI was performed on a 1.5T unit using T2-, T1-, and diffusion-weighted and echo-planar sequences. Pathologies were categorized into infarction with/without hemorrhagic components, subchorionic/intervillous thrombi/hemorrhages, retroplacental hematoma, massive perivillous fibrin deposition, and chorioamnionitis. Pathohistological examination was performed postnatally within a median of seven days between MR examination and delivery. RESULTS AND DISCUSSION Pathologically, 26 placentas showed infarctions (96.2% on MR scans), two retroplacental hematomas were detected by MRI and confirmed by pathology, and 9 of 14 subchorionic hematomas were confirmed. Six of eight intervillous hemorrhages were seen on MRI, and three of six cases of severe chorioamnionitis were diagnosed prenatally. Placental hemorrhages (retroplacental hematoma, intervillous thrombi, subchorionic hematoma), and ischemic lesions could be detected with fetal MRI, while chorioamnionitis and even massive perivillous fibrin deposition showed few signal changes, probably reflecting small macroscopic changes in the placenta. Fetal MRI, therefore, seems to be a promising tool for the assessment of placental insufficiency.

Disruption of nigrostriatal and cerebellothalamic pathways in dopamine responsive Holmes’ tremor

Holmes’ tremor is an unusual combination of rest, postural and kinetic tremor of the extremities. Medical treatment of this condition still remains unsatisfactory. The case of a 20-year-old female patient is reported who developed right-sided Holmes’ tremor 9 months after a left-sided, cavernoma induced midbrain/pontine haemorrhage at the age of 16 years. Beta-CIT single photon emission computed tomography revealed abolished dopamine transporter activity in the left basal ganglia and striatum, in accordance with missing ipsilateral tegmento-frontal connectivity (medial forebrain bundle), demonstrated by diffusion tensor MRI. Tractography showed reduced fibre connectivity of the superior and middle cerebellar peduncles on the lesioned side. Administration of pramipexole and L-DOPA led to a clinically significant reduction in tremor severity. In conclusion, our results support the notion that Holmes’ tremor was a result of diminished striatal dopaminergic input in our patient.

Epilepsy surgery in children and adolescents with malformations of cortical development—-Outcome and impact of the new ILAE classification on focal cortical dysplasia

UNLABELLED To determine long-term efficacy and safety of epilepsy surgery in children and adolescents with malformations of cortical development (MCD) and to identify differences in seizure outcome of the various MCD subgroups. Special focus was set on the newly introduced International League Against Epilepsy (ILAE) classification of focal cortical dysplasia (FCD). STUDY DESIGN This is a single center retrospective cross-sectional analysis of prospectively collected data. INCLUSION CRITERIA age at surgery <18 years, pre-surgical evaluation and epilepsy surgery performed at the Vienna pediatric epilepsy center, histologically proven MCD, complete follow-up data for at least 12 months. Clinical variables evaluated: type and localization of MCD, type of surgery and a variety of clinical characteristics reported to be associated with (un-)favorable outcomes. MCD were classified following the existing classification schemes (Barkovich et al., 2012. Brain. 135, 1348-1369; Palmini et al., 2004. Neurology. 62, S2-S8) and the ILAE classification for FCD recently proposed by Blümcke in 2011. Seizure outcome was classified using the ILAE classification proposed by Wieser in 2001. RESULTS 60 Patients (51.7% male) were included. Follow up was up to 14 (mean 4.4 ± 3.2) years. Mean age at surgery was 8.0 ± 6.0 (median 6.0) years; mean age at epilepsy onset was 2.9 ± 3.2 (median 2.0) years; duration of epilepsy before surgery was 4.8 ± 4.4 (median 3.0) years. 80% of the patients were seizure free at last follow-up. AEDs were successfully withdrawn in 56.7% of all patients. Extended surgery, lesion localization in the temporal lobes and absence of inter-ictal spikes in postsurgical EEG recordings were predictive of favorable seizure outcomes after surgery. However, no association was found between outcome and MCD sub-types. Epilepsy surgery is highly effective in carefully selected drug-resistant children with MCD. Surrogate markers for complete resection of the epileptogenic zone remain the only significant predictors for seizure freedom after surgery.

Fetal diffusion imaging: pearls and solutions.

Abstract Recently, diffusion-weighted (DWI) magnetic resonance imaging of the fetus has evolved from a basic research application to an important diagnostic imaging tool in fetal magnetic resonance imaging. Although technically challenging and still plagued with several sources of artifacts, DWI can add clinically important information, which cannot be provided by any other prenatal imaging modality. Its potential to noninvasively probe tissue structures on the basis of Brownian molecular motion enables the detection of early changes associated with acute fetal diseases, as well as structural alterations of functionally diverse compartments of different fetal organs. In this article, the current clinical applications of fetal brain and body DWI are outlined, as well as its current limitations.

In vivo tractography of fetal association fibers.

Association fibers connect different cortical areas within the same hemisphere and constitute an essential anatomical substrate for a diverse range of higher cognitive functions. So far a comprehensive description of the prenatal in vivo morphology of these functionally important pathways is lacking. In the present study, diffusion tensor imaging (DTI) and tractography were used to visualize major association fiber tracts and the fornix in utero in preselected non-motion degraded DTI datasets of 24 living unsedated fetuses between 20 and 34 gestational weeks (GW). The uncinate fasciculus and inferior fronto-occipital fasciculus were depicted as early as 20 GW, while in vivo 3D visualization of the inferior longitudinal fasciculus, cingulum and fornix was successful in older fetuses during the third trimester. Provided optimal scanning conditions, in utero DTI and tractography have the potential to provide a more accurate anatomical definition of developing neuronal networks in the human fetal brain. Knowledge about the normal prenatal 3D association tract morphology may serve as reference for their assessment in common developmental diseases.

Magnetic resonance methods in fetal neurology

Fetal magnetic resonance imaging (MRI) has become an established clinical adjunct for the in-vivo evaluation of human brain development. Normal fetal brain maturation can be studied with MRI from the 18th week of gestation to term and relies primarily on T2-weighted sequences. Recently diffusion-weighted sequences have gained importance in the structural assessment of the fetal brain. Diffusion-weighted imaging provides quantitative information about water motion and tissue microstructure and has applications for both developmental and destructive brain processes. Advanced magnetic resonance techniques, such as spectroscopy, might be used to demonstrate metabolites that are involved in brain maturation, though their development is still in the early stages. Using fetal MRI in addition to prenatal ultrasound, morphological, metabolic, and functional assessment of the fetus can be achieved. The latter is not only based on observation of fetal movements as an indirect sign of activity of the fetal brain but also on direct visualization of fetal brain activity, adding a new component to fetal neurology. This article provides an overview of the MRI methods used for fetal neurologic evaluation, focusing on normal and abnormal early brain development.