Peter C. Brugger

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.

Fetal MRI: techniques and protocols

The development of ultrafast sequences has led to a significant improvement in fetal MRI. Imaging protocols have to be adjusted to the rapidly developing fetal central nervous system (CNS) and to the clinical question. Sequence parameters must be changed to cope with the respective developmental stage, to produce images free from motion artefacts and to provide optimum visualization of the region and focus of interest. In contrast to postnatal studies, every suspect fetal CNS abnormality requires examination of the whole fetus and the extrafetal intrauterine structures including the uterus. This approach covers both aspects of fetal CNS disorders: isolated and complex malformations and cerebral lesions arising from the impaired integrity of the feto-placental unit.

Prenatal ultrasound and fetal MRI: the comparative value of each modality in prenatal diagnosis.

Fetal MRI is used with increasing frequency as an adjunct to ultrasound (US) in prenatal diagnosis. In this review, we discuss the relative value of both prenatal US and MRI in evaluating fetal and extra-fetal structures for a variety of clinical indications. Advantages and disadvantages of each imaging modality are addressed. In summary, MRI has advantages in demonstrating pathology of the brain, lungs, complex syndromes, and conditions associated with reduction of amniotic fluid. At present, US is the imaging method of choice during the first trimester, and in the diagnosis of cardiovascular abnormalities, as well as for screening. In some conditions, such as late gestational age, increased maternal body mass index, skeletal dysplasia, and metabolic disease, neither imaging method may provide sufficient diagnostic information.

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).

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.

Preterm birth and disruptive cerebellar development: Assessment of perinatal risk factors

OBJECTIVE Abnormal cerebellar development was recently recognized to be related to prematurity. Aim of the present study was to evaluate preterm birth and possible peri- and postnatal risk factors associated with this type of brain injury. PATIENTS AND METHODS We report on a series of 35 very low birth weight infants (birth weight 986+/-257g S.D.) born between 24 and 32 weeks of gestation (27.0+/-1.8 weeks of gestation S.D.) sustaining disruption of cerebellar development after preterm birth. Perinatal medical records of study patients were compared to 41 preterm control infants (birth weight 900+/-358g S.D., gestational age 26.3+/-2.1 weeks S.D.) with normal cerebellar development on MRI scan. RESULTS A severely compromised postnatal condition with consecutive intubation and catecholamine support was found to be significant risk factor. Additional supratentorial hemorrhagic brain injury followed by posthemorrhagic hydrocephalus, neurosurgical interventions and hemosiderin deposits on the cerebellar surface were significantly related to disruptive cerebellar development. No other differences in perinatal factors were found between the groups. CONCLUSION Premature birth between 24 and 32 gestational weeks associated with poor postnatal conditions and complicated supratentorial hemorrhagic brain lesions represents a high-risk situation for disruption of cerebellar development.

Investigation of normal organ development with fetal MRI.

The understanding of the presentation of normal organ development on fetal MRI forms the basis for recognition of pathological states. During the second and third trimesters, maturational processes include changes in size, shape and signal intensities of organs. Visualization of these developmental processes requires tailored MR protocols. Further prerequisites for recognition of normal maturational states are unequivocal intrauterine orientation with respect to left and right body halves, fetal proportions, and knowledge about the MR presentation of extrafetal/intrauterine organs. Emphasis is laid on the demonstration of normal MR appearance of organs that are frequently involved in malformation syndromes. In addition, examples of time-dependent contrast enhancement of intrauterine structures are given.

What does magnetic resonance imaging add to the prenatal ultrasound diagnosis of facial clefts

Ultrasound is the modality of choice for prenatal detection of cleft lip and palate. Because its accuracy in detecting facial clefts, especially isolated clefts of the secondary palate, can be limited, magnetic resonance imaging (MRI) is used as an additional method for assessing the fetus. The aim of this study was to investigate the role of fetal MRI in the prenatal diagnosis of facial clefts.

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.