Swati Mody

Cross-Hemispheric Functional Connectivity in the Human Fetal Brain

fMRI enables noninvasive direct quantification of neural network connectivity in the healthy human fetus. Connecting the Dots on Normal Brain Development Functional connections between different areas of the human brain develop and mature over time. Abnormalities in such connections have been implicated in many common disorders, ranging from developmental problems such as attention deficit hyperactivity disorder and autism to adult-onset diseases such as schizophrenia and Alzheimer’s disease. Abnormal patterns of brain connections likely originate during in utero development, but it is difficult to determine what happens in the brain during the prenatal period in healthy fetuses. Imaging studies of premature neonates have shed some light on this problem, but any infant born prematurely is no longer in a physiological environment for normal brain development, and anything that caused a premature delivery could have also changed the pattern of connections in the infant’s brain. Imaging of healthy full-term neonates can also help map the patterns of infant brain connectivity, but knowing the state of an infant’s brain at the time of birth is not enough to determine the developmental trajectory that it took in utero. Now, Thomason and colleagues used resting-state functional magnetic resonance imaging (MRI) to map the brain connections of 25 healthy singleton fetuses between 24 and 39 weeks of gestation. Their imaging data confirmed the presence of bilateral functional connections in the fetal brain, as well as regional connections within each hemisphere. As expected, the connection pattern varied with the age of the fetus, such that connection strength increased as the fetuses approached full term. Further research will be needed to determine how abnormal brain connectivity patterns evolve over time, and how they differ from the healthy infant patterns presented here. In addition, the quality of prenatal MRI data is still limited by fetal movement, and future improvements in MRI technology will be required to address this problem and refine the process of fetal MRI imaging. The current report by Thomason et al. provides a foundation for such future studies and presents a map of fetal brain connections that can serve as a starting point for research in this field. Compelling evidence indicates that psychiatric and developmental disorders are generally caused by disruptions in the functional connectivity (FC) of brain networks. Events occurring during development, and in particular during fetal life, have been implicated in the genesis of such disorders. However, the developmental timetable for the emergence of neural FC during human fetal life is unknown. We present the results of resting-state functional magnetic resonance imaging performed in 25 healthy human fetuses in the second and third trimesters of pregnancy (24 to 38 weeks of gestation). We report the presence of bilateral fetal brain FC and regional and age-related variation in FC. Significant bilateral connectivity was evident in half of the 42 areas tested, and the strength of FC between homologous cortical brain regions increased with advancing gestational age. We also observed medial to lateral gradients in fetal functional brain connectivity. These findings improve understanding of human fetal central nervous system development and provide a basis for examining the role of insults during fetal life in the subsequent development of disorders in neural FC.

Age-Related Increases in Long-Range Connectivity in Fetal Functional Neural Connectivity Networks In Utero

Highlights • We examined patterns of connectivity in human fetal brain networks.• The fetal brain demonstrates cerebral-cerebellar and cortical-subcortical connectivity.• Many forms of cerebral connectivity are present by the third trimester.• Default mode network connections were evident in fetuses older than 35 weeks.• Long-range functional connectivity is more prominent in older fetuses.

Intrinsic functional brain architecture derived from graph theoretical analysis in the human fetus.

The human brain undergoes dramatic maturational changes during late stages of fetal and early postnatal life. The importance of this period to the establishment of healthy neural connectivity is apparent in the high incidence of neural injury in preterm infants, in whom untimely exposure to ex-uterine factors interrupts neural connectivity. Though the relevance of this period to human neuroscience is apparent, little is known about functional neural networks in human fetal life. Here, we apply graph theoretical analysis to examine human fetal brain connectivity. Utilizing resting state functional magnetic resonance imaging (fMRI) data from 33 healthy human fetuses, 19 to 39 weeks gestational age (GA), our analyses reveal that the human fetal brain has modular organization and modules overlap functional systems observed postnatally. Age-related differences between younger (GA <31 weeks) and older (GA≥31 weeks) fetuses demonstrate that brain modularity decreases, and connectivity of the posterior cingulate to other brain networks becomes more negative, with advancing GA. By mimicking functional principles observed postnatally, these results support early emerging capacity for information processing in the human fetal brain. Current technical limitations, as well as the potential for fetal fMRI to one day produce major discoveries about fetal origins or antecedents of neural injury or disease are discussed.

MR imaging of the fetal brain at 1.5T and 3.0T field strengths: comparing specific absorption rate (SAR) and image quality

Abstract Objectives: Our two objectives were to evaluate the feasibility of fetal brain magnetic resonance imaging (MRI) using a fast spin echo sequence at 3.0T field strength with low radio frequency (rf) energy deposition (as measured by specific absorption rate: SAR) and to compare image quality, tissue contrast and conspicuity between 1.5T and 3.0T MRI. Methods: T2 weighted images of the fetal brain at 1.5T were compared to similar data obtained in the same fetus using a modified sequence at 3.0T. Quantitative whole-body SAR and normalized image signal to noise ratio (SNR), a nominal scoring scheme based evaluation of diagnostic image quality, and tissue contrast and conspicuity for specific anatomical structures in the brain were compared between 1.5T and 3.0T. Results: Twelve pregnant women underwent both 1.5T and 3.0T MRI examinations. The image SNR was significantly higher (P=0.03) and whole-body SAR was significantly lower (P<0.0001) for images obtained at 3.0T compared to 1.5T. All cases at both field strengths were scored as having diagnostic image quality. Images from 3.0T MRI (compared to 1.5T) were equal (57%; 21/37) or superior (35%; 13/37) for tissue contrast and equal (61%; 20/33) or superior (33%, 11/33) for conspicuity. Conclusions: It is possible to obtain fetal brain images with higher resolution and better SNR at 3.0T with simultaneous reduction in SAR compared to 1.5T. Images of the fetal brain obtained at 3.0T demonstrated superior tissue contrast and conspicuity compared to 1.5T.

Measuring Venous Blood Oxygenation in Fetal Brain using Susceptibility Weighted Imaging

To evaluate fetal cerebral venous blood oxygenation, Yv, using principles of MR susceptometry.

Clinical and neuroimaging findings in neonatal herpes simplex virus infection.

In a retrospective review of infants with neonatal herpes simplex virus disease (n=29), we found bilateral multilobar (n=8), pontine (n=3), thalamic (n=6), and internal capsule and corticospinal tract (n=5) involvement on magnetic resonance imaging (MRI). Diffusion-weighted imaging (n=6) performed early revealed additional involvement than detected by conventional MRI. Neurodevelopmental sequelae were correlated with MRI abnormalities. Our findings demonstrate that MRI, including diffusion-weighted imaging, is a valuable prognostic adjunct in neonatal herpes simplex virus disease.

MR venography of the fetal brain using susceptibility weighted imaging.

To evaluate the feasibility of performing fetal brain magnetic resonance venography using susceptibility weighted imaging (SWI).

Non-invasive fetal lung assessment using diffusion-weighted imaging

The main goal was to develop a reproducible method for estimating the diffusion of water in human fetal lung tissue using diffusion‐weighted imaging (DWI). A secondary objective was to determine the relationship of the apparent diffusion coefficients (ADCs) in the fetal lung to menstrual age and total lung volume.

Prenatal diagnostic challenges and pitfalls for schizencephaly.

Schizencephaly is a developmental anomaly that causes unilateral or bilateral clefts of the cerebral hemisphere as a result of disordered neuronal migration. The clefts are lined by gray matter that can extend medially from the subarachnoid cerebrospinal fluid space into the lateral ventricle as part of a disease spectrum that includes porencephaly. Closed-lip schizencephaly (Type 1) occurs when the gray-matter lined walls are in contact with each other (1). By contrast, the open lip variety (Type 2) has separated lips with a cleft of cerebrospinal fluid that extends to the ventricles (2). Barkovich and co-workers (3) have reported that the clinical manifestations of affected infants are related to the size and location of the cleft defect. Late prenatal schizencephaly has been well documented. We now report well-documented case that demonstrates diagnostic challenges and pitfalls associated with its early diagnosis by 2D/3D ultrasonography and magnetic resonance imaging (MR).

Occipital meningoencephalocele in a preterm neonate

A preterm (33 weeks) male neonate was born to a 34-year-old mother by caesarean section. The mother had a history of chronic hypertension, type 1 diabetes mellitus, stroke and asthma. Her medications included enoxaparin, insulin, nifedipine, methyldopa, inhaled albuterol and inhaled corticosteroids. She received regular prenatal care. The obstetric ultrasound done at 21 weeks of gestation revealed an occipital encephalocele, measuring ∼3.3×2.0×2.5 cm in size and protruding through a 0.95 cm cranial defect in the occipital area. The baby had a spontaneous cry at birth with Apgar score of 9 and 9 at …