Quantitative Magnetic Resonance Imaging for Neurodevelopmental Outcome Prediction in Neonates Born Extremely Premature-An Exploratory Study.

PURPOSE: Neonates born at < 28 weeks of gestation are at risk for neurodevelopmental delay. The aim of this study was to identify quantitative MR-based metrics for the prediction of neurodevelopmental outcomes in extremely preterm neonates. METHODS: T1-/T2-relaxation times (T1R/T2R), ADC, and fractional anisotropy (FA) of the left/right posterior limb of the internal capsule (PLIC) and the brainstem were determined at term-equivalent ages in a sample of extremely preterm infants (n = 33). Scores for cognitive, language, and motor outcomes were collected at one year corrected-age. Pearson's correlation analyses detected relationships between quantitative measures and outcome data. Stepwise regression procedures identified imaging metrics to estimate neurodevelopmental outcomes. RESULTS: Cognitive outcomes correlated significantly with T2R (r = 0.412; p = 0.017) and ADC (r = -0.401; p = 0.021) (medulla oblongata). Furthermore, there were significant correlations between motor outcomes and T1R (pontine tegmentum (r = 0.346; p = 0.049), midbrain (r = 0.415; p = 0.016), right PLIC (r = 0.513; p = 0.002), and left PLIC (r = 0.504; p = 0.003)); T2R (right PLIC (r = 0.405; p = 0.019)); ADC (medulla oblongata (r = -0.408; p = 0.018) and pontine tegmentum (r = -0.414; p = 0.017)); and FA (pontine tegmentum (r = -0.352; p = 0.045)). T2R/ADC (medulla oblongata) (cognitive outcomes (R2 = 0.296; p = 0.037)) and T1R (right PLIC)/ADC (medulla oblongata) (motor outcomes (R2 = 0.405; p = 0.009)) revealed predictive potential for neurodevelopmental outcomes. CONCLUSION: There are relationships between relaxometry­/DTI-based metrics determined by neuroimaging near term and neurodevelopmental outcomes collected at one year of age. Both modalities bear prognostic potential for the prediction of cognitive and motor outcomes. Thus, quantitative MRI at term-equivalent ages represents a promising approach with which to estimate neurologic development in extremely preterm infants.

Fetal MRI based brain atlas analysis detects initial in utero effects of prenatal alcohol exposure.

Prenatal alcohol exposure (PAE) can change the normal trajectory of human fetal brain development and may lead to long-lasting neurodevelopmental changes in the form of fetal alcohol spectrum disorders. Currently, early prenatal patterns of alcohol-related central nervous system changes are unclear and it is unknown if small amounts of PAE may result in early detectable brain anomalies. This super-resolution fetal magnetic resonance imaging (MRI) study aimed to identify regional effects of PAE on human brain structure. Fetuses were prospectively assessed using atlas-based semi-automated 3-dimensional tissue segmentation based on 1.5 T and 3 T fetal brain MRI examinations. After expectant mothers completed anonymized PRAMS and TACE questionnaires for PAE, fetuses without gross macroscopic brain abnormalities were identified and analyzed. Linear mixed-effects modeling of regional brain volumes was conducted and multiple comparisons were corrected using the Benjamini-Hochberg procedure. In total, 500 pregnant women were recruited with 51 reporting gestational alcohol consumption. After excluding confounding comorbidities, 24 fetuses (26 observations) were identified with PAE and 52 age-matched controls without PAE were analyzed. Patients with PAE showed significantly larger volumes of the corpus callosum (P ≤ 0.001) and smaller volumes of the periventricular zone (P = 0.001). Even minor (1-3 standard drinks per week) PAE changed the neurodevelopmental trajectory.

The Prenatal Origins of Human Brain Asymmetry: Lessons Learned from a Cohort of Fetuses with Body Lateralization Defects.

Knowledge about structural brain asymmetries of human fetuses with body lateralization defects-congenital diseases in which visceral organs are partially or completely incorrectly positioned-can improve our understanding of the developmental origins of hemispheric brain asymmetry. This study investigated structural brain asymmetry in 21 fetuses, which were diagnosed with different types of lateralization defects; 5 fetuses with ciliopathies and 26 age-matched healthy control cases, between 22 and 34 gestational weeks of age. For this purpose, a database of 4007 fetal magnetic resonance imagings (MRIs) was accessed and searched for the corresponding diagnoses. Specific temporal lobe brain asymmetry indices were quantified using in vivo, super-resolution-processed MR brain imaging data. Results revealed that the perisylvian fetal structural brain lateralization patterns and asymmetry indices did not differ between cases with lateralization defects, ciliopathies, and normal controls. Molecular mechanisms involved in the definition of the right/left body axis-including cilium-dependent lateralization processes-appear to occur independently from those involved in the early establishment of structural human brain asymmetries. Atypically inverted early structural brain asymmetries are similarly rare in individuals with lateralization defects and may have a complex, multifactorial, and neurodevelopmental background with currently unknown postnatal functional consequences.

Comparison of the Visibility of Fetal Tooth Buds on 1.5 and 3 Tesla MRI.

Dental anomalies coincide with genetic disorders, and prenatal identification may contribute to a more accurate diagnosis. The aim of this study was to assess whether fetal Magnet Resonance Imaging (MRI) is suitable to visualize and investigate intrauterine dental development in the upper jaw, and to compare the quality of visibility of tooth buds between 1.5 Tesla (T) and 3T images. MR images of fetuses Gestational Week (GW) 26.71 ± 4.97 from 286 pregnant women with diagnoses unrelated to dental anomalies were assessed by three raters. We compared the visibility between groups and field strengths in five gestational age groups, using chi square and Fisher's exact tests. All ten primary tooth buds were identifiable in 5.4% at GW 18-21, in 75.5% at GW 26-29, and in 90.6% at GW 34+. Before GW 30, more tooth buds were identifiable on 3T images than on 1.5T images. Statistical significance was only reached for identification of incisors (p = 0.047). Therefore, 1.5T and 3T images are viable to visualize tooth buds, particularly after GW 25, and their analysis may serve as diagnostic criterion. MRI tooth bud data might have an impact on various fields of research, such as the maldevelopment of teeth and their causes. Analyzing tooth buds as an additional diagnostic criterion is not time consuming, and could lead to an improvement of syndrome diagnosis.

The MRI spectrum of congenital cytomegalovirus infection.

Human cytomegalovirus (CMV) is an ubiquitous pathogen, with a high worldwide seroprevalence. When acquired in the prenatal period, congenital CMV (cCMV) is a major cause of neurodevelopmental sequelae and hearing loss. cCMV remains an underdiagnosed condition, with no systematic screening implemented in pregnancy or in the postnatal period. Therefore, imaging takes a prominent role in prenatal diagnosis of cCMV. With the prospect of new viable therapies, accurate and timely diagnosis becomes paramount, as well as identification of fetuses at risk for neurodevelopmental sequelae. Fetal magnetic resonance imaging (MRI) provides a complementary method to ultrasound (US) in fetal brain and body imaging. Anterior temporal lobe lesions are the most specific finding, and MRI is superior to US in their detection. Other findings such as ventriculomegaly, cortical malformations and calcifications, as well as hepatosplenomegaly, liver signal changes and abnormal effusions are unspecific. However, when seen in combination these should raise the suspicion of fetal infection, highlighting the need for a full fetal assessment. Still, some fetuses deemed normal on prenatal imaging are symptomatic at birth or develop delayed cCMV-associated symptoms, leaving room for improvement of diagnostic tools. Advanced MR sequences may help in this field and in determining prognosis, but further studies are needed.

Fetal MRI for dummies: what the fetal medicine specialist should know about acquisitions and sequences.

Fetal MRI is an increasingly used tool in the field of prenatal diagnosis. While US remains the first line screening tool, as an adjuvant imaging tool, MRI has been proven to increase diagnostic accuracy and change patient counseling. Further, there are instances when US may not be sufficient for diagnosis. As a multidisciplinary field, it is important that every person involved in the referral, diagnosis, counseling and treatment of the patients is familiar with the basic principles, indications and findings of fetal MRI. The purpose of the current paper is to equip radiologists and non-radiologists with basic MRI principles and essential topics in patient preparation and provide illustrative examples of when fetal MRI may be used. This aims to aid the referring clinician in better selecting and improve patient counseling prior to arrival in the radiology department and, ultimately, patient care.

Echo-planar FLAIR Sequence Improves Subplate Visualization in Fetal MRI of the Brain.

Background The cortical plate (future cortex) is readily identifiable in utero at MRI. However, MRI evaluation of the remaining brain layers is limited by the poor T2 contrast between the subplate and the underlying intermediate zone (IZ). Purpose To compare the delineation of fetal brain lamination between T2-weighted single-shot fast spin-echo (SSFSE) and echo-planar imaging (EPI) fluid-attenuated inversion recovery (FLAIR) images, and to quantify differences in the depiction of brain layering between the two sequences. Materials and Methods Consecutive fetal brain MRI examinations performed between January 2014 and March 2018 with T2-weighted SSFSE and EPI-FLAIR images were reviewed. Two neuroradiologists evaluated the visibility of brain layers by using a three-point grading system, and findings were compared by using the sign test. One rater performed region-of-interest analysis in the cortical plate (CP), subplate (gyral crest and sulcal bottom), and IZ. Signal intensity (SI) ratios between adjacent brain compartments were calculated and compared by using the paired t test. Reader agreement was assessed by using weighted κ values. Results A total of 259 MRI examinations (mean gestational age [GA], 26.9 weeks ± 5.6) were included in the qualitative analysis, and 72 MRI examinations (mean GA, 27.4 weeks ± 5.5) were included in the quantitative analysis. Subplate identification on EPI-FLAIR images was superior to that on T2-weighted SSFSE images (subplate visualization [complete + partial]: frontal lobe, n = 243 vs n = 117; temporal lobe, n = 244 vs n = 137; parietal lobe n = 240 vs n = 93; and occipital lobe, n = 241 vs n = 97, respectively; P < .001), with higher interrater reliability (κ = 0.91-0.95 for EPI-FLAIR images and 0.80-0.87 for T2-weighted SSFSE images). SI ratios between the IZ and subplate were significantly higher on EPI-FLAIR images in all lobes (EPI-FLAIR images: 1.6-2.1; T2-weighted SSFSE images:1.2-1.2; P < .001). Subplate-to-CP ratios were not statistically significant between the two sequences (EPI-FLAIR:1.8-2.4; T2-weighted SSFSE: 2.0-2.2; P < .001). Conclusion The echo-planar fluid-attenuated inversion recovery sequence improves visualization of fetal brain lamination compared with the T2-weighted single-shot fast spin-echo sequence, as established by quantitative and qualitative methods. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Rossi in this issue.

Mens inversus in corpore inverso? Language lateralization in a boy with situs inversus totalis.

Situs inversus totalis is a rare condition where the visceral organs are organized as a mirror image of default organ position. In this study we picture the co-development between brain and visceral organs in a case of situs inversus totalis from a fetal stage to adolescence and compare our findings to an age-, gender-, and education-matched control with normal position of thoracic and abdominal organs. We show that in this case of situs inversus, functional and structural brain lateralization do not coincide with visceral organ situs. Furthermore, cognitive development in situs inversus is normal. To our knowledge, this is the first report of antenatal cerebral origins of structural and functional brain asymmetry in a case of situs inversus totalis.

Low prevalence of fetal-type posterior cerebral artery in patients with basilar tip aneurysms.

BACKGROUND: Basilar tip aneurysms (BTA) are multifactorial in origin, with luminal forces playing a major role in their formation. Considering the reduced hemodynamic stress on the basilar apex in the fetal-type posterior cerebral artery (fPCA), we hypothesize that BTA should be less common in patients with this variant. OBJECTIVE: To investigate, in a retrospective case-control study, the frequency of fPCA in patients with and without BTA. MATERIALS AND METHODS: We collected clinical and imaging data from consecutive patients with BTA undergoing catheter angiography between July 2010 and July 2015, and from a randomly selected, age- and sex-matched non-BTA control population from our prospective database. Anatomical variants of the distal basilar artery region were assessed in the two groups and compared using parametric and non-parametric tests. RESULTS: Fifty-nine BTA cases and 337 controls were included. fPCA was present in 3% of patients with BTA and 23% in the control group (p<0.001; OR=0.11, 95% CI 0.03 to 0.48). Basilar tip disposition was cranial in 49% of BTA and 63% of non-BTA cases (p=0.04; OR=0.57, 95% CI 0.33 to 0.99); a caudal disposition was found in 24% and 6% of cases, respectively (p<0.001; OR=4.65, 95% CI 2.21 to 9.80). CONCLUSIONS: We found a statistically significant association between the absence of fPCA and BTA. Our findings underline the importance of hemodynamic stress in the formation of intracranial aneurysms, and suggest that fPCA is a protective variant for formation of BTA.

Fetal MRI at 3T-ready for routine use?

Fetal MR now plays an important role in the clinical work-up of pregnant females. It is performed mainly at 1.5 T. However, the desire to obtain a more precise fetal depiction or the fact that some institutions have access only to a 3.0 T scanner has resulted in a growing interest in performing fetal MR at 3.0 T. The aim of this article was to provide a reference for the use of 3.0 T MRI as a prenatal diagnostic method.