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.

T1-weighted fast fluid-attenuated inversion-recovery sequence (T1-FFLAIR) enables the visualization and quantification of fetal brain myelination in utero.

OBJECTIVES: To investigate the advantage of T1-weighted fast fluid-attenuated inversion-recovery MRI sequence without (T1-FFLAIR) and with compressed sensing technology (T1-FFLAIR-CS), which shows improved T1-weighted contrast, over standard used T1-weighted fast field echo (T1-FFE) sequence for the assessment of fetal myelination. MATERIALS AND METHODS: This retrospective single-center study included 115 consecutive fetal brain MRI examinations (63 axial and 76 coronal, mean gestational age (GA) 28.56 ± 5.23 weeks, range 19-39 weeks). Two raters, blinded to GA, qualitatively assessed a fetal myelin total score (MTS) on each T1-weighted sequence at five brain regions (medulla oblongata, pons, mesencephalon, thalamus, central region). One rater performed region-of-interest quantitative analysis (n = 61) at the same five brain regions. Pearson correlation analysis was applied for correlation of MTS and of the signal intensity ratios (relative to muscle) with GA on each T1-weighted sequence. Fetal MRI-based results were compared with myelination patterns of postmortem fetal human brains (n = 46; GA 18 to 42), processed by histological and immunohistochemical analysis. RESULTS: MTS positively correlated with GA on all three sequences (all r between 0.802 and 0.908). The signal intensity ratios measured at the five brain regions correlated best with GA on T1-FFLAIR (r between 0.583 and 0.785). T1-FFLAIR demonstrated significantly better correlations with GA than T1-FFE for both qualitative and quantitative analysis (all p < 0.05). Furthermore, T1-FFLAIR enabled the best visualization of myelinated brain structures when compared to histology. CONCLUSION: T1-FFLAIR outperforms the standard T1-FFE sequence in the visualization of fetal brain myelination, as demonstrated by qualitative and quantitative methods. CLINICAL RELEVANCE STATEMENT: T1-weighted fast fluid-attenuated inversion-recovery sequence (T1-FFLAIR) provided best visualization and quantification of myelination in utero that, in addition to the relatively short acquisition time, makes feasible its routine application in fetal MRI for the assessment of brain myelination. KEY POINTS: • So far, the assessment of fetal myelination in utero was limited due to the insufficient contrast. • T1-weighted fast fluid-attenuated inversion-recovery sequence allows a qualitative and quantitative assessment of fetal brain myelination. • T1-weighted fast fluid-attenuated inversion-recovery sequence outperforms the standard used T1-weighted sequence for visualization and quantification of myelination in utero.

Influence of dilution on arterial-phase artifacts and signal intensity on gadoxetic acid-enhanced liver MRI.

OBJECTIVES: To investigate the effect of saline-diluted gadoxetic acid, done for arterial-phase (AP) artifact reduction, on signal intensity (SI), and hence focal lesion conspicuity on MR imaging. METHODS: We retrospectively examined 112 patients who each had at least two serial gadoxetic acid-enhanced liver MRIs performed at 1 ml/s, first with non-diluted (ND), then with 1:1 saline-diluted (D) contrast. Two blinded readers independently analyzed the artifacts and graded dynamic images using a 5-point scale. The absolute SI of liver parenchyma, focal liver lesions (if present), aorta, and portal vein at the level of the celiac trunk and the SI of the paraspinal muscle were measured in all phases. The signal-to-norm (SINorm) of the vascular structures, hepatic parenchyma and focal lesions, and the contrast-to-norm (CNorm) of focal liver lesions were calculated. RESULTS: AP artifacts were significantly reduced with dilution. Mean absolute contrast-enhanced liver SI was significantly higher on the D exams compared to the ND exams. Likewise, SINorm of liver parenchyma was significantly higher in all contrast-enhanced phases except transitional phase on the D exams. SINorm values in the AP for the aorta and in the PVP for portal vein were significantly higher on the diluted exams. The CNorm was not significantly different between ND and D exams for lesions in any imaging phase. The interclass correlation coefficient was excellent (0.89). CONCLUSION: Gadoxetic acid dilution injected at 1ml/s produces images with significantly fewer AP artifacts but no significant loss in SINorm or CNorm compared to standard non-diluted images. KEY POINTS: • Diluted gadoxetic acid at slow injection (1 ml/s) yielded images with higher SINorm of the liver parenchyma and preserved CNorm for focal liver lesions. • Gadoxetic acid-enhanced MRI injected at 1 ml/s is associated with arterial-phase (AP) artifacts in 31% of exams, which may degrade image quality and limits focal liver lesion detection. • Saline dilution of gadoxetic acid 1:1 combined with a slow injection rate of 1 ml/s significantly reduced AP artifacts from 31 to 9% and non-diagnostic AP artifacts from 16 to 1%.

Brainstem and cerebellar volumes at magnetic resonance imaging are smaller in fetuses with congenital heart disease.

BACKGROUND: Congenital heart disease is associated with an increased risk of smaller brain volumes and structural brain damage, and impaired growth of supratentorial brain structures in utero has been linked to poor neurodevelopmental outcomes. However, little is known on brainstem and cerebellar volumes in fetuses with congenital heart disease. Moreover, it is not clear whether impaired infratentorial growth, if present, is associated with only certain types of fetal cardiac defects or with supratentorial brain growth, and whether altered biometry is already present before the third trimester. OBJECTIVE: This study aimed to investigate brainstem and cerebellar volumes in fetuses with congenital heart disease and to compare them to infratentorial brain volumes in fetuses with normal hearts. Secondarily, the study aimed to identify associations between infratentorial brain biometry and the type of cardiac defects, supratentorial brain volumes, and gestational age. STUDY DESIGN: In this retrospective case-control study, 141 magnetic resonance imaging studies of 135 fetuses with congenital heart disease and 141 magnetic resonance imaging studies of 125 controls with normal hearts at 20 to 37 gestational weeks (median, 25 weeks) were evaluated. All cases and controls had normal birthweight and no evidence of structural brain disease or genetic syndrome. Six types of congenital heart disease were included: tetralogy of Fallot (n=32); double-outlet right ventricle (n=22); transposition of the great arteries (n=27); aortic obstruction (n=24); hypoplastic left heart syndrome (n=22); and hypoplastic right heart syndrome (n=14). First, brainstem and cerebellar volumes of each fetus were segmented and compared between cases and controls. In addition, transverse cerebellar diameters, vermian areas, and supratentorial brain and cerebrospinal fluid volumes were quantified and differences assessed between cases and controls. Volumetric differences were further analyzed according to types of cardiac defects and supratentorial brain volumes. Finally, volume ratios were created for each brain structure ([volume in fetus with congenital heart disease/respective volume in control fetus] × 100) and correlated to gestational age. RESULTS: Brainstem (cases, 2.1 cm3 vs controls, 2.4 cm3; P<.001) and cerebellar (cases, 3.2 cm3 vs controls, 3.4 cm3; P<.001) volumes were smaller in fetuses with congenital heart disease than in controls, whereas transverse cerebellar diameters (P=.681) and vermian areas (P=.947) did not differ between groups. Brainstem and cerebellar volumes differed between types of cardiac defects. Overall, the volume ratio of cases to controls was 80.8% for the brainstem, 90.5% for the cerebellum, and 90.1% for the supratentorial brain. Fetuses with tetralogy of Fallot and transposition of the great arteries were most severely affected by total brain volume reduction. Gestational age had no effect on volume ratios. CONCLUSION: The volume of the infratentorial brain, which contains structures considered crucial to brain function, is significantly smaller in fetuses with congenital heart disease than in controls from midgestation onward. These findings suggest that impaired growth of both supra- and infratentorial brain structures in fetuses with congenital heart disease occurs in the second trimester. Further research is needed to elucidate associations between fetal brain volumes and neurodevelopmental outcomes in congenital heart disease.

Abnormal Extracardiac Development in Fetuses With Congenital Heart Disease.

BACKGROUND: Knowledge about extracardiac anomalies (ECA) in fetal congenital heart disease (CHD) can improve our understanding of the developmental origins of various outcomes in these infants. The prevalence and spectrum of ECA, including structural brain anomalies (SBA), on magnetic resonance imaging (MRI) in fetuses with different types of CHD and at different gestational ages, is unknown. OBJECTIVES: The purpose of this study was to evaluate ECA rates and types on MRI in fetuses with different types of CHD and across gestation. METHODS: A total of 429 consecutive fetuses with CHD and MRI between 17 and 38 gestational weeks were evaluated. ECA and SBA rates were assessed for each type of CHD and classified by gestational age (<25 or ≥25 weeks) at MRI. RESULTS: Of all 429 fetuses with CHD, 243 (56.6%) had ECA on MRI, and 109 (25.4%) had SBA. Among the 191 fetuses with normal genetic testing results, the ECA rate was 54.5% and the SBA rate 19.4%. Besides SBA, extrafetal (21.2%) and urogenital anomalies (10.7%) were the most prevalent ECA on MRI in all types of CHD. Predominant SBA were anomalies of hindbrain-midbrain (11.0% of all CHD), dorsal prosencephalon (10.0%) development, and abnormal cerebrospinal fluid spaces (10.5%). There was no difference in the prevalence or pattern of ECA between early (<25 weeks; 45.7%) and late (≥25 weeks; 54.3%) fetal MRI. CONCLUSIONS: ECA and SBA rates on fetal MRI are high across all types of CHD studied, and ECA as well as SBA are already present from midgestation onward.

Diagnostic quality of 3Tesla postmortem magnetic resonance imaging in fetuses with and without congenital heart disease.

BACKGROUND: Postmortem confirmation of prenatally diagnosed congenital heart disease after termination of pregnancy and evaluation of potential cardiac defects after spontaneous fetal or neonatal death are essential. Conventional autopsy rates are decreasing, and 1.5Tesla magnetic resonance imaging has demonstrated limited diagnostic accuracy for postmortem cardiovascular assessment. OBJECTIVE: This study aimed to evaluate the feasibility and image quality of cardiac 3Tesla postmortem magnetic resonance imaging and to assess its diagnostic accuracy in detecting fetal heart defects compared with conventional autopsy. Secondarily, the study aimed to explore whether clinical factors affect the quality of 3Tesla postmortem magnetic resonance imaging. STUDY DESIGN: A total of 222 consecutive fetuses between 12 and 41 weeks' gestation, who underwent 3Tesla postmortem magnetic resonance imaging and conventional autopsy after spontaneous death or termination of pregnancy for fetal malformations, were included. First, 3Tesla postmortem magnetic resonance imaging of each fetus was rated as diagnostic or nondiagnostic for fetal cardiac assessment by 2 independent raters. The image quality of individual cardiac structures was then further evaluated by visual grading analysis. Finally, the presence or absence of a congenital heart defect was assessed by 2 radiologists and compared with autopsy results. RESULTS: Overall, 87.8% of 3Tesla postmortem magnetic resonance imaging examinations were rated as diagnostic for the fetal heart. Diagnostic imaging rates of individual cardiac structures at 3Tesla postmortem magnetic resonance imaging ranged from 85.1% (atrioventricular valves) to 94.6% (pericardium), with an interrater agreement of 0.82 (0.78-0.86). Diagnostic imaging of the fetal aortic arch and the systemic veins at 3Tesla postmortem magnetic resonance imaging was possible from 12+5 weeks' gestation onward in 90.1% and 92.3% of cases, respectively. A total of 55 fetuses (24.8%) had at least 1 cardiac anomaly according to autopsy, 164 (73.9%) had a normal heart, and in 3 fetuses (1.4%), autopsy was nondiagnostic for the heart. Considering all examinations rated as diagnostic, 3Tesla postmortem magnetic resonance imaging provided high diagnostic accuracy for the detection of fetal congenital heart defects with a sensitivity of 87.8%, a specificity of 97.9%, and concordance with autopsy of 95.3%. 3Tesla postmortem magnetic resonance imaging was less accurate in young fetuses (<20 weeks compared with ≥20 weeks; P<.001), in fetuses with low birthweight (≤100 g compared with >100 g; P<.001), in cases after spontaneous fetal death (compared with other modes of death; P=.012), in cases with increasing latency between death and 3Tesla postmortem magnetic resonance imaging (P<.001), and in cases in which there was a high degree of maceration (maceration score of 3 compared with a score from 0 to 2; P=.004). CONCLUSION: Diagnostic 3Tesla postmortem magnetic resonance imaging assessment of the fetal heart is feasible in most fetuses from 12 weeks' gestation onward. In diagnostic images, sensitivity and, particularly, specificity in the detection of congenital heart disease are high compared with conventional autopsy. Owing to its high diagnostic accuracy, we suggest that 3Tesla postmortem magnetic resonance imaging may serve as a suitable imaging modality with which to direct a targeted conventional autopsy when pathology resources are limited or to provide a virtual autopsy when full autopsy is declined by the parents.