Jean A. Tkach

Quantitative Magnetic Resonance Imaging of Bronchopulmonary Dysplasia in the Neonatal Intensive Care Unit Environment

RATIONALE Bronchopulmonary dysplasia (BPD) is a prevalent yet poorly characterized pulmonary complication of premature birth; the current definition is based solely on oxygen dependence at 36 weeks postmenstrual age without objective measurements of structural abnormalities across disease severity. OBJECTIVES We hypothesize that magnetic resonance imaging (MRI) can spatially resolve and quantify the structural abnormalities of the neonatal lung parenchyma associated with premature birth. METHODS Using a unique, small-footprint, 1.5-T MRI scanner within our neonatal intensive care unit (NICU), diagnostic-quality MRIs using commercially available sequences (gradient echo and spin echo) were acquired during quiet breathing in six patients with BPD, six premature patients without diagnosed BPD, and six full-term NICU patients (gestational ages, 23-39 wk) at near term-equivalent age, without administration of sedation or intravenous contrast. Images were scored by a radiologist using a modified Ochiai score, and volumes of high- and low-signal intensity lung parenchyma were quantified by segmentation and threshold analysis. MEASUREMENTS AND MAIN RESULTS Signal increases, putatively combinations of fibrosis, edema, and atelectasis, were present in all premature infants. Infants with diagnosed BPD had significantly greater volume of high-signal lung (mean ± SD, 26.1 ± 13.8%) compared with full-term infants (7.3 ± 8.2%; P = 0.020) and premature infants without BPD (8.2 ± 6.4%; P = 0.026). Signal decreases, presumably alveolar simplification, only appeared in the most severe BPD cases, although cystic appearance did increase with severity. CONCLUSIONS Pulmonary MRI reveals quantifiable, significant differences between patients with BPD, premature patients without BPD, and full-term control subjects. These methods could be implemented to individually phenotype disease, which may impact clinical care and predict future outcomes.

MRI in the Neonatal ICU: Initial Experience Using a Small-Footprint 1.5-T System

OBJECTIVE The objective of our study was to develop a small 1.5-T MRI system for neonatal imaging that can be installed in the neonatal ICU (NICU) and to evaluate its performance in 15 neonates. SUBJECTS AND METHODS A 1.5-T MR system designed for orthopedic use was adapted for neonatal imaging. Modifications included raising and leveling the magnet, construction of a patient table, and integration of imaging electronics from a high-performance adult-sized scanner. The system was used to perform MR examinations of the brain, abdomen, and chest in 15 medically stable neonates using standard clinical protocols. The scanning time was limited to 60 minutes. The MR examinations were performed without administering sedation to the patients. ECG, heart rate, oxygen saturation, and temperature were monitored continuously throughout the examination. The images were evaluated by two pediatric radiologists for overall study quality, motion artifact, spatial resolution, signal-to-noise ratio, and contrast. RESULTS All 15 neonates were successfully imaged without sedation. No adverse MRI-related events were noted. In total, 19 brain and seven abdominal examinations were performed. Six chest and two cardiac examinations were also obtained. Gross (versus physiologic) subject motion proved to be the most influential factor in determining overall study and image quality. High-quality diagnostic images were obtained at each anatomic location. CONCLUSION The customized neonatal MRI system provides state-of-the-art MRI capabilities in the NICU.

Retrospective respiratory self-gating and removal of bulk motion in pulmonary UTE MRI of neonates and adults.

To implement pulmonary three‐dimensional (3D) radial ultrashort echo‐time (UTE) MRI in non‐sedated, free‐breathing neonates and adults with retrospective motion tracking of respiratory and intermittent bulk motion, to obtain diagnostic‐quality, respiratory‐gated images.

Pulmonary MRI of neonates in the intensive care unit using 3D ultrashort echo time and a small footprint MRI system.

To determine the feasibility of pulmonary magnetic resonance imaging (MRI) of neonatal lung structures enabled by combining two novel technologies: first, a 3D radial ultrashort echo time (UTE) pulse sequence capable of high spatial resolution full‐chest imaging in nonsedated quiet‐breathing neonates; and second, a unique, small‐footprint 1.5T MRI scanner design adapted for neonatal imaging and installed within the neonatal intensive care unit (NICU).

Functional MRI evidence for fine motor praxis dysfunction in children with persistent speech disorders

UNLABELLED Children with persistent speech disorders (PSD) often present with overt or subtle motor deficits; the possibility that speech disorders and motor deficits could arise from a shared neurological base is currently unknown. Functional MRI (fMRI) was used to examine the brain networks supporting fine motor praxis in children with PSD and without clinically identified fine motor deficits. METHODS This case-control study included 12 children with PSD (mean age 7.42 years, four female) and 12 controls (mean age 7.44 years, four female). Children completed behavioral evaluations using standardized motor assessments and parent reported functional measures. During fMRI scanning, participants completed a cued finger tapping task contrasted passive listening. A general linear model approach identified brain regions associated with finger tapping in each group and regions that differed between groups. The relationship between regional fMRI activation and fine motor skill was assessed using a regression analysis. RESULTS Children with PSD had significantly poorer results for rapid speech production and fine motor praxis skills, but did not differ on classroom functional skills. Functional MRI results showed that children with PSD had significantly more activation in the cerebellum during finger tapping. Positive correlations between performance on a fine motor praxis test and activation multiple cortical regions were noted for children with PSD but not for controls. CONCLUSIONS Over-activation in the cerebellum during a motor task may reflect a subtle abnormality in the non-speech motor neural circuitry in children with PSD.

Quantification of neonatal lung parenchymal density via ultrashort echo time MRI with comparison to CT

To demonstrate that ultrashort echo time (UTE) magnetic resonance imaging (MRI) can achieve computed tomography (CT)‐like quantification of lung parenchyma in free‐breathing, non‐sedated neonates. Because infant CTs are used sparingly, parenchymal disease evaluation via UTE MRI has potential for translational impact.

Neonatal imaging using an on-site small footprint MR scanner

With its soft-tissue definition, multiplanar capabilities and advanced imaging techniques, magnetic resonance imaging (MRI) for neonatal care can provide better understanding of pathology, allowing for improved care and counseling to families. However, MR imaging in neonates is often difficult due to patient instability and the complex support necessary for survival. In our institution, we have installed a small footprint magnet in the neonatal intensive care unit (NICU) to minimize patient risks and provide the ability to perform MR imaging safely in this population. With this system, we have been able to provide more information with regard to central nervous system disorders, abdominal pathology, and pulmonary and airway abnormalities, and have performed postmortem imaging as an alternative or supplement to pathological autopsy. In our experience, an MR scanner situated within the NICU has allowed for safer and more expedited imaging of this vulnerable population.

Wavelet-space correlation imaging for high-speed MRI without motion monitoring or data segmentation.

This study aims to (i) develop a new high‐speed MRI approach by implementing correlation imaging in wavelet‐space, and (ii) demonstrate the ability of wavelet‐space correlation imaging to image human anatomy with involuntary or physiological motion.

Evaluation of Neonatal Lung Volume Growth by Pulmonary Magnetic Resonance Imaging in Patients with Congenital Diaphragmatic Hernia

Objective To evaluate postnatal lung volume in infants with congenital diaphragmatic hernia (CDH) and determine if a compensatory increase in lung volume occurs during the postnatal period. Study design Using a novel pulmonary magnetic resonance imaging method for imaging neonatal lungs, the postnatal lung volumes in infants with CDH were determined and compared with prenatal lung volumes obtained via late gestation magnetic resonance imaging. Results Infants with left‐sided CDH (2 mild, 9 moderate, and 1 severe) were evaluated. The total lung volume increased in all infants, with the contralateral lung increasing faster than the ipsilateral lung (mean ± SD: 4.9 ± 3.0 mL/week vs 3.4 ± 2.1 mL/week, P = .005). In contrast to prenatal studies, the volume of lungs of infants with more severe CDH grew faster than the lungs of infants with more mild CDH (Spearmans &rgr;=‐0.086, P = .01). Although the contralateral lung volume grew faster in both mild and moderate groups, the majority of total lung volume growth in moderate CDH came from increased volume of the ipsilateral lung (42% of total lung volume increase in the moderate group vs 32% of total lung volume increase in the mild group, P = .09). Analysis of multiple clinical variables suggests that increased weight gain was associated with increased compensatory ipsilateral lung volume growth (&rgr; = 0.57, P = .05). Conclusions These results suggest a potential for postnatal catch‐up growth in infants with pulmonary hypoplasia and suggest that weight gain may increase the volume growth of the more severely affected lung.

Neonatal Pulmonary MRI of Bronchopulmonary Dysplasia Predicts Short-term Clinical Outcomes

Rationale: Bronchopulmonary dysplasia (BPD) is a serious neonatal pulmonary condition associated with premature birth, but the underlying parenchymal disease and trajectory are poorly characterized. The current National Institute of Child Health and Human Development (NICHD)/NHLBI definition of BPD severity is based on degree of prematurity and extent of oxygen requirement. However, no clear link exists between initial diagnosis and clinical outcomes. Objectives: We hypothesized that magnetic resonance imaging (MRI) of structural parenchymal abnormalities will correlate with NICHD‐defined BPD disease severity and predict short‐term respiratory outcomes. Methods: A total of 42 neonates (20 severe BPD, 6 moderate, 7 mild, 9 non‐BPD control subjects; 40 ± 3‐wk postmenstrual age) underwent quiet‐breathing structural pulmonary MRI (ultrashort echo time and gradient echo) in a neonatal ICU‐sited, neonatal‐sized 1.5 T scanner, without sedation or respiratory support unless already clinically prescribed. Disease severity was scored independently by two radiologists. Mean scores were compared with clinical severity and short‐term respiratory outcomes. Outcomes were predicted using univariate and multivariable models, including clinical data and scores. Measurements and Main Results: MRI scores significantly correlated with severities and predicted respiratory support at neonatal ICU discharge (P < 0.0001). In multivariable models, MRI scores were by far the strongest predictor of respiratory support duration over clinical data, including birth weight and gestational age. Notably, NICHD severity level was not predictive of discharge support. Conclusions: Quiet‐breathing neonatal pulmonary MRI can independently assess structural abnormalities of BPD, describe disease severity, and predict short‐term outcomes more accurately than any individual standard clinical measure. Importantly, this nonionizing technique can be implemented to phenotype disease, and has potential to serially assess efficacy of individualized therapies.