BACKGROUND: Secondary and retrospective use of hospital-hosted clinical data provides a time- and cost-efficient alternative to prospective clinical trials for biomarker development. This study aims to create a retrospective clinical dataset of Magnetic Resonance Images (MRI) and clinical records of neonatal hypoxic ischemic encephalopathy (HIE), from which clinically-relevant analytic algorithms can be developed for MRI-based HIE lesion detection and outcome prediction. METHODS: This retrospective study will use clinical registries and big data informatics tools to build a multi-site dataset that contains structural and diffusion MRI, clinical information including hospital course, short-term outcomes (during infancy), and long-term outcomes (~ 2 years of age) for at least 300 patients from multiple hospitals. DISCUSSION: Within machine learning frameworks, we will test whether the quantified deviation from our recently-developed normative brain atlases can detect abnormal regions and predict outcomes for individual patients as accurately as, or even more accurately, than human experts. Trial Registration Not applicable. This study protocol mines existing clinical data thus does not meet the ICMJE definition of a clinical trial that requires registration.

Intraoperative tissue deformation, known as brain shift, decreases the benefit of using preoperative images to guide neurosurgery. Non-rigid registration of preoperative magnetic resonance (MR) to intraoperative ultrasound (iUS) has been proposed as a means to compensate for brain shift. We focus on the initial registration from MR to predurotomy iUS. We present a method that builds on previous work to address the need for accuracy and generality of MR-iUS registration algorithms in multi-site clinical data. High-dimensional texture attributes were used instead of image intensities for image registration and the standard difference-based attribute matching was replaced with correlation-based attribute matching. A strategy that deals explicitly with the large field-of-view mismatch between MR and iUS images was proposed. Key parameters were optimized across independent MR-iUS brain tumor datasets acquired at 3 institutions, with a total of 43 tumor patients and 758 reference landmarks for evaluating the accuracy of the proposed algorithm. Despite differences in imaging protocols, patient demographics and landmark distributions, the algorithm is able to reduce landmark errors prior to registration in three data sets (5.37±4.27, 4.18±1.97 and 6.18±3.38 mm, respectively) to a consistently low level (2.28±0.71, 2.08±0.37 and 2.24±0.78 mm, respectively). This algorithm was tested against 15 other algorithms and it is competitive with the state-of-the-art on multiple datasets. We show that the algorithm has one of the lowest errors in all datasets (accuracy), and this is achieved while sticking to a fixed set of parameters for multi-site data (generality). In contrast, other algorithms/tools of similar performance need per-dataset parameter tuning (high accuracy but lower generality), and those that stick to fixed parameters have larger errors or inconsistent performance (generality but not the top accuracy). Landmark errors were further characterized according to brain regions and tumor types, a topic so far missing in the literature.

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This study used a swine model of mildly hypothermic prolonged circulatory arrest and found that the addition of 2.4% inhaled hydrogen gas to inspiratory gases during and after the ischemic insult significantly decreased neurologic and renal injury compared with controls. With proper precautions, inhalational hydrogen may be administered safely through conventional ventilators and may represent a complementary therapy that can be easily incorporated into current workflows. In the future, inhaled hydrogen may diminish the sequelae of ischemia that occurs in congenital heart surgery, cardiac arrest, extracorporeal life-support events, acute myocardial infarction, stroke, and organ transplantation.