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.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

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.

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.

Functional MRI may identify critical windows of opportunity for drug delivery and distinguish between early treatment responders and non-responders. Using diffusion-weighted, dynamic contrast-enhanced, and dynamic susceptibility contrast MRI, as well as pro-angiogenic and pro-inflammatory blood markers, we prospectively studied the physiologic tumor-related changes in fourteen newly diagnosed glioblastoma patients during standard therapy. 153 MRI scans and blood collection were performed before chemoradiation (baseline), weekly during chemoradiation (week 1-6), monthly before each cycle of adjuvant temozolomide (pre-C1-C6), and after cycle 6. The apparent diffusion coefficient, volume transfer coefficient (K), and relative cerebral blood volume (rCBV) and flow (rCBF) were calculated within the tumor and edema regions and compared to baseline. Cox regression analysis was used to assess the effect of clinical variables, imaging, and blood markers on progression-free (PFS) and overall survival (OS). After controlling for additional covariates, high baseline rCBV and rCBF within the edema region were associated with worse PFS (microvessel rCBF: HR = 7.849, p = 0.044; panvessel rCBV: HR = 3.763, p = 0.032; panvessel rCBF: HR = 3.984; p = 0.049). The same applied to high week 5 and pre-C1 K within the tumor region (week 5 K: HR = 1.038, p = 0.003; pre-C1 K: HR = 1.029, p = 0.004). Elevated week 6 VEGF levels were associated with worse OS (HR = 1.034; p = 0.004). Our findings suggest a role for rCBV and rCBF at baseline and K and VEGF levels during treatment as markers of response. Functional imaging changes can differ substantially between tumor and edema regions, highlighting the variable biologic and vascular state of tumor microenvironment during therapy.

BACKGROUND: Sturge-Weber syndrome (SWS) is often accompanied by seizures, stroke-like episodes, hemiparesis, and visual field deficits. This study aimed to identify early pathophysiologic changes that exist before the development of clinical symptoms and to evaluate if the apparent diffusion coefficient (ADC) map is a candidate early biomarker of seizure risk in patients with SWS. METHODS: This is a prospective cross-sectional study using quantitative ADC analysis to predict onset of epilepsy. Inclusion criteria were presence of the port wine birthmark, brain MRI with abnormal leptomeningeal capillary malformation (LCM) and enlarged deep medullary veins, and absence of seizures or other neurological symptoms. We used our recently developed normative, age-specific ADC atlases to quantitatively identify ADC abnormalities, and correlated presymptomatic ADC abnormalities with risks for seizures. RESULTS: We identified eight patients (three girls) with SWS, age range of 40 days to nine months. One patient had predominantly LCM, deep venous anomaly, and normal ADC values. This patient did not develop seizures. The remaining seven patients had large regions of abnormal ADC values, and all developed seizures; one of seven patients had late onset seizures. CONCLUSIONS: Larger regions of decreased ADC values in the affected hemisphere, quantitatively identified by comparison with age-matched normative ADC atlases, are common in young children with SWS and were associated with later onset of seizures in this small study. Our findings suggest that quantitative ADC maps may identify patients at high risk of seizures in SWS, but larger prospective studies are needed to determine sensitivity and specificity.

The growth of multiparametric imaging protocols has paved the way for quantitative imaging phenotypes that predict treatment response and clinical outcome, reflect underlying cancer molecular characteristics and spatiotemporal heterogeneity, and can guide personalized treatment planning. This growth has underlined the need for efficient quantitative analytics to derive high-dimensional imaging signatures of diagnostic and predictive value in this emerging era of integrated precision diagnostics. This paper presents cancer imaging phenomics toolkit (CaPTk), a new and dynamically growing software platform for analysis of radiographic images of cancer, currently focusing on brain, breast, and lung cancer. CaPTk leverages the value of quantitative imaging analytics along with machine learning to derive phenotypic imaging signatures, based on two-level functionality. First, image analysis algorithms are used to extract comprehensive panels of diverse and complementary features, such as multiparametric intensity histogram distributions, texture, shape, kinetics, connectomics, and spatial patterns. At the second level, these quantitative imaging signatures are fed into multivariate machine learning models to produce diagnostic, prognostic, and predictive biomarkers. Results from clinical studies in three areas are shown: (i) computational neuro-oncology of brain gliomas for precision diagnostics, prediction of outcome, and treatment planning; (ii) prediction of treatment response for breast and lung cancer, and (iii) risk assessment for breast cancer.