BOston Neonatal Brain Injury Dataset for Hypoxic Ischemic Encephalopathy (BONBID-HIE): Part I. MRI and Manual Lesion Annotation.

Hypoxic ischemic encephalopathy (HIE) is a brain injury that occurs in 1 ~ 5/1000 term neonates. Accurate identification and segmentation of HIE-related lesions in neonatal brain magnetic resonance images (MRIs) is the first step toward predicting prognosis, identifying high-risk patients, and evaluating treatment effects. It will lead to a more accurate estimation of prognosis, a better understanding of neurological symptoms, and a timely prediction of response to therapy. We release the first public dataset containing neonatal brain diffusion MRI and expert annotation of lesions from 133 patients diagnosed with HIE. HIE-related lesions in brain MRI are often diffuse (i.e., multi-focal), and small (over half the patients in our data having lesions occupying <1% of brain volume). Segmentation for HIE MRI data is remarkably different from, and arguably more challenging than, other segmentation tasks such as brain tumors with focal and relatively large lesions. We hope that this dataset can help fuel the development of MRI lesion segmentation methods for HIE and small diffuse lesions in general.

Ketone ester supplementation suppresses cardiac inflammation and improves cardiac energetics in a swine model of acute myocardial infarction.

BACKGROUND: Myocardial infarction (MI) is a major risk factor for the development of heart failure with reduce ejection fraction (HFrEF). While previous studies have focused on HFrEF, the cardiovascular effects of ketone bodies in acute MI are unclear. We examined the effects of oral ketone supplementation as a potential treatment strategy in a swine acute MI model. METHODS: Farm pigs underwent percutaneous balloon occlusion of the LAD for 80 min followed by 72 h reperfusion period. Oral ketone ester or vehicle was administered during reperfusion and continued during the follow-up period. RESULTS: Oral KE supplementation induced ketonemia 2-3 mmol/l within 30 min after ingestion. KE increased ketone (ßHB) extraction in healthy hearts without affecting glucose and fatty acid (FA) consumption. During reperfusion, the MI hearts consumed less FA with no change in glucose consumption, whereas hearts from MI-KE-fed animals consumed more ßHB and FA, as well as improved myocardial ATP production. A significant elevation of infarct T2 values indicative of inflammation was found only in untreated MI group compared to sham. Concordantly, cardiac expression of inflammatory markers, oxidative stress, and apoptosis were reduced by KE. RNA-seq analysis identified differentially expressed genes related to mitochondrial energy metabolism and inflammation. CONCLUSIONS: Oral KE supplementation induced ketosis and enhanced myocardial ßHB extraction in both healthy and infarcted hearts. Acute oral supplementation with KE favorably altered cardiac substrate uptake and utilization, improved cardiac ATP levels, and reduced cardiac inflammation following MI.

Contrast-Enhanced Cardiac Magnetic Resonance Imaging With a Manganese-Based Alternative to Gadolinium for Tissue Characterization of Acute Myocardial Infarction.

Background Late gadolinium enhancement cardiac magnetic resonance imaging is an effective and reproducible method for characterizing myocardial infarction. However, gadolinium-based contrast agents are contraindicated in patients with acute and chronic renal insufficiency. In addition, several recent studies have noted tissue deposition of free gadolinium in patients who have undergone serial contrast-enhanced magnetic resonance imaging. There is a clinical need for alternative forms of magnetic resonance imaging contrast agents that are acceptable in the setting of renal insufficiency. Methods and Results Three days after 80 minutes of ischemia/reperfusion of the left anterior descending coronary artery, cardiac magnetic resonance imaging was performed to assess myocardial lesion burden using both contrast agents. Late gadolinium enhancement cardiac magnetic resonance imaging was examined 10 and 15 minutes after contrast injection. Contrast agents were administered in alternating manner with a 2- to 3-hour washout period between contrast agent injections. Lesion evaluation and image processing were performed using Segment Medviso software. Mean infarct size and transmurality, measured using RVP-001, were not different compared with those measured using late gadolinium enhancement images. Bland-Altman analysis demonstrated a nominal bias of 0.13 mL (<1% of average total lesion volume) for RVP-001 in terms of gross infarct size measurement. Conclusions The experimental manganese-based contrast agent RVP-001 appears to be an effective agent for assessment of myocardial infarction location, size, and transmurality, and it may be useful as an alternative to gadolinium-based agents.

Partitioning the Two-Leg Spin Ladder in Ba2Cu1 - x Zn x TeO6: From Magnetic Order through Spin-Freezing to Paramagnetism.

Ba2CuTeO6 has attracted significant attention as it contains a two-leg spin ladder of Cu2+ cations that lies in close proximity to a quantum critical point. Recently, Ba2CuTeO6 has been shown to accommodate chemical substitutions, which can significantly tune its magnetic behavior. Here, we investigate the effects of substitution for non-magnetic Zn2+ impurities at the Cu2+ site, partitioning the spin ladders. Results from bulk thermodynamic and local muon magnetic characterization on the Ba2Cu1 - x Zn x TeO6 solid solution (0 ≤ x ≤ 0.6) indicate that Zn2+ partitions the Cu2+ spin ladders into clusters and can be considered using the percolation theory. As the average cluster size decreases with increasing Zn2+ substitution, there is an evolving transition from long-range order to spin-freezing as the critical cluster size is reached between x = 0.1 to x = 0.2, beyond which the behavior became paramagnetic. This demonstrates well-controlled tuning of the magnetic disorder, which is highly topical across a range of low-dimensional Cu2+-based materials. However, in many of these cases, the chemical disorder is also relatively strong in contrast to Ba2CuTeO6 and its derivatives. Therefore, Ba2Cu1 - x Zn x TeO6 provides an ideal model system for isolating the effect of defects and segmentation in low-dimensional quantum magnets.

Single breath-hold CINE imaging with combined simultaneous multislice and region-optimized virtual coils.

PURPOSE: To investigate the feasibility of combining simultaneous multislice (SMS) and region-optimized virtual coils (ROVir) for single breath-hold CINE imaging. METHOD: ROVir is a recent virtual coil approach that allows reduced-field of view (FOV) imaging by localizing the signal from a region-of-interest (ROI) and/or suppressing the signal from unwanted spatial regions. In this work, ROVir is used for reduced-FOV SMS bSSFP CINE imaging, which enables whole heart CINE with a single breath-hold acquisition. RESULTS: Reduced-FOV CINE with either SMS-only or ROVir-only resulted in significant aliasing, with severely reduced image quality when compared to the full FOV reference CINE, while the visual appearance of aliasing was substantially reduced with the proposed SMS+ROVir. The end diastolic volume, end systolic volume, and ejection fraction obtained using the proposed approach were similar to the clinical reference (correlations of 0.92, 0.94, and 0.88, respectively with p < 0 . 05 $$ p<0.05 $$ in each case, and biases of 0.1, 1.6 mL, and - 0 . 6 % $$ -0.6\% $$ , respectively). No statistically significant differences for these parameters were found with a Wilcoxon rank test (p = 0.96, 0.20, and 0.40, respectively). CONCLUSION: We demonstrated that reduced-FOV CINE imaging with SMS+ROVir enables single breath-hold whole-heart imaging without compromising visual image quality or quantitative cardiac function parameters.

Accelerated and quantitative three-dimensional molecular MRI using a generative adversarial network.

PURPOSE: To substantially shorten the acquisition time required for quantitative three-dimensional (3D) chemical exchange saturation transfer (CEST) and semisolid magnetization transfer (MT) imaging and allow for rapid chemical exchange parameter map reconstruction. METHODS: Three-dimensional CEST and MT magnetic resonance fingerprinting (MRF) datasets of L-arginine phantoms, whole-brains, and calf muscles from healthy volunteers, cancer patients, and cardiac patients were acquired using 3T clinical scanners at three different sites, using three different scanner models and coils. A saturation transfer-oriented generative adversarial network (GAN-ST) supervised framework was then designed and trained to learn the mapping from a reduced input data space to the quantitative exchange parameter space, while preserving perceptual and quantitative content. RESULTS: The GAN-ST 3D acquisition time was 42-52 s, 70% shorter than CEST-MRF. The quantitative reconstruction of the entire brain took 0.8 s. An excellent agreement was observed between the ground truth and GAN-based L-arginine concentration and pH values (Pearson's r > 0.95, ICC > 0.88, NRMSE < 3%). GAN-ST images from a brain-tumor subject yielded a semi-solid volume fraction and exchange rate NRMSE of 3 . 8 ± 1 . 3 % $$ 3.8\pm 1.3\% $$ and 4 . 6 ± 1 . 3 % $$ 4.6\pm 1.3\% $$ , respectively, and SSIM of 96 . 3 ± 1 . 6 % $$ 96.3\pm 1.6\% $$ and 95 . 0 ± 2 . 4 % $$ 95.0\pm 2.4\% $$ , respectively. The mapping of the calf-muscle exchange parameters in a cardiac patient, yielded NRMSE < 7% and SSIM > 94% for the semi-solid exchange parameters. In regions with large susceptibility artifacts, GAN-ST has demonstrated improved performance and reduced noise compared to MRF. CONCLUSION: GAN-ST can substantially reduce the acquisition time for quantitative semi-solid MT/CEST mapping, while retaining performance even when facing pathologies and scanner models that were not available during training.

Asynchronous magnetic resonance elastography: Shear wave speed reconstruction using noise correlation of incoherent waves.

PURPOSE: The noninvasive measurement of biological tissue elasticity is an evolving technology that enables the robust characterization of soft tissue mechanics for a wide array of biomedical engineering and clinical applications. We propose, design, and implement here a new MRI technique termed asynchronous magnetic resonance elastography (aMRE) that pushes the measurement technology toward a driverless implementation. This technique can be added to clinical MRI scanners without any additional specialized hardware. THEORY: Asynchronous MRE is founded on the theory of diffuse wavefields and noise correlation previously developed in ultrasound to reconstruct shear wave speeds using seemingly incoherent wavefields. Unlike conventional elastography methods that solve an inverse problem, aMRE directly reconstructs a pixel-wise mapping of wave speed using the spatial-temporal statistics of the measured wavefield. METHODS: Incoherent finger tapping served as the wave-generating source for all aMRE measurements. Asynchronous MRE was performed on a phantom using a Siemens Prismafit as an experimental validation of the theory. It was further performed on thigh muscles as a proof-of-concept implementation of in vivo imaging using a Siemens Skyra scanner. RESULTS: Numerical and phantom experiments show an accurate reconstruction of wave speeds from seemingly noisy wavefields. The proof-of-concept thigh experiments also show that the aMRE protocol can reconstruct a pixel-wise mapping of wave speeds. CONCLUSION: Asynchronous MRE is shown to accurately reconstruct shear wave speeds in phantom experiments and remains at the proof-of-concept stage for in vivo imaging. After further validation and improvements, it has the potential to lower both the technical and monetary barriers of entry to measuring tissue elasticity.

A soft robotic sleeve mimicking the haemodynamics and biomechanics of left ventricular pressure overload and aortic stenosis.

Preclinical models of aortic stenosis can induce left ventricular pressure overload and coarsely control the severity of aortic constriction. However, they do not recapitulate the haemodynamics and flow patterns associated with the disease. Here we report the development of a customizable soft robotic aortic sleeve that can mimic the haemodynamics and biomechanics of aortic stenosis. By allowing for the adjustment of actuation patterns and blood-flow dynamics, the robotic sleeve recapitulates clinically relevant haemodynamics in a porcine model of aortic stenosis, as we show via in vivo echocardiography and catheterization studies, and a combination of in vitro and computational analyses. Using in vivo and in vitro magnetic resonance imaging, we also quantified the four-dimensional blood-flow velocity profiles associated with the disease and with bicommissural and unicommissural defects re-created by the robotic sleeve. The design of the sleeve, which can be adjusted on the basis of computed tomography data, allows for the design of patient-specific devices that may guide clinical decisions and improve the management and treatment of patients with aortic stenosis.

Feasibility study of clinical target volume definition for soft-tissue sarcoma using muscle fiber orientations derived from diffusion tensor imaging.

Objective.Soft-tissue sarcoma spreads preferentially along muscle fibers. We explore the utility of deriving muscle fiber orientations from diffusion tensor MRI (DT-MRI) for defining the boundary of the clinical target volume (CTV) in muscle tissue.Approach.We recruited eight healthy volunteers to acquire MR images of the left and right thigh. The imaging session consisted of (a) two MRI spin-echo-based scans, T1- and T2-weighted; (b) a diffusion weighted (DW) spin-echo-based scan using an echo planar acquisition with fat suppression. The thigh muscles were auto-segmented using the convolutional neural network. DT-MRI data were used as a geometry encoding input to solve the anisotropic Eikonal equation with the Hamiltonian Fast-Marching method. The isosurfaces of the solution modeled the CTV boundary.Main results.The auto-segmented muscles of the thigh agreed with manually delineated with the Dice score ranging from 0.8 to 0.94 for different muscles. To validate our method of deriving muscle fiber orientations, we compared anisotropy of the isosurfaces across muscles with different anatomical orientations within a thigh, between muscles in the left and right thighs of each subject, and between different subjects. The fiber orientations were identified reproducibly across all comparisons. We identified two controlling parameters, the distance from the gross tumor volume to the isosurface and the eigenvalues ratio, to tailor the proposed CTV to the satisfaction of the clinician.Significance.Our feasibility study with healthy volunteers shows the promise of using muscle fiber orientations derived from DW MRI data for automated generation of anisotropic CTV boundary in soft tissue sarcoma. Our contribution is significant as it serves as a proof of principle for combining DT-MRI information with tumor spread modeling, in contrast to using moderately informative 2D CT planes for the CTV delineation. Such improvements will positively impact the cancer centers with a small volume of sarcoma patients.

Mental health needs in a large urban school district: Findings from a web-based survey.

OBJECTIVE: To explore the mental health needs of students, and the professional development and support needs of teachers and school health professionals, as a way to foster community engagement and help set priorities for a comprehensive school mental health system in the Detroit Public Schools Community District (DPSCD). SETTING: The study team surveyed all DPSCD staff in June 2019 and all students in grades 8-12 between October and December 2019. STUDY DESIGN: A descriptive study based on anonymous, web-based surveys focused on student trauma exposure and mental health symptoms, student mental health resource utilization, staff burnout, and professional development needs. DATA COLLECTION: All students (grades 8-12) and district staff were eligible to participate; the student survey was made available in six languages. Parents/guardians could opt children out; schools could exclude children unable to complete the survey independently. Student surveys were administered in school; staff surveys were sent via email. PRINCIPAL FINDINGS: Thirty-four percent of DPSCD students reported moderate/severe depression symptoms; 22% had seriously considered suicide in the past year. Rates exceed national averages; 37% of students with severe depression and 34% of those with suicidal ideation had not accessed mental health supports. Staff indicated high levels of burnout and substantial interest in learning about self-care strategies or coping with vicarious trauma. Over 75% of teachers and school mental health professionals expressed interest in learning about best practices for supporting students impacted by trauma or mental illness. CONCLUSIONS: A large number of DPSCD students are experiencing symptoms of depression and anxiety, and many students who need care are not accessing it. Addressing the mental health needs of students is a high priority for staff, but they need more training and support, as well as support for their own vicarious trauma and high levels of burnout.

'Tablet burden' in patients with metastatic breast cancer.

UNLABELLED: The implications for patients with cancer, of the 'tablet burden' resulting from increasing use of oral anticancer drugs and medication for co-morbidities have not previously been well explored. AIM: We sought to (i) quantify tablet burden in women with metastatic breast cancer (MBC), (ii) establish which groups of drug contribute most to this burden and (iii) gain insight into patients' attitudes towards oral anti-cancer treatment. METHODS: One hundred patients with MBC anonymously completed a questionnaire describing their medication histories and attitudes towards their tablets. RESULTS: The patients (mean age 60, range 31-95) were all female and taking a median of six tablets (range 0-31) daily; 37 patients were taking >10 tablets. Oral anticancer treatment constituted the category of treatment taken by the highest proportion of patients, followed by symptomatic cancer treatments, proton pump inhibitors and cardiovascular medication. Numerically, however, symptomatic drugs accounted for 44% of all tablets and specific anti-cancer treatment for 15%; medication not directly related to the cancer accounted for the remaining 40% of tablets. A quarter of patients reported inconvenience in taking their tablets, the main reason being tablet size and one third reported forgetting their tablets at least once a week. Nearly two thirds of patients expressing a preference favoured oral anticancer treatment, the commonest reason being greater convenience. CONCLUSION: Tablet burden is considerable for many patients with MBC and can be problematic. A significant proportion of tablets represent treatment for co-morbidities, the significance of which may be questionable in women with MBC.

Irregular rhythm adversely influences calcium handling in ventricular myocardium: implications for the interaction between heart failure and atrial fibrillation.

BACKGROUND: Despite adequate rate control, the combination of atrial fibrillation with heart failure (HF) has been shown, in a number of studies, to hasten HF progression. In this context, we aimed to test the hypothesis that an irregular ventricular rhythm causes an alteration in ventricular cardiomyocyte excitation-contraction coupling which contributes to the progression of HF. METHODS AND RESULTS: We investigated the effects of electrical field stimulation (average frequency 2 Hz) in an irregular versus regular drive train pattern on the expression of calcium-handling genes and proteins in rat ventricular myocytes. The effect of rhythm on intracellular calcium transients was examined using Fura-2AM fluorescence spectroscopy. In conjunction, calcium-handling protein expression was examined in left ventricular samples obtained from end-stage HF patients, in patients with either persistent atrial fibrillation or sinus rhythm. Compared with regularly paced ventricular cardiomyocytes, in cells paced irregularly for 24 hours, there was a significant reduction in the expression of sarcoplasmic reticulum calcium (Ca(2+)) ATPase together with reduced serine-16 phosphorylation of phospholamban. These findings were accompanied by a 59% reduction (P<0.01) in the peak Ca2+ transient in irregulary paced myocytes compared with those with regular pacing. Consistent with these observations, we observed a 54% (P<0.05) decrease in sarcoplasmic reticulum Ca(2+)ATPase protein expression and an 85% (P<0.01) reduction in the extent of phosphorylation of phospholamban in the left ventricular myocardium of HF patients in atrial fibrillation compared with those in sinus rhythm. CONCLUSIONS: Together, these data demonstrate that ventricular rhythmicity contributes significantly to excitation-contraction coupling by altering the expression and activity of key calcium-handling proteins. These data suggest that control of rhythm may be of benefit in patients with HF.