Ultrasound Shear Wave Elastography Helps Discriminate Low‐grade From High‐grade Bowel Wall Fibrosis in Ex Vivo Human Intestinal Specimens

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135467/1/jum201433122115.pd

A Novel Collaborative Self-Supervised Learning Method for Radiomic Data

The computer-aided disease diagnosis from radiomic data is important in many medical applications. However, developing such a technique relies on annotating radiological images, which is a time-consuming, labor-intensive, and expensive process. In this work, we present the first novel collaborative self-supervised learning method to solve the challenge of insufficient labeled radiomic data, whose characteristics are different from text and image data. To achieve this, we present two collaborative pretext tasks that explore the latent pathological or biological relationships between regions of interest and the similarity and dissimilarity information between subjects. Our method collaboratively learns the robust latent feature representations from radiomic data in a self-supervised manner to reduce human annotation efforts, which benefits the disease diagnosis. We compared our proposed method with other state-of-the-art self-supervised learning methods on a simulation study and two independent datasets. Extensive experimental results demonstrated that our method outperforms other self-supervised learning methods on both classification and regression tasks. With further refinement, our method shows the potential advantage in automatic disease diagnosis with large-scale unlabeled data available.Comment: 14 pages, 7 figure

Comparison of noncontrast MRI magnetization transfer and T2‐Weighted signal intensity ratios for detection of bowel wall fibrosis in a Crohn's disease animal model

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113105/1/jmri24815.pd

Surveillance of fetal lung lesions using the congenital pulmonary airway malformation volume ratio: natural history and outcomes

ObjectivesThe congenital pulmonary airway malformation volume ratio (CVR) is a widely used sonographic measure of relative mass size in fetuses with lung malformations. The purposes of this study were to examine serial CVR measurements to understand longitudinal growth patterns and to determine correlation with postnatal imaging.MethodsAn institutional review boardâ approved retrospective review was performed on fetuses referred for an echogenic lung malformation between 2002 and 2014. For each fetus, the CVR was prospectively calculated using 2D ultrasound and followed with advancing gestation.ResultsBased on 40 fetuses, the mean initial CVR was 0.51â ±â 0.07 at 20.5â ±â 0.3â weeks of gestation. The CVR increased after 24â weeks of gestation (pâ =â 0.0014), peaking at a CVR of 0.96â ±â 0.11 at 25.5â ±â 0.05â weeks, followed by a significant decrease in the CVR to 0.43â ±â 0.07 prior to term (pâ <â 0.0001). However, approximately one third showed no appreciable increase in size. The mean CVR was significantly correlated with postnatal chest computed tomography (CT) size dimensions (pâ =â 0.0032) and likelihood for lung resection (pâ =â 0.0055).ConclusionsFetal lung malformations tend to follow one of two distinct growth patterns, characterized by either (1) a maximal CVR between 25 and 26â weeks of gestation or (2) minimal change in relative growth. The mean CVR correlates with postnatal CT size and operative management. © 2015 John Wiley & Sons, Ltd.What’s already known about the topic?The congenital pulmonary airway malformation volume ratio (CVR) is a common prenatal ultrasound measure of relative mass size in fetuses with lung malformations.The initial CVR and maximum CVR have been shown to be predictive of hydrops and neonatal respiratory compromise, respectively.What does this study add?Gestational age is important when interpreting CVR measurements because two thirds of lesions increase in size at 25â 26â weeks before spontaneous involution occurs.The mean CVR correlates with size measured by postnatal computed tomography scan.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136421/1/pd4761_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136421/2/pd4761.pd

Safety of gadolinium‐based contrast material in sickle cell disease

Purpose: To assess the safety of intravenously administered gadolinium‐based contrast material in sickle cell disease (SCD) patients. Materials and Methods: All pediatric and adult SCD patients evaluated by magnetic resonance imaging (MRI) at our institution between January 1995 and July 2009 were identified. The medical records of SCD patients who underwent contrast‐enhanced MRI as well as an equal‐sized cohort of SCD patients who underwent unenhanced MRI were reviewed for adverse (vaso‐occlusive and hemolytic) events within 1 week following imaging. Results: Eight (five mild and three moderate) adverse events were documented within 1 week following contrast‐enhanced MRI (38 patients and 61 contrast injections), while six (five mild and one moderate) similar events occurred within 1 week following unenhanced MRI (61 patients and 61 unenhanced MRI examinations). This difference in the number of adverse events was not statistically significant (odds ratio = 1.4; 95% confidence interval [CI] 0.4, 5.2). No severe adverse event occurred in either patient cohort. Conclusion: Gadolinium‐based contrast materials do not appear to be associated with increased risk of vaso‐occlusive or hemolytic adverse events when administered to SCD patients. Larger, prospective studies using multiple gadolinium‐based contrast materials would be useful to confirm the results of our investigation. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87070/1/22666_ftp.pd

Computed Tomography With Intravenous Contrast Alone: The Role of Intra‐abdominal Fat on the Ability to Visualize the Normal Appendix in Children

Background Computed tomography ( CT ) with enteric contrast is frequently used to evaluate children with suspected appendicitis. The use of CT with intravenous ( IV ) contrast alone ( CT IV ) may be sufficient, however, particularly in patients with adequate intra‐abdominal fat ( IAF ). Objectives The authors aimed 1) to determine the ability of radiologists to visualize the normal (nondiseased) appendix with CT IV in children and to assess whether IAF adequacy affects this ability and 2) to assess the association between IAF adequacy and patient characteristics. Methods This was a retrospective 16‐center study using a preexisting database of abdominal CT scans. Children 3 to 18 years who had CT IV scan and measured weights and for whom appendectomy history was known from medical record review were included. The sample was chosen based on age to yield a sample with and without adequate IAF . Radiologists at each center reread their site's CT IV scans to assess appendix visualization and IAF adequacy. IAF was categorized as “adequate” if there was any amount of fat completely surrounding the cecum and “inadequate” if otherwise. Results A total of 280 patients were included, with mean age of 10.6 years (range = 3.1 to 17.9 years). All 280 had no history of prior appendectomy; therefore, each patient had a presumed normal appendix. A total of 102 patients (36.4%) had adequate IAF . The proportion of normal appendices visualized with CT IV was 72.9% (95% confidence interval [ CI ] = 67.2% to 78.0%); the proportions were 89% (95% CI  = 81.5% to 94.5%) and 63% (95% CI  = 56.0% to 70.6%) in those with and without adequate IAF (95% CI for difference of proportions = 16% to 36%). Greater weight and older age were strongly associated with IAF adequacy (p < 0.001), with weight appearing to be a stronger predictor, particularly in females. Although statistically associated, there was noted overlap in the weights and ages of those with and without adequate IAF . Conclusions Protocols using CT with IV contrast alone to visualize the appendix can reasonably include weight, age, or both as considerations for determining when this approach is appropriate. However, although IAF will more frequently be adequate in older, heavier patients, highly accurate prediction of IAF adequacy appears challenging solely based on age and weight. Resumen Tomografía Computarizada Únicamente con Contraste Intravenoso: El Papel de la Grasa Intrabadominal en la Capacidad para Visualizar el Apéndice Normal en los Niños Introduction La tomografía computarizada ( TC ) con contraste entérico es usada frecuentemente para evaluar a los niños con sospecha de apendicitis. El uso de la TC únicamente con contraste intravenoso ( TC IV ) puede ser suficiente, especialmente en pacientes con adecuada grasa intrabdominal ( GIA ). Objetivos 1) Determinar la capacidad de los radiólogos para visualizar el apéndice normal (sin enfermedad) con TC IV en niños, y valorar si la cantidad de GIA afecta a esta capacidad; y 2) valorar la asociación entre la idoneidad de la GIA y las características del paciente. Metodología Estudio retrospectivo de 16 hospitales que utilizó una base de datos prexistente de TC abdominales. Se incluyó a los niños entre 3 y 18 años que tenían una TC IV , una medida del peso e historia de apendectomía conocida por la revisión de la historia clínica. La muestra se eligió en base a la edad con el fin de conseguir una muestra con y sin GIA adecuada. Los radiólogos de cada centro releyeron las TC IV de sus centros para valorar la visualización del apéndice y la adecuación de la GIA . La GIA se clasificó como “adecuada” si había cualquier cantidad de grasa completamente alrededor del ciego e “inadecuada” si era de otra manera. Resultados Se incluyeron 280 pacientes, con una media de edad de 10,6 años (rango 3,1 a 17,9 años). Ninguno tenía historia previa de apendectomía; por lo tanto todos los pacientes tuvieron un apéndice presumiblemente normal. Ciento dos pacientes (36,4%) tuvieron GIA adecuada. El porcentaje de apéndices normales visualizados con TC IV fue de 72,9% ( IC 95% = 67,2% a 78,0%); la proporción fue 89% ( IC 95% = 81,5% a 94,5%), y 63% ( IC 95% = 56,0% a 70,6%) en aquéllos con y sin GIA adecuada ( IC 95% para la diferencia de proporciones = 16% a 36%). El mayor peso y la mayor edad se asociaron fuertemente con la adecuación de la GIA (p < 0,001), y el peso resultó ser el mayor factor predictivo, especialmente en mujeres. Aunque se asoció estadísticamente, se vio un solapamiento en los pesos y edades de aquéllos con y sin GIA adecuada. Conclusiones Los protocolos que usan la TC IV para visualizar el apéndice pueden razonablemente incluir el peso, la edad, o ambas como consideraciones para determinar cuándo esta aproximación es apropiada. Sin embargo, aunque la cantidad de GIA será frecuentemente más apropiada en los pacientes más mayores y de mayor peso, la predicción certera de adecuación de GIA es altamente desafiante si se basa sólo en la edad y el peso.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99695/1/acem12185.pd

Abundant Quantitative Trait Loci Exist for DNA Methylation and Gene Expression in Human Brain

A fundamental challenge in the post-genome era is to understand and annotate the consequences of genetic variation, particularly within the context of human tissues. We present a set of integrated experiments that investigate the effects of common genetic variability on DNA methylation and mRNA expression in four human brain regions each from 150 individuals (600 samples total). We find an abundance of genetic cis regulation of mRNA expression and show for the first time abundant quantitative trait loci for DNA CpG methylation across the genome. We show peak enrichment for cis expression QTLs to be approximately 68,000 bp away from individual transcription start sites; however, the peak enrichment for cis CpG methylation QTLs is located much closer, only 45 bp from the CpG site in question. We observe that the largest magnitude quantitative trait loci occur across distinct brain tissues. Our analyses reveal that CpG methylation quantitative trait loci are more likely to occur for CpG sites outside of islands. Lastly, we show that while we can observe individual QTLs that appear to affect both the level of a transcript and a physically close CpG methylation site, these are quite rare. We believe these data, which we have made publicly available, will provide a critical step toward understanding the biological effects of genetic variation

New Frontiers-class Uranus Orbiter: Exploring the feasibility of achieving multidisciplinary science with a mid-scale mission

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Defining the Critical Hurdles in Cancer Immunotherapy

ABSTRACT: Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators, others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet be overcome to improve outcomes of patients with cancer

Defining the critical hurdles in cancer immunotherapy

Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer