Advanced Imaging Research Center

Dallas, Texas, United States

Advanced Imaging Research Center

Dallas, Texas, United States

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News Article | May 9, 2017
Site: www.eurekalert.org

DALLAS - May 9, 2017 - UT Southwestern research investigating the blood glucose-regulatory actions of the hormone ghrelin may have implications for development of new treatments for diabetes. Blood glucose is tightly regulated by the opposing actions of the hormones insulin and glucagon. Earlier studies led by Dr. Roger Unger, Professor of Internal Medicine at UT Southwestern Medical Center, demonstrated that experimentally deleting or neutralizing receptors for glucagon can prevent or correct dangerously high blood glucose levels in different models of diabetes. "Dr. Unger's research suggested that high or unopposed glucagon action that results from insulin deficiency is the main culprit in the development of high blood glucose - known as hyperglycemia - in diabetes," said Dr. Jeffrey Zigman, Professor of Internal Medicine and Psychiatry at UT Southwestern and senior author of the study, published online today in the journal Diabetes. "He proposed that blocking or neutralizing glucagon action may serve as a new treatment for Type 1 and Type 2 diabetes. This idea formed the basis of our current study," Dr. Zigman added. Like glucagon and insulin, ghrelin also plays an important role in blood glucose control. But because the hormone was only discovered in the 1990s, ghrelin's actions on blood glucose haven't been studied as much as those of glucagon and insulin. The UTSW research team wanted to learn more about the role of ghrelin in diabetes. "We studied mice that lacks glucagon receptors. When we tried to make these animals diabetic by giving them an agent that destroys insulin-producing cells, the mice did not develop diabetes. Their blood sugar was normal. In addition to these results, we found that their ghrelin levels were high," said Dr. Zigman, who holds the Kent and Jodi Foster Distinguished Chair in Endocrinology, in Honor of Daniel Foster, M.D., the Mr. and Mrs. Bruce G. Brookshire Professorship in Medicine, and The Diana and Richard C. Strauss Professorship in Biomedical Research. In a related set of studies, when the researchers blocked the action of the elevated ghrelin, doing so caused the animals' blood sugar levels to drop below normal, he added. "These findings suggest that when glucagon activity is blocked, circulating levels of ghrelin rise, which helps to prevent dangerously low blood sugars from developing, a condition known as hypoglycemia," Dr. Zigman said. Pharmaceutical companies are now developing drugs targeting glucagon receptors to treat diabetes, including antibodies that will neutralize glucagon receptors or drugs that will block glucagon receptors, he added. "The body's normal ghrelin response should protect diabetic individuals being treated with agents that target glucagon receptors from experiencing hypoglycemia," Dr. Zigman said. Since the current study focused on a Type 1 diabetes model, researchers next plan to examine the coordinated actions of the ghrelin and glucagon systems in a Type 2 diabetes model. They also want to study the impact of ghrelin on hypoglycemia. "A potential side effect with any treatment that lowers blood sugar is that hypoglycemia may develop," Dr. Zigman said. "We would like to determine whether the administration of ghrelin or a compound that mimics the action of ghrelin could help correct that hypoglycemia." Lead author of the study is Dr. Bharath Mani, Instructor of Internal Medicine, and the co-senior authors include Dr. Unger, who holds the Touchstone/West Distinguished Chair in Diabetes Research, and Dr. Eric Berglund, Assistant Professor in the Advanced Imaging Research Center and of Pharmacology. Other contributing UTSW researchers are Dr. Aki Uchida, postdoctoral research fellow; Dr. Young Lee, Assistant Professor of Internal Medicine; and Sherri Osborne-Lawrence, senior research scientist. The study received support from the National Institutes of Health, the Novo Nordisk Foundation Center for Basic Metabolic Research, and the Hilda & Preston Davis Foundation. UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 18 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The faculty of more than 2,700 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 100,000 hospitalized patients, 600,000 emergency room cases, and oversee approximately 2.2 million outpatient visits a year. This news release is available on our website at http://www. . To automatically receive news releases from UT Southwestern via email, subscribe at http://www. .


Viswanathan S.,Advanced Imaging Research Center | Viswanathan S.,University of Texas at Dallas | Kovacs Z.,Advanced Imaging Research Center | Kovacs Z.,University of Texas at Dallas | And 6 more authors.
Chemical Reviews | Year: 2010

Alternatives to gadolinium-based metal chelates for Magnetic Resonance Imaging (MRI) have been reported. Magnetic resonance imaging (MRI) has been immensely valuable in diagnostic clinical imaging over the last few decades owing to its exceptional spatial and anatomical resolution. A conceptually different approach to contrast enhancement is based on chemical exchange saturation transfer (CEST). The contact relaxation enhancement is a through-bond effect and can be quite significant for directly coordinated atoms, but its strength rapidly decreases as the number of bonds increases. Chemical exchange in such cases can involve the conventional magnetization transfer (MT) techniques, which entails exchange of magnetization between a semisolid macromolecular phase and bulk water or the more recent CEST techniques that involve exchange between protons of solutes and bulk water. The discovery of paramagnetic lanthanide DOTA-tetra-amide complexes with extremely slow water exchange kinetics has further stimulated new ideas about CEST-based contrast agents.


News Article | December 1, 2015
Site: www.cemag.us

What if a diabetic never had to prick a finger to monitor his or her blood-glucose levels, and instead could rely on an internal, nanoscale device to analyze blood continuously and transmit readings to a hand-held scanner? That’s the life-transforming medical technology that Kyungsuk Yum, an assistant professor in the Materials Science and Engineering Department at The University of Texas at Arlington, is developing with support from a $100,000 Texas Medical Research Collaborative grant. Yum’s innovation depends on an injectable, near-infrared optical biosensor nanotube that would read a person’s blood glucose constantly and an optical glucose scanner that can access the data collected by nanotube. “Continuous blood glucose monitoring is essential in every diabetic’s life,” Yum says. “This device could unlock continuous information vital to a diabetic’s quality of life.” The American Diabetes Association estimates that more than 29 million people live with diabetes in the United States. That’s nearly 10 percent of the population. According to the World Health Organization, about 371 million worldwide have the disease. Yum became interested in this research because he wanted to help people with diabetes. “It is a huge societal problem,” Yum says. “I believe this nanotube sensing technology has that potential and could potentially provide a better way to manage diabetes and improve the quality of life for people with diabetes.” Early research on single-walled carbon nanotube-based optical biosensing technology was published in high-profile journals like Nature Nanotechnology, Journal of the American Chemical Society, Angewandte Chemie, and ACS Nano. Most recently, a review paper on this topic was published in the March 2015 edition of Biotechnology Journal. Yum joined UTA in 2013 following postdoctoral research appointments at the University of California, Berkeley, and the Massachusetts Institute of Technology. He is also a faculty affiliate of The University of Texas at Dallas and UT Southwestern Medical Center in Dallas. The Yum Research Group at UTA focuses on integrating man-made and nature's micro- and nano-scale materials, processes and systems for engineering innovation. The lab works on research projects at the intersection of physical sciences and engineering, and life sciences and biomedicine at that micro- and nano-scale. He applied for a 2015 Texas Medical Research Collaborative grant to further some aspect of the work and collaborated with A. Dean Sherry, University of Texas at Dallas chemistry professor and director of the Advanced Imaging Research Center at UT Southwestern Medical Center. The Texas Medical Research Collaborative is a research partnership among universities, health care providers and corporations supporting health care. Current diabetes technology offers patients two options. One requires that a tube be inserted through the abdomen for use of a continuous glucose monitoring system. The more common method requires a finger prick that provides blood for an external system called a glucometer.  The drawback to the sensor system is that it reads glucose levels in the patient’s tissue, which is not as accurate as blood readings. Plus, the continuous glucose-monitoring sensor needs to be calibrated multiple times a day and changed out every five to seven days. The drawback to the glucometer is that it requires painful finger pricks throughout the day. Khosrow Behbehani, dean of the UTA College of Engineering, says Yum’s work is representative of biomedical innovation that will improve health and the human condition, which is aligned with one of the core themes of UTA’s Strategic Plan 2020: Bold Solutions | Global Impact. “It’s compelling work that could improve the way diabetics live every day,” Behbehani says. “When research touches lives in such a way, it can dramatically affect the health care of millions of people.”


Abstract: What if a diabetic never had to prick a finger to monitor his or her blood-glucose levels, and instead could rely on an internal, nanoscale device to analyze blood continuously and transmit readings to a hand-held scanner? That's the life-transforming medical technology that Kyungsuk Yum, an assistant professor in the Materials Science and Engineering Department at The University of Texas at Arlington, is developing with support from a $100,000 Texas Medical Research Collaborative grant. Yum's innovation depends on an injectable, near-infrared optical biosensor nanotube that would read a person's blood glucose constantly and an optical glucose scanner that can access the data collected by nanotube. "Continuous blood glucose monitoring is essential in every diabetic's life," Yum said. "This device could unlock continuous information vital to a diabetic's quality of life." The American Diabetes Association estimates that more than 29 million people live with diabetes in the United States. That's nearly 10 percent of the population. According to the World Health Organization, about 371 million worldwide have the disease. Yum became interested in this research because he wanted to help people with diabetes. "It is a huge societal problem," Yum said. "I believe this nanotube sensing technology has that potential and could potentially provide a better way to manage diabetes and improve the quality of life for people with diabetes." Early research on single-walled carbon nanotube-based optical biosensing technology was published in high-profile journals like Nature Nanotechnology, Journal of the American Chemical Society, Angewandte Chemie and ACS Nano. Most recently, a review paper on this topic was published in the March 2015 of Biotechnology Journal. Yum joined UTA in 2013 following postdoctoral research appointments at the University of California, Berkeley, and the Massachusetts Institute of Technology. He is also a faculty affiliate of The University of Texas at Dallas and UT Southwestern Medical Center in Dallas. The Yum Research Group at UTA focuses on integrating man-made and nature's micro- and nano-scale materials, processes and systems for engineering innovation. The lab works on research projects at the intersection of physical sciences and engineering, and life sciences and biomedicine at that micro- and nano-scale. He applied for a 2015 Texas Medical Research Collaborative grant to further some aspect of the work and collaborated with A. Dean Sherry, University of Texas at Dallas chemistry professor and director of the Advanced Imaging Research Center at UT Southwestern Medical Center. The Texas Medical Research Collaborative is a research partnership among universities, health care providers and corporations supporting health care. Current diabetes technology offers patients two options. One requires that a tube be inserted through the abdomen for use of a continuous glucose monitoring system. The more common method requires a finger prick that provides blood for an external system called a glucometer. The drawback to the sensor system is that it reads glucose levels in the patient's tissue, which is not as accurate as blood readings. Plus, the continuous glucose-monitoring sensor needs to be calibrated multiple times a day and changed out every five to seven days. The drawback to the glucometer is that it requires painful finger pricks throughout the day. Khosrow Behbehani, dean of the UTA College of Engineering, said Yum's work is representative of biomedical innovation that will improve health and the human condition, which is aligned with one of the core themes of UTA's Strategic Plan 2020: Bold Solutions | Global Impact. "It's compelling work that could improve the way diabetics live every day," Behbehani said. "When research touches lives in such a way, it can dramatically affect the health care of millions of people." About University of Texas at Arlington The University of Texas at Arlington is a comprehensive research institution of more than 51,000 students in campus-based and online degree programs and is the second-largest institution in The University of Texas System. The Chronicle of Higher Education ranked UT Arlington as one of the 20 fastest-growing public research universities in the nation in 2014. U.S. News & World Report ranks UT Arlington fifth in the nation for undergraduate diversity. The University is a Hispanic-Serving Institution and is ranked as a "Best for Vets" college by Military Times magazine. Visit http://www.uta.edu to learn more, and find UT Arlington rankings and recognition at http://www.uta.edu/uta/about/rankings.php . For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.


News Article | December 20, 2016
Site: www.eurekalert.org

DALLAS - Dec. 20, 2016 - UT Southwestern Medical Center researchers have invented a transistor-like threshold sensor that can illuminate cancer tissue, helping surgeons more accurately distinguish cancerous from normal tissue. In this latest study, researchers were able to demonstrate the ability of the nanosensor to illuminate tumor tissue in multiple mouse models. The study is published in Nature Biomedical Engineering. "We synthesized an imaging probe that stays dark in normal tissues but switches on like a light bulb when it reaches solid tumors. The purpose is to allow surgeons to see tumors better during surgery," said senior author Dr. Jinming Gao, Professor of Oncology, Pharmacology and Otolaryngology with the Harold C. Simmons Comprehensive Cancer Center. The nanosensor amplifies pH signals in tumor cells to more accurately distinguish them from normal cells. "Cancer is a very diverse set of diseases, but it does have some universal features. Tumors do not have the same pH as normal tissue. Tumors are acidic, and they secrete acids into the surrounding tissue. It's a very consistent difference and was discovered in the 1920's," said Dr. Baran Sumer, Associate Professor of Otolaryngology, and co-senior author of the study. The researchers hope the improved surgical technology can eventually benefit cancer patients in multiple ways. "This new digital nanosensor-guided surgery potentially has several advantages for patients, including more accurate removal of tumors, and greater preservation of functional normal tissues," said Dr. Sumer. "These advantages can improve both survival and quality of life." For example, this technology may help cancer patients who face side effects such as incontinence after rectal cancer surgery. "The new technology also can potentially assist radiologists by helping them to reduce false rates in imaging, and assist cancer researchers with non-invasive monitoring of drug responses," said Dr. Gao. According to the National Cancer Institute, there are 15.5 million cancer survivors in the U.S., representing 4.8 percent of the population. The number of cancer survivors is projected to increase by 31 percent, to 20.3 million, by 2026. Dr. Sumer and Dr. Gao were joined in this study by Dr. Gang Huang, Instructor of Pharmacology; Dr. Xian-Jin Xie, Professor of Clinical Sciences; Dr. Rolf Brekken, Professor of Surgery and Pharmacology and an Effie Marie Cain Research Scholar; and Dr. Xiankai Sun, Director of Cyclotron and Radiochemistry Program in Department of Radiology and Advanced Imaging Research Center, Associate Professor of Radiology, and holder of the Dr. Jack Krohmer Professorship in Radiation Physics; Dr. Joel Thibodeaux, Assistant Professor of Pathology and Director of Cytopathology, Parkland Memorial Hospital. Additional UT Southwestern researchers who contributed to the study include: Dr. Tian Zhao, Dr. Xinpeng Ma, Mr. Yang Li, Dr. Zhiqiang Lin, Dr. Min Luo, Dr. Yiguang Wang, Mr. Shunchun Yang and Ms. Zhiqun Zeng in the Harold C. Simmons Comprehensive Cancer Center; and Dr. Saleh Ramezani in the Department of Radiology. Dr. Gao and Dr. Sumer are scientific co-founders of OncoNano Medicine, Inc. The authors declare competing financial interests in the full-text of the Nature Biomedical Engineering article. UT Southwestern Medical Center has licensed the technology to OncoNano Medicine and has a financial interest in the research described in the article. Funding for the project includes grants from the Cancer Prevention and Research Institute of Texas. Dr. Gao and Dr. Sumer are investigators for two Academic Research grants and OncoNano Medicine was the recipient of a CPRIT Product Development Research grant. Research reported in this press release was supported by the National Cancer Institute under Award Number R01 CA192221 and the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The Harold C. Simmons Comprehensive Cancer Center is the only NCI-designated Comprehensive Cancer Center in North Texas and one of just 47 NCI-designated Comprehensive Cancer Centers in the nation. Simmons Cancer Center includes 13 major cancer care programs. In addition, the Center's education and training programs support and develop the next generation of cancer researchers and clinicians. Simmons Cancer Center is among only 30 U.S. cancer research centers to be designated by the NCI as a National Clinical Trials Network Lead Academic Participating Site. UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. The faculty of almost 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in about 80 specialties to more than 100,000 hospitalized patients and oversee approximately 2.2 million outpatient visits a year. This news release is available on our website at http://www. . To automatically receive news releases from UT Southwestern via email, subscribe at http://www.


Lu H.,Advanced Imaging Research Center | Yezhuvath U.S.,Advanced Imaging Research Center | Xiao G.,University of Texas Southwestern Medical Center
Human Brain Mapping | Year: 2010

The power of fMRI in assessing neural activities is hampered by inter-subject variations in basal physiologic parameters, which may not be related to neural activation but has a modulatory effect on fMRI signals. Therefore, normalization of fMRI signals with these parameters is useful in reducing variations and improving sensitivity of this important technique. Recently, we have shown that basal venous oxygenation is a significant modulator of fMRI signals and individuals with higher venous oxygenation tend to have lower fMRI signals. In this study, we aim to test the utility of venous oxygenation normalization in distinguishing subject groups. A "model" condition was used in which two visual stimuli with different flashing frequencies were used to stimulate two subject groups, respectively, thereby simulating the situation of control and patient groups. It was found that visualevoked BOLD signal is significantly correlated with baseline venous T2 (P 1/4 0.0003) and inclusion of physiologic modulator in the regression analysis can substantially reduce P values of group-level statistical tests. When applied to voxel-wise analysis, the normalization process can allow the detection of more significant voxels. The utility of other basal parameters, including blood pressure, heart rate, arterial oxygenation, and end-tidal CO2, in BOLD normalization was also assessed and it was found that the improvement was less significant. Time-to-peak of the BOLD responses was also studied and it was found that subjects with higher basal venous oxygenation tend to slower BOLD responses. © 2009 Wiley-Liss, Inc.


Krishnamurthy L.C.,Advanced Imaging Research Center | Krishnamurthy L.C.,University of Texas at Arlington | Liu P.,Advanced Imaging Research Center | Ge Y.,New York University | Lu H.,Advanced Imaging Research Center
Magnetic Resonance in Medicine | Year: 2014

Purpose Measurement of venous oxygenation (Yv) is a critical step toward quantitative assessment of brain oxygen metabolism, a key index in many brain disorders. The present study aims to develop a noninvasive, rapid, and reproducible method to measure Yv in a vessel-specific manner. Theory The method, T2-Relaxation-Under-Phase-Contrast MRI, utilizes complex subtraction of phase-contrast to isolate pure blood signal, applies nonslice-selective T2-preparation to measure T2, and converts T2 to oxygenation using a calibration plot. Methods Following feasibility demonstration, several technical aspects were examined, including validation with an established global Yv technique, test-retest reproducibility, sensitivity to detect oxygenation changes due to hypoxia and caffeine challenges, applicability of echo-planar-imaging (EPI) acquisition to shorten scan duration, and ability to study veins with a caliber of 1-2 mm. Results T2-Relaxation-Under-Phase-Contrast was able to simultaneously measure Yv in all major veins in the brain, including sagittal sinus, straight sinus, great vein, and internal cerebral vein. T 2-Relaxation-Under-Phase-Contrast results showed an excellent agreement with the reference technique, high sensitivity to oxygenation changes, and test-retest variability of 3.5 ± 1.0%. The use of segmented-EPI was able to reduce the scan duration to 1.5 minutes. It was also feasible to study pial veins and deep veins. Conclusion T2-Relaxation-Under-Phase- Contrast MRI is a promising technique for vessel-specific oxygenation measurement. © 2013 Wiley Periodicals, Inc.


Xu F.,Advanced Imaging Research Center | Uh J.,Advanced Imaging Research Center | Liu P.,Advanced Imaging Research Center | Lu H.,Advanced Imaging Research Center
Magnetic Resonance in Medicine | Year: 2012

A T 2-relaxation-under-spin-tagging technique was recently developed to estimate cerebral blood oxygenation, providing potentials for noninvasive assessment of the brain's oxygen consumption. A limitation of the current sequence is the need for long repetition time, as shorter repetition time causes an over-estimation in blood R 2. This study proposes a post-saturation T 2-relaxation-under-spin-tagging by placing a non-selective 90° pulse after the signal acquisition to reset magnetization in the whole brain. This scheme was found to eliminate estimation bias at a slight cost of precision. To improve the precision, echo time of the sequence was optimized and it was found that a modest echo time shortening of 3.4 ms can reduce the estimation error by 49%. We recommend the use of postsaturation T 2-relaxation-under-spin-tagging sequence with a repetition time of 3000 ms and a echo time of 3.6 ms, which allows the determination of global venous oxygenation with scan duration of 1 min 12 s and an estimation precision of ±1% (in units of oxygen saturation percentage). © 2011 Wiley Periodicals, Inc.


Campbell N.,NYU Langone Medical Center | Rosenkrantz A.B.,NYU Langone Medical Center | Pedrosa I.,Advanced Imaging Research Center
Topics in Magnetic Resonance Imaging | Year: 2014

Renal cell carcinoma (RCC) is most commonly diagnosed as an incidental finding on cross-sectional imaging and represents a significant clinical challenge. Although most patients have a surgically curable lesion at the time of diagnosis, the variability in the biologic behavior of the different histologic subtypes and tumor grade of RCC, together with the increasing array of management options, creates uncertainty for the optimal clinical approach to individual patients. State-of-the-art magnetic resonance imaging (MRI) provides a comprehensive assessment of renal lesions that includes multiple forms of tissue contrast as well as functional parameters, which in turn provides information that helps to address this dilemma. In this article, we review this evolving and increasingly comprehensive role of MRI in the detection, characterization, perioperative evaluation, and assessment of the treatment response of renal neoplasms. We emphasize the ability of the imaging "phenotype" of renal masses on MRI to help predict the histologic subtype, grade, and clinical behavior of RCC. © 2014 Lippincott Williams and Wilkins.


Hooks J.C.,Advanced Imaging Research Center
Biopolymers | Year: 2011

Multimeric interactions that occur in biology provide impetus for chemists to explore new types of synthetic multivalent ligands that alter cellular functions by mechanisms inaccessible to natural substances. While many different molecules such as peptides, antibody fragments, carbohydrates and organic moieties have been used in developing multimeric ligands, it is worth exploring other important molecular types that have hardly been tested in developing multimeric compounds. Peptoids are one such class of compounds with highly facile synthesis as well as much better biologically amenable qualities. Recently, we identified two HCC4017 lung cancer cell targeting peptoids. Here we explore the possibility of synthesizing multimers of these compounds completely through a solid phase synthesis approach. We have synthesized mini-libraries of homodimers, homotrimers and most importantly, heterodimers of our lung cancer specific compounds. The idea is to develop series of compounds that only differs by the linker portion, which is readily adjustable within the library. The purpose of this is to find the optimal distance between each monomeric unit of the multimer that allows them to perfectly interact with their individual biological targets displayed on the cell surface. Future screens of these minilibraries will identify the multimers with improved binding affinities.

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