Radiology Commons^™

Chloroquine-Inducible Par-4 Secretion Is Essential For Tumor Cell Apoptosis And Inhibition Of Metastasis, Ravshan Burikhanov, Nikhil Hebbar, Sunil K. Noothi, Nidhi Shukla, James Sledziona, Nathália Araujo, Meghana Kudrimoti, Qing Jun Wang, David S. Watt, Danny R. Welch, Jodi Maranchie, Akihiro Harada, Vivek M. Rangnekar

Radiation Medicine Faculty Publications

The induction of tumor suppressor proteins capable of cancer cell apoptosis represents an attractive option for the re-purposing of existing drugs. We report that the anti-malarial drug, chloroquine (CQ), is a robust inducer of Par-4 secretion from normal cells in mice and cancer patients in a clinical trial. CQ-inducible Par-4 secretion triggers paracrine apoptosis of cancer cells and also inhibits metastatic tumor growth. CQ induces Par-4 secretion via the classical secretory pathway that requires the activation of p53. Mechanistically, p53 directly induces Rab8b, a GTPase essential for vesicle transport of Par-4 to the plasma membrane prior to secretion. Our findings …

Validation, Optimization, And Image Processing Of Spiral Cine Dense Magnetic Resonance Imaging For The Quantification Of Left And Right Ventricular Mechanics, Gregory J. Wehner

Theses and Dissertations--Biomedical Engineering

Recent evidence suggests that cardiac mechanics (e.g. cardiac strains) are better measures of heart function compared to common clinical metrics like ejection fraction. However, commonly-used parameters of cardiac mechanics remain limited to just a few measurements averaged over the whole left ventricle. We hypothesized that recent advances in cardiac magnetic resonance imaging (MRI) could be extended to provide measures of cardiac mechanics throughout the left and right ventricles (LV and RV, respectively).

Displacement Encoding with Stimulated Echoes (DENSE) is a cardiac MRI technique that has been validated for measuring LV mechanics at a magnetic field strength of 1.5 T but …

Mammogram And Tomosynthesis Classification Using Convolutional Neural Networks, Xiaofei Zhang

Theses and Dissertations--Computer Science

Mammography is the most widely used method of screening for breast cancer. Traditional mammography produces two-dimensional X-ray images, while advanced tomosynthesis mammography produces reconstructed three-dimensional images. Due to high variability in tumor size and shape, and the low signal-to-noise ratio inherent to mammography, manual classification yields a significant number of false positives, thereby contributing to an unnecessarily large number of biopsies performed to reduce the risk of misdiagnosis. Achieving high diagnostic accuracy requires expertise acquired over many years of experience as a radiologist.

The convolutional neural network (CNN) is a popular deep-learning construct used in image classification. The convolutional process …

Cardiac Chemical Exchange Saturation Transfer Mr Imaging Tracking Of Cell Survival Or Rejection In Mouse Models Of Cell Therapy, Ashley L. Pumphrey, Shaojing Ye, Zhengshi Yang, Jennifer Simkin, John C. Gensel, Ahmed Abdel-Latif, Moriel H. Vandsburger

Saha Cardiovascular Research Center Faculty Publications

Purpose:

To examine whether cardiac chemical exchange saturation transfer (CEST) imaging can be serially and noninvasively used to probe cell survival or rejection after intramyocardial implantation in mice.

Materials and Methods:

Experiments were compliant with the National Institutes of Health Guidelines on the Use of Laboratory Animals and approved by the Institutional Animal Care and Use Committee. One million C2C12 cells labeled with either europium (Eu) 10-(2-hydroxypropyl)-1,4,7-tetraazacyclododecane-1,4,7-triacetic acid (HP-DO3A) or saline via the hypotonic swelling technique were implanted into the anterior-lateral left ventricular wall in C57BL/6J (allogeneic model, n = 17) and C3H (syngeneic model, n = 13) mice. Imaging …

Properties And Optimization Of Respiratory Navigator Gating For Spiral Cine Dense Cardiac Mri, Sean Michael Hamlet

Theses and Dissertations--Electrical and Computer Engineering

Cardiac magnetic resonance (MR) imaging can non-invasively assess heart function. Displacement encoding with stimulated echoes (DENSE) is an advanced cardiac MR imaging technique that measures tissue displacement and can be used to quantify cardiac mechanics (e.g. strain and torsion). When combined with clinical risk factors, cardiac mechanics have been shown to be better predictors of mortality than traditional measures of heart function.

End-expiratory breath-holds are typically used to minimize respiratory motion artifacts. Unfortunately, requiring subjects to breath-hold introduces limitations with the duration of image acquisition and quality of data acquired, especially in patients with limited ability to hold their breath. …

New Findings, Classification And Long-Term Follow-Up Study Based On Mri Characterization Of Brainstem Encephalitis Induced By Enterovirus 71, Hongwu Zeng, Feiqiu Wen, Wenxian Huang, Yungen Gan, Weibin Zeng, Ranran Chen, Yanxia He, Yonker Wang, Zaiyi Liu, Changhong Liang, Kelvin K. L. Wong

Radiology Faculty Publications

Background To report the diversity of MRI features of brainstem encephalitis (BE) induced by Enterovirus 71. This is supported by implementation and testing of our new classification scheme in order to improve the diagnostic level on this specific disease.

Methods Neuroimaging of 91 pediatric patients who got EV71 related BE were hospitalized between March, 2010 to October, 2012, were analyzed retrospectively. All patients underwent pre- and post-contrast MRI scan. Thereafter, 31 patients were randomly called back for follow-up MRI study during December 2013 to August 2014. The MRI signal patterns of BE primary lesion were analyzed and classified according to …

Diffuse Optical Measurements Of Head And Neck Tumor Hemodynamics For Early Prediction Of Chemoradiation Therapy Outcomes, Lixin Dong, Mahesh Kudrimoti, Daniel Irwin, Li Chen, Sameera Kumar, Yu Shang, Chong Huang, Ellis L. Johnson, Scott D. Stevens, Brent J. Shelton, Guoqiang Yu

Biomedical Engineering Faculty Publications

This study used a hybrid near-infrared diffuse optical instrument to monitor tumor hemodynamic responses to chemoradiation therapy for early prediction of treatment outcomes in patients with head and neck cancer. Forty-seven patients were measured once per week to evaluate the hemodynamic status of clinically involved cervical lymph nodes as surrogates for the primary tumor response. Patients were classified into two groups: complete response (CR) (n = 29) and incomplete response (IR) (n = 18). Tumor hemodynamic responses were found to be associated with clinical outcomes (CR/IR), wherein the associations differed depending on human papillomavirus (HPV-16) status. In HPV-16 …

Radiation-Enhanced Therapeutic Targeting Of Galectin-1 Enriched Malignant Stroma In Triple Negative Breast Cancer, Meenakshi Upreti, Amar Jyoti, Sara E. Johnson, Elden P. Swindell, Dana L. Napier, Pallavi Sethi, Ryan Chan, Jonathan M. Feddock, Heidi L. Weiss, Thomas V. O'Halloran, B. Mark Evers

Pharmaceutical Sciences Faculty Publications

Currently there are no FDA approved targeted therapies for Triple Negative Breast Cancer (TNBC). Ongoing clinical trials for TNBC have focused primarily on targeting the epithelial cancer cells. However, targeted delivery of cytotoxic payloads to the non-transformed tumor associated-endothelium can prove to be an alternate approach that is currently unexplored. The present study is supported by recent findings on elevated expression of stromal galectin-1 in clinical samples of TNBC and our ongoing findings on stromal targeting of radiation induced galectin-1 by the anginex-conjugated arsenic-cisplatin loaded liposomes using a novel murine tumor model. We demonstrate inhibition of tumor growth and metastasis …

Peripheral (Deep) But Not Periventricular Mri White Matter Hyperintensities Are Increased In Clinical Vascular Dementia Compared To Alzheimer's Disease, Charles D. Smith, Eleanor S. Johnson, Linda J. Van Eldik, Gregory A. Jicha, Frederick A. Schmitt, Peter T. Nelson, Richard J. Kryscio, Richard R. Murphy, Clinton V. Wellnitz

Neurology Faculty Publications

Background and purpose: Vascular dementia (VAD) is a complex diagnosis at times difficult to distinguish from Alzheimer's disease (AD). MRI scans often show white matter hyperintensities (WMH) in both conditions. WMH increase with age, and both VAD and AD are associated with aging, thus presenting an attribution conundrum. In this study, we sought to show whether the amount of WMH in deep white matter (dWMH), versus periventricular white matter (PVH), would aid in the distinction between VAD and AD, independent of age. Methods: Blinded semiquantitative ratings of WMH validated by objective quantitation of WMH volume from standardized MRI image acquisitions. …

Mri Signal Intensity Differentiation Of Brainstem Encephalitis Induced By Enterovirus 71: A Classification Approach For Acute And Convalescence Stages, Hongwu Zeng, Wenxian Huang, Feiqiu Wen, Yonker Wang, Yungen Gan, Weibin Zeng, Ranran Chen, Yanxia He, Zaiyi Liu, Changhong Liang, Kelvin K. L. Wong

Radiology Faculty Publications

Background: The objective of this study is to assess standardized histograms of signal intensities of T1 signal and T2 signal on sagittal view without enhancement during (1) acute stage, and (2) convalescence stage of pediatric patients with Enterovirus 71 related brainstem encephalitis (BE), and with respect to (3) healthy normal.

Methods: Our subjects were hospitalized between March 2010 and October 2012, and underwent pre- and post-contrast MRI studies. The research question to be answered is whether the comparison of the MRI image intensity histograms and relevant statistical quantification can add new knowledge to the diagnosis of BE patients. So, both …

Vena Cava Filter Utilization And Retrieval: A Quality Of Care Issue, Joshua Brown

Theses and Dissertations--Pharmacy

Vena cava filters (VCFs) are mechanical devices implanted in the inferior vena cava to trap thrombi from travelling to the pulmonary circulation, resulting in pulmonary embolism. VCFs are available as permanent or non-permanent, retrievable devices and are generally indicated for use in patients unable to receive systemic anticoagulation or at exceedingly high risk for pulmonary embolism (PE). Retrievable devices allow for removal of the VCF once the contraindication to anticoagulation or high risk of PE has abated. Since the introduction of retrievable VCFs in the early 2000’s, use of VCFs has increased three-fold, with >85% of all VCFs placed being …

A Prospective Analysis Of Factors Associated With Decreased Physical Activity In Patients With Cirrhosis Undergoing Transplant Evaluation, Anna Christina Dela Cruz, Valery Vilchez, Sooyeon Kim, Benjamin Barnes, Abhishek Ravinuthala, Anthony Zanni, Roberto Galuppo, Achuthan Sourianarayanane, Trushar Patel, Erin Colleen Maynard, Malay B. Shah, Michael F. Daily, Timothy L. Uhl, Karyn A. Esser, Roberto Gedaly

Internal Medicine Faculty Publications

BACKGROUND: Physical activity has been associated with improved recovery time after transplantation. Handgrip strength has been related to post-transplant outcomes.

AIM: To evaluate predictors of physical activity and grip strength in cirrhotic patients undergoing liver transplant evaluation.

METHODS: Single center, prospective analysis.

RESULTS: A hundred patients were evaluated (54% male, mean age 53 ± 9). Common etiologies of liver disease were non-alcoholic hepatitis (27%), hepatitis C (22%), and alcoholic liver disease (21%). Mean MELD score was 13.5. Forty one percent had a history of smoking. Ninety-three patients completed the International Physical Activity Questionnaire. The median total physical activity score of …

Plant-Derived Sac Domain Of Par-4 (Prostate Apoptosis Response 4) Exhibits Growth Inhibitory Effects In Prostate Cancer Cells, Shayan Sarkar, Sumeet Jain, Vineeta Rai, Dipak K. Sahoo, Sumita Raha, Sujit Suklabaidya, Shantibhusan Senapati, Vivek M. Rangnekar, Indu B. Maiti, Nrisingha Dey

Radiation Medicine Faculty Publications

The gene Par-4 (Prostate Apoptosis Response 4) was originally identified in prostate cancer cells undergoing apoptosis and its product Par-4 showed cancer specific pro-apoptotic activity. Particularly, the SAC domain of Par-4 (SAC-Par-4) selectively kills cancer cells leaving normal cells unaffected. The therapeutic significance of bioactive SAC-Par-4 is enormous in cancer biology; however, its large scale production is still a matter of concern. Here we report the production of SAC-Par-4-GFP fusion protein coupled to translational enhancer sequence (5′ AMV) and apoplast signal peptide (aTP) in transgenic Nicotiana tabacum cv. Samsun NN plants under the control of a unique recombinant promoter M24. …

Radiobiological Evaluation Of Intensity Modulated Radiation Therapy Treatments Of Patients With Head And Neck Cancer: A Dual-Institutional Study, G. Narayanasamy, A. P. Pyakuryal, S. Pandit, J. Vincent, C. Lee, P. Mavroidis, N. Papanikolaou, Mahesh Kudrimoti, T. T. Sio

Radiation Medicine Faculty Publications

In clinical practice, evaluation of clinical efficacy of treatment planning stems from the radiation oncologist's experience in accurately targeting tumors, while keeping minimal toxicity to various organs at risk (OAR) involved. A more objective, quantitative method may be raised by using radiobiological models. The purpose of this work is to evaluate the potential correlation of OAR-related toxicities to its radiobiologically estimated parameters in simultaneously integrated boost (SIB) intensity modulated radiation therapy (IMRT) plans of patients with head and neck tumors at two institutions. Lyman model for normal tissue complication probability (NTCP) and the Poisson model for tumor control probability (TCP) …

Case 213: Primary Spenic Angiosarcoma, John J. Krol, Vera V. Krol, Adrian Dawkins, Halemane S. Ganesh

Radiology Faculty Publications

A 75-year-old woman with a medical history of gastroesophageal reflux disease and type II diabetes presented to the hospital with a 3-month history of gradually worsening headaches, vague upper abdominal pain, and lower back pain. The patient denied fevers, night sweats, contact with sick individuals, occupational exposure to infection, bleeding, immunodeficiency, intravenous drug use, alcohol or tobacco abuse, history of malignancy, family history of genetic disorders, and international travel. Physical examination revealed a skin-colored mass protruding from the right side of her forehead, but there were no other notable abnormalities. Her diabetes was managed with diet, and the only prescription …

Case 213, John J. Krol, Vera V. Krol, Adrian Dawkins, Halemane S. Ganesh

Radiology Faculty Publications

No abstract provided.

Variability In Eit Images Of Lung Ventilation As A Function Of Electrode Planes And Body Positions, Jie Zhang, Robert Patterson

Radiology Faculty Publications

This study is aimed at investigating the variability in resistivity changes in the lung region as a function of air volume, electrode plane and body position. Six normal subjects (33.8 ± 4.7 years, range from 26 to 37 years) were studied using the Sheffield Electrical Impedance Tomography (EIT) portable system. Three transverse planes at the level of second intercostal space, the level of the xiphisternal joint, and midway between upper and lower locations were chosen for measurements. For each plane, sixteen electrodes were uniformly positioned around the thorax. Data were collected with the breath held at end expiration and after …

Regulation Of The Proapoptotic Functions Of Prostate Apoptosis Response-4 (Par-4) By Casein Kinase 2 In Prostate Cancer Cells, A De Thonel, A Hazoumé, V Kochin, K Isoniemi, G Jego, E Fourmaux, A Hammann, H Mjahed, O Filhol, O Micheau, P Rocchi, V Mezger, J E Eriksson, Vivek M. Rangnekar, C Garrido

Radiation Medicine Faculty Publications

The proapoptotic protein, prostate apoptosis response-4 (Par-4), acts as a tumor suppressor in prostate cancer cells. The serine/threonine kinase casein kinase 2 (CK2) has a well-reported role in prostate cancer resistance to apoptotic agents or anticancer drugs. However, the mechanistic understanding on how CK2 supports survival is far from complete. In this work, we demonstrate both in rat and humans that (i) Par-4 is a new substrate of the survival kinase CK2 and (ii) phosphorylation by CK2 impairs Par-4 proapoptotic functions. We also unravel different levels of CK2-dependent regulation of Par-4 between species. In rats, the phosphorylation by CK2 at …

Paracrine Apoptotic Effect Of P53 Mediated By Tumor Suppressor Par-4, Ravshan Burikhanov, Tripti Shrestha-Bhattarai, Nikhil Hebbar, Shirley Qiu, Yanming Zhao, Gerard P. Zambetti, Vivek M. Rangnekar

Radiation Medicine Faculty Publications

The guardian of the genome, p53, is often mutated in cancer and may contribute to therapeutic resistance. Given that p53 is intact and functional in normal tissues, we harnessed its potential to inhibit the growth of p53-deficient cancer cells. Specific activation of p53 in normal fibroblasts selectively induced apoptosis in p53-deficient cancer cells. This paracrine effect was mediated by p53-dependent secretion of the tumor suppressor Par-4. Accordingly, the activation of p53 in normal mice, but not p53⁻/⁻ or Par-4⁻/⁻ mice, caused systemic elevation of Par-4, which induced apoptosis of p53-deficient tumor cells. Mechanistically, p53 …

A Feasibility Study Using Tomodirect For Craniospinal Irradiation, Ulrich W. Langner, Janelle A. Molloy, John F. Gleason Jr., Jonathan M. Feddock

Radiation Medicine Faculty Publications

The feasibility of delivering craniospinal irradiation (CSI) with TomoDirect is investigated. A method is proposed to generate TomoDirect plans using standard three-dimensional (3D) beam arrangements on Tomotherapy with junctioning of these fields to minimize hot or cold spots at the cranial/spinal junction. These plans are evaluated and compared to a helical Tomotherapy and a three-dimensional conformal therapy (3D CRT) plan delivered on a conventional linear accelerator (linac) for CSI. The comparison shows that a TomoDirect plan with an overlap between the cranial and spinal fields might be preferable over Tomotherapy plans because of decreased low dose to large volumes of …

Towards Omni-Tomography -- Grand Fusion Of Multiple Modalities For Simultaneous Interior Tomography, Ge Wang, Jie Zhang, Hao Gao, Victor Weir, Hengyong Yu, Wenxiang Cong, Xiaochen Xu, Haiou Shen, James Bennett, Mark Furth, Yue Wang, Michael Vannier

Radiology Faculty Publications

We recently elevated interior tomography from its origin in computed tomography (CT) to a general tomographic principle, and proved its validity for other tomographic modalities including SPECT, MRI, and others. Here we propose "omni-tomography", a novel concept for the grand fusion of multiple tomographic modalities for simultaneous data acquisition in a region of interest (ROI). Omni-tomography can be instrumental when physiological processes under investigation are multi-dimensional, multi-scale, multi-temporal and multi-parametric. Both preclinical and clinical studies now depend on in vivo tomography, often requiring separate evaluations by different imaging modalities. Over the past decade, two approaches have been used for multimodality …

Inverse Relationship Between Psa And Il-8 In Prostate Cancer: An Insight Into A Nf-Κb-Mediated Mechanism, Yong Xu, Daret K. St. Clair, Fang Fang, William H. St. Clair

Toxicology and Cancer Biology Faculty Publications

Background: Prostate specific antigen (PSA) is traditionally used as an indicator for the presence of prostate cancer (PCa) and radiotherapy is generally used to treat inoperable and locally advanced PCa. However, how cellular PSA level is associated with sensitivity of PCa to radiotherapy is unknown. The previous finding that the RelB-based NF-κB alternative pathway differentially regulates PSA and interleukin-8 (IL-8) in aggressive PCa has directed our attention to the role of RelB in the response of PCa to radiotherapy.

Methodology/Principal Findings: RelB and its targets PSA and IL-8 in PCa cells were manipulated by ectopic expression in PCa …

Patient Discomfort Associated With The Use Of Intra-Arterial Iodinated Contrast Media: A Meta-Analysis Of Comparative Randomized Controlled Trials, Peter A. Mccullough, Patrizio Capasso

Radiology Faculty Publications

BACKGROUND: Discomfort characterized by pain and warmth are common adverse effects associated with the use of intra-arterial iodinated contrast media (CM). The objective of this review was to pool patient-reported outcomes available from head-to-head randomized controlled trials (RCTs) and to compare the discomfort rates associated with iso-osmolar contrast media (IOCM; i.e., iodixanol) to those reported with various low-osmolar contrast media (LOCM).

METHODS: A review of the literature published between 1990 and 2009 available through Medline, Medline Preprints, Embase, Biological Abstracts, BioBase, Cab Abstracts, International Pharmaceutical Abstracts, Life Sciences Collection, Inside Conferences, Energy Database, Engineering Index and Technology Collection was performed …

Identification Of A Unique Core Domain Of Par-4 Sufficient For Selective Apoptosis Induction In Cancer Cells, Vivek M. Rangnekar

Radiation Medicine Faculty Patents

The present invention relates to Par-4 mutants which cause apoptosis in cancer cells which are sensitive to Par-4 and also induce apoptosis in cancer cells which are resistant to Par-4. The present invention also relates to methods of using the Par-4 mutant to treat certain cancers, as well as to kits, vectors, and polypeptides for same.

Method Of Discrete Orthogonal Basis Restoration, Edward B. Moody

Radiology Faculty Patents

A method is described for utilizing discrete orthogonal basis to restore signal system, such as radio or sound waves and/or image system such as photographs or medical images that become distorted while being acquired, transmitted and/or received. The signal or image systems are of the linear type and may be represented by the equation [B] [o]= [i] wherein [o] is an original signal or image, [i] is a degraded signal or image and [B] is a system transfer function matrix. The method involves estimating a signal-to-noise ratio for a restored signal or image. Next, is the selecting of a set …