TcSUH.net

Biophysics Laboratory

John Miller — Mon, 02 May 2011 20:17:09 +0000

The Biophysics Laboratory is headed by Professor John H. Miller, Jr.

Mission: study and develop novel applications of sensitive magnetic sensors, known as Superconducting QUantum Interference Devices (SQUIDs), and utilize other electromagnetic techniques, such as impedance spectroscopy and harmonic generation spectroscopy, for the study of biological systems.

Current Projects/Achievements:

APPLICATIONS OF HIGH-Tc SUPERCONDUCTING QUANTUM INTERFERENCE DEVICES

Impedance Magnetocardiography: Impedance magnetocardiography (IMCG) measures impedance changes in the thorax as the heart pumps blood during its cardiac cycle, providing information about stroke volume and cardiac output of blood flow. We use high-Tc SQUIDs to measure the magnetic fields produced by tiny ac currents introduced via electrodes.

Chemomagnetism: We have discovered that numerous chemical reactions generate tiny magnetic fields due to the motion of ions. We measure such fields using SQUIDs, and have found that many reactions exhibit ‘avalanche-like’ behavior in their dynamics.

IMPEDANCE SPECTROSCOPY OF BIOLOGICAL SYSTEMS

Cytoskeletal proteins: Alpha-beta tubulin heterodimers have a large electric dipole moment, which plays a major role in their self assembly to form microtubules. Our frequency-dependent admittance measurements show that the ac conductivity of tubulin suspensions peaks at the critical concentration for microtubule polymerization and reveal a large electric charge per dimer.

Dielectric response of whole cells: Our group has shown that the low-frequency ‘alpha’ dielectric response correlates with cell concentration and cellular membrane potential, providing a powerful noninvasive assay of cells in suspension.

HARMONIC GENERATION SPECTROSCOPY OF BIOLOGICAL SYSTEMS

Pumps in the plasma membrane: Using SQUIDs to directly probe induced currents, we have observed 2nd and higher harmonics generated by proton pumps in response to sinusoidal fields.

Light activated behavior in chloroplasts and plants: Plants and other photosynthetic organisms are ideal “model organisms” because much of their enzyme activity is light activated. We observe significant differences in both linear and nonlinear (harmonic) response to ac electric fields, which depend on the presence or absence of light.

Detection of enzyme activity in the mitochondrial electron transport chain: We observe features in frequency-dependent harmonics generated by mitochondria and whole cells that appear to correlate with activity of complexes responsible for the production of ATP.

Detection of mitochondrial dysfunction in diabetes & heart disease: Mitochondrial dysfunction plays a major role in type-2 diabetes, heart disease, cancer, and numerous specific mitochondrial disorders. We have initiated a collaboration with Methodist Hospital physicians to develop and validate sensors capable of detecting mitochondrial dysfunction in patients with diabetes and heart disease.

High Frequency Characterization Laboratory

Jarek Wosik — Mon, 02 May 2011 20:12:02 +0000

The High Frequency Characterization Laboratory is headed by Professor Jarek Wosik.

Mission: the main focus of this laboratory is to make scientific and engineering contributions towards the utilization at microwave- and radio-frequencies (rf) of HTS thin films and devices in bio-medicine and an improved understanding of high frequency properties of HTS materials at high dc and rf fields.

There is a promising niche market for both clinical and research applications of HTS single or phased array surface probes for high-resolution MRI. Especially successful development of multi-elements HTS phased array MRI coil may accelerate the recognition of HTS coils as the market applications. There could also be a moderate but significant market in biology research labs and clinics for low-field MRI using either cooled copper or HTS based MRI probes.

Active projects: the laboratory is currently engaged in various projects related to …

Sensors for Lymph Node Staging

Audrius Brazdeikis — Mon, 02 May 2011 19:35:09 +0000

Many primary tumors spread via lymphatic drainage, therefore lymph node staging and localization of pathological lymph nodes remains a cornerstone in choosing the most appropriate intervention. Non-invasive methods such as ultrasonography, CT, PET to stage regional lymph nodes have not shown to be accurate. Sentinel lymph nodes (SLN) can also be mapped using MRI techniques, but this application does not allow probe guided surgery.

One of the successes of the first “UK-Texas Bioscience Collaboration Initiative” was the development of a proof-of-concept HTS SQUID-based device that detects very small concentrations of iron oxide based contrast agents used for MRI. For the purpose of SLN detection, the probe was configured to detect a commercially available, FDA-approved dextran-coated superparamagnetic iron oxide. An initial clinical evaluation of the magnetometer was undertaken at the University College London Hospital. Ten patients with newly diagnosed breast cancer underwent sentinel node biopsy with Endorem® (Feridex I.V.), blue dye and radiocolloid injections. In some cases pre-operative MRI was performed as well as lymphoscintigraphy to compare the imaging capabilities of the different methods. In each of the 10 patients, the SLN biopsy procedure was successful, and a total of 19 sentinel nodes were retrieved using the prototype hand-held magnetometer.

Our group has recently built an improved HTS SQUID system (SentiMag-One) for magnetically guided surgery. The SQUID system is installed at the Guy’s Hospital in London and currently being used in a clinical trial of breast cancer run by our collaborator Michael Douek, MD.

The presence of metastases in regional lymph nodes is important not just in breast cancer but in a variety of cancers. Our current research focuses on multimodal imaging capability and developing ultra-sensitive specialized probes for both preoperative planning and intraoperative use, and magnetic histology applications.

For further information contact the project leader Prof. Audrius Brazdeikis

Clinical research

L. Johnson, Q.A. Pankhurst, A. Purushotham, A. Brazdeikis, and M. Douek, “Magnetic Sentinel Lymph Node Detection for Breast Cancer,” Cancer Research 70 (24), P1-01-23 (2010).
T. Joshi, Q. Pankhurst, S. Hattersley, A. Brazdeikis, M. Hall-Craggs, E. De Vita, A. Bainbridge, R. Sainsbury, A. Sharma and M. Douek, “Magnetic nanoparticles for detecting cancer spread”, Breast Cancer Research and Treatment, 106, pp. S129 (2007).
T. Joshi, Q. Pankhurst, S. Hattersley, A. Brazdeikis, M. Hall-Craggs, E. De Vita, A. Bainbridge, R. Sainsbury, A. Sharma and M. Douek, “Magnetic nanoparticles for detecting sentinel lymph nodes”, European Journal of Surgical Oncology (EJSO), 33 (9), 1135 (2007).

Media mentions

A hand-held magnetic probe made by physicists could find a place in cancer surgery, Top down bottom up: Opposites attract, Nature Nanotechnology 2, 15 (2007)
Probe Developed To Detect Spread Of Breast Cancer, Science Daily, March 7, 2007
Probe to detect spread of breast cancer co-developed by UH scientist, UH News Release, March 5, 2007
UH-UK Biomedical Researchers Design Ultrasensitive Magnetic Probe to Detect Spread of Breast Cancer, UH NSM News, February 13, 2007

Technology transfer activities

2009 – The SentiMag technology licensed to Endomagnetics Ltd.

Our Collaborators
Our external faculty collaborators: Michael Douek, MD (Department of Research Oncology, Kings College London, UK). Partnerships in pursuing novel biomedical solutions: Endomagnetics Ltd. (London, UK)

Project Status
This project is currently active

Nanoparticle Imaging & Theranostics

Audrius Brazdeikis — Mon, 02 May 2011 17:34:24 +0000

A distinct advantage of choosing magnetic nanoparticles is the transparency of tissue to magnetic fields permitting detection, localization, manipulation and thermal activation of nanoparticles within the body. There are many potential diagnostic and therapy applications such as study of cell biophysics, novel bio-assays and bio-forensics, drug delivery, detection and removal of bio-toxins, and advanced theranostics.

Our research focuses on development of novel nanoparticle sensing and imaging technologies based on SQUID sensors for detecting early signs of acute graft rejection in organ transplantation, myocardial tissue injury, and to characterize vulnerable plaque. We use COMSOL modeling to design and optimize practical implementations of new high magnetic gradient devices for more precise targeting of magnetic nanocarriers in human and animal models.

A custom-built scanning SQUID system is employed for magnetic measurements in an unshielded laboratory environment for imaging the minute magnetic field perturbations associated with the biocompatible nanoparticles.

Unlike other heating sources, e.g. optical fibers, radiofrequency and microwave probes, and antennas, various nanoparticles show remarkable heating effects by converting the electromagnetic energy into heat when exposed to an external electrical or magnetic field. When exposed to alternating magnetic fields magnetic nanoparticles will heat up and induce cytotoxic hyperthermia in a tumor which can be a useful treatment option for destruction of many malignancies, both primary and metastatic lesions, as well as solid cancers.

Our research focuses on characterization of nanoparticles for magnetic hyperthermia applications and development of techniques to improve the therapeutic modality on a cellular level.

Publications

Dana E Gheorghe, Lili Cui, Christof Karmonik, Audrius Brazdeikis, Jose M Penaloza, Rebekah A Drezek, and Malavosklish Bikram, “Gold-Silver Alloy Nanoshells: A New Candidate for Nanotherapeutics and Diagnostics”, Nanoscale Research Letters 2011 Oct 13;6:554. (Electronic version online)
S. Sarangi, I. C. Tan, and A. Brazdeikis, “Brownian relaxation of interacting magnetic particles in a colloid subjected to a pulsatile magnetic field”, Journal of Nanoscience and Nanotechnology, 11 (5), pp. 4136-4141 (2011).
S. Sarangi, I. C. Tan, and A. Brazdeikis, “Magnetic Imaging Method Based on Magnetic Relaxation of Magnetic Nanoparticles”, Journal of Applied Physics, 105 (9), pp. 093926-5 (2009).
Gyu Leem, Subhasis Sarangi, Shishan Zhang, Irene Rusakova, Audrius Brazdeikis, Dmitri Litvinov, and T. Randall Lee, “Surfactant-Controlled Size and Shape Evolution of Magnetic Nanoparticles”, Journal of Crystal Growth and Design, 9 (1), pp 32–34 (2009).
I.-C Tan and A. Brazdeikis, “Novel Biomagnetic Sensing Technique for Characterization of Inflammatory Tissues” IEEE Transactions on Magnetics, 46 (6), 2409-2411, (2007).

Our Collaborators
Our internal faculty collaborators: T. Randall Lee, Ph.D (UH Chemistry) and Malavosklish (Liz) Bikram, Ph.D. (UH Pharmacological and Pharmaceutical Sciences). Our external faculty collaborators: Paolo Decuzzi, Ph.D (The Methodist Hospital Research Institute) and Lon J. Wilson Ph.D (Rice University).

Project Status
This project is currently active

Prenatal Diagnostics & Neuroassesment

Audrius Brazdeikis — Thu, 28 Apr 2011 21:00:26 +0000

There is a strong demand to develop new diagnostics tools for accurate assessment of the neurophysiological development of the fetus as more pre- and full-term babies survive with various disorders. In fact, the rate of premature birth has increased by more than 30 percent in two decades, and now accounts for more than 500,000 babies a year who are born at least three weeks early. Increased sophistication of neonatal intense care units has lead to the improved survival rates of these younger and sicker preterm babies, however, the cost to society to care for these babies is already reaching $26 billion each year, according to the National Institute of Medicine.

Important parameter for the diagnostic use is the basal fetal heart rate (FHR) disclosing the presence or absence of accelerations and decelerations and baseline variability associated with the development of Autonomic Nervous System (ANS). Present technology is not adequate to consistently evaluate changes in FHRV through gestation

In the last few years, advantages and medical relevance of the fetal magnetocardiography (fetal-MCG) have been shown. Fetal-MCG is the measurement of magnetic fields (a few pT in amplitude) emitted by the fetal heart from small currents by electrically active cells of the heart muscle. The measurements are taken by SQUID sensors in one or several spatial locations above the pregnant abdomen and provide information which is complementary to that provided by direct, contact electro-physiological measurements.

Typically, the quality of fetal-magnetocardiographic recording is significantly higher than that of the corresponding electric or Doppler recordings. Fetal biomagnetic signals are unaffected by poor electrical conductivity of the vernix caseosa, a waxy substance which forms on the fetal skin at about 25 weeks’ gestation and impedes the transmission of fetal bioelectric signals.

http://www.youtube.com/watch?v=gVDbatiXRyE

The overall goal of this project is to develop a novel clinical diagnostic method based on superconducting SQUID device technology to identify a fetus at risk for neurological injury or death, so that timely and appropriate intervention can be carried out before the underlying condition causes irreversible damage.

National TV news broadcasts on fetal SQUID diagnostics developed by our group

“New device helps detect problems in preemies sooner”, ABC 27 WKOW (Madison, WI), April 19, 2010
“Fetal Heart Sensor” WSOC-TV (Charlotte, NC), April 27, 2010
“Oh Baby! Checking Fetal Health Earlier”, FOX 4 TV (Florida) June 2, 2010
“Detecting Heart Problems Before Birth” WTAJ News (Central PA), May 27, 2010
“There’s a new way to monitor the heart of an unborn baby”, WFRV News (Green Bay, WI), May 2, 2010

Publications

Audrius Brazdeikis and Nikhil S. Padhye, “Biomagnetic Measurements for Assessment of Fetal Neuromaturation and Well-Being” in “New Developments in Biomedical Engineering”, Domenico Campolo (Ed.), ISBN: 978-953-7619-57-2, INTECH 2010, pp. 425-446.
Nikhil S. Padhye, Member, Amber L. Williams, Asif Z. Khattak, Robert E. Lasky, M. Terese Verklan, and Audrius Brazdeikis, “Heart Rate Variability as a Measure of Neonatal Pain Response and Fetal Autonomic Development”, Proceedings of the 4th International Conference on Computer Applications in Electrical Engineering Recent Advances (CERA 2010).
Nikhil S. Padhye, M. Terese Verklan, Audrius Brazdeikis, Amber L. Williams, Asif Z. Khattak, and Robert E. Lasky, “A Comparison of Fetal and Neonatal Heart Rate Variability at Similar Post-Menstrual Ages”, IEEE Engineering in Medicine and Biology Society Proceedings, EMBS, 30, pp. 2801-2804 (2008).
A. Brazdeikis, G. J. Vázquez-Flores, I.C. Tan, N.S. Padhye, and M.T. Verklan, “Acquisition of Fetal Magnetocardiograms in an Unshielded Hospital Setting”, IEEE Transactions on Applied Superconductivity, 17 (2), 823-826, (2007).
M.T. Verklan, N.S. Padhye, and A. Brazdeikis, “Analysis of Fetal Heart Rate Variability Obtained by Magnetocardiography” The Journal of Perinatal and Neonatal Nursing, 20, 343-347, (2006).
N.S. Padhye, A. Brazdeikis and M.T. Verklan, “Complexity Changes in Fetal Heart Rate Variability”, IEEE Engineering in Medicine and Biology Society Proceedings, EMBS, 28, pp. 461-463, (2006).
A. Brazdeikis, C.W. Chu, P. Cherukuri, S. Litovsky, M. Naghavi, “Changes in magnetocardiogram patterns of infarcted-reperfused myocardium after injection of superparamagnetic contrast media,” Neurology and Clinical Neurophysiology, 16, 1-4, (2004).
A. Brazdeikis, A.K. Guzeldere, N.S. Padhye, and M.T. Verklan, “Evaluation of the performance of a QRS detector for extracting the heart interbeat RR time series from fetal magnetocardiography recordings”, IEEE Engineering in Medicine and Biology Society Proceedings, EMBS, 26, pp. 369-372, (2004).
N.S. Padhye, A. Brazdeikis, and M.T. Verklan, “Monitoring fetal development with magnetocardiography”, IEEE Engineering in Medicine and Biology Society Proceedings, EMBS, 26, pp. 3609-3610, (2004).

Our Collaborators

Research was conducted both at TCSUH and at several location of the Memorial Hermann Hospital. Our external faculty collaborators: Terese M. Verklan, Ph.D (University of Texas Health Science Center), Nikhil S. Padhye, Ph.D (University of Texas Health Science Center).

Project Status
This project is currently active

Biomagnetic Imaging and Nanomedicine Laboratory

Audrius Brazdeikis — Wed, 27 Apr 2011 19:57:34 +0000

The Biomagnetic Imaging and Nanomedicine Laboratory is headed by Professor Audrius Brazdeikis.

Mission: the main focus of this Laboratory is to develop and investigate the use of Superconducting QUantum Interference Device (SQUID)-based sensors for new emerging biomedical imaging applications and diagnostic applications.

Instrumentation: Laboratory is equipped with state-of-the-art SQUID instrumentation (HTS and LTS) for single- and multi-channel acquisition, low temperature measurement and characterization, data acquisition, computer-controlled sub-mm spatial resolution X-Y translation stages, general laboratory instruments (function/arbitrary waveform generators, dynamic signal analyzers, lock-in-amplifiers, digital oscilloscopes, etc), stereomicroscopes, vaccuum systems, Helmholtz coils for calibrating, balancing and maintaining LTS and HTS SQUID systems. Laboratory personnel also has access to shared TcSUH facilities such as XRD, SEM, TEM and the SQUID magnetometer – Magnetic Property Measurement System (Quantum Design) for magnetic characterization of nanoparticles.

Laboratory is also equipped with 3 workstations complete with licenses for Matlab®, Labview®, Visual Studio®.NET and a computer-aided design (CAD) software, Solid Works® for mechanical design.

Active projects: the laboratory is currently engaged in various projects related to prenatal (fetal) diagnostics, nanoparticle imaging, and sensors for lymph node staging.

Magnetocardiography

Audrius Brazdeikis — Sat, 23 Apr 2011 20:00:26 +0000

Non-invasive diagnostic methods that are sensitive but also specific enough to identify subjects with very early stages of heart disease would be an important addition to the technologies currently available. Magnetocardiography (MCG) is a very sensitive method for detecting cardiac bioelectrical activity non-invasively by an array of super-sensitive magnetic field sensors (superconductor sensors). It is one of the most promising applications of superconducting technology, although its clinical use have been somewhat limited, partly due to the lack of reliable hardware and inconclusive data interpretation, and partly due to the absence of clinically validated analysis procedures.

TCSUH Magnetocardiography Project

Our major goal was aimed at evaluation of the potential benefits of magnetic imaging of the heart and to provide the basis for understanding the factors that govern the spatio-temporal resolution of Superconducting Quantum Interference Device – SQUID images in biomagnetic studies on adult cardiac ischemia. The demonstration that this technology can be used to address an important clinical problem will provide the impetus for using related technologies to develop novel biomedical sensors and non-invasive diagnostic methods, spur development of the research infrastructure needed to support new or emerging related areas of superconducting technology.

Our Approach

At Biomagnetic Imaging Laboratory we focused on non-invasive mapping of weak biomagnetic signals around the thorax in unshielded hospital environment. We investigated various factors that determine sufficient signal-to-noise ratio and spatio-temporal signal resolution for practical clinical applications. We were engaged in exploring, developing and implementing innovative physical and mathematical formulations, and algorithms for analysis of clinical magnetocardiogram data, based on patient data recorded both at rest and under conditions of controlled cardiac stress (stress magnetocardiography), and validated by comparison with a “gold standard” for functional cardiac pathology such as SPECT (Single Photon Emission Computed Tomography) to assess MCG sensitivity and specificity.

Our multidisciplinary research was aimed at developing clinically viable diagnostic methods, based on fast detection, acquisition, processing and visualization of cardiac magnetic signal, primarily focusing on how to process and map MCG data into clinically useful representations, and assessing the extent, and severity of coronary heart disease both qualitatively, and quantitatively.

Our Collaborators

Research was conducted both at TCSUH and at a dedicated research facility located in the Methodist Hospital. Our external faculty collaborators: Addison A. Taylor, M.D., Ph.D (Baylor College of Medicine).

Project Status
This project is currently inactive

Hello world!

Audrius Brazdeikis — Fri, 22 Apr 2011 21:54:24 +0000

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