Selected Publications
Improved PHIP Polarization using a Low Noise Precision Voltage Controlled Current Source
Jose Agraz, Alexander Grunfeld, Karl Cunningham, Shawn Wagner, Debiao Li
Existing para-hydrogen induced polarization (PHIP) instrumentation relies on magnetic fields to hyperpolarize substances. These hyperpolarized substances have enhanced magnetic resonance imaging (MRI) signals over 10,000 fold, allowing for MRI at the molecular level. Required magnetic fields are generated by energizing a solenoid coil with current produced by a voltage controlled voltage source (VCVS), also known as a power supply. A VCVS lacks the current regulation necessary to keep magnetic field fluctuations to a minimum, which results in low PHIP polarization. A voltage controlled current source (VCCS) is an electric circuit that generates a steady flow of electrons proportional to an input voltage. A low noise VCCS provides the solenoid current flow regulation necessary to generate a stable static magnetic field (B o ). We discuss the design and implementation of a low noise, high stability, VCCS for magnetic field generation with minimum variations. We show that a precision, low noise, voltage reference driving a metal oxide semiconductor field effect transistor (MOSFET) based current sink, results in the current flow control necessary for generating a low noise and high stability B o . In addition, this work: (1) compares current stability for ideal VCVS and VCCS models using transfer functions (TF), (2) develops our VCCS design’s TF, (3) measures our VCCS design’s thermal & 1/f noise, and (4) measures and compares hydroxyethyl-propionate (HEP) polarization obtained using a VCVS and our VCCS. The hyperpolarization of HEP was done using a PHIP instrument developed in our lab. Using our VCCS design, HEP polarization magnitude data show a statistically significant increase in polarization over using a VCVS. Circuit schematic, bill of materials, board layout, TF derivation, and Matlab simulations code are included as supplemental files.
VCCS Diagram & resulting Hyperpolarization
PHIP Instrumentation Pinch Valve System for Sample Delivery, Process and Collection
Jose Agraz, Alexander Grunfeld, Karl Cunningham, Shawn Wagner, Debiao Li
Molecular imaging enables the in vivo visualization of cellular function. The hyperpolarization of substances used as endogenous imaging contrast agents allows for imaging at the molecular level. Hyperpolarization modalities such as the para-hydrogen induced polarization (PHIP) method, use sample management to capture, process and deliver samples. Current PHIP instrumentation lack a sterile sample management system to process samples. We discuss the development of a sterile pinch valve design for the collection, reaction and delivery of samples in PHIP instrumentation and show how the use of disposable hosing results in sterile samples. In addition this work shows; 1) Increased hose wall thickness at the pinch valve and solenoid pulse allows the design to perform at PHIP method pressures, 2) Testing of the system’s sample delivery, process and collection by hyperpolarizing hydroxyethyl-propionate (HEP). This work results in sterile samples, with repeatable reaction kinetics, while reducing pinch valve wear and tear and minimum stray magnetic fields and solenoid overheating.
Valve System Diagram
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LabVIEW-based control software for para-hydrogen induced polarization instrumentation
Jose Agraz, Alexander Grunfeld, Karl Cunningham, Shawn Wagner, Debiao Li
The elucidation of cell metabolic mechanisms is the modern underpinning of the diagnosis, treatment, and in some cases the prevention of disease. ParaHydrogen induced polarization (PHIP) enhances magnetic resonance imaging (MRI) signals over 10 000 fold, allowing for the MRI of cell metabolic mechanisms. This signal enhancement is the result of hyperpolarizing endogenous substances used as contrast agents during imaging. PHIP instrumentation hyperpolarizes Carbon-13 (13C) based substances using a process requiring control of a number of factors: chemical reaction timing, gas flow, monitoring of a static magnetic field (Bo), radio frequency (RF) irradiation timing, reaction temperature, and gas pressures. Current PHIP instruments manually control the hyperpolarization process resulting in the lack of the precise control of factors listed above, resulting in non-reproducible results. We discuss the design and implementation of a LabVIEW based computer program that automatically and precisely controls the delivery and manipulation of gases and samples, monitoring gas pressures, environmental temperature, and RF sample irradiation. We show that the automated control over the hyperpolarization process results in the hyperpolarization of hydroxyethylpropionate. The implementation of this software provides the fast prototyping of PHIP instrumentation for the evaluation of a myriad of 13 C based endogenous contrast agents used in molecular imaging
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LabView Front Panel
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Quantitative Characterization of a Catalyzed PHIP Reaction
Shawn Wagner, Jose Agraz, Debiao Li
Hyperpolarization by field cycling and RF transfer utilizing parahydrogen requires a fast addition of hydrogen to preserve the spin alignment of the parahydrogen.1 To effectively utilize PHIP to produce the highest hyperpolarization, characterization of the reaction kinetics is required. The purpose of this research is to demonstrate how to systematically characterize the reaction kinetics to calibrate and evaluate instrument performance using a common PHIP standard, 2-hydroxyethyl acrylate (HEA). The exact timing for a 100% complete reaction can be predicted by determining the rate constants for temperature, hydrogen pressure, HEA concentration, and catalyst concentration. The objective is to define conditions for our instrumentation which will allow us to complete the reaction quicker than previously published data by other researchers with the end goal to be able to increase the efficiency of PHIP methods
Hyperpolarization Effect
Affordable Hyperpolarization by Parahydrogen Induced Polarization
Shawn Wagner, Jose Agraz, Debiao Li
Knowledge of the longitudinal relaxation time (T1) of nanoparticles is useful for developing long lived nuclear magnetic resonance (NMR) signal for molecular targeting. Currently, dynamic nuclear polarization (DNP) has been employed to increase the NMR signal by 30,000-100,000 times the normal signal. This has been useful for obtaining metabolic data for the utilization of 13C-pyruvate in cell cultures and in vivo animal models.1,2 However, the T1 of pyruvate is about 35 seconds which limits this molecule from being an effective tracking agent or molecular marker. Other ½ spin nuclei like yttrium (89Y) and silicon (29Si) can have much longer T1 values. Recent literature has suggested that the T1 value in silicon particles is size dependent because the dominate relaxation is a result of spin diffusion from the surface to the core.3,4 The hypothesis was that oxygen serves as a relaxation source for the surface silicon nuclei and dipole–dipole coupling between 29-silicon drives relaxation into the core of the particles by spin diffusion. In this work, we measured the T1 values of silicon nanoparticles of various sizes to verify whether the hypothesis is true
Carbon Weak Bond
Polarization Loss from Magnetic Field Noise
Shawn Wagner, Jose Agraz, Debiao Li
Hyperpolarization by RF irradiation spin transfer utilizing parahydrogen requires low magnetic fields. These fields have been created with solenoids using current to determine the field strength. This abstract is intended to show how noise in the current results in magnet field noise, leading to sporadic loss of polarization in echo sequences. We will demonstrate how coherent and random noise results in variations in the polarization refocusing. The loss in temporal refocusing is a crucial issue in the reliability of RF irradiation spin transfer PHIP hyperpolarization, since the last part of such sequences contains an echo period in the transverse plane.
Polarized Molecule
Finger Force Sensor Instrumentation Design
Jose Agraz, Alexander Grunfeld, Daniel Muse, Robert Pozos
Carpal tunnel syndrome (CTS) refers to a class of injuries characterized by compression of the median nerve in the carpal tunnel. CTS injuries cause pain, weakness, and numbness in the hands and are common among video gamers and workers that maintain their wrists in ergonomically unfavorable positions. Current CTS qualification methods are well documented, whereas the condition of the hand muscles is often overlooked. At present, there is no simple, inexpensive, and portable instrument that quantifies finger force values pre and
post clinical intervention. Our design measures finger force using force sensors placed on the surface of individual keys on an ergonomically designed keyboard, which allows finger force measurements for all five fingers, individually or as a group. In this work we; 1) Show a clear difference in finger force between an uninjured and injured hand and further correlated it to forearm electromyography (EMG), and 2) Use the system in a pilot study to evaluate the apparatus usefulness through the testing of the significance of finger force before and after fatigue. Finger force signals from the subjects' index finger were collected and force peaks extracted from the raw data. The resulting data was analyzed using the variance (ANOVA) test. Although, there was no statistical significance between the finger force applied, the system proved accurate, rugged, and flexible to accommodate fine tuning changes on hardware and software, with a minimum of dead time during the pilot study. Thus, this tool offers a great platform for further finger force studies.
Finger Force Instrument
LabVIEW based control software for finger force sensor instrumentation design
Jose Agraz, Robert Pozos
This report describes National Instruments (NI) LabVIEW software for the control of finger force instrumentation for the quantification of Repetitive Stress Injury (RSI), Carpal Tunnel Syndrome (CTS), or other applications requiring automated data acquisition of applied finger force using resistive type force sensors. The quantification of finger force requires the precise data collection from resistive force sensors for all five fingers and keyboard key switches. This abstract describes how a LabVIEW based software application allows for the precise control over data force collection for all fingers and key switches, while acquiring human subject's study information, isometric & datalogging finger force, and providing the user with visual force measurements feedback. The implementation of this software provides a fast prototyping for evaluating finger force instrumentation. While no other LabVIEW based software application is available to date for this finger force data collection, our system proved rugged and flexible enough to accommodate fine tuning changes on hardware and software, with a minimum of dead time during usage.
Finger Force Software
Effects of polarization rotation in the detection and tracking of orbiting objects using LabVIEW
Jose Agraz, Alexander Grunfeld, Daniel Muse, F Allston, Robert Pozos
The detection and tracking of orbiting space debris is vital for spacecraft safety and satellite longevity. The United States Air Force Space Surveillance System (AFSSS) uses a continuous wave (CW), multiplestatic site radar system designed to detect, catalog, & track objects orbiting over the continental United States. Object position data collected by the AFSSS stations is categorized by the operation center and sent to the North American Aerospace Defense Command (NORAD) to issue warnings to the aerospace community. The AFSSS was designed using cost effective linear polarization for their transmitter's (vertical polarized) and receiver's antennae (horizontal polarized). When the vertically transmitted polarized radio frequency (RF) fence is crossed by an orbiting object, the object rotates the RF polarization, resulting in a RF horizontally polarized echo. However, charged particles in the ionosphere often randomly rotate the RF polarization as RF travels through the atmosphere. The AFSSS receivers' antennae lack the equipment to detect vertically polarized RF echoes, which leads to a substantial loss of RF echo signal and degradation in AFSSS performance. A LabVIEW-based Monitor Receiver System (MRS) was designed to receive vertical & horizontal polarized signals of a selected target. By comparing signals received using the MRS vertically & horizontally polarized antennae, we show that there is significant signal power transfer from horizontal polarized to vertical polarized echoes, as a result of signal polarization rotation. In addition, this work: 1) Compares control of antennae direction models using transfer functions (TF), 2) Develops a proportional integral derivative (PID) controller TF for improved antennae positioning, 3) Tracks John Glenn 1998 space shuttle trip. This makes the MRS a viable tool for evaluating AFSSS performance and future modifications to increase detection and tracking of orbiting objects.
Detecting John Glenn
in space
Delta-Shaped Piezoelectric Ultrasonic Motor for Two-Dimensional Positioning
Seung-Ho Park, Jose Agraz, Safakcan Tuncdemir, Young-Deog Kim, Richard E. Eitel, Amanda Baker, Clive A. Randall and Kenji Uchino
By fabricating on from lambda-shaped motors, bimorph delta-shaped motors have been developed and tested. A delta motor consists of two piezoelectric layers (bimorph structure) with four input electrodes and one common ground electrode – separated by an inactive bar that aids dimensional control in the sintering process. Two driving sources with a 90° phase difference were used for the x-, z-, and diagonal-axis direction driving. The design of the motor was modified and optimized by changing the relative dimensions and angle of the motor with the aid of ATILA finite element method (FEM) software. The optimum design with a small bandwidth between resonance modes, which provides the largest elliptical displacement, was fabricated using thick films. The fabricated motor size was below 10 mm2 with several hundreds of nano meter motion at the tip. The speed of revolution, torque and efficiency in the two-dimensional space were measured.
PZT Motor