Spectral characterization of flash and high flux x-ray radiographic sources with a magnetic Compton spectrometer.

In this work, we present a new analysis method applied to revitalize permanent magnet Compton spectrometers used to measure photon energy spectra in the MeV range. The inversion of the measured electron distribution to determine the original photon distribution is achieved via a method of consistent coupled radiation transport and magnetic field mapping of the input photon spectra to the measured electron distribution. The method of linear least squares was used to perform the unfolding of the electron distribution to the initial photon spectra, without any assumptions made regarding the electron distribution. We present an application of this method to data from a nominal 19.4 MeV flash radiographic source (the first axis of the Dual Axis Radiographic Hydro-Test Facility) capable of generating 500 R @ 1 m in ∼60 ns and a medical therapy source (a Scanditronix M22, Microtron) capable of variable energies with nominal endpoints of 6, 10, 15, and 20 MeV and an output of ∼1000-2000 R/min @ 1 m. The results provide agreement between the modeled and unfolded experimentally measured photon spectra as quantified by statistical tests, from 1.5 to 20 MeV. Experimental results are presented as well as a discussion of the novel MCNP6-based simulations and methods for reconstruction of the spectra.

Calibration of two compact permanent magnet spectrometers for high current electron linear induction accelerators.

In this work, two compact, permanent magnet, electron spectrometers have been built to measure the electron beam energy at the Dual Axis Radiographic Hydrodynamic Test facility. Using H- and OH- anions, the spectrometers were calibrated at the Special Technologies Laboratory in Santa Barbara, California (USA). The spectrometers were mounted on a custom drift tube that allows the magnet assemblies to be translated, which increases the path length of the electrons traveling through the magnetic field and therefore increases the upper bound of the measurable electron kinetic energy. The measurable range of electron kinetic energies is between 2.8 MeV-4.1 MeV for the first spectrometer and 14.1 MeV-21.1 MeV for the second spectrometer, with an overall measurement uncertainty of 0.32%.

Detection and differentiation of norovirus genogroups I and II from clinical stool specimens using real-time PCR.

A real-time RT-PCR assay was designed to detect and differentiate norovirus genogroups I (GI) and II (GII), with primers and probes targeting the nonstructural polyprotein gene. Stool samples (n = 100) submitted for routine testing by the BioFire FilmArray® GI panel were also tested by the norovirus GI/GII real-time PCR assays. When compared to the FilmArray GI panel, the norovirus real-time PCR assay demonstrated a sensitivity of 77.5% (62/80) and specificity of 95% (19/20). Specimens yielding discordant results (n = 19) were tested at two outside laboratories for adjudication. Following discordant resolution, the adjusted sensitivity and specificity of the norovirus real-time PCR assays were 96.9% (63/65) and 100% (35/35), respectively. These results suggest that the real-time PCR assays are able to accurately detect and differentiate norovirus GI/GII from clinical stool specimens. Furthermore, our report highlights a potential issue with the specificity of the BioFire FilmArray® norovirus assay, which warrants additional investigation.

Comparison of polystyrene scintillator fiber array and monolithic polystyrene for neutron imaging and radiography.

The neutron imaging diagnostic at the National Ignition Facility has been operating since 2011 generating neutron images of deuterium-tritium (DT) implosions at peak compression. The current design features a scintillating fiber array, which allows for high imaging resolution to discern small-scale structure within the implosion. In recent years, it has become clear that additional neutron imaging systems need to be constructed in order to provide 3D reconstructions of the DT source and these additional views need to be on a shorter line of sight. As a result, there has been increased effort to identify new image collection techniques that improve upon imaging resolution for these next generation neutron imaging systems, such as monolithic deuterated scintillators. This work details measurements performed at the Weapons Neutron Research Facility at Los Alamos National Laboratory that compares the radiographic abilities of the fiber scintillator with a monolithic scintillator, which may be featured in a future short line of sight neutron imaging systems.

Comparative evaluation of three commercial systems for detection of high-risk human papillomavirus in cervical and vaginal ThinPrep PreservCyt samples and correlation with biopsy results.

Genital human papillomavirus (HPV) is the etiologic agent of more than 99% of all cervical cancers worldwide, with 14 genotypes being considered oncogenic or "high risk" because of their association with severe dysplasia and cervical carcinoma. Among these 14 high-risk types, HPV-16 and -18 account for approximately 70% of cervical cancers. The aim of this study was to evaluate three FDA-approved HPV nucleic acid-based tests for the ability to predict high-grade cervical intraepithelial neoplasias (CIN2 or worse) in corresponding tissue biopsy specimens. Residual specimens (total n = 793, cervical n = 743, vaginal n = 50) collected in ThinPrep PreservCyt medium with a cytologic result of ≥ atypical squamous cells of undetermined significance were tested by the Hybrid Capture 2 (HC2) assay (Qiagen, Gaithersburg, MD), the cobas HPV test (Roche Diagnostics, Indianapolis, IN), and the APTIMA HPV assay (Hologic, San Diego, CA). Genotyping for HPV-16 and HPV-18 was simultaneously performed by the cobas HPV test. Results were compared to cervical or vaginal biopsy findings, when they were available (n = 350). Among the 350 patients with corresponding biopsy results, 81 (23.1%) showed ≥ CIN2 by histopathology. The ≥ CIN2 detection sensitivity was 91.4% by the cobas and APTIMA assays and 97.5% by HC2 assay. The specificities of the cobas, APTIMA, and HC2 assays were 31.2, 42.0, and 27.1%, respectively. When considering only positive HPV-16 and/or HPV-18 genotype results, the cobas test showed a sensitivity and a specificity of 51.9 and 86.6%, respectively. While the HC2, cobas, and APTIMA assays showed similar sensitivities for the detection of ≥ CIN2 lesions, the specificities of the three tests varied, with the greatest specificity (86.6%) observed when the HPV-16 and/or HPV-18 genotypes were detected.

Polarization enhancement technique for nuclear quadrupole resonance detection.

We demonstrate a dramatic increase in the signal-to-noise ratio (SNR) of a nuclear quadrupole resonance (NQR) signal by using a polarization enhancement technique. By first applying a static magnetic field to pre-polarize one spin subsystem of a material, and then allowing that net polarization to be transferred to the quadrupole subsystem, we increased the SNR of a sample of ammonium nitrate by one-order of magnitude.

On a ghost artefact in ultra low field magnetic resonance relaxation imaging.

Nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) are widely used techniques across numerous disciplines. While typically implemented at fields >1T, there has been continuous interest in the methods at much lower fields for reasons of cost, material contrast, or application. There have been numerous demonstrations of MR at much lower fields (from 1µT to 1mT), the so-called ultra-low field (ULF) regime. Approaches to ULF MR have included superconducting quantum interference device (SQUID) sensor technology for ultra-sensitive detection and the use of pulsed pre-polarizing fields to enhance the signal strength. There are many advantages to working in the ULF regime. However, due to the low strength of the measurement field, acquisition of MRI at ULF is more susceptible to ambient fields that cause image distortions. Imaging artifacts can be caused by transients associated with non-ideal field switching and from remnant fields in magnetic shielding, among other causes. In this paper, we introduce a general theoretical framework that describes effects of non-ideal measurement field inversion/rotation due to presence of these transient fields. We illustrate imaging artifacts via simulated and experimental examples.

Inhibition controls for qualitative real-time PCR assays: are they necessary for all specimen matrices?

A retrospective analysis of 386,706 specimens representing a variety of matrix types used in qualitative real-time PCR assays determined the overall inhibition rate to be 0.87% when the inhibition control was added preextraction to 5,613 specimens and 0.01% when the inhibition control was added postextraction but preamplification in 381,093 specimens. Inhibition rates of ≤ 1% were found for all specimen matrix types except urine and formalin-fixed, paraffin-embedded tissue.

Comparison of six real-time PCR assays for qualitative detection of cytomegalovirus in clinical specimens.

In this study, we compared the performance of six real-time PCR assays for the qualitative detection of cytomegalovirus (CMV) in clinical samples other than plasma. Two hundred specimens (respiratory [n = 72], urine [n = 67], cerebrospinal fluid [CSF] [n = 25], tissue [n = 18], amniotic fluid [n = 10], and bone marrow [n = 8]) submitted for routine testing by CMV real-time PCR analyte-specific reagents (ASR) (Roche Diagnostics, Indianapolis, IN) were also tested by a laboratory-developed test (LDT) and 4 commercially available PCR assays: EraGen Multicode (Luminex, Austin, TX), Focus Simplexa (Focus Diagnostics, Cypress, CA), Elitech MGB Alert CMV (Fisher Scientific, Hanover Park, IL), and Abbott CMV (Abbott Park, IL). Nucleic acid was extracted using the MagNA Pure system (Roche Diagnostics) and subsequently tested by each PCR method. Results were analyzed by comparing each assay to a "consensus result," which was defined as the result obtained from at least 4 of the 6 assays. In addition to the prospective samples, 13 lower respiratory samples with known positive results by CMV shell vial were tested by each PCR method. Following testing of the 200 prospective specimens, the Abbott, Elitech, EraGen, and Focus PCR assays demonstrated a sensitivity of 100% (46/46), while the Roche analyte-specific reagents (ASR) and LDT showed sensitivities of 89% (41/46) and 98% (45/46), respectively. Percent specificities ranged from 97% (149/154) by Elitech to 100% (154/154) by the LDT. Among the 13 shell vial-positive lower respiratory samples, the percent sensitivities ranged from 69% (9/13) by Elitech to 92% (12/13) by the LDT. The Abbott, EraGen, Elitech, Focus, and LDT PCR assays performed similarly (κ ≥ 0.89) for the detection of CMV in clinical specimens and demonstrated increased sensitivity compared to the Roche ASR.

Non-cryogenic anatomical imaging in ultra-low field regime: hand MRI demonstration.

Ultra-low field (ULF) MRI with a pulsed prepolarization is a promising method with potential for applications where conventional high-, mid-, and low-field medical MRI cannot be used due to cost, weight, or other restrictions. Previously, successful ULF demonstrations of anatomical imaging were made using liquid helium-cooled SQUIDs and conducted inside a magnetically shielded room. The Larmor frequency for these demonstrations was ∼3 kHz. In order to make ULF MRI more accessible, portable, and inexpensive, we have recently developed a non-cryogenic system. To eliminate the requirement for a magnetically shielded room and improve the detection sensitivity, we increased the frequency to 83.6 kHz. While the background noise at these frequencies is greatly reduced, this is still within the ULF regime and most of its advantages such as simplicity in magnetic field generation hardware, and less stringent requirements for uniform fields, remaining. In this paper we demonstrate use of this system to image a human hand with up to 1.5mm resolution. The signal-to-noise ratio was sufficient to reveal anatomical features within a scan time of less than 7 min. This prototype can be scaled up for constructing head and full body scanners, and work is in progress toward demonstration of head imaging.

Magnetic Resonance Relaxometry at Low and Ultra low Fields.

Nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) are ubiquitous tools in science and medicine. NMR provides powerful probes of local and macromolecular chemical structure and dynamics. Recently it has become possible and practical to perform MR at very low fields (from 1 µT to 1 mT), the so-called ultra-low field (ULF) regime. Pulsed pre-polarizing fields greatly enhance the signal strength and allow flexibility in signal acquisition sequences. Improvements in SQUID sensor technology allow ultra-sensitive detection in a pulsed field environment.In this regime the proton Larmor frequencies (1 Hz - 100 kHz) of ULF MR overlap (on a time scale of 10 µs to 100 ms) with "slow" molecular dynamic processes such as diffusion, intra-molecular motion, chemical reactions, and biological processes such as protein folding, catalysis and ligand binding. The frequency dependence of relaxation at ultra-low fields may provide a probe for biomolecular dynamics on the millisecond timescale (protein folding and aggregation, conformational motions of enzymes, binding and structural fluctuations of coupled domains in allosteric mechanisms) relevant to host-pathogen interactions, biofuels, and biomediation. Also this resonance-enhanced coupling at ULF can greatly enhance contrast in medical applications of ULF-MRI resulting in better diagnostic techniques.We have developed a number of instruments and techniques to study relaxation vs. frequency at the ULF regime. Details of the techniques and results are presented.Ultra-low field methods are already being applied at LANL in brain imaging, and detection of liquid explosives at airports. However, the potential power of ultra-low field MR remains to be fully exploited.

MRI with an atomic magnetometer suitable for practical imaging applications.

Conventionally implemented MRI is performed in a strong magnetic field, typically >1T. The high fields, however, can lead to many limitations. To overcome these limitations, ultra-low field (ULF) [or microtesla] MRI systems have been proposed and implemented. To-date such systems rely on low-Tc Superconducting Quantum Interference Devices (SQUIDs) leading to the requirement of cryogens. In this letter, we report ULF-MRI obtained with a non-cryogenic atomic magnetometer. This demonstration creates opportunities for developing inexpensive and widely applicable MRI scanners.

Detection of 3He spins with ultra-low field nuclear magnetic resonance employing SQUIDs for application to a neutron electric dipole moment experiment.

The precession of (3)He spins is detected with ultra-low field NMR. The absolute strength of the NMR signal is accurately measured and agrees closely with theoretical calculations. The sensitivity is analyzed for applications to a neutron electric dipole moment (nEDM) fundamental symmetry experiment under development.

Toward direct neural current imaging by resonant mechanisms at ultra-low field.

A variety of techniques have been developed to noninvasively image human brain function that are central to research and clinical applications endeavoring to understand how the brain works and to detect pathology (e.g. epilepsy, schizophrenia, etc.). Current methods can be broadly divided into those that rely on hemodynamic responses as indicators of neural activity (e.g. fMRI, optical, and PET) and methods that measure neural activity directly (e.g. MEG and EEG). The approaches all suffer from poor temporal resolution, poor spatial localization, or indirectly measuring neural activity. It has been suggested that the proton spin population will be altered by neural activity resulting in a measurable effect on the NMR signal that can be imaged by MRI methods. We present here the physical basis and experimental evidence for the resonant interaction between magnetic fields such as those arising from neural activity, with the spin population in ultra-low field (microT) NMR experiments. We demonstrate through the use of current phantoms that, in the case of correlated zero-mean current distributions such as those one might expect to result from neural activity, resonant interactions will produce larger changes in the observed NMR signal than dephasing. The observed resonant interactions reported here might one day form the foundation of a new functional neuroimaging modality ultimately capable of simultaneous direct neural activity and brain anatomy tomography.

Real-time PCR in clinical microbiology: applications for routine laboratory testing.

Real-time PCR has revolutionized the way clinical microbiology laboratories diagnose many human microbial infections. This testing method combines PCR chemistry with fluorescent probe detection of amplified product in the same reaction vessel. In general, both PCR and amplified product detection are completed in an hour or less, which is considerably faster than conventional PCR detection methods. Real-time PCR assays provide sensitivity and specificity equivalent to that of conventional PCR combined with Southern blot analysis, and since amplification and detection steps are performed in the same closed vessel, the risk of releasing amplified nucleic acids into the environment is negligible. The combination of excellent sensitivity and specificity, low contamination risk, and speed has made real-time PCR technology an appealing alternative to culture- or immunoassay-based testing methods for diagnosing many infectious diseases. This review focuses on the application of real-time PCR in the clinical microbiology laboratory.

On concomitant gradients in low-field MRI.

Growing interest in magnetic resonance imaging (MRI) at ultra-low magnetic fields (ULF, approximately muT fields) has been motivated by several advantages over its counterparts at higher magnetic fields. These include narrow line widths, the possibility of novel imaging schemes, reduced imaging artifacts from susceptibility variations within a sample, and reduced system cost and complexity. In addition, ULF NMR/MRI with superconducting quantum interference devices is compatible with simultaneous measurements of biomagnetic signals, a capability conventional systems cannot offer. Acquisition of MRI at ULF must, however, account for concomitant gradients that would otherwise result in severe image distortions. In this paper, we introduce the general theoretical framework that describes concomitant gradients, explain why such gradients are more problematic at low field, and present possible approaches to correct for these unavoidable gradients in the context of a non-slice-selective MRI protocol.

Comparison of specimen processing and nucleic acid extraction by the swab extraction tube system versus the MagNA Pure LC system for laboratory diagnosis of herpes simplex virus infections by LightCycler PCR.

A total of 563 specimens (234 dermal and 329 genital swabs) from patients suspected of having herpes simplex virus (HSV) infections were processed using two different extraction methods (the MagNA Pure LC system and the swab extraction tube system [SETS]); HSV DNA was amplified by LightCycler PCR. HSV DNA was detected in 157 of 563 specimens (27.9%) processed by the MagNA Pure LC system and in 179 of 563 specimens (31.8%) processed by SETS (P < 0.0001). There was no specimen processed by the MagNA Pure LC extraction method that was positive only for HSV DNA. Of 157 specimens positive by both methods, HSV DNA copy levels were higher (using cycle crossover points [cycle threshold {C(T)}]) with SETS (mean C(T), 25.9 cycles) than with the MagNA Pure LC system (mean C(T), 32.0 cycles) (P < 0.0001). The time to process 32 samples was longer with the MagNA Pure LC extraction system (90 min) than with SETS (35 min). HSV DNA extraction using SETS is faster, less expensive, and more sensitive than the MagNA Pure LC system and could replace the latter for the laboratory diagnosis of HSV infections using LightCycler PCR.

Neutron-detected tomography of impurity-seeded superfluid helium.

We describe a neutron radiography technique that can be used to map the distribution of 3He impurities in liquid 4He, providing direct and quantitative access to underlying transport processes. Images reflecting finite normal- and superfluid-component 4He velocity fields are presented.

Noise-free magnetoencephalography recordings of brain function.

Perhaps the greatest impediment to acquiring high-quality magnetoencephalography (MEG) recordings is the ubiquitous ambient magnetic field noise. We have designed and built a whole-head MEG system using a helmet-like superconducting imaging surface (SIS) surrounding the array of superconducting quantum interference device (SQUID) magnetometers used to measure the MEG signal. We previously demonstrated that the SIS passively shields the SQUID array from ambient magnetic field noise, independent of frequency, by 25-60 dB depending on sensor location. SQUID 'reference sensors' located on the outside of the SIS helmet measure ambient magnetic fields in very close proximity to the MEG magnetometers while being nearly perfectly shielded from all sources in the brain. The fact that the reference sensors measure no brain signal yet are located in close proximity to the MEG sensors enables very accurate estimation and subtraction of the ambient field noise contribution to the MEG sensors using an adaptive algorithm. We have demonstrated total ambient noise reduction factors in excess of 10(6) (> 120 dB). The residual noise for most MEG SQUID channels is at or near the intrinsic SQUID noise floor, typically 2-3 fT Hz-1/2. We are recording MEG signals with greater signal-to-noise than equivalent EEG measurements.

Simultaneously detected biomagnetic signals and NMR.

We have obtained 1H NMR spectra simultaneously with high temporal resolution biomagnetic signals such as the magnetocardiogram (MCG) and magnetomyogram (MMG). The NMR spectra are acquired at measurement fields of 2-50 microT, with corresponding proton Larmor frequencies of 80-2000 Hz. Our measurements demonstrate a method suitable for MR imaging with concurrent measurement of biomagnetic signals that can provide sub-millisecond temporal resolution. The narrow line widths, reduction in susceptibility noise and enhanced spectral resolution at ultra low fields provide a new and extremely sensitive measurement method that may enable direct imaging of biological currents by detecting the phase or frequency shifts produced by magnetic fields arising from those currents. The results of our simultaneous measurements of NMR with MCG and MMG are compared to results from a current phantom to investigate the exciting potential of direct MRI of bioelectric currents.