Two-dimensional and three-dimensional oxygen mapping by 3He-MRI validation in a lung phantom

The aim of this study was to validate oxygen-sensitive 3He-MRI in noninvasive determination of the regional, two- and three-dimensional distribution of oxygen partial pressure. In a gas-filled elastic silicon ventilation bag used as a lung phantom, oxygen sensitive two- and three-dimensional 3He-MRI measurements were performed at different oxygen concentrations which had been equilibrated in a range of normal and pathologic values. The oxygen partial pressure distribution was determined from 3He-MRI using newly developed software allowing for mapping of oxygen partial pressure. The reference bulk oxygen partial pressure inside the phantom was measured by conventional respiratory gas analysis. In two-dimensional measurements, image-based and gas-analysis results correlated with r=0.98; in three-dimensional measurements the between-methods correlation coefficient was r=0.89. The signal-to-noise ratio of three-dimensional measurements was about half of that of two-dimensional measurements and became critical (below 3) in some data sets. Oxygen-sensitive 3He-MRI allows for noninvasive determination of the two- and three-dimensional distribution of oxygen partial pressure in gas-filled airspaces.

Comparison of (31)P saturation and inversion magnetization transfer in human liver and skeletal muscle using a clinical MR system and surface coils.

(31)P MRS magnetization transfer ((31)P-MT) experiments allow the estimation of exchange rates of biochemical reactions, such as the creatine kinase equilibrium and adenosine triphosphate (ATP) synthesis. Although various (31)P-MT methods have been successfully used on isolated organs or animals, their application on humans in clinical scanners poses specific challenges. This study compared two major (31)P-MT methods on a clinical MR system using heteronuclear surface coils. Although saturation transfer (ST) is the most commonly used (31)P-MT method, sequences such as inversion transfer (IT) with short pulses might be better suited for the specific hardware and software limitations of a clinical scanner. In addition, small NMR-undetectable metabolite pools can transfer MT to NMR-visible pools during long saturation pulses, which is prevented with short pulses. (31)P-MT sequences were adapted for limited pulse length, for heteronuclear transmit-receive surface coils with inhomogeneous B1 , for the need for volume selection and for the inherently low signal-to-noise ratio (SNR) on a clinical 3-T MR system. The ST and IT sequences were applied to skeletal muscle and liver in 10 healthy volunteers. Monte-Carlo simulations were used to evaluate the behavior of the IT measurements with increasing imperfections. In skeletal muscle of the thigh, ATP synthesis resulted in forward reaction constants (k) of 0.074 ± 0.022 s(-1) (ST) and 0.137 ± 0.042 s(-1) (IT), whereas the creatine kinase reaction yielded 0.459 ± 0.089 s(-1) (IT). In the liver, ATP synthesis resulted in k = 0.267 ± 0.106 s(-1) (ST), whereas the IT experiment yielded no consistent results. ST results were close to literature values; however, the IT results were either much larger than the corresponding ST values and/or were widely scattered. To summarize, ST and IT experiments can both be implemented on a clinical body scanner with heteronuclear transmit-receive surface coils; however, ST results are much more robust against experimental imperfections than the current implementation of IT.

Diagnostic confidence and image quality of CT pulmonary angiography at 100 kVp in overweight and obese patients.

AIM To compare image quality and diagnostic confidence of 100 kVp CT pulmonary angiography (CTPA) in patients with body weights (BWs) below and above 100kg. MATERIALS AND METHODS The present retrospective study comprised 216 patients (BWs of 75-99kg, 114 patients; 100-125kg, 88 patients; >125kg, 14 patients), who received 100 kVp CTPA to exclude pulmonary embolism. The attenuation was measured and the contrast-to-noise ratio (CNR) was calculated in the pulmonary trunk. Size-specific dose estimates (SSDEs) were evaluated. Three blinded radiologists rated subjective image quality and diagnostic confidence. Results between the BW groups and between three body mass index (BMI) groups (BMI <25kg/m(2), BMI = 25-29.9kg/m(2), and BMI ≥30kg/m(2), i.e., normal weight, overweight, and obese patients) were compared using the Kruskal-Wallis test. RESULTS Vessel attenuation was higher and SDDE was lower in the 75-99kg group than at higher BWs (p-values between <0.001 and 0.03), with no difference between the 100-125 and >125kg groups (p = 0.892 and 1). Subjective image quality and diagnostic confidence were not different among the BW groups (p = 0.225 and 1). CNR was lower (p < 0.006) in obese patients than in normal weight or overweight subjects. Diagnostic confidence was not different in the BMI groups (p = 0.105). CONCLUSION CTPA at 100 kVp tube voltage can be used in patients weighing up to 125kg with no significant deterioration of subjective image quality and confidence. The applicability of 100 kVp in the 125-150kg BW range needs further testing in larger collectives.

Prospective randomised comparison of diagnostic confidence and image quality with normal-dose and low-dose CT pulmonary angiography at various body weights.

OBJECTIVES To find a threshold body weight (BW) below 100 kg above which computed tomography pulmonary angiography (CTPA) using reduced radiation and a reduced contrast material (CM) dose provides significantly impaired quality and diagnostic confidence compared with standard-dose CTPA. METHODS In this prospectively randomised study of 501 patients with suspected pulmonary embolism and BW <100 kg, 246 were allocated into the low-dose group (80 kVp, 75 ml CM) and 255 into the normal-dose group (100 kVp, 100 ml CM). Contrast-to-noise ratio (CNR) in the pulmonary trunk was calculated. Two blinded chest radiologists independently evaluated subjective image quality and diagnostic confidence. Data were compared between the normal-dose and low-dose groups in five BW subgroups. RESULTS Vessel attenuation did not differ between the normal-dose and low-dose groups within each BW subgroup (P = 1.0). The CNR was higher with the normal-dose compared with the low-dose protocol (P < 0.006) in all BW subgroups except for the 90-99 kg subgroup (P = 0.812). Subjective image quality and diagnostic confidence did not differ between CT protocols in all subgroups (P between 0.960 and 1.0). CONCLUSIONS Subjective image quality and diagnostic confidence with 80 kVp CTPA is not different from normal-dose protocol in any BW group up to 100 kg. KEY POINTS • 80 kVp CTPA is safe in patients weighing <100 kg • Reduced radiation and iodine dose still provide high vessel attenuation • Image quality and diagnostic confidence with low-dose CTPA is good • Diagnostic confidence does not deteriorate in obese patients weighing <100 kg.

Cold Microwave-Enabled Protein Detection and Quantification.

Protein screening/detection is an essential tool in many laboratories. Owing to the relatively large time investments that are required by standard protocols, the development of methods with higher throughput while maintaining an at least comparable signal-to-noise ratio is highly beneficial in many research areas. This chapter describes how cold microwave technology can be used to enhance the rate of molecular interactions and provides protocols for dot blots, Western blots, and ELISA procedures permitting a completion of all incubation steps (blocking and antibody steps) within 24-45 min.

Simultaneous multi-slice readout-segmented echo planar imaging for accelerated diffusion-weighted imaging of the breast

OBJECTIVES Readout-segmented echo planar imaging (rs-EPI) significantly reduces susceptibility artifacts in diffusion-weighted imaging (DWI) of the breast compared to single-shot EPI but is limited by longer scan times. To compensate for this, we tested a new simultaneous multi-slice (SMS) acquisition for accelerated rs-EPI. MATERIALS AND METHODS After approval by the local ethics committee, eight healthy female volunteers (age, 38.9±13.1 years) underwent breast MRI at 3T. Conventional as well as two-fold (2× SMS) and three-fold (3× SMS) slice-accelerated rs-EPI sequences were acquired at b-values of 50 and 800s/mm(2). Two independent readers analyzed the apparent diffusion coefficient (ADC) in fibroglandular breast parenchyma. The signal-to-noise ratio (SNR) was estimated based on the subtraction method. ADC and SNR were compared between sequences by using the Friedman test. RESULTS The acquisition time was 4:21min for conventional rs-EPI, 2:35min for 2× SMS rs-EPI and 1:44min for 3× SMS rs-EPI. ADC values were similar in all sequences (mean values 1.62×10(-3)mm(2)/s, p=0.99). Mean SNR was 27.7-29.6, and no significant differences were found among the sequences (p=0.83). CONCLUSION SMS rs-EPI yields similar ADC values and SNR compared to conventional rs-EPI at markedly reduced scan time. Thus, SMS excitation increases the clinical applicability of rs-EPI for DWI of the breast.

Comparison of Routine Brain Imaging at 3 T and 7 T.

OBJECTIVE The aim of this study was to compare quantitative and semiquantitative parameters (signal-to-noise ratio [SNR], contrast-to-noise ratio [CNR], image quality, diagnostic confidence) from a standard brain magnetic resonance imaging examination encompassing common neurological disorders such as demyelinating disease, gliomas, cerebrovascular disease, and epilepsy, with comparable sequence protocols and acquisition times at 3 T and at 7 T. MATERIALS AND METHODS Ten healthy volunteers and 4 subgroups of 40 patients in total underwent comparable magnetic resonance protocols with standard diffusion-weighted imaging, 2D and 3D turbo spin echo, 2D and 3D gradient echo and susceptibility-weighted imaging of the brain (10 sequences) at 3 T and 7 T. The subgroups comprised patients with either lesional (n = 5) or nonlesional (n = 4) epilepsy, intracerebral tumors (n = 11), demyelinating disease (n = 11) (relapsing-remitting multiple sclerosis [MS, n = 9], secondary progressive MS [n = 1], demyelinating disease not further specified [n = 1]), or chronic cerebrovascular disorders [n = 9]). For quantitative analysis, SNR and CNR were determined. For a semiquantitative assessment of the diagnostic confidence, a 10-point scale diagnostic confidence score (DCS) was applied. Two experienced radiologists with additional qualification in neuroradiology independently assessed, blinded to the field strength, 3 pathology-specific imaging criteria in each of the 4 disease groups and rated their diagnostic confidence. The overall image quality was semiquantitatively assessed using a 4-point scale taking into account whether diagnostic decision making was hampered by artifacts or not. RESULTS Without correction for spatial resolution, SNR was higher at 3 T except in the T2 SPACE 3D, DWI single shot, and DIR SPACE 3D sequences. The SNR corrected by the ratio of 3 T/7 T voxel sizes was higher at 7 T than at 3 T in 10 of 11 sequences (all except for T1 MP2RAGE 3D).In CNR, there was a wide variation between sequences and patient cohorts, but average CNR values were broadly similar at 3 T and 7 T.DCS values for all 4 pathologic entities were higher at 7 T than at 3 T. The DCS was significantly higher at 7 T for diagnosis and exclusion of cortical lesions in vascular disease. A tendency to higher DCS at 7 T for cortical lesions in MS was observed, and for the depiction of a central vein and iron deposits within MS lesions. Despite motion artifacts, DCS values were higher at 7 T for the diagnosis and exclusion of hippocampal sclerosis in mesial temporal lobe epilepsy (improved detection of the hippocampal subunits). Interrater agreement was 69.7% at 3 T and 93.3% at 7 T. There was no significant difference in the overall image quality score between 3 T and 7 T taking into account whether diagnostic decision making was hampered by artifacts or not. CONCLUSIONS Ultra-high-field magnetic resonance imaging at 7 T compared with 3 T yielded an improved diagnostic confidence in the most frequently encountered neurologic disorders. Higher spatial resolution and contrast were identified as the main contributory factors.

The Interstellar Neutral He haze in the heliosphere: what can we learn?

Neutral interstellar helium has been observed by the Interstellar Boundary Explorer (IBEX) since 2009, with a signal-to-noise ratio well above 1000. Because of the geometry of the observations, the signal observed from January to March each year is the easiest to identify. However, as we show via simulations, the portion of the signal in the range of intensities from 10(-3) to 10(-2) of the peak value, previously mostly left out from the analysis, may provide important information about the details of the distribution function of interstellar He gas in front of the heliosphere. In particular, these observations may inform us about possible departures of the parent interstellar He population from equilibrium. We compare the expected distribution of the signal for the canonical assumption of a single Maxwell-Boltzmann population with the distributions for a superposition of the Maxwell-Boltzmann primary population and the recently discovered Warm Breeze, and for a single primary population given by a kappa function. We identify the regions on the sky where the differences between those cases are expected to be the most visible against the background. We discuss the diagnostic potential of the fall peak of the interstellar signal, reduced by a factor of 50 due to the Compton-Getting effect but still above the detection limit of IBEX. We point out the strong energy dependence of the fall signal and suggest that searching for this signal in the data could bring an independent assessment of the low-energy measurement threshold of the IBEX-Lo sensor.

Chemical Composition of Micrometer-Sized Filaments in an Aragonite Host by a Miniature Laser Ablation/Ionization Mass Spectrometer

Detection of extraterrestrial life is an ongoing goal in space exploration, and there is a need for advanced instruments and methods for the detection of signatures of life based on chemical and isotopic composition. Here, we present the first investigation of chemical composition of putative microfossils in natural samples using a miniature laser ablation/ionization time-of-flight mass spectrometer (LMS). The studies were conducted with high lateral (similar to 15 mu m) and vertical (similar to 20-200 nm) resolution. The primary aim of the study was to investigate the instrument performance on micrometer-sized samples both in terms of isotope abundance and element composition. The following objectives had to be achieved: (1) Consider the detection and calculation of single stable isotope ratios in natural rock samples with techniques compatible with their employment of space instrumentation for biomarker detection in future planetary missions. (2) Achieve a highly accurate chemical compositional map of rock samples with embedded structures at the micrometer scale in which the rock matrix is easily distinguished from the micrometer structures. Our results indicate that chemical mapping of strongly heterogeneous rock samples can be obtained with a high accuracy, whereas the requirements for isotope ratios need to be improved to reach sufficiently large signal-to-noise ratio (SNR). Key Words: Biogenicity-Biomarkers-Biosignatures-Filaments-Fossilization. Astrobiology 15, 669-682.

Methodological and physiological test-retest reliability of (13) C-MRS glycogen measurements in liver and in skeletal muscle of patients with type 1 diabetes and matched healthy controls.

Glycogen is a major substrate in energy metabolism and particularly important to prevent hypoglycemia in pathologies of glucose homeostasis such as type 1 diabetes mellitus (T1DM). (13) C-MRS is increasingly used to determine glycogen in skeletal muscle and liver non-invasively; however, the low signal-to-noise ratio leads to long acquisition times, particularly when glycogen levels are determined before and after interventions. In order to ease the requirements for the subjects and to avoid systematic effects of the lengthy examination, we evaluated if a standardized preparation period would allow us to shift the baseline (pre-intervention) experiments to a preceding day. Based on natural abundance (13) C-MRS on a clinical 3 T MR system the present study investigated the test-retest reliability of glycogen measurements in patients with T1DM and matched controls (n = 10 each group) in quadriceps muscle and liver. Prior to the MR examination, participants followed a standardized diet and avoided strenuous exercise for two days. The average coefficient of variation (CV) of myocellular glycogen levels was 9.7% in patients with T1DM compared with 6.6% in controls after a 2 week period, while hepatic glycogen variability was 13.3% in patients with T1DM and 14.6% in controls. For comparison, a single-session test-retest variability in four healthy volunteers resulted in 9.5% for skeletal muscle and 14.3% for liver. Glycogen levels in muscle and liver were not statistically different between test and retest, except for hepatic glycogen, which decreased in T1DM patients in the retest examination, but without an increase of the group distribution. Since the CVs of glycogen levels determined in a "single session" versus "within weeks" are comparable, we conclude that the major source of uncertainty is the methodological error and that physiological variations can be minimized by a pre-study standardization. For hepatic glycogen examinations, familiarization sessions (MR and potentially strenuous interventions) are recommended. Copyright © 2016 John Wiley & Sons, Ltd.

Fast magnetic resonance temperature imaging for focused ultrasound thermal therapy

The current standard for temperature sensitive imaging using magnetic resonance (MR) is 2-D, spoiled, fast gradient-echo (fGRE) phase-difference imaging exploiting temperature dependent changes in the proton resonance frequency (PRF). The echo-time (TE) for optimal sensitivity is larger than the typical repetition time (TR) of an fGRE sequence. Since TE must be less than TR in the fGRE sequence, this limits the technique's achievable sensitivity, spatial, and temporal resolution. This adversely affects both accuracy and volume coverage of the measurements. Accurate measurement of the rapid temperature changes associated with pulsed thermal therapies, such as high-intensity focused ultrasound (FUS), at optimal temperature sensitivity requires faster acquisition times than those currently available. ^ Use of fast MR acquisition strategies, such as interleaved echo-planar and spiral imaging, can provide the necessary increase in temporal performance and sensitivity while maintaining adequate signal-to-noise and in-plane spatial resolution. This research explored the adaptation and optimization of several fast MR acquisition methods for thermal monitoring of pulsed FUS thermal therapy. Temperature sensitivity, phase-difference noise and phase-difference to phase-difference-to noise ratio for the different pulse sequences were evaluated under varying imaging parameters in an agar gel phantom to establish optimal sequence parameters for temperature monitoring. The temperature sensitivity coefficient of the gel phantom was measured, allowing quantitative temperature extrapolations. ^ Optimized fast sequences were compared based on the ability to accurately monitor temperature changes at the focus of a high-intensity focused ultrasound unit, volume coverage, and contrast-to-noise ratio in the temperature maps. Operating parameters, which minimize complex phase-difference measurement errors introduced by use of the fast-imaging methods, were established. ^

Multiple gradient echo propeller (MGREP) MRI: Technical development and potential applications

The PROPELLER (Periodically Rotated Overlapping Parallel Lines with Enhanced Reconstruction) magnetic resonance imaging (MRI) technique has inherent advantages over other fast imaging methods, including robust motion correction, reduced image distortion, and resistance to off-resonance effects. These features make PROPELLER highly desirable for T2*-sensitive imaging, high-resolution diffusion imaging, and many other applications. However, PROPELLER has been predominantly implemented as a fast spin-echo (FSE) technique, which is insensitive to T2* contrast, and requires time-inefficient signal averaging to achieve adequate signal-to-noise ratio (SNR) for many applications. These issues presently constrain the potential clinical utility of FSE-based PROPELLER. ^ In this research, our aim was to extend and enhance the potential applications of PROPELLER MRI by developing a novel multiple gradient echo PROPELLER (MGREP) technique that can overcome the aforementioned limitations. The MGREP pulse sequence was designed to acquire multiple gradient-echo images simultaneously, without any increase in total scan time or RF energy deposition relative to FSE-based PROPELLER. A new parameter was also introduced for direct user-control over gradient echo spacing, to allow variable sensitivity to T2* contrast. In parallel to pulse sequence development, an improved algorithm for motion correction was also developed and evaluated against the established method through extensive simulations. The potential advantages of MGREP over FSE-based PROPELLER were illustrated via three specific applications: (1) quantitative T2* measurement, (2) time-efficient signal averaging, and (3) high-resolution diffusion imaging. Relative to the FSE-PROPELLER method, the MGREP sequence was found to yield quantitative T2* values, increase SNR by ∼40% without any increase in acquisition time or RF energy deposition, and noticeably improve image quality in high-resolution diffusion maps. In addition, the new motion algorithm was found to improve the performance considerably in motion-artifact reduction. ^ Overall, this work demonstrated a number of enhancements and extensions to existing PROPELLER techniques. The new technical capabilities of PROPELLER imaging, developed in this thesis research, are expected to serve as the foundation for further expanding the scope of PROPELLER applications. ^

In-vivo diffusion tensor imaging of rat spinal cord with a phased array coil at 7T

Magnetic resonance imaging (MRI) is a non-invasive technique that offers excellent soft tissue contrast for characterizing soft tissue pathologies. Diffusion tensor imaging (DTI) is an MRI technique that has shown to have the sensitivity to detect subtle pathology that is not evident on conventional MRI. ^ Rats are commonly used as animal models in characterizing the spinal cord pathologies including spinal cord injury (SCI), cancer, multiple sclerosis, etc. These pathologies could affect both thoracic and cervical regions and complete characterization of these pathologies using MRI requires DTI characterization in both the thoracic and cervical regions. Prior to the application of DTI for investigating the pathologic changes in the spinal cord, it is essential to establish DTI metrics in normal animals. ^ To date, in-vivo DTI studies of rat spinal cord have used implantable coils for high signal-to-noise ratio (SNR) and spin-echo pulse sequences for reduced geometric distortions. Implantable coils have several disadvantages including: (1) the invasive nature of implantation, (2) loss of SNR due to frequency shift with time in the longitudinal studies, and (3) difficulty in imaging the cervical region. While echo planar imaging (EPI) offers much shorter acquisition times compared to spin-echo imaging, EPI is very sensitive to static magnetic field inhomogeneities and the existing shimming techniques implemented on the MRI scanner do not perform well on spinal cord because of its geometry. ^ In this work, an integrated approach has been implemented for in-vivo DTI characterization of rat spinal cord in the thoracic and cervical regions. A three element phased array coil was developed for improved SNR and extended spatial coverage. A field-map shimming technique was developed for minimizing the geometric distortions in EPI images. Using these techniques, EPI based DWI images were acquired with optimized diffusion encoding scheme from 6 normal rats and the DTI-derived metrics were quantified. ^ The phantom studies indicated higher SNR and smaller bias in the estimated DTI metrics than the previous studies in the cervical region. In-vivo results indicated no statistical difference in the DTI characteristics of either gray matter or white matter between the thoracic and cervical regions. ^

Improved Techniques for Acquisition and Analysis of Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Detecting Vascular Permeability in the Central Nervous System

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive technique for quantitative assessment of the integrity of blood-brain barrier and blood-spinal cord barrier (BSCB) in the presence of central nervous system pathologies. However, the results of DCE-MRI show substantial variability. The high variability can be caused by a number of factors including inaccurate T1 estimation, insufficient temporal resolution and poor contrast-to-noise ratio. My thesis work is to develop improved methods to reduce the variability of DCE-MRI results. To obtain fast and accurate T1 map, the Look-Locker acquisition technique was implemented with a novel and truly centric k-space segmentation scheme. In addition, an original multi-step curve fitting procedure was developed to increase the accuracy of T1 estimation. A view sharing acquisition method was implemented to increase temporal resolution, and a novel normalization method was introduced to reduce image artifacts. Finally, a new clustering algorithm was developed to reduce apparent noise in the DCE-MRI data. The performance of these proposed methods was verified by simulations and phantom studies. As part of this work, the proposed techniques were applied to an in vivo DCE-MRI study of experimental spinal cord injury (SCI). These methods have shown robust results and allow quantitative assessment of regions with very low vascular permeability. In conclusion, applications of the improved DCE-MRI acquisition and analysis methods developed in this thesis work can improve the accuracy of the DCE-MRI results.

Design, Calibration, and Evaluation of Depth-of-Interaction-Capable PET Detector Modules

High-resolution, small-bore PET systems suffer from a tradeoff between system sensitivity, and image quality degradation. In these systems long crystals allow mispositioning of the line of response due to parallax error and this mispositioning causes resolution blurring, but long crystals are necessary for high system sensitivity. One means to allow long crystals without introducing parallax errors is to determine the depth of interaction (DOI) of the gamma ray interaction within the detector module. While DOI has been investigated previously, newly available solid state photomultipliers (SSPMs) well-suited to PET applications and allow new modules for investigation. Depth of interaction in full modules is a relatively new field, and so even if high performance DOI capable modules were available, the appropriate means to characterize and calibrate the modules are not. This work presents an investigation of DOI capable arrays and techniques for characterizing and calibrating those modules. The methods introduced here accurately and reliably characterize and calibrate energy, timing, and event interaction positioning. Additionally presented is a characterization of the spatial resolution of DOI capable modules and a measurement of DOI effects for different angles between detector modules. These arrays have been built into a prototype PET system that delivers better than 2.0 mm resolution with a single-sided-stopping-power in excess of 95% for 511 keV g's. The noise properties of SSPMs scale with the active area of the detector face, and so the best signal-to-noise ratio is possible with parallel readout of each SSPM photodetector pixel rather than multiplexing signals together. This work additionally investigates several algorithms for improving timing performance using timing information from multiple SSPM pixels when light is distributed among several photodetectors.