T1 relaxation time of ISMRM/NIST T1 phantom spheres at 7 T.

T1 relaxation times of the 14 T1 phantom spheres that make up the standard International Society for Magnetic Resonance in Medicine (ISMRM)/National Institute of Standards and Technology (NIST) system phantom are reported at 7 T. T1 values of six of the 14 T1 spheres at 7 T (with T1 > 270 ms) have been reported previously, but, to the best of our knowledge, not all of the T1s of the 14 T1 spheres at 7 T have been reported before. Given the increasing number of 7-T MRI systems in clinical settings and the increasing need for T1 phantoms that cover a wide range of T1 relaxation times to evaluate rapid T1 mapping techniques at 7 T, it is of high interest to obtain accurate T1 values for all the ISMRM/NIST T1 spheres at 7 T. In this work, T1 relaxation time was measured on a 7-T MRI scanner using an inversion-recovery spin-echo pulse sequence and derived by curve fitting to a signal equation that exhibits insensitivity to B 1 + inhomogeneity. Day-to-day reproducibility was within 0.4% and differences between two different RF coils within 1.5%. T1s of a subset of the 14 spheres were also measured by NMR at 7 T for comparison, and the T1 results were consistent between the MRI and NMR measurements. T1 measurements performed at 3 T on the same 14 spheres using the same sequence and fitting method yielded good agreement (mean percentage difference of -0.4%) with the reference T1 values available from the NIST, reflecting the accuracy of the reported technique despite being without the standard phantom housing. We found that the T1 values of all 14 NiCl2 spheres are consistently lower at 7 T than at 3 T. Although our results were well reproduced, this study represents initial work to quantify the 7-T T1 values of all 14 NIST T1 spheres outside of the standard housing and does not warrant reproducibility of the ISMRM/NIST system phantom as a whole. A future study to assess the T1 values of a version of the ISMRM/NIST system phantom that fits inside typical commercial coils at 7 T will be very helpful. Nonetheless, the details on our acquisition and curve-fitting methods reported here allow the T1 measurements to be reproduced elsewhere. The T1 values of all 14 spheres reported here will be valuable for the development of quantitative MR fingerprinting and rapid T1 mapping for a large variety of research projects, not only in neuroimaging but also in body MRI, musculoskeletal MRI, and gadolinium contrast-enhanced MRI, each of which is concerned with much shortened T1.

Developing a medical device-grade T2 phantom optimized for myocardial T2 mapping by cardiovascular magnetic resonance.

INTRODUCTION: A long T2 relaxation time can reflect oedema, and myocardial inflammation when combined with increased plasma troponin levels. Cardiovascular magnetic resonance (CMR) T2 mapping therefore has potential to provide a key diagnostic and prognostic biomarkers. However, T2 varies by scanner, software, and sequence, highlighting the need for standardization and for a quality assurance system for T2 mapping in CMR. AIM: To fabricate and assess a phantom dedicated to the quality assurance of T2 mapping in CMR. METHOD: A T2 mapping phantom was manufactured to contain 9 T1 and T2 (T1|T2) tubes to mimic clinically relevant native and post-contrast T2 in myocardium across the health to inflammation spectrum (i.e., 43-74 ms) and across both field strengths (1.5 and 3 T). We evaluated the phantom's structural integrity, B0 and B1 uniformity using field maps, and temperature dependence. Baseline reference T1|T2 were measured using inversion recovery gradient echo and single-echo spin echo (SE) sequences respectively, both with long repetition times (10 s). Long-term reproducibility of T1|T2 was determined by repeated T1|T2 mapping of the phantom at baseline and at 12 months. RESULTS: The phantom embodies 9 internal agarose-containing T1|T2 tubes doped with nickel di-chloride (NiCl2) as the paramagnetic relaxation modifier to cover the clinically relevant spectrum of myocardial T2. The tubes are surrounded by an agarose-gel matrix which is doped with NiCl2 and packed with high-density polyethylene (HDPE) beads. All tubes at both field strengths, showed measurement errors up to ≤ 7.2 ms [< 14.7%] for estimated T2 by balanced steady-state free precession T2 mapping compared to reference SE T2 with the exception of the post-contrast tube of ultra-low T1 where the deviance was up to 16 ms [40.0%]. At 12 months, the phantom remained free of air bubbles, susceptibility, and off-resonance artifacts. The inclusion of HDPE beads effectively flattened the B0 and B1 magnetic fields in the imaged slice. Independent temperature dependency experiments over the 13-38 °C range confirmed the greater stability of shorter vs longer T1|T2 tubes. Excellent long-term (12-month) reproducibility of measured T1|T2 was demonstrated across both field strengths (all coefficients of variation < 1.38%). CONCLUSION: The T2 mapping phantom demonstrates excellent structural integrity, B0 and B1 uniformity, and reproducibility of its internal tube T1|T2 out to 1 year. This device may now be mass-produced to support the quality assurance of T2 mapping in CMR.

Relaxation measurements of an MRI system phantom at low magnetic field strengths.

OBJECTIVE: Temperature controlled T1 and T2 relaxation times are measured on NiCl2 and MnCl2 solutions from the ISMRM/NIST system phantom at low magnetic field strengths of 6.5 mT, 64 mT and 550 mT. MATERIALS AND METHODS: The T1 and T2 were measured of five samples with increasing concentrations of NiCl2 and five samples with increasing concentrations of MnCl2. All samples were scanned at 6.5 mT, 64 mT and 550 mT, at sample temperatures ranging from 10 °C to 37 °C. RESULTS: The NiCl2 solutions showed little change in T1 and T2 with magnetic field strength, and both relaxation times decreased with increasing temperature. The MnCl2 solutions showed an increase in T1 and a decrease in T2 with increasing magnetic field strength, and both T1 and T2 increased with increasing temperature. DISCUSSION: The low field relaxation rates of the NiCl2 and MnCl2 arrays in the ISMRM/NIST system phantom are investigated and compared to results from clinical field strengths of 1.5 T and 3.0 T. The measurements can be used as a benchmark for MRI system functionality and stability, especially when MRI systems are taken out of the radiology suite or laboratory and into less traditional environments.

Aqueous Dispersion of Manganese-Zinc Ferrite Nanoparticles Protected by PEG as a T2 MRI Temperature Contrast Agent.

Mixed manganese-zinc ferrite nanoparticles coated with PEG were studied for their potential usefulness in MRI thermometry as temperature-sensitive contrast agents. Particles in the form of an 8.5 nm core coated with a 3.5 nm layer of PEG were fabricated using a newly developed, one-step method. The composition of Mn0.48Zn0.46Fe2.06O4 was found to have a strong thermal dependence of magnetization in the temperature range between 5 and 50 °C. Nanoparticles suspended in an agar gel mimicking animal tissue and showing non-significant impact on cell viability in the biological test were studied with NMR and MRI over the same temperature range. For the concentration of 0.017 mg/mL of Fe, the spin-spin relaxation time T2 increased from 3.1 to 8.3 ms, while longitudinal relaxation time T1 shows a moderate decrease from 149.0 to 125.1 ms. A temperature map of the phantom exposed to the radial temperature gradient obtained by heating it with an 808 nm laser was calculated from T2 weighted spin-echo differential MR images. Analysis of temperature maps yields thermal/spatial resolution of 3.2 °C at the distance of 2.9 mm. The experimental relaxation rate R2 data of water protons were compared with those obtained from calculations using a theoretical model incorporating the motion averaging regime.

A standard system phantom for magnetic resonance imaging.

PURPOSE: A standard MRI system phantom has been designed and fabricated to assess scanner performance, stability, comparability and assess the accuracy of quantitative relaxation time imaging. The phantom is unique in having traceability to the International System of Units, a high level of precision, and monitoring by a national metrology institute. Here, we describe the phantom design, construction, imaging protocols, and measurement of geometric distortion, resolution, slice profile, signal-to-noise ratio (SNR), proton-spin relaxation times, image uniformity and proton density. METHODS: The system phantom, designed by the International Society of Magnetic Resonance in Medicine ad hoc committee on Standards for Quantitative MR, is a 200 mm spherical structure that contains a 57-element fiducial array; two relaxation time arrays; a proton density/SNR array; resolution and slice-profile insets. Standard imaging protocols are presented, which provide rapid assessment of geometric distortion, image uniformity, T1 and T2 mapping, image resolution, slice profile, and SNR. RESULTS: Fiducial array analysis gives assessment of intrinsic geometric distortions, which can vary considerably between scanners and correction techniques. This analysis also measures scanner/coil image uniformity, spatial calibration accuracy, and local volume distortion. An advanced resolution analysis gives both scanner and protocol contributions. SNR analysis gives both temporal and spatial contributions. CONCLUSIONS: A standard system phantom is useful for characterization of scanner performance, monitoring a scanner over time, and to compare different scanners. This type of calibration structure is useful for quality assurance, benchmarking quantitative MRI protocols, and to transition MRI from a qualitative imaging technique to a precise metrology with documented accuracy and uncertainty.

MRI-visible liquid crystal thermometer.

PURPOSE: MRI parameters, such as T1 , T2 , and ADC, of tissue-mimicking materials in MRI phantoms can exhibit temperature dependence, and bore temperatures can vary over a 10°C range across different MRI systems. If this variation is not accurately corrected for, the quantitative nature of reference or phantom measurements is irrelevant. Available thermometers require opening the phantoms to probe the temperature, which can introduce contaminants that may affect the stability and accuracy of the phantom. An integrated, MRI-visible thermometer that can be read using typical imaging protocols is needed. THEORY AND METHODS: An MRI-compatible thermometer was designed using liquid crystals (LCs) that exhibit rapid transitions between the LC cholesteric state and isotropic state in the room temperature range spanning 17°C to 23°C in 1.0°C increments. The LC thermometer was assessed visually and using superconducting quantum interference device magnetometry, NMR, and MRI techniques. RESULTS: The signal generated from the LC thermometer was visible with spin-echo and gradient-echo MRI images. The LC state transition temperatures were visually referenced to a National Institute of Standards and Technology-traceable thermometer, and these LC state transitions were confirmed using superconducting quantum interference device magnetometry and NMR. CONCLUSIONS: The LC MR-visible thermometer had measurable changes in relative signal with temperature, which were invariant to a variety of imaging sequences used.

Low-field magnetic resonance imaging of roots in intact clayey and silty soils.

The development of a robust method to non-invasively visualize root morphology in natural soils has been hampered by the opaque, physical, and structural properties of soils. In this work we describe a novel technology, low field magnetic resonance imaging (LF-MRI), for imaging energy sorghum (Sorghum bicolor (L.) Moench) root morphology and architecture in intact soils. The use of magnetic fields much weaker than those used with traditional MRI experiments reduces the distortion due to magnetic material naturally present in agricultural soils. A laboratory based LF-MRI operating at 47 mT magnetic field strength was evaluated using two sets of soil cores: 1) soil/root cores of Weswood silt loam (Udifluventic Haplustept) and a Belk clay (Entic Hapluderts) from a conventionally tilled field, and 2) soil/root cores from rhizotrons filled with either a Houston Black (Udic Haplusterts) clay or a sandy loam purchased from a turf company. The maximum soil water nuclear magnetic resonance (NMR) relaxation time T2 (4 ms) and the typical root water relaxation time T2 (100 ms) are far enough apart to provide a unique contrast mechanism such that the soil water signal has decayed to the point of no longer being detectable during the data collection time period. 2-D MRI projection images were produced of roots with a diameter range of 1.5-2.0 mm using an image acquisition time of 15 min with a pixel resolution of 1.74 mm in four soil types. Additionally, we demonstrate the use of a data-driven machine learning reconstruction approach, Automated Transform by Manifold Approximation (AUTOMAP) to reconstruct raw data and improve the quality of the final images. The application of AUTOMAP showed a SNR (Signal to Noise Ratio) improvement of two fold on average. The use of low field MRI presented here demonstrates the possibility of applying low field MRI through intact soils to root phenotyping and agronomy to aid in understanding of root morphology and the spatial arrangement of roots in situ.

Assessing effects of scanner upgrades for clinical studies.

BACKGROUND: Scanner upgrades due to software and hardware changes are an inevitable part of MR research and, without quality assurance protocols, can jeopardize studies. PURPOSE: To evaluate changes in T1 relaxation time by inversion recovery (IR) and variable flip angle (VFA) measurements on a 3T system that underwent an "everything but the magnet" upgrade. STUDY TYPE: Longitudinal. PHANTOM: An International Society of Magnetic Resonance in Medicine / National Institute of Standards and Technology (ISMRM/NIST) system phantom with repeated measurements across multiple (n = 3) days. FIELD STRENGTH/SEQUENCE: T1 IR, VFA at 3T. ASSESSMENT: The T1 measurements by IR and VFA were compared with the nuclear magnetic resonance (NMR) measurements, which constitute the known values for the ISMRM/NIST system phantom, to determine the measurement error. STATISTICAL TESTS: Descriptive. RESULTS: The T1 VFA measurement errors were distributed around zero (-15% to +10%) on the original system and then the errors were distributed entirely above zero post-upgrade (+5% to 30%). The T1 IR results had a dramatic increase in error distribution (±5% original, ±20% post-upgrade) prior to the identification of signal saturation as an issue. Once the signal saturation was accounted for, the T1 IR errors decreased to ±10% post-upgrade. DATA CONCLUSION: The T1 VFA measurement differences between the original and post-upgrade systems can be entirely attributed to contributions from B1 . The T1 IR measurements demonstrate the need for quantitative quality assurance (QA) processes. The site under study passed the QA protocols in place, which did not identify the increased T1 error, nor the signal saturation issue. To improve on this study, we would make systematic, quantitative measurements at intervals less than a year and following any hardware or software upgrade. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019. J. Magn. Reson. Imaging 2019;50:1948-1954.

Recommendations towards standards for quantitative MRI (qMRI) and outstanding needs.

LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019.

Molecular hydrogen and catalytic combustion in the production of hyperpolarized 83Kr and 129Xe MRI contrast agents.

Hyperpolarized (hp) (83)Kr is a promising MRI contrast agent for the diagnosis of pulmonary diseases affecting the surface of the respiratory zone. However, the distinct physical properties of (83)Kr that enable unique MRI contrast also complicate the production of hp (83)Kr. This work presents a previously unexplored approach in the generation of hp (83)Kr that can likewise be used for the production of hp (129)Xe. Molecular nitrogen, typically used as buffer gas in spin-exchange optical pumping (SEOP), was replaced by molecular hydrogen without penalty for the achievable hyperpolarization. In this particular study, the highest obtained nuclear spin polarizations were P =29% for(83)Kr and P= 63% for (129)Xe. The results were reproduced over many SEOP cycles despite the laser-induced on-resonance formation of rubidium hydride (RbH). Following SEOP, the H2 was reactively removed via catalytic combustion without measurable losses in hyperpolarized spin state of either (83)Kr or (129)Xe. Highly spin-polarized (83)Kr can now be purified for the first time, to our knowledge, to provide high signal intensity for the advancement of in vivo hp (83)Kr MRI. More generally, a chemical reaction appears as a viable alternative to the cryogenic separation process, the primary purification method of hp(129)Xe for the past 2 1/2 decades. The inherent simplicity of the combustion process will facilitate hp (129)Xe production and should allow for on-demand continuous flow of purified and highly spin-polarized (129)Xe.

Accuracy, repeatability, and interplatform reproducibility of T1 quantification methods used for DCE-MRI: Results from a multicenter phantom study.

PURPOSE: To determine the in vitro accuracy, test-retest repeatability, and interplatform reproducibility of T1 quantification protocols used for dynamic contrast-enhanced MRI at 1.5 and 3 T. METHODS: A T1 phantom with 14 samples was imaged at eight centers with a common inversion-recovery spin-echo (IR-SE) protocol and a variable flip angle (VFA) protocol using seven flip angles, as well as site-specific protocols (VFA with different flip angles, variable repetition time, proton density, and Look-Locker inversion recovery). Factors influencing the accuracy (deviation from reference NMR T1 measurements) and repeatability were assessed using general linear mixed models. Interplatform reproducibility was assessed using coefficients of variation. RESULTS: For the common IR-SE protocol, accuracy (median error across platforms = 1.4-5.5%) was influenced predominantly by T1 sample (P < 10-6 ), whereas test-retest repeatability (median error = 0.2-8.3%) was influenced by the scanner (P < 10-6 ). For the common VFA protocol, accuracy (median error = 5.7-32.2%) was influenced by field strength (P = 0.006), whereas repeatability (median error = 0.7-25.8%) was influenced by the scanner (P < 0.0001). Interplatform reproducibility with the common VFA was lower at 3 T than 1.5 T (P = 0.004), and lower than that of the common IR-SE protocol (coefficient of variation 1.5T: VFA/IR-SE = 11.13%/8.21%, P = 0.028; 3 T: VFA/IR-SE = 22.87%/5.46%, P = 0.001). Among the site-specific protocols, Look-Locker inversion recovery and VFA (2-3 flip angles) protocols showed the best accuracy and repeatability (errors < 15%). CONCLUSIONS: The VFA protocols with 2 to 3 flip angles optimized for different applications achieved acceptable balance of extensive spatial coverage, accuracy, and repeatability in T1 quantification (errors < 15%). Further optimization in terms of flip-angle choice for each tissue application, and the use of B1 correction, are needed to improve the robustness of VFA protocols for T1 mapping. Magn Reson Med 79:2564-2575, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Quantitative magnetic resonance imaging phantoms: A review and the need for a system phantom.

The MRI community is using quantitative mapping techniques to complement qualitative imaging. For quantitative imaging to reach its full potential, it is necessary to analyze measurements across systems and longitudinally. Clinical use of quantitative imaging can be facilitated through adoption and use of a standard system phantom, a calibration/standard reference object, to assess the performance of an MRI machine. The International Society of Magnetic Resonance in Medicine AdHoc Committee on Standards for Quantitative Magnetic Resonance was established in February 2007 to facilitate the expansion of MRI as a mainstream modality for multi-institutional measurements, including, among other things, multicenter trials. The goal of the Standards for Quantitative Magnetic Resonance committee was to provide a framework to ensure that quantitative measures derived from MR data are comparable over time, between subjects, between sites, and between vendors. This paper, written by members of the Standards for Quantitative Magnetic Resonance committee, reviews standardization attempts and then details the need, requirements, and implementation plan for a standard system phantom for quantitative MRI. In addition, application-specific phantoms and implementation of quantitative MRI are reviewed. Magn Reson Med 79:48-61, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

A table-top PXI based low-field spectrometer for solution dynamic nuclear polarization.

We present the development of a portable dynamic nuclear polarization (DNP) instrument based on the PCI eXtensions for Instrumentation platform. The main purpose of the instrument is for study of 1 H polarization enhancements in solution through the Overhauser mechanism at low magnetic fields. A DNP probe set was constructed for use at 6.7 mT, using a modified Alderman-Grant resonator at 241 MHz for saturation of the electron transition. The solenoid for detection of the enhanced 1 H signal at 288 kHz was constructed with Litz wire. The largest observed 1 H enhancements (ε) at 6.7 mT for 14 N-CTPO radical in air saturated aqueous solution was ε~65. A concentration dependence of the enhancement is observed, with maximum ε at 5.5 mM. A low resonator efficiency for saturation of the electron paramagnetic resonance transition results in a decrease in ε for the 10.3 mM sample. At high incident powers (42 W) and long pump times, capacitor heating effects can also decrease the enhancement. The core unit and program described here could be easily adopted for multi-frequency DNP work, depending on available main magnets and selection of the "plug and play" arbitrary waveform generator, digitizer, and radiofrequency synthesizer PCI eXtensions for Instrumentatione cards.

Repeatability of magnetic resonance fingerprinting T1 and T2 estimates assessed using the ISMRM/NIST MRI system phantom.

PURPOSE: The purpose of this study was to evaluate accuracy and repeatability of T1 and T2 estimates of a MR fingerprinting (MRF) method using the ISMRM/NIST MRI system phantom. METHODS: The ISMRM/NIST MRI system phantom contains multiple compartments with standardized T1 , T2 , and proton density values. Conventional inversion-recovery spin echo and spin echo methods were used to characterize the T1 and T2 values in the phantom. The phantom was scanned using the MRF-FISP method over 34 consecutive days. The mean T1 and T2 values were compared with the values from the spin echo methods. The repeatability was characterized as the coefficient of variation of the measurements over 34 days. RESULTS: T1 and T2 values from MRF-FISP over 34 days showed a strong linear correlation with the measurements from the spin echo methods (R2 = 0.999 for T1 ; R2 = 0.996 for T2 ). The MRF estimates over the wide ranges of T1 and T2 values have less than 5% variation, except for the shortest T2 relaxation times where the method still maintains less than 8% variation. CONCLUSION: MRF measurements of T1 and T2 are highly repeatable over time and across wide ranges of T1 and T2 values. Magn Reson Med 78:1452-1457, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Design of a breast phantom for quantitative MRI.

PURPOSE: We present a breast phantom designed to enable quantitative assessment of measurements of T1 relaxation time, apparent diffusion coefficient (ADC), and other attributes of breast tissue, with long-term support from a national metrology institute. MATERIALS AND METHODS: A breast phantom was created with two independent, interchangeable units for diffusion and T1 /T2 relaxation, each with flexible outer shells. The T1 unit was filled with corn syrup solution and grapeseed oil to mimic the relaxation behavior of fibroglandular and fatty tissues, respectively. The diffusion unit contains plastic tubes filled with aqueous solutions of polyvinylpyrrolidone (PVP) to modulate the ADC. The phantom was imaged at 1.5T and 3.0T using magnetic resonance imaging (MRI) scanners and common breast coils from multiple manufacturers to assess T1 and T2 relaxation time and ADC values. RESULTS: The fibroglandular mimic exhibited target T1 values on 1.5T and 3.0T clinical systems (25-75 percentile range: 1289 to 1400 msec and 1533 to 1845 msec, respectively) across all bore temperatures. PVP solutions mimicked the range of ADC values from malignant tumors to normal breast tissue (40% PVP median: 633 × 10(-6) mm(2) /s to 0% PVP median: 2231 × 10(-6) mm(2) /s) at temperatures of 17-24°C. The interchangeable phantom units allowed both the diffusion and T1 /T2 units to be tested on the left and right sides of the coil to assess any variation. CONCLUSION: This phantom enables T1 and ADC measurements, fits in a variety of clinical breast coils, and can serve as a quality control tool to facilitate the standardization of quantitative measurements for breast MRI. J. Magn. Reson. Imaging 2016;44:610-619.

Combustion resistance of the 129Xe hyperpolarized nuclear spin state.

Using a methane-xenon mixture for spin exchange optical pumping, MRI of combustion was enabled. The (129)Xe hyperpolarized nuclear spin state was found to sufficiently survive the complete passage through the harsh environment of the reaction zone. A velocity profile (V(z)(z)) of a flame was recorded to demonstrate the feasibility of MRI velocimetry of transport processes in combustors.

Multi-site, multi-platform comparison of MRI T1 measurement using the system phantom.

Recent innovations in quantitative magnetic resonance imaging (MRI) measurement methods have led to improvements in accuracy, repeatability, and acquisition speed, and have prompted renewed interest to reevaluate the medical value of quantitative T1. The purpose of this study was to determine the bias and reproducibility of T1 measurements in a variety of MRI systems with an eye toward assessing the feasibility of applying diagnostic threshold T1 measurement across multiple clinical sites. We used the International Society of Magnetic Resonance in Medicine/National Institute of Standards and Technology (ISMRM/NIST) system phantom to assess variations of T1 measurements, using a slow, reference standard inversion recovery sequence and a rapid, commonly-available variable flip angle sequence, across MRI systems at 1.5 tesla (T) (two vendors, with number of MRI systems n = 9) and 3 T (three vendors, n = 18). We compared the T1 measurements from inversion recovery and variable flip angle scans to ISMRM/NIST phantom reference values using Analysis of Variance (ANOVA) to test for statistical differences between T1 measurements grouped according to MRI scanner manufacturers and/or static field strengths. The inversion recovery method had minor over- and under-estimations compared to the NMR-measured T1 values at both 1.5 T and 3 T. Variable flip angle measurements had substantially greater deviations from the NMR-measured T1 values than the inversion recovery measurements. At 3 T, the measured variable flip angle T1 for one vendor is significantly different than the other two vendors for most of the samples throughout the clinically relevant range of T1. There was no consistent pattern of discrepancy between vendors. We suggest establishing rigorous quality control procedures for validating quantitative MRI methods to promote confidence and stability in associated measurement techniques and to enable translation of diagnostic threshold from the research center to the entire clinical community.

Detection of tobacco smoke deposition by hyperpolarized krypton-83 MRI.

Despite the importance of the tobacco smoke particulate matter in the lungs to the etiology of pulmonary disease in cigarette smokers, little is currently known about the spatial distribution of particle deposition or the persistence of the resulting deposits in humans, and no satisfactory technique currently exists to directly observe tobacco smoke condensate in airways. In this proof-of-principle work, hyperpolarized (hp) 83Kr MRI and NMR spectroscopy are introduced as probes for tobacco smoke deposition in porous media. A reduction in the hp-83Kr longitudinal (T1) relaxation of up to 95% under near-ambient humidity, pressure and temperature conditions was observed when the krypton gas was brought into contact with surfaces that had been exposed to cigarette smoke. This smoke-induced acceleration of the 83Kr self-relaxation was observed for model glass surfaces that, in some experiments, were coated with bovine lung surfactant extract. However, a similar effect was not observed with hp-(129)Xe indicating that the 83Kr sensitivity to smoke deposition was not caused by paramagnetic species but rather by quadrupolar relaxation due to high adsorption affinity for the smoke deposits. The 83Kr T1 differences between smoke-treated and untreated surfaces were sufficient to produce a strong contrast in variable flip angle FLASH hp-83Kr MRI, suggesting that hp-83Kr may be a promising contrast agent for in vivo pulmonary MRI.

Pulmonary MRI contrast using Surface Quadrupolar Relaxation (SQUARE) of hyperpolarized (83)Kr.

Hyperpolarized (83)Kr has previously been demonstrated to enable MRI contrast that is sensitive to the chemical composition of the surface in a porous model system. Methodological advances have lead to a substantial increase in the (83)Kr hyperpolarization and the resulting signal intensity. Using the improved methodology for spin exchange optical pumping of isotopically enriched (83)Kr, internal anatomical details of ex vivo rodent lung were resolved with hyperpolarized (83)Kr MRI after krypton inhalation. Different (83)Kr relaxation times were found between the main bronchi and the parenchymal regions in ex vivo rat lungs. The T1 weighted hyperpolarized (83)Kr MRI provided a first demonstration of surface quadrupolar relaxation (SQUARE) pulmonary MRI contrast.

Validating excised rodent lungs for functional hyperpolarized xenon-129 MRI.

Ex vivo rodent lung models are explored for physiological measurements of respiratory function with hyperpolarized (hp) (129)Xe MRI. It is shown that excised lung models allow for simplification of the technical challenges involved and provide valuable physiological insights that are not feasible using in vivo MRI protocols. A custom designed breathing apparatus enables MR images of gas distribution on increasing ventilation volumes of actively inhaled hp (129)Xe. Straightforward hp (129)Xe MRI protocols provide residual lung volume (RV) data and permit for spatially resolved tracking of small hp (129)Xe probe volumes during the inhalation cycle. Hp (129)Xe MRI of lung function in the excised organ demonstrates the persistence of post mortem airway responsiveness to intravenous methacholine challenges. The presented methodology enables physiology of lung function in health and disease without additional regulatory approval requirements and reduces the technical and logistical challenges with hp gas MRI experiments. The post mortem lung functional data can augment histological measurements and should be of interest for drug development studies.