Enhanced 129 Xe T1 relaxation in whole blood and in the presence of SPIONs at low magnetic field strengths.

PURPOSE: To compare the effect of superparamagnetic iron oxide nanoparticles (SPIONs) on the T1 of 129 Xe and 1 H and to measure the relaxation of 129 Xe in blood at low and high magnetic field strengths. METHODS: 129 Xe and 1 H T1 relaxometry was performed at low- and high-field strengths in samples containing different SPION concentrations, while imaging was used to compare the contrast obtainable in these two field regimes. In vivo experiments at variable field strengths were performed to determine the depolarization of 129 Xe in blood and the feasibility of in vivo dissolved-phase spectroscopy and imaging at low field. RESULTS: The SPION relaxivity was substantially greater at low field for 1 H, increasing from 0.92 ± 0.06 mM s-1 at 11.7T to 31.5 ± 1.8 mM s-1 at 0.6 mT, and for 129 Xe, which increased from 0.13 ± 0.03 mM s-1 at 11.7T to 7.32 ± 0.71 mM s-1 at 2.1 mT. The additional MR signal loss increased from 0.7% at 9.4T to 20.6 ± 4.2% at 0.6 mT for 1 H and from -0.7 ± 3.4% at 9.4T to 12.7 ± 3.5% at 2.1 mT for 129 Xe. Blood was found to depolarize 129 Xe below 3T in a manner inversely proportional to the field strength. In vitro studies at 2.1 mT suggest 129 Xe relaxation times below 5 s in blood dilutions as low as 0.4% volume. CONCLUSION: SPIONs longitudinal relaxivity increases at low field both for 1 H and 129 Xe. The depolarization of xenon in blood, which is found to increase below 3T, effectively prevents in vivo dissolved-phase spectroscopy and imaging at low-field strengths.

Background-Free Detection of Spin-Exchange Dynamics at Ultra-Low Magnetic Field.

Ultra-low field nuclear magnetic resonance spectroscopy (NMR) and imaging (MRI) inherently suffer from a low signal-to-noise ratio due to the small thermal polarization of nuclear spins. Transfer of polarization from a pre-polarized spin system to a thermally polarized spin system via the Spin Polarization Induced Nuclear Overhauser Effect (SPINOE) could potentially be used to overcome this limitation. SPINOE is particularly advantageous at ultra-low magnetic field, where the transferred polarization can be several orders of magnitude higher than thermal polarization. Here we demonstrate direct detection of polarization transfer from highly polarized 129 Xe gas spins to 1 H spins in solution via SPINOE. At ultra-low field, where thermal nuclear spin polarization is close to background noise levels and where different nuclei can be simultaneously detected in a single spectrum, the dynamics of the polarization transfer can be observed in real time. We show that by simply bubbling hyperpolarized 129 Xe into solution, we can enhance 1 H polarization levels by a factor of up to 151-fold. While our protocol leads to lower enhancements than those previously reported under extreme Xe gas pressures, the methodology is easily repeatable and allows for on-demand enhanced spectroscopy. SPINOE at ultra-low magnetic field could also be employed to study 129 Xe interactions in solutions.

Longitudinal nuclear spin relaxation of 129 Xe in solution and in hollow fiber membranes at low and high magnetic field strengths.

PURPOSE: To measure dissolved-phase 129 Xe T1 values at high and low magnetic fields and the field dependence of 129 Xe depolarization by hollow fiber membranes used to infuse hyperpolarized xenon in solution. METHODS: Dissolved-phase T1 measurements were made at 11.7T and 2.1 mT by bubbling xenon in solution and by using a variable delay to allow spins to partially relax back to thermal equilibrium before probing their magnetization. At high field, relaxation values were compared to those obtained by using the small flip angle method. For depolarization studies, we probed the magnetization of the polarized gas diffusing through an exchange membrane module placed at different field strengths. RESULTS: Total loss of polarization was observed for xenon diffusing through hollow fiber membranes at low field, while significant polarization loss (>20%) was observed at magnetic fields up to 2T. Dissolved-phase 129 Xe T1 values were found consistently shorter at 2.1 mT compared to 11.7T. In addition, both O2 and Xe gas concentrations in solution were found to significantly affect dissolved-phase 129 Xe T1 values. CONCLUSION: Dissolved-phase 129 Xe measurements are feasible at low field, but to assess the feasibility of in vivo dissolved-phase imaging and spectroscopy the T1 of xenon in blood will need to be measured. Both O2 and Xe concentrations in solution are found to greatly affect  dissolved-phase 129 Xe T1 values and may explain, along with RF miscalibration, the large discrepancy in previously reported results.

In vivo hyperCEST imaging: Experimental considerations for a reliable contrast.

PURPOSE: HyperCEST contrast relies on the reduction of the solvent signal after selective saturation of the solute magnetization. The scope of this work is to outline the experimental conditions needed to obtain a reliable hyperCEST contrast in vivo, where the "solvent" signal (ie, the dissolved-phase signal) may change over time due to the increase in xenon (Xe) accumulation into tissue. METHODS: Hyperpolarized 129 Xe was delivered to mice at a constant volume and rate using a mechanical ventilator, which triggered the saturation, excitation, and acquisition of the MR signal during the exhale phase of the breath cycle-either every breath or every 2, 3, or 4 breaths. Serial Z-spectra and hyperCEST images were acquired before and after a bolus injection of cucurbit[6]uril to assess possible signal fluctuations and instabilities. RESULTS: The intensity of the dissolved-phase Xe signal was observed to first increase immediately after the beginning of the hyperpolarized gas inhalation and NMR acquisition, and then decrease before reaching a steady-state condition. Once a steady-state dissolved-phase magnetization was established, a reliable hyperCEST contrast, exceeding 40% signal reduction, was observed. CONCLUSION: A reliable hyperCEST contrast can only be obtained after establishing a steady-state dissolved phase 129 Xe magnetization. Under stable physiological conditions, a steady-state dissolved-phase Xe magnetization is only achieved after a series of Xe inhalations and RF excitations, and it requires synchronization of the breathing rate with the MR acquisition.

Low-boiling Point Perfluorocarbon Nanodroplets as Dual-Phase Dual-Modality MR/US Contrast Agent.

Detection of bare gas microbubbles by magnetic resonance (MR) at low concentrations typically used in clinical contrast-ultrasound studies was recently demonstrated using hyperCEST. Despite the enhanced sensitivity achieved with hyperCEST, in vivo translation is challenging as on-resonance saturation of the gas-phase core of microbubbles consequently results in saturation of the gas-phase hyperpolarized 129 Xe within the lungs. Alternatively, microbubbles can be condensed into the liquid phase to form perfluorocarbon nanodroplets, where 129 Xe resonates at a chemical shift that is separated from the gas-phase signal in the lungs. For ultrasound applications, nanodroplets can be acoustically reverted back into their microbubble form to act as a phase-change contrast agent. Here, we show that low-boiling point perfluorocarbons, both in their liquid and gas form, generate phase-dependent hyperCEST contrast. Magnetic resonance detection of ultrasound-mediated phase transition demonstrates that these perfluorocarbons could be used as a dual-phase dual-modality MR/US contrast agent.

Comparison of single breath hyperpolarized 129 Xe MRI with dynamic 19 F MRI in cystic fibrosis lung disease.

PURPOSE: To quantitatively compare dynamic 19 F and single breath hyperpolarized 129 Xe MRI for the detection of ventilation abnormalities in subjects with mild cystic fibrosis (CF) lung disease. METHODS: Ten participants with stable CF and a baseline FEV1 > 70% completed a single imaging session where dynamic 19 F and single breath 129 Xe lung ventilation images were acquired on a 3T MRI scanner. Ventilation defect percentages (VDP) values between 19 F early-breath, 19 F maximum-ventilation, 129 Xe low-resolution, and 129 Xe high-resolution images were compared. Dynamic 19 F images were used to determine gas wash-in/out rates in regions of ventilation congruency and mismatch between 129 Xe and 19 F. RESULTS: VDP values from high-resolution 129 Xe images were greater than from low-resolution images (P = .001), although these values were significantly correlated (r = 0.68, P = .03). Early-breath 19 F VDP and max-vent 19 F VDP also showed significant correlation (r = 0.75, P = .012), with early-breath 19 F VDP values being significantly greater (P < .001). No correlation in VDP values were detected between either 19 F method or high-res 129 Xe images. In addition, the location and volume of ventilation defects were often different when comparing 129 Xe and 19 F images from the same subject. Areas of ventilation congruence displayed the expected ventilation kinetics, while areas of ventilation mismatch displayed abnormally slow gas wash-in and wash-out. CONCLUSION: In CF subjects, ventilation abnormalities are identified by both 19 F and HP 129 Xe imaging. However, these ventilation abnormalities are not entirely congruent. 19 F and HP 129 Xe imaging provide complementary information that enable differentiation of normally ventilated, slowly ventilated, and non-ventilated regions in the lungs.

Magnetic Resonance Detection of Gas Microbubbles via HyperCEST: A Path Toward Dual Modality Contrast Agent.

Gas microbubbles are an established clinical ultrasound contrast agent. They could also become a powerful magnetic resonance (MR) intravascular contrast agent, but their low susceptibility-induced contrast requires high circulating concentrations or the addition of exogenous paramagnetic nanoparticles for MR detection. In order to detect clinical in vivo concentrations of raw microbubbles via MR, an alternative detection scheme must be used. HyperCEST is an NMR technique capable of indirectly detecting signals from very dilute molecules (concentrations well below the NMR detection threshold) that exchange hyperpolarized 129 Xe. Here, we use quantitative hyperCEST to show that microbubbles are very efficient hyperCEST agents. They can accommodate and saturate millions of 129 Xe atoms at a time, allowing for their indirect detection at concentrations as low as 10 femtomolar. The increased MR sensitivity to microbubbles achieved via hyperCEST can bridge the gap for microbubbles to become a dual modality contrast agent.

Accurate quantification of brown adipose tissue mass by xenon-enhanced computed tomography.

Detection and quantification of brown adipose tissue (BAT) mass remains a major challenge, as current tomographic imaging techniques are either nonspecific or lack the necessary resolution to quantify BAT mass, especially in obese phenotypes, in which this tissue may be present but inactive. Here, we report quantification of BAT mass by xenon-enhanced computed tomography. We show that, during stimulation of BAT thermogenesis, the lipophilic gas xenon preferentially accumulates in BAT, leading to a radiodensity enhancement comparable to that seen in the lungs. This enhancement is mediated by a selective reduction in BAT vascular resistance, which greatly increases vascular perfusion of BAT. This enhancement enables precise identification and quantification of BAT mass not only in lean, but also in obese, mouse phenotypes, in which this tissue is invisible to conventional tomographic imaging techniques. The method is developed and validated in rodents and then applied in macaques to assess its feasibility in larger species.

Magnetic resonance imaging of obesity and metabolic disorders: Summary from the 2019 ISMRM Workshop.

More than 100 attendees from Australia, Austria, Belgium, Canada, China, Germany, Hong Kong, Indonesia, Japan, Malaysia, the Netherlands, the Philippines, Republic of Korea, Singapore, Sweden, Switzerland, the United Kingdom, and the United States convened in Singapore for the 2019 ISMRM-sponsored workshop on MRI of Obesity and Metabolic Disorders. The scientific program brought together a multidisciplinary group of researchers, trainees, and clinicians and included sessions in diabetes and insulin resistance; an update on recent advances in water-fat MRI acquisition and reconstruction methods; with applications in skeletal muscle, bone marrow, and adipose tissue quantification; a summary of recent findings in brown adipose tissue; new developments in imaging fat in the fetus, placenta, and neonates; the utility of liver elastography in obesity studies; and the emerging role of radiomics in population-based "big data" studies. The workshop featured keynote presentations on nutrition, epidemiology, genetics, and exercise physiology. Forty-four proffered scientific abstracts were also presented, covering the topics of brown adipose tissue, quantitative liver analysis from multiparametric data, disease prevalence and population health, technical and methodological developments in data acquisition and reconstruction, newfound applications of machine learning and neural networks, standardization of proton density fat fraction measurements, and X-nuclei applications. The purpose of this article is to summarize the scientific highlights from the workshop and identify future directions of work.

Calibration of methylene-referenced lipid-dissolved xenon frequency for absolute MR temperature measurements.

PURPOSE: Absolute MR temperature measurements are currently difficult because they require precalibration procedures specific for tissue types and conditions. Reference of the lipid-dissolved 129 Xe resonance frequency to temperature-insensitive methylene protons (rLDX) has been proposed to remove the effect of macro- and microscopic susceptibility gradients to obtain absolute temperature information. The scope of this work is to evaluate the rLDX chemical shift (CS) dependence on lipid composition to estimate the precision of absolute temperature measurements in lipids. METHODS: Neat triglycerides, vegetable oils, and samples of freshly excised human and rodent adipose tissue (AT) are prepared under 129 Xe atmosphere and studied using high-resolution NMR. The rLDX CS is measured as a function of temperature. 1 H spectra are also acquired and the consistency of methylene-referenced water proton and rLDX CS values are compared in human AT. RESULTS: Although rLDX CS shows a dependence on lipid composition, in human and rodent AT samples the rLDX shows consistent CS values with a similar temperature dependence (-0.2058 ± 0.0010) ppm/°C × T (°C) + (200.15 ± 0.03) ppm, enabling absolute temperature measurements with an accuracy of 0.3°C. Methylene-referenced water CS values present variations of up to 4°C, even under well-controlled conditions. CONCLUSIONS: The rLDX can be used to obtain accurate absolute temperature measurements in AT, opening new opportunities for hyperpolarized 129 Xe MR to measure tissue absolute temperature.

Effect of microscopic susceptibility gradients on chemical-shift-based fat fraction quantification in supraclavicular fat.

BACKGROUND: Susceptibility differences between fat and water can cause changes in the water-fat frequency separation that can negatively affect the accuracy of fat fraction techniques. This may be especially relevant for brown adipose tissue, as MRI fat fraction techniques have been proposed for its detection. PURPOSE: To assess the effect of microscopic magnetic susceptibility gradients on the water-fat frequency separation and its impact on chemical-shift-based fat fraction quantification techniques in the supraclavicular fat, where brown adipose tissue is commonly found in humans. STUDY TYPE: Prospective. POPULATION/SUBJECTS/PHANTOM/SPECIMEN/ANIMAL MODEL: Subjects: 11 healthy volunteers, mean age of 26 and mean BMI of 23, three overweight volunteers, mean age of 38 and mean BMI of 33. Phantoms: bovine phantom and intralipid fat emulsion. Simulations: various water-fat distributions. FIELD STRENGTH/SEQUENCE: Six-echo gradient echo chemical-shift-encoded sequence at 3T. ASSESSMENT: Fat fraction values as obtained from a water-fat spectral model accounting for susceptibility-induced water-fat frequency variations were directly compared to traditional spectral models that assume constant water-fat frequency separation. STATISTICAL TESTS: Two-tail t-tests were used for significance testing (p < 0.05.) A Bayesian Information Criterion difference of 6 between fits was taken as strong evidence of an improved model. RESULTS: Phantom experiments and simulation results showed variations of the water-fat frequency separation up to 0.4 ppm and 0.6 ppm, respectively. In the supraclavicular area, the water-fat frequency separation produced by magnetic susceptibility gradients varied by as much as ±0.4 ppm, with a mean of 0.08 ± 0.14 ppm, producing a mean difference in fat fraction of -1.26 ± 5.26%. DATA CONCLUSION: In the supraclavicular fat depot, microscopic susceptibility gradients that exist within a voxel between water and fat compartments can produce variations in the water-fat frequency separation. These variations may produce fat fraction quantification errors of 5% when a spectral model with a fixed water-fat frequency separation is applied, which could impact MR brown fat techniques. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:141-151.

Correlation distance dependence of the resonance frequency of intermolecular zero quantum coherences and its implication for MR thermometry.

PURPOSE: Because the resonance frequency of water-fat intermolecular zero-quantum coherences (iZQCs) reflects the water-fat frequency separation at the microscopic scale, these frequencies have been proposed and used as a mean to obtain more accurate temperature information. The purpose of this work was to investigate the dependence of the water-fat iZQC resonance frequency on sample microstructure and on the specific choice of the correlation distance. METHODS: The effect of water-fat susceptibility gradients on the water-methylene iZQC resonance frequency was first computed and then measured for different water-fat emulsions and for a mixture of porcine muscle and fat. Similar measurements were also performed for mixed heteronuclear spin systems. RESULTS: A strong dependence of the iZQC resonance frequency on the sample microstructure and on the specific choice of the correlation distance was found for spin systems like water and fat that do not mix, but not for spin systems that mix at the molecular level. CONCLUSIONS: Because water and fat spins do not mix at the molecular level, the water-fat iZQC resonance frequency and its temperature coefficient are not only affected by sample microstructure but also by the specific choice of the correlation distance. Magn Reson Med 79:1429-1438, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Simple and robust referencing system enables identification of dissolved-phase xenon spectral frequencies.

PURPOSE: To assess the effect of macroscopic susceptibility gradients on the gas-phase referenced dissolved-phase 129 Xe (DPXe) chemical shift (CS) and to establish the robustness of a water-based referencing system for in vivo DPXe spectra. METHODS: Frequency shifts induced by spatially varying magnetic susceptibility are calculated by finite-element analysis for the human head and chest. Their effect on traditional gas-phase referenced DPXe CS is then assessed theoretically and experimentally. A water-based referencing system for the DPXe resonances that uses the local water protons as reference is proposed and demonstrated in vivo in rats. RESULTS: Across the human brain, macroscopic susceptibility gradients can induce an apparent variation in the DPXe CS of up to 2.5 ppm. An additional frequency shift as large as 6.5 ppm can exist between DPXe and gas-phase resonances. By using nearby water protons as reference for the DPXe CS, the effect of macroscopic susceptibility gradients is eliminated and consistent CS values are obtained in vivo, regardless of shimming conditions, region of interest analyzed, animal orientation, or lung inflation. Combining in vitro and in vivo spectroscopic measurements finally enables confident assignment of some of the DPXe peaks observed in vivo. CONCLUSION: To use hyperpolarized xenon as a biological probe in tissues, the DPXe CS in specific organs/tissues must be reliably measured. When the gas-phase is used as reference, variable CS values are obtained for DPXe resonances. Reliable peak assignments in DPXe spectra can be obtained by using local water protons as reference. Magn Reson Med 80:431-441, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

A pilot study on the correlation between fat fraction values and glucose uptake values in supraclavicular fat by simultaneous PET/MRI.

PURPOSE: To assess the spatial correlation between MRI and 18F-fludeoxyglucose positron emission tomography (FDG-PET) maps of human brown adipose tissue (BAT) and to measure differences in fat fraction (FF) between glucose avid and non-avid regions of the supraclavicular fat depot using a hybrid FDG-PET/MR scanner. METHODS: In 16 healthy volunteers, mean age of 30 and body mass index of 26, FF, R2*, and FDG uptake maps were acquired simultaneously using a hybrid PET/MR system while employing an individualized cooling protocol to maximally stimulate BAT. RESULTS: Fourteen of the 16 volunteers reported BAT-positive FDG-PET scans. MR FF maps of BAT correlate well with combined FDG-PET/MR maps of BAT only in subjects with intense glucose uptake. The results indicate that the extent of the spatial correlation positively correlates with maximum FDG uptake in the supraclavicular fat depot. No consistent, significant differences were found in FF or R2* between FDG avid and non-avid supraclavicular fat regions. In a few FDG-positive subjects, a small but significant linear decrease in BAT FF was observed during BAT stimulation. CONCLUSION: MR FF, when used in conjunction with FDG uptake maps, can be seen as a valuable, radiation-free alternative to CT and can be used to measure tissue hydration and lipid consumption in some subjects. Magn Reson Med 78:1922-1932, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Accurate MR thermometry by hyperpolarized 129 Xe.

PURPOSE: To investigate the temperature dependence of the resonance frequency of lipid-dissolved xenon (LDX) and to assess the accuracy of LDX-based MR thermometry. METHODS: The chemical shift temperature dependence of water protons, methylene protons, and LDX was measured from samples containing tissues with varying fat contents using a high-resolution NMR spectrometer. LDX results were then used to acquire relative and absolute temperature maps in vivo and the results were compared with PRF-based MR thermometry. RESULTS: The temperature dependence of proton resonance frequency (PRF) is strongly affected by the specific distribution of water and fat. A redistribution of water and fat compartments can reduce the apparent temperature dependence of the water chemical shift from -0.01 ppm/°C to -0.006 ppm, whereas the LDX chemical shift shows a consistent temperature dependence of -0.21 ppm/°C. The use of the methylene protons resonance frequency as internal reference improves the accuracy of LDX-based MR thermometry, but degrades that of PRF-based MR thermometry, as microscopic susceptibility gradients affected lipid and water spins differently. CONCLUSION: The LDX resonance frequency, with its higher temperature dependence, provides more accurate and precise temperature measurements, both in vitro and in vivo. More importantly, the resonance frequency of nearby methylene protons can be used to extract absolute temperature information. Magn Reson Med 78:1070-1079, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

NMR Hyperpolarization Techniques of Gases.

Nuclear spin polarization can be significantly increased through the process of hyperpolarization, leading to an increase in the sensitivity of nuclear magnetic resonance (NMR) experiments by 4-8 orders of magnitude. Hyperpolarized gases, unlike liquids and solids, can often be readily separated and purified from the compounds used to mediate the hyperpolarization processes. These pure hyperpolarized gases enabled many novel MRI applications including the visualization of void spaces, imaging of lung function, and remote detection. Additionally, hyperpolarized gases can be dissolved in liquids and can be used as sensitive molecular probes and reporters. This Minireview covers the fundamentals of the preparation of hyperpolarized gases and focuses on selected applications of interest to biomedicine and materials science.

Detection of brown adipose tissue and thermogenic activity in mice by hyperpolarized xenon MRI.

The study of brown adipose tissue (BAT) in human weight regulation has been constrained by the lack of a noninvasive tool for measuring this tissue and its function in vivo. Existing imaging modalities are nonspecific and intrinsically insensitive to the less active, lipid-rich BAT of obese subjects, the target population for BAT studies. We demonstrate noninvasive imaging of BAT in mice by hyperpolarized xenon gas MRI. We detect a greater than 15-fold increase in xenon uptake by BAT during stimulation of BAT thermogenesis, which enables us to acquire background-free maps of the tissue in both lean and obese mouse phenotypes. We also demonstrate in vivo MR thermometry of BAT by hyperpolarized xenon gas. Finally, we use the linear temperature dependence of the chemical shift of xenon dissolved in adipose tissue to directly measure BAT temperature and to track thermogenic activity in vivo.

Remote detection of hyperpolarized 129Xe resonances via multiple distant dipolar field interactions with 1H.

A remote detection scheme utilizing the distant dipolar field interaction between two different spin species was proposed by Granwehr et al. [J. Magn. Reson. 176(2), 125 (2005)]. In that sequence 1H spins were detected indirectly via their dipolar field interaction with 129Xe spins, which served as the sensing spins. Here we propose a modification of the proposed detection scheme that takes advantage of the longer T1 relaxation time of xenon to create a long lasting dipolar field with which the fast relaxing 1H spins are allowed to interact many times during a single acquisition. This new acquisition scheme improves detection sensitivity, but it also presents some challenges.

Cytomegalovirus infection in patients who underwent allogeneic hematopoietic stem cell transplantation in Portugal: a five-year retrospective review.

Cytomegalovirus (CMV) infection is 1 of the leading causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (aHSCT), mainly within the first 100 days after transplantation. We aimed to characterize CMV infection in a cohort of 305 patients with different malignancies undergoing aHSCT at the Portuguese Institute of Oncology of Porto between January 2008 and December 2012. In total, 184 patients (60.3%) developed CMV infection, mainly viral reactivations rather than primary infections (96.2% versus 3.8%, respectively). The majority of patients (166 of 184) developed CMV infection ≤100 days after transplantation, with median time to infection of 29 days (range, 0 to 1285) and median duration of infection of 10 days (range, 2 to 372). Multivariate analysis revealed that CMV infection was increased in donor (D)-/recipient (R)+ and D+/R+ (odds ratio [OR], 10.5; 95% confidence interval [CI], 4.35 to 25.4; P < .001) and in patients with mismatched or unrelated donors (OR, 2.54; 95% CI, 1.34 to 4.80; P = .004). Cox regression model showed that the risk of death was significantly increased in patients >38 years old (OR, 1.89; 95% CI, 1.14 to 3.12; P = .0137), who underwent transplantation with peripheral blood (OR, 3.02; 95% CI, 1.33 to 6.86; P = .008), with mismatched or unrelated donor (OR, 2.16; 95% CI, 1.48 to 3.13; P < .001), and who developed CMV infection (OR, 1.76; 95% CI, 1.07 to 2.90; P = .025). Moreover, patients who developed CMV infection had a significantly reduced median post-transplantation survival (16 versus 36 months; P = .002).

Molecular MRI for sensitive and specific detection of lung metastases.

Early and specific detection of metastatic cancer cells in the lung (the most common organ targeted by metastases) could significantly improve cancer treatment outcomes. However, the most widespread lung imaging methods use ionizing radiation and have low sensitivity and/or low specificity for cancer cells. Here we address this problem with an imaging method to detect submillimeter-sized metastases with molecular specificity. Cancer cells are targeted by iron oxide nanoparticles functionalized with cancer-binding ligands, then imaged by high-resolution hyperpolarized (3)He MRI. We demonstrate in vivo detection of pulmonary micrometastates in mice injected with breast adenocarcinoma cells. The method not only holds promise for cancer imaging but more generally suggests a fundamentally unique approach to molecular imaging in the lungs.