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Stroke remains a major burden on patients, families, and healthcare professionals, despite major advances in prevention, acute treatment, and rehabilitation. Preclinical basic research can help to better define mechanisms contributing to stroke pathology, and identify therapeutic interventions that can decrease ischemic injury and improve outcomes. Animal models play an essential role in this process, and mouse models are particularly well-suited due to their genetic accessibility and relatively low cost. Here, we review the focal cerebral ischemia models with an emphasis on the middle cerebral artery occlusion technique, a "gold standard" in surgical ischemic stroke models. Also, we highlight several histologic, genetic, and in vivo imaging approaches, including mouse stroke MRI techniques, that have the potential to enhance the rigor of preclinical stroke evaluation. Together, these efforts will pave the way for clinical interventions that can mitigate the negative impact of this devastating disease. [ABSTRACT FROM AUTHOR]

Author(s): Yuan Zheng [1]; G. Wilson Miller [2]; William A. Tobias [1]; Gordon D. Cates (corresponding author) [1, 2] Magnetic resonance imaging (MRI) provides fine spatial resolution, spectral sensitivity and [...]

Purpose: To develop and test compressed sensing–based multiframe 3D MRI of grid‐tagged hyperpolarized gas in the lung. Theory and Methods: Applying grid‐tagging RF pulses to inhaled hyperpolarized gas results in images in which signal intensity is predictably and sparsely distributed. In the present work, this phenomenon was used to produce a sampling pattern in which k‐space is undersampled by a factor of approximately seven, yet regions of high k‐space energy remain densely sampled. Three healthy subjects received multiframe 3D 3He tagging MRI using this undersampling method. Images were collected during a single exhalation at eight timepoints spanning the breathing cycle from end‐of‐inhalation to end‐of‐exhalation. Grid‐tagged images were used to generate 3D displacement maps of the lung during exhalation, and time‐resolved maps of principal strains and fractional volume change were generated from these displacement maps using finite‐element analysis. Results: Tags remained clearly resolvable for 4–6 timepoints (5–8 s) in each subject. Displacement maps revealed noteworthy temporal and spatial nonlinearities in lung motion during exhalation. Compressive normal strains occurred along all three principal directions but were primarily oriented in the head–foot direction. Fractional volume changes displayed clear bilateral symmetry, but with the lower lobes displaying slightly higher change than the upper lobes in 2 of the 3 subjects. Conclusion: We developed a compressed sensing–based method for multiframe 3D MRI of grid‐tagged hyperpolarized gas in the lung during exhalation. This method successfully overcomes previous challenges for 3D dynamic grid‐tagging, allowing time‐resolved biomechanical readouts of lung function to be generated. [ABSTRACT FROM AUTHOR]

We demonstrate a method for simulating restricted diffusion of hyperpolarized gases in lung airspaces that does not rely on an idealized analytic model of alveolar structure. Instead, the restricting geometry was generated from digital representations of histological sections of actual lung tissue obtained from a rabbit model of emphysema. Monte-Carlo simulations of restricted diffusion were performed in the short-time-scale regime, for which the time-dependent diffusivity is quantitatively related to the surface-to-volume ratio (S/V) of the pore space. In each of the eight samples studied, the S/V extracted from the simulated time-dependent diffusivity curves differed by less than 3% from direct assessment of S/V using image-processing methods. Simulated MRI measurements of apparent diffusion coefficients (ADCs) were performed in three representative lung sections to determine the effect of realistic gradient pulse shapes on the extracted S/V values. It was confirmed that ADCs measured at short diffusion times using either narrow or square gradient pulses yield accurate S/V values based on previously derived theoretical relationships. Simulations of triangular and sinusoidal diffusion-sensitizing gradients were then used to quantify the modifications required to extract accurate S/V values from ADC measurements obtained using more realistic gradient waveforms. Index Terms--Apparent diffusion coefficient, hyperpolarized gas, lung surface-to-volume ratio, magnetic resonance imaging.

Hyperpolarized (HP) 129Xe MRI uniquely images pulmonary ventilation, gas exchange, and terminal airway morphology rapidly and safely, providing novel information not possible using conventional imaging modalities or pulmonary function tests. As such, there is mounting interest in expanding the use of biomarkers derived from HP 129Xe MRI as outcome measures in multi‐site clinical trials across a range of pulmonary disorders. Until recently, HP 129Xe MRI techniques have been developed largely independently at a limited number of academic centers, without harmonizing acquisition strategies. To promote uniformity and adoption of HP 129Xe MRI more widely in translational research, multi‐site trials, and ultimately clinical practice, this position paper from the 129Xe MRI Clinical Trials Consortium (https://cpir.cchmc.org/XeMRICTC) recommends standard protocols to harmonize methods for image acquisition in HP 129Xe MRI. Recommendations are described for the most common HP gas MRI techniques—calibration, ventilation, alveolar‐airspace size, and gas exchange—across MRI scanner manufacturers most used for this application. Moreover, recommendations are described for 129Xe dose volumes and breath‐hold standardization to further foster consistency of imaging studies. The intention is that sites with HP 129Xe MRI capabilities can readily implement these methods to obtain consistent high‐quality images that provide regional insight into lung structure and function. While this document represents consensus at a snapshot in time, a roadmap for technical developments is provided that will further increase image quality and efficiency. These standardized dosing and imaging protocols will facilitate the wider adoption of HP 129Xe MRI for multi‐site pulmonary research. [ABSTRACT FROM AUTHOR]

Purpose: To characterize the differences between histogram‐based and image‐based algorithms for segmentation of hyperpolarized gas lung images. Methods: Four previously published histogram‐based segmentation algorithms (ie, linear binning, hierarchical k‐means, fuzzy spatial c‐means, and a Gaussian mixture model with a Markov random field prior) and an image‐based convolutional neural network were used to segment 2 simulated data sets derived from a public (n = 29 subjects) and a retrospective collection (n = 51 subjects) of hyperpolarized 129Xe gas lung images transformed by common MRI artifacts (noise and nonlinear intensity distortion). The resulting ventilation‐based segmentations were used to assess algorithmic performance and characterize optimization domain differences in terms of measurement bias and precision. Results: Although facilitating computational processing and providing discriminating clinically relevant measures of interest, histogram‐based segmentation methods discard important contextual spatial information and are consequently less robust in terms of measurement precision in the presence of common MRI artifacts relative to the image‐based convolutional neural network. Conclusions: Direct optimization within the image domain using convolutional neural networks leverages spatial information, which mitigates problematic issues associated with histogram‐based approaches and suggests a preferred future research direction. Further, the entire processing and evaluation framework, including the newly reported deep learning functionality, is available as open source through the well‐known Advanced Normalization Tools ecosystem. [ABSTRACT FROM AUTHOR]

Focused ultrasound (FUS) mediated blood–brain barrier disruption (BBBD) targets the delivery of systemically‐administered therapeutics to the central nervous system. Preclinical investigations of BBBD have been performed on different anesthetic backgrounds; however, the influence of the choice of anesthetic on the molecular response to BBBD is unknown, despite its potential to critically affect interpretation of experimental therapeutic outcomes. Here, using bulk RNA sequencing, we comprehensively examined the transcriptomic response of both normal brain tissue and brain tissue exposed to FUS‐induced BBBD in mice anesthetized with either isoflurane with medical air (Iso) or ketamine/dexmedetomidine (KD). In normal murine brain tissue, Iso alone elicited minimal differential gene expression (DGE) and repressed pathways associated with neuronal signaling. KD alone, however, led to massive DGE and enrichment of pathways associated with protein synthesis. In brain tissue exposed to BBBD (1 MHz, 0.5 Hz pulse repetition frequency, 0.4 MPa peak‐negative pressure), we systematically evaluated the relative effects of anesthesia, microbubbles, and FUS on the transcriptome. Of particular interest, we observed that gene sets associated with sterile inflammatory responses and cell–cell junctional activity were induced by BBBD, regardless of the choice of anesthesia. Meanwhile, gene sets associated with metabolism, platelet activity, tissue repair, and signaling pathways, were differentially affected by BBBD, with a strong dependence on the anesthetic. We conclude that the underlying transcriptomic response to FUS‐mediated BBBD may be powerfully influenced by anesthesia. These findings raise considerations for the translation of FUS‐BBBD delivery approaches that impact, in particular, metabolism, tissue repair, and intracellular signaling. [ABSTRACT FROM AUTHOR]

Background: Deformable image registration (DIR)‐based lung ventilation mapping is attractive due to its simplicity, and also challenging due to its susceptibility to errors and uncertainties. In this study, we explored the use of 3D Hyperpolarized (HP) gas tagging MRI to evaluate DIR‐based lung ventilation. Method and Material: Three healthy volunteers included in this study underwent both 3D HP gas tagging MRI (t‐MRI) and 3D proton MRI (p‐MRI) using balanced steady‐state free precession pulse sequence at end of inhalation and end of exhalation. We first obtained the reference displacement vector fields (DVFs) from the t‐MRIs by tracking the motion of each tagging grid between the exhalation and the inhalation phases. Then, we determined DIR‐based DVFs from the p‐MRIs by registering the images at the two phases with two commercial DIR algorithms. Lung ventilations were calculated from both the reference DVFs and the DIR‐based DVFs using the Jacobian method and then compared using cross correlation and mutual information. Results: The DIR‐based lung ventilations calculated using p‐MRI varied considerably from the reference lung ventilations based on t‐MRI among all three subjects. The lung ventilations generated using Velocity AI were preferable for the better spatial homogeneity and accuracy compared to the ones using MIM, with higher average cross correlation (0.328 vs 0.262) and larger average mutual information (0.528 vs 0.323). Conclusion: We demonstrated that different DIR algorithms resulted in different lung ventilation maps due to underlining differences in the DVFs. HP gas tagging MRI provides a unique platform for evaluating DIR‐based lung ventilation. [ABSTRACT FROM AUTHOR]

Purpose: To develop a rapid pulse sequence for volumetric MR thermometry. Methods: Simulations were carried out to assess temperature deviation, focal spot distortion/blurring, and focal spot shift across a range of readout durations and maximum temperatures for Cartesian, spiral‐out, and retraced spiral‐in/out (RIO) trajectories. The RIO trajectory was applied for stack‐of‐spirals 3D imaging on a real‐time imaging platform and preliminary evaluation was carried out compared to a standard 2D sequence in vivo using a swine brain model, comparing maximum and mean temperatures measured between the two methods, as well as the temporal standard deviation measured by the two methods. Results: In simulations, low‐bandwidth Cartesian trajectories showed substantial shift of the focal spot, whereas both spiral trajectories showed no shift while maintaining focal spot geometry. In vivo, the 3D sequence achieved real‐time 4D monitoring of thermometry, with an update time of 2.9–3.3 s. Conclusion: Spiral imaging, and RIO imaging in particular, is an effective way to speed up volumetric MR thermometry. Magn Reson Med 79:3122–3127, 2018. © 2017 International Society for Magnetic Resonance in Medicine. [ABSTRACT FROM AUTHOR]

Purpose To evaluate T2 [ABSTRACT FROM AUTHOR]

Purpose To develop a three-dimensional, free-breathing, late gadolinium enhancement (3D FB-LGE) cardiovascular magnetic resonance (CMR) technique, and to compare it with clinically used two-dimensional breath-hold LGE (2D BH-LGE). Methods The proposed 3D FB-LGE method consisted of inversion preparation, inversion delay, fat saturation, outer volume suppression, one-dimensional projection navigators, and a segmented stack of spirals acquisition. The 3D FB-LGE and 2D BH-LGE scans were performed on 29 cardiac patients. Qualitative analysis and quantitative analysis (in patients with scar) were performed. Results No significant differences were noted between the 3D FB-LGE and 2D BH-LGE data sets in terms of overall image quality score (2D: 4.69 ± 0.60 versus 3D: 4.55 ± 0.51, P = 0.46) and image artifact score (2D: 1.10 ± 0.31 versus 3D: 1.17 ± 0.38; P = 0.63). The average difference in fractional scar volume between the 3D and 2D methods was 1.9% (n = 5). Acquisition time was significantly shorter for the 3D FB-LGE over 2D BH-LGE by a factor of 2.83 ± 0.77 ( P < 0.0001). Conclusions The 3D FB-LGE is a viable option for patients, particularly in acute settings or in patients who are unable to comply with breath-hold instructions. Magn Reson Med 77:1533-1543, 2017. © 2016 International Society for Magnetic Resonance in Medicine [ABSTRACT FROM AUTHOR]

Purpose: To evaluate regional anisotropy of lung-airspace orientation by assessing the dependence of helium-3 ((3) He) apparent diffusion coefficient (ADC) values on the direction of diffusion sensitization at two field strengths.Materials and Methods: Hyperpolarized (3) He diffusion-weighted magnetic resonance imaging (MRI) of the lung was performed at 0.43T and 1.5T in 12 healthy volunteers. A gradient-echo pulse sequence was used with a bipolar diffusion-sensitization gradient applied separately along three orthogonal directions. ADC maps, median ADC values, and signal-to-noise ratios were calculated from the diffusion-weighted images. Two readers scored the ADC maps for increased values at lung margins, major fissures, or within focal central regions.Results: ADC values were found to depend on the direction of diffusion sensitization (P < 0.01, except for craniocaudal vs. anteroposterior directions at 1.5T) and were increased at the lateral and medial surfaces for left-right diffusion sensitization (12 of 12 subjects); at the apex and base (9 of 12), and along the major fissure (8 of 12), for craniocaudal diffusion sensitization; and at the most anterior and posterior lung (10 of 12) for anteroposterior diffusion sensitization. Median ADC values at 0.43T (0.201 ± 0.017, left-right; 0.193 ± 0.019, craniocaudal; and 0.187 ± 0.017 cm(2) /s, anteroposterior) were slightly lower than those at 1.5T (0.205 ± 0.017, 0.197 ± 0.017 and 0.194 ± 0.016 cm(2) /s, respectively; P < 0.05).Conclusion: These findings indicate that diffusion-weighted hyperpolarized (3) He MRI can detect regional anisotropy of lung-airspace orientation, including that associated with preferential orientation of terminal airways near pleural surfaces. [ABSTRACT FROM AUTHOR]

Purpose To develop and validate a method for acquiring helium-3 (3He) and proton (1H) three-dimensional (3D) image sets of the human lung with isotropic spatial resolution within a 10-s breath-hold by using compressed sensing (CS) acceleration, and to assess the fidelity of undersampled images compared with fully sampled images. Methods The undersampling scheme for CS acceleration was optimized and tested using 3He ventilation data. Rapid 3D acquisition of both 3He and 1H data during one breath-hold was then implemented, based on a balanced steady-state free-precession pulse sequence, by random undersampling of k-space with reconstruction by means of minimizing the L1 norm and total variance. CS-reconstruction fidelity was evaluated quantitatively by comparing fully sampled and retrospectively undersampled image sets. Results Helium-3 and 1H 3D image sets of the lung with isotropic 3.9-mm resolution were acquired during a single breath-hold in 12 s and 8 s using acceleration factors of 2 and 3, respectively. Comparison of fully sampled and retrospectively undersampled 3He and 1H images yielded mean absolute errors <10% and structural similarity indices >0.9. Conclusion By randomly undersampling k-space and using CS reconstruction, high-quality 3He and 1H 3D image sets with isotropic 3.9-mm resolution can be acquired within an 8-s breath-hold. Magn Reson Med 74:1110-1115, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: During high-intensity focused ultrasound (HIFU) surgical procedures, there is a need to rapidly ablate pathological tissue while minimizing damage to healthy tissue. Current techniques are limited by relatively long procedure times and risks of off-target heating of healthy tissue. One possible solution is the use of microbubbles, which can improve the efficiency of thermal energy delivery during HIFU procedures. However, microbubbles also suffer from limitations such as low spatial selectivity and short circulation time in vivo. In this study, the use of a dual-perfluorocarbon nanodroplet that can enhance thermal ablation, yet retains high spatial selectivity and circulation half-life, was evaluated in vivo and compared to traditional microbubble agents during HIFU ablations of rat liver. Methods: High-intensity focused ultrasound (1.1 MHz, 4.1 MPa, 15-s continuous wave) was applied to rat liver in vivo, and heating was monitored during sonication by magnetic resonance thermometry. Thermometry data were analyzed to quantify temperature rise and ablated area, both at the target and prefocally, for HIFU applied 5, 15, or 95 min after intravenous injection of either nanodroplet or microbubble agents. Sham control experiments (no injected agents) were also performed. Results: At all three time points, nanodroplets significantly enhanced thermal delivery to the target, achieving temperatures 130 % higher and ablated areas 30 times larger than no-agent control sonications. Nanodroplets did not significantly enhance off-target surface heating. Microbubbles also resulted in significantly greater thermal delivery, but heating was concentrated at the proximal surface of the animal, causing skin burns. Furthermore, microbubbles resulted in lower thermal delivery to the desired target than even the control case, with the notable exception of the 95-min time point. Conclusions: Results indicate that the nanodroplet formulation studied here can substantially increase thermal delivery at the acoustic focus while avoiding prefocal heating. In contrast, microbubbles resulted in greater prefocal heating and less heating at the target. Furthermore, nanodroplets are sufficiently stable to enhance HIFU ablation in vivo for at least 1.5 h after injection. The use of a dual-perfluorocarbon nanodroplet formulation as described herein could substantially reduce HIFU procedure times without increasing the risk of skin burns. [ABSTRACT FROM AUTHOR]

Purpose: Transcranial magnetic resonance-guided focused ultrasound (TcMRgFUS) brain treatment systems compensate for skull-induced beam aberrations by adjusting the phase and amplitude of individual ultrasound transducer elements. These corrections are currently calculated based on a preacquired computed tomography (CT) scan of the patient's head. The purpose of the work presented here is to demonstrate the feasibility of using ultrashort echo-time magnetic resonance imaging (UTE MRI) instead of CT to calculate and apply aberration corrections on a clinical TcMRgFUS system. Methods: Phantom experiments were performed in three ex-vivo human skulls filled with tissuemimicking hydrogel. Each skull phantom was imaged with both CT and UTE MRI. The MR images were then segmented into "skull" and "not-skull" pixels using a computationally efficient, thresholdbased algorithm, and the resulting 3D binary skull map was converted into a series of 2D virtual CT images. Each skull was mounted in the head transducer of a clinical TcMRgFUS system (ExAblate Neuro, Insightec, Israel), and transcranial sonications were performed using a power setting of approximately 750 acoustic watts at several different target locations within the electronic steering range of the transducer. Each target location was sonicated three times: once using aberration corrections calculated from the actual CT scan, once using corrections calculated from the MRI-derived virtual CT scan, and once without applying any aberration correction. MR thermometry was performed in conjunction with each 10-s sonication, and the highest single-pixel temperature rise and surrounding-pixel mean were recorded for each sonication. Results: The measured temperature rises were ~45% larger for aberration-corrected sonications than for noncorrected sonications. This improvement was highly significant (p < 10-4). The difference between the single-pixel peak temperature rise and the surrounding-pixel mean, which reflects the sharpness of the thermal focus, was also significantly larger for aberration-corrected sonications. There was no significant difference between the sonication results achieved using CT-based and MR-based aberration correction. Conclusions: The authors have demonstrated that transcranial focal heating can be significantly improved in vitro by using UTE MRI to compute skull-induced ultrasound aberration corrections. Their results suggest that UTE MRI could be used instead of CT to implement such corrections on current 0.7 MHz clinical TcMRgFUS devices. The MR image acquisition and segmentation procedure demonstrated here would add less than 15 min to a clinical MRgFUS treatment session. [ABSTRACT FROM AUTHOR]

The field of proton lung MRI is advancing on a variety of fronts. In the realm of functional imaging, it is now possible to use arterial spin labeling (ASL) and oxygen-enhanced imaging techniques to quantify regional perfusion and ventilation, respectively, in standard units of measurement. By combining these techniques into a single scan, it is also possible to quantify the local ventilation-perfusion ratio, which is the most important determinant of gas-exchange efficiency in the lung. To demonstrate potential for accurate and meaningful measurements of lung function, this technique was used to study gravitational gradients of ventilation, perfusion, and ventilation-perfusion ratio in healthy subjects, yielding quantitative results consistent with expected regional variations. Such techniques can also be applied in the time domain, providing new tools for studying temporal dynamics of lung function. Temporal ASL measurements showed increased spatial-temporal heterogeneity of pulmonary blood flow in healthy subjects exposed to hypoxia, suggesting sensitivity to active control mechanisms such as hypoxic pulmonary vasoconstriction, and illustrating that to fully examine the factors that govern lung function it is necessary to consider temporal as well as spatial variability. Further development to increase spatial coverage and improve robustness would enhance the clinical applicability of these new functional imaging tools. In the realm of structural imaging, pulse sequence techniques such as ultrashort echo-time radial k-space acquisition, ultrafast steady-state free precession, and imaging-based diaphragm triggering can be combined to overcome the significant challenges associated with proton MRI in the lung, enabling high-quality three-dimensional imaging of the whole lung in a clinically reasonable scan time. Images of healthy and cystic fibrosis subjects using these techniques demonstrate substantial promise for non-contrast pulmonary angiography and detailed depiction of airway disease. Although there is opportunity for further optimization, such approaches to structural lung imaging are ready for clinical testing. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Magnetic-resonance spectroscopy and imaging using hyperpolarized xenon-129 show great potential for evaluation of the most important function of the human lung -- gas exchange. In particular, chemical shift saturation recovery (CSSR) xenon-129 spectroscopy provides important physiological information for the lung as a whole by characterizing the dynamic process of gas exchange, while dissolved-phase (DP) xenon-129 imaging captures the time-averaged regional distribution of gas uptake by lung tissue and blood. Herein, we present recent advances in assessing lung function using CSSR spectroscopy and DP imaging in a total of 45 subjects (23 healthy, 13 chronic obstructive pulmonary disease (COPD) and 9 asthma). From CSSR acquisitions, the COPD subjects showed red blood cell to tissue-plasma (RBC-to-TP) ratios below the average for the healthy subjects ( p < 0.001), but significantly higher septal wall thicknesses as compared with the healthy subjects ( p < 0.005); the RBC-to-TP ratios for the asthmatic subjects fell outside two standard deviations (either higher or lower) from the mean of the healthy subjects, although there was no statistically significant difference for the average ratio of the study group as a whole. Similarly, from the 3D DP imaging acquisitions, we found that all the ratios (TP to gas phase (GP), RBC to GP, RBC to TP) measured in the COPD subjects were lower than those from the healthy subjects ( p < 0.05 for all ratios), while these ratios in the asthmatic subjects differed considerably between subjects. Despite having been performed at different lung inflation levels, the RBC-to-TP ratios measured by CSSR and 3D DP imaging were fairly consistent with each other, with a mean difference of 0.037 (ratios from 3D DP imaging larger). In ten subjects the RBC-to-GP ratios obtained from the 3D DP imaging acquisitions were also highly correlated with their diffusing capacity of the lung for carbon monoxide per unit alveolar volume ratios measured by pulmonary function testing ( R = 0.91). Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose To develop a breathhold acquisition for regional mapping of ventilation and the fractions of hyperpolarized xenon-129 (Xe129) dissolved in tissue (lung parenchyma and plasma) and red blood cells (RBCs), and to perform an exploratory study to characterize data obtained in human subjects. Materials and Methods A three-dimensional, multi-echo, radial-trajectory pulse sequence was developed to obtain ventilation (gaseous Xe129), tissue, and RBC images in healthy subjects, smokers, and asthmatics. Signal ratios (total dissolved Xe129 to gas, tissue-to-gas, RBC-to-gas, and RBC-to-tissue) were calculated from the images for quantitative comparison. Results Healthy subjects demonstrated generally uniform values within coronal slices, and a gradient in values along the anterior-to-posterior direction. In contrast, images and associated ratio maps in smokers and asthmatics were generally heterogeneous and exhibited values mostly lower than those in healthy subjects. Whole-lung values of total dissolved Xe129 to gas, tissue-to-gas, and RBC-to-gas ratios in healthy subjects were significantly larger than those in diseased subjects. Conclusion Regional maps of tissue and RBC fractions of dissolved Xe129 were obtained from a short breathhold acquisition, well tolerated by healthy volunteers and subjects with obstructive lung disease. Marked differences were observed in spatial distributions and overall amounts of Xe129 dissolved in tissue and RBCs among healthy subjects, smokers and asthmatics. J. Magn. Reson. Imaging 2014;39:346-359. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose: To propose and test the feasibility of a novel method for quantifying 3D regional pulmonary kinematics from hyperpolarized helium-3 tagged MRI in human subjects using a tailored image processing pipeline and a recently developed nonrigid registration framework. Materials and Methods: Following image acquisition, inspiratory and expiratory tagged 3He magnetic resonance (MR) images were preprocessed using various image filtering techniques to enhance the tag surfaces. Segmentation of the three orthogonal sets of tag planes in each lung produced distinct point-set representations of the tag surfaces. Using these labeled point-sets, deformation fields and corresponding strain maps were obtained via nonrigid point-set registration. Kinematic analysis was performed on three volunteers. Results: Tag lines in inspiratory and expiratory images were coregistered producing a continuous 3D correspondence mapping. Average displacement and directional strains were calculated in three subjects in the inferior, mid, and superior portions of the right and left lungs. As expected, the predominant direction of displacements with expiration is from inferior to superior. Conclusion: Kinematic quantitation of pulmonary motion using tagged 3He MRI is feasible using the applied image preprocessing filtering techniques and nonrigid point-set registration. Potential benefits from regional pulmonary kinematic quantitation include the facilitation of diagnosis and local assessment of disease progression. J. Magn. Reson. Imaging 2010;31:1236-1241. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

A pulse-sequence strategy was developed for generating regional maps of alveolar oxygen partial pressure ( pO2) in a single 6-sec breath hold, for use in human subjects with impaired lung function. Like previously described methods, pO2 values are obtained by measuring the oxygen-induced T1 relaxation of inhaled hyperpolarized 3He. Unlike other methods, only two 3He images are acquired: one with reverse-centric and the other with centric phase-encoding order. This phase-encoding arrangement minimizes the effects of regional flip-angle variations, so that an accurate map of instantaneous pO2 can be calculated from two images acquired a few seconds apart. By combining this phase-encoding strategy with variable flip angles, the vast majority of the hyperpolarized magnetization goes directly into the T1 measurement, minimizing noise in the resulting pO2 map. The short-breath-hold pulse sequence was tested in phantoms containing known O2 concentrations. The mean difference between measured and prepared pO2 values was 1 mm Hg. The method was also tested in four healthy volunteers and three lung-transplant patients. Maps of healthy subjects were largely uniform, whereas focal regions of abnormal pO2 were observed in diseased subjects. Mean pO2 values varied with inhaled O2 concentration. Mean pO2 was consistent with normal steady-state values in subjects who inhaled 3He diluted only with room air. Magn Reson Med 63:127-136, 2010. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Purpose: To investigate short- and long-time-scale (3)He diffusion in asthma.Materials and Methods: A hybrid MRI sequence was developed to obtain co-registered short- and long-time-scale apparent diffusion coefficient (ADC) maps during a single breath-hold. The study groups were: asthma (n = 14); healthy (n = 14); chronic obstructive pulmonary disease (COPD) (n = 9). Correlations were made between mean-ADC and %ADC-abn (abnormal) (%pixels with ADC > mean +2 SD of healthy) at both time scales and spirometry. Sensitivities were determined using receiver operating characteristic (ROC) analysis.Results: For asthmatics, the short- and long-time-scale group-mean ADCs were 0.254 +/- 0.032 cm(2)/s and 0.0237 +/- 0.0055 cm(2)/s, respectively, representing a 9% and 27% (P = 0.038 and P = 0.005) increase compared to the healthy group. The group-mean %ADC-abn were 6.4% +/- 3.7% and 17.5% +/- 14.2%, representing a 107% and 272% (P = 0.004 and P = 0.006) increase. For COPD much greater elevations were observed. %ADC-abn provided better discrimination than mean-ADC between asthmatic and healthy subjects. In asthmatics ADC did not correlate with spirometry.Conclusion: With long-time scale (3)He diffusion magnetic resonance imaging (MRI) changes in lung microstructure were detected in asthma that more conspicuous regionally than at the short time scale. The hybrid diffusion method is a novel means of identifying small airway disease. [ABSTRACT FROM AUTHOR]

Purpose To investigate short- and long-time-scale 3He diffusion in asthma. Materials and Methods A hybrid MRI sequence was developed to obtain coregistered short- and long-time-scale apparent diffusion coefficient (ADC) maps during a single breath-hold. The study groups were: asthma ( n = 14); healthy ( n = 14); chronic obstructive pulmonary disease (COPD) ( n = 9). Correlations were made between mean-ADC and %ADC-abn (abnormal) (%pixels with ADC > mean +2 SD of healthy) at both time scales and spirometry. Sensitivities were determined using receiver operating characteristic (ROC) analysis. Results For asthmatics, the short- and long-time-scale group-mean ADCs were 0.254 ± 0.032 cm2/s and 0.0237 ± 0.0055 cm2/s, respectively, representing a 9% and 27% ( P = 0.038 and P = 0.005) increase compared to the healthy group. The group-mean %ADC-abn were 6.4% ± 3.7% and 17.5% ± 14.2%, representing a 107% and 272% ( P = 0.004 and P = 0.006) increase. For COPD much greater elevations were observed. %ADC-abn provided better discrimination than mean-ADC between asthmatic and healthy subjects. In asthmatics ADC did not correlate with spirometry. Conclusion With long-time scale 3He diffusion magnetic resonance imaging (MRI) changes in lung microstructure were detected in asthma that more conspicuous regionally than at the short time scale. The hybrid diffusion method is a novel means of identifying small airway disease. J. Magn. Reson. Imaging 2008;28:80-88. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

A stimulated-echo-based technique was developed to measure the regional apparent diffusion coefficient (ADC) of hyperpolarized 3He during a single breathhold for diffusion times of 25 ms or greater. Compared to previous methods, a substantially shorter minimum diffusion time was achieved by decoupling diffusion sensitization from image acquisition. A hyperpolarized-gas phantom was used to validate the method, which was then tested in four healthy subjects in whom regional ADC maps were acquired with diffusion times of 50, 200, and 1500 ms and a tag wavelength of 5 or 10 mm. ADC values from healthy subjects were in good agreement with reported literature values and decreased with increasing diffusion time. Mean ADC values were ≈0.07, 0.03, and 0.015 cm2/s for diffusion times of 50, 200, and 1500 ms, respectively. ADC maps were generally homogeneous, with similar mean values when measured with the same parameters in different subjects. Magn Reson Med 59:673-678, 2008. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Purpose: To measure lung motion between end-inhalation and end-exhalation using a hyperpolarized helium-3 (HP (3)He) magnetic resonance (MR) tagging technique.Methods and Materials: Three healthy volunteers underwent MR tagging studies after inhalation of 1 L HP (3)He gas diluted with nitrogen. Multiple-slice two-dimensional and volumetric three-dimensional MR tagged images of the lungs were obtained at end-inhalation and end-exhalation, and displacement vector maps were computed.Results: The grids of tag lines in the HP (3)He MR images were well defined at end-inhalation and remained evident at end-exhalation. Displacement vector maps clearly demonstrated the regional lung motion and deformation that occurred during exhalation. Discontinuity and differences in motion pattern between two adjacent lung lobes were readily resolved.Conclusions: Hyperpolarized helium-3 MR tagging technique can be used for direct in vivo measurement of respiratory lung motion on a regional basis. This technique may lend new insights into the regional pulmonary biomechanics and thus provide valuable information for the deformable registration of lung. [ABSTRACT FROM AUTHOR]

A stimulated-echo-based technique was developed to measure the long-time-scale apparent diffusion coefficient (ADC) of hyperpolarized 3He during a single breath-hold acquisition. Computer simulations were used to evaluate the performance of the technique and guide the selection of appropriate parameter values for obtaining accurate ADC values. The technique was used in 10 healthy subjects and two subjects with chronic obstructive pulmonary disease (COPD) to measure the global ADC for diffusion times between a few tenths of a second and several seconds, and to acquire spatial maps of the ADC for a diffusion time of 1.5 s. The reproducibility of the technique and its sensitivity to the direction of diffusion sensitization were also investigated. In healthy subjects, global ADC values decreased by severalfold over the range of diffusion times measured (mean values = 0.039 and 0.023 cm2/s at diffusion times of 0.61 and 1.54 s, respectively). ADC maps were generally uniform, with mean values similar to the corresponding global values. For the two COPD subjects, global ADC values were substantially greater than those of every healthy subject at all diffusion times measured. In addition, regional elevations of ADC values were far more conspicuous on long-time-scale ADC maps than on short-time-scale ADC maps. Magn Reson Med, 2006. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The article discusses a research examining delivery of systemically administered gene therapies to brain tumors. It mentions that augmentation of brain tumor interstitial flow through magnetic resonance image focused ultrasound promotes brain-penetrating nanoparticle dispersion and transfection across the blood-brain barrier (BBB) and blood-tumor barrier (BTB).

Purpose: To develop a dynamic magnetic resonance imaging (MRI) tagging technique using hyperpolarized helium-3 (HP He-3) to track lung motion. Methods and Materials: An accelerated non-Cartesian k-space trajectory was used to gain acquisition speed, at the cost of introducing image artifacts, providing a viable strategy for obtaining whole-lung coverage with adequate temporal resolution. Multiple-slice two-dimensional dynamic images of the lung were obtained in three healthy subjects after inhaling He-3 gas polarized to 35%–40%. Displacement, strain, and ventilation maps were computed from the observed motion of the grid peaks. Results: Both temporal and spatial variations of pulmonary mechanics were observed in normal subjects, including shear motion between different lobes of the same lung. Conclusion: These initial results suggest that dynamic imaging of grid-tagged hyperpolarized magnetization may potentially be a powerful tool for observing and quantifying pulmonary biomechanics on a regional basis and for assessing, validating, and improving lung deformable image registration algorithms. [Copyright &y& Elsevier]

Background: Cerebral cavernous malformations (CCMs) are vascular neoplasms in the brain that can cause debilitating symptoms. Current treatments pose significant risks to some patients, motivating the development of new nonsurgical options. We recently discovered that focused ultrasound-mediated blood-brain barrier opening (FUS) arrests CCM formation and growth. Here, we build on this discovery and assess the ability of FUS to deliver model therapeutics into CCMs., Methods: Quantitative T1 mapping MRI sequences were used with 1 kDa (MultiHance; MH) and 17 kDa (GadoSpin D; GDS) contrast agents to assess the FUS-mediated delivery and penetration of model small molecule drugs and biologics, respectively, into CCMs of Krit1 mutant mice., Results: FUS elevated the rate of MH delivery to both the lesion core (4.6-fold) and perilesional space (6.7-fold). Total MH delivery more than doubled in the lesion core and tripled in the perilesional space when FUS was applied immediately prior to MH injection. For the model biologic drug (i.e. GDS), FUS was of greater relative benefit, resulting in 21.7-fold and 3.8-fold delivery increases to the intralesional and perilesional spaces, respectively., Conclusions: FUS is capable of impelling the delivery and penetration of therapeutics into the complex and disorganized CCM microenvironment. Benefits to small molecule drug delivery are more evident in the perilesional space, while benefits to biologic delivery are more evident in CCM cores. These findings, when combined with ability of FUS alone to control CCMs, highlight the potential of FUS to serve as a powerful non-invasive therapeutic platform for CCM.

Hyperpolarized 129 Xe MRI comprises a unique array of structural and functional lung imaging techniques. Technique standardization across sites is increasingly important given the recent FDA approval of 129 Xe as an MR contrast agent and as interest in 129 Xe MRI increases among research and clinical institutions. Members of the 129 Xe MRI Clinical Trials Consortium (Xe MRI CTC) have agreed upon best practices for each of the key aspects of the 129 Xe MRI workflow, and these recommendations are summarized in a recent publication. This work provides practical information to develop an end-to-end workflow for collecting 129 Xe MR images of lung ventilation according to the Xe MRI CTC recommendations. Preparation and administration of 129 Xe for MR studies will be discussed and demonstrated, with specific topics including choice of appropriate gas volumes for entire studies and for individual MR scans, preparation and delivery of individual 129 Xe doses, and best practices for monitoring subject safety and 129 Xe tolerability during studies. Key MR technical considerations will also be covered, including pulse sequence types and optimized parameters, calibration of 129 Xe flip angle and center frequency, and 129 Xe MRI ventilation image analysis.

Purpose: To assess the effect of lung volume on measured values and repeatability of xenon 129 ( 129 Xe) gas uptake metrics in healthy volunteers and participants with chronic obstructive pulmonary disease (COPD)., Materials and Methods: This Health Insurance Portability and Accountability Act-compliant prospective study included data (March 2014-December 2015) from 49 participants (19 with COPD [mean age, 67 years ± 9 (SD)]; nine women]; 25 older healthy volunteers [mean age, 59 years ± 10; 20 women]; and five young healthy women [mean age, 23 years ± 3]). Thirty-two participants underwent repeated 129 Xe and same-breath-hold proton MRI at residual volume plus one-third forced vital capacity (RV+FVC/3), with 29 also undergoing one examination at total lung capacity (TLC). The remaining 17 participants underwent imaging at TLC, RV+FVC/3, and residual volume (RV). Signal ratios between membrane, red blood cell (RBC), and gas-phase compartments were calculated using hierarchical iterative decomposition of water and fat with echo asymmetry and least-squares estimation (ie, IDEAL). Repeatability was assessed using coefficient of variation and intraclass correlation coefficient, and volume relationships were assessed using Spearman correlation and Wilcoxon rank sum tests., Results: Gas uptake metrics were repeatable at RV+FVC/3 (intraclass correlation coefficient = 0.88 for membrane/gas; 0.71 for RBC/gas, and 0.88 for RBC/membrane). Relative ratio changes were highly correlated with relative volume changes for membrane/gas ( r = -0.97) and RBC/gas ( r = -0.93). Membrane/gas and RBC/gas measured at RV+FVC/3 were significantly lower in the COPD group than the corresponding healthy group ( P ≤ .001). However, these differences lessened upon correction for individual volume differences ( P = .23 for membrane/gas; P = .09 for RBC/gas)., Conclusion: Dissolved-phase 129 Xe MRI-derived gas uptake metrics were repeatable but highly dependent on lung volume during measurement. Keywords: Blood-Air Barrier, MRI, Chronic Obstructive Pulmonary Disease, Pulmonary Gas Exchange, Xenon Supplemental material is available for this article © RSNA, 2023., Competing Interests: Disclosures of conflicts of interest: W.J.G. No relevant relationships. K.Q. No relevant relationships. M.H. No relevant relationships. L.Z. National Key R&D Program of China 2022ZD0118004, the Alzheimer’s Association through AARF-18-566347, the Zhejiang Provincial Natural Science Foundation of China under grant no. LGJ22H180004, 2020R01003, 2022C03057, the Fundamental Research Funds for the Central Universities 2021FZZX002-05, MOE Frontier Science Center for Brain Science & Brain-Machine Integration, Zhejiang University, DOBI Medical; systems and methods for accelerated MR thermometry. US10722137B2. Samuel Fielden, Li Zhao, Wilson Miller, Xue Feng, Max Wintermark, Kim Butts Pauly, Craig H. Meyer. 2020-07-28 System and Method for Improved Spin-Echo-Based Magnetic Resonance Imaging. US16498672. David C. Alsop, Li Zhao. 2021-11-02. N.J.T. No relevant relationships. J.T.P. No relevant relationships. J.F.M. No relevant relationships. Y.M.S. NIH funding HL132177. A.M.R. No relevant relationships. T.A.A. Grant/contract for Polarean Clinical Trial, consultant for Polarean, speaker for Polarean. J.P.M. NIH-NHLBI R01 HL109618 grants; research grant from Siemens Medical Solutions not related to the content of this manuscript. G.W.M. Grants from National Institutes of Health (R01 HL109618, R01 HL105586, R01 CA172595; payments paid to University of Virginia)., (© 2023 by the Radiological Society of North America, Inc.)

Background: Cerebral cavernous malformations, also known as cavernous angiomas, are blood vessel abnormalities comprised of clusters of grossly enlarged and hemorrhage-prone capillaries. The prevalence in the general population, including asymptomatic cases, is estimated to be 0.5%. Some patients develop severe symptoms, including seizures and focal neurological deficits, whereas others remain asymptomatic. The causes of this remarkable presentation heterogeneity within a primarily monogenic disease remain poorly understood., Methods: We established a chronic mouse model of cerebral cavernous malformations, induced by postnatal ablation of Krit1 with Pdgfb-CreERT2 , and examined lesion progression in these mice with T2-weighted 7T magnetic resonance imaging (MRI). We also established a modified protocol for dynamic contrast-enhanced MRI and produced quantitative maps of gadolinium tracer gadobenate dimeglumine. After terminal imaging, brain slices were stained with antibodies against microglia, astrocytes, and endothelial cells., Results: These mice develop cerebral cavernous malformations lesions gradually over 4 to 5 months of age throughout the brain. Precise volumetric analysis of individual lesions revealed nonmonotonous behavior, with some lesions temporarily growing smaller. However, the cumulative lesional volume invariably increased over time and after about 2 months followed a power trend. Using dynamic contrast-enhanced MRI, we produced quantitative maps of gadolinium in the lesions, indicating a high degree of heterogeneity in lesional permeability. MRI properties of the lesions were correlated with cellular markers for endothelial cells, astrocytes, and microglia. Multivariate comparisons of MRI properties of the lesions with cellular markers for endothelial and glial cells revealed that increased cell density surrounding lesions correlates with stability, whereas denser vasculature within and surrounding the lesions may correlate with high permeability., Conclusions: Our results lay a foundation for better understanding individual lesion properties and provide a comprehensive preclinical platform for testing new drug and gene therapies for controlling cerebral cavernous malformations., Competing Interests: Disclosures None.

Hyperpolarized (HP) 129 Xe MRI uniquely images pulmonary ventilation, gas exchange, and terminal airway morphology rapidly and safely, providing novel information not possible using conventional imaging modalities or pulmonary function tests. As such, there is mounting interest in expanding the use of biomarkers derived from HP 129 Xe MRI as outcome measures in multi-site clinical trials across a range of pulmonary disorders. Until recently, HP 129 Xe MRI techniques have been developed largely independently at a limited number of academic centers, without harmonizing acquisition strategies. To promote uniformity and adoption of HP 129 Xe MRI more widely in translational research, multi-site trials, and ultimately clinical practice, this position paper from the 129 Xe MRI Clinical Trials Consortium (https://cpir.cchmc.org/XeMRICTC) recommends standard protocols to harmonize methods for image acquisition in HP 129 Xe MRI. Recommendations are described for the most common HP gas MRI techniques-calibration, ventilation, alveolar-airspace size, and gas exchange-across MRI scanner manufacturers most used for this application. Moreover, recommendations are described for 129 Xe dose volumes and breath-hold standardization to further foster consistency of imaging studies. The intention is that sites with HP 129 Xe MRI capabilities can readily implement these methods to obtain consistent high-quality images that provide regional insight into lung structure and function. While this document represents consensus at a snapshot in time, a roadmap for technical developments is provided that will further increase image quality and efficiency. These standardized dosing and imaging protocols will facilitate the wider adoption of HP 129 Xe MRI for multi-site pulmonary research., (© 2021 International Society for Magnetic Resonance in Medicine.)

Many deep learning (DL) frameworks have demonstrated state-of-the-art performance in the super-resolution (SR) task of magnetic resonance imaging, but most performances have been achieved with simulated low-resolution (LR) images rather than LR images from real acquisition. Due to the limited generalizability of the SR network, enhancement is not guaranteed for real LR images because of the unreality of the training LR images. In this study, we proposed a DL-based SR framework with an emphasis on data construction to achieve better performance on real LR MR images. The framework comprised two steps: (a) downsampling training using a generative adversarial network (GAN) to construct more realistic and perfectly matched LR/high-resolution (HR) pairs. The downsampling GAN input was real LR and HR images. The generator translated the HR images to LR images and the discriminator distinguished the patch-level difference between the synthetic and real LR images. (b) SR training was performed using an enhance4d deep super-resolution network (EDSR). In the controlled experiments, three EDSRs were trained using our proposed method, Gaussian blur, and k-space zero-filling. As for the data, liver MR images were obtained from 24 patients using breath-hold serial LR and HR scans (only HR images were used in the conventional methods). The k-space zero-filling group delivered almost zero enhancement on the real LR images and the Gaussian group produced a considerable number of artifacts. The proposed method exhibited significantly better resolution enhancement and fewer artifacts compared with the other two networks. Our method outperformed the Gaussian method by an improvement of 0.111 ± 0.016 in the structural similarity index and 2.76 ± 0.98 dB in the peak signal-to-noise ratio. The blind/reference-less image spatial quality evaluator metric of the conventional Gaussian method and proposed method were 46.6 ± 4.2 and 34.1 ± 2.4, respectively., (© 2021 Institute of Physics and Engineering in Medicine.)