RF shimming in the cervical spinal cord at 7 T.

PURPOSE: Advancing the development of 7 T MRI for spinal cord imaging is crucial for the enhanced diagnosis and monitoring of various neurodegenerative diseases and traumas. However, a significant challenge at this field strength is the transmit field inhomogeneity. Such inhomogeneity is particularly problematic for imaging the small, deep anatomical structures of the cervical spinal cord, as it can cause uneven signal intensity and elevate the local specific absorption ratio, compromising image quality. This multisite study explores several RF shimming techniques in the cervical spinal cord. METHODS: Data were collected from 5 participants between two 7 T sites with a custom 8Tx/20Rx parallel transmission coil. We explored two radiofrequency (RF) shimming approaches from an MRI vendor and four from an open-source toolbox, showcasing their ability to enhance transmit field and signal homogeneity along the cervical spinal cord. RESULTS: The circularly polarized (CP), coefficient of variation (CoV), and specific absorption rate (SAR) efficiency shim modes showed the highest B1 + efficiency, and the vendor-based "patient" and "volume" modes showed the lowest B1 + efficiency. The coefficient of variation method produced the highest CSF/spinal cord contrast on T2*-weighted scans (ratio of 1.27 ± 0.03), and the lowest variation of that contrast along the superior-inferior axis. CONCLUSION: The study's findings highlight the potential of RF shimming to advance 7 T MRI's clinical utility for central nervous system imaging by enabling more homogenous and efficient spinal cord imaging. Additionally, the research incorporates a reproducible Jupyter Notebook, enhancing the study's transparency and facilitating peer verification.

A birdcage transmit, 24-channel conformal receive array coil for sensitive 31P magnetic resonance spectroscopic imaging of the human brain at 7 T.

Phosphorus (31P) magnetic resonance spectroscopic imaging (MRSI) can serve as a critical tool for more direct quantification of brain energy metabolism, tissue pH, and cell membrane turnover. However, the low concentration of 31P metabolites in biological tissue may result in low signal-to-noise ratio (SNR) in 31P MRS images. In this work, we present an innovative design and construction of a 31P radiofrequency coil for whole-brain MRSI at 7 T. Our coil builds on current literature in ultra-high field 31P coil design and offers complete coverage of the brain, including the cerebellum and brainstem. The coil consists of an actively detunable volume transmit (Tx) resonator and a custom 24-channel receive (Rx) array. The volume Tx resonator is a 16-rung high-pass birdcage coil. The Rx coil consists of a 24-element phased array composed of catered loop shapes and sizes built onto a custom, close-fitting, head-shaped housing. The Rx array was designed to provide complete coverage of the head, while minimizing mutual coupling. The Rx configuration had a mean S 11 $$ {S}_{11} $$ reflection coefficient better than -20 decibels (dB) when the coil was loaded with a human head. The mean mutual coupling ( S 21 $$ {S}_{21} $$ ) among Rx elements, when loaded with a human head, was -16 dB. In phantom imaging, the phased array produced a central SNR that was 4.4-fold higher than the corresponding central SNR when operating the 31P birdcage as a transceiver. The peripheral SNR was 12-fold higher when applying the optimized phased array. In vivo 3D 31P MRSI experiments produced high-quality spectra in the cerebrum gray and white matter, as well as in the cerebellum. Characteristic phosphorus metabolites related to adenosine triphosphate metabolism and cell membrane turnover were distinguishable across all brain regions. In summary, our results demonstrate the potential of our novel coil for accurate, whole-brain 31P metabolite quantification.

An 8-Channel Transceiver Coil for Carotid Artery Imaging at 7T Using an Optimized Shield Design.

OBJECTIVE: To design and fabricate a transmit/receive (T/R) radiofrequency (RF) coil array for MRI of the carotid arteries at 7T with optimal shielding to improve transmit performance in parallel transmit (pTx) mode. METHODS: The carotid coil included 8 total RF elements, with left and right subarrays, each consisting of 4 overlapping loops with RF shields. Electromagnetic (EM) simulations were performed to optimize and improve the transmit performance of the array by determining the optimal distance between the RF shield and each subarray. EM simulations were further used to calculate local specific absorption rate (SAR) matrices. Based on the SAR matrices, virtual observation points (VOPs) were applied to ensure safety during parallel transmission. The efficacy of the coil design was evaluated by measuring coil performance metrics when imaging a phantom and by acquiring in-vivo images. RESULTS: The optimal distance between the RF shield and each subarray was determined to be 45 mm. This resulted in a maximum B1+ efficiency of 1.23 µT/ √W in the carotid arteries and a peak, 10-g-average SAR per Watt of 0.86 kg-1 when transmitting in the nominal CP+ mode. Optimizing the RF shield resulted in up to 37% improvement in B1+ efficiency and 14% improvement in SAR efficiency compared to an unshielded design. CONCLUSION AND SIGNIFICANCE: Optimizing the distance between the RF shield and coil array provided significant improvement in the transmit characteristics of the bilateral carotid coil. The bilateral coil topology provides a compelling platform for imaging the carotid arteries with high field MRI.

Feasibility of Dynamic Inhaled Gas MRI-Based Measurements Using Acceleration Combined with the Stretched Exponential Model.

Dynamic inhaled gas (3He/129Xe/19F) MRI permits the acquisition of regional fractional-ventilation which is useful for detecting gas-trapping in lung-diseases such as lung fibrosis and COPD. Deninger's approach used for analyzing the wash-out data can be substituted with the stretched-exponential-model (SEM) because signal-intensity is attenuated as a function of wash-out-breath in 19F lung imaging. Thirteen normal-rats were studied using 3He/129Xe and 19F MRI and the ventilation measurements were performed using two 3T clinical-scanners. Two Cartesian-sampling-schemes (Fast-Gradient-Recalled-Echo/X-Centric) were used to test the proposed method. The fully sampled dynamic wash-out images were retrospectively under-sampled (acceleration-factors (AF) of 10/14) using a varying-sampling-pattern in the wash-out direction. Mean fractional-ventilation maps using Deninger's and SEM-based approaches were generated. The mean fractional-ventilation-values generated for the fully sampled k-space case using the Deninger method were not significantly different from other fractional-ventilation-values generated for the non-accelerated/accelerated data using both Deninger and SEM methods (p > 0.05 for all cases/gases). We demonstrated the feasibility of the SEM-based approach using retrospective under-sampling, mimicking AF = 10/14 in a small-animal-cohort from the previously reported dynamic-lung studies. A pixel-by-pixel comparison of the Deninger-derived and SEM-derived fractional-ventilation-estimates obtained for AF = 10/14 (≤16% difference) has confirmed that even at AF = 14, the accuracy of the estimates is high enough to consider this method for prospective measurements.

Physical activity levels, pulmonary function, and MRI in children born extremely preterm: A comparison between children with and without bronchopulmonary dysplasia.

INTRODUCTION: Children with a history of bronchopulmonary dysplasia (BPD) may have lower physical activity levels, but evidence to date is mixed. This study compared physical activity levels between children born extremely preterm with and without history of BPD, and examined their associations with pulmonary magnetic resonance imaging (MRI) and pulmonary function test (PFT) indices. METHODS: This multicentre cross-sectional study included children aged 7-9 years born extremely preterm, with and without BPD. Children wore a pedometer for 1 week, then completed the Physical Activity Questionnaire (PAQ), pulmonary MRI, and PFT. Spearman correlations and multivariable linear regression modeling were performed. RESULTS: Of 45 children, 28 had a history of moderate-severe BPD. There were no differences in any physical activity outcomes by BPD status. Higher average daily step count and higher average daily moderate-to-vigorous physical activity (MVPA) were each correlated with greater forced vital capacity (r = 0.41 and 0.58), greater MRI lung proton density at full expiration (r = 0.42 and 0.49), and lower lung clearance index (r = -0.50 and -0.41). After adjusting for MRI total proton density and BPD status, a 5% increase in forced expiratory volume at 1 s was associated with 738 (95% CI: 208, 1268) more steps per day and 0.1 (0.0, 0.2) more hours of MVPA, respectively. CONCLUSION: School-aged children born extremely preterm have similar physical activity levels to their peers, regardless of history of BPD. MRI and PFT measures suggestive of gas trapping and/or airflow obstruction are associated with lower physical activity levels.

Inter- and intravisit repeatability of free-breathing MRI in pediatric cystic fibrosis lung disease.

PURPOSE: The purpose of this study is to assess the intra- and interscan repeatability of free-breathing phase-resolved functional lung (PREFUL) MRI in stable pediatric cystic fibrosis (CF) lung disease in comparison to static breath-hold hyperpolarized 129-xenon MRI (Xe-MRI) and pulmonary function tests. METHODS: Free-breathing 1-hydrogen MRI and Xe-MRI were acquired from 15 stable pediatric CF patients and seven healthy age-matched participants on two visits, 1 month apart. Same-visit MRI scans were also performed on a subgroup of the CF patients. Following the PREFUL algorithm, regional ventilation (RVent) and regional flow volume loop cross-correlation maps were determined from the free-breathing data. Ventilation defect percentage (VDP) was determined from RVent maps (VDPRVent ), regional flow volume loop cross-correlation maps (VDPCC ), VDPRVent ∪ VDPCC , and multi-slice Xe-MRI. Repeatability was evaluated using Bland-Altman analysis, coefficient of repeatability (CR), and intraclass correlation. RESULTS: Minimal bias and no significant differences were reported for all PREFUL MRI and Xe-MRI VDP parameters between intra- and intervisits (all P > 0.05). Repeatability of VDPRVent , VDPCC , VDPRVent ∪ VDPCC , and multi-slice Xe-MRI were lower between the two-visit scans (CR = 14.81%, 15.36%, 16.19%, and 9.32%, respectively) in comparison to the same-day scans (CR = 3.38%, 2.90%, 1.90%, and 3.92%, respectively). pulmonary function tests showed high interscan repeatability relative to PREFUL MRI and Xe-MRI. CONCLUSION: PREFUL MRI, similar to Xe-MRI, showed high intravisit repeatability but moderate intervisit repeatability in CF, which may be due to inherent disease instability, even in stable patients. Thus, PREFUL MRI may be considered a suitable outcome measure for future treatment response studies.

Clinical Feasibility of Structural and Functional MRI in Free-Breathing Neonates and Infants.

BACKGROUND: Evaluation of structural lung abnormalities with magnetic resonance imaging (MRI) has previously been shown to be predictive of clinical neonatal outcomes in preterm birth. MRI during free-breathing with phase-resolved functional lung (PREFUL) may allow for complimentary functional information without exogenous contrast. PURPOSE: To investigate the feasibility of structural and functional pulmonary MRI in a cohort of neonates and infants with no cardiorespiratory disease. Macrovascular pulmonary blood flows were also evaluated. STUDY TYPE: Prospective. POPULATION: Ten term infants with no clinically defined cardiorespiratory disease were imaged. Infants recruited from the general population and neonatal intensive care unit (NICU) were studied. FIELD STRENGTH/SEQUENCE: T1 -weighted VIBE, T2 -weighted BLADE uncorrected for motion. Ultrashort echo time (UTE) and 3D-flow data were acquired during free-breathing with self-navigation and retrospective reconstruction. Single slice 2D-gradient echo (GRE) images were acquired during free-breathing for PREFUL analysis. Imaging was performed at 3 T. ASSESSMENT: T1 , T2 , and UTE images were scored according to the modified Ochiai scheme by three pediatric body radiologists. Ventilation/perfusion-weighted maps were extracted from free-breathing GRE images using PREFUL analysis. Ventilation and perfusion defect percent (VDP, QDP) were calculated from the segmented ventilation and perfusion-weighted maps. Time-averaged cardiac blood velocities from three-dimensional-flow were evaluated in major pulmonary arteries and veins. STATISTICAL TEST: Intraclass correlation coefficient (ICC). RESULTS: The ICC of replicate structural scores was 0.81 (95% CI: 0.45-0.95) across three observers. Elevated Ochiai scores, VDP, and QDP were observed in two NICU participants. Excluding these participants, mean ± standard deviation structural scores were 1.2 ± 0.8, while VDP and QDP were 1.0% ± 1.1% and 0.4% ± 0.5%, respectively. Main pulmonary arterial blood flows normalized to body surface area were 3.15 ± 0.78 L/min/m2 . DATA CONCLUSION: Structural and functional pulmonary imaging is feasible using standard clinical MRI hardware (commercial whole-body 3 T scanner, table spine array, and flexible thoracic array) in free-breathing infants. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Pulmonary Magnetic Resonance Imaging of Ex-Preterm Children with and without Bronchopulmonary Dysplasia.

Rationale: Children born prematurely, particularly those with bronchopulmonary dysplasia, have persisting lung abnormalities requiring longitudinal monitoring. Pulmonary ultrashort echo time magnetic resonance imaging (MRI) measurements may provide sensitive markers of persisting lung abnormalities and have not been evaluated in school-aged children born prematurely. Objectives: To compare pulmonary MRI and pulmonary function test measurements in preterm-born school-aged children with and without bronchopulmonary dysplasia. Methods: Children aged 7-9 years, born extremely preterm, with and without bronchopulmonary dysplasia, were recruited from three centers. Participants underwent pulmonary ultrashort echo time MRI and pulmonary function tests. Primary outcomes included total proton density and proton density at full expiration, measured using MRI. Multiple linear regression analysis was performed, adjusting for gestational age and bronchopulmonary dysplasia. Associations between MRI and pulmonary function were tested. Results: Thirty-five children were included in the primary analysis (24 with bronchopulmonary dysplasia, 11 without); 29 completed pulmonary function tests, of whom 11 (38%) had airflow limitation. Children with bronchopulmonary dysplasia had 44% (95% confidence interval [CI], 10-66%) lower mean total proton density (mean ± standard deviation, 3.6 ± 2.6) than those without (6.1 ± 4.0). Those with bronchopulmonary dysplasia had 25% (95% CI, 3-42%) lower proton density at full expiration than those without. Lower total proton density and proton density at full expiration were moderately correlated with greater residual volume, residual volume/total lung capacity, and lung clearance index (Spearman correlations for total proton density: -0.42, -0.57, and -0.53, respectively. Spearman correlations for proton density at full expiration: -0.28, -0.57, and -0.45, respectively). Conclusions: School-aged preterm-born children with bronchopulmonary dysplasia have parenchymal tissue abnormalities measured using ultrashort MRI proton density, compared with those without. MRI proton density correlated with pulmonary function measures indicative of gas trapping. Clinical trial registered with www.clinicaltrials.gov (NCT02921308).

Navigation of Microrobots by MRI: Impact of Gravitational, Friction and Thrust Forces on Steering Success.

INTRODUCTION: Magnetic resonance navigation (MRN) uses MRI gradients to steer magnetic drug-eluting beads (MDEBs) across vascular bifurcations. We aim to experimentally verify our theoretical forces balance model (gravitational, thrust, friction, buoyant and gradient steering forces) to improve the MRN targeted success rate. METHOD: A single-bifurcation phantom (3 mm inner diameter) made of poly-vinyl alcohol was connected to a cardiac pump at 0.8 mL/s, 60 beats/minutes with a glycerol solution to reproduce the viscosity of blood. MDEB aggregates (25 ± 6 particles, 200 [Formula: see text]) were released into the main branch through a 5F catheter. The phantom was tilted horizontally from - 10° to +25° to evaluate the MRN performance. RESULTS: The gravitational force was equivalent to 71.85 mT/m in a 3T MRI. The gradient duration and amplitude had a power relationship (amplitude=78.717 [Formula: see text]). It was possible, in 15° elevated vascular branches, to steer 87% of injected aggregates if two MRI gradients are simultaneously activated ([Formula: see text] = +26.5 mT/m, [Formula: see text]= +18 mT/m for 57% duty cycle), the flow velocity was minimized to 8 cm/s and a residual pulsatile flow to minimize the force of friction. CONCLUSION: Our experimental model can determine the maximum elevation angle MRN can perform in a single-bifurcation phantom simulating in vivo conditions.

Comparison of Functional Free-Breathing Pulmonary 1H and Hyperpolarized 129Xe Magnetic Resonance Imaging in Pediatric Cystic Fibrosis.

RATIONALE AND OBJECTIVES: Phase resolved functional lung (PREFUL) magnetic resonance imaging (MRI) is a free-breathing 1H-based technique that produces maps of fractional ventilation (FV). This study compared ventilation defect percent (VDP) calculated using PREFUL to hyperpolarized (HP) 129Xe MRI and pulmonary function tests in pediatric cystic fibrosis (CF). MATERIALS AND METHODS: 27 pediatric participants were recruited (mean age 13.0 ± 2.7), including 6 with clinically stable CF, 11 CF patients undergoing a pulmonary exacerbation (PEx), and 10 healthy controls. Spirometry was performed to measure forced expiratory volume in 1 second (FEV1), along with nitrogen multiple breath washout to measure lung clearance index (LCI). VDP was calculated from single central coronal slice PREFUL FV maps and the corresponding HP 129Xe slice. RESULTS: The stable CF group had a normal FEV1 (p = 0.41) and elevated LCI (p = 0.007). The CF PEx group had a decreased FEV1 (p < 0.0001) and elevated LCI (p < 0.0001). PREFUL and HP 129Xe VDP were significantly different between the CF PEx and healthy groups (p < 0.05). In the stable CF group, PREFUL and HP 129Xe VDP were not significantly different from the healthy group (p = 0.18 and 0.08, respectively). There was a correlation between PREFUL and HP 129Xe VDP (R2 = 0.31, p = 0.004), and both parameters were significantly correlated with FEV1 and LCI. CONCLUSION: PREFUL MRI is feasible in pediatric CF, distinguishes patients undergoing pulmonary exacerbations compared to healthy subjects, and correlates with HP 129Xe MRI as well as functional measures of disease severity. PREFUL MRI does not require breath-holds and is straight forward to implement on any MRI scanner.

Predictive Value of In Vivo MR Spectroscopy With Semilocalization by Adiabatic Selective Refocusing in Differentiating Clear Cell Renal Cell Carcinoma From Other Subtypes.

OBJECTIVE. The purpose of this study is to evaluate the diagnostic value of in vivo MR spectroscopy (MRS) with semilocalization by adiabatic selective refocusing (semi-LASER MRS) in differentiating clear cell renal cell carcinoma (RCC) from the non-clear cell subtype. SUBJECTS AND METHODS. Sixteen patients with biopsy-proven RCC or masses highly suspicious for RCC were prospectively recruited to participate in the study. Single-voxel 1H spectra were acquired using a 3-T MRI system, with a semi-LASER sequence acquired for renal tumors in 14 patients and for healthy renal tissue (control tissue) in 12 patients. Offline processing of the MR spectra was performed. MRI and spectra analysis were performed independently by radiologists who were blinded to the reference histopathologic findings. RESULTS. Semi-LASER MRS was diagnostic for nine of 11 patients (82%) with histopathologically proven clear cell RCC, showing a strong lipid peak in seven patients and a weaker lipid resonance in two others, whereas control spectra showed weakly positive findings in only one patient. MRS findings were negative for lipid resonance in two of three patients (67%) with non-clear cell tumors and were weakly positive in another patient. Semi-LASER MRS had a high sensitivity and positive predictive value of 82% and 90%, respectively, in addition to a specificity of 67%, a negative predictive value of 50%, and overall accuracy of 79% for the detection of clear cell RCC. Lipid resonance was detected by MRS for four of six clear cell RCCs with no intravoxel fat on chemical-shift MRI. CONCLUSION. The preliminary results of the present study show that semi-LASER MRS is promising for the noninvasive discrimination of clear cell RCC from non-clear cell RCC on the basis of detection of lipid resonance and that it provides an incremental yield compared with chemical-shift MRI.

Assessing the feasibility of hyperpolarized 129 Xe multiple-breath washout MRI in pediatric cystic fibrosis.

PURPOSE: To assess the feasibility of hyperpolarized 129 Xe multiple-breath washout MRI in pediatric cystic fibrosis (CF) participants with preserved lung function. Fractional ventilation (r), defined as the fractional gas replacement per breath, was mapped using 2 signal models: (1) constant T1 and (2) variable T1 as a function of the hyperpolarized gas washout. METHODS: A total of 17 pediatric participants were recruited (mean age 11.7 ± 2.8 years), including 7 children with clinically stable CF and 10 aged-matched healthy controls. Pulmonary function tests were performed, including spirometry, to measure the forced expiratory volume in 1 second and nitrogen multiple-breath washout to measure the lung clearance index. Hyperpolarized 129 Xe MRI was performed during consecutive breaths of air following a single 129 Xe inhalation, and fractional ventilation maps were calculated. RESULTS: The forced expiratory volume in 1 second was similar in both groups (P = .32), but there was a statistically significant difference in lung clearance index between healthy and CF participants (P = .001). With variable T1 modeling, CF participants had a mean r of 0.44 ± 0.08 and healthy participants had a mean r of 0.37 ± 0.12 (P = .20). With constant T1 modeling, CF participants had a mean r' of 0.48 ± 0.08, and healthy participants had a mean r' of 0.43 ± 0.12 (P = .32). Therefore, assuming a constant T1 leads to a relative bias in r of 15.1% ± 6.4% and 20.8% ± 7.4% for CF and healthy participants, respectively (P = .12). CONCLUSION: This study demonstrates that hyperpolarized 129 Xe multiple-breath washout imaging is feasible in pediatric participants with CF, and inclusion of variable T1 modeling reduces bias in the fractional ventilation measurements.

Hyperpolarized 129 Xe imaging of embryonic stem cell-derived alveolar-like macrophages in rat lungs: proof-of-concept study using superparamagnetic iron oxide nanoparticles.

PURPOSE: To measure regional changes in hyperpolarized 129 Xe MRI signal and apparent transverse relaxation ( T2∗ ) because of instillation of SPION-labeled alveolar-like macrophages (ALMs) in the lungs of rats and compare to histology. METHODS: MRI was performed in 6 healthy mechanically ventilated rats before instillation, as well as 5 min and 1 h after instillation of 4 million SPION-labeled ALMs into either the left or right lung. T2∗ maps were calculated from 2D multi-echo data at each time point and changes in T2∗ were measured and compared to control rats receiving 4 million unlabeled ALMs. Histology of the ex vivo lungs was used to compare the regional MRI findings with the locations of the SPION-labeled ALMs. RESULTS: Regions of signal loss were observed immediately after instillation of unlabeled and SPION-labeled ALMs and persisted at least 1 h in the case of the SPION-labeled ALMs. This was reflected in the measurements of T2∗ . One hour after the instillation of SPION-labeled ALMs, the T2∗ decreased to 54.0 ± 7.0% of the baseline, compared to a full recovery to baseline after the instillation of unlabeled ALMs. Histology confirmed the co-localization of SPION-labeled ALMs with regions of signal loss and T2∗ decreases for each rat. CONCLUSION: Hyperpolarized 129 Xe MRI can detect the presence of SPION-labeled ALMs in the airways 1 h after instillation. This approach is promising for targeting and tracking of stem cells for the treatment of lung disease.

Chemical shift of 129 Xe dissolved in red blood cells: Application to a rat model of bronchopulmonary dysplasia.

PURPOSE: To measure the chemical shift of hyperpolarized 129 Xe dissolved in the red blood cells(δRBC ) of a cohort of rats exposed to hyperoxia and intermittent hypoxia (IH) to mimic human bronchopulmonary dysplasia, and to investigate the effect of xenon-blood distribution time on δRBC . METHODS: δRBC was measured from spectra acquired using a chemical shift saturation recovery sequence from 15 Sprague-Dawley rats exposed to hyperoxia-IH and 10 age-matched control rats. Sensitization to the xenon-blood distribution time was achieved by varying the time between saturation pulses, τ. δRBC was compared with blood fraction measured by histology of the cohort and blood oxygenation measured directly using pulse oximetry following a hypoxic challenge in an identically exposed cohort. RESULTS: The mean δRBC in the hyperoxia-IH exposed rats was 0.55 ± 0.04 ppm lower than that of the healthy cohort (P = .0038), and this difference did not depend on τ (P = .996). The blood fraction of the exposed cohort was lower than that of the healthy cohort (P = .0397). Oximetry measurements showed that the baseline arterial oxygen saturation (Sa O2 ) of each cohort was not different (P = .72), but after a hypoxic challenge, the Sa O2 of the exposed cohort was lower than that of the healthy cohort (P = .003). CONCLUSION: δRBC is reduced in rats exposed to hyperoxia-IH compared with control rats. The change in δRBC is consistent with enhanced blood oxygen desaturation of the exposed cohort measured by pulse oximetry during a hypoxic challenge. This suggests that the observed change in δRBC reflects enhanced desaturation in the hyperoxia-IH exposed cohort compared with the healthy cohort.

A two-center analysis of hyperpolarized 129Xe lung MRI in stable pediatric cystic fibrosis: Potential as a biomarker for multi-site trials.

BACKGROUND: The ventilation defect percent (VDP), measured from hyperpolarized (HP) 129Xe magnetic resonance imaging (MRI), is sensitive to functional changes in cystic fibrosis (CF) lung disease. The purpose of this study was to measure and compare VDP from HP 129Xe MRI acquired at two institutions in stable pediatric CF subjects with preserved lung function. METHODS: This retrospective analysis included 26 participants from two institutions (18 CF, 8 healthy, age range 10-17). Pulmonary function tests, N2 multiple breath washout (to measure lung clearance index, LCI), and HP 129Xe MRI were performed. VDP measurements were compared between two trained analysts using mean-anchored linear binning. Correlations were investigated for VDP compared to the forced expiratory volume in one second (FEV1) and LCI. RESULTS: VDP measurements agreed for the two analysts with an intraclass correlation coefficient of 0.99. In the combined dataset, VDP measured by Analyst 1 was 5.96 ±â€¯1.82% and 15.96 ±â€¯6.76% for the healthy and CF groups, respectively (p = .0004). Analyst 2 showed similar differences between healthy and CF (p = .0003). VDP measured by either analyst was shown to correlate with FEV1 (R2 = 0.33, p = .003; and R2 = 0.26, p = .009 for Analysts 1 and 2, respectively) and LCI (R2 = 0.76, p < .0001; and R2 = 0.77, p < .0001 for Analysts 1 and 2, respectively). CONCLUSION: HP 129Xe MRI provides a robust measurement of ventilation heterogeneity in stable pediatric CF subjects at two sites. Since measurements performed at two sites yielded similar VDP values with near-identical values between different analysts, implementation of the technique in multi-center trials in CF appears feasible.

Hyperpolarised 129Xe magnetic resonance imaging to monitor treatment response in children with cystic fibrosis.

Pulmonary magnetic resonance imaging using hyperpolarised 129Xe gas (XeMRI) can quantify ventilation inhomogeneity by measuring the percentage of unventilated lung volume (ventilation defect per cent (VDP)). While previous studies have demonstrated its sensitivity for detecting early cystic fibrosis (CF) lung disease, the utility of XeMRI to monitor response to therapy in CF is unknown. The aim of this study was to assess the ability of XeMRI to capture treatment response in paediatric CF patients undergoing inpatient antibiotic treatment for a pulmonary exacerbation.15 CF patients aged 8-18 years underwent XeMRI, spirometry, plethysmography and multiple-breath nitrogen washout at the beginning and end of inpatient treatment of a pulmonary exacerbation. VDP was calculated from XeMRI images obtained during a static breath hold using semi-automated k-means clustering and linear binning approaches.XeMRI was well tolerated. VDP, lung clearance index and the forced expiratory volume in 1 s all improved with treatment; however, response was not uniform in individual patients. Of all outcome measures, VDP showed the largest relative improvement (-42.1%, 95% CI -52.1--31.9%, p<0.0001).These data support further investigation of XeMRI as a tool to capture treatment response in CF lung disease.

Hyperpolarized Gas Magnetic Resonance Imaging of Pediatric Cystic Fibrosis Lung Disease.

Conventional pulmonary function tests appear normal in early cystic fibrosis (CF) lung disease. Therefore, new diagnostic approaches are required that can detect CF lung disease in children and monitor treatment response. Hyperpolarized (HP) gas (129Xe and 3He) magnetic resonance imaging (MRI) is a powerful, emergent tool for mapping regional lung function and may be well suited for studying pediatric CF. HP gas MRI is well tolerated, reproducible, and it can be performed longitudinally without the need for ionizing radiation. In particular, quantification of the distribution of ventilation, or ventilation defect percent (VDP), has been shown to be a sensitive indicator of CF lung disease and correlates well with pulmonary function tests. This article presents the current state of CF diagnosis and treatment and describes the potential role of HP gas MRI for detection of early CF lung disease and following the effects of interventions. The typical HP gas imaging workflow is described, along with a discussion of image analysis to calculate VDP, dosing considerations, and the reproducibility of VDP. The potential use of VDP as an outcome measure in CF is discussed, by considering the correlation with pulmonary function measures, preliminary interventional studies, and case studies involving longitudinal imaging and pulmonary exacerbations. Finally, emerging HP gas imaging techniques such as multiple breath washout imaging are introduced, followed by a discussion of future directions. Overall, HP gas MRI biomarkers are expected to provide sensitive outcome measures that can be used in disease surveillance as well as interventional studies involving novel CF therapies.

19 F MRI of the Lungs Using Inert Fluorinated Gases: Challenges and New Developments.

Fluorine-19 (19 F) MRI using inhaled inert fluorinated gases is an emerging technique that can provide functional images of the lungs. Inert fluorinated gases are nontoxic, abundant, relatively inexpensive, and the technique can be performed on any MRI scanner with broadband multinuclear imaging capabilities. Pulmonary 19 F MRI has been performed in animals, healthy human volunteers, and in patients with lung disease. In this review, the technical requirements of 19 F MRI are discussed, along with various imaging approaches used to optimize the image quality. Lung imaging is typically performed in humans using a gas mixture containing 79% perfluoropropane (PFP) or sulphur hexafluoride (SF6 ) and 21% oxygen. In lung diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF), ventilation defects are apparent in regions that the inhaled gas cannot access. 19 F lung images are typically acquired in a single breath-hold, or in a time-resolved, multiple breath fashion. The former provides measurements of the ventilation defect percent (VDP), while the latter provides measurements of gas replacement (ie, fractional ventilation). Finally, preliminary comparisons with other functional lung imaging techniques are discussed, such as Fourier decomposition MRI and hyperpolarized gas MRI. Overall, functional 19 F lung MRI is expected to complement existing proton-based structural imaging techniques, and the combination of structural and functional lung MRI will provide useful outcome measures in the future management of pulmonary diseases in the clinic. Level of Evidence: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:343-354.

Effect of T1 relaxation on ventilation mapping using hyperpolarized 129 Xe multiple breath wash-out imaging.

PURPOSE: To investigate the effect of incorporating T1 as a function of wash-out breath number (T1 (n)) on estimation of fractional ventilation (r) using hyperpolarized 129 Xe multiple breath wash-out (MBWO) imaging in rats. METHODS: MBWO imaging was performed in 8 healthy mechanically ventilated rats at several inter-image delay times (τ) and tidal volumes (TV). r maps were calculated from the imaging data using a model of T1 (n) (assuming that the longitudinal relaxation rate of 129 Xe in the lung is directly proportional to pA O2 ) and compared to r maps obtained by assuming a fixed T1 measured before wash-out breaths (r'). RESULTS: Fractional ventilation was overestimated by up to 19.3% when T1 was fixed. An inverse relationship between bias (Δr) and ventilation was observed at all τ and TV. Additionally, Δr significantly increased when TV was decreased (F statistic F(2,7) = 48.97, P < 10-4 ). Histograms from r' maps were significantly more skewed toward lower values as compared to r histograms at all τ and TV (P < 0.05) except TV = Vdose - 1 mL. CONCLUSION: Analysis of hyperpolarized 129 Xe MBWO imaging using a model incorporating T1 (n) corrects for an overestimating bias in the mapping of fractional ventilation in mechanically ventilated rats introduced by assuming a fixed T1 .