Quantitative contrast-enhanced MRI with superparamagnetic nanoparticles using ultrashort time-to-echo pulse sequences.
ABSTRACT: PURPOSE:Conventional MRI using contrast agents is semiquantitative because it is inherently sensitive to extravoxular susceptibility artifacts, field inhomogeneity, partial voluming, perivascular effects, and motion/flow artifacts. Herein we demonstrate a quantitative contrast-enhanced MRI technique using ultrashort time-to-echo pulse sequences for measuring clinically relevant concentrations of ferumoxytol, a superparamagnetic iron oxide nanoparticle contrast agent with high sensitivity and precision in vitro and in vivo. METHODS:The method achieves robust, reproducible results by using rapid signal acquisition at ultrashort time-to-echo (UTE) to produce positive contrast images with pure T1 weighting and little T2* decay. The spoiled gradient echo equation is used to transform UTE intensities directly into concentration using experimentally determined relaxivity constants and image acquisition parameters. RESULTS:A multiparametric optimization of acquisition parameters revealed an optimal zone capable of producing high-fidelity measurements. Clinically relevant intravascular concentrations of ferumoxytol were measured longitudinally in mice with high sensitivity and precision (?7.1% error). MRI measurements were independently validated by elemental iron analysis of sequential blood draws. Automated segmentation of ferumoxytol concentration yielded high quality three-dimensional images for visualization of perfusion. CONCLUSIONS:This ability to longitudinally quantify blood pool CA concentration is unique to quantitative UTE contrast-enhanced (QUTE-CE) MRI and makes QUTE-CE MRI competitive with nuclear imaging.
Project description:The purpose of this work was to use 3D radial ultrashort echo time (UTE) MRI to perform whole-lung oxygen-enhanced (OE) imaging in humans. Eight healthy human subjects underwent two 3D radial UTE MRI acquisitions (TE = 0.08 ms): one while breathing 21% O2 and the other while breathing 100% O2. Scans were each performed over 5 min of free breathing, using prospective respiratory gating. For comparison purposes, conventional echo time (TE = 2.1 ms) images were acquired simultaneously during each acquisition using a radial " outward-inward" k-space trajectory. 3D percent OE maps were generated from these images. 3D OE maps showing lung signal enhancement were generated successfully in seven subjects (technical failure in one subject). Mean percent signal enhancement was 6.6% ± 1.8%, near the value predicted by theory of 6.3%. No significant enhancement was seen using the conventional echo time data, confirming the importance of UTE for this acquisition strategy. 3D radial UTE MRI shows promise as a method for OE MRI that enables whole-lung coverage and isotropic spatial resolution, in comparison to existing 2D OE methods, which rely on a less time-efficient inversion recovery pulse sequence. These qualities may help OE MRI become a viable low-cost method for 3D imaging of lung function in human subjects.
Project description:BACKGROUND:This is an exploratory study using a novel imaging modality, quantitative ultrashort time-to-echo, contrast enhanced (QUTE-CE) magnetic resonance imaging to evaluate the permeability of the blood-brain barrier in a rat model of type 2 diabetes with the presumption that small vessel disease is a contributing factor to neuropathology in diabetes. METHODS:The BBZDR/Wor rat, a model of type 2 diabetes, and age-matched controls were studied for changes in blood-brain barrier permeability. QUTE-CE, a quantitative vascular biomarker, generated angiographic images with over 500,000 voxels that were registered to a 3D MRI rat brain atlas providing site-specific information on blood-brain barrier permeability in 173 different brain areas. RESULTS:In this model of diabetes, without the support of insulin treatment, there was global capillary pathology with over 84% of the brain showing a significant increase in blood-brain barrier permeability over wild-type controls. Areas of the cerebellum and midbrain dopaminergic system were not significantly affected. CONCLUSION:Small vessel disease as assessed by permeability in the blood-brain barrier in type 2 diabetes is pervasive and includes much of the brain. The increase in blood-brain barrier permeability is a likely contributing factor to diabetic encephalopathy and dementia.
Project description:To assess the feasibility of spatial-temporal constrained reconstruction for accelerated regional lung perfusion using highly undersampled dynamic contrast-enhanced (DCE) three-dimensional (3D) radial MRI with ultrashort echo time (UTE).A combined strategy was used to accelerate DCE MRI for 3D pulmonary perfusion with whole lung coverage. A highly undersampled 3D radial UTE MRI acquisition was combined with an iterative constrained reconstruction exploiting principal component analysis and wavelet soft-thresholding for dimensionality reduction in space and time. The performance of the method was evaluated using a 3D fractal-based DCE digital lung phantom. Simulated perfusion maps and contrast enhancement curves were compared with ground truth using the structural similarity index (SSIM) to determine robust threshold and regularization levels. Feasibility studies were then performed in a canine and a human subject with 3D radial UTE (TE=0.08 ms) acquisition to assess feasibility of mapping regional 3D perfusion.The method was able to accurately recover perfusion maps in the phantom with a nominal isotropic spatial resolution of 1.5 mm (SSIM of 0.949). The canine and human subject studies demonstrated feasibility for providing artifact-free perfusion maps in a simple 3D breath-held acquisition.The proposed method is promising for fast and flexible 3D pulmonary perfusion imaging. Magn Reson
Project description:A method called Quantitative Ultra-Short Time-to-Echo Contrast Enhanced (QUTE-CE) Magnetic Resonance Imaging (MRI) which utilizes superparamagnetic iron oxide nanoparticles (SPIONs) as a contrast agent to yield positive contrast angiograms with high clarity and definition is applied to the whole live rat brain. QUTE-CE MRI intensity data are particularly well suited for measuring quantitative cerebral blood volume (qCBV). A global map of qCBV in the awake resting-state with unprecedented detail was created via application of a 3D MRI rat brain atlas with 173 segmented and annotated brain areas. From this map we identified two distributed, integrated neural circuits showing the highest capillary densities in the brain. One is the neural circuitry involved with the primary senses of smell, hearing and vision and the other is the neural circuitry of memory. Under isoflurane anesthesia, these same circuits showed significant decreases in qCBV suggesting a role in consciousness. Neural circuits in the brainstem associated with the reticular activating system and the maintenance of respiration, body temperature and cardiovascular function showed an increase in qCBV with anesthesia. During awake CO2 challenge, 84 regions showed significant increases relative to an awake baseline state. This CO2 response provides a measure of cerebral vascular reactivity and regional perfusion reserve with the highest response measured in the somatosensory cortex. These results demonstrate the utility of QUTE-CE MRI for qCBV analysis and offer a new perspective on brain function and vascular organization.
Project description:OBJECTIVE: Direct in vivo MRI of dental hard tissues by applying ultrashort echo time (UTE) MRI techniques has recently been reported. The objective of the presented study is to clinically evaluate the applicability of UTE MRI for the identification of caries lesions. METHODS: 40 randomly selected patients (mean age 41 ± 15 years) were enrolled in this study. 39 patients underwent a conventional clinical assessment, dental bitewing X-ray and a dental MRI investigation comprising a conventional turbo-spin echo (TSE) and a dedicated UTE scan. One patient had to be excluded owing to claustrophobia. In four patients, the clinical treatment of the lesions was documented by intraoral pictures, and the resulting volume of the cavity after excavation was documented by dental imprints and compared with the MRI findings. RESULTS: In total, 161 lesions were identified. 157 (97%) were visible in the UTE images, 27 (17%) in the conventional TSE images and 137 (85%) in the X-ray images. In total, 14 teeth could not be analysed by MR owing to artefacts caused by dental fillings. All lesions appear significantly larger in the UTE images as compared with the X-ray and TSE images. In situ measurements confirm the accuracy of the lesion dimensions as observed in the UTE images. CONCLUSION: The presented data provide evidence that UTE MR imaging can be applied for the identification of caries lesions. Although the current data suggest an even higher sensitivity of UTE MRI, some limitations must be expected from dental fillings.
Project description:Magnetic resonance imaging (MRI) visualization of meniscal signal is particularly challenging as the highly organized ultrastructure of meniscal fibrocartilage yields very short T2 values (?6 ms) and a paucity of signal intensity during conventional image acquisition.The purpose of this study was to evaluate the feasibility of imaging postoperative menisci using an experimental, quantitative ultrashort echo time (UTE) MRI pulse sequence. This sequence acquires short echo images (echo time (TE) ?0.3 ms) to produce multi-echo images for quantitative T2* calculations that provide an objective measure of collagen organization.MRI scans of the knee were acquired at 6- and 12-month intervals on a clinical 3.0 T scanner following meniscal surgery in eight patients (ages 13-41), four of whom underwent repair and the other four partial meniscectomy. Conventional MRI sequences were qualitatively evaluated for meniscal morphology and signal and correlated with quantitative UTE results.A wide range of mean T2* values for both postsurgical groups was measured, and these values changed for each patient between the 6- and 12-month intervals. In many instances, the UTE sequence demonstrated quantitative differences between the two time intervals that were not detected with conventional sequences.This pilot study presents preliminary, observational data to be used as a baseline for future studies. Although the T2* values did not reveal a trend in either group or correlate with expected signal changes on conventional MRI, we speculate that the UTE sequence may detect ultrastructural alterations in meniscal composition that are otherwise not perceived with routine fast spin echo (FSE) sequences.
Project description:BACKGROUND:Current R2*-MRI techniques for measuring hepatic iron content (HIC) use various acquisition types and fitting models. PURPOSE:To evaluate the accuracy and precision of R2*-HIC acquisition and fitting methods. STUDY TYPE:Signal simulations, phantom study, and prospective in vivo cohort. POPULATION:In all, 132 patients (58/74 male/female, mean age 17.7 years). FIELD STRENGTH/SEQUENCE:2D-multiecho gradient-echo (GRE) and ultrashort echo time (UTE) acquisitions at 1.5T. ASSESSMENT:Synthetic MR signals were created to mimic published GRE and UTE methods, using different R2* values (25-2000 s-1 ) and signal-to-noise ratios (SNR). Phantoms with varying iron concentrations were scanned at 1.5T. In vivo data were analyzed from 132 patients acquired at 1.5T. R2* was estimated by fitting using three signal models. Accuracy and precision of R2* measurements for UTE acquisition parameters (SNR, echo spacing [?TE], maximum echo time [TEmax ]) and fitting methods were compared for simulated, phantom, and in vivo datasets. STATISTICAL TESTS:R2* accuracy was determined from the relative error and by linear regression analysis. Precision was evaluated using coefficient of variation (CoV) analysis. RESULTS:In simulations, all models had high R2* accuracy (error <5%) and precision (CoV <10%) for all SNRs, shorter ?TE (?0.5 msec), and longer TEmax (?10.1 msec); except the constant offset model overestimated R2* at the lowest SNR. In phantoms and in vivo, all models produced similar R2* values for different SNRs and shorter ?TEs (slopes: 0.99-1.06, R2 > 0.99, P < 0.001). In all experiments, R2* results degraded for high R2* values with longer ?TE (?1 msec). In vivo, shorter and longer TEmax gave similar R2* results (slopes: 1.02-1.06, R2 > 0.99, P < 0.001) for the noise subtraction model for 25?R2*?2000 s-1 . However, both quadratic and constant offset models, using shorter TEmax (?4.7 msec) overestimated R2* and yielded high CoVs up to ?170% for low R2* (<250 s-1 ). DATA CONCLUSION:UTE with TEmax ? 10.1 msec and ?TE ? 0.5 msec yields accurate R2* estimates over the entire clinical HIC range. Monoexponential fitting with noise subtraction is the most robust signal model to changes in UTE parameters and achieves the highest R2* accuracy and precision. LEVEL OF EVIDENCE:2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1475-1488.
Project description:This work's aim was to minimize the acquisition time of a radial 3D ultra-short echo-time (UTE) sequence and to provide fully automated, gradient delay compensated, and therefore artifact free, reconstruction. The radial 3D UTE sequence (echo time 60 ?s) was implemented as single echo acquisition with center-out readouts and improved time efficient spoiling on a clinical 3T scanner without hardware modifications. To assess the sequence parameter dependent gradient delays each acquisition contained a quick calibration scan and utilized the phase of the readouts to detect the actual k-space center. This calibration scan does not require any user interaction. To evaluate the robustness of this automatic delay estimation phantom experiments were performed and 19 in vivo imaging data of the head, tibial cortical bone, feet and lung were acquired from 6 volunteers. As clinical application of this fast 3D UTE acquisition single breath-hold lung imaging is demonstrated. The proposed sequence allowed very short repetition times (TR~1ms), thus reducing total acquisition time. The proposed, fully automated k-phase based gradient delay calibration resulted in accurate delay estimations (difference to manually determined optimal delay -0.13 ± 0.45 ?s) and allowed unsupervised reconstruction of high quality images for both phantom and in vivo data. The employed fast spoiling scheme efficiently suppressed artifacts caused by incorrectly refocused echoes. The sequence proved to be quite insensitive to motion, flow and susceptibility artifacts and provides oversampling protection against aliasing foldovers in all directions. Due to the short TR, acquisition times are attractive for a wide range of clinical applications. For short T2* mapping this sequence provides free choice of the second TE, usually within less scan time as a comparable dual echo UTE sequence.