Fast high-resolution electric properties tomography using three-dimensional quantitative transient-state imaging-based water fraction estimation.

In this study, we aimed to develop a fast and robust high-resolution technique for clinically feasible electrical properties tomography based on water content maps (wEPT) using Quantitative Transient-state Imaging (QTI), a multiparametric transient state-based method that is similar to MR fingerprinting. Compared with the original wEPT implementation based on standard spin-echo acquisition, QTI provides robust electrical properties quantification towards B1 + inhomogeneities and full quantitative relaxometry data. To validate the proposed approach, 3D QTI data of 12 healthy volunteers were acquired on a 1.5 T scanner. QTI-provided T1 maps were used to compute water content maps of the tissues using an empirical relationship based on literature ex-vivo measurements. Assuming that electrical properties are modulated mainly by tissue water content, the water content maps were used to derive electrical conductivity and relative permittivity maps. The proposed technique was compared with a conventional phase-only Helmholtz EPT (HH-EPT) acquisition both within whole white matter, gray matter, and cerebrospinal fluid masks, and within different white and gray matter subregions. In addition, QTI-based wEPT was retrospectively applied to four multiple sclerosis adolescent and adult patients, compared with conventional contrast-weighted imaging in terms of lesion delineation, and quantitatively assessed by measuring the variation of electrical properties in lesions. Results obtained with the proposed approach agreed well with theoretical predictions and previous in vivo findings in both white and gray matter. The reconstructed maps showed greater anatomical detail and lower variability compared with standard phase-only HH-EPT. The technique can potentially improve delineation of pathology when compared with conventional contrast-weighted imaging and was able to detect significant variations in lesions with respect to normal-appearing tissues. In conclusion, QTI can reliably measure conductivity and relative permittivity of brain tissues within a short scan time, opening the way to the study of electric properties in clinical settings.

Magnetic resonance fingerprinting-based myelin water fraction mapping for the assessment of white matter maturation and integrity in typical development and leukodystrophies.

A quantitative biomarker for myelination, such as myelin water fraction (MWF), would boost the understanding of normative and pathological neurodevelopment, improving patients' diagnosis and follow-up. We quantified the fraction of a rapidly relaxing pool identified as MW using multicomponent three-dimensional (3D) magnetic resonance fingerprinting (MRF) to evaluate white matter (WM) maturation in typically developing (TD) children and alterations in leukodystrophies (LDs). We acquired DTI and 3D MRF-based R1, R2 and MWF data of 15 TD children and 17 LD patients (9 months-12.5 years old) at 1.5 T. We computed normative maturation curves in corpus callosum and corona radiata and performed WM tract profile analysis, comparing MWF with R1, R2 and fractional anisotropy (FA). Normative maturation curves demonstrated a steep increase for all tissue parameters in the first 3 years of age, followed by slower growth for MWF while R1, R2R2 and FA reached a plateau. Unlike FA, MWF values were similar for regions of interest (ROIs) with different degrees of axonal packing, suggesting independence from fiber bundle macro-organization and higher myelin specificity. Tract profile analysis indicated a specific spatial pattern of myelination in the major fiber bundles, consistent across subjects. LD were better distinguished from TD by MWF rather than FA, showing reduced MWF with respect to age-matched controls in both ROI-based and tract analysis. In conclusion, MRF-based MWF provides myelin-specific WM maturation curves and is sensitive to alteration due to LDs, suggesting its potential as a biomarker for WM disorders. As MRF allows fast simultaneous acquisition of relaxometry and MWF, it can represent a valuable diagnostic tool to study and follow up developmental WM disorders in children.

Simultaneous relaxometry and morphometry of human brain structures with 3D magnetic resonance fingerprinting: a multicenter, multiplatform, multifield-strength study.

Relaxation times and morphological information are fundamental magnetic resonance imaging-derived metrics of the human brain that reflect the status of the underlying tissue. Magnetic resonance fingerprinting (MRF) enables simultaneous acquisition of T1 and T2 maps inherently aligned to the anatomy, allowing whole-brain relaxometry and morphometry in a single scan. In this study, we revealed the feasibility of 3D MRF for simultaneous brain structure-wise morphometry and relaxometry. Comprehensive test-retest scan analyses using five 1.5-T and three 3.0-T systems from a single vendor including different scanner types across 3 institutions demonstrated that 3D MRF-derived morphological information and relaxation times are highly repeatable at both 1.5 T and 3.0 T. Regional cortical thickness and subcortical volume values showed high agreement and low bias across different field strengths. The ability to acquire a set of regional T1, T2, thickness, and volume measurements of neuroanatomical structures with high repeatability and reproducibility facilitates the ability of longitudinal multicenter imaging studies to quantitatively monitor changes associated with underlying pathologies, disease progression, and treatments.

Three dimensional MRF obtains highly repeatable and reproducible multi-parametric estimations in the healthy human brain at 1.5T and 3T.

Magnetic resonance fingerprinting (MRF) is highly promising as a quantitative MRI technique due to its accuracy, robustness, and efficiency. Previous studies have found high repeatability and reproducibility of 2D MRF acquisitions in the brain. Here, we have extended our investigations to 3D MRF acquisitions covering the whole brain using spiral projection k-space trajectories. Our travelling head study acquired test/retest data from the brains of 12 healthy volunteers and 8 MRI systems (3 systems at 3 T and 5 at 1.5 T, all from a single vendor), using a study design not requiring all subjects to be scanned at all sites. The pulse sequence and reconstruction algorithm were the same for all acquisitions. After registration of the MRF-derived PD T1 and T2 maps to an anatomical atlas, coefficients of variation (CVs) were computed to assess test/retest repeatability and inter-site reproducibility in each voxel, while a General Linear Model (GLM) was used to determine the voxel-wise variability between all confounders, which included test/retest, subject, field strength and site. Our analysis demonstrated a high repeatability (CVs 0.7-1.3% for T1, 2.0-7.8% for T2, 1.4-2.5% for normalized PD) and reproducibility (CVs of 2.0-5.8% for T1, 7.4-10.2% for T2, 5.2-9.2% for normalized PD) in gray and white matter. Both repeatability and reproducibility improved when compared to similar experiments using 2D acquisitions. Three-dimensional MRF obtains highly repeatable and reproducible estimations of T1 and T2, supporting the translation of MRF-based fast quantitative imaging into clinical applications.

Repeatability and reproducibility of human brain morphometry using three-dimensional magnetic resonance fingerprinting.

Three-dimensional (3D) Magnetic resonance fingerprinting (MRF) permits whole-brain volumetric quantification of T1 and T2 relaxation values, potentially replacing conventional T1-weighted structural imaging for common brain imaging analysis. The aim of this study was to evaluate the repeatability and reproducibility of 3D MRF in evaluating brain cortical thickness and subcortical volumetric analysis in healthy volunteers using conventional 3D T1-weighted images as a reference standard. Scan-rescan tests of both 3D MRF and conventional 3D fast spoiled gradient recalled echo (FSPGR) were performed. For each sequence, the regional cortical thickness and volume of the subcortical structures were measured using standard automatic brain segmentation software. Repeatability and reproducibility were assessed using the within-subject coefficient of variation (wCV), intraclass correlation coefficient (ICC), and mean percent difference and ICC, respectively. The wCV and ICC of cortical thickness were similar across all regions with both 3D MRF and FSPGR. The percent relative difference in cortical thickness between 3D MRF and FSPGR across all regions was 8.0 ± 3.2%. The wCV and ICC of the volume of subcortical structures across all structures were similar between 3D MRF and FSPGR. The percent relative difference in the volume of subcortical structures between 3D MRF and FSPGR across all structures was 7.1 ± 3.6%. 3D MRF measurements of human brain cortical thickness and subcortical volumes are highly repeatable, and consistent with measurements taken on conventional 3D T1-weighted images. A slight, consistent bias was evident between the two, and thus careful attention is required when combining data from MRF and conventional acquisitions.

Accelerated 3D whole-brain T1, T2, and proton density mapping: feasibility for clinical glioma MR imaging.

PURPOSE: Advanced MRI-based biomarkers offer comprehensive and quantitative information for the evaluation and characterization of brain tumors. In this study, we report initial clinical experience in routine glioma imaging with a novel, fully 3D multiparametric quantitative transient-state imaging (QTI) method for tissue characterization based on T1 and T2 values. METHODS: To demonstrate the viability of the proposed 3D QTI technique, nine glioma patients (grade II-IV), with a variety of disease states and treatment histories, were included in this study. First, we investigated the feasibility of 3D QTI (6:25 min scan time) for its use in clinical routine imaging, focusing on image reconstruction, parameter estimation, and contrast-weighted image synthesis. Second, for an initial assessment of 3D QTI-based quantitative MR biomarkers, we performed a ROI-based analysis to characterize T1 and T2 components in tumor and peritumoral tissue. RESULTS: The 3D acquisition combined with a compressed sensing reconstruction and neural network-based parameter inference produced parametric maps with high isotropic resolution (1.125 × 1.125 × 1.125 mm3 voxel size) and whole-brain coverage (22.5 × 22.5 × 22.5 cm3 FOV), enabling the synthesis of clinically relevant T1-weighted, T2-weighted, and FLAIR contrasts without any extra scan time. Our study revealed increased T1 and T2 values in tumor and peritumoral regions compared to contralateral white matter, good agreement with healthy volunteer data, and high inter-subject consistency. CONCLUSION: 3D QTI demonstrated comprehensive tissue assessment of tumor substructures captured in T1 and T2 parameters. Aiming for fast acquisition of quantitative MR biomarkers, 3D QTI has potential to improve disease characterization in brain tumor patients under tight clinical time-constraints.

Retrospective rigid motion correction of three-dimensional magnetic resonance fingerprinting of the human brain.

PURPOSE: To obtain three-dimensional (3D), quantitative and motion-robust imaging with magnetic resonance fingerprinting (MRF). METHODS: Our acquisition is based on a 3D spiral projection k-space scheme. We compared different orderings of trajectory interleaves in terms of rigid motion-correction robustness. In all tested orderings, we considered the whole dataset as a sum of 56 segments of 7-s duration, acquired sequentially with the same flip angle schedule. We performed a separate image reconstruction for each segment, producing whole-brain navigators that were aligned to the first segment using normalized correlation. The estimated rigid motion was used to correct the k-space data, and the aligned data were matched with the dictionary to obtain motion-corrected maps. RESULTS: A significant improvement on the motion-affected maps after motion correction is evident with the suppression of motion artifacts. Correlation with the motionless baseline improved by 20% on average for both T1 and T2 estimations after motion correction. In addition, the average motion-induced quantification bias of 70 ms for T1 and 18 ms for T2 values was reduced to 12 ms and 6 ms, respectively, improving the reliability of quantitative estimations. CONCLUSION: We established a method that allows correcting 3D rigid motion on a 7-s timescale during the reconstruction of MRF data using self-navigators, improving the image quality and the quantification robustness.

Multi-site repeatability and reproducibility of MR fingerprinting of the healthy brain at 1.5 and 3.0 T.

Fully-quantitative MR imaging methods are useful for longitudinal characterization of disease and assessment of treatment efficacy. However, current quantitative MRI protocols have not been widely adopted in the clinic, mostly due to lengthy scan times. Magnetic Resonance Fingerprinting (MRF) is a new technique that can reconstruct multiple parametric maps from a single fast acquisition in the transient state of the MR signal. Due to the relative novelty of this technique, the repeatability and reproducibility of quantitative measurements obtained using MRF has not been extensively studied. Our study acquired test/retest data from the brains of nine healthy volunteers, each scanned on five MRI systems (two at 3.0 T and three at 1.5 T, all from a single vendor) located at two different centers. The pulse sequence and reconstruction algorithm were the same for all acquisitions. After registration of the MRF-derived M0, T1 and T2 maps to an anatomical atlas, coefficients-of-variation (CVs) were computed to assess test/retest repeatability and inter-site reproducibility in each voxel, while a General Linear Model (GLM) was used to determine the voxel-wise variability between all confounders, which included test/retest, subject, field strength and site. Our analysis demonstrated an excellent repeatability (CVs of 2-3% for T1, 5-8% for T2, 3% for normalized-M0) and a good reproducibility (CVs of 3-8% for T1, 8-14% for T2, 5% for normalized-M0) in grey and white matter.

Silent T2* and T2 encoding using ZTE combined with BURST.

PURPOSE: To obtain T2* and T2 -weighted images as well as quantitative T2* , T2 , and susceptibility maps with a novel, silent 3D imaging method, which combines zero-echo-time (ZTE) imaging with gradient- and spin-echo BURST encoding. METHODS: After a segment of standard ZTE encoding with multiple 3D radial k-space spokes, the direction of traversing k-space is reversed while excitation is switched off. This recalls gradient echoes for each spoke/excitation. This results in multiple images: one FID image from ZTE and multiple BURST echo images at different echo times weighted by a T2* decay. By adding a pair of 180° pulses with an appropriate wait period, it is also possible to obtain spin echoes, leading to T2 -weighted images. Data is reconstructed using standard 3D gridding and Fourier transformation. In vivo feasibility was demonstrated by imaging the brain of multiple healthy volunteers. RESULTS: It is possible to acquire high-quality T2* - and T2 -weighted brain images in a silent manner. From images acquired with gradient-echo ZTE-BURST, it is possible to extract quantitative T2* and magnetic susceptibility maps, whereas the spin echo version yields T2 maps. CONCLUSION: ZTE combined with BURST enables silent acquisition of T2* - and T2 -weighted images with good image quality.

Magnetic resonance fingerprinting with dictionary-based fat and water separation (DBFW MRF): A multi-component approach.

PURPOSE: To obtain a fast and robust fat-water separation with simultaneous estimation of water T1 , fat T1 , and fat fraction maps. METHODS: We modified an MR fingerprinting (MRF) framework to use a single dictionary combination of a water and fat dictionary. A variable TE acquisition pattern with maximum TE = 4.8 ms was used to increase the fat-water separability. Radiofrequency (RF) spoiling was used to reduce the size of the dictionary by reducing T2 sensitivity. The technique was compared both in vitro and in vivo to an MRF method that incorporated 3-point Dixon (DIXON MRF), as well as Cartesian IDEAL with different acquisition parameters. RESULTS: The proposed dictionary-based fat-water separation technique (DBFW MRF) successfully provided fat fraction, water, and fat T1 , B0 , and B1+ maps both in vitro and in vivo. The fat fraction and water T1 values obtained with DBFW MRF show excellent agreement with DIXON MRF as well as with the reference values obtained using a Cartesian IDEAL with a long TR (concordance correlation coefficient: 0.97/0.99 for fat fraction-water T1 ). Whereas fat fraction values with Cartesian IDEAL were degraded in the presence of T1 saturation, MRF methods successfully estimated and accounted for T1 in the fat fraction estimates. CONCLUSION: The DBFW MRF technique can successfully provide T1 and fat fraction quantification in under 20 s per slice, intrinsically correcting T1 biases typical of fast Dixon techniques. These features could improve the diagnostic quality and use of images in presence of fat.

Flexible and efficient optimization of quantitative sequences using automatic differentiation of Bloch simulations.

PURPOSE: To investigate a computationally efficient method for optimizing the Cramér-Rao Lower Bound (CRLB) of quantitative sequences without using approximations or an analytical expression of the signal. METHODS: Automatic differentiation was applied to Bloch simulations and used to optimize several quantitative sequences without the need for approximations or an analytical expression. The results were validated with in vivo measurements and comparisons to prior art. Multi-echo spin echo and DESPO T1 were used as benchmarks to verify the CRLB implementation. The CRLB of the Magnetic Resonance Fingerprinting (MRF) sequence, which has a complicated analytical formulation, was also optimized using automatic differentiation. RESULTS: The sequence parameters obtained for multi-echo spin echo and DESPO T1 matched results obtained using conventional methods. In vivo, MRF scans demonstrate that the CRLB optimization obtained with automatic differentiation can improve performance in presence of white noise. For MRF, the CRLB optimization converges in 1.1 CPU hours for NTR = 400 and has O(NTR) asymptotic runtime scaling for the calculation of the CRLB objective and gradient. CONCLUSIONS: Automatic differentiation can be used to optimize the CRLB of quantitative sequences without using approximations or analytical expressions. For MRF, the runtime is computationally efficient and can be used to investigate confounding factors as well as MRF sequences with a greater number of repetitions.

Elabela/Toddler Is an Endogenous Agonist of the Apelin APJ Receptor in the Adult Cardiovascular System, and Exogenous Administration of the Peptide Compensates for the Downregulation of Its Expression in Pulmonary Arterial Hypertension.

BACKGROUND: Elabela/toddler (ELA) is a critical cardiac developmental peptide that acts through the G-protein-coupled apelin receptor, despite lack of sequence similarity to the established ligand apelin. Our aim was to investigate the receptor pharmacology, expression pattern, and in vivo function of ELA peptides in the adult cardiovascular system, to seek evidence for alteration in pulmonary arterial hypertension (PAH) in which apelin signaling is downregulated, and to demonstrate attenuation of PAH severity with exogenous administration of ELA in a rat model. METHODS: In silico docking analysis, competition binding experiments, and downstream assays were used to characterize ELA receptor binding in human heart and signaling in cells expressing the apelin receptor. ELA expression in human cardiovascular tissues and plasma was determined using real-time quantitative polymerase chain reaction, dual-labeling immunofluorescent staining, and immunoassays. Acute cardiac effects of ELA-32 and [Pyr1]apelin-13 were assessed by MRI and cardiac catheterization in anesthetized rats. Cardiopulmonary human and rat tissues from PAH patients and monocrotaline- and Sugen/hypoxia-exposed rats were used to show changes in ELA expression in PAH. The effect of ELA treatment on cardiopulmonary remodeling in PAH was investigated in the monocrotaline rat model. RESULTS: ELA competed for binding of apelin in human heart with overlap for the 2 peptides indicated by in silico modeling. ELA activated G-protein- and ß-arrestin-dependent pathways. We detected ELA expression in human vascular endothelium and plasma. Comparable to apelin, ELA increased cardiac contractility, ejection fraction, and cardiac output and elicited vasodilatation in rat in vivo. ELA expression was reduced in cardiopulmonary tissues from PAH patients and PAH rat models, respectively. ELA treatment significantly attenuated elevation of right ventricular systolic pressure and right ventricular hypertrophy and pulmonary vascular remodeling in monocrotaline-exposed rats. CONCLUSIONS: These results show that ELA is an endogenous agonist of the human apelin receptor, exhibits a cardiovascular profile comparable to apelin, and is downregulated in human disease and rodent PAH models, and exogenous peptide can reduce the severity of cardiopulmonary remodeling and function in PAH in rats. This study provides additional proof of principle that an apelin receptor agonist may be of therapeutic use in PAH in humans.

MR fingerprinting with simultaneous B1 estimation.

PURPOSE: MR fingerprinting (MRF) can be used for quantitative estimation of physical parameters in MRI. Here, we extend the method to incorporate B1 estimation. METHODS: The acquisition is based on steady state free precession MR fingerprinting with a Cartesian trajectory. To increase the sensitivity to the B1 profile, abrupt changes in flip angle were introduced in the sequence. Slice profile and B1 effects were included in the dictionary and the results from two- and three-dimensional (3D) acquisitions were compared. Acceleration was demonstrated using retrospective undersampling in the phase encode directions of 3D data exploiting redundancy between MRF frames at the edges of k-space. RESULTS: Without B1 estimation, T2 and B1 were inaccurate by more than 20%. Abrupt changes in flip angle improved B1 maps. T1 and T2 values obtained with the new MRF methods agree with classical spin echo measurements and are independent of the B1 field profile. When using view sharing reconstruction, results remained accurate (error <10%) when sampling under 10% of k-space from the 3D data. CONCLUSION: The methods demonstrated here can successfully measure T1, T2, and B1. Errors due to slice profile can be substantially reduced by including its effect in the dictionary or acquiring data in 3D. Magn Reson Med 76:1127-1135, 2016. © 2015 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Combining MRI with PET for partial volume correction improves image-derived input functions in mice.

Accurate kinetic modelling using dynamic PET requires knowledge of the tracer concentration in plasma, known as the arterial input function (AIF). AIFs are usually determined by invasive blood sampling, but this is prohibitive in murine studies due to low total blood volumes. As a result of the low spatial resolution of PET, image-derived input functions (IDIFs) must be extracted from left ventricular blood pool (LVBP) ROIs of the mouse heart. This is challenging because of partial volume and spillover effects between the LVBP and myocardium, contaminating IDIFs with tissue signal. We have applied the geometric transfer matrix (GTM) method of partial volume correction (PVC) to 12 mice injected with 18F-FDG affected by a Myocardial Infarction (MI), of which 6 were treated with a drug which reduced infarction size [1]. We utilised high resolution MRI to assist in segmenting mouse hearts into 5 classes: LVBP, infarcted myocardium, healthy myocardium, lungs/body and background. The signal contribution from these 5 classes was convolved with the point spread function (PSF) of the Cambridge split magnet PET scanner and a non-linear fit was performed on the 5 measured signal components. The corrected IDIF was taken as the fitted LVBP component. It was found that the GTM PVC method could recover an IDIF with less contamination from spillover than an IDIF extracted from PET data alone. More realistic values of Ki were achieved using GTM IDIFs, which were shown to be significantly different (p<0.05) between the treated and untreated groups.

Functional assessment of the mouse heart by MRI with a 1-min acquisition.

In vivo assessment of heart function in mice is important for basic and translational research in cardiology. MRI is an accurate tool for the investigation of the anatomy and function in the preclinical setting; however, the long scan duration limits its usage. We aimed to reduce the acquisition time of cine MRI to 1 min. We employed spatiotemporal compressed sensing and parallel imaging to accelerate retrospectively gated cine MRI. We compared the functional parameters derived from full and undersampled data in Cartesian and radial MRI by means of Bland-Altman plots. We found that the scan time for the whole heart could be reduced to 2 min with Cartesian sampling and to 1 min with radial sampling. Despite a reduction in the signal-to-noise ratio, the accuracy in the estimation of left and right ventricular volumes was preserved for all tested subjects. This method can be used to perform accurate functional MRI examinations in mice for high-throughput phenotyping or translational studies.

Impaired limbic cortico-striatal structure and sustained visual attention in a rodent model of schizophrenia.

BACKGROUND: N-methyl-d-aspartate receptor (NMDAR) dysfunction is thought to contribute to the pathophysiology of schizophrenia. Accordingly, NMDAR antagonists such as phencyclidine (PCP) are used widely in experimental animals to model cognitive impairment associated with this disorder. However, it is unclear whether PCP disrupts the structural integrity of brain areas relevant to the profile of cognitive impairment in schizophrenia. METHODS: Here we used high-resolution magnetic resonance imaging and voxel-based morphometry to investigate structural alterations associated with sub-chronic PCP treatment in rats. RESULTS: Sub-chronic exposure of rats to PCP (5mg/kg twice daily for 7 days) impaired sustained visual attention on a 5-choice serial reaction time task, notably when the attentional load was increased. In contrast, sub-chronic PCP had no significant effect on the attentional filtering of a pre-pulse auditory stimulus in an acoustic startle paradigm. Voxel-based morphometry revealed significantly reduced grey matter density bilaterally in the hippocampus, anterior cingulate cortex, ventral striatum, and amygdala. PCP-treated rats also exhibited reduced cortical thickness in the insular cortex. CONCLUSIONS: These findings demonstrate that sub-chronic NMDA receptor antagonism is sufficient to produce highly-localized morphological abnormalities in brain areas implicated in the pathogenesis of schizophrenia. Furthermore, PCP exposure resulted in dissociable impairments in attentional function.

Detection of pathological contrast enhancement with synthetic brain imaging from quantitative multiparametric MRI.

BACKGROUND AND PURPOSE: We aimed to test whether synthetic T1-weighted imaging derived from a post-contrast Quantitative Transient-state Imaging (QTI) acquisition enabled revealing pathological contrast enhancement in intracranial lesions. METHODS: The analysis included 141 patients who underwent a 3 Tesla-MRI brain exam with intravenous contrast media administration, with the post-contrast acquisition protocol comprising a three-dimensional fast spoiled gradient echo (FSPGR) sequence and a QTI acquisition. Synthetic T1-weighted images were generated from QTI-derived quantitative maps of relaxation times and proton density. Two neuroradiologists assessed synthetic and conventional post-contrast T1-weighted images for the presence and pattern of pathological contrast enhancement in intracranial lesions. Enhancement volumes were quantitatively compared. RESULTS: Using conventional imaging as a reference, synthetic T1-weighted imaging was 93% sensitive in revealing the presence of contrast enhancing lesions. The agreement for the presence/absence of contrast enhancement was almost perfect both between readers (k = 1 for both conventional and synthetic imaging) and between sequences (k = 0.98 for both readers). In 91% of lesions, synthetic T1-weighted imaging showed the same pattern of contrast enhancement visible in conventional imaging. Differences in enhancement pattern in the remaining lesions can be due to the lower spatial resolution and the longer acquisition delay from contrast media administration of QTI compared to FSPGR. Overall, enhancement volumes appeared larger in synthetic imaging. CONCLUSIONS: QTI-derived post-contrast synthetic T1-weighted imaging captures pathological contrast enhancement in most intracranial enhancing lesions. Further comparative studies employing quantitative imaging with higher spatial resolution is needed to support our data and explore possible future applications in clinical trials.

A fast protocol for infarct quantification in mice.

PURPOSE: To demonstrate and validate a late gadolinium enhancement (LGE) imaging protocol, optimized for tissue viability assessment in interventional mouse models of myocardial infarction. MATERIALS AND METHODS: The method uses an efficient sampling scheme using multiple slices in a single heartbeat interleaving slice packages between alternate TRs. Sampling multiple slices instead of multiple echoes or multiple k-lines achieves higher SNR efficiency, and images covering the whole heart can be obtained in 3 min. Saturation effects are exploited for an optimum compromise between contrast and speed. RESULTS: The images obtained show high hyperenhancement with good contrast-to-noise. It is shown that inversion time optimization can be reliably omitted with this scheme, and that measured infarct sizes correlate well with histological measures. CONCLUSION: Our protocol offers a new efficient tool for the measurement of infarct size in mouse models of heart disease.

Generating Synthetic Radiological Images with PySynthMRI: An Open-Source Cross-Platform Tool.

Synthetic MR Imaging allows for the reconstruction of different image contrasts from a single acquisition, reducing scan times. Commercial products that implement synthetic MRI are used in research. They rely on vendor-specific acquisitions and do not include the possibility of using custom multiparametric imaging techniques. We introduce PySynthMRI, an open-source tool with a user-friendly interface that uses a set of input images to generate synthetic images with diverse radiological contrasts by varying representative parameters of the desired target sequence, including the echo time, repetition time and inversion time(s). PySynthMRI is written in Python 3.6, and it can be executed under Linux, Windows, or MacOS as a python script or an executable. The tool is free and open source and is developed while taking into consideration the possibility of software customization by the end user. PySynthMRI generates synthetic images by calculating the pixelwise signal intensity as a function of a set of input images (e.g., T1 and T2 maps) and simulated scanner parameters chosen by the user via a graphical interface. The distribution provides a set of default synthetic contrasts, including T1w gradient echo, T2w spin echo, FLAIR and Double Inversion Recovery. The synthetic images can be exported in DICOM or NiFTI format. PySynthMRI allows for the fast synthetization of differently weighted MR images based on quantitative maps. Specialists can use the provided signal models to retrospectively generate contrasts and add custom ones. The modular architecture of the tool can be exploited to add new features without impacting the codebase.

Quantitative T1 mapping detects blood-brain barrier breakdown in apparently non-enhancing multiple sclerosis lesions.

OBJECTIVES: The disruption of the blood-brain barrier (BBB) is a key and early feature in the pathogenesis of demyelinating multiple sclerosis (MS) lesions and has been neuropathologically demonstrated in both active and chronic plaques. The local overt BBB disruption in acute demyelinating lesions is captured as signal hyperintensity in post-contrast T1-weighted images because of the contrast-related shortening of the T1 relaxation time. On the contrary, the subtle BBB disruption in chronic lesions is not visible at conventional radiological evaluation but it might be of clinical relevance. Indeed, persistent, subtle BBB leakage might be linked to low-grade inflammation and plaque evolution. Here we hypothesised that 3D Quantitative Transient-state Imaging (QTI) was able to reveal and measure T1 shortening (ΔT1) reflecting small amounts of contrast media leakage in apparently non-enhancing lesions (ANELs). MATERIALS AND METHODS: Thirty-four patients with relapsing remitting MS were included in the study. All patients underwent a 3 T MRI exam of the brain including conventional sequences and QTI acquisitions (1.1 mm isotropic voxel) performed both before and after contrast media administration. For each patient, a ΔT1 map was obtained via voxel-wise subtraction of pre- and post- contrast QTI-derived T1 maps. ΔT1 values measured in ANELs were compared with those recorded in enhancing lesions and in the normal appearing white matter. A reference distribution of ΔT1 in the white matter was obtained from datasets acquired in 10 non-MS patients with unrevealing MR imaging. RESULTS: Mean ΔT1 in ANELs (57.45 ± 48.27 ms) was significantly lower than in enhancing lesions (297.71 ± 177.52 ms; p < 0. 0001) and higher than in the normal appearing white matter (36.57 ± 10.53 ms; p < 0.005). Fifty-two percent of ANELs exhibited ΔT1 higher than those observed in the white matter of non-MS patients. CONCLUSIONS: QTI-derived quantitative ΔT1 mapping enabled to measure contrast-related T1 shortening in ANELs. ANELs exhibiting ΔT1 values that deviate from the reference distribution in non-MS patients may indicate persistent, subtle, BBB disruption. Access to this information may be proved useful to better characterise pathology and objectively monitor disease activity and response to therapy.