The central pattern of weakness of ALS: Morphological correlates in whole-body muscle MRI.

OBJECTIVE: Monosynaptically cortically innervated α-motoneurons are early and strongly involved in amyotrophic lateral sclerosis (ALS). Consequently, the muscles that receive the strongest direct corticomotoneuronal input are the clinically most affected. To objectify this concept in vivo through morphological image correlates, whole-body magnetic resonance imaging (MRI) with muscle signal analysis was performed in patients with ALS compared to healthy controls. METHODS: Modified Dixon-based whole-body MRI was acquired in patients with ALS (n = 33) and matched healthy controls (n = 30). Manual labeling of limb muscle MRI was performed, and a specific subset of nine muscles, selected as pairs of muscle groups with different corticomotoneuronal input, was analyzed per subject based on their volume, fat fraction, and functional remaining muscle area (fRMA). RESULTS: Statistical analysis of 978 muscles in total revealed significantly decreased volumes, decreased fRMA, and increased fat fraction in the muscles of patients with ALS compared to controls. The clinical degree of pareses of directly innervated muscles was significantly worse than that of less directly innervated muscles in each comparison. The muscles receiving stronger direct corticomotoneuronal input showed more pronounced morphological involvement compared to those with less monosynaptic corticomotoneuronal input (fRMA, significant in three pairwise comparisons). INTERPRETATION: In conclusion, whole-body MRI-based muscle analysis provided additional evidence for a characteristic pattern of pareses in ALS. This technical approach (parameterization and quantification of muscle alterations from MRI) to patients with ALS could pave the way for the future establishment of a diagnostic algorithm of muscle MRI for ALS and may serve as a biomarker.

Multi-network approach for image segmentation in non-contrast enhanced cardiac 3D MRI of arrhythmic patients.

Left atrial appendage (LAA) is the source of thrombi formation in more than 90% of strokes in patients with nonvalvular atrial fibrillation. Catheter-based LAA occlusion is being increasingly applied as a treatment strategy to prevent stroke. Anatomical complexity of LAA makes percutaneous occlusion commonly performed under transesophageal echocardiography (TEE) and X-ray (XR) guidance especially challenging. Image fusion techniques integrating 3D anatomical models derived from pre-procedural imaging into the live XR fluoroscopy can be applied to guide each step of the LAA closure. Cardiac magnetic resonance (CMR) imaging gains in importance for radiation-free evaluation of cardiac morphology as alternative to gold-standard TEE or computed tomography angiography (CTA). Manual delineation of cardiac structures from non-contrast enhanced CMR is, however, labor-intensive, tedious, and challenging due to the rather low contrast. Additionally, arrhythmia often impairs the image quality in ECG synchronized acquisitions causing blurring and motion artifacts. Thus, for cardiac segmentation in arrhythmic patients, there is a strong need for an automated image segmentation method. Deep learning-based methods have shown great promise in medical image analysis achieving superior performance in various imaging modalities and different clinical applications. Fully-convolutional neural networks (CNNs), especially U-Net, have become the method of choice for cardiac segmentation. In this paper, we propose an approach for automatic segmentation of cardiac structures from non-contrast enhanced CMR images of arrhythmic patients based on CNNs implemented in a multi-stage pipeline. Two-stage implementation allows subdividing the task into localization of the relevant cardiac structures and segmentation of these structures from the cropped sub-regions obtained from previous step leading to efficient and effective way of automated cardiac segmentation.

Impact of cardiac and respiratory motion on the 3D accuracy of image-guided interventions on monoplane systems.

PURPOSE: Image-guided intervention (IGI) systems have the potential to increase the efficiency in interventional cardiology but face limitations from motion. Even though motion compensation approaches have been proposed, the resulting accuracy has rarely been quantified using in vivo data. The purpose of this study is to investigate the potential benefit of motion-compensation in IGS systems. METHODS: Patients scheduled for left atrial appendage closure (LAAc) underwent pre- and postprocedural non-contrast-enhanced cardiac magnetic resonance imaging (CMR). According to the clinical standard, the final position of the occluder device was routinely documented using x-ray fluoroscopy (XR). The accuracy of the IGI system was assessed retrospectively based on the distance of the 3D device marker location derived from the periprocedural XR data and the respective location as identified in the postprocedural CMR data. RESULTS: The assessment of the motion-compensation depending accuracy was possible based on the patient data. With motion synchronization, the measured accuracy of the IGI system resulted similar to the estimated accuracy, with almost negligible distances of the device marker positions identified in CMR and XR. Neglection of the cardiac and/or respiratory phase significantly increased the mean distances, with respiratory motion mainly reducing the accuracy with rather low impact on the precision, whereas cardiac motion decreased the accuracy and the precision of the image guidance. CONCLUSIONS: In the presented work, the accuracy of the IGI system could be assessed based on in vivo data. Motion consideration clearly showed the potential to increase the accuracy in IGI systems. Where the general decrease in accuracy in non-motion-synchronized data did not come unexpected, a clear difference between cardiac and respiratory motion-induced errors was observed for LAAc data. Since sedation and intervention location close to the large vessels likely impacts the respiratory motion contribution, an intervention-specific accuracy analysis may be useful for other interventions.

Cardiac magnetic resonance imaging for preprocedural planning of percutaneous left atrial appendage closure.

Introduction: Percutaneous closure of the left atrial appendage (LAA) facilitates stroke prevention in patients with atrial fibrillation. Optimal device selection and positioning are often challenging due to highly variable LAA shape and dimension and thus require accurate assessment of the respective anatomy. Transesophageal echocardiography (TEE) and x-ray fluoroscopy (XR) represent the gold standard imaging techniques. However, device underestimation has frequently been observed. Assessment based on 3-dimensional computer tomography (CTA) has been reported as more accurate but increases radiation and contrast agent burden. In this study, the use of non-contrast-enhanced cardiac magnetic resonance imaging (CMR) to support preprocedural planning for LAA closure (LAAc) was investigated. Methods: CMR was performed in thirteen patients prior to LAAc. Based on the 3-dimensional CMR image data, the dimensions of the LAA were quantified and optimal C-arm angulations were determined and compared to periprocedural data. Quantitative figures used for evaluation of the technique comprised the maximum diameter, the diameter derived from perimeter and the area of the landing zone of the LAA. Results: Perimeter- and area-based diameters derived from preprocedural CMR showed excellent congruency compared to those measured periprocedurally by XR, whereas the respective maximum diameter resulted in significant overestimation (p < 0.05). Compared to TEE assessment, CMR-derived diameters resulted in significantly larger dimensions (p < 0.05). The deviation of the maximum diameter to the diameters measured by XR and TEE correlated well with the ovality of the LAA. C-arm angulations used during the procedures were in agreement with those determined by CMR in case of circular LAA. Discussion: This small pilot study demonstrates the potential of non-contrast-enhanced CMR to support preprocedural planning of LAAc. Diameter measurements based on LAA area and perimeter correlated well with the actual device selection parameters. CMR-derived determination of landing zones facilitated accurate C-arm angulation for optimal device positioning.

MRI-based training model for left atrial appendage closure.

PURPOSE: Percutaneous closure of the left atrial appendage (LAA) reduces the risk of embolic stroke in patients with atrial fibrillation. Thereby, the optimal transseptal puncture (TSP) site differs due to the highly variable anatomical shape of the LAA, which is rarely considered in existing training models. Based on non-contrast-enhanced magnetic resonance imaging (MRI) volumes, we propose a training model for LAA closure with interchangeable and patient-specific LAA enabling LAA-specific identification of the TSP site best suited. METHODS: Based on patient-specific MRI data, silicone models of the LAAs were produced using a 3D-printed cast model. In addition, an MRI-derived 3D-printed base model was set up, including the right and left atrium with predefined passages in the septum, mimicking multiple TSP sites. The various silicone models and a tube mimicking venous access were connected to the base model. Empirical use of the model allowed the demonstration of its usability. RESULTS: Patient-specific silicone models of the LAA could be generated from all LAA patient MRI datasets. The influence of various combinations regarding TSP sites and LAA shapes could be demonstrated as well as the technical functionality of the occluder system. Via the attached tube mimicking the venous access, the correct handling of the deployment catheter even in case of not optimal puncture site could be practiced. CONCLUSION: The proposed contrast-agent and radiation-free MRI-based training model for percutaneous LAA closure enables the pre-interventional assessment of the influence of the TSP site on the access of patient-specific LAA shapes. A straightforward replication of this work is measured by using clinically available imaging protocols and a widespread 3D printer technique to build the model.

Computed tomography angiography/magnetic resonance imaging-based preprocedural planning and guidance in the interventional treatment of structural heart disease.

Preprocedural planning and periprocedural guidance based on image fusion are widely established techniques supporting the interventional treatment of structural heart disease. However, these two techniques are typically used independently. Previous works have already demonstrated the benefits of integrating planning details into image fusion but are limited to a few applications and the availability of the proprietary tools used. We propose a vendor-independent approach to integrate planning details into periprocedural image fusion facilitating guidance during interventional treatment. In this work, we demonstrate the feasibility of integrating planning details derived from computer tomography and magnetic resonance imaging into periprocedural image fusion with open-source and commercially established tools. The integration of preprocedural planning details into periprocedural image fusion has the potential to support safe and efficient interventional treatment of structural heart disease.

Reproducibility of functional lung parameters derived from free-breathing non-contrast-enhanced 2D ultrashort echo-time.

Background: Imaging the lung parenchyma with magnetic resonance imaging (MRI) is challenging due to cardiac and respiratory motion, the low proton density and short T2* relaxation time, and therefore not well established in the clinical routine. As a further step in facilitating lung MRI for longitudinal monitoring, this study aimed to assess the reproducibility of 2D ultrashort echo time (UTE)-derived lung function parameters in healthy subjects. Methods: In this study, a 2D UTE technique was combined with tiny golden angle (tyGA) ordering. Data were acquired either during breath-holds (BH) or continuously during free-breathing (FB) at a field strength of 3T. Retrospective self-gating (image- and k-space-based) was used to reconstruct respiratory and cardiac multistage images from the FB acquisitions. The reproducibility of functional lung parameters derived from BH and FB acquisitions was assessed for three independent examinations (M1-3). M1 and M2 were acquired within 2 h, whereas M3 was acquired at least 14 d after M1/2. Different respiratory and cardiac phases were reconstructed for three coronal slices. Quantitative analysis including proton fraction (fP ), apparent signal-to-noise ratio (apparent SNR), fractional ventilation (FV), and perfusion (f) was performed by two independent observers, and inter-measurement and inter-observer repeatability were assessed. Results: All scans could be performed successfully in all volunteers. Intraclass correlation coefficients (ICC) of inter-measurement and inter-observer variability, and Bland-Altman analysis showed good to very good reproducibility. Larger breathing amplitudes were observed in the BH acquisitions, which also showed lower reproducibility when compared with the FB acquisitions. For the FB approach, the ICC ranged between 0.70 and 0.98 for all measurements, and ranged between 0.86 and 0.97 for the two observers. No bias or significant differences were observed between the three measurements or the two observers in healthy volunteers. Conclusions: The study proves the feasibility of FB 2D tyGA UTE for lung imaging. Functional parameters derived from FB acquisitions are reproducible in healthy volunteers, allowing for further investigation of this technique in patients with various underlying diseases.

Real-Time Spiral CMR Is Superior to Conventional Segmented Cine-Imaging for Left-Ventricular Functional Assessment in Patients with Arrhythmia.

(1) Background: Segmented Cartesian Cardiovascular magnetic resonance (CMR) often fails to deliver robust assessment of cardiac function in patients with arrhythmia. We aimed to assess the performance of a tiny golden-angle spiral real-time CMR sequence at 1.5 T for left-ventricular (LV) volumetry in patients with irregular heart rhythm; (2) Methods: We validated the real-time sequence against the standard breath-hold segmented Cartesian sequence in 32 patients, of whom 11 presented with arrhythmia. End-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF) were assessed. In arrhythmic patients, real-time and standard Cartesian acquisitions were compared against a reference echocardiographic modality; (3) Results: In patients with sinus rhythm, good agreements and correlations were found between the segmented and real-time methods, with only minor, non-significant underestimation of EDV for the real-time sequence (135.95 ± 30 mL vs. 137.15 ± 31, p = 0.164). In patients with arrhythmia, spiral real-time CMR yielded superior image quality to the conventional segmented imaging, allowing for excellent agreement with the reference echocardiographic volumetry. In contrast, in this cohort, standard Cartesian CMR showed significant underestimation of LV-ESV (106.72 ± 63.51 mL vs. 125.47 ± 72.41 mL, p = 0.026) and overestimation of LVEF (42.96 ± 10.81% vs. 39.02 ± 11.72%, p = 0.039); (4) Conclusions: Real-time spiral CMR improves image quality in arrhythmic patients, allowing reliable assessment of LV volumetry.

Tiny golden angle ultrashort echo-time lung imaging in mice.

Imaging the lung parenchyma with MRI is particularly difficult in small animals due to the high respiratory and heart rates, and ultrashort T2* at high magnetic field strength caused by the high susceptibilities induced by the air-tissue interfaces. In this study, a 2D ultrashort echo-time (UTE) technique was combined with tiny golden angle (tyGA) ordering. Data were acquired continuously at 11.7 T and retrospective center-of-k-space gating was applied to reconstruct respiratory multistage images. Lung (proton) density (fP ), T2*, signal-to-noise ratio (SNR), fractional ventilation (FV) and perfusion (f) were quantified, and the application to dynamic contrast agent (CA)-enhanced (DCE) qualitative perfusion assessment tested. The interobserver and intraobserver and interstudy reproducibility of the quantitative parameters were investigated. High-quality images of the lung parenchyma could be acquired in all animals. Over all lung regions a mean T2* of 0.20 ± 0.05 ms was observed. FV resulted as 0.31 ± 0.13, and a trend towards lower SNR values during inspiration (EX: SNR = 12.48 ± 6.68, IN: SNR = 11.79 ± 5.86) and a significant (P < 0.001) decrease in lung density (EX: fP  = 0.69 ± 0.13, IN: fP  = 0.62 ± 0.13) were observed. Quantitative perfusion results as 34.63 ± 9.05 mL/cm3 /min (systole) and 32.77 ± 8.55 mL/cm3 /min (diastole) on average. The CA dynamics could be assessed and, because of the continuous nature of the data acquisition, reconstructed at different temporal resolutions. Where a good to excellent interobserver reproducibility and an excellent intraobserver reproducibility resulted, the interstudy reproducibility was only fair to good. In conclusion, the combination of tiny golden angles with UTE (2D tyGA UTE) resulted in a reliable imaging technique for lung morphology and function in mice, providing uniform k-space coverage and thus low-artefact images of the lung parenchyma after gating.

Quantification of Biventricular Myocardial Strain Using CMR Feature Tracking: Reproducibility in Small Animals.

Myocardial strain is a well-validated parameter for evaluating myocardial contraction. Cardiovascular magnetic resonance myocardial feature tracking (CMR-FT) is a novel method for the quantitative measurements of myocardial strain from routine cine acquisitions. In this study, we investigated the influence of temporal resolution on tracking accuracy of CMR-FT and the intraobserver, interobserver, and interstudy reproducibilities for biventricular strain analysis in mice from self-gated CMR at 11.7 T. 12 constitutive nexilin knockout (Nexn-KO) mice, heterozygous (Het, N = 6) and wild-type (WT, N = 6), were measured with a well-established self-gating sequence twice within two weeks. CMR-FT measures of biventricular global and segmental strain parameters were derived. Interstudy, intraobserver, and interobserver reproducibilities were investigated. For the assessment of the impact of the temporal resolution for the outcome in CMR-FT, highly oversampled semi-4 chamber and midventricular short-axis data were acquired and reconstructed with 10 to 80 phases per cardiac cycle. A generally reduced biventricular myocardial strain was observed in Nexn-KO Het mice. Excellent intraobserver and interobserver reproducibility was achieved in all global strains (ICC range from 0.76 to 0.99), where global right ventricle circumferential strain (RCSSAX) showed an only good interobserver reproducibility (ICC 0.65, 0.11-0.89). For interstudy reproducibility, left ventricle longitudinal strain (LLSLAX) was the most reproducible measure of strain (ICC 0.90, 0.71-0.97). The left ventricle radial strain (LRSSAX) (ICC 0.50, 0.10-0.83) showed fair reproducibility and RCSSAX (ICC 0.36, 0.14-0.74) showed only poor reproducibility. In general, compared with global strains, the segmental strains showed relatively lower reproducibility. A minimal temporal resolution of 20 phases per cardiac cycle appeared sufficient for CMR-FT strain analysis. The analysis of myocardial strain from high-resolution self-gated cine images by CMR-FT provides a highly reproducible method for assessing myocardial contraction in small rodent animals. Especially, global LV longitudinal and circumferential strain revealed excellent reproducibility of intra- and interobserver and interstudy measurements.

2D Ultrashort Echo-Time Functional Lung Imaging.

BACKGROUND: Imaging of the lung by MRI is challenging due to the intrinsic low proton density and rapid T2 * relaxation. MRI methods providing lung parenchyma and function are in demand. PURPOSE: To investigate the feasibility of two-dimensional ultrashort echo-time (2D UTE) imaging for lung function assessment. STUDY TYPE: Prospective. POPULATION: Eleven healthy volunteers. FIELD STRENGTH/SEQUENCE: 3T, 2D tiny golden angle UTE (2D-tyUTE). ASSESSMENT: The applicability of breath-hold (BH) and self-gated (SG) 2D-tyUTE for quantification of the lung parenchyma signal-to-noise ratio (SNR), proton fraction (fP ), fractional ventilation (FV), and perfusion (f) was investigated. Dependencies on repetition time (BHS/I1/I2 ) and respiratory phase (expiration [EX], inspiration [IN]) were investigated and compared between smokers and nonsmokers. STATISTICAL TESTS: Analysis of variance (ANOVA), Kendell's W. RESULTS: Significant differences of SNR (EX: 10.98 ± 3.19(BHS ), 14.58 ± 3.89(BHI1 ), 17.59 ± 4.92(BHI2 ), 11.00 ± 5.42(SG); IN: 7.17 ± 2.07(BHS ), 9.51 ± 2.37(BHI1 ), 10.49 ± 2.33(BHI2 ), 10.00 ± 4.14(SG)) (P < 0.05 for all cases) were observed between the different approaches. Where fP in expiration (0.41 ± 0.13) was independent of the BH imaging technique, it was slightly higher in SG (0.44 ± 0.06). FV was reproducible among the BH techniques (0.41 ± 0.10), but significantly lower in SG (0.21 ± 0.06) (P < 0.05). A moderate correlation (R2 = 0.47, P < 0.01) was observed between the breathing amplitude and FV. No significant differences between BH and SG were observed for the perfusion analysis (EX: 3.50 ± 1.29 mL/min/mL [BHS ]; IN: 2.36 ± 1.05 mL/min/mL [BHS ]). Significant differences in fP were found between smokers (0.48 ± 0.11 BH) and nonsmokers (0.37 ± 0.12 BH) in expiration. DATA CONCLUSION: This study demonstrates the feasibility of 2D-tyUTE for successful quantification of relevant lung function parameters at 3T within clinically attractive acquisition times. The low spatial resolution into the slice selection direction may limit the final sensitivity and needs further clinical evaluation. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1 J. MAGN. RESON. IMAGING 2020;52:1637-1644.

Feasibility of real-time cardiac MRI in mice using tiny golden angle radial sparse.

Cardiovascular magnetic resonance imaging has proven valuable for the assessment of structural and functional cardiac abnormalities. Even although it is an established imaging method in small animals, the long acquisition times of gated or self-gated techniques still limit its widespread application. In this study, the application of tiny golden angle radial sparse MRI (tyGRASP) for real-time cardiac imaging was tested in 12 constitutive nexilin (Nexn) knock-out (KO) mice, both heterozygous (Het, N = 6) and wild-type (WT, N = 6), and the resulting functional parameters were compared with a well-established self-gating approach. Real-time images were reconstructed for different temporal resolutions of between 16.8 and 79.8 ms per image. The suggested approach was additionally tested for dobutamine stress and qualitative first-pass perfusion imaging. Measurements were repeated twice within 2 weeks for reproducibility assessment. In direct comparison with the high-quality, self-gated technique, the real-time approach did not show any significant differences in global function parameters for acquisition times below 50 ms (rest) and 31.5 ms (stress). Compared with WT, the end-diastolic volume (EDV) and end-systolic volume (ESV) were markedly higher (P < 0.05) and the ejection fraction (EF) was significantly lower in the Het Nexn-KO mice at rest (P < 0.001). For the stress investigation, a clear decrease of EDV and ESV, and an increase in EF, but maintained stroke volume, could be observed in both groups. Combined with ECG-triggering, tyGRASP provided first-pass perfusion data with a temporal resolution of one image per heartbeat, allowing the quantitative assessment of upslope curves in the blood-pool and myocardium. Excellent inter-study reproducibility was achieved in all the functional parameters. The tyGRASP is a valuable real-time MRI technique for mice, which significantly reduces the scan time in preclinical cardiac functional imaging, providing sufficient image quality for deriving accurate functional parameters, and has the potential to investigate real-time and beat-to-beat changes.

Sliding window reduced FOV reconstruction for real-time cardiac imaging.

BACKGROUND: Current functional cardiovascular imaging protocols mostly rely on electrocardiogram (ECG) gating and breathholding. The resulting image quality can substantially suffer from insufficient patient cooperation or severe arrhythmia. Real-time imaging can mitigate these effects but requires highly accelerated techniques, usually relying on non-cartesian trajectories and Compressed Sensing (CS). METHODS: We investigate a sliding window reduced field of view (FOV) Echo Planar Imaging (EPI) technique for real-time cardiac MRI. Segmented EPI has been combined with a subtraction technique for reducing the FOV in cardiac applications to the region of the beating heart. Residual respiratory motion, potentially impairing the image quality, has been addressed by continuous update of the static image fraction, which is derived from a low-temporal resolution sliding window reconstruction. For further acceleration, the proposed technique was combined with parallel imaging. RESULTS: The sliding window reduced FOV technique was proven feasible to reconstruct images of diagnostic image quality at a temporal resolution of 36.5ms per image. Semi-quantitative evaluation of image quality showed significant improvement over the existing rFOV method (p=0.039). Derived functional parameters show comparable results as with the BH-CINE reference. However, a trend to a slight underestimation of the largest and smallest in-plane volumes is observed. CONCLUSION: The proposed technique is feasible of providing real-time cardiac MRI with a temporal resolution better than 40ms without the need of computably complex reconstruction techniques.