AI-assisted automatic MRI-based tongue volume evaluation in motor neuron disease (MND).

PURPOSE: Motor neuron disease (MND) causes damage to the upper and lower motor neurons including the motor cranial nerves, the latter resulting in bulbar involvement with atrophy of the tongue muscle. To measure tongue atrophy, an operator independent automatic segmentation of the tongue is crucial. The aim of this study was to apply convolutional neural network (CNN) to MRI data in order to determine the volume of the tongue. METHODS: A single triplanar CNN of U-Net architecture trained on axial, coronal, and sagittal planes was used for the segmentation of the tongue in MRI scans of the head. The 3D volumes were processed slice-wise across the three orientations and the predictions were merged using different voting strategies. This approach was developed using MRI datasets from 20 patients with 'classical' spinal amyotrophic lateral sclerosis (ALS) and 20 healthy controls and, in a pilot study, applied to the tongue volume quantification to 19 controls and 19 ALS patients with the variant progressive bulbar palsy (PBP). RESULTS: Consensus models with softmax averaging and majority voting achieved highest segmentation accuracy and outperformed predictions on single orientations and consensus models with union and unanimous voting. At the group level, reduction in tongue volume was not observed in classical spinal ALS, but was significant in the PBP group, as compared to controls. CONCLUSION: Utilizing single U-Net trained on three orthogonal orientations with consequent merging of respective orientations in an optimized consensus model reduces the number of erroneous detections and improves the segmentation of the tongue. The CNN-based automatic segmentation allows for accurate quantification of the tongue volumes in all subjects. The application to the ALS variant PBP showed significant reduction of the tongue volume in these patients and opens the way for unbiased future longitudinal studies in diseases affecting tongue volume.

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.

The future of CMR: All-in-one vs. real-time CMR (Part 2).

Cardiac Magnetic Resonance (CMR) protocols can be lengthy and complex, which has driven the research community to develop new technologies to make these protocols more efficient and patient-friendly. Two different approaches to improving CMR have been proposed, specifically "all-in-one" CMR, where several contrasts and/or motion states are acquired simultaneously, and "real-time" CMR, in which the examination is accelerated to avoid the need for breathholding and/or cardiac gating. The goal of this two-part manuscript is to describe these two different types of emerging rapid CMR protocols. To this end, the vision of all-in-one and real-time imaging are described, along with techniques which have been devised and tested along the pathway of clinical implementation. The pros and cons of the different methods are presented, and the remaining open needs of each are detailed. Part 1 tackles the "All-in-One" approaches, and Part 2 focuses on the "Real-Time" approaches along with an overall summary of these emerging methods.

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.

AI-assisted quantification of hypothalamic atrophy in amyotrophic lateral sclerosis by convolutional neural network-based automatic segmentation.

The hypothalamus is a small structure of the brain with an essential role in metabolic homeostasis, sleep regulation, and body temperature control. Some neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and dementia syndromes are reported to be related to hypothalamic volume alterations. Despite its crucial role in human body regulation, neuroimaging studies of this structure are rather scarce due to work-intensive operator-dependent manual delineations from MRI and lack of automated segmentation tools. In this study we present a fully automatic approach based on deep convolutional neural networks (CNN) for hypothalamic segmentation and volume quantification. We applied CNN of U-Net architecture with EfficientNetB0 backbone to allow for accurate automatic hypothalamic segmentation in seconds on a GPU. We further applied our approach for the quantification of the normalized hypothalamic volumes to a large neuroimaging dataset of 432 ALS patients and 112 healthy controls (without the ground truth labels). Using the automated volumetric analysis, we could reproduce hypothalamic atrophy findings associated with ALS by detecting significant volume differences between ALS patients and controls at the group level. In conclusion, a fast and unbiased AI-assisted hypothalamic quantification method is introduced in this study (whose acceptance rate based on the outlier removal strategy was estimated to be above 95%) and made publicly available for researchers interested in the conduction of hypothalamus studies at a large scale.

Inhibition of Survivin Homodimerization Decreases Neuroblastoma Cell Growth.

Increased expression of BIRC5/survivin, a crucial regulator of the mitotic spindle checkpoint, is associated with poor prognosis in neuroblastoma (NB), the most common extracranial tumor of childhood. Transcriptional inhibitors of survivin have been tested in adult cancers and inhibitors of survivin homodimerization are emerging. We compared genetic inhibition of survivin transcription with the inhibition of survivin homodimerization by S12 and LQZ-7I, chosen from a larger panel of survivin dimerization inhibitors with activity against NB cells. Mice hemizygous for Birc5 were crossed with NB-prone TH-MYCN mice to generate Birc5+/-/MYCNtg/+ mice. The marked decrease of survivin transcription in these mice did not suffice to attenuate the aggressiveness of NB, even when tumors were transplanted into wild-type mice to assure that immune cell function was not compromised by the lack of survivin. In contrast, viability, clonogenicity and anchorage-independent growth of NB cells were markedly decreased by S12. S12 administered systemically to mice with subcutaneous NB xenotransplants decreased intratumoral hemorrhage, albeit not tumor growth. LQZ-7I, which directly targets the survivin dimerization interface, was efficacious in controlling NB cell growth in vitro at markedly lower concentrations compared to S12. LQZ-7I abrogated viability, clonogenicity and anchorage-independent growth, associated with massively distorted mitotic spindle formation. In vivo, LQZ-7I effectively reduced tumor size and cell proliferation of NB cells in CAM assays without apparent toxicity to the developing chick embryo. Collectively, these findings show that inhibiting survivin homodimerization with LQZ-7I holds promise for the treatment of NB and merits further investigation.

Development of N-Terminally Modified Variants of the CXCR4-Antagonistic Peptide EPI-X4 for Enhanced Plasma Stability.

EPI-X4, a natural peptide CXCR4 antagonist, shows potential for treating inflammation and cancer, but its short plasma stability limits its clinical application. We aimed to improve the plasma stability of EPI-X4 analogues without compromising CXCR4 antagonism. Our findings revealed that only the peptide N-terminus is prone to degradation. Consequently, incorporating d-amino acids or acetyl groups in this region enhanced peptide stability in plasma. Notably, EPI-X4 leads 5, 27, and 28 not only retained their CXCR4 binding and antagonism but also remained stable in plasma for over 8 h. Molecular dynamic simulations showed that these modified analogues bind similarly to CXCR4 as the original peptide. To further increase their systemic half-lives, we conjugated these stabilized analogues with large polymers and albumin binders. These advances highlight the potential of the optimized EPI-X4 analogues as promising CXCR4-targeted therapeutics and set the stage for more detailed preclinical assessments.

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.

NF-κB is a critical mediator of post-mitotic senescence in oligodendrocytes and subsequent white matter loss.

BACKGROUND: Inflammaging represents an accepted concept where the immune system shifts to a low-grade chronic pro-inflammatory state without overt infection upon aging. In the CNS, inflammaging is mainly driven by glia cells and associated with neurodegenerative processes. White matter degeneration (WMD), a well-known process in the aging brain, manifests in myelin loss finally resulting in motor, sensory and cognitive impairments. Oligodendrocytes (OL) are responsible for homeostasis and maintenance of the myelin sheaths, which is a complex and highly energy demanding process sensitizing these cells to metabolic, oxidative and other forms of stress. Yet, the immediate impact of chronic inflammatory stress like inflammaging on OL homeostasis, myelin maintenance and WMD remains open. METHODS: To functionally analyze the role of IKK/NF-κB signaling in the regulation of myelin homeostasis and maintenance in the adult CNS, we established a conditional mouse model allowing NF-κB activation in mature myelinating oligodendrocytes. IKK2-CAPLP-CreERT2 mice were characterized by biochemical, immunohistochemical, ultrastructural and behavioral analyses. Transcriptome data from isolated, primary OLs and microglia cells were explored by in silico pathway analysis and validated by complementary molecular approaches. RESULTS: Chronic NF-κB activation in mature OLs leads to aggravated neuroinflammatory conditions phenocopying brain inflammaging. As a consequence, IKK2-CAPLP-CreERT2 mice showed specific neurological deficits and impaired motoric learning. Upon aging, persistent NF-κB signaling promotes WMD in these mice as ultrastructural analysis revealed myelination deficits in the corpus callosum accompanied by impaired myelin protein expression. RNA-Seq analysis of primary oligodendrocytes and microglia cells uncovers gene expression signatures associated with activated stress responses and increased post mitotic cellular senescence (PoMiCS) which was confirmed by elevated senescence-associated ß-galactosidase activity and SASP gene expression profile. We identified an elevated integrated stress response (ISR) characterized by phosphorylation of eIF2α as a relevant molecular mechanism which is able to affect translation of myelin proteins. CONCLUSIONS: Our findings demonstrate an essential role of IKK/NF-κB signaling in mature, post-mitotic OLs in regulating stress-induced senescence in these cells. Moreover, our study identifies PoMICS as an important driving force of age-dependent WMD as well as of traumatic brain injury induced myelin defects.

Parahydrogen-Polarized Fumarate for Preclinical in Vivo Metabolic Magnetic Resonance Imaging.

We present a versatile method for the preparation of hyperpolarized [1-13C]fumarate as a contrast agent for preclinical in vivo MRI, using parahydrogen-induced polarization (PHIP). To benchmark this process, we compared a prototype PHIP polarizer to a state-of-the-art dissolution dynamic nuclear polarization (d-DNP) system. We found comparable polarization, volume, and concentration levels of the prepared solutions, while the preparation effort is significantly lower for the PHIP process, which can provide a preclinical dose every 10 min, opposed to around 90 min for d-DNP systems. With our approach, a 100 mM [1-13C]-fumarate solution of volumes up to 3 mL with 13-20% 13C-hyperpolarization after purification can be produced. The purified solution has a physiological pH, while the catalyst, the reaction side products, and the precursor material concentrations are reduced to nontoxic levels, as confirmed in a panel of cytotoxicity studies. The in vivo usage of the hyperpolarized fumarate as a perfusion agent in healthy mice and the metabolic conversion of fumarate to malate in tumor-bearing mice developing regions with necrotic cell death is demonstrated. Furthermore, we present a one-step synthesis to produce the 13C-labeled precursor for the hydrogenation reaction with high yield, starting from 13CO2 as a cost-effective source for 13C-labeled compounds.

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.

Ageing-induced shrinkage of intervessel pit membranes in xylem of Clematis vitalba modifies its mechanical properties as revealed by atomic force microscopy.

Bordered pit membranes of angiosperm xylem are anisotropic, mesoporous media between neighbouring conduits, with a key role in long distance water transport. Yet, their mechanical properties are poorly understood. Here, we aim to quantify the stiffness of intervessel pit membranes over various growing seasons. By applying an AFM-based indentation technique "Quantitative Imaging" we measured the effective elastic modulus (E effective) of intervessel pit membranes of Clematis vitalba in dependence of size, age, and hydration state. The indentation-deformation behaviour was analysed with a non-linear membrane model, and paired with magnetic resonance imaging to visualise sap-filled and embolised vessels, while geometrical data of bordered pits were obtained using electron microscopy. E effective was transformed to the geometrically independent apparent elastic modulus E apparent and to aspiration pressure P b. The material stiffness (E apparent) of fresh pit membranes was with 57 MPa considerably lower than previously suggested. The estimated pressure for pit membrane aspiration was 2.20+28 MPa. Pit membranes from older growth rings were shrunken, had a higher material stiffness and a lower aspiration pressure than current year ones, suggesting an irreversible, mechanical ageing process. This study provides an experimental-stiffness analysis of hydrated intervessel pit membranes in their native state. The estimated aspiration pressure suggests that membranes are not deflected under normal field conditions. Although absolute values should be interpreted carefully, our data suggest that pit membrane shrinkage implies increasing material stiffness, and highlight the dynamic changes of pit membrane mechanics and their complex, functional behaviour for fluid transport.

Evaluation of the EPR Effect in the CAM-Model by Molecular Imaging with MRI and PET Using 89Zr-Labeled HSA.

Mouse models are commonly used to study the biodistribution of novel radioligands, but alternative models corresponding to the 3Rs principles, such as the chorioallantoic membrane (CAM) model, are highly required. While there are promising data from the CAM model regarding target-specific radiolabeled compounds, its utility for assessing macromolecule biodistribution and analyzing the EPR effect remains to demonstrated. Using 89Zr-labeled human serum albumin, the accumulation of nontarget-specific macromolecules in CAM and mouse xenograft models was studied using PET and MRI. Therefore, the radioligand [89Zr]Zr-DFO-HSA was analyzed in both chicken embryos (n = 5) and SCID mice (n = 4), each with TZM-bl and PC-3 tumor entities. Dynamic PET and anatomical MRI, as well as ex vivo biodistribution analyses, were performed to assess ligand distribution over 24 h. Histological staining and autoradiography verified the intratumoral accumulation. The tumors were successfully visualized for CAM and mouse models by PET, and the albumin influx from the blood into the respective tumors did not differ significantly. The accumulation and retention of HSA in tumors due to the EPR effect was demonstrated for both models. These results highlight that the CAM model is a potential alternative to the mouse model for initial studies with novel radiolabeled macromolecules with respect to the 3Rs principles.

Synthesis, radiolabeling, and preclinical in vivo evaluation of 68Ga-radiolabelled nanodiamonds.

PURPOSE: Nanodiamonds (NDs) represent a new class of nanoparticles and have gained increasing interest in medical applications. Modifying the surface coating by attaching binding ligands or imaging probes can transform NDs into multi-modal targeting probes. This study evaluated the biokinetics and biodistribution of 68Ga-radiolabelled NDs in a xenograft model. PROCEDURES: NDs were coated with an albumin-derived copolymer modified with desferrioxamine to provide a chelator for radiolabeling. In vivo studies were conducted in AR42J tumor-bearing CD1 mice to evaluate biodistribution and tumor accumulation of the NDs. RESULTS: Coated NDs were successfully radiolabeled using 68Ga at room temperature with radiolabeling efficiencies up to 91.8 ± 3.2 % as assessed by radio-TLC. In vivo studies revealed the highest accumulation in the liver and spleen, whereas tumor radioactivity concentration was low. CONCLUSIONS: Radiolabeling of coated NDs could be achieved. However, the obtained results indicate these coated NDs' limitations in their biodistribution within the conducted studies.

Preclinical PET and MR Evaluation of 89Zr- and 68Ga-Labeled Nanodiamonds in Mice over Different Time Scales.

Nanodiamonds (NDs) have high potential as a drug carrier and in combination with nitrogen vacancies (NV centers) for highly sensitive MR-imaging after hyperpolarization. However, little remains known about their physiological properties in vivo. PET imaging allows further evaluation due to its quantitative properties and high sensitivity. Thus, we aimed to create a preclinical platform for PET and MR evaluation of surface-modified NDs by radiolabeling with both short- and long-lived radiotracers. Serum albumin coated NDs, functionalized with PEG groups and the chelator deferoxamine, were labeled either with zirconium-89 or gallium-68. Their biodistribution was assessed in two different mouse strains. PET scans were performed at various time points up to 7 d after i.v. injection. Anatomical correlation was provided by additional MRI in a subset of animals. PET results were validated by ex vivo quantification of the excised organs using a gamma counter. Radiolabeled NDs accumulated rapidly in the liver and spleen with a slight increase over time, while rapid washout from the blood pool was observed. Significant differences between the investigated radionuclides were only observed for the spleen (1 h). In summary, we successfully created a preclinical PET and MR imaging platform for the evaluation of the biodistribution of NDs over different time scales.

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.

Intravoxel incoherent motion (IVIM) MRI in pediatric patients with synovitis of the knee joint: a prospective pilot study.

BACKGROUND: Diagnosing synovial inflammation by administration of gadolinium-based contrast agents is limited by invasiveness and possible side effects, especially in children and adolescents. PURPOSE: We investigated diagnostic accuracy of diffusion-weighted (DWI) MRI with intravoxel incoherent motion (IVIM) imaging compared to contrast-enhanced MRI for detecting synovitis of the knee in a population of pediatrics and young adults. In addition we compared quantitative measures of synovial diffusion and perfusion to a group of healthy volunteers. METHODS: In this prospective study, 8 pediatric patients with 10 symptomatic knees (6 girls and 2 boys, mean age 13 years) with known or suspected synovitis underwent pre- and post-contrast 3.0 T MRI of the knee joint and additional DWI sequences between October 2016 and July 2019. For comparison we enrolled 5 healthy young adults (2 women and 3 men, median age 27 years) with contrast-free MRI of both knees. Post-contrast T1w images and DWI images at b = 1000s/mm2 with apparent diffusion coefficient (ADC) maps of patients were separately rated by two independent and blinded readers with different levels of experience for the presence or absence and degree of synovitis along with the level of confidence. We measured signal intensity on DWI of synovium, joint effusion and muscle with regions of interests and calculated the IVIM-parameters tissue diffusion coefficient (D) and perfusion fraction (f) for patients and volunteers. RESULTS: All patients showed at least some synovial contrast enhancement, 8 (80%) children knees were diagnosed with synovitis on contrast-enhanced (= ce)-T1w, the diagnostic standard. Ratings by the first and second reader on ce-T1w and DWI showed full agreement (kappa = 1) in diagnosing synovitis and substantial agreement (k = 0,655) for the degree of synovial enhancement. Interobserver agreement on DWI showed fair agreement (k = 0,220) between both readers. Diagnostic confidence was lower on DWI. Mean D- and f-values of muscle was comparable between patients and volunteers. Effusion mean D was higher, mean f was lower, synovial mean D was lower, mean f higher in patients than in volunteers. All differences were statistically significant (p < 0.001). CONCLUSIONS: Diffusion-weighted MRI with IVIM imaging remains a promising, though reader-dependent alternative to i.v. contrast-enhanced imaging in pediatric patients to reliably diagnose, or rule out, synovitis of the knee joint. We detected significantly restricted synovial diffusion and increased perfusion in patients compared to healthy volunteers. TRIAL REGISTRATION: Ethical Comitee University Hospital Ulm, Nr. 320/16.

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.