High T2 Research Articles

Highly Sensitive Early Diagnosis of Kidney Damage Using Renal Clearable Zwitterion-Coated Ferrite Nanoprobe via Magnetic Resonance Imaging In Vivo.

Iron oxide nanoprobes exhibit substantial potential in magnetic resonance imaging (MRI) of kidney diseases and can eliminate the nephrotoxicity of gadolinium-based contrast agents (GBCAs). Nevertheless, there is an extreme shortage of highly sensitive and renal clearable iron oxide nanoprobes suitable for early kidney damage detection through MRI. Herein, a renal clearable ultra-small ferrite nanoprobe (UMFNPs@ZDS) is proposed for highly sensitive early diagnosis of kidney damage via structural and functional MRI in vivo for the first time. The nanoprobe comprises a ferrite core coated with a zwitterionic layer, and possesses a high T1 relaxivity (12.52 mm-1s-1), a small hydrodynamic size (6.43nm), remarkable water solubility, excellent biocompatibility, and impressive renal clearable ability. In a rat model of unilateral ureteral obstruction (UUO), the nanoprobe-based MRI can not only accurately visualize the locations of renal injury, but also provide comprehensive functional data including peak value, peak time, relative renal function (RRF), and clearance percentage via MRI. The findings prove the immense potential of ferrite nanoprobes as a superior alternative to GBCAs for the early diagnosis of kidney damage.

A Multilevel Analysis of Changes in Psychological Demands over Time on Employee Burnout

In pursuing this study, we were interested in the effect of changes in psychological demands over time on burnout. We were also interested in examining the moderating role resources could play between changes in job demands over time and employee burnout. Multilevel regression analyses of repeated measures were conducted to capture the hierarchical structure of the data (time (Level 1, n = 537 (12-month period between T1 and T2)); employees (Level 2, n = 289)) nested in firms (Level 3, n = 34). To measure change in psychological demands, the distribution of psychological demands at T1 and T2 were dichotomized at the T1 median. Following this dichotomization, four groups were created: low T1 and low T2; high T1 and low T2; low T1 and high T2, high T1 and high T2. In terms of direct associations, an increase in psychological demands over time was associated with emotional exhaustion and cynicism but not professional efficacy. Locus of control, self-esteem, and social support from supervisors were also directly associated with burnout. As for interaction effects, social support from coworkers attenuated the effect of changes in psychological demands over time (i.e., increasing psychological demands) on cynicism. In other words, employees facing greater psychological demands over time (increasing psychological demands) and benefitting from social support from their coworkers had less cynicism. Our findings offer meaningful insights into possible ways of lowering burnout levels. Based on the results obtained, psychological demands, social support, locus of control, and self-esteem should be considered valuable intervention targets.

Zero-DeepSub: Zero-shot deep subspace reconstruction for rapid multiparametric quantitative MRI using 3D-QALAS.

To develop and evaluate methods for (1) reconstructing 3D-quantification using an interleaved Look-Locker acquisition sequence with T2 preparation pulse (3D-QALAS) time-series images using a low-rank subspace method, which enables accurate and rapid T1 and T2 mapping, and (2) improving the fidelity of subspace QALAS by combining scan-specific deep-learning-based reconstruction and subspace modeling. A low-rank subspace method for 3D-QALAS (i.e., subspace QALAS) and zero-shot deep-learning subspace method (i.e., Zero-DeepSub) were proposed for rapid and high fidelity T1 and T2 mapping and time-resolved imaging using 3D-QALAS. Using an ISMRM/NIST system phantom, the accuracy and reproducibility of the T1 and T2 maps estimated using the proposed methods were evaluated by comparing them with reference techniques. The reconstruction performance of the proposed subspace QALAS using Zero-DeepSub was evaluated in vivo and compared with conventional QALAS at high reduction factors of up to nine-fold. Phantom experiments showed that subspace QALAS had good linearity with respect to the reference methods while reducing biases and improving precision compared to conventional QALAS, especially for T2 maps. Moreover, in vivo results demonstrated that subspace QALAS had better g-factor maps and could reduce voxel blurring, noise, and artifacts compared to conventional QALAS and showed robust performance at up to nine-fold acceleration with Zero-DeepSub, which enabled whole-brain T1, T2, and PD mapping at 1 mm isotropic resolution within 2 min of scan time. The proposed subspace QALAS along with Zero-DeepSub enabled high fidelity and rapid whole-brain multiparametric quantification and time-resolved imaging.

Chitosan‐Based Nanogels Containing Ln3+ Chelates (Ln=Gd, Dy) as T1 and T2 MRI Probes

AbstractNovel nanogels, characterized by high stability and incorporating macrocyclic chelates of Gd(III) and Dy(III), were synthesized and assessed for their effectiveness as T1 and T2 relaxation agents, respectively. In this specific design, we employed octacoordinated bifunctional Gd‐1,7‐DOTAGA2 chelate to cross‐link chitosan chains. The results revealed that the sample exhibited a relaxivity value at clinical magnetic field strengths (1.5 T), approximately seven times higher than that of currently available clinical contrast agents and good MRI contrast efficacy at both 7.1 and 1 T. Furthermore, the nanogel displayed excellent stability in biological fluids, with no discernible interactions with serum biomolecules and no release of metal. In addition to Gd(III)‐based probes commonly used as T1 positive contrast agents, the nanogel with the corresponding Dy‐1,7‐DOTAGA2 chelate was prepared to explore its potential as a T2 MRI probe. Dy‐based nanogel demonstrated notably elevated transverse relaxivity values compared to the free chelate at high magnetic fields (>3 T) and significant T2 MRI contrast at 7.1 T, a capability often lacking when employing an equivalent concentration of a low‐molecular‐weight Dy(III) complex. The characterization of paramagnetic complexes was completed through the measurement of 1H NMRD profiles and 17O NMR data.

Regular Running Is Related to the Knee Joint Cartilage Structure in Healthy Adults.

The purpose of this study was to determine whether regular running distance and biomechanics are related to medial central femur cartilage (MCFC) structure. The cross-sectional study sample consisted of 1164 runners and nonrunners aged 18-65 yr. Participants completed questionnaires on physical activity and their running history. We performed quantitative magnetic resonance imaging of knee cartilage-T2 relaxation time (T2) mapping (high T2 indicates cartilage degeneration)-and a running biomechanical analysis using a three-dimensional motion capture system. A 14-d monitoring of the physical activity was conducted. Those aged 35-49 yr were at 84% higher odds of having MCFC T2 in the highest level (85th percentile, P < 0.05) compared with youngest adults indicating that MCFC structures may be altered with aging. Being male was associated with 34% lower odds of having T2 at the highest level ( P < 0.05) compared with females. Nonrunners and runners with the highest weekly running distance were more likely to have a high T2 compared with runners with running distance of 6-20 km·wk -1 ( P < 0.05). In addition, the maximal knee internal adduction moment was associated with a 19% lower odds of having T2 at the highest level ( P < 0.05). Females compared with males and a middle-aged cohort compared with the younger cohort seemed to be associated with the degeneration of MCFC structures. Runners who ran 6-20 km·wk -1 were associated with a higher quality of their MCFC compared with highly active individuals and nonrunners. Knee frontal plane biomechanics was related to MCFC structure indicating a possibility of modifying the medial knee collagen fibril network through regular running.

Magnetic Resonance Angiography with Hour-Scale Duration after Single Low-Dose Administration of Biocompatible Gadolinium Oxide Nanoprobe.

Long-term contrast-enhanced angiography offers significant advantages in theranostics for diverse vascular diseases, particularly in terms of real-time dynamic monitoring during acute vascular events; However, achieving vascular imaging with a duration of hours through a single administration of low-dose contrast agent remains challenging. Herein, a hyaluronic acid-templated gadolinium oxide (HA@Gd2O3) nanoprobe-enhanced magnetic resonance angiography (MRA) is proposed to address this bottleneck issue for the first time. The HA@Gd2O3 nanoprobe synthesized from a facile one-pot biomineralization method owns ultrasmall size, good biocompatibility, optimal circulation half-life (≈149 min), and a relatively high T1 relaxivity (r1) under both clinical 3 T (8.215 mM-1s-1) and preclinical 9.4 T (4.023 mM-1s-1) equipment. The HA@Gd2O3 nanoprobe-enhanced MRA highlights major vessels readily with significantly improved contrast, extended imaging duration for at least 2 h, and ultrahigh resolution of 0.15mm under 9.4 T, while only requiring half clinical dosage of Gd. This technique can enable rapid diagnosis and real-time dynamic monitoring of vascular changes in a model of acute superior mesenteric vein thrombosis with only a single injection of nanoprobe. The HA@Gd2O3 nanoprobe-enhanced MRA provides a sophisticated approach for long-term (hour scale) vascular imaging with ultrahigh resolution and high contrast through single administration of low-dose contrast agent.

Native myocardial T1 mapping: influence of spatial resolution on quantitative results and reproducibility.

Myocardial mapping techniques can be used to quantitatively assess alterations in myocardial tissue properties. This study aims to evaluate the influence of spatial resolution on quantitative results and reproducibility of native myocardial T1 mapping in cardiac magnetic resonance imaging (MRI). In this cross-sectional study with prospective data collection between October 2019 and February 2020, 50 healthy adults underwent two identical cardiac MRI examinations in the radiology department on the same day. T1 mapping was performed using a MOLLI 5(3)3 sequence with higher (1.4 mm × 1.4 mm) and lower (1.9 mm × 1.9 mm) in-plane spatial resolution. Global quantitative results of T1 mapping were compared between high-resolution and low-resolution acquisitions using paired t-test. Intra-class correlation coefficient (ICC) and Bland-Altman statistics (absolute and percentage differences as means ± SD) were used for assessing test-retest reproducibility. There was no significant difference between global quantitative results acquired with high vs. low-resolution T1 mapping. The reproducibility of global T1 values was good for high-resolution (ICC: 0.88) and excellent for low-resolution T1 mapping (ICC: 0.95, P=0.003). In subgroup analyses, inferior test-retest reproducibility was observed for high spatial resolution in women compared to low spatial resolution (ICC: 0.71 vs. 0.91, P=0.001) and heart rates >77 bpm (ICC: 0.53 vs. 0.88, P=0.004). Apical segments had higher T1 values and variability compared to other segments. Regional T1 values for basal (ICC: 0.81 vs. 0.89, P=0.023) and apical slices (ICC: 0.86 vs. 0.92, P=0.024) showed significantly higher reproducibility in low-resolution compared to high-resolution acquisitions but without differences for midventricular slice (ICC: 0.91 vs. 0.92, P=0.402). Based on our data, we recommend a spatial resolution on the order of 1.9 mm × 1.9 mm for native myocardial T1 mapping using a MOLLI 5(3)3 sequence at 1.5 T particularly in individuals with higher heart rates and women.

Cardiovascular magnetic resonance imaging and clinical follow-up in patients with clinically suspected myocarditis after COVID-19 vaccination

The purpose of this study was to evaluate cardiovascular magnetic resonance (CMR) findings and their relationship to longer-term clinical outcomes in patients with suspected myocarditis following coronavirus disease 2019 (COVID-19) vaccination. Consecutive adult patients who underwent clinically indicated CMR for evaluation of suspected myocarditis following messenger ribonucleic acid (mRNA)-based COVID-19 vaccination at a single center between 2021 and 2022 were retrospectively evaluated. Patients were classified based on the revised Lake Louise criteria for T1-based abnormalities (late gadolinium enhancement [LGE] or high T1 values) and T2-based abnormalities (regional T2-hyperintensity or high T2 values). Eighty-nine patients were included (64% [57/89] male, mean age 34±13years, 38% [32/89] mRNA-1273, and 62% [52/89] BNT162b2). On baseline CMR, 42 (47%) had at least one abnormality; 25 (28%) met both T1- and T2-criteria; 17 (19%) met T1-criteria but not T2-criteria; and 47 (53%) did not meet either. The interval between vaccination and CMR was shorter in those who met T1- and T2-criteria (28days, IQR 8-69) compared to those who met T1-criteria only (110days, IQR 66-255, p<0.001) and those who did not meet either (120days, interquartile range (IQR) 80-252, p<0.001). In the subset of 21 patients who met both T1- and T2-criteria at baseline and had follow-up CMR, myocardial edema had resolved and left ventricular ejection fraction had normalized in all at median imaging follow-up of 214days (IQR 132-304). However, minimal LGE persisted in 10 (48%). At median clinical follow-up of 232days (IQR 156-405, n=60), there were no adverse cardiac events. However, mild cardiac symptoms persisted in 7 (12%). In a cohort of patients who underwent clinically indicated CMR for suspected myocarditis following COVID-19 vaccination, 47% had at least one abnormality at baseline CMR. Detection of myocardial edema was associated with the timing of CMR after vaccination. There were no adverse cardiac events. However, minimal LGE persisted in 48% at follow-up.

Optic neuritis: a review of diagnostic imaging modalities and effective management approaches

Optic neuritis (ON) is a medical condition characterized by an acute inflammation of the optic nerve, usually caused by multiple sclerosis (MS). However, there are other causes such as infectious diseases, granulomatous disease, paraneoplastic disorders, and demyelination disorders. Usually, the commonest presentation is unilateral painful loss of vision. This study aimed to review the diagnostic imaging modalities and effective management approaches of ON. ON can be diagnosed through different modalities such as magnetic resonance imaging, which is the modality of choice to assess ON, providing crucial insights into the structural and functional changes within the optic nerve. In ON, the retrobulbar intra-orbital segment of the optic nerve often exhibits noticeable characteristics, including swelling and a high T2 signal. In addition, optical coherence tomography is a new, noninvasive tool for direct visualization of the head of the optic nerve that can detect thinner retinal nerve fiber layers diagnosing ON. In treating ON and MS, the main aim is to reduce the recurrence and severity of the attacks to minimize the subsequent disability. The utilization of disease-modifying drugs contributes to delaying the onset of subsequent episodes, reducing the occurrence of MS relapses, and minimizing the formation of demyelinating lesions.

Ultrasmall catechol-PEG-anchored ferrite nanoparticles for highly sensitive magnetic resonance angiography.

Highly sensitive iron oxide nanoparticles with stable, safe and efficient surface functionalization, as potential substitutes for gadolinium-based contrast agents (GBCAs) with increasing biosafety concerns, exhibit great potential for high-performance magnetic resonance angiography (MRA). Herein, we developed ultrasmall catechol-PEG-anchored ferrite nanoparticles (PEG-UMFNPs) for highly sensitive MRA. The obtained nanoprobe has a high T1 relaxivity value (7.2 mM-1 s-1) due to its ultrasmall size and Mn doping. It has a suitable hydrodynamic size of 20 nm, which prevents rapid vascular extravasation and renal clearance and prolongs its blood circulation time. In vivo MRA at 3.0 T using the nanoprobe shows that the arteries and veins of rats, even blood vessels as small as 0.32 mm, are distinctly visible, and the contrast enhancement can last for at least 1 h. In addition, due to the outstanding contrast enhancement and long circulation time, the stenosis and recanalization process of the rat's carotid artery can be continuously monitored with a single injection of the nanoprobe. Our study indicates that PEG-UMFNPs are outstanding MR imaging nanoprobes that can be used to diagnose vascular diseases without the biosafety issues of GBCAs.

Ultrasound and magnetic resonance imaging neurography assessment of diagnostic criteria in patients with carpal tunnel syndrome using electrophysiological tests as gold standard: A prospective study.

Evaluating peripheral neuropathy mainly relies on physical examination, patient history, and electrophysiological studies. High-resolution ultrasound is a fast, noninvasive modality for dynamic nerve assessment that enables the length of the nerve to be examined. Magnetic resonance imaging is preferred for examining deeper nerves with a high contrast resolution; its use shows excellent benefit in patients with atypical presentation, equivocal diagnosis, suspected secondary causes, and postsurgical relapse. We aimed to assess the measurements and criteria for both ultrasound and magnetic resonance neurography for the diagnosis of carpal tunnel syndrome, based mainly on the three measurements assessed by Buchberger et al. This prospective study was conducted to test diagnostic accuracy. Thirty-two patients who presented clinically with, and were diagnosed by electrophysiological tests as having, carpal tunnel syndrome participated. Superficial ultrasound of the wrist joint was performed on all participants, followed by magnetic resonance imaging within 1 week of ultrasonography. The three main parameters of cross-sectional area measurement, distal nerve flattening, and flexor retinaculum bowing indices showed positive occurrences of 93.7%, 59.4%, and 59.4%, respectively; 90.6% of patients had decreased nerve echotexture. The diagnostic ability of magnetic resonance imaging was decreased when cross-sectional area measurements were used: positive results were achieved in 81.2% of patients, but the positive results showing the distal tunnel nerve increased flattening and bowed flexor retinaculum slightly decreased to 56.2% for each. A high T2 signal of the median nerve was observed in 90.6% of patients. In an agreement analysis, we found a statistically significant difference that supported the use of ultrasound as a primary diagnostic modality for carpal tunnel syndrome. However, magnetic resonance imaging improved tissue characterization and was a good diagnostic modality, with a statistically significant difference, for cases of secondary carpal tunnel syndrome, detection of the underlying entrapping cause, and early abnormality detection in the innervated muscle. Our results demonstrate that ultrasound examination can be used as the first imaging modality after physician evaluation, with results comparable to those of electrophysiological studies for evaluating carpal tunnel syndrome and determining its cause. Magnetic resonance neurography examination is the second step in detecting secondary causes in cases with suspected early muscle denervation changes that cannot be elicited by ultrasound or in cases with equivocal results.

Characterization of white matter lesions in multiple sclerosis using proton density and T1-relaxation measures

PurposeAlthough lesion dissemination in time is a defining characteristic of multiple sclerosis (MS), there is a limited understanding of lesion heterogeneity. Currently, conventional sequences such as fluid attenuated inversion recovery (FLAIR) and T1-weighted (T1W) data are used to assess MS lesions qualitatively. Estimating water content could provide a measure of local tissue rarefaction, or reduced tissue density, resulting from chronic inflammation. Our goal was to utilize the proton spin density (PD), derived from a rapid, multi-contrast STAGE (strategically acquired gradient echo) protocol to characterize white matter (WM) lesions seen on T2W, FLAIR and T1W data. Materials and methodsTwenty (20) subjects with relapsing-remitting MS were scanned at 3 T using T1W, T2-weighted, FLAIR and strategically acquired gradient echo (STAGE) sequences. PD and T1 maps were derived from the STAGE data. Disease severity scores, including Extended Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC), were correlated with total, high PD and high T1 lesion volumes. A probability map of high PD regions and all lesions across all subjects was generated. Five perilesional normal appearing WM (NAWM) bands surrounding the lesions were generated to compare the median PD and T1 values in each band with the lesional values and the global WM. ResultsT1W intensity was negatively correlated with PD as expected (R = −0.87, p < 0.01, R2 = 0.756) and the FLAIR signal was suppressed for high PD volumes within the lesions, roughly for PD ≥ 0.85. The threshold for high PD and T1 regions was set to 0.909 and 1953.6 ms, respectively. High PD regions showed a high probability of occurrence near the boundary of the lateral ventricles. EDSS score and nine-hole peg test (dominant and non-dominant hand) were significantly correlated with the total lesion volume and the volumes of high PD and T1 regions (p < 0.05). There was a significant difference in PD/T1 values between the high PD/T1 regions within the lesions and the remaining lesional tissue (p < 0.001). In addition, the PD values of the first NAWM perilesional band directly adjacent to the lesional boundary displayed a significant difference (p < 0.05) compared to the global WM. ConclusionLesions with high PD and T1s had the highest probability of occurrence at the boundary of the lateral ventricles and likely represent chronic lesions with significant local tissue rarefaction. Moreover, the perilesional NAWM exhibited subtly increasing PD and T1 values from the NAWM up to the lesion boundary. Unlike on the T1 maps, the perilesional band adjacent to the lesion boundary possessed a significantly higher PD value than the global WM PD values. This shows that PD maps were sensitive to the subtle changes in NAWM surrounding the lesions.

MRI of Neuroinflammation Using a Folate Receptor β‐Targeted Nanoparticle Contrast Agent

AbstractBackgroundNeuroinflammation plays an important role in Alzheimer’s disease (AD) pathogenesis and disease progression leading to cognitive decline. Current efforts for non‐invasive imaging of neuroinflammation are based on using PET radiotracers. An MRI‐based contrast agent for imaging of neuroinflammation would be highly desirable due to widespread use of MRI in imaging of neurological disorders. Folate receptor β, a marker of pro‐inflammatory phenotype, is expressed in microglia. In this work, we investigated a folate‐targeted liposomal‐Gd contrast agent for molecular MRI of neuroinflammation in mouse models of AD.Method In vivo studies were performed in APP/PSEN1 mice, a model of amyloid pathology, and P301S mice, a model of tau pathology. Transgenic mice and wild‐type (WT) littermates (n = 6/genotype, 24 total) underwent pre‐contrast MRI using T1‐weighted spin echo sequences with 160 µm in‐plane resolution and 1.2 mm slice thickness. Delayed MRI was performed 4 days after systemic administration of a high T1 relaxivity liposomal‐Gd contrast agent bearing folic acid molecules. Animals were euthanized after the final imaging session for microscopic analysis of brain. Signal changes between pre‐contrast and post‐contrast MRI were determined in target regions of the brain.ResultTransgenic APP/PSEN1 and P301S mice demonstrated signal enhancement in post‐contrast T1w‐MRI compared to pre‐contrast MRI. In comparison, WT control mice did not show signal enhancement in post‐contrast MRI. APP/PSEN1 transgenic mice exhibited greater relative enhancement (+5.9%, p&lt;0.005) and lower inter‐subject variance than P301S mice (3.9%, p&lt;0.05). Immunofluorescence analysis demonstrated higher burden of activated microglia in brains of transgenic mice compared to WT control mice.ConclusionA folate receptor β‐targeted liposomal‐Gd contrast agent enables in vivo MRI of neuroinflammation in mouse models of Alzheimer’s disease. Such imaging agents could play an important role in monitoring of Alzheimer’s disease progression leading to cognitive decline and evaluation of therapies that target neuroinflammation.

Multinodal Cervical Angiomyomatous Hamartoma.

Angiomyomatous hamartoma (AMH) is a rare benign lesion of the lymph nodes. Angiomyomatous hamartoma tends to be found in inguinal lymph nodes, and usually in a single lymph node. We present a rare care case of a 53-year-old presenting with a neck lump, found to be AMH involving multiple lymph nodes in her neck. To our knowledge, this is the first case presenting with multiple nodes in this location. There are a limited number of case reports describing magnetic resonance imaging (MRI) features of AMH lesions located in inguinal and head and neck regions. Our MRI findings revealed the mass had intermediate T1 enhancement, high T2 signal enhancement, and high post-gadolinium enhancement and fat saturation of the lesion. Angiomyomatous hamartoma is a histological diagnosis, distinguished from other similar nodal vascular lesions by a number of key features: including the presence of central nodal distribution, muscular blood vessel walls, adipose tissue, and HMB45 negative staining. Early recognition of this benign lesion may have implications for a patient's clinical course and surgical requirements.

Longitudinal mediation effects of activity meaning on the association between activity performance and quality of life among older adults with disabilities

BackgroundPhysical limitations may hinder older adults with physical disabilities’ capability to perform various activities, which can affect their quality of life (QOL). Accomplishing meaningful activities may mitigate the impact of limited activity performance on their QOL. This longitudinal study aims to investigate how activity meaning mediates the relationship between activity performance and QOL among older adults with disabilities.MethodsData for this longitudinal study was collected from 813 community-dwelling older adults aged 60 and above who had physical disabilities, over a two year interval. Path analysis was used to examine the cross-sectional and longitudinal mediation effects from activity performance, through activity meaning, to QOL.ResultsAt the same wave, high IADL performance or social activity performance, and high QOL was indirectly associated through high IADL meaning or social meaning. As for longitudinal association, high T1 IADL performance was associated with better T2 QOL through high T1 and T2 IADL meaning. Similarly, high T1 social activity performance also contributed to T2 QOL through high T1 and T2 social activity meaning. Additionally, social activity performance exhibited higher influence on QOL than that of IADL.ConclusionsBoth IADL and social activities have distinct impacts on the QOL of older adults with disabilities. To improve the current and future QOL of older adults with disabilities, professionals must prioritize their involvement in the most meaningful activities while being sensitive to and supportive of their preferences and valued lifestyles.

Myocardial inflammation in Fabry disease: correlations between myocardial histology, T2 mapping, and troponin

Abstract Background Myocardial inflammation likely plays a key role in cardiac Fabry disease (FD), supported by the frequent observation using cardiac MRI (CMR) of high T2 mapping values, mainly in areas of late gadolinium enhancement, LGE), typically representing oedema, and increased troponin (myocardial injury). Purpose To characterize inflammation in FD cardiomyopathy by comparing myocardial histology, T2 mapping and troponin. Methods Fifteen FD patients (67% females; 51 years old, range 39-62), undergoing 3 tests: biopsy (either RV endomyocardial biopsy, n=10, or myectomy, n=5); CMR (1.5T: cines, LGE, native T1/T2 mapping quantified in the sampling area); and troponin assessment (high sensitivity TnI). Mapping values were compared to local healthy volunteers. Left ventricle hypertrophy (LVH) was defined as either MWT ≥12mm or indexed LV mass above sex specific reference ranges. Tissue was stained using Haematoxylin-Eosin and Azan Mallory trichrome. Inflammatory cell staining used CD68 and CD3 antibodies. An abnormal inflammatory infiltrate was defined according to ESC criteria as ≥14 leukocytes/mm2 (up to 4monocytes/mm2, CD3+T-lymphocytes&amp;gt;7cells/mm2) and its distribution classified as focal (&amp;lt;30% of the specimen), multifocal (30-60%), diffuse (&amp;gt;60%). Results Median LV ejection fraction was 63% (58-67); indexed end diastolic volume 83ml/m2 (68-91). Seven patients had LVH. 8 patients had low native T1 and 6 had infero-lateral LGE. Median septal T2 value was 50ms (47-52) with 3 (all females) above local upper limit value (ULV). TnI was increased in 6 pts (40%; median value 54ng/L [38-128]). Histology showed mild inflammatory infiltrates in 8 pts (46%), none diffuse (focal 4, multifocal 4). Seven were mixed - T lymphocytes and macrophages, one was exclusively macrophages. Inflammatory foci were quiescent (n=5), or associated to myocytes injury not typical of ischemic damage and fibrosis (n=3). None had histologically visible myocardial oedema. Patients with inflammatory infiltrates had higher T2 values (52ms [50-54] vs 47ms [46-51]; p=0.043) but the same troponin (18ng/L [3-82] vs 14ms [3-24], p=0.215) (figure 1). The 3 patients with high T2 all had inflammatory cells associated to histologic myocyte injury (figure 2). Conclusion For the first time we correlate histology with T2 and myocardial injury in FD. In this small study, mild myocardial macrophage/lymphocyte infiltrates are common in FD and are associated to higher T2 values. Abnormal T2 septal elevation is less common (it is known common in the basal inferolateral wall however) and when present, infiltration with histological myocyte damage is found.

Investigating the cardiac manifestations of IgG4-related disease using cardiac magnetic resonance imaging

Abstract Introduction IgG4-related disease (IgG4-RD) is a relapsing-remitting immune-mediated condition that affects multiple organ systems. Case reports of suspected cardiovascular involvement in IgG4-RD have emerged though no study has systematically assessed the cardiovascular phenotype of IgG4-RD using cardiac magnetic resonance (CMR) imaging. Purpose We systematically assessed patients with IgG4-RD using CMR to identify the cardiovascular manifestations, and compared them to controls. Methods We recruited 11 patients with histologically-confirmed IgG4-RD (6 female, 61±11 years, 9 with active disease (8 with pancreatic involvement, 3 parotid, 5 bile ducts, 5 kidneys and 3 cardiovascular)). Patients underwent CMR at 1.5T including cine, myocardial tagging, native T1-mapping, late gadolinium enhancement (LGE), extracellular volume (ECV) and quantitative stress perfusion mapping. Results were compared to 10 healthy controls with no cardiac disease (50% female, 35±8 years). Results are presented as mean ± standard deviation (SD) unless otherwise stated. Results Patients with IgG4-RD had similar cardiac geometry to the reference group (Table 1), with similar biventricular and bi-atrial volumes. However, despite similar biventricular ejection fractions compared to controls (patient LVEF: 55-67%, RVEF: 51-65%), IgG4-RD patients showed significantly reduced global longitudinal strain (GLS) (-16.8 ± 2.3% vs -18.7 ± 1.6%, p=0.045). Furthermore, 64% (7/11) of IgG4-RD patients showed LGE, 6 of whom showed non-ischaemic patterns (Figure 1). Male IgG4-RD patients (n=5) as a group showed a significantly higher average myocardial T1 value relative to the reference group, with 3/5 male patients having an abnormally high myocardial T1 (above the 2SD limit of normal). Female IgG4-RD patients (n=6) had similar and normal myocardial T1 values to the reference group. ECV did not significantly differ between the two groups. IgG4-RD patients showed a significantly reduced global myocardial perfusion reserve (MPR), including two patients with a qualitative inducible perfusion defect. Only 3 out of the 11 IgG4-RD patients had a completely normal CMR. Conclusion Patients with IgG4-RD show frequent cardiac abnormalities as revealed by advanced CMR phenotyping. These include subclinical systolic dysfunction, ischaemic and non-ischaemic myocardial fibrosis, reduced myocardial perfusion reserve, and elevated myocardial T1 times. These abnormalities have been described in inflammatory cardiovascular diseases, supporting a plausible pathophysiological link with IgG4-RD. Future work in larger and multicentre cohorts is warranted, to systematically define the novel cardiovascular phenotype of IgG4-RD.Table 1Figure 1

Abstract 14282: Electrocardiography Rules out Myocardial Abnormalities on Cardiac Magnetic Resonance Imaging in Post-Hospitalized COVID-19 Patients: A Multicenter Observational Study

Introduction: The diagnostic performance of EKG in ruling out myocardial abnormalities following COVID-19 is unclear. Aim: To assess the ability of EKG to exclude cardiac abnormalities on cardiac magnetic resonance imaging (CMR) in post-hospitalised COVID-19 patients. Methods: Post-hospitalized patients (n=212) &amp; comorbidities matched controls (n=38) underwent CMR and 12-lead EKG. EKG assessments included depolarization &amp; repolarization abnormalities [ QTc , corrected QT dispersion ( QTc disp ), JT ( JTc ) &amp; T peak-end ( cTPe ) intervals]. CMR abnormalities were defined as reduced left ventricular ejection fraction (LVEF), high T1 &amp; T2 Z scores and high extracellular volume and pathological late gadolinium enhancement. Results: At 5.6 months post-discharge, patients had a higher burden of EKG abnormalities vs controls (72.2% vs 42.1%, p=0.001 ) (Figure A) . CMR abnormalities were comparable despite patients having lower LVEF. Abnormal EKG findings and prolonged repolarization were more common in patients with CMR abnormalities vs patients with normal CMR and controls ( Figure A &amp; B ). Area-under-the-receiver-operating curve (AUROC) of routine EKG abnormalities to discriminate abnormal CMR was 0.56 (95% CI 0.47-0.65), p=0.185. Inclusion of JTc &amp; QTc disp improved the AUROC to 0.64 (95% CI 0.55-0.74), p=0.002. Inclusion of JTc ≥340ms &amp; QTc disp ≥40ms improved the sensitivity from 81.6% to 99.9% with higher negative predictive value (84.7% to 99.9%) ( Figure A ). Conclusions: Post-hospitalized COVID-19 patients have more EKG abnormalities than comorbidities-matched controls. A normal EKG with normal repolarization is effective in ruling out significant CMR abnormalities.

Abstract 17854: Imaging Intravascular Macrophages Using Micro-Sized Superparamagnetic Decoys

Introduction: During inflammatory processes, intravascular macrophages are capable of phagocytizing circulating debris in the circulation. Hypothesis: Intravenous injection of contrast-loaded decoys could be used to label intravascular macrophages and map their distribution by non-invasive imaging. Methods: We synthetized superparamagnetic decoys with hydrodynamic diameters from 20 nm to 4.5 μm. Experimental models of neuroinflammation (intrastriatal injection of LPS or TNF) and ischemic stroke (thrombin model and ferric chloride model) were performed in mice. High resolution 3D T2*-weighted MRI sequences were performed after intravenous injection of the superparamagnetic decoys. Results: In experimental models of neuroinflammation, intravenous injection of superparamagnetic decoys with a diameter of 1 μm (but neither smaller nor larger particles) reveals intravascular phagocytic cells in the cerebral circulation, in a dose dependent manner. In ischemic stroke, we found that intravenous injection of the decoys leads to numerous signal voids in the vessels in and around the infarct core at 48 hours (Figure 1a-b). Interestingly, the intravascular phagocytic activity appears much higher in permanent rather than transient models of ischemic stroke. Pre-treatment with anti-CD11a blocking antibodies significantly reduced the number of intravascular macrophages in stroke. Histological studies confirmed that injected decoys are phagocytized by intravascular cells which express typical markers of the monocyte/macrophage lineage including CX3CR1 dependent GFP expression and CD68 (Figure 1c). Conclusions: Intravenous injection of superparamagnetic decoys in the micrometer size range allows to image intravascular macrophages. This new method allows to study the pathophysiological roles of intravascular macrophages in experimental models and could be easily translated to humans.

Partial ectopic posterior pituitary

Ectopic posterior pituitary is one of the leading causes of pituitary dwarfism related to a growth hormone deficiency. It can be either isolated or associated to other abnormalities, the most widely known being the pituitary stalk interruption syndrome [1]. Although it is a rare entity, partial ectopy consists of the coexistence of both an orthotopic and an ectopic posterior pituitary gland [2,3] (Figure 1A). It appears as a T1 hyperintensity or bright spot at the posterior sellae, consistent with the normally expected neurohypophysis [4]. A second midline bright spot located in the infundibulum (Figure 1B), or above the optic chiasm or at the floor of the third ventricle is considered the ectopic posterior pituitary gland. It features high T1 signal intensity with and without fat suppression, making it easy to distinguish from a lipoma or a supra sellar dermoid with lipid content. Contrast enhancement is similar to the normal pituitary parenchyma (Figure 1C).