Low T2 Research Articles

Elite athlete status, gender and mitchell sports classification strongly influence native t1 mapping times

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Amsterdam Movement Sciences and the Dutch Olympic Committee. Background Cardiac magnetic resonance imaging (CMR) T1 mapping is an established tool for tissue characterisation. This is of particular interest in athletes as differentiation of the ‘grey zone’ between physiological adaptation to sports and pathology can be highly challenging. To correctly interpret individual T1 times, T1 times are conventionally compared to normal values derived from healthy controls. However, whether these values can be applied to elite athletes with different types of cardiac adaptation is unknown. Purpose To determine differences in native T1 times between elite athletes and healthy non-athletic controls and to determine differences in athletes with different types of cardiac remodelling. Methods This is a cross-sectional analysis of elite athletes included in the ELITE cohort. ELITE collects the preparticipation cardiovascular screenings data from all athletes that perform at the highest national, international and/or Olympic level in the Netherlands. All athletes were sixteen years or older. The screening includes cardiovascular magnetic resonance imaging on a Siemens Avanto fit 1.5T machine with cine-imaging, delayed hyperenhancement and a three-pulse shortened modified look-locker inversion recovery 5(3)3 sequence. For this analysis, all athletes with a history of cardiovascular disease or pathological late gadolinium enhancement were excluded. Athletes were classified according to the Mitchell Sports Classification based on the intensity (low (L) / moderate (M) / high (H)) of the dynamic (D) and static components (S). Native- and post-contrast T1 mapping times were calculated by manually tracing the endocardial- and epicardial contours. Results A total of 117 elite athletes (44% women; mean age 26±6.5; Mitchell sports classification: 47 HS/HD, 8 HS/LD, 5 HS/MD, 36 LS/HD, 16 MS/HD, 3 MS/MD, 3 missing) and 48 healthy non-athletic controls (54% women; mean age 39±15.1). Men had lower t1 times compared to women, both in athletes (949ms vs 964ms, p<0.05) and controls (969ms vs 1000ms, p<0.05). Moreover, elite athletes had a lower global native T1 time compared to healthy non-athletic controls (955 vs 983, p<0.05). There were significant differences in native T1 time between the Mitchel Sport classifications (Kruskal-Wallis p<0.05); left ventricular mass (LVM) (R=-0.47, p<0.05) and LVM divided by left ventricular end-diastolic volume (R=-0.4, p<0.05) were both negatively correlated with native T1 mapping time. Conclusion Men demonstrate markedly shorter T1 times compared to women in both athletes and controls. Moreover, native T1 times were associated with markers for cardiac remodelling. Sex- and athlete-specific characteristics should be taken into account when interpreting T1 times in athletes.

Realizing Near-Infrared (NIR)-Triggered Type-I PDT and PTT by Maximizing the Electronic Exchange Energy of Perylene Diimide-Based Photosensitizers

Development of near-infrared (NIR) Type-I photosensitizers is attracting tremendous attention to overcome the limitation of traditional O2-dependent Type-II photosensitizers, but huge challenges remain. Herein, a promising concept was put forward by lowering the energy of the lowest triplet excited state (T1) of the photosensitizer below the threshold for oxygen sensitization via maximizing the electronic exchange energy. By taking advantage of the low energy intramolecular charge transfer (ICT) state, pyrrolidine as an electron donor is conjugated at the bay position of perylenediimide (PDI) to produce PDIPy that acts as a novel photosensitizer with NIR absorbance and low T1 energy level. With the application of PDIPy, Type-I PDT is realized via effective generation of O2• –. Supramolecular nanoparticles (NanoPDIPy) assembling from PDIPy showed excellent in vitro and in vivo phototherapeutic efficacy against cancer in either normoxia or hypoxia upon 730 nm laser irradiation.

Ultrashort time-to-echo MR morphology of cartilaginous endplate correlates with disc degeneration in the lumbar spine.

Using ultrashort echo time (UTE) MRI, we determined prevalence of abnormal cartilaginous endplate (CEP), and the relationship between CEP and disc degeneration in human lumbar spines. Lumbar spines from 71 cadavers (age 14-74years) were imaged at 3T using sagittal UTE and spin echo T2 map sequences. On UTE images, CEP morphology was defined as "normal" with linear high signal intensity or "abnormal" with focal signal loss and/or irregularity. On spin echo images, disc grade and T2 values of the nucleus pulposus (NP) and annulus fibrosus (AF) were determined. 547 CEPs and 284 discs were analysed. Effects of age, sex, and level on CEP morphology, disc grade, and T2 values were determined. Effects of CEP abnormality on disc grade, T2 of NP, and T2 of AF were also determined. Overall prevalence of CEP abnormality was 33% and it tended to increase with older ages (p = 0.08) and at lower spinal levels of L5 than L2 or L3 (p = 0.001). Disc grades were higher and T2 values of the NP were lower in older spines (p < 0.001) and at lower disc level of L4-5 (p < 0.05). We found significant association between CEP and disc degeneration; discs adjacent to abnormal CEPs had high grades (p < 0.01) and lower T2 values of the NP (p < 0.05). These results suggest that abnormal CEPs are frequently found, and it associates significantly with disc degeneration, suggesting an insight into pathoetiology of disc degeneration.

Deep-learning-based biomarker of spinal cartilage endplate health using ultra-short echo time magnetic resonance imaging.

T2* relaxation times in the spinal cartilage endplate (CEP) measured using ultra-short echo time magnetic resonance imaging (UTE MRI) reflect aspects of biochemical composition that influence the CEP's permeability to nutrients. Deficits in CEP composition measured using T2* biomarkers from UTE MRI are associated with more severe intervertebral disc degeneration in patients with chronic low back pain (cLBP). The goal of this study was to develop an objective, accurate, and efficient deep-learning-based method for calculating biomarkers of CEP health using UTE images. Multi-echo UTE MRI of the lumbar spine was acquired from a prospectively enrolled cross-sectional and consecutive cohort of 83 subjects spanning a wide range of ages and cLBP-related conditions. CEPs from the L4-S1 levels were manually segmented on 6,972 UTE images and used to train neural networks utilizing the u-net architecture. CEP segmentations and mean CEP T2* values derived from manually- and model-generated segmentations were compared using Dice scores, sensitivity, specificity, Bland-Altman, and receiver-operator characteristic (ROC) analysis. Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were calculated and related to model performance. Compared with manual CEP segmentations, model-generated segmentations achieved sensitives of 0.80-0.91, specificities of 0.99, Dice scores of 0.77-0.85, area under the receiver-operating characteristic curve values of 0.99, and precision-recall (PR) AUC values of 0.56-0.77, depending on spinal level and sagittal image position. Mean CEP T2* values and principal CEP angles derived from the model-predicted segmentations had low bias in an unseen test dataset (T2* bias =0.33±2.37 ms, angle bias =0.36±2.65°). To simulate a hypothetical clinical scenario, the predicted segmentations were used to stratify CEPs into high, medium, and low T2* groups. Group predictions had diagnostic sensitivities of 0.77-0.86 and specificities of 0.86-0.95. Model performance was positively associated with image SNR and CNR. The trained deep learning models enable accurate, automated CEP segmentations and T2* biomarker computations that are statistically similar to those from manual segmentations. These models address limitations with inefficiency and subjectivity associated with manual methods. Such techniques could be used to elucidate the role of CEP composition in disc degeneration etiology and guide emerging therapies for cLBP.

Multi-territorial Acute Ischemic Stroke with low T2* signal—an MRI marker for differentiating infective endocarditis from cancer-related stroke (P11-5.011)

Multi-territorial Acute Ischemic Stroke with low T2* signal—an MRI marker for differentiating infective endocarditis from cancer-related stroke (P11-5.011)

Incremental significance of myocardial oedema for prognosis in hypertrophic cardiomyopathy.

To explore the prognosis of myocardial oedema measured by T2 mapping in hypertrophic cardiomyopathy (HCM). A total of 674 patients with HCM (age: 50 ± 15 years, 60.5% males) who underwent cardiovascular magnetic resonance were prospectively enrolled from 2011 to 2020. One hundred healthy controls (age: 48 ± 19 years, 58.0% males) were included for comparison. Myocardial oedema was quantitatively measured by T2 mapping in both global and segmental myocardium. The endpoints were defined as a combination of cardiovascular death and appropriate implantable cardioverter defibrillator discharge. During a median follow-up of 36 months (interquartile range: 24-60 months), 55 patients (8.2%) had cardiovascular events. Patients with cardiovascular events had a higher T2 max, T2 min, and T2 global values (all P < 0.001) than patients who remained event free. Survival analysis demonstrated that patients with HCM with late gadolinium enhancement [LGE(+)] and T2 max ≥44.9 ms had a higher risk of developing cardiovascular events (P < 0.001). A multivariate Cox regression analysis showed that T2 max, T2 min, and T2 global provided significant prognostic value to predict cardiovascular events (all P < 0.001). According to the C-index (0.825, 0.814), net reclassification index (0.612, 0.536, both P < 0.001), and integrative discrimination index (0.029, 0.029, both P < 0.05), T2 max or T2 min significantly increased the predictive performance of established risk factors, including extensive LGE. Patients with HCM with LGE(+) and higher T2 had worse prognosis than those with LGE(+) and lower T2.

The Efficacy of Microfracture Combined with Extracorporeal Shock Wave Therapy for Treating Osteochondral Lesion of the Talus and the Quality of Regenerated Cartilage: A Retrospective Cohort Study and MRI Assessment.

osteochondral lesion of the talus (OLT) is a common disease in the physically active population, and extracorporeal shock wave therapy (ESWT) is a noninvasive treatment. We hypothesized that microfracture (MF) combined with ESWT may have great potential to become a novel combination treatment of OLT. the OLT patients who received MF + ESWT or MF + platelet-rich plasma (PRP) injection were retrospectively included, with a minimal follow up of 2y. The daily activating VAS, exercising VAS, and American Orthopedic Foot and Ankle Society Ankle-Hindfoot Score (AOFAS) were used to assess the efficacy and functional outcome, and ankle MRI T2 mapping was used to evaluate the quality of regenerated cartilage in the OLT patients. only transient synovium-stimulated complications were found during the treatment sessions; the complication rate and daily activating VAS did not have differences between groups. MF + ESWT had a higher AOFAS and a lower T2 mapping value than MF + PRP at the 2y follow up. the MF + ESWT had superior efficacy for treating OLT, which resulted in better ankle function and more hyaline-like regenerated cartilage, superior to the traditional MF + PRP.

Scyllo-inositol: Transverse relaxation time constant at 3T and concentration changes associated with aging and alcohol use.

The goals of this study were to measure the apparent transverse relaxation time constant, T2 , of scyllo-inositol (sIns) in young and older healthy adults' brains and to investigate the effect of alcohol usage on sIns in young and older healthy adults' brains, using proton magnetic resonance spectroscopy (MRS) at 3T. Twenty-nine young adults (age 21 ± 1years) and 24 older adults (age 74 ± 3years) participated in this study. MRS data were acquired from two brain regions (the occipital cortex and posterior cingulate cortex) at 3T. The T2 of sIns was measured using a localization by adiabatic selective refocusing (LASER) sequence at various echo times, while the sIns concentrations were measured using a short-echo-time stimulated echo acquisition mode (STEAM) sequence. A trend towards lower T2 relaxation values of sIns in older adults was observed, although these were not significant. sIns concentration was higher with age in both brain regions and was significantly higher in the young when considering alcohol consumption of more than two drinks per week. This study shows that differences in sIns can be found in two distinct regions of the brain across two age groups, potentially reflecting normal aging. In addition, it is important to take into account alcohol consumption when reporting the sIns level in the brain.

Magnetic resonance imaging to assess the brain response to fasting in glioblastoma-bearing rats as a model of cancer anorexia

BackgroundGlobal energy balance is a vital process tightly regulated by the brain that frequently becomes dysregulated during the development of cancer. Glioblastoma (GBM) is one of the most investigated malignancies, but its appetite-related disorders, like anorexia/cachexia symptoms, remain poorly understood.MethodsWe performed manganese enhanced magnetic resonance imaging (MEMRI) and subsequent diffusion tensor imaging (DTI), in adult male GBM-bearing (n = 13) or control Wistar rats (n = 12). A generalized linear model approach was used to assess the effects of fasting in different brain regions involved in the regulation of the global energy metabolism: cortex, hippocampus, hypothalamus and thalamus. The regions were selected on the contralateral side in tumor-bearing animals, and on the left hemisphere in control rats. An additional DTI-only experiment was completed in two additional GBM (n = 5) or healthy cohorts (n = 6) to assess the effects of manganese infusion on diffusion measurements.ResultsMEMRI results showed lower T1 values in the cortex (p-value < 0.001) and thalamus (p-value < 0.05) of the fed ad libitum GBM animals, as compared to the control cohort, consistent with increased Mn2+ accumulation. No MEMRI-detectable differences were reported between fed or fasting rats, either in control or in the GBM group. In the MnCl2-infused cohorts, DTI studies showed no mean diffusivity (MD) variations from the fed to the fasted state in any animal cohort. However, the DTI-only set of acquisitions yielded remarkably decreased MD values after fasting only in the healthy control rats (p-value < 0.001), and in all regions, but thalamus, of GBM compared to control animals in the fed state (p-value < 0.01). Fractional anisotropy (FA) decreased in tumor-bearing rats due to the infiltrate nature of the tumor, which was detected in both diffusion sets, with (p-value < 0.01) and without Mn2+ administration (p-value < 0.001).ConclusionsOur results revealed that an altered physiological brain response to fasting occurred in hunger related regions in GBM animals, detectable with DTI, but not with MEMRI acquisitions. Furthermore, the present results showed that Mn2+ induces neurotoxic inflammation, which interferes with diffusion MRI to detect appetite-induced responses through MD changes.

New bone formation at the sacroiliac joint in axial spondyloarthritis: characterization of backfill in MRI and CT.

MRI findings of the SI joint space in axial SpA (axSpA) include inflammation and fat metaplasia inside an erosion; the latter is also termed 'backfill'. We compared such lesions with CT to better characterize whether they represent new bone formation. We identified patients with axSpA who underwent both CT and MRI of the SI joints in two prospective studies. MRI datasets were jointly screened by three readers for joint space-related findings and grouped into three categories: type A-high short tau inversion recovery (STIR) and low T1 signal; type B-high signal in both sequences; type C-low STIR and high T1 signal. Image fusion was used to identify MRI lesions in CT before we measured Hounsfield units (HU) in each lesion and surrounding cartilage and bone. Ninety-seven patients with axSpA were identified and we included 48 type A, 88 type B, and 84 type C lesions (maximum 1 lesion per type and joint). The HU values were 73.6 (s.d. 15.0) for cartilage, 188.0 (s.d. 69.9) for spongious bone, 1086.0 (s.d. 100.3) for cortical bone, 341.2 (s.d. 96.7) for type A, 359.3 (s.d. 153.5) for type B and 446.8 (s.d. 123.0) for type C lesions. Lesion HU values were significantly higher than those for cartilage and spongious bone, but lower than those for cortical bone (P < 0.001). Type A and B lesions showed similar HU values (P = 0.93), whereas type C lesions were denser (P < 0.001). All joint space lesions show increased density and might contain calcified matrix, suggesting new bone formation, with a gradual increase in the proportion of calcified matrix towards type C lesions (backfill).

An NMR study of the role of coir fibers in the hydration and drying of cement paste at early age

Natural fibers such as coir fibers have been increasingly explored as reinforcement in the cementitious composite to promote sustainable and economical construction. However, the in-situ application of this composite presents challenges due to the complex interplay of water behaviors, involving the hydrophilicity of natural fibers, the hydration of cement and the evaporation due to drying. Although these water-related processes play a crucial role in achieving the desired properties, they have been relatively underreported in the literature. This study aims to investigate the role of coir fibers in the water distribution and pore size distribution during the early age (initial 3 days) of cement paste hydration under drying conditions. Accordingly, Nuclear Magnetic Resonance (NMR) methods involving the moisture profiling and transverse relaxation are used to monitor the water distribution and pore size distribution in time but also in space. The samples are made by adding water-saturated coir fibers to the cement paste at different dosages (0, 1%, 2% and 4%). The effects of drying and coir fiber dosages on the samples are evaluated. The results show that drying leads to a moisture gradient and a larger transverse relaxation time T2, i.e., a coarser pore structure near the drying surface. By adding the saturated coir fibers, the moisture gradient caused by drying is decreased and spread out along the sample. As the coir fiber content increases, the water content along the sample and the total water content of the sample increase. As a result, the samples with coir fibers exhibit a lower T2, i.e., a denser pore structure near the drying surface. Coir fibers are shown to eliminate the adverse effect of drying on cement hydration through three effects, including the internal curing, improved water transport and crack control. The results from this study reveal the promising potential of coir fibers for in-situ construction applications.

Quantitative association of cerebral blood flow, relaxation times and proton density in young and middle-aged primary insomnia patients: A prospective study using three-dimensional arterial spin labeling and synthetic magnetic resonance imaging.

To quantitatively measure the T1 value, T2 value, proton density (PD) value, and cerebral blood flow (CBF) in young and middle-aged primary insomnia (PI) patients, and analyze the correlations between relaxation times, PD, and CBF to explore potential brain changes. Cranial magnetic resonance (MR) images of 44 PI patients and 30 healthy subjects were prospectively collected for analysis. The T1, T2, PD, and CBF values of the frontal lobe, parietal lobe, temporal lobe, and occipital lobe were independently measured using three-dimensional arterial spin labeling (3D-ASL), synthetic magnetic resonance imaging (syMRI) and a whole-brain automatic segmentation method. The differences of these imaging indices were compared between PI patients and healthy subjects. Follow-up MR images were obtained from PI patients after 6 months to compare with pre-treatment images. The Wilcoxon signed rank test and Spearman rank were used for statistical analysis. Bilateral CBF asymmetry was observed in 38 patients, with significant differences in both the T2 value and CBF between the four lobes of the brain (p < 0.01). However, no significant difference was found in the T1 and PD values between the bilateral lobes. A negative correlation was found between CBF and T2 values in the right four lobes of patients with primary insomnia (PI). During follow-up examinations, five PI patients showed a disappearance of insomnia symptoms and a decrease in CBF in both brain lobes. Insomnia symptoms may be associated with high CBF, and most PI patients have higher CBF and lower T2 values in the right cerebral hemispheres. The right hemisphere appears to play a critical role in the pathophysiology of PI. The 3D-ASL and syMRI technologies can provide a quantitative imaging basis for investigating the brain conditions and changes in young and middle-aged PI patients.

Increased cardiac involvement in Fabry disease using blood-corrected native T1 mapping

Fabry disease (FD) is a rare lysosomal storage disorder resulting in myocardial sphingolipid accumulation which is detectable by cardiovascular magnetic resonance as low native T1. However, myocardial T1 contains signal from intramyocardial blood which affects variability and consequently measurement precision and accuracy. Correction of myocardial T1 by blood T1 increases precision. We therefore deployed a multicenter study of FD patients (n = 218) and healthy controls (n = 117) to investigate if blood-correction of myocardial native T1 increases the number of FD patients with low T1, and thus reclassifies FD patients as having cardiac involvement. Cardiac involvement was defined as a native T1 value 2 standard deviations below site-specific means in healthy controls for both corrected and uncorrected measures. Overall low T1 was 135/218 (62%) uncorrected vs. 145/218 (67%) corrected (p = 0.02). With blood-correction, 13/83 previously normal patients were reclassified to low T1. This reclassification appears clinically relevant as 6/13 (46%) of reclassified had focal late gadolinium enhancement or left ventricular hypertrophy as signs of cardiac involvement. Blood-correction of myocardial native T1 increases the proportion of FD subjects with low myocardial T1, with blood-corrected results tracking other markers of cardiac involvement. Blood-correction may potentially offer earlier detection and therapy initiation, but merits further prospective studies.

Airway epithelial type-2 alarmin profiles: Blood eosinophil counts remain in memory.

Epithelial cytokines are involved in the orchestration of T1/T2 inflammatory patterns. We question the persistence of this trait in air-liquid interface (ALI) epithelial cultures and whether this local orientation can be related to systemic patterns (e.g., blood eosinophil counts [BECs]). We investigated alarmin release related to high versus low T2 phenotypes associated with chronic airway diseases. ALIs were reconstituted from 32 control, 40 chronic obstructive pulmonary disease, and 20 asthmatic patients. Interleukin-8 (IL-8; a T1-cytokine), IL-25, IL-33, and thymic stromal lymphopoietin (T2-alarmins) concentrations were assessed in subnatants at steady state and used to explain blood neutrophil and eosinophil counts. IL-25 and IL-8 levels were highest in asthma ALI-subnatants, whereas IL-33 was sparsely detected. Thymic stromal lymphopoietin levels were similar among groups. All asthma cell cultures were T1-high/T2-high, while chronic obstructive pulmonary disease and controls tended to be mixed. BECs were independently explained by both disease and in-culture T2-alarmin levels, irrespective of the T2-alarmin considered. The epithelial ALI-T2 signature was more frequently high in patients with a BEC > 300/mm3 . Despite removal from an in vivo environment for ≥2 months, ALIs release disease-specific cytokine "cocktails" into their subnatants, suggesting continued persistence of alarmin orientation in differentiated cell line environments.

New Insights into the Spread of MRS-Based Water T2 Values Observed in Highly Fatty Replaced Muscles.

The reference standard for assessing water T2 (T2,H2O ) at high fat fraction (FF) is 1 H MRS. T2,H2O (T2,H2O,MRS ) dependence on FF (FFMRS ) has recently been demonstrated in muscle at high FF (i.e. ≥60%). To investigate the relationship between T2,H2O,MRS and FFMRS in the thigh/leg muscles of patients with neuromuscular diseases and to compare with quantitative MRI. Retrospective case-control study. A total of 151 patients with neuromuscular disorders (mean age ± standard deviation = 52.5 ± 22.6 years, 54% male), 44 healthy volunteers (26.5 ± 13.0 years, 57% male). A 3-T; single-voxel stimulated echo acquisition mode (STEAM) MRS, multispin echo (MSE) imaging (for T2 mapping, T2,H2O,MRI ), three-point Dixon imaging (for FFMRI and mapping). Mono-exponential and bi-exponential models were fitted to water T2 decay curves to extract T2,H2O,MRS and FFMRS . Water resonance full-width-at-half-maximum (FWHM) and B0 spread (∆B0 ) values were calculated. T2,H2O,MRI (mean), FFMRI (mean, kurtosis, and skewness), and (mean) values were estimated in the MRS voxel. Mann-Whitney U tests, Kruskal-Wallis tests. A P-value <0.05 was considered statistically significant. Normal T2,H2O,MRS threshold was defined as the 90th percentile in healthy controls: 30.3 msec. T2,H2O,MRS was significantly higher in all patients with FFMRS < 60% compared to healthy controls. We discovered two subgroups in patients with FFMRS ≥ 60%: one with T2,H2O,MRS ≥ 30.3 msec and one with T2,H2O,MRS < 30.3 msec including abnormally low T2,H2O,MRS . The latter subgroup had significantly higher water resonance FWHM, ∆B0 , FFMRI kurtosis, and skewness values but nonsignificantly different (P = 1.00) and long T2,H2O,MRS component and its fraction (P > 0.11) based on the bi-exponential analysis. The findings suggest that the cause for (abnormally) T2,H2O,MRS at high FFMRS is biophysical, due to differences in susceptibility between muscle and fat (increased FWHM and ∆B0 ), rather than pathophysiological such as compartmentation changes, which would be reflected by the bi-exponential analysis. 3 TECHNICAL EFFICACY: Stage 3.

The temporal cost of deploying attention limits accurate target identification in rapid serial visual presentation

Lag-1 sparing is a common exception to the attentional blink, where a target presented directly after T1 can be identified and reported accurately. Prior work has proposed potential mechanisms for lag 1 sparing, including the boost and bounce model and the attentional gating model. Here, we apply a rapid serial visual presentation task to investigate the temporal limitations of lag 1 sparing by testing three distinct hypotheses. We found that endogenous engagement of attention to T2 requires between 50 and 100 ms. Critically, faster presentation rates yielded lower T2 performance, whereas decreased image duration did not impair T2 detection and report. These observations were reinforced by subsequent experiments controlling for short-term learning and capacity-dependent visual processing effects. Thus, lag-1 sparing was limited by the intrinsic dynamics of attentional boost engagement rather than by earlier perceptual bottlenecks such as insufficient exposure to images in the stimulus stream or visual processing capacity limitations. Taken together, these findings support the boost and bounce theory over earlier models that focus only on attentional gating or visual short-term memory storage, informing our understanding of how the human visual system deploys attention under challenging temporal constraints.

Magnetic resonance imaging of human variegated squirrel bornavirus 1 (VSBV-1) encephalitis reveals diagnostic pattern indistinguishable from Borna disease virus 1 (BoDV-1) encephalitis but typical for bornaviruses

ABSTRACT Human bornavirus encephalitis is an emerging disease caused by the variegated squirrel bornavirus 1 (VSBV-1) and the Borna disease virus 1 (BoDV-1). While characteristic brain magnetic resonance imaging (MRI) changes have been described for BoDV-1 encephalitis, only scarce diagnostic data in VSBV-1 encephalitis exist. We systematically analysed brain MRI scans from all known VSBV-1 encephalitis patients. Initial and follow-up scans demonstrated characteristic T2 hyperintense lesions in the limbic system and the basal ganglia, followed by the brainstem. No involvement of the cerebellar cortex was seen. Deep white matter affection occurred in a later stage of the disease. Strict symmetry of pathologic changes was seen in 62%. T2 hyperintense areas were often associated with low T1 signal intensity and with mass effect. Sinusitis in three patients on the first MRI and an early involvement of the limbic system suggest an olfactory route of VSBV-1 entry. The viral spread could occur per continuitatem to adjacent anatomical brain regions or along specific neural tracts to more distant brain regions. The number and extent of lesions did not correlate with the length of patients’ survivals. The overall pattern closely resembles that described for BoDV-1 encephalitis. The exact bornavirus species can thus not be deduced from imaging results alone, and molecular testing and serology should be performed to confirm the causative bornavirus. As VSBV-1 is likely of tropical origin, and MRI investigations are increasingly available globally, imaging techniques might be helpful to facilitate an early presumptive diagnosis of VSBV-1 encephalitis when molecular and/or serological testing is not available.

Comprehensive cardiac magnetic resonance T1, T2, and extracellular volume mapping to define Duchenne cardiomyopathy

BackgroundCardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD). Cardiac magnetic resonance (CMR) parametric mapping sequences offer insights into disease pathophysiology. We propose a novel approach by leveraging T2 mapping in conjunction with T1 and extracellular volume (ECV) mapping to perform a virtual myocardial biopsy. While previous work has attempted to describe myocardial changes in DMD, our inclusion of T2 mapping enables comprehensive categorization of myocardial tissue characteristics of fibrosis, edema, and fat to better understand the pathological composition of the myocardium with disease progression. MethodsDMD patients (n = 49; median: 12 years-old) underwent CMR, including T1, T2, and ECV. Categories were defined as normal, isolated high T1 (normal ECV, high T1, normal T2), fibrosis (high ECV, normal or high T1, normal T2), edema (normal or high ECV, normal or high T1, high T2), fat (normal ECV, low T1, high T2) or fibrofatty (high ECV, low T1, high T2). ResultsMedian left ventricular ejection fraction (LVEF) was 59% with 27% having LVEF < 55%. Those with normal LVEF and no late gadolinium enhancement (37%) were younger in age (10.5 ± 2.6 vs. 15.0 ± 4.3 years-old, p < 0.001). Native T1 was elevated in at least one slice in 82% of patients. Those with high T2 at any slice (27%) were older (p = 0.005) and had lower LVEF (p = 0.005) compared with subjects with normal T2 (73%). The most common myocardial characterization was fibrosis (43%) followed by isolated high T1 (24%). Of the 13 with high T2, ten were categorized as edema, two as fibrofatty, and one as fat. ConclusionCMR parametric mapping sequences offer insights into Duchenne cardiomyopathy pathophysiology, which should drive development of therapeutic interventions aimed at these targets. Myocardial fibrosis is common in DMD. Patients with elevated T2 were older and had lower LVEF. Though fat infiltration was present, the majority of subjects with elevated T2 met criteria for myocardial edema.

Cardiac Magnetic Resonance Strain in Beta Thalassemia Major Correlates with Cardiac Iron Overload.

Beta thalassemia major (Beta-TM) is an inherited condition which presents at around two years of life. Patients with Beta-;TM may develop cardiac iron toxicity secondary to transfusion dependence. Cardiovascular magnetic resonance (CMR) T2*, a technique designed to quantify myocardial iron deposition, is a driving component of disease management. A decreased T2* value represents increasing cardiac iron overload. The clinical manifestation is a decline in ejection fraction (EF). However, there may be early subclinical changes in cardiac function that are not detected by changes in EF. CMR-derived strain assesses myocardial dysfunction prior to decline in EF. Our primary aim was to assess the correlation between CMR strain and T2* in the Beta-TM population. Circumferential and longitudinal strain was analyzed. Pearson's correlation was calculated for T2* values and strain in the Beta-TM population. We identified 49 patients and 18 controls. Patients with severe disease (low T2*) were found to have decreased global circumferential strain (GCS) in comparison to other T2* groups. A correlation was identified between GCS and T2* (r = 0.5; p < 0.01). CMR-derived strain can be a clinically useful tool to predict early myocardial dysfunction in Beta-TM.

Iron Overload Following Hematopoietic Stem Cell Transplantation: Prevalence, Severity, and Management in Children and Adolescents with Malignant and Nonmalignant Diseases

Iron overload (IOL) is a frequently reported complication following hematopoietic stem cell transplantation (HSCT) that has been investigated extensively in the field of hemoglobinopathies but has not been thoroughly characterized after HSCT in pediatric malignancies. Our aim was to assess prevalence, severity, risk factors, and management of IOL, as defined using biochemical (serum ferritin) and radiologic tools (T2*-weighted magnetic resonance imaging [MRI]), in a cohort of pediatric patients who underwent HSCT for either malignant or benign diseases. This monocentric, retrospective, observational study included all the 163 patients alive and in continuous remission at 24 months post-HSCT out of the 219 consecutive children and adolescents who underwent HSCT at our institution between 2012 and 2018, were included in the study. IOL was classified into 4 categories: absent, mild, moderate, and severe. Among the 163 patients, 73% had some degree of IOL (mild in 37%, moderate in 29%, and severe in 7%). Moderate/severe IOL was more frequent among patients diagnosed with a malignant disease versus those with a benign disease (43% versus 19%; P = .0065). Trend lines for serum ferritin showed a "bell-shaped" distribution, with the highest levels recorded during the first 6 months post-HSCT, followed by a spontaneous reduction. Both pre-HSCT (1659 ng/mL versus 617 ng/mL; P < .001) and maximum post-HSCT (2473 ng/mL versus 1591 ng/mL; P < .001) median ferritin levels were statistically higher in the patients with malignancies. Radiologic assessment of IOL confirmed a more severe degree in patients with malignant disorders compared to those with benign disorders (median T2*-MRI, 4.20 msec [interquartile range (IQR), 3.0 to 6.40 msec] versus 7.40 msec [IQR, 4.90 to 11.00 msec]; P = .008). T2* levels were associated with the number of transfusions performed (P = .0006), with a steeper drop in T2* values for the first 20 transfusions and a milder slope for subsequent transfusions. T2* and ferritin values showed a statistically significant negative exponential relationship (P < .0001), although a ferritin level ≥1000 ng/mL showed poor specificity (48%) and low positive predictive value (53%) for discriminating moderate-to-severe IOL from absent-mild IOL as assessed by T2*-MRI, but with high sensitivity (92%) and negative predictive value (91%). In a multivariable model, >20 transfusions (odds ratio [OR], 4.07; 95% confidence interval [CI], 1.61 to 10.68; P = .003) and higher pre-HSCT ferritin level (P < .001) were associated with the risk of developing moderate-to-severe IOL. Use of a sibling donor (OR, .29; 95% CI, .10 to .77; P=.015) and a nonmalignancy (OR, .27; 95% CI, .08 to .82; P=.026) were protective factors. Phlebotomy (66%), low-dose oral chelators (9%), or a combined approach (25%) were started at a median of 12 months after HSCT in 78% of the patients with IOL. Six percent of the patients treated exclusively with phlebotomy (median, 14, significantly higher in patients >40 kg) discontinued phlebotomy owing to poor venous access, lack of compliance, or hypotension, whereas 39% of patients treated with chelators developed mild renal or hepatic side effects that resolved after tapering or discontinuation. Patients with malignancies showed statistically higher pre-HSCT and post-HSCT ferritin levels and lower T2* values. High ferritin level recorded on T2*-MRI showed unsatisfactory diagnostic accuracy in predicting IOL; thus, T2*-MRI should be considered a key tool for confirming IOL after HSCT in patients with an elevated serum ferritin level. IOL treatment is feasible after HSCT.