Lymph node metastasis is a crucial factor in cancer prognosis; however, no clinically approved contrast agents are available for its accurate detection via medical imaging. The contribution of macrophage uptake to nanoparticle (NP) accumulation during lymphatic drainage has been a subject of ongoing debate. Herein, we report a novel lymph node imaging strategy designed to enhance lymph node retention while evading macrophage clearance through nanoprobe surface modification, thereby improving the diagnostic accuracy of lymph node metastases. We engineered a series of Pluronic F127-based NPs as magnetic resonance imaging (MRI) contrast agents, incorporating manganese (Mn) porphyrin molecules bearing varied functional groups (-CH3, -OH, -COOH, -NH2, and -B(OH)2). The influence of these surface modifications on physicochemical properties and macrophage-evading capabilities was investigated. Notably, boronic acid-functionalized Mn-porphyrin NPs exhibited exceptional macrophage evasion, demonstrating significantly reduced macrophage uptake in vitro and prolonged blood circulation in vivo relative to NPs modified with alternative functional groups. In a lymph node metastasis model, boronic acid-modified Mn-porphyrin NPs administered via local footpad injection (0.005 mmol Mn/kg) achieved optimal lymph node MRI contrast with an extended imaging window. Furthermore, in New Zealand rabbits, even at lower doses (0.0025 mmol Mn/kg), boronic acid-modified Mn-porphyrin NPs provided excellent lymphatic system visualization, highlighting the potential for further translational studies. In summary, this study confirms the feasibility of a boronic acid group modification strategy that evades macrophage uptake and utilizes lymphatic drainage to diagnose lymph node metastasis, offering valuable insights for the development of next-generation macrophage-evading nanoprobes.
BackgroundThe 2022 European Society of Cardiology on cardio-oncology guidelines emphasized anthracycline chemotherapy's dose-dependent cardiotoxicity, identifying reduced left ventricular (LV) strain as a sensitive biomarker for early myocardial injury. However, left atrial (LA) structural/functional changes assessed via cardiac magnetic resonance (CMR) remain underexplored.MethodsThis cross-sectional cohort study included 109 pediatric leukemia patients (2015–2021) and 40 age-matched controls. Leukemia patients were stratified into low-/high-dose anthracycline groups. CMR parameters (LA ejection fraction [LAEF], LV strain [LVS], LA strain [LAS], and left atrioventricular coupling index [LACI]) were analyzed. Linear regression evaluated strain-LACI relationships; Spearman's correlation assessed LAS-LVS associations.ResultsLeukemia patients exhibited higher LA contraction strain (Ɛa: 24% vs. 21%, p = 0.025) but lower total/passive LAEF [73 ± 8 vs. 78 ± 7; 50 [40,56] vs. 59 [53,65]] and higher LV ejection fraction (64.5 ± 5.5 vs. 62.4 ± 5.7) than that in controls. LAS-LVS correlations were stronger in controls (r = 0.32–0.52) than leukemia (r = 0–0.27). Among leukemia patients, low-dose patients had higher active LAEF (48 ± 14 vs. 39 ± 16) and weaker LAS-LVS correlations than high-dose group(r = 0–0.28 vs. r = 0–0.42), while high-dose group showed elevated LACI (β=9.68, p = 0.018) correlating with the cumulative anthracycline dose.ConclusionsAnthracyclines disrupt LA-LV coordination in pediatric leukemia, with higher doses exacerbating atrial strain impairment. These findings highlight CMR-derived strain parameters as critical for monitoring anthracycline-induced cardiac impairment.
The triglyceride-glucose(TyG) index, a surrogate marker of insulin resistance, has been linked to cardiac dysfunction; however, its underlying associated pathways in patients with type 2 diabetes mellitus(T2DM) remain unclear. This study used cardiac magnetic resonance(CMR) to explore the association of TyG index with subclinical left ventricular(LV) myocardial dysfunction and whether imaging indicators statistically mediate this relationship. In this retrospective cross-sectional study, a total of 235 T2DM patients who underwent CMR examination were included and assigned to three groups based on the tertiles of their TyG indexes as follows: low(< 8.73, n = 78), moderate(8.73–9.36, n = 79), and high TyG index(≥ 9.36, n = 78) groups. LV geometry, function, myocardial energetic efficiency index (MEEi), resting first-pass perfusion, and global peak strain in radial(GRPS), circumferential(GCPS), and longitudinal(GLPS) directions were measured. Univariate and multivariate linear regression models and exploratory mediation analysis were used to analyze the associations of TyG index on LV global strain. Compared with the low and moderate TyG index groups, the high TyG index group had significantly higher LV remodeling index, lower LV global function index, lower MEEi, impaired resting myocardial perfusion, and reduced LV global peak strain (all p ≤ 0.002). Multivariate analysis showed that TyG index remained independently associated with reduced LV strain after adjusting for confounders (GRPS β = −0.261; GCPS β = 0.271; GLPS β = 0.381; all p < 0.001). And MEEi and upslope were also independently associated with reduced LV GRPS and GLPS (all p < 0.05). Further mediation analysis revealed the statistically mediated proportions of the association between the TyG index and LV global strain were 8.2–8.6
Background:Magnetic resonance imaging (MRI) is an ideal method for the detection of osteonecrosis in children with acute lymphoblastic leukemia (ALL), but some children struggle to adhere to the procedure due to its lengthy examination time. This study evaluated the feasibility of synthetic MRI for knee examinations in children with ALL. Methods:This prospective study included 33 children with ALL who underwent conventional and synthetic MRI. Participants were categorized into Group A (>8 years, n=23) and Group B (≤8 years, n=10). Scan time, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), motion artifacts, image quality score, lesion detection, and T2 values were compared using paired t-tests, Wilcoxon signed-rank tests, Cohen's kappa, and Bland-Altman analysis, with Bonferroni correction (α=0.003). Results:Synthetic MRI significantly reduced scan time (Group A: 286±74 vs. 504±64 s, P<0.001; Group B: 254±8 vs. 461±17 s, P=0.002). No significant SNR or CNR differences were found between synthetic and conventional T1-weighted imaging (T1WI) (P>0.003). Synthetic proton density-weighted imaging (PDWI) showed lower SNR (P<0.003) but similar CNR (P>0.003). In T1WI, motion artifacts were comparable between synthetic and conventional MRI in Group A (P=0.166) but were more pronounced with synthetic MRI in Group B (P=0.038). In PDWI, synthetic images exhibited significantly greater motion artifacts in both Group A and Group B (P=0.011 and P=0.023, respectively). Image noise was higher in synthetic T1WI and PDWI (P<0.050). Lesion detection showed excellent agreement (κ=0.86-0.96), though two Group B cases were nondiagnostic. T2 values showed no significant inter-method differences in either group (P>0.003). Conclusions:For pediatric leukemia patients capable of maintaining stillness, synthetic MRI shortens acquisition time while preserving diagnostic accuracy and quantitative precision. However, due to motion susceptibility, its clinical use should be limited to cooperative children.
Abstract Background Duchenne muscular dystrophy (DMD)‐associated cardiomyopathy is a leading causes of premature death, yet treatment options remain limited. In this study, we developed the easily accessible engineered exosomes for treatment of DMD‐associated cardiomyopathy and explored the underlying mechanisms in DmdΔ4 mice, a model harboring hot spot mutation in the dystrophin gene. Methods DmdΔ4 mice and their cardiomyopathy phenotype were confirmed by Sanger sequencing, pathological staining, flow cytometry, immunoblotting, single‐cell sequencing and echocardiographic analysis. Engineered exosomes, exosomes‐ cardiac homing peptide (Exo‐CHP), were synthesised and characterised by click chemistry and miRNA sequence, separately. The targeted ability and the therapeutic effects of Exo‐CHP were studied in vitro and in vivo. Primary cardiomyocytes were used to study the underlying mechanism of Exo‐CHP. Results DmdΔ4 mice showed an obvious cardiomyopathy‐associated phenotype. Exo‐CHP can target myocardium and mitigate pathological progression of cardiomyopathy in DmdΔ4 mice. The therapeutic effects of intravenously delivered Exo‐CHP significantly reduced myocardial inflammation, fibrosis and improved the mice's cardiac function. The rescue effects were mediated through the regulation of gene expression at the transcriptomic level, prevention of dystrophin protein complex degradation, and inhibition of intracellular calcium influx and calpain protease activity. The miR‐21 knockdown Exo‐CHP can counteract the protective effects of Exo‐CHP on the calcium content and membrane integrity of primary DmdΔ4‐derived cardiomyocytes. Conclusions Our study demonstrated the feasibility, efficacy and the possible mechanism of mesenchymal stromal cell‐derived engineered exosomes, positioning them as a potential cell‐free intervention for DMD‐associated cardiomyopathy.
BACKGROUND:Kawasaki disease (KD) is associated with various myocardial injuries, including myocardial perfusion abnormality. This study aims to assess the distribution of myocardial perfusion abnormality in patients with KD and explore their relationships with left ventricular (LV) remodeling. METHODS:This prospective single-center study enrolled children with KD who underwent fully quantitative CMR rest perfusion. Myocardial blood flow (MBF) was measured and corrected based on the heart rate-blood pressure product (MBFcor). Statistical analyses included ANOVA, Pearson correlation and multivariate linear regression. RESULTS:Eighty-seven patients with KD (mean age, 7.5 ± 2.2 years) and 33 age- and sex-matched controls (mean age, 8.2 ± 2.8 years) were included. Global MBFcor was lower in patients than in controls, especially among patients during the acute phase. Subgroup analysis showed that patients with Z score ≥ 5 had significant decreases in global MBFcor, as well as regional MBFcor in the territories of the left anterior descending artery (LAD) and left circumflex artery (LCX) (p < 0.05 for all). Global MBFcor and regional MBFcor in the territories of the LAD and LCX were correlated with Z score among patients with KD. Covariate-adjusted multivariable regression analyses demonstrated that Z score and the acute phase were independently associated with global MBFcor. Furthermore, global MBFcor was negatively associated with increased LV mass index. CONCLUSIONS:Fully quantitative CMR rest first-pass perfusion revealed decreased myocardial perfusion in children with KD. Z score and the acute phase were independently associated with decreased myocardial perfusion; decreased MBFcor was associated with LV mass index.
Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder that is due to mutations in the dystrophin gene which encodes the dystrophin protein. Many patients face an increased risk of bone fragility and develop secondary osteoporosis as a result of the combined effects of progressive muscle weakness, immobilization, and the osteotoxic properties of glucocorticoids (GCs). The present study showed that the prevalence of low BMD and fracture in DMD patients reached as high as 0.62 and 0.38, respectively, with contributing risk factors extending beyond GCs and loss of ambulation to include older age, vitamin D deficiency, fat mass accumulation, and hormonal imbalances. Therefore, clinical trials of bone-protective therapies and strategies to improve bone health in boys with DMD are urgently warranted. Poor skeletal health, characterized by rapid bone mineral density decline, causes substantial morbidity in patients with Duchenne muscular dystrophy (DMD). The present systematic review and meta-analysis aimed to review comprehensive findings on the prevalence and risk factors of low bone mineral density (BMD) and fractures in DMD. PubMed, Embase, Cochrane library, and Web of Science databases were systematically searched for studies reporting prevalence of fractures, low BMD, or data on risk factors in DMD patients. Random‑effects meta‑analyses estimated pooled prevalence of low BMD and fractures. Subgroup analyses examined variations by region, GCs use, fracture location, and ambulatory stage. A total of 43 studies involving 4940 patients were reviewed. The prevalence of low BMD from 0.16 to 0.93, with an overall prevalence of 0.62 (95
BACKGROUND:Dp140-related mutations associate with neurodevelopmental impairments in Duchenne muscular dystrophy (DMD), their effects on cortical similarity network organization remain unclear. PURPOSE:To characterize alterations in morphometric similarity networks (MSN) in DMD with different Dp140 genotypes, assess their associations with clinical phenotypes and gene expression. STUDY TYPE:Prospective. POPULATION:One hundred and fifteen boys with DMD (75 Dp140-: 9.63 ± 2.25 years; 40 Dp140+: 10.99 ± 2.25 years) and 69 healthy controls (all male, 10.65 ± 2.43 years). FIELD STRENGTH/SEQUENCE:Gradient echo at 3 T. ASSESSMENT:MRI were processed using FreeSurfer and GRETNA. Behavior data were based on Wechsler Intelligence Scale for children-Fourth edition while transcriptional profiles were from the Allen Human Brain Atlas. STATISTICAL TESTS:Independent T-tests, chi-square tests, general linear models, permutation testing, multivariable linear regression, mediation analyses, partial least squares regression, spatial permutation tests (Spin test), Gene Ontology enrichment analysis and cell-type analysis. FDR-corrected p < 0.05 and p spin < 0.05 were considered significant. RESULTS:Dp140- subgroup had lower working memory index (WMI) than Dp140+ DMD (81.63 ± 15.48 vs. 90.78 ± 15.31; p = 0.01, Cohen's d = 0.179). Dp140- DMD showed reduced cortical similarity in bilateral lateral prefrontal cortex and parietal cortex regions, increased modular segregation (Hedge's g = -0.298, 95% CI [-0.408, -0.187]), and more hubs loss within frontal parietal network (FPN). The indirect effect of Dp140 genotype on WMI through mean FPN cortical similarity was significant (β = -0.121, p = 0.03, 95% CI [-0.282, -0.001]). The Dp140-specific MSN changes were spatially associated with transcriptional profile, which are enriched in neuronal projection development pathways of excitatory neurons (p spin < 0.05). DATA CONCLUSION:By linking genotype, neuroimaging, and transcriptional data, these findings offer further insight into mechanisms possibly involved in working memory deficits among Dp140- DMD. EVIDENCE LEVEL:2. TECHNICAL EFFICACY:Stage 2.
Diabetic cardiomyopathy (DCM) is a common and serious complication in patients with diabetes, and early detection and monitoring are essential to improving clinical outcomes. This study introduces a noninvasive method to visualize cardiac macromolecule-free radicals, enabling the detection of oxidative stress damage in the early stages of DCM. The approach utilizes DEPMPO-biotin to capture free radicals, while avidin-BGEC serves as molecular probes to target and visualize these adducts using magnetic resonance imaging (MRI). Following intraperitoneal injection, avidin-BGEC selectively accumulated in the hearts of diabetic mice, resulting in increased T1 signal intensity (28.6% in diabetic mice vs 4.38% in controls) and decreased T1 relaxation time (727 ms in diabetic mice vs 30.8 ms in controls). This strategy also detected elevated oxidative stress levels in 4 week old Leprdb/db diabetic mice, which showed a 16.8% increase compared to a 3.10% increase in the controls (P < 0.5). Histochemical staining confirmed the high enrichment of avidin-BGEC within cardiomyocytes, colocalized with free radicals. This molecule capture and imaging system represents a promising paradigm for the early detection of DCM, which could enhance clinical practices regarding timely diagnosis and monitoring.
Currently, the low survival rate and poor prognosis of patients with nasopharyngeal carcinoma are ascribed to the lack of early and accurate diagnosis and resistance to radiotherapy. In parallel, the integration of imaging-guided diagnosis and precise treatment has gained much attention in the field of theranostic nanotechnology. However, constructing dual-modal imaging-guided nanotheranostics with desired imaging performance as well as great biocompatibility remains challenging. Therefore, we developed a simple but multifunctional nanotheranostic GdCPP for the early and accurate diagnosis and efficient treatment of nasopharyngeal carcinoma (NPC), which combined fluorescence imaging and magnetic resonance imaging (MRI) onto a single nanoplatform for imaging-guided subsequent photodynamic therapy (PDT). GdCPP had an appropriate particle size (81.93 ± 0.69 nm) and was highly stable, resulting in sufficient tumor accumulation, which along with massive reactive oxygen species (ROS) generation upon irradiation further significantly killed tumor cells. Moreover, GdCPP owned much stronger r1 relaxivity (9.396 mM-1 s-1) compared to clinically used Gd-DTPA (5.034 mM-1 s-1) and exhibited better T1WI MRI performance. Under dual-modal imaging-guided PDT, GdCPP achieved efficient therapeutic outcomes without causing any noticeable tissue damage. The results of in vitro and in vivo studies indicated that GdCPP may be a suitable candidate for dual-modal imaging-guided precision tumor therapy.
Background:The "Heart-Brain Axis" (HBA) represents an emerging interdisciplinary domain in which cardiac dysfunction is increasingly recognized to affect brain development, particularly with the advancement of imaging technologies such as MRI. Despite growing interest, the literature remains fragmented and lacks systematic synthesis. Methods:We performed a bibliometric analysis of 6,446 English-language articles and reviews in the Web of Science Core Collection (1984-2025), using VOSviewer, CiteSpace, SCImago Graphica, and Excel to map knowledge structures, research hotspots, and collaborative networks. A PubMed dataset (n = 6,389; 1984-2025) provided validation, comparing annual publication trends and high-frequency keyword structures. Results:The annual publication trends showed strong concordance between the WoSCC and PubMed datasets (Pearson r = 0.988, R2 = 0.976). Keyword co-occurrence analysis identified four primary clusters: "Technology & Development", "Function & Regulation", "Risk & Pathology", and "Hemodynamics & Perfusion". In the WoSCC keyword co-occurrence network, representative high-TLS keywords included "MRI" (TLS = 2799), "functional connectivity" (TLS = 1,224), "dementia" (TLS = 1,425), and "hemodynamics" (TLS = 1,036). The United States, Germany, and the United Kingdom were the leading contributors, with prominent institutions including the University of Toronto and Harvard Medical School. Citation bursts and recent keywords such as "artificial intelligence" reflect the technological evolution of the field. Conclusion:This study provides a systematic overview of HBA research trends and thematic evolution. The sustained growth in publications reflects increasing academic attention. Findings offer insights for researchers, clinicians, and policymakers, emphasizing future directions including AI integration and multi-organ network modeling.
Background:Cardiovascular complications are the primary cause of mortality in patients with Duchenne muscular dystrophy (DMD). However, the dynamic progression underlying myocardial damage in DMD has not yet been fully elucidated. This study aimed to quantitatively assess myocardial dysfunction in patients with DMD across different age groups via cardiac magnetic resonance (CMR) tissue tracking technology. Methods:Between August 2018 and January 2020, 110 patients with DMD diagnosed at the Pediatric Neurology Outpatient Department of West China Second University Hospital were consecutively and prospectively included in the study. The patients were categorized into three age groups: 3-6, 7-10, and 11-14 years. Based on left ventricular ejection fraction (LVEF), the patients were further divided into a normal LVEF group (LVEF ≥55%) and a decreased LVEF group (LVEF <55%). Furthermore, based on the presence of delayed enhancement, patients were classified into late gadolinium enhancement (LGE)-positive and LGE-negative groups. Additionally, 69 healthy controls were recruited for comparison. Left ventricular functional parameters and CMR tissue tracking-related parameters, such as global and regional myocardial strain of the left ventricle, were assessed. These included radial, circumferential, and longitudinal peak strains at the base, middle, and apex of the left ventricle. Statistical analyses were conducted via the t-test. Results:A total of 99 patients and 61 healthy controls were included in the study. In comparison to the control group (n=21), patients aged 3-6 years in the DMD group (n=15) did not exhibit any decline. Patients aged 7-10 years in the DMD group (n=63), as compared with the control group (n=18), had lower LVEF (59.58%±7.09% vs. 63.39%±5.27%, P=0.044) and left ventricular global radial (37.34%±9.78% vs. 42.95%±9.22%, P=0.03), circumferential (-20.75%±3.77% vs. -22.09%±2.46%, P=0.03), and longitudinal (-13.91%±2.81% vs. -15.69%±2.52%, P=0.04) strain. Patients aged 11-14 years in the DMD group (n=21), as compared with the control group (n=22), demonstrated an even greater reduction in strain in the left ventricle for all parameters, except for LVEF. For patients in the normal LVEF group (n=77) or LGE-negative group (n=51), despite there being no significant difference in cardiac function compared with the control group, the global and regional myocardial strain of left ventricle was decreased. Conclusions:Myocardial dysfunction predominantly manifests in DMD among children older than 7 years, exhibiting a subtle progression that exacerbates with advancing age. The myocardial injury tends to develop from the basal epicardium toward the apical and endocardial regions.