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13 pages, 508 KiB  
Article
Chiari-like Malformation and Syringomyelia in Pomeranians: A Longitudinal Study
by Mees R. Jansma, Marieke van den Heuvel, Kenny Bossens, Erik Noorman, Michelle Hermans and Paul J. J. Mandigers
Vet. Sci. 2025, 12(7), 677; https://doi.org/10.3390/vetsci12070677 - 18 Jul 2025
Abstract
Background: Chiari-like malformation (CM) and syringomyelia (SM) are commonly observed conditions in Pomeranian dogs. Affected dogs may develop clinical signs that significantly impact quality of life. Therefore, it is crucial to select only unaffected dogs for breeding. However, the progression of CM/SM has [...] Read more.
Background: Chiari-like malformation (CM) and syringomyelia (SM) are commonly observed conditions in Pomeranian dogs. Affected dogs may develop clinical signs that significantly impact quality of life. Therefore, it is crucial to select only unaffected dogs for breeding. However, the progression of CM/SM has not been fully elucidated. Dogs that are unaffected or mildly affected may progress to severe SM over time. The primary aim of this study is to investigate the progression of CM/SM through repeated MRI scans. A secondary objective is to evaluate the effect of furosemide treatment on syrinx sizes, given its frequent prescription. Methods: Pomeranians that underwent two CM/SM screenings between 2015 and 2025 were included. CM/SM classifications were assessed, and quantitative syrinx measurements were conducted. Maximum syrinx diameter (MSD) and maximum syrinx-to-spinal cord diameter ratio (MSD/SCD-r) were measured and documented. Dogs were classified based on the progression of SM. Furosemide treatment was documented, and its effect on syrinx size was compared with that in dogs not receiving furosemide. Results: At the time of the second MRI, 39.6% of dogs either developed SM or showed substantial progression, whereas 12.5% demonstrated partial recovery. Of the dogs initially classified as free from SM, 20.7% had developed the condition. A significant increase was observed in both MSD (p = 0.0058) and MSD/SCD-r (p = 0.0038) between MRI1 and MRI2. Notably, the change in MSD between MRI1 and MRI2 was statistically significantly smaller in dogs treated with furosemide compared to untreated dogs (p = 0.030). Conclusions: These findings indicate that syrinx dimensions are dynamic and may fluctuate over time, although a general trend toward progression is observed. Furthermore, furosemide may mitigate the progression of SM. Full article
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15 pages, 3326 KiB  
Article
Radiomics and Machine Learning Approaches for the Preoperative Classification of In Situ vs. Invasive Breast Cancer Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE–MRI)
by Luana Conte, Rocco Rizzo, Alessandra Sallustio, Eleonora Maggiulli, Mariangela Capodieci, Francesco Tramacere, Alessandra Castelluccia, Giuseppe Raso, Ugo De Giorgi, Raffaella Massafra, Maurizio Portaluri, Donato Cascio and Giorgio De Nunzio
Appl. Sci. 2025, 15(14), 7999; https://doi.org/10.3390/app15147999 - 18 Jul 2025
Abstract
Accurate preoperative distinction between in situ and invasive Breast Cancer (BC) is critical for clinical decision-making and treatment planning. Radiomics and Machine Learning (ML) have shown promise in enhancing diagnostic performance from breast MRI, yet their application to this specific task remains underexplored. [...] Read more.
Accurate preoperative distinction between in situ and invasive Breast Cancer (BC) is critical for clinical decision-making and treatment planning. Radiomics and Machine Learning (ML) have shown promise in enhancing diagnostic performance from breast MRI, yet their application to this specific task remains underexplored. The aim of this study was to evaluate the performance of several ML classifiers, trained on radiomic features extracted from DCE–MRI and supported by basic clinical information, for the classification of in situ versus invasive BC lesions. In this study, we retrospectively analysed 71 post-contrast DCE–MRI scans (24 in situ, 47 invasive cases). Radiomic features were extracted from manually segmented tumour regions using the PyRadiomics library, and a limited set of basic clinical variables was also included. Several ML classifiers were evaluated in a Leave-One-Out Cross-Validation (LOOCV) scheme. Feature selection was performed using two different strategies: Minimum Redundancy Maximum Relevance (MRMR), mutual information. Axial 3D rotation was used for data augmentation. Support Vector Machine (SVM), K Nearest Neighbors (KNN), Random Forest (RF), and Extreme Gradient Boosting (XGBoost) were the best-performing models, with an Area Under the Curve (AUC) ranging from 0.77 to 0.81. Notably, KNN achieved the best balance between sensitivity and specificity without the need for data augmentation. Our findings confirm that radiomic features extracted from DCE–MRI, combined with well-validated ML models, can effectively support the differentiation of in situ vs. invasive breast cancer. This approach is quite robust even in small datasets and may aid in improving preoperative planning. Further validation on larger cohorts and integration with additional imaging or clinical data are recommended. Full article
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16 pages, 2427 KiB  
Review
Pancreatic Cancer Resectability After Neoadjuvant Treatment: An Imaging Challenge
by Ioannis Christofilis, Charikleia Triantopoulou and Spiros Delis
Diagnostics 2025, 15(14), 1810; https://doi.org/10.3390/diagnostics15141810 - 18 Jul 2025
Abstract
Background: Assessing pancreatic ductal adenocarcinoma (PDAC) resectability after neoadjuvant therapy (NAT) remains a diagnostic challenge. Traditional computed tomography (CT) criteria often fail to distinguish viable tumor from fibrosis, necessitating a reassessment of imaging-based standards. Methods: A comprehensive literature review was conducted using PubMed, [...] Read more.
Background: Assessing pancreatic ductal adenocarcinoma (PDAC) resectability after neoadjuvant therapy (NAT) remains a diagnostic challenge. Traditional computed tomography (CT) criteria often fail to distinguish viable tumor from fibrosis, necessitating a reassessment of imaging-based standards. Methods: A comprehensive literature review was conducted using PubMed, focusing on prospective and retrospective studies over the past 25 years that evaluated the role of CT and complementary imaging modalities (MRI, PET-CT) in predicting resectability post-NAT in non-metastatic PDAC. Studies with small sample sizes or case reports were excluded. Results: Across studies, conventional CT parameters—particularly >180° vascular encasement—showed a limited correlation with histologic invasion or surgical outcomes after NAT. Persistent vessel contact on CT often reflected fibrosis, rather than active tumor. Dynamic changes, such as regression in the tumor–vessel interface and vessel lumen restoration, correlated more accurately with R0 resection. Adjunct markers like CA 19-9 response and patient performance status further improved resectability prediction. Conclusions: CT-based resectability assessment after NAT should transition from static morphologic criteria to response-based interpretation. Multidisciplinary evaluation integrating radiologic, biochemical, and clinical findings is essential to guide surgical decision-making and improve patient outcomes. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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29 pages, 2281 KiB  
Systematic Review
The Pathway Is Clear but the Road Remains Unpaved: A Scoping Review of Implementation of Tools for Early Detection of Cerebral Palsy
by Álvaro Hidalgo-Robles, Javier Merino-Andrés, Mareme Rose Samb Cisse, Manuel Pacheco-Molero, Irene León-Estrada and Mónica Gutiérrez-Ortega
Children 2025, 12(7), 941; https://doi.org/10.3390/children12070941 - 17 Jul 2025
Viewed by 105
Abstract
Background/Objectives: International guidelines recommend the combined use of the General Movement Assessment (GMA), Hammersmith Infant Neurological Examination (HINE), and magnetic resonance imaging (MRI) to support early and accurate diagnosis of cerebral palsy (CP). However, their implementation remains inconsistent. This study aimed to [...] Read more.
Background/Objectives: International guidelines recommend the combined use of the General Movement Assessment (GMA), Hammersmith Infant Neurological Examination (HINE), and magnetic resonance imaging (MRI) to support early and accurate diagnosis of cerebral palsy (CP). However, their implementation remains inconsistent. This study aimed to map their reported global use and identify associated enablers and barriers. Methods: A scoping review was conducted following JBI and PRISMA-ScR guidelines. Systematic searches were performed in PubMed, Cochrane, PEDro, ProQuest, Web of Science, and Scopus. Eligible studies were charted and thematically analyzed, focusing on tools use and implementation factors at individual, organizational, and system levels. Results: Fourteen articles (seven surveys, seven implementation studies) from seven countries met the inclusion criteria. While awareness of GMA, HINE, and MRI was generally high, routine clinical use was limited—particularly outside structured implementation initiatives. Major barriers emerged at the system level (e.g., limited training access, time constraints, lack of standardized referral pathways) and social level (e.g., unclear leadership and coordination). Conclusions: The limited integration of GMA, HINE, and MRI into routine practice reflects a persistent “know–do” gap in early CP detection. Since implementation is shaped by the dynamic interplay of capability, opportunity, and motivation, bridging this gap demands sustained and equitable action—by addressing system-wide barriers, supporting professional development, and embedding early detection within national care pathways. Full article
(This article belongs to the Special Issue Children with Cerebral Palsy and Other Developmental Disabilities)
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26 pages, 19416 KiB  
Article
Identification and Characterization of a Translational Mouse Model for Blood–Brain Barrier Leakage in Cerebral Small Vessel Disease
by Ruxue Jia, Gemma Solé-Guardia, Vivienne Verweij, Jessica M. Snabel, Bram Geenen, Anil Man Tuladhar, Robert Kleemann, Amanda J. Kiliaan and Maximilian Wiesmann
Int. J. Mol. Sci. 2025, 26(14), 6706; https://doi.org/10.3390/ijms26146706 - 12 Jul 2025
Viewed by 227
Abstract
Blood–brain barrier (BBB) dysfunction is a hallmark of cerebral small vessel disease (cSVD). This study aimed to identify a mouse model that replicates BBB impairment and shares key cSVD risk factors. Transgenic db/db and LDLr−/−.Leiden mice, both prone to obesity and [...] Read more.
Blood–brain barrier (BBB) dysfunction is a hallmark of cerebral small vessel disease (cSVD). This study aimed to identify a mouse model that replicates BBB impairment and shares key cSVD risk factors. Transgenic db/db and LDLr−/−.Leiden mice, both prone to obesity and hypertension, were compared to C57BL/6J controls. BBB leakage was assessed using DCE-MRI and sodium fluorescein (NaFl); cerebral blood flow (CBF) by MRI. Dyslipidemia and vascular inflammation were measured by plasma tests. Tight junction integrity, endothelial dysfunction (glucose transporter 1, GLUT-1) and neuroinflammation were evaluated with immunohistochemistry and PCR. Both transgenic models developed an obese phenotype with hyperinsulinemia, but only LDLr−/−.Leiden mice showed human-like dyslipidemia. When fed a high-fat diet (HFD) or HFD plus cholesterol, LDLr−/−.Leiden mice showed reduced CBF, endothelial dysfunction (lowered GLUT-1), elevated vascular inflammation (ICAM-1, VCAM-1, S-selectin), and BBB leakage, as evidenced by DCE-MRI and NaFl, together with reduced ZO-1 and claudin-5 expression. Contrastingly, db/db mice showed endothelial dysfunction without BBB leakage. Neuroinflammation (IBA-1, GFAP) was observed only in LDLr−/−.Leiden groups, consistent with BBB disruption. These findings indicate that LDLr−/−.Leiden mice, but not db/db mice, are a promising translational model for studying BBB dysfunction in cSVD, offering insights into disease mechanisms and a platform for therapeutic development. Full article
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19 pages, 2049 KiB  
Review
DSC Perfusion MRI Artefact Reduction Strategies: A Short Overview for Clinicians and Scientific Applications
by Chris W. J. van der Weijden, Ingomar W. Gutmann, Joost F. Somsen, Gert Luurtsema, Tim van der Goot, Fatemeh Arzanforoosh, Miranda C. A. Kramer, Anne M. Buunk, Erik F. J. de Vries, Alexander Rauscher and Anouk van der Hoorn
J. Clin. Med. 2025, 14(13), 4776; https://doi.org/10.3390/jcm14134776 - 6 Jul 2025
Viewed by 374
Abstract
MRI perfusion is used to diagnose and monitor neurological conditions such as brain tumors, stroke, dementia, and traumatic brain injury. Dynamic Susceptibility Contrast (DSC) is the most widely available quantitative MRI technique for perfusion imaging. Even in its most basic implementation, DSC MRI [...] Read more.
MRI perfusion is used to diagnose and monitor neurological conditions such as brain tumors, stroke, dementia, and traumatic brain injury. Dynamic Susceptibility Contrast (DSC) is the most widely available quantitative MRI technique for perfusion imaging. Even in its most basic implementation, DSC MRI provides critical hemodynamic metrics like cerebral blood flow (CBF), blood volume (CBV), mean transit time (MTT), and time between the peak of arterial input and residue function (Tmax), through the dynamic tracking of a gadolinium-based contrast agent. Notwithstanding its high clinical importance and widespread use, the reproducibility and diagnostic reliability are impeded by a lack of standardized pre-processing protocols and quality controls. A comprehensive literature review and the authors’ aggregated experience identified common DSC MRI artefacts and corresponding pre-processing methods. Pre-processing methods to correct for artefacts were evaluated for their practical applicability and validation status. A consensus on the pre-processing was established by a multidisciplinary team of experts. Acquisition-related artefacts include geometric distortions, slice timing misalignment, and physiological noise. Intrinsic artefacts include motion, B1 inhomogeneities, Gibbs ringing, and noise. Motion can be mitigated using rigid-body alignment, but methods for addressing B1 inhomogeneities, Gibbs ringing, and noise remain underexplored for DSC MRI. Pre-processing of DSC MRI is critical for reliable diagnostics and research. While robust methods exist for correcting geometric distortions, motion, and slice timing issues, further validation is needed for methods addressing B1 inhomogeneities, Gibbs ringing, and noise. Implementing adequate mitigation methods for these artefacts could enhance reproducibility and diagnostic accuracy, supporting the growing reliance on DSC MRI in neurological imaging. Finally, we emphasize the crucial importance of pre-scan quality assurance with phantom scans. Full article
(This article belongs to the Special Issue Recent Advancements in Nuclear Medicine and Radiology)
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18 pages, 6379 KiB  
Article
Assessing Extreme Precipitation in Northwest China’s Inland River Basin Under a Novel Low Radiative Forcing Scenario
by Mingjie Yang, Lianqing Xue, Tao Lin, Peng Zhang and Yuanhong Liu
Water 2025, 17(13), 2009; https://doi.org/10.3390/w17132009 - 4 Jul 2025
Viewed by 308
Abstract
Accelerating climate change poses significant risks to water security and ecological stability in arid regions due to the increasing frequency and intensity of extreme precipitation events. As a climate-sensitive area, the inland river basin (IRB) of Northwest China—a critical water source for local [...] Read more.
Accelerating climate change poses significant risks to water security and ecological stability in arid regions due to the increasing frequency and intensity of extreme precipitation events. As a climate-sensitive area, the inland river basin (IRB) of Northwest China—a critical water source for local ecosystems and socioeconomic activities—remains insufficiently studied in terms of future extreme precipitation dynamics. This study evaluated the spatiotemporal evolution of extreme precipitation in the IRB under a new low radiative forcing scenario (SSP1-1.9) by employing four global climate models (GCMs: GFDL-ESM4, MRI-ESM2, MIROC6, and IPSL-CM6A-LR). Eight core extreme precipitation indices were analyzed to quantify changes during the near future (NF: 2021–2050) and far future (FF: 2071–2100) periods. Our research demonstrated that all four models were capable of capturing seasonal patterns and exhibited inherent uncertainty. The annual total precipitation (PRCPTOT) in mountainous regions showed minimal variation, while desert areas were projected to experience a 2-6-fold increase in precipitation in the NF and FF. The Precipitation Intensity Index (SDII) weakened by approximately −10% in mountainous areas but strengthened by around +10% in desert regions. Most mountainous areas showed an increase in the maximum consecutive dry days (CDD), whereas desert regions exhibited extended maximum consecutive wet days (CWD). Moderate rainfall (P1025) variations primarily ranged between −5% and +20%, with greater fluctuations in desert areas. Heavy rainfall (PG25) fluctuated between −40% and +40%, reflecting stark contrasts in extreme precipitation between arid basins and mountainous zones. The maximum 1-day precipitation (Rx1day) and maximum 5-day precipitation (Rx5day) both showed significant increases, which indicated heightened risks from extreme rainfall events in the future. Moreover, the IRB region experienced increased total precipitation, enhanced rainfall intensity, more frequent alternations between drought and precipitation, more frequent moderate-to-heavy rainfall days, and higher daily precipitation extremes in both the NF and FF periods. These findings provide critical data for regional development planning and emergency response strategy formulation. Full article
(This article belongs to the Section Hydrology)
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17 pages, 451 KiB  
Review
Biomarkers and Neuropsychological Tools in Attention-Deficit/Hyperactivity Disorder: From Subjectivity to Precision Diagnosis
by Ion Andrei Hurjui, Ruxandra Maria Hurjui, Loredana Liliana Hurjui, Ionela Lacramioara Serban, Irina Dobrin, Mihai Apostu and Romeo Petru Dobrin
Medicina 2025, 61(7), 1211; https://doi.org/10.3390/medicina61071211 - 3 Jul 2025
Viewed by 320
Abstract
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with chronic inattention, hyperactivity, and impulsivity and is linked with significant functional impairment. Despite being highly prevalent, diagnosis of ADHD continues to rely on subjective assessment reports of behavior and is often delayed or inaccurate. [...] Read more.
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with chronic inattention, hyperactivity, and impulsivity and is linked with significant functional impairment. Despite being highly prevalent, diagnosis of ADHD continues to rely on subjective assessment reports of behavior and is often delayed or inaccurate. This review summarizes current advances in biomarkers and neuropsychological tests for the improvement of ADHD diagnosis and treatment. Key biomarkers are neuroimaging methods (e.g., structural and functional MRI), electrophysiological measures (e.g., EEG, ERP), and biochemical measures (e.g., cortisol, vitamin D). Additionally, novel experimental measures, e.g., eye-tracking, pupillometry, and microbiome analysis, hold the promise to be objective and dynamic measures of ADHD symptoms. The review also comments on the impact of the burden of ADHD on quality of life, e.g., emotional well-being, academic achievement, and social functioning. Additionally, differences between individuals, such as age, sex, comorbidities, and the impact of social and family support, are also addressed in relation to ADHD outcomes. In summary, we highlight the potential of these emerging biomarkers and tools to revolutionize ADHD diagnosis and guide personalized treatment strategies. These insights have significant implications for improving patient outcomes. Full article
(This article belongs to the Section Psychiatry)
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11 pages, 3678 KiB  
Article
Plug-and-Play Self-Supervised Denoising for Pulmonary Perfusion MRI
by Changyu Sun, Yu Wang, Cody Thornburgh, Ai-Ling Lin, Kun Qing, John P. Mugler and Talissa A. Altes
Bioengineering 2025, 12(7), 724; https://doi.org/10.3390/bioengineering12070724 - 1 Jul 2025
Viewed by 361
Abstract
Pulmonary dynamic contrast-enhanced (DCE) MRI is clinically useful for assessing pulmonary perfusion, but its signal-to-noise ratio (SNR) is limited. A self-supervised learning network-based plug-and-play (PnP) denoising model was developed to improve the image quality of pulmonary perfusion MRI. A dataset of patients with [...] Read more.
Pulmonary dynamic contrast-enhanced (DCE) MRI is clinically useful for assessing pulmonary perfusion, but its signal-to-noise ratio (SNR) is limited. A self-supervised learning network-based plug-and-play (PnP) denoising model was developed to improve the image quality of pulmonary perfusion MRI. A dataset of patients with suspected pulmonary diseases was used. Asymmetric pixel-shuffle downsampling blind-spot network (AP-BSN) training inputs were two-dimensional background-subtracted perfusion images without clean ground truth. The AP-BSN is incorporated into a PnP model (PnP-BSN) for balancing noise control and image fidelity. Model performance was evaluated by SNR, sharpness, and overall image quality from two radiologists. The fractal dimension and k-means segmentation of the pulmonary perfusion images were calculated for comparing denoising performance. The model was trained on 29 patients and tested on 8 patients. The performance of PnP-BSN was compared to denoising convolutional neural network (DnCNN) and a Gaussian filter. PnP-BSN showed the highest reader scores in terms of SNR, sharpness, and overall image quality as scored by two radiologists. The expert scoring results for DnCNN, Gaussian, and PnP-BSN were 2.25 ± 0.65, 2.44 ± 0.73, and 3.56 ± 0.73 for SNR; 2.62 ± 0.52, 2.62 ± 0.52, and 3.38 ± 0.64 for sharpness; and 2.16 ± 0.33, 2.34 ± 0.42, and 3.53 ± 0.51 for overall image quality (p < 0.05 for all). PnP-BSN outperformed DnCNN and a Gaussian filter for denoising pulmonary perfusion MRI, which led to improved quantitative fractal analysis. Full article
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20 pages, 1795 KiB  
Systematic Review
An Updated Systematic Review and Meta-Analysis of Diagnostic Accuracy of Dynamic Contrast Enhancement and Diffusion-Weighted MRI in Differentiating Benign and Malignant Non-Mass Enhancement Lesions
by Vera Nevyta Tarigan, Nungky Kusumaningtyas, Nina I. S. H. Supit, Edwin Sanjaya, Malvin Chandra, Callistus Bruce Henfry Sulay and Gilbert Sterling Octavius
J. Clin. Med. 2025, 14(13), 4628; https://doi.org/10.3390/jcm14134628 - 30 Jun 2025
Viewed by 385
Abstract
Objectives: This study systematically evaluates the diagnostic accuracy of dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) values. Methods: The literature search started and ended on 10 June 2024. We searched MEDLINE, Cochrane Library, Pubmed, Science Direct, [...] Read more.
Objectives: This study systematically evaluates the diagnostic accuracy of dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) values. Methods: The literature search started and ended on 10 June 2024. We searched MEDLINE, Cochrane Library, Pubmed, Science Direct, and Google Scholar. Our research question could be formulated as “In women with NME detected by MRI, how accurate are DCE and DWI in ruling in and ruling out malignancy when the diagnosis is compared to histopathology analysis with or without a clinical follow-up?”. The meta-analysis was conducted using the STATA 17 software with the “midas” commands. The study protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO) database. Results: Fifty-four studies involving 6121 NME lesions were analyzed. The combined use of DCE-MRI and DWI demonstrated the highest diagnostic accuracy (AUC: 0.91; 95% CI: 0.88–0.93), followed by DWI alone (AUC: 0.85; 95% CI: 0.81–0.87) and ADC (AUC: 0.77; 95% CI: 0.74–0.81). DCE-MRI alone showed the lowest performance (AUC: 0.68; 95% CI: 0.64–0.72). Significant heterogeneity was observed across all modalities, with I2 values exceeding 95% in several analyses. The likelihood ratio scattergram indicated that no modality reliably confirmed or excluded malignancy. Conclusions: While the combination of DCE-MRI and DWI achieves the highest diagnostic accuracy, no modality can reliably differentiate benign from malignant NME lesions. Standardized imaging protocols and refined diagnostic descriptors are needed for clinical improvement. Full article
(This article belongs to the Special Issue Breast Cancer: Clinical Diagnosis and Personalized Therapy)
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20 pages, 3490 KiB  
Article
Isocitrate Dehydrogenase-Wildtype Glioma Adapts Toward Mutant Phenotypes and Enhanced Therapy Sensitivity Under D-2-Hydroxyglutarate Exposure
by Geraldine Rocha, Clara Francés-Gómez, Javier Megías, Lisandra Muñoz-Hidalgo, Pilar Casanova, Jose F. Haro-Estevez, Vicent Teruel-Martí, Daniel Monleón and Teresa San-Miguel
Biomedicines 2025, 13(7), 1584; https://doi.org/10.3390/biomedicines13071584 - 28 Jun 2025
Viewed by 445
Abstract
Background/Objectives: Isocitrate dehydrogenase (IDH) mutations are hallmark features in subsets of gliomas, producing the oncometabolite D-2-hydroxyglutarate (2HG). Although IDH mutations are associated with better clinical outcomes, their relationship with tumor progression is complex. This study aimed to investigate, in vitro [...] Read more.
Background/Objectives: Isocitrate dehydrogenase (IDH) mutations are hallmark features in subsets of gliomas, producing the oncometabolite D-2-hydroxyglutarate (2HG). Although IDH mutations are associated with better clinical outcomes, their relationship with tumor progression is complex. This study aimed to investigate, in vitro and in vivo, the phenotypic consequences of IDH mutation and 2HG exposure in glioblastoma (GBM) under normoxic and hypoxic conditions and under temozolomide (TMZ) and radiation exposure. Methods: Experiments were conducted using IDH-wildtype (IDH-wt) and IDH-mutant (IDH-mut) glioma cell lines under controlled oxygen conditions. Functional assays included cell viability, cell cycle analysis, apoptosis profiling, migration, and surface marker expression via flow cytometry. Orthotopic xenografts were established in immunocompromised mice to assess in vivo tumor growth and morphology, followed by MRI and histological analysis. Treatments included TMZ, radiation, and 2HG at varying concentrations. Statistical analyses were performed using SPSS and RStudio. Results:IDH-wt cells exhibited faster proliferation and greater adaptability under hypoxia, while IDH-mut cells showed cell cycle arrest and limited growth. 2HG recapitulated IDH-mut features in IDH-wt cells, including increased apoptosis under TMZ, reduced proliferation, and altered CD24/CD44 expression. In vivo, IDH-wt tumors were larger and more infiltrative, while 2HG administration reduced tumor volume and promoted compact morphology. Notably, migration was initially similar across genotypes but increased in IDH-mut and 2HG-treated IDH-wt cells over time, though suppressed under therapeutic stress. Conclusions: IDH mutation and 2HG modulate glioma cell biology, including cell cycle dynamics, proliferation rates, migration, and apoptosis. While the IDH mutation and its metabolic product confer initial growth advantages, they enhance treatment sensitivity and reduce invasiveness, highlighting potential vulnerabilities for targeted therapy. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapy of Gliomas)
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25 pages, 418 KiB  
Review
Emerging Diagnostic Approaches for Musculoskeletal Disorders: Advances in Imaging, Biomarkers, and Clinical Assessment
by Rahul Kumar, Kiran Marla, Kyle Sporn, Phani Paladugu, Akshay Khanna, Chirag Gowda, Alex Ngo, Ethan Waisberg, Ram Jagadeesan and Alireza Tavakkoli
Diagnostics 2025, 15(13), 1648; https://doi.org/10.3390/diagnostics15131648 - 27 Jun 2025
Viewed by 701
Abstract
Musculoskeletal (MSK) disorders remain a major global cause of disability, with diagnostic complexity arising from their heterogeneous presentation and multifactorial pathophysiology. Recent advances across imaging modalities, molecular biomarkers, artificial intelligence applications, and point-of-care technologies are fundamentally reshaping musculoskeletal diagnostics. This review offers a [...] Read more.
Musculoskeletal (MSK) disorders remain a major global cause of disability, with diagnostic complexity arising from their heterogeneous presentation and multifactorial pathophysiology. Recent advances across imaging modalities, molecular biomarkers, artificial intelligence applications, and point-of-care technologies are fundamentally reshaping musculoskeletal diagnostics. This review offers a novel synthesis by unifying recent innovations across multiple diagnostic imaging modalities, such as CT, MRI, and ultrasound, with emerging biochemical, genetic, and digital technologies. While existing reviews typically focus on advances within a single modality or for specific MSK conditions, this paper integrates a broad spectrum of developments to highlight how use of multimodal diagnostic strategies in combination can improve disease detection, stratification, and clinical decision-making in real-world settings. Technological developments in imaging, including photon-counting detector computed tomography, quantitative magnetic resonance imaging, and four-dimensional computed tomography, have enhanced the ability to visualize structural and dynamic musculoskeletal abnormalities with greater precision. Molecular imaging and biochemical markers such as CTX-II (C-terminal cross-linked telopeptides of type II collagen) and PINP (procollagen type I N-propeptide) provide early, objective indicators of tissue degeneration and bone turnover, while genetic and epigenetic profiling can elucidate individual patterns of susceptibility. Point-of-care ultrasound and portable diagnostic devices have expanded real-time imaging and functional assessment capabilities across diverse clinical settings. Artificial intelligence and machine learning algorithms now automate image interpretation, predict clinical outcomes, and enhance clinical decision support, complementing conventional clinical evaluations. Wearable sensors and mobile health technologies extend continuous monitoring beyond traditional healthcare environments, generating real-world data critical for dynamic disease management. However, standardization of diagnostic protocols, rigorous validation of novel methodologies, and thoughtful integration of multimodal data remain essential for translating technological advances into improved patient outcomes. Despite these advances, several key limitations constrain widespread clinical adoption. Imaging modalities lack standardized acquisition protocols and reference values, making cross-site comparison and clinical interpretation difficult. AI-driven diagnostic tools often suffer from limited external validation and transparency (“black-box” models), impacting clinicians’ trust and hindering regulatory approval. Molecular markers like CTX-II and PINP, though promising, show variability due to diurnal fluctuations and comorbid conditions, complicating their use in routine monitoring. Integration of multimodal data, especially across imaging, omics, and wearable devices, remains technically and logistically complex, requiring robust data infrastructure and informatics expertise not yet widely available in MSK clinical practice. Furthermore, reimbursement models have not caught up with many of these innovations, limiting access in resource-constrained healthcare settings. As these fields converge, musculoskeletal diagnostics methods are poised to evolve into a more precise, personalized, and patient-centered discipline, driving meaningful improvements in musculoskeletal health worldwide. Full article
(This article belongs to the Special Issue Advances in Musculoskeletal Imaging: From Diagnosis to Treatment)
27 pages, 708 KiB  
Systematic Review
Mapping the Olfactory Brain: A Systematic Review of Structural and Functional Magnetic Resonance Imaging Changes Following COVID-19 Smell Loss
by Hanani Abdul Manan, Rafaela de Jesus, Divesh Thaploo and Thomas Hummel
Brain Sci. 2025, 15(7), 690; https://doi.org/10.3390/brainsci15070690 - 27 Jun 2025
Viewed by 426
Abstract
Background: Olfactory dysfunction (OD)—including anosmia and hyposmia—is a common and often persistent outcome of viral infections. This systematic review consolidates findings from structural and functional MRI studies to explore how COVID-19 SARS-CoV-2-induced smell loss alters the brain. Considerable heterogeneity was observed across studies, [...] Read more.
Background: Olfactory dysfunction (OD)—including anosmia and hyposmia—is a common and often persistent outcome of viral infections. This systematic review consolidates findings from structural and functional MRI studies to explore how COVID-19 SARS-CoV-2-induced smell loss alters the brain. Considerable heterogeneity was observed across studies, influenced by differences in methodology, population characteristics, imaging timelines, and OD classification. Methods: Following PRISMA guidelines, we conducted a systematic search of PubMed/MEDLINE, Scopus, and Web of Science to identify MRI-based studies examining COVID-19’s SARS-CoV-2 OD. Twenty-four studies were included and categorized based on imaging focus: (1) olfactory bulb (OB), (2) olfactory sulcus (OS), (3) grey and white matter changes, (4) task-based brain activation, and (5) resting-state functional connectivity. Demographic and imaging data were extracted and analyzed accordingly. Results: Structural imaging revealed consistent reductions in olfactory bulb volume (OBV) and olfactory sulcus depth (OSD), especially among individuals with OD persisting beyond three months, suggestive of inflammation and neurodegeneration in olfactory-associated regions like the orbitofrontal cortex and thalamus. Functional MRI studies showed increased connectivity in early-stage OD within regions such as the piriform and orbitofrontal cortices, possibly reflecting compensatory activity. In contrast, prolonged OD was associated with reduced activation and diminished connectivity, indicating a decline in olfactory processing capacity. Disruptions in the default mode network (DMN) and limbic areas further point to secondary cognitive and emotional effects. Diffusion tensor imaging (DTI) findings—such as decreased fractional anisotropy (FA) and increased mean diffusivity (MD)—highlight white matter microstructural compromise in individuals with long-term OD. Conclusions: COVID-19’s SARS-CoV-2 olfactory dysfunction is associated with a range of cerebral alterations that evolve with the duration and severity of smell loss. Persistent dysfunction correlates with greater neural damage, underscoring the need for longitudinal neuroimaging studies to better understand recovery dynamics and guide therapeutic strategies. Full article
(This article belongs to the Section Sensory and Motor Neuroscience)
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8 pages, 1848 KiB  
Article
Different Kinetics of Complement Opsonization, Immune Uptake, and IL-6 Cytokine Response After Bolus Injection of Superparamagnetic Iron Oxide Nanoworms in Mice
by Yue Li and Dmitri Simberg
J. Nanotheranostics 2025, 6(3), 16; https://doi.org/10.3390/jnt6030016 - 27 Jun 2025
Cited by 1 | Viewed by 248 | Correction
Abstract
Superparamagnetic iron oxide (SPIO) nanoparticles are a promising platform for drug delivery and magnetic resonance imaging (MRI). However, complement activation and immune recognition remain major barriers to their clinical translation. Previously, we reported that dextran-coated SPIO nanoworms (NWs) trigger potent complement activation and [...] Read more.
Superparamagnetic iron oxide (SPIO) nanoparticles are a promising platform for drug delivery and magnetic resonance imaging (MRI). However, complement activation and immune recognition remain major barriers to their clinical translation. Previously, we reported that dextran-coated SPIO nanoworms (NWs) trigger potent complement activation and infusion reactions. Here, we systematically map the temporal sequence of immune events following SPIO NW administration, including C3 opsonization, granulocyte uptake, and cytokine release. In both in vitro and in vivo models, C3 deposition occurred rapidly, peaking at approximately 5 min post-incubation or post-injection. Higher Fe/plasma ratios led to reduced C3 deposition per particle, although the absolute amount of C3 bound was greater in vivo than in vitro. Notably, C3 dissociation from the particle surface exhibited a consistent half-life of ~14 min, independent of the NW injected dose and circulation time. Immune uptake by blood granulocytes was delayed relative to opsonization, becoming prominent only at 60 min post-injection. Further, cytokine release, measured by plasma IL-6 levels, displayed an even slower profile, with peak expression at 6 h post-injection. Together, these results reveal a distinct sequential immune response to SPIO NWs: rapid C3 opsonization, delayed cellular uptake, and late cytokine response. Understanding these dynamics provides a basis for developing strategies to inhibit complement activation and improve the hemocompatibility of SPIO-based theranostic agents. Full article
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17 pages, 2381 KiB  
Article
Predictive Factors for Response to Percutaneous Bleomycin in Lymphatic–Venous Malformations of the Head and Neck
by Thanat Kanthawang, Yuttapol Hirun, Kittisak Unsrisong, Jirapong Vongsfak and Withawat Vuthiwong
J. Clin. Med. 2025, 14(13), 4505; https://doi.org/10.3390/jcm14134505 - 25 Jun 2025
Viewed by 280
Abstract
Background/Objectives: This study aims to identify baseline imaging parameters, across various imaging modalities, that can predict the response to bleomycin sclerotherapy in patients with head and neck lymphatic–venous malformations (LVMs). Methods: A retrospective analysis of 80 patients (85 lesions) treated at a tertiary [...] Read more.
Background/Objectives: This study aims to identify baseline imaging parameters, across various imaging modalities, that can predict the response to bleomycin sclerotherapy in patients with head and neck lymphatic–venous malformations (LVMs). Methods: A retrospective analysis of 80 patients (85 lesions) treated at a tertiary care center between January 2018 and December 2022 was conducted. Imaging modalities, including CT, MRI, ultrasonography, and dynamic digital radiographic images, were reviewed for lesion characteristics. Factors including lesion type, volume, morphology, location, and contrast opacification patterns were analyzed for their association with treatment response, defined as a >50% reduction in lesion size and symptom improvement. Univariable and multivariable logistic regression analyses were performed. Results: Of 85 lesions, 45 (52.9%) responded to treatment. Univariable analysis showed that pure lymphatic malformations (OR = 6.12, p = 0.004), macrocystic components (OR = 10, p = 0.016), cavitary morphology on dynamic digital radiographic images (OR = 8.90, p < 0.001), neck location (OR = 4, p = 0.03), and deep-seated lesions (OR = 3.69, p = 0.03) were significantly associated with better outcomes. Multivariable analysis identified cavitary morphology as the strongest predictor (p = 0.04). A combination of cavitary morphology, macrocystic components, and pure LM type yielded the highest predictive accuracy (AUC = 0.80, p = 0.03). Conclusions: The presence of lymphatic channels or large cystic venous spaces—such as macrocystic features on imaging or cavitary morphology—along with neck or deep-seated lesion location, predicts a favorable response to bleomycin sclerotherapy in head and neck LVMs. Full article
(This article belongs to the Section Nuclear Medicine & Radiology)
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