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Intracellular Fraction Research Articles

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971 Articles

Published in last 50 years

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  • Extracellular Fraction
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Oscillating gradient spin echo diffusion time effects implicate variations in neurite beading for the heterogeneous reduced diffusion in human acute ischemic stroke lesions.

Monte Carlo simulations and short diffusion time measurements have suggested neurite beading and swelling as the underlying mechanism of reduced diffusion in acute stroke, although the observed diffusion time dependence is often heterogeneous and not yet fully understood. This study aimed to investigate the heterogeneity of diffusion time effects in ischemic lesions and explore the potential microstructural basis with Monte Carlo simulations. Pulsed gradient spin echo (PGSE, diffusion time 40 ms) and oscillating gradient spin echo (OGSE 40 Hz, diffusion time ˜5.1 ms) were acquired within 5 min in 39 acute ischemic stroke patients at 3 T. Mean, axial, and radial diffusivity differences between OGSE and PGSE (ΔMD/ΔAD/ΔRD) were compared between lesion and contralateral tissues (white and gray matter). Monte Carlo diffusion simulations of beaded axons for the experimental waveforms were used to investigate the effects of neurite morphology on time-dependent diffusivity changes. PGSE yielded the typical mean diffusivity (MD) reduction of -40 ± 10% in ischemic lesions, whereas it was less at -29 ± 11% for OGSE 40 Hz. The OGSE-PGSE diffusion time difference was greater in lesions (ΔMD = 0.12 ± 0.06 × 10-3 mm2/s) than contralateral white matter (ΔMD = 0.04 ± 0.06 × 10-3 mm2/s), consistent with larger beading amplitude (0.18-0.43) and intracellular volume fraction (0.61-0.78) in lesions. ΔMD maps revealed regional variation with the largest effects in internal capsule and corona radiata. This study found greater diffusion time effects in ischemic regions with purportedly larger axons. Monte Carlo simulations further support that the pronounced OGSE-PGSE diffusivity differences are expected in large axons with high beading amplitude.

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  • Journal IconMagnetic resonance in medicine
  • Publication Date IconJun 24, 2025
  • Author Icon Mi Zhou + 11
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Mapping the Brain’s Role in Osteoarthritis: New Evidence for Prevention

PurposeThis study explores the causal link between brain structural parameters and Osteoarthritis (OA), aiming to prevent OA progression.Patients and MethodsWe used two-sample Mendelian randomization. In addition to European OA data with a sample size of 484,598, Firth correction OA data from the same source, and SPA correction OA data were included as outcome data. 3913 brain imaging-derived phenotypes (IDPs) from the UK Biobank were used as exposure data. Weighted median, MR Egger, and IVW validated causal correlations. Analyses of sensitivity and heterogeneity validated the robustness of the findings.ResultsThirteen brain regions significantly linked to OA. Increased fractional anisotropy (FA) in the cingulate hippocampal gyrus (OR: 0.99, 95% CI: 0.98–1.00, P = 0.003), orientation diffusion(OD) in the fornix and Stria terminalis (OR: 0.99, 95% CI: 0.98–1.00, P = 0.004) and isotropic volume fraction (ISOVF) (OR: 0.99, 95% CI: 0.99–1.00, P = 0.039) in the fornix, as well as an increase in OD in the posterior thalamic radiation (R) (OR: 0.99, 95% CI: 0.98–1.00, P = 0.047) reduce OA risk as protective factors. Increased subparietal lobule area (OR: 0.99, 95% CI: 0.98–1.00, P = 0.045) and middle temporal gyrus volume (OR: 0.98, 95% CI: 0.97–1.00, P = 0.029) also demonstrated a protective effect against OA. Conversely, OA risk was increased by increases in the medial thalamic tract’s OD (OR: 1.01, 95% CI: 1.00–1.02, P = 0.034), the cerebral peduncle’s intracellular volume fraction (ICVF) (OR: 1.01, 95% CI: 1.00–1.01, P = 0.010), the anterior limb of the internal capsule’s ISOVF (OR: 1.01, 95% CI: 1.00–1.01, P = 0.033), and the posterior thalamic radiation(L) ‘s MO (OR: 1.02, 95% CI: 1.00–1.03, P = 0.024). Interestingly, lateral orbitofrontal volume decreased (R: OR: 0.99, 95% CI: 0.98–1.00, P = 0.013; L: OR: 0.99, 95% CI: 0.98–1.00, P = 0.038), while medial orbitofrontal increased risk (OR: 1.02, 95% CI: 1.00–1.04, P = 0.024).ConclusionOur findings provide genetic evidence for the prevention of OA based on the bone-brain axis and suggest a clinical strategy for integrated pain-psychomotor intervention through neural nociceptive modulation, limbic circuit stabilization, and motor pathway enhancement.

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  • Journal IconJournal of Multidisciplinary Healthcare
  • Publication Date IconJun 24, 2025
  • Author Icon Jingkai Di + 6
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Associations of Handgrip Strength and Testosterone With Cerebral White Matter Hyperintensity and Microstructural Injury

ABSTRACTBackgroundWhite matter hyperintensity (WMH) is one of the key imaging markers of cerebral small vessel disease (CSVD) and white matter microstructural injury may occur earlier than WMH. However, the associations of handgrip strength (HGS) and serum total testosterone (STT) with WMH and microstructural injury have not been thoroughly investigated. Therefore, we aimed to explore the associations of HGS and STT with WMH and microstructural injury, measured by fractional anisotropy (FA), mean diffusivity (MD), intracellular volume fraction (ICVF), and isotropic volume fraction (ISOVF).MethodsA total of 34 832 participants from the UK Biobank (aged 64.15 ± 7.75 years, 50.9% male) were included in the study. Cross‐sectional analyses were conducted using three linear regression models to assess the relationships between HGS, STT and neuroimaging outcomes. Sensitivity analyses were performed to validate the robustness of the linear regression results. Longitudinal, mediation and Mendelian randomization (MR) analyses were conducted to explore the longitudinal impact of HGS on WMH, the mediating effects of STT between HGS and neuroimaging outcomes, and probable causal relationships between HGS, STT and WMH.ResultsA greater HGS was linearly associated with a smaller WMH volume (β = −0.006642, p < 0.001) and fuller microstructure (p < 0.001). These relationships persisted when stratified by sex or age decade and were supported by the results of the longitudinal analysis (β = −26.4, p = 0.0145). In females, STT was found to be linearly negatively related to WMH volume (β = −0.109, p < 0.001), MD and ISOVF, and linearly positively related to FA and ICVF (p < 0.001). In males, STT was linearly negatively linked to WMH volume (β = −0.016, p < 0.001) and MD (β = −1.6 ×10−7, p = 0.007), and positively associated to ICVF (β = 0.00012, p = 0.043). STT mediated the association between HGS and WMH volume (mediation proportion: 1.06% in males and 1.57% in females), and the possible causality was suggested for males through MR analysis: the positive causality between HGS and STT (p = 0.0394) and the negative causality between STT and WMH (p = 0.0787).ConclusionsOur study revealed that greater HGS was linearly associated with reduced WMH volume and less white matter microstructural injury, mediated by STT. Improving muscle function may contribute to deferring white matter damage and preventing stroke and dementia, offering a feasible secondary prevention measure for CSVD.

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  • Journal IconJournal of Cachexia, Sarcopenia and Muscle
  • Publication Date IconJun 1, 2025
  • Author Icon Yuna Li + 9
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Microstructural Characterization of Short Association Fibers Related to Long‐Range White Matter Tracts in Normative Development

ABSTRACTShort association fibers (SAFs) in the superficial white matter play a key role in mediating local cortical connections but have not been well‐studied as innovations in whole‐brain diffusion tractography have only recently been developed to study superficial white matter. Characterizing SAFs and their relationship to long‐range white matter tracts is crucial to advance our understanding of neurodevelopment during the period from childhood to young adulthood. This study aims to (1) map SAFs in relation to long‐range white matter tracts, (2) characterize typical neurodevelopmental changes across these white matter pathways, and (3) investigate the relationship between microstructural changes in SAFs and long‐range white matter tracts. Leveraging a cohort of 616 participants ranging in age from 5.6 to 21.9 years old, we performed quantitative diffusion tractography and advanced diffusion modeling with diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI). Robust linear regression models were applied to analyze microstructural features, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), intracellular volume fraction (ICVF), isotropic volume fraction (ISOVF), and orientation dispersion index (ODI). Our results reveal that both SAFs and long‐range tracts exhibit similar overall developmental patterns, characterized by negative associations of MD, AD, and RD with age and positive associations of FA, ICVF, ISOVF, and ODI with age. Notably, FA, AD, and ODI exhibit significant differences between SAFs and long‐range tracts, suggesting distinct neurodevelopmental trajectories between superficial and deep white matter. In addition, significant differences were found in MD, RD, and ICVF between males and females, highlighting variations in neurodevelopment. This normative study provides insights into typical microstructural changes of SAFs and long‐range white matter tracts during development, laying a foundation for future research to investigate atypical development and dysfunction in disease pathology.

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  • Journal IconHuman Brain Mapping
  • Publication Date IconJun 1, 2025
  • Author Icon Chloe Cho + 5
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The gray matter microstructure and psychological resilience in patients with depression: A preliminary study using DSI/NODDI imaging.

The gray matter microstructure and psychological resilience in patients with depression: A preliminary study using DSI/NODDI imaging.

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  • Journal IconJournal of psychiatric research
  • Publication Date IconJun 1, 2025
  • Author Icon Liaoming Gao + 12
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Bioinformatics analyses of the proteome of Holothuria tubulosa coelomic fluid and the first evidence of primary cilium in coelomocyte cells

The holothurian immune system is characterized by complex defense mechanisms that act through humoral and cellular pathways. Coelomocites are the cellular component of coelomic fluid, and they are involved in host defense, stress response, wound healing, organ regeneration, and tissue homeostasis. The close phylogenetic relationship between Holothuria tubulosa and chordate phylum makes it a good model for studying the evolution of immune processes. To elucidate the immune landscape in H. tubulosa, we applied an approach combining proteomic analysis of coelomic fluid separated into cellular fraction and extracellular fraction and bioinformatics and in silico analyses. A Search Tool for the Retrieval of Interacting Genes/Protein analysis indicated a highly functional homology to the human protein of immune recognition factors, non-canonical immune-related proteins, signaling molecules, and effector protein, cytoskeleton, and actin remodeling, and provided the first evidence in invertebrate immune cells of an intracellular protein fraction linked to ancestral structure resembling primary cilium involved in cell signaling.

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  • Journal IconFrontiers in Immunology
  • Publication Date IconMay 15, 2025
  • Author Icon Laura La Paglia + 9
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Application of neurite orientation dispersion and density imaging in characterizing brain microstructural changes in classical trigeminal neuralgia and a comparison between the left and right sides.

Diffusion tensor imaging can detect brain white matter changes in classical trigeminal neuralgia (TN). However, it lacks specificity for individual tissue microstructural features, such as neurite density, orientation dispersions, and extracellular edema. Neurite orientation dispersion and density imaging (NODDI), a novel diffusion magnetic resonance imaging (MRI) technique, can provide these distinct indices. We characterized brain microstructural alterations in patients with unilateral TN using NODDI and compared the difference between left- and right-side TN (LTN and RTN, respectively). Diffusion-weighted imaging was performed on 39 patients with LTN, 37 patients with RTN, and 37 healthy controls. Neurite orientation dispersion and density imaging-related indices, including the intracellular volume fraction (Vic), orientation dispersion index (ODI), and isotropic volume fraction (Fiso), were estimated and compared using tract-based spatial statistics and voxel-based region-of-interest analysis. The LTN and RTN groups exhibited microstructural abnormalities in white and gray matter as measured by decreased fractional anisotropy and Vic and elevated Fiso, respectively. These alterations were associated with clinical features and were mainly located in the frontal lobe, corona radiata, internal capsule, and thalamus. The angular variation of neurites, characterized by ODI, exhibited no significant changes between TN and control groups. Patients with classical TN of either side exhibited reduced Vic and increased Fiso, which indicated decreased density of axons and dendrites and neuroinflammatory edema in bilateral hemispheres. Neurite orientation dispersion and density imaging is a useful technique for in vivo diffusion MRI of white and gray matter in the brain, which provides additional metrics and information closely related to the tissue microstructure that merits further study of TN pathogenesis.

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  • Journal IconPain
  • Publication Date IconMay 6, 2025
  • Author Icon Ying Xiong + 5
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A deep learning approach to multi-fiber parameter estimation and uncertainty quantification in diffusion MRI.

Diffusion MRI (dMRI) is the primary imaging modality used to study brain microstructure in vivo. Reliable and computationally efficient parameter inference for common dMRI biophysical models is a challenging inverse problem, due to factors such as variable dimensionalities (reflecting the unknown number of distinct white matter fiber populations in a voxel), low signal-to-noise ratios, and non-linear forward models. These challenges have led many existing methods to use biologically implausible simplified models to stabilize estimation, for instance, assuming shared microstructure across all fiber populations within a voxel. In this work, we introduce a novel sequential method for multi-fiber parameter inference that decomposes the task into a series of manageable subproblems. These subproblems are solved using deep neural networks tailored to problem-specific structure and symmetry, and trained via simulation. The resulting inference procedure is largely amortized, enabling scalable parameter estimation and uncertainty quantification across all model parameters. Simulation studies and real imaging data analysis using the Human Connectome Project (HCP) demonstrate the advantages of our method over standard alternatives. In the case of the standard model of diffusion, our results show that under HCP-like acquisition schemes, estimates for extra-cellular parallel diffusivity are highly uncertain, while those for the intra-cellular volume fraction can be estimated with relatively high precision.

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  • Journal IconMedical image analysis
  • Publication Date IconMay 1, 2025
  • Author Icon William Consagra + 2
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Cluster Analysis of VERDICT MRI for Cancer Tissue Characterization in Neuroendocrine Tumors.

Diffusion MRI models accounting for varying diffusion times and high b-values, such as VERDICT, hold potential for non-invasively characterizing tumor tissue types, potentially enabling improved tumor grading, and treatment evaluation. Furthermore, cluster analysis can aid in identifying multidimensional patterns in the diffusion MRI (dMRI) data that are not apparent when analyzing individual parameters in isolation. The aim of this study was to evaluate how well cluster analysis of VERDICT parameters can be used for intratumor tissue characterization compared to ADC in a mouse model of human small intestine neuroendocrine tumor (GOT1), and to validate the method by histological analysis. Mice implanted with GOT1 were irradiated and subsequently imaged using a dMRI protocol designed for estimation of VERDICT parameters and ADC values. Histological analysis using hematoxylin and eosin (H&E), Masson's trichrome, and Ki67 staining identified three distinct tumor tissue types: necrotic, fibrotic, and viable tumor tissue. ROIs were drawn on regions of high and low ADC, which spatially matched with necrosis or fibrosis, and viable tumor tissue, respectively. Among the VERDICT parameters, the cell radius index (R) was most effective in distinguishing between necrotic and fibrotic tissue, whereas the intracellular fraction (fIC) was the most effective in differentiating viable from non-viable tissue. A Gaussian mixture model (GMM) of three clusters, representing each tumor tissue type, was fitted to R and fIC of all tumor voxel data. VERDICT cluster maps corresponded well with the histology classification maps overall. Fibrotic tissue corresponded best with the cluster of low fIC and low R, necrotic tissue with the cluster of low fIC and high R, and viable tumor tissue with the cluster of high fIC and intermediate R. In conclusion, GMM cluster analysis of VERDICT MRI data shows potential in differentiating necrotic, fibrotic, and viable tumor tissue in irradiated GOT1 tumors.

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  • Journal IconNMR in biomedicine
  • Publication Date IconApr 28, 2025
  • Author Icon Lukas Lundholm + 5
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Compartmentalization of sodium in the human brain: a mini-review of 23Na-MRI methods

Sodium magnetic resonance imaging is a non-invasive technique that provides information about sodium levels in tissues. It has significant applications in brain research due to the important role of sodium in both normal brain function and pathological processes. Total sodium concentration is the most widely used derived metric; it offers insights into sodium content across different brain regions. However, the functional role of sodium is closely linked to its distribution within intra- and extracellular spaces. Sodium osmotic homeostasis affects the intracellular volume fraction, a parameter that can be altered in various neurological disorders. Unfortunately, distinguishing intracellular from extracellular sodium nuclear magnetic resonance signals is challenging, even with the use of contrast agents. In recent years, several methodologies have been proposed to study sodium compartmentalization in humans, typically involving tailored acquisition techniques and modeling approaches. This mini-review provides a brief overview of the challenges, methodologies, and potential applications of compartmentalized sodium MR imaging in human neuroscience.

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  • Journal IconFrontiers in Physics
  • Publication Date IconApr 23, 2025
  • Author Icon Irene Egidi + 2
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Saccharomyces cerevisiae’s Response to Dysprosium Exposure

Lanthanide biosorption is important for recycling value-added materials. Previously, we analyzed dysprosium (Dy) absorption in screening strains of the unpopular yeast species Schizoblastosporion sp. However, it would be more desirable to use the well-known yeast Saccharomyces cerevisiae to make an easy-to-breed and efficient Dy-absorbing strain. Thus, we analyzed the physiological response and gene regulation of S. cerevisiae under Dy-absorbing conditions. The Dy content was measured using an inductively coupled plasma atomic emission spectrometer (ICP-AES). Transcriptional regulation was compared under Dy-absorbing and non-absorbing conditions through mRNA analysis and quantitative real-time polymerase chain reaction (qRT-PCR). In the yeast cells, approximately 40% of the Dy was located in the cell wall fraction, and the remaining 60% was located in the intracellular fraction. qRT-PCR analysis showed that the expression of four genes, NCW2, PIR1, CRH1, and OLE1, was upregulated, and that of ATP14 was downregulated. These results suggest that NCW2, PIR1, and CRH1 were responsible for cell wall rearrangement; OLE1 initiated repair of the oxidative damage to the membrane lipids; and intracellular oxidation was caused by an imperfect ATP14 product.

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  • Journal IconApplied Sciences
  • Publication Date IconApr 17, 2025
  • Author Icon Masao Kishida + 1
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When CEST meets diffusion: Multi‐echo diffusion‐encoded CEST (dCEST) MRI to measure intracellular and extracellular CEST signal distributions

PurposeTo develop a multi‐echo, diffusion‐encoded chemical exchange saturation transfer (dCEST) imaging technique for estimating the intracellular and extracellular/intravascular contributions to the conventional CEST signal.MethodsA dCEST pulse sequence was developed to quantify the signal fractions, transverse relaxation times (T2), and apparent diffusion coefficient (ADC) of the intracellular and extracellular/intravascular water compartments. dCEST images were acquired across a wide range of TE, b‐values, RF saturation strengths, and frequency offsets. The data were analyzed using a two‐compartment model with distinct diffusivities and T2 values. Intracellular and extracellular fractions of conventional water‐saturation spectra (Z‐spectra) and corresponding amide proton transfer (APT) signals were estimated from human brain scans of healthy volunteers at 3 T.ResultsThe multi‐echo diffusion results showed that the intracellular water fractions were significantly higher than the extracellular water fractions, whereas the intracellular T2 values were shorter than those of the extracellular/intravascular compartments. The ADC for the intracellular compartment was significantly lower than that of the extracellular compartment. The dCEST analysis showed that the average intracellular and extracellular fractions of the Z‐spectra were 85 ± 7% and 15 ± 4%, respectively. The overall intracellular APT‐weighted values were higher than the total (i.e., intracellular + extracellular) APT‐weighted values.ConclusionsThe dCEST imaging technique provides valuable insight into the source of signals in conventional CEST MRI, offering potential utility for clinical applications.

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  • Journal IconMagnetic Resonance in Medicine
  • Publication Date IconApr 14, 2025
  • Author Icon Sultan Z Mahmud + 1
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Secretome analysis of the chitinolytic machinery of Chitiniphilus shinanonensis and its implication in chitooligosaccharide production.

Secretome analysis of the chitinolytic machinery of Chitiniphilus shinanonensis and its implication in chitooligosaccharide production.

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  • Journal IconCarbohydrate polymers
  • Publication Date IconApr 1, 2025
  • Author Icon T Swaroopa Rani + 5
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Development of a Nomogram for Predicting Tuberous Sclerosis Complex Genotypes in Children Using Advanced Diffusion MRI and Clinical Data.

Development of a Nomogram for Predicting Tuberous Sclerosis Complex Genotypes in Children Using Advanced Diffusion MRI and Clinical Data.

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  • Journal IconAcademic radiology
  • Publication Date IconApr 1, 2025
  • Author Icon Hui Sun + 14
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Accelerated MR cell size imaging through parallel acquisition technique (PAT) and simultaneous multi-slice (SMS) with local principal component analysis (LPCA) enhancement.

Accelerated MR cell size imaging through parallel acquisition technique (PAT) and simultaneous multi-slice (SMS) with local principal component analysis (LPCA) enhancement.

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  • Journal IconMagnetic resonance imaging
  • Publication Date IconApr 1, 2025
  • Author Icon Tianxiong Wu + 9
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Advantages of time-dependent diffusion MRI for quantitative microstructural mapping in breast tumors.

Time-dependent diffusion MRI (TD-MRI) can measure tumor tissue microstructure, but its effectiveness in differentiating benign from malignant breast tumors is unclear. This study aims to investigate the diagnostic value of TD-MRI microstructural features for distinguishing between benign and malignant breast tumors. This prospective study included 44 patients with malignant breast tumors and 28 with benign tumors. All subjects underwent the IMPULSED protocol on a 3.0-T MRI scanner. Imaging data were analyzed using least squares fitting in MATLAB, yielding Dex (extracellular diffusivity), Vin (intracellular volume fraction), Dmean (cell diameter), Vin/Dmean, and ADC values. The molecular subtypes of breast cancer are classified based on immunohistochemistry (IHC) results. Malignant tumors exhibited significantly lower Dmean (17.37 ± 2.74 µm vs. 22.47 ± 3.85µm, p<0.0001), higher Vin (0.41 ± 0.13% vs. 0.19 ± 0.10%, p<0.0001), and higher Vin/Dmean (2.13 ± 0.66 vs. 0.93 ± 0.61, p<0.0001) compared to benign tumors. No significant difference was found in Dex (2.15 ± 0.28 um2/ms vs. 2.25 ± 0.31 um2/ms, p>0.05). Strong correlations were observed: positive between ADC and Dmean, and negative between ADC and both Vin and Vin/Dmean. AUC values for Vin (0.92; 95% CI: 0.86-0.99), and Vin/Dmean (0.91; 95% CI: 0.83-0.98) surpassed those for ADC. TD-MRI microstructure mapping effectively differentiates benign from malignant breast tumors, highlighting its potential to improve diagnostic accuracy for lesions.

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  • Journal IconFrontiers in oncology
  • Publication Date IconMar 25, 2025
  • Author Icon Lei Bao + 10
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Imaging Microstructural Parameters of Breast Tumor in Patient Using Time-Dependent Diffusion: A Feasibility Study.

Objectives: To explore the feasibility of time-dependent diffusion in clinical applications of breast MRI, as well as the capacity of quantitative microstructural mapping for characterizing the cellular properties in malignant and benign breast tumors. Methods: 38 patients with 45 lesions were enrolled. Diffusion MRI acquisition was conducted with a combination of pulsed gradient spin-echo sequences (PGSE) and oscillating gradient spin-echo (OGSE) on a 3T MRI scanner. The microstructural parameters including cellularity extracellular diffusivity (Dex), mean cell size, intracellular volume fraction (νin), and the apparent diffusion coefficient (ADC) values were calculated. Each parameter was compared using the unpaired t-test between malignant and benign tumors. The area under the receiver operating characteristic curve (AUC) values was used to evaluate the diagnostic performance of different indices. Results: The mean diameter, Dex, ADC0Hz, ADC25Hz, and ADC50Hz were significantly lower in the malignant group than in the benign group (p < 0.001), while νin and cellularity were significantly higher in the malignant group (p < 0.001). All the microstructural parameters and time-dependent ADC values achieved high accuracy in differentiating between malignant and benign tumors of the breast. For microstructural parameters, the AUC of the cellularity was greater than others (AUC = 0.936). In an immunohistochemical subgroup comparison, the PR-positive group had significantly lower νin and cellularity, and significantly elevated Dex and ADC0Hz compared to the negative groups (p < 0.05). When combining diffusion parameters (cellularity, diameter, and ADC25Hz), the highest diagnostic performance was obtained with an AUC of 0.969. Conclusions: DWI with a short diffusion time is capable of providing additional microstructural parameters in differentiating between benign and malignant breast tumors. The time-dependent diffusion MRI parameters have the potential to serve as a non-invasive tool to probe the differences in the internal structures of breast lesions.

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  • Journal IconDiagnostics (Basel, Switzerland)
  • Publication Date IconMar 24, 2025
  • Author Icon Shuyi Peng + 5
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Enduring differential patterns of neuronal loss and myelination along 6-month pulsatile gonadotropin-releasing hormone therapy in individuals with Down syndrome

Despite major progress in understanding the impact of the triplicated chromosome 21 on the brain and behaviour in Down syndrome, our knowledge of the underlying neurobiology in humans is still limited. We sought to address some of the pertinent questions about the drivers of brain structure differences and their associations with cognitive function in Down syndrome. To this aim, in a pilot magnetic resonance imaging (MRI) study, we monitored brain anatomy in individuals with Down syndrome receiving pulsatile gonadotropin-releasing hormone (GnRH) therapy over 6 months in comparison with typically developed age- and sex-matched healthy controls. We analysed cross-sectional (Down syndrome/healthy controls n = 11/27; Down syndrome—2 females/9 males, age 26.7 ± 5.0 years old; healthy controls—8 females/19 males, age 24.1 ± 2.5 years old) and longitudinal (Down syndrome/healthy controls n = 8/13; Down syndrome—1 female/7 males, age 26.4 ± 5.3 years old; healthy controls—4 females/9 males, 24.7 ± 2.2 years old) relaxometry and diffusion-weighted MRI data alongside standard cognitive assessment. The statistical tests looked for cross-sectional baseline differences and for differential changes over time between Down syndrome and healthy controls. The post hoc analysis confined to the Down syndrome group, tested for potential time-dependent interactions between individuals’ overall cognitive performance and associated brain anatomy changes. The brain MRI statistical analyses covered both grey and white matter regions across the whole brain allowing for investigation of regional volume, macromolecular/myelin and iron content, additionally to diffusion tensor and neurite orientation and dispersion density characterization across major white matter tracts. The cross-sectional analysis showed reduced frontal, temporal and cerebellar volumes in Down syndrome with only the cerebellar differences remaining significant after adjustment for the presence of microcephaly (Pfamily-wise-corrected < 0.05). The volume reductions were paralleled by decreased cortical and subcortical macromolecular/myelin content confined to the cortical motor system, thalamus and basal ganglia (Pfamily-wise-corrected < 0.05). All major white matter tracts showed a ubiquitous mean diffusivity and intracellular volume fraction reduction contrasted with no differences in magnetization transfer saturation metrics (Pfamily-wise-corrected < 0.05). Compared with healthy controls over the same period, Down syndrome individuals under GnRH therapy showed cognitive improvement (Montreal Cognitive Assessment from 11.4 ± 5.5 to 15.1 ± 5.6; P < 0.01) on the background of stability of the observed differential neuroanatomical patterns. Despite the lack of adequate Down syndrome control group, we interpret the obtained cross-sectional and longitudinal findings in young adults as evidence for predominant neurodevelopmental neuronal loss due to dysfunctional neurogenesis without signs for short-term myelin loss.

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  • Journal IconBrain Communications
  • Publication Date IconMar 22, 2025
  • Author Icon Michela Adamo + 11
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Evaluating the Diagnostic Performance of MR Cytometry Imaging in Differentiating Benign and Malignant Breast Tumors.

MR cytometry is a class of diffusion-MRI-based methods that characterize tumor microstructures at the cellular level. It involves multicompartmental biophysical modeling of multi-b and multiple diffusion time data to generate microstructural parameters, which may improve differentiation of benign and malignant breast tumors. To implement MR cytometry imaging with transcytolemmal water exchange (JOINT and EXCHANGE) to differentiate benign and malignant breast tumors, and to compare the classification efficacy of IMPULSED, JOINT, and EXCHANGE. Prospective. 115 patients with pathologically confirmed breast tumors (25 benign and 90 malignant). 3T; pulsed gradient spin-echo (PGSE) diffusion-weighted imaging (DWI) and oscillating gradient spin-echo (OGSE) DWI at 25 and 50 Hz. Tumor regions were delineated by two radiologists on DWI. Time-dependent ADC and microstructural parameters (cell diameter , intracellular volume fraction , water exchange rate constant , extracellular diffusivity and intracellular intrinsic diffusivity ) were calculated. Classification performance was assessed in the original cohort and in an age-adjusted cohort (excluding older malignant patients to eliminate significant age differences). Mann-Whitney U-tests compared benign and malignant tumor values. Multivariable logistic regression used a stepwise approach based on the likelihood ratio test. The area under the receiver operating characteristic (AUC) was computed and compared by using the DeLong test. In the full analysis (25 benign, 90 malignant), microstructural parameters from methods incorporating transcytolemmal water exchange (JOINT and EXCHANGE) demonstrated superior performance (AUC: ADC, 0.822; IMPULSED, 0.840; JOINT, 0.902; EXCHANGE, 0.905). Combining different metrics further improved classification (AUC: IMPULSED [ , ], 0.942; JOINT [ , ], 0.956; EXCHANGE [ , ], 0.954; [ ], 0.927). These improvements were also observed in the age-adjusted analysis (25 benign, 42 malignant). MR cytometry outperformed ADC in distinguishing benign and malignant breast tumors. Incorporating transcytolemmal water exchange into biophysical modeling further improved its diagnostic performance. 1 Technical Efficacy: Stage 2.

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  • Journal IconJournal of magnetic resonance imaging : JMRI
  • Publication Date IconMar 11, 2025
  • Author Icon Fan Liu + 10
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Risk Stratification Prediction of Endometrial Cancer Using Microstructural Mapping Based on Time‐Dependent Diffusion MRI

ABSTRACTTime‐dependent diffusion MRI (td‐dMRI) has potential in characterizing microstructural features; however, its value in imaging endometrioid endometrial adenocarcinoma (EEA) remains uncertain. Patients surgically confirmed with EEA were finally enrolled in our study. The td‐dMRI data were acquired using pulsed gradient spin echo sequence and oscillating gradient spin echo sequences. The microstructural markers, including cell diameter, intracellular volume fraction (Vin), cellularity, and extracellular diffusivity (Dex), were fitted with the imaging microstructural parameters using a limited spectrally edited diffusion (IMPULSED) model. The parameters were compared between low‐ and high‐risk groups and between low‐ and high‐proliferation groups. The diagnostic performance was evaluated using receiver‐operating characteristic curve and logistic regression analysis. Diameter, Dex, ADCPGSE, ADCN1, and ADCN2 were significantly low, whereas cellularity, ΔADC1 and ΔADC2 were significantly high in the high‐risk and high‐proliferation groups. Cellularity, ΔADC1, and ΔADC2 demonstrated excellent diagnostic efficacy in predicting both risk stratification and proliferation status. Cellularity was the only independent predictor for risk stratification, which exhibited a satisfactory positive correlation with cell density in histopathologic examination. The diagnostic potential of td‐dMRI‐based microstructural mapping was demonstrated to noninvasively probe the pathologic characteristics of patients with EEA in a clinical setting, which provided a valuable contribution to surgical guidance.

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  • Journal IconCancer Science
  • Publication Date IconMar 10, 2025
  • Author Icon Yu Zhao + 12
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