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INTRODUCTION: Although ischemia-reperfusion (I/R) injury varies between cortical and subcortical regions, its effects on specific regions remain unclear. In this study, we used various magnetic resonance imaging (MRI) techniques to examine the spatiotemporal dynamics of I/R injury within the salvaged ischemic penumbra (IP) and reperfused ischemic core (IC) of a rodent model, with the aim of enhancing therapeutic strategies by elucidating these dynamics. MATERIALS AND METHODS: A total of 17 Sprague-Dawley rats were subjected to 1 h of transient middle cerebral artery occlusion with a suture model. MRI, including diffusion tensor imaging (DTI), T2-weighted imaging, perfusion-weighted imaging, and T1 mapping, was conducted at multiple time points for up to 5 days during the I/R phases. The spatiotemporal dynamics of blood-brain barrier (BBB) modifications were characterized through changes in T1 within the IP and IC regions and compared with mean diffusivity (MD), T2, and cerebral blood flow. RESULTS: During the I/R phases, the MD of the IC initially decreased, normalized after recanalization, decreased again at 24 h, and peaked on day 5. By contrast, the IP remained relatively stable. Both the IP and IC exhibited hyperperfusion, with the IP reaching its peak at 24 h, followed by resolution, whereas hyperperfusion was maintained in the IC until day 5. Despite hyperperfusion, the IP maintained an intact BBB, whereas the IC experienced persistent BBB leakage. At 24 h, the IC exhibited an increase in the T2 signal, corresponding to regions exhibiting BBB disruption at 5 days. CONCLUSIONS: Hyperperfusion and BBB impairment have distinct patterns in the IP and IC. Quantitative T1 mapping may serve as a supplementary tool for the early detection of malignant hyperemia accompanied by BBB leakage, aiding in precise interventions after recanalization. These findings underscore the value of MRI markers in monitoring ischemia-specific regions and customizing therapeutic strategies to improve patient outcomes.
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Circulação Cerebrovascular , Ratos Sprague-Dawley , Traumatismo por Reperfusão , Animais , Ratos , Traumatismo por Reperfusão/diagnóstico por imagem , Masculino , Modelos Animais de Doenças , Barreira Hematoencefálica/diagnóstico por imagem , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Isquemia Encefálica/diagnóstico por imagem , Angiografia por Ressonância Magnética/métodosRESUMO
BACKGROUND: This study investigates the potential of diffusion tensor imaging (DTI) in identifying penumbral volume (PV) compared to the standard gadolinium-required perfusion-diffusion mismatch (PDM), utilizing a stack-based ensemble machine learning (ML) approach with enhanced explainability. METHODS: Sixteen male rats were subjected to middle cerebral artery occlusion. The penumbra was identified using PDM at 30 and 90 min after occlusion. We used 11 DTI-derived metrics and 14 distance-based features to train five voxel-wise ML models. The model predictions were integrated using stack-based ensemble techniques. ML-estimated and PDM-defined PVs were compared to evaluate model performance through volume similarity assessment, the Pearson correlation analysis, and Bland-Altman analysis. Feature importance was determined for explainability. RESULTS: In the test rats, the ML-estimated median PV was 106.4 mL (interquartile range 44.6-157.3 mL), whereas the PDM-defined median PV was 102.0 mL (52.1-144.9 mL). These PVs had a volume similarity of 0.88 (0.79-0.96), a Pearson correlation coefficient of 0.93 (p < 0.001), and a Bland-Altman bias of 2.5 mL (2.4% of the mean PDM-defined PV), with 95% limits of agreement ranging from -44.9 to 49.9 mL. Among the features used for PV prediction, the mean diffusivity was the most important feature. CONCLUSIONS: Our study confirmed that PV can be estimated using DTI metrics with a stack-based ensemble ML approach, yielding results comparable to the volume defined by the standard PDM. The model explainability enhanced its clinical relevance. Human studies are warranted to validate our findings. RELEVANCE STATEMENT: The proposed DTI-based ML model can estimate PV without the need for contrast agent administration, offering a valuable option for patients with kidney dysfunction. It also can serve as an alternative if perfusion map interpretation fails in the clinical setting. KEY POINTS: ⢠Penumbral volume can be estimated by DTI combined with stack-based ensemble ML. ⢠Mean diffusivity was the most important feature used for predicting penumbral volume. ⢠The proposed approach can be beneficial for patients with kidney dysfunction.
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Imagem de Tensor de Difusão , Aprendizado de Máquina , Animais , Masculino , Ratos , Imagem de Tensor de Difusão/métodos , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Ratos Sprague-DawleyRESUMO
OBJECTIVE: This study developed a diagnostic tool combining machine learning (ML) segmentation and radiomic texture analysis (RTA) for bone density screening using chest low-dose computed tomography (LDCT). METHODS: A total of 197 patients who underwent LDCT followed by dual-energy X-ray absorptiometry were analyzed. First, an autosegmentation model was trained using LDCT to delineate the thoracic vertebral body (VB). Second, a two-level classifier was developed using radiomic features extracted from VBs for the hierarchical pairwise classification of each patient's bone status. All the patients were initially classified as either normal or abnormal, and all patients with abnormal bone density were then subdivided into an osteopenia group and an osteoporosis group. The performance of the classifier was evaluated through fivefold cross-validation. RESULTS: The model for automated VB segmentation achieved a Sorenson-Dice coefficient of 0.87 ± 0.01. Furthermore, the area under the receiver operating characteristic curve scores for the two-level classifier were 0.96 ± 0.01 for detecting abnormal bone density (accuracy = 0.91 ± 0.02; sensitivity = 0.93 ± 0.03; specificity = 0.89 ± 0.03) and 0.98 ± 0.01 for distinguishing osteoporosis (accuracy = 0.94 ± 0.02; sensitivity = 0.95 ± 0.03; specificity = 0.93 ± 0.03). The testing prediction accuracy levels for the first- and second-level classifiers were 0.92 ± 0.04 and 0.94 ± 0.05, respectively. The overall testing prediction accuracy of our method was 0.90 ± 0.05. CONCLUSION: The combination of ML segmentation and RTA for automated bone density prediction based on LDCT scans is a feasible approach that could be valuable for osteoporosis screening during lung cancer screening. KEY POINTS: ⢠This study developed an automatic diagnostic tool combining machine learning-based segmentation and radiomic texture analysis for bone density screening using chest low-dose computed tomography. ⢠The developed method enables opportunistic screening without quantitative computed tomography or a dedicated phantom. ⢠The developed method could be integrated into the current clinical workflow and used as an adjunct for opportunistic screening or for patients who are ineligible for screening with dual-energy X-ray absorptiometry.
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Neoplasias Pulmonares , Osteoporose , Humanos , Detecção Precoce de Câncer , Osteoporose/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Densidade Óssea , Estudos RetrospectivosRESUMO
The molecular heterogeneity of gene expression profiles of glioblastoma multiforme (GBM) are the most important prognostic factors for tumor recurrence and drug resistance. Thus, the aim of this study was to identify potential target genes related to temozolomide (TMZ) resistance and GBM recurrence. The genomic data of patients with GBM from The Cancer Genome Atlas (TCGA; 154 primary and 13 recurrent tumors) and a local cohort (29 primary and 4 recurrent tumors), samples from different tumor regions from a local cohort (29 tumor and 25 peritumoral regions), and Gene Expression Omnibus data (GSE84465, single-cell RNA sequencing; 3589 cells) were included in this study. Critical gene signatures were identified based an analysis of differentially expressed genes (DEGs). DEGs were further used to evaluate gene enrichment levels among primary and recurrent GBMs and different tumor regions through gene set enrichment analysis. Protein-protein interactions (PPIs) were incorporated into gene regulatory networks to identify the affected metabolic pathways. The enrichment levels of 135 genes were identified in the peritumoral regions as being risk signatures for tumor recurrence. Fourteen genes (DVL1, PRKACB, ARRB1, APC, MAPK9, CAMK2A, PRKCB, CACNA1A, ERBB4, RASGRF1, NF1, RPS6KA2, MAPK8IP2, and PPM1A) derived from the PPI network of 135 genes were upregulated and involved in the regulation of cancer stem cell (CSC) development and relevant signaling pathways (Notch, Hedgehog, Wnt, and MAPK). The single-cell data analysis results indicated that 14 key genes were mainly expressed in oligodendrocyte progenitor cells, which could produce a CSC niche in the peritumoral region. The enrichment levels of 336 genes were identified as biomarkers for evaluating TMZ resistance in the solid tumor region. Eleven genes (ARID5A, CDC42EP3, CDKN1A, FLT3, JUNB, MAP2K3, MYBPC2, RGS14, RNASEK, TBC1D30, and TXNDC11) derived from the PPI network of 336 genes were upregulated and may be associated with a high risk of TMZ resistance; these genes were identified in both the TCGA and local cohorts. Furthermore, the expression patterns of ARID5A, CDKN1A, and MAP2K3 were identical to the gene signatures of TMZ-resistant cell lines. The identified enrichment levels of the two gene sets expressed in tumor and peritumoral regions are potentially helpful for evaluating TMZ resistance in GBM. Moreover, these key genes could be used as biomarkers, potentially providing new molecular strategies for GBM treatment.
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PURPOSE: Targeted superparamagnetic iron oxide (SPIO) nanoparticles are a promising tool for molecular magnetic resonance imaging (MRI) diagnosis. Lipid-coated SPIO nanoparticles have a nonfouling property that can reduce nonspecific binding to off-target cells and prevent agglomeration, making them suitable contrast agents for molecular MRI diagnosis. PD-L1 is a poor prognostic factor for patients with glioblastoma. Most recurrent glioblastomas are temozolomide resistant. Diagnostic probes targeting PD-L1 could facilitate early diagnosis and be used to predict responses to targeted PD-L1 immunotherapy in patients with primary or recurrent glioblastoma. We conjugated lipid-coated SPIO nanoparticles with PD-L1 antibodies to identify PD-L1 expression in glioblastoma or temozolomide-resistant glioblastoma by using MRI. METHODS: The synthesized PD-L1 antibody-conjugated SPIO (PDL1-SPIO) nanoparticles were characterized using dynamic light scattering, zeta potential assays, transmission electron microscopy images, Prussian blue assay, in vitro cell affinity assay, and animal MRI analysis. RESULTS: PDL1-SPIO exhibited a specific binding capacity to PD-L1 of the mouse glioblastoma cell line (GL261). The presence and quantity of PDL1-SPIO in temozolomide-resistant glioblastoma cells and tumor tissue were confirmed through Prussian blue staining and in vivo T2* map MRI, respectively. CONCLUSION: This is the first study to demonstrate that PDL1-SPIO can specifically target temozolomide-resistant glioblastoma with PD-L1 expression in the brain and can be quantified through MRI analysis, thus making it suitable for the diagnosis of PD-L1 expression in temozolomide-resistant glioblastoma in vivo.
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Glioblastoma , Animais , Antígeno B7-H1 , Linhagem Celular Tumoral , Meios de Contraste , Compostos Férricos , Glioblastoma/diagnóstico por imagem , Glioblastoma/tratamento farmacológico , Humanos , Lipídeos , Nanopartículas Magnéticas de Óxido de Ferro , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita , Camundongos , Temozolomida/farmacologiaRESUMO
Characterization of immunophenotypes in glioblastoma (GBM) is important for therapeutic stratification and helps predict treatment response and prognosis. Radiomics can be used to predict molecular subtypes and gene expression levels. However, whether radiomics aids immunophenotyping prediction is still unknown. In this study, to classify immunophenotypes in patients with GBM, we developed machine learning-based magnetic resonance (MR) radiomic models to evaluate the enrichment levels of four immune subsets: Cytotoxic T lymphocytes (CTLs), activated dendritic cells, regulatory T cells (Tregs), and myeloid-derived suppressor cells (MDSCs). Independent testing data and the leave-one-out cross-validation method were used to evaluate model effectiveness and model performance, respectively. We identified five immunophenotypes (G1 to G5) based on the enrichment level for the four immune subsets. G2 had the worst prognosis and comprised highly enriched MDSCs and lowly enriched CTLs. G3 had the best prognosis and comprised lowly enriched MDSCs and Tregs and highly enriched CTLs. The average accuracy of T1-weighted contrasted MR radiomics models of the enrichment level for the four immune subsets reached 79% and predicted G2, G3, and the "immune-cold" phenotype (G1) according to our radiomics models. Our radiomic immunophenotyping models feasibly characterize the immunophenotypes of GBM and can predict patient prognosis.
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OBJECTIVE: To investigate whether the diffusion tensor imaging-derived metrics are capable of differentiating the ischemic penumbra (IP) from the infarct core (IC), and determining stroke onset within the first 4.5 hours. MATERIALS AND METHODS: All procedures were approved by the local animal care committee. Eight of the eleven rats having permanent middle cerebral artery occlusion were included for analyses. Using a 7 tesla magnetic resonance system, the relative cerebral blood flow and apparent diffusion coefficient maps were generated to define IP and IC, half hour after surgery and then every hour, up to 6.5 hours. Relative fractional anisotropy, pure anisotropy (rq) and diffusion magnitude (rL) maps were obtained. One-way analysis of variance, receiver operating characteristic curve and nonlinear regression analyses were performed. RESULTS: The evolutions of tensor metrics were different in ischemic regions (IC and IP) and topographic subtypes (cortical, subcortical gray matter, and white matter). The rL had a significant drop of 40% at 0.5 hour, and remained stagnant up to 6.5 hours. Significant differences (p < 0.05) in rL values were found between IP, IC, and normal tissue for all topographic subtypes. Optimal rL threshold in discriminating IP from IC was about -29%. The evolution of rq showed an exponential decrease in cortical IC, from -26.9% to -47.6%; an rq reduction smaller than 44.6% can be used to predict an acute stroke onset in less than 4.5 hours. CONCLUSION: Diffusion tensor metrics may potentially help discriminate IP from IC and determine the acute stroke age within the therapeutic time window.
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Isquemia Encefálica/diagnóstico , Imagem de Tensor de Difusão , Infarto da Artéria Cerebral Média/diagnóstico , Animais , Área Sob a Curva , Isquemia Encefálica/diagnóstico por imagem , Mapeamento Encefálico , Circulação Cerebrovascular/fisiologia , Modelos Animais de Doenças , Substância Cinzenta/diagnóstico por imagem , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Curva ROC , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Substância Branca/diagnóstico por imagemRESUMO
BACKGROUND: This study investigated diffusion-weighted (DWI) magnetic resonance imaging (MRI) as an alternative to fat-suppressed T2-weighted imaging (FS-T2WI) for assessment of partial-thickness rotator cuff tears (RCTs). METHODS: Patients with arthroscopy proven partial-thickness RCTs who also received MRI (FS-T2WI and DWI) before surgery were prospectively included. Receiver operating characteristic curves were used to compare DWI vs. FS-T2WI using lesion-to-muscle signal intensity ratios. A cutoff point for predicting partial-thickness tears was determined using the Youden index. RESULTS: Included were 146 patients, with a mean age of 48.3 years (range, 19-86 years), of whom 43 had full-thickness RCTs, 67 had partial-thickness RCTs, and 36 had no tears. Areas under receiver operating characteristic curves for diagnosing partial-thickness tears were significantly higher for DWI (0.910) than for FS-T2WI (0.822, P = .016). Lesion-to-muscle signal intensity ratio cutoff values were 1.06 for DWI vs. 1.65 for FS-T2WI, respectively. The sensitivity and accuracy of DWI (89.1% [98 of 110] and 87.7% [128 of 146], respectively) for diagnosing partial-thickness and full-thickness tears were higher than for FS-T2WI (65.5% [72 of 110] and 72.6% [106 of 146], respectively). FS-T2WI, however, had higher specificity (94.4% [34 of 36]) than DWI (83.3% [30 of 36]). CONCLUSIONS: DWI is more accurate and sensitive than FS-T2WI for diagnosing partial-thickness RCTs.