Microvascular fractal dimension predicts prognosis and response to chemotherapy in glioblastoma: an automatic image analysis study

Chen, Cong; He, Zhi Cheng; Shi, Yu; Zhou, Wenchao; Zhang, Xia; Wu, Hai bo; Xiao, Yao; Luo, Wan chun; Cui, Yinghui; Bao, Shideng; Kung, Hsiang Fu; Bian, Xiu Wu; Ping, Yi

doi:10.1038/s41374-018-0055-2

Cited by 25 publications

(19 citation statements)

References 55 publications

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“…Fractal dimension measures the complexity of structures. In our study, a significant increase of mvFD was found in malignant breast lesions, indicating that malignant lesions have more dense, irregularly branched and twisted microvessel structures, which is consistent with the findings of other studies on oral cancer [ 45 ], renal cell carcinoma [ 19 ] and glioblastoma [ 46 ].…”

Section: Discussionsupporting

confidence: 93%

Quantitative Biomarkers for Cancer Detection Using Contrast-Free Ultrasound High-Definition Microvessel Imaging: Fractal Dimension, Murray’s Deviation, Bifurcation Angle & Spatial Vascularity Pattern

Ternifi

Wang

Polley

et al. 2021

IEEE Trans. Med. Imaging

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A growing body of evidence indicates that there is a strong correlation between microvascular morphological features and malignant tumors. Therefore, quantification of these features might allow more accurate differentiation of benign and malignant tumors. The main objective of this research project is to improve the quantification of microvascular networks depicted in contrast-free ultrasound microvessel images. To achieve this goal, a new series of quantitative microvessel morphological parameters are introduced for differentiation of breast masses using contrast-free ultrasound-based high-definition microvessel imaging (HDMI). Using HDMI, we quantified and analyzed four new parameters: 1) microvessel fractal dimension (mvFD), a marker of tumor microvascular complexity, 2) Murray's deviation (MD), the diameter mismatch, defined as the deviation from Murray's law, 3) Bifurcation angle (BA), abnormally decreased angle, and 4) spatial vascular pattern (SVP), indicating tumor vascular distribution pattern, either intratumoral or peritumoral. The new biomarkers have been tested on 60 patients with breast masses. Validation of the feature's extraction algorithm was performed using a synthetic data set. All the proposed parameters had the power to discriminate the breast lesion malignancy (p < 0.05), displaying BA as the most sensitive test, with a sensitivity of 90.6%, and mvFD as the most specific test, with a specificity of 92%. The results of all four new biomarkers showed an AUC=0.889, sensitivity of 80% and specificity of 91.4% In conclusion, the added value of the proposed quantitative morphological parameters, as new biomarkers of angiogenesis within breast masses, paves the way for more accurate breast cancer detection with higher specificity.

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Section: Discussionsupporting

confidence: 93%

Quantitative Biomarkers for Cancer Detection Using Contrast-Free Ultrasound High-Definition Microvessel Imaging: Fractal Dimension, Murray’s Deviation, Bifurcation Angle & Spatial Vascularity Pattern

Ternifi

Wang

Polley

et al. 2021

IEEE Trans. Med. Imaging

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“…Pericytes represent a specialized mesenchymal cell type within the tumor perivascular niche and potentiates tumor vascular functions, tumor metastasis and immune cell infiltration. 9 , 30 – 32 Pericytes in GBMs exhibit excessive outgrowth 33 and are pivotal for maintaining the integrity of the BTB. 10 In this study, we reveal that pericytes directly interact with GBM cells residing in the perivascular niche to enhance DNA repair and induce TMZ chemoresistance.…”

Section: Discussionmentioning

confidence: 99%

Pericytes augment glioblastoma cell resistance to temozolomide through CCL5-CCR5 paracrine signaling

et al. 2021

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Glioblastoma (GBM) is a prevalent and highly lethal form of glioma, with rapid tumor progression and frequent recurrence. Excessive outgrowth of pericytes in GBM governs the ecology of the perivascular niche, but their function in mediating chemoresistance has not been fully explored. Herein, we uncovered that pericytes potentiate DNA damage repair (DDR) in GBM cells residing in the perivascular niche, which induces temozolomide (TMZ) chemoresistance. We found that increased pericyte proportion correlates with accelerated tumor recurrence and worse prognosis. Genetic depletion of pericytes in GBM xenografts enhances TMZ-induced cytotoxicity and prolongs survival of tumor-bearing mice. Mechanistically, C-C motif chemokine ligand 5 (CCL5) secreted by pericytes activates C-C motif chemokine receptor 5 (CCR5) on GBM cells to enable DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-mediated DDR upon TMZ treatment. Disrupting CCL5-CCR5 paracrine signaling through the brain-penetrable CCR5 antagonist maraviroc (MVC) potently inhibits pericyte-promoted DDR and effectively improves the chemotherapeutic efficacy of TMZ. GBM patient-derived xenografts with high CCL5 expression benefit from combined treatment with TMZ and MVC. Our study reveals the role of pericytes as an extrinsic stimulator potentiating DDR signaling in GBM cells and suggests that targeting CCL5-CCR5 signaling could be an effective therapeutic strategy to improve chemotherapeutic efficacy against GBM.

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“…Morphological parameters [ 20 , 29 ], including number of vessel ( NV ), number of branch points ( NB ), vessel density ( VD ), vessel diameter ( D ) and distance metric ( τ ), were measured. Moreover, four new parameters, microvessel fractal dimension ( mvFD ) [ 29 – 31 ]. Murray’s deviation ( MD ) [ 29 , 32 – 34 ], bifurcation angle ( BA ) [ 29 , 35 – 37 ], and spatial vascular pattern ( SVP ) [ 29 , 38 ], calculated by vessel density ratio ( VDR ) [ 29 , 32 , 34 , 39 ], were also extracted from the HDMI image for characterizing the tumor microvessels.…”

Section: Methodsmentioning

confidence: 99%

Hybrid high-definition microvessel imaging/shear wave elastography improves breast lesion characterization

Ternifi

Larson

et al. 2022

Breast Cancer Res

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Background Low specificity in current breast imaging modalities leads to increased unnecessary follow-ups and biopsies. The purpose of this study is to evaluate the efficacy of combining the quantitative parameters of high-definition microvasculature imaging (HDMI) and 2D shear wave elastography (SWE) with clinical factors (lesion depth and age) for improving breast lesion differentiation. Methods In this prospective study, from June 2016 through April 2021, patients with breast lesions identified on diagnostic ultrasound and recommended for core needle biopsy were recruited. HDMI and SWE were conducted prior to biopsies. Two new HDMI parameters, Murray’s deviation and bifurcation angle, and a new SWE parameter, mass characteristic frequency, were included for quantitative analysis. Lesion malignancy prediction models based on HDMI only, SWE only, the combination of HDMI and SWE, and the combination of HDMI, SWE and clinical factors were trained via elastic net logistic regression with 70% (360/514) randomly selected data and validated with the remaining 30% (154/514) data. Prediction performances in the validation test set were compared across models with respect to area under the ROC curve as well as sensitivity and specificity based on optimized threshold selection. Results A total of 508 participants (mean age, 54 years ± 15), including 507 female participants and 1 male participant, with 514 suspicious breast lesions (range, 4–72 mm, median size, 13 mm) were included. Of the lesions, 204 were malignant. The SWE-HDMI prediction model, combining quantitative parameters from SWE and HDMI, with AUC of 0.973 (95% CI 0.95–0.99), was significantly higher than the result predicted with the SWE model or HDMI model alone. With an optimal cutoff of 0.25 for the malignancy probability, the sensitivity and specificity were 95.5% and 89.7%, respectively. The specificity was further improved with the addition of clinical factors. The corresponding model defined as the SWE-HDMI-C prediction model had an AUC of 0.981 (95% CI 0.96–1.00). Conclusions The SWE-HDMI-C detection model, a combination of SWE estimates, HDMI quantitative biomarkers and clinical factors, greatly improved the accuracy in breast lesion characterization.

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Microvascular fractal dimension predicts prognosis and response to chemotherapy in glioblastoma: an automatic image analysis study

Cited by 25 publications

References 55 publications

Quantitative Biomarkers for Cancer Detection Using Contrast-Free Ultrasound High-Definition Microvessel Imaging: Fractal Dimension, Murray’s Deviation, Bifurcation Angle & Spatial Vascularity Pattern

Quantitative Biomarkers for Cancer Detection Using Contrast-Free Ultrasound High-Definition Microvessel Imaging: Fractal Dimension, Murray’s Deviation, Bifurcation Angle & Spatial Vascularity Pattern

Pericytes augment glioblastoma cell resistance to temozolomide through CCL5-CCR5 paracrine signaling

Hybrid high-definition microvessel imaging/shear wave elastography improves breast lesion characterization

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