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12 pages, 1486 KiB

Open AccessArticle

Elucidating Early Radiation-Induced Cardiotoxicity Markers in Preclinical Genetic Models Through Advanced Machine Learning and Cardiac MRI

by Dayeong An and El-Sayed Ibrahim

J. Imaging 2024, 10(12), 308; https://doi.org/10.3390/jimaging10120308 - 1 Dec 2024

Viewed by 1128

Abstract

Radiation therapy (RT) is widely used to treat thoracic cancers but carries a risk of radiation-induced heart disease (RIHD). This study aimed to detect early markers of RIHD using machine learning (ML) techniques and cardiac MRI in a rat model. SS.BN3 consomic rats, which have a more subtle RIHD phenotype compared to Dahl salt-sensitive (SS) rats, were treated with localized cardiac RT or sham at 10 weeks of age. Cardiac MRI was performed 8 and 10 weeks post-treatment to assess global and regional cardiac function. ML algorithms were applied to differentiate sham-treated and irradiated rats based on early changes in myocardial function. Despite normal global left ventricular ejection fraction in both groups, strain analysis showed significant reductions in the anteroseptal and anterolateral segments of irradiated rats. Gradient boosting achieved an F1 score of 0.94 and an ROC value of 0.95, while random forest showed an accuracy of 88%. These findings suggest that ML, combined with cardiac MRI, can effectively detect early preclinical changes in RIHD, particularly alterations in regional myocardial contractility, highlighting the potential of these techniques for early detection and monitoring of radiation-induced cardiac dysfunction. Full article

(This article belongs to the Special Issue Progress and Challenges in Biomedical Image Analysis)

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25 pages, 3152 KiB

Open AccessArticle

Dynamic NIR Fluorescence Imaging and Machine Learning Framework for Stratifying High vs. Low Notch-Dll4 Expressing Host Microenvironment in Triple-Negative Breast Cancer

by Shayan Shafiee, Jaidip Jagtap, Mykhaylo Zayats, Jonathan Epperlein, Anjishnu Banerjee, Aron Geurts, Michael Flister, Sergiy Zhuk and Amit Joshi

Cancers 2023, 15(5), 1460; https://doi.org/10.3390/cancers15051460 - 25 Feb 2023

Cited by 4 | Viewed by 2511

Abstract

Delta like canonical notch ligand 4 (Dll4) expression levels in tumors are known to affect the efficacy of cancer therapies. This study aimed to develop a model to predict Dll4 expression levels in tumors using dynamic enhanced near-infrared (NIR) imaging with indocyanine green (ICG). Two rat-based consomic xenograft (CXM) strains of breast cancer with different Dll4 expression levels and eight congenic xenograft strains were studied. Principal component analysis (PCA) was used to visualize and segment tumors, and modified PCA techniques identified and analyzed tumor and normal regions of interest (ROIs). The average NIR intensity for each ROI was calculated from pixel brightness at each time interval, yielding easily interpretable features including the slope of initial ICG uptake, time to peak perfusion, and rate of ICG intensity change after reaching half-maximum intensity. Machine learning algorithms were applied to select discriminative features for classification, and model performance was evaluated with a confusion matrix, receiver operating characteristic curve, and area under the curve. The selected machine learning methods accurately identified host Dll4 expression alterations with sensitivity and specificity above 90%. This may enable stratification of patients for Dll4 targeted therapies. NIR imaging with ICG can noninvasively assess Dll4 expression levels in tumors and aid in effective decision making for cancer therapy. Full article

(This article belongs to the Special Issue Biophotonics and Imaging for Cancer Screening, Diagnosis and Treatment Monitoring)

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27 pages, 5632 KiB

Open AccessArticle

Two Loci Contribute to Age-Related Hearing Loss Resistance in the Japanese Wild-Derived Inbred MSM/Ms Mice

by Shumpei P. Yasuda, Yuki Miyasaka, Xuehan Hou, Yo Obara, Hiroshi Shitara, Yuta Seki, Kunie Matsuoka, Ai Takahashi, Eri Wakai, Hiroshi Hibino, Toyoyuki Takada, Toshihiko Shiroishi, Ryo Kominami and Yoshiaki Kikkawa

Biomedicines 2022, 10(9), 2221; https://doi.org/10.3390/biomedicines10092221 - 7 Sep 2022

Cited by 5 | Viewed by 2797

Abstract

An MSM/Ms strain was established using Japanese wild mice, which exhibit resistance to several phenotypes associated with aging, such as obesity, inflammation, and tumorigenesis, compared to common inbred mouse strains. MSM/Ms strain is resistant to age-related hearing loss, and their auditory abilities are sustained for long durations. The age-related hearing loss 3 (ahl3) locus contributes to age-related hearing in MSM/Ms strain. We generated ahl3 congenic strains by transferring a genomic region on chromosome 17 from MSM/Ms mice into C57BL/6J mice. Although C57BL/6J mice develop age-related hearing loss because of the ahl allele of the cadherin 23 gene, the development of middle- to high-frequency hearing loss was significantly delayed in an ahl3 congenic strain. Moreover, the novel age-related hearing loss 10 (ahl10) locus associated with age-related hearing resistance in MSM/Ms strain was mapped to chromosome 12. Although the resistance effects in ahl10 congenic strain were slightly weaker than those in ahl3 congenic strain, slow progression of age-related hearing loss was confirmed in ahl10 congenic strain despite harboring the ahl allele of cadherin 23. These results suggest that causative genes and polymorphisms of the ahl3 and ahl10 loci are important targets for the prevention and treatment of age-related hearing loss. Full article

(This article belongs to the Special Issue Genetic Research on Hearing Loss)

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12 pages, 279 KiB

Open AccessReview

Y Chromosome, Hypertension and Cardiovascular Disease: Is Inflammation the Answer?

by Shanzana I. Khan, Karen L. Andrews, Garry L. Jennings, Amanda K. Sampson and Jaye P. F. Chin-Dusting

Int. J. Mol. Sci. 2019, 20(12), 2892; https://doi.org/10.3390/ijms20122892 - 13 Jun 2019

Cited by 27 | Viewed by 4213

Abstract

It is now becomingly increasingly evident that the functions of the mammalian Y chromosome are not circumscribed to the induction of male sex. While animal studies have shown variations in the Y are strongly accountable for blood pressure (BP), this is yet to be confirmed in humans. We have recently shown modulation of adaptive immunity to be a significant mechanism underpinning Y-chromosome-dependent differences in BP in consomic strains. This is paralleled by studies in man showing Y chromosome haplogroup is a significant predictor for coronary artery disease through influencing pathways of immunity. Furthermore, recent studies in mice and humans have shown that Y chromosome lineage determines susceptibility to autoimmune disease. Here we review the evidence in animals and humans that Y chromosome lineage influences hypertension and cardiovascular disease risk, with a novel focus on pathways of immunity as a significant pathway involved. Full article

(This article belongs to the Special Issue Endothelial Dysfunction: Pathophysiology and Molecular Mechanisms)

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