Here we detail the design, fabrication, and use of a microfluidic device to evaluate the deformability of a large number of individual cells in an efficient manner. Typically, data for ~10(2) cells can be acquired within a 1 hr experiment. An automated image analysis program enables efficient post-experiment analysis of image data, enabling processing to be complete within a few hours. Our device geometry is unique in that cells must deform through a series of micron-scale constrictions, thereby enabling the initial deformation and time-dependent relaxation of individual cells to be assayed. The applicability of this method to human promyelocytic leukemia (HL-60) cells is demonstrated. Driving cells to deform through micron-scale constrictions using pressure-driven flow, we observe that human promyelocytic (HL-60) cells momentarily occlude the first constriction for a median time of 9.3 msec before passaging more quickly through the subsequent constrictions with a median transit time of 4.0 msec per constriction. By contrast, all-trans retinoic acid-treated (neutrophil-type) HL-60 cells occlude the first constriction for only 4.3 msec before passaging through the subsequent constrictions with a median transit time of 3.3 msec. This method can provide insight into the viscoelastic nature of cells, and ultimately reveal the molecular origins of this behavior.

Artificial intelligence (AI) applications in breast imaging span a wide range of tasks including decision support, risk assessment, patient management, quality assessment, treatment response assessment and image enhancement. However, their integration into the clinical workflow has been slow due to the lack of a consensus on data quality, benchmarked robust implementation, and consensus-based guidelines to ensure standardization and generalization. Contrast-enhanced mammography (CEM) has improved sensitivity and specificity compared to current standards of breast cancer diagnostic imaging i.e., mammography (MG) and/or conventional ultrasound (US), with comparable accuracy to MRI (current diagnostic imaging benchmark), but at a much lower cost and higher throughput. This makes CEM an excellent tool for widespread breast lesion characterization for all women, including underserved and minority women. Underlining the critical need for early detection and accurate diagnosis of breast cancer, this review examines the limitations of conventional approaches and reveals how AI can help overcome them. The Methodical approaches, such as image processing, feature extraction, quantitative analysis, lesion classification, lesion segmentation, integration with clinical data, early detection, and screening support have been carefully analysed in recent studies addressing breast cancer detection and diagnosis. Recent guidelines described by Checklist for Artificial Intelligence in Medical Imaging (CLAIM) to establish a robust framework for rigorous evaluation and surveying has inspired the current review criteria.

To date, studies investigating radiomics-based predictive models have tended to err on the side of data-driven or exploratory analysis of many thousands of extracted features. In particular, spatial assessments of texture have proven to be especially adept at assessing for features of intratumoral heterogeneity in oncologic imaging, which likewise may correspond with tumor biology and behavior. These spatial assessments can be generally classified as spatial filters, which detect areas of rapid change within the grayscale in order to enhance edges and/or textures within an image, or neighborhood-based methods, which quantify gray-level differences of neighboring pixels/voxels within a set distance. Given the high dimensionality of radiomics datasets, data dimensionality reduction methods have been proposed in an attempt to optimize model performance in machine learning studies; however, it should be noted that these approaches should only be applied to training data in order to avoid information leakage and model overfitting. While area under the curve of the receiver operating characteristic is perhaps the most commonly reported assessment of model performance, it is prone to overestimation when output classifications are unbalanced. In such cases, confusion matrices may be additionally reported, whereby diagnostic cut points for model predicted probability may hold more clinical significance to clinical colleagues with respect to related forms of diagnostic testing.

Objectives

To evaluate the performance of machine learning-augmented MRI-based radiomics models for predicting response to neoadjuvant chemotherapy (NAC) in soft tissue sarcomas.

Methods

Forty-four subjects were identified retrospectively from patients who received NAC at our institution for pathologically proven soft tissue sarcomas. Only subjects who had both a baseline MRI prior to initiating chemotherapy and a post-treatment scan at least 2 months after initiating chemotherapy and prior to surgical resection were included. 3D ROIs were used to delineate whole-tumor volumes on pre- and post-treatment scans, from which 1708 radiomics features were extracted. Delta-radiomics features were calculated by subtraction of baseline from post-treatment values and used to distinguish treatment response through univariate analyses as well as machine learning-augmented radiomics analyses.

Results

Though only 4.74% of variables overall reached significance at p ≤ 0.05 in univariate analyses, Laws Texture Energy (LTE)-derived metrics represented 46.04% of all such features reaching statistical significance. ROC analyses similarly failed to predict NAC response, with AUCs of 0.40 (95% CI 0.22-0.58) and 0.44 (95% CI 0.26-0.62) for RF and AdaBoost, respectively.

Conclusion

Overall, while our result was not able to separate NAC responders from non-responders, our analyses did identify a subset of LTE-derived metrics that show promise for further investigations. Future studies will likely benefit from larger sample size constructions so as to avoid the need for data filtering and feature selection techniques, which have the potential to significantly bias the machine learning procedures.

Recent advancements in artificial intelligence (AI) and machine learning offer numerous opportunities in musculoskeletal radiology to potentially bolster diagnostic accuracy, workflow efficiency, and predictive modeling. AI tools have the capability to assist radiologists in many tasks ranging from image segmentation, lesion detection, and more. In bone and soft tissue tumor imaging, radiomics and deep learning show promise for malignancy stratification, grading, prognostication, and treatment planning. However, challenges such as standardization, data integration, and ethical concerns regarding patient data need to be addressed ahead of clinical translation. In the realm of musculoskeletal oncology, AI also faces obstacles in robust algorithm development due to limited disease incidence. While many initiatives aim to develop multitasking AI systems, multidisciplinary collaboration is crucial for successful AI integration into clinical practice. Robust approaches addressing challenges and embodying ethical practices are warranted to fully realize AI's potential for enhancing diagnostic accuracy and advancing patient care.

Claudins, the integral tight junction (TJ) proteins that regulate paracellular permeability and cell polarity, are frequently dysregulated in cancer; however, their role in neoplastic progression is unclear. Here, we demonstrated that knockout of Cldn18, a claudin family member highly expressed in lung alveolar epithelium, leads to lung enlargement, parenchymal expansion, increased abundance and proliferation of known distal lung progenitors, the alveolar epithelial type II (AT2) cells, activation of Yes-associated protein (YAP), increased organ size, and tumorigenesis in mice. Inhibition of YAP decreased proliferation and colony-forming efficiency (CFE) of Cldn18-/- AT2 cells and prevented increased lung size, while CLDN18 overexpression decreased YAP nuclear localization, cell proliferation, CFE, and YAP transcriptional activity. CLDN18 and YAP interacted and colocalized at cell-cell contacts, while loss of CLDN18 decreased YAP interaction with Hippo kinases p-LATS1/2. Additionally, Cldn18-/- mice had increased propensity to develop lung adenocarcinomas (LuAd) with age, and human LuAd showed stage-dependent reduction of CLDN18.1. These results establish CLDN18 as a regulator of YAP activity that serves to restrict organ size, progenitor cell proliferation, and tumorigenesis, and suggest a mechanism whereby TJ disruption may promote progenitor proliferation to enhance repair following injury.

Introduction

1.5 Tesla (1.5T) remain a significant field strength for brain imaging worldwide. Recent computer simulations and clinical studies at 3T MRI have suggested that dynamic susceptibility contrast (DSC) MRI using a 30° flip angle ("low-FA") with model-based leakage correction and no gadolinium-based contrast agent (GBCA) preload provides equivalent relative cerebral blood volume (rCBV) measurements to the reference-standard acquisition using a single-dose GBCA preload with a 60° flip angle ("intermediate-FA") and model-based leakage correction. However, it remains unclear whether this holds true at 1.5T. The purpose of this study was to test this at 1.5T in human high-grade glioma (HGG) patients.

Methods

This was a single-institution cross-sectional study of patients who had undergone 1.5T MRI for HGG. DSC-MRI consisted of gradient-echo echo-planar imaging (GRE-EPI) with a low-FA without preload (30°/P-); this then subsequently served as a preload for the standard intermediate-FA acquisition (60°/P+). Both normalized (nrCBV) and standardized relative cerebral blood volumes (srCBV) were calculated using model-based leakage correction (C+) with IBNeuro™ software. Whole-enhancing lesion mean and median nrCBV and srCBV from the low- and intermediate-FA methods were compared using the Pearson's, Spearman's and intraclass correlation coefficients (ICC).

Results

Twenty-three HGG patients composing a total of 31 scans were analyzed. The Pearson and Spearman correlations and ICCs between the 30°/P-/C+ and 60°/P+/C+ acquisitions demonstrated high correlations for both mean and median nrCBV and srCBV.

Conclusion

Our study provides preliminary evidence that for HGG patients at 1.5T MRI, a low FA, no preload DSC-MRI acquisition can be an appealing alternative to the reference standard higher FA acquisition that utilizes a preload.