Purpose: To evaluate in vivo T mapping as quantitative, imaging-based biomarker for meniscal degeneration in humans, by studying the correlation between T relaxation time and degree of histological degeneration as reference standard.
Methods: In this prospective validation study, 13 menisci from seven patients with radiographic knee osteoarthritis (median age 67 years, three males) were included. Menisci were obtained during total knee replacement surgery. All patients underwent pre-operative magnetic resonance imaging using a 3-T MR scanner which included a T mapping pulse sequence with multiple echoes. Histological analysis of the collected menisci was performed using the Pauli score, involving surface integrity, cellularity, matrix organization, and staining intensity. Mean T relaxation times were calculated in meniscal regions of interest corresponding with the areas scored histologically, using a multi-slice multi-echo postprocessing algorithm. Correlation between T mapping and histology was assessed using a generalized least squares model fit by maximum likelihood.
Results: The mean T relaxation time was 22.4 ± 2.7 ms (range 18.5-27). The median histological score was 10, IQR 7-11 (range 4-13). A strong correlation between T relaxation time and histological score was found (r = 0.84, CI 95% 0.64-0.93).
Conclusion: In vivo T mapping of the human meniscus correlates strongly with histological degeneration, suggesting that T mapping enables the detection and quantification of early compositional changes of the meniscus in knee OA.
Key Points: • Prospective histology-based study showed that in vivo T mapping of the human meniscus correlates strongly with histological degeneration. • Meniscal T mapping allows detection and quantifying of compositional changes, without need for contrast or special MRI hardware. • Meniscal T mapping provides a biomarker for early OA, potentially allowing early treatment strategies and prevention of OA progression.
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http://dx.doi.org/10.1007/s00330-019-06091-1 | DOI Listing |
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University of Michigan-Ann Arbor, Ann Arbor, MI, United States.
Up to 90% of high-grade serous ovarian cancer (HGSC) patients will develop resistance to platinum-based chemotherapy, posing substantial therapeutic challenges due to a lack of universally druggable targets. Leveraging BenevolentAI's AI-driven approach to target discovery, we screened potential AI-predicted therapeutic targets mapped to unapproved tool compounds in patient-derived 3D models. This identified TNIK, which is modulated by NCB-0846, as a novel target for platinum-resistant HGSC.
View Article and Find Full Text PDFACS Chem Neurosci
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School of Molecular and Life Sciences, Faculty of Science and Engineering, Curtin University, Bentley, WA 6845, Australia.
Natural aging is associated with mild memory loss and cognitive decline, and age is the greatest risk factor for neurodegenerative diseases, such as Alzheimer's disease. There is substantial evidence that oxidative stress is a major contributor to both natural aging and neurodegenerative disease, and coincidently, levels of redox active metals such as Fe and Cu are known to be elevated later in life. Recently, a pronounced age-related increase in Cu content has been reported to occur in mice and rats around a vital regulatory brain region, the subventricular zone of lateral ventricles.
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