Application of Imaging Technology to Humans

Recent development of imaging technology has been remarkable and has given great impact to life science research. Moreover, attempts to apply this novel technique to humans and practice it in clinical medicine have also started. Especially, some articles report the utility of imaging living tissues that do not require any labeling in recent years. This “non-labeling imaging” technique has a great potential in human application and clinical medicine practice. In this review, we describe the application of imaging technology to humans, mainly focusing on the diagnosis of cancer by non-labeling imaging with multiphoton excitation microscopy.The version of record of this article, first published in Make Life Visible, is available online at Publisher’s website: https://doi.org/https://doi.org/10.1007/978-981-13-7908-6_2

Imaging the bone-immune cell interaction in bone destruction

Bone is a highly dynamic organ that is continuously being remodeled by the reciprocal interactions between bone and immune cells. We have originally established an advanced imaging system for visualizing the in vivo behavior of osteoclasts and their precursors in the bone marrow cavity using two-photon microscopy. Using this system, we found that the blood-enriched lipid mediator, sphingosine-1-phosphate, controlled the migratory behavior of osteoclast precursors. We also developed pH-sensing chemical fluorescent probes to detect localized acidification by bone-resorbing osteoclasts on the bone surface in vivo, and identified two distinct functional states of differentiated osteoclasts, “bone-resorptive” and “non-resorptive.” Here, we summarize our studies on the dynamics and functions of bone and immune cells within the bone marrow. We further discuss how our intravital imaging techniques can be applied to evaluate the mechanisms of action of biological agents in inflammatory bone destruction. Our intravital imaging techniques would be beneficial for studying the cellular dynamics in arthritic inflammation and bone destruction in vivo and would also be useful for evaluating novel therapies in animal models of bone-destroying diseases.Hasegawa T., Kikuta J., Ishii M.. Imaging the bone-immune cell interaction in bone destruction. Frontiers in Immunology 10, 596 (2019); https://doi.org/10.3389/fimmu.2019.00596

The effects of vitamin D on immune system and inflammatory diseases

Immune cells, including dendritic cells, macrophages, and T and B cells, express the vitamin D receptor and 1α-hydroxylase. In vitro studies have shown that 1,25-dihydroxyvitamin D, the active form of vitamin D, has an anti-inflammatory effect. Recent epidemiological evidence has indicated a significant association between vitamin D deficiency and an increased incidence, or aggravation, of infectious diseases and inflammatory autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. However, the impact of vitamin D on treatment and prevention, particularly in infectious diseases such as the 2019 coronavirus disease (COVID-19), remains controversial. Here, we review recent evidence associated with the relationship between vitamin D and inflammatory diseases and describe the underlying immunomodulatory effect of vitamin D.Ao T., Kikuta J., Ishii M.. The effects of vitamin D on immune system and inflammatory diseases. Biomolecules 11, 1624 (2021); https://doi.org/10.3390/biom11111624

Imaging the Bone-Immune Cell Interaction in Bone Destruction

Bone is a highly dynamic organ that is continuously being remodeled by the reciprocal interactions between bone and immune cells. We have originally established an advanced imaging system for visualizing the in vivo behavior of osteoclasts and their precursors in the bone marrow cavity using two-photon microscopy. Using this system, we found that the blood-enriched lipid mediator, sphingosine-1-phosphate, controlled the migratory behavior of osteoclast precursors. We also developed pH-sensing chemical fluorescent probes to detect localized acidification by bone-resorbing osteoclasts on the bone surface in vivo, and identified two distinct functional states of differentiated osteoclasts, “bone-resorptive” and “non-resorptive.” Here, we summarize our studies on the dynamics and functions of bone and immune cells within the bone marrow. We further discuss how our intravital imaging techniques can be applied to evaluate the mechanisms of action of biological agents in inflammatory bone destruction. Our intravital imaging techniques would be beneficial for studying the cellular dynamics in arthritic inflammation and bone destruction in vivo and would also be useful for evaluating novel therapies in animal models of bone-destroying diseases

Intravital imaging of orthotopic and ectopic bone

Bone homeostasis is dynamically regulated by a balance between bone resorption by osteoclasts and bone formation by osteoblasts. Visualizing and evaluating the dynamics of bone cells in vivo remain difficult using conventional technologies, including histomorphometry and imaging analysis. Over the past two decades, multiphoton microscopy, which can penetrate thick specimens, has been utilized in the field of biological imaging. Using this innovative technique, the in vivo dynamic motion of bone metabolism-related cells and their interactions has been revealed. In this review, we summarize previous approaches used for bone imaging and provide an overview of current bone tissue imaging methods using multiphoton excitation microscopy.Hashimoto K., Kaito T., Kikuta J., et al. Intravital imaging of orthotopic and ectopic bone. Inflammation and Regeneration 40, 26 (2020); https://doi.org/10.1186/s41232-020-00135-6