Intraoperative intravital microscopy permits the study of human tumour vessels

Abstract

Tumour vessels have been studied extensively as they are critical sites for drug delivery, anti-angiogenic therapies and immunotherapy. As a preclinical tool, intravital microscopy (IVM) allows for in vivo real-time direct observation of vessels at the cellular level. However, to date there are no reports of intravital high-resolution imaging of human tumours in the clinical setting. Here we report the feasibility of IVM examinations of human malignant disease with an emphasis on tumour vasculature as the major site of tumour-host interactions. Consistent with preclinical observations, we show that patient tumour vessels are disorganized, tortuous and ∼50% do not support blood flow. Human tumour vessel diameters are larger than predicted from immunohistochemistry or preclinical IVM, and thereby have lower wall shear stress, which influences delivery of drugs and cellular immunotherapies. Thus, real-time clinical imaging of living human tumours is feasible and allows for detection of characteristics within the tumour microenvironment.

Molecular mobility and activity in an intravital imaging setting – implications for cancer progression and targeting

“…IVM has already been employed in human melanoma patients to image intravenously infused fluorescein to assess tumour vasculature and vascular patency (Fisher et al, 2016). By imaging tumour vessels through an incision into the skin, blood vessels were found to have an enlarged diameter in the in vivo setting compared with previous findings from fixed tumour tissues, further emphasising the importance of imaging cells and tissues in vivo in their native environment.…”

A new possibility in fertility preservation: The artificial ovary

“…Besides PET/CT, near infrared spectroscopy and hyperspectral imaging may enable oxygenation monitoring of the transplanted tissue in vivo early enough to predict functionality (Holmer et al, ; Jarraya, Mohamed, Sofiene, & Kolsi, ; Manley, ). An intravital microscopy that allows real‐time in vivo observation of the vessels at the cellular level can also be adapted to monitor neo‐angiogenesis in the graft (Fisher et al, ; Pang et al, ).…”

“…(Holmer et al, 2016;Jarraya, Mohamed, Sofiene, & Kolsi, 2016;Manley, 2014). An intravital microscopy that allows real-time in vivo observation of the vessels at the cellular level can also be adapted to monitor neo-angiogenesis in the graft (Fisher et al, 2016;Pang et al, 2015). Offspring through natural mating (Carroll & Gosden, 1993) 2008 (Silber et al, 2005;Silber et al, 2008;Silber & Gosden, 2007) (J.…”

Imaging the pharmacology of nanomaterials by intravital microscopy: Toward understanding their biological behavior

“…Targeted fluorescent molecular probes for instance targeting the cancer markers prostate-specific membrane antigen (PSMA) [132] and cathepsins [133] enable intraoperative fluorescence imaging at the time of tumor resection to identify tumor margins. Bedside IVM systems have also been developed for cutaneous imaging in melanoma, and have been primarily useful for quantifying the tumor vasculature’s structure, permeability, and perfusion [134]. IVM has not been widely used for NP imaging in the clinic; however, the progress in endoscopic and laparoscopic fluorescence imaging [126,132,133] combined with the demonstrated safety and routine use of various NPs and fluorescent dyes in patients suggests that such applications are feasible.…”

“…IVM of dyes, particles, and cells in microvasculature, including through THG imaging, also enables direct measurement of fluid flow and single-cell movement along capillary walls. These features can then be mapped to vessel structure information to glean an array of mechanical properties [134,275,276]. Computational studies of vascular perfusion [277] and its effect on tumor growth [278] or thrombosis [279] are all examples of IVM data-driven modeling.…”