Organ‐to‐Cell‐Scale Health Assessment Using Geographical Information System Approaches with Multibeam Scanning Electron Microscopy

Abstract

This study combines novel multibeam electron microscopy with a geographical information system approach to create a first, seamless, navigable anatomic map of the human hip and its cellular inhabitants. Using spatial information acquired by localizing relevant map landmarks (e.g. cells, blood vessels), network modeling will enable disease epidemiology studies in populations of cells inhabiting tissues and organs.

Live Tissue Imaging to Elucidate Mechanical Modulation of Stem Cell Niche Quiescence

“…However, previous studies have demonstrated that ovine periosteal‐derived cell morphological patterns of phenotype remain the same as those for human PDCs , . Although we ultimately aim to translate the current approach to the human condition, access to sufficient quantities of fresh human periosteum with and without prestress is currently not ethically or practically feasible, although cutting edge imaging technologies enabling seamless imaging from the organ to the nano‐length scale promise an exciting future in this regard , . Quantitative characterization of ovine periosteum as a stem cell niche provides a critical step in the clinical translation of periosteum's regenerative power in the context of the ovine model and its recent application to limited human patients .…”

Translating Periosteum's Regenerative Power: Insights From Quantitative Analysis of Tissue Genesis With a Periosteum Substitute Implant

“…Finally, multimodal, high‐resolution imaging of anatomical cross‐sections at cellular scale resolution enables not only in situ assessment of tissue genesis by stem cells but also assessment of interactions of cells with absorbable and nonabsorbable materials commonly used in reconstructive surgery [57]. Cutting‐edge imaging modalities will enable seamless imaging of the periosteum and its cellular inhabitants, from the organ to subcellular length scale, enabling observation of PDCs in their native milieu and in interaction with novel functional materials of the future [77–78].…”

Creating High-Resolution Multiscale Maps of Human Tissue Using Multi-beam SEM

“…Already, a few recent studies in connectomics have utilized mSEM to render volumetric image data from murine specimens sectioned with a microtome and reconstruct neuronal circuits with single-synapse resolution [14]. Multiscale imaging of interfaces between musculoskeletal tissue compartments could reveal precise architectures of tight junctions that control functional barrier properties, which exert profound effects on human physiology [1,2,12,32]. …”

“…Its novel design enables the analysis of nanoscale morphologies across macroscopic specimens by implementing parallel electron beams and a multi-channel detector [10,11]. Multi-beam SEM is capable of reducing acquisition time by more than one order of magnitude and, therefore, of imaging larger surface areas with remarkable resolution [11], paving the path for seamless multiscale imaging of organ systems down to the cellular and even molecular scale [12]. As a consequence, this technology has drawn interest within the scientific community, particularly in areas related to brain connectomics [13,14] and cross-scale musculoskeletal mechanobiology [2,10].…”

“…Already, a few recent studies in connectomics have utilized mSEM to render volumetric image data from murine specimens and reconstruct neuronal circuits with single-synapse resolution [13,14]. Another recent study from our lab demonstrated the feasibility of using high resolution, navigable multiscale maps of human tissue, created for the first time with mSEM, to assess organ- to cell-scale health using epidemiological approaches [12]. Here we describe technical challenges and solutions for the creation of such maps for biomedical applications, using human sample datasets obtained with a mSEM prototype.…”