Structure, Composition and Histology Core

Structure and composition across physiological length-scales (e.g., organ, tissue, cell, matrix, nanoscale-levels) are key intermediate traits that link gene expression with functional outcomes. Genetic and/or environmental perturbations affecting gene expression often lead to measurable changes in these intermediate traits that have mechanical and other functional consequences. Accurately quantifying structure and composition at different length scales is therefore essential to advancing our understanding of the molecular and mechanical mechanisms underlying musculoskeletal health and disease; to develop and evaluate treatment strategies; and to ultimately translate these strategies to the clinic. The Structure, Composition and Histology Core will provide access to the instruments and expertise that will enable Center investigators to quantify these intermediate traits and to accelerate their research programs.

Services include ex vivo micro-Computed Tomography (CT) and ex vivo nano-Computed Tomography (nano-CT), Raman spectroscopy, and Histology as the major components.

The ex vivo microComputed Tomography (microCT) and nanoCT systems provide full 3-D reconstructed images of hard and soft biological tissues, as well as non-biological materials. The Dental School core has an ex vivo Scanco 100 microCT and the Orthopaedic Research Laboratories ex vivo scanner is a GE Phoenix nanotom-m nanoCT. See the websites listed below for details of system capabilities.

Raman spectroscopy services will be provided by Dr. Gurjit Mandair, who is located in the School of Dentistry. We provide guidance on sample preparation (fresh or embedded), compositional analysis (soft/hard tissues), and training on our Raman microscope/fiber-optic probe instruments

Histology is an essential component of all in vivo musculoskeletal studies. This core will enhance existing research by centralizing histologic efforts to achieve high quality and reasonably priced histology for center investigators, and to ensure, in collaboration with the other cores, a cost-effective, efficient, integrated, hierarchical approach to the evaluation of tissue phenotypes. Procedures are posted on the website.

The Histology part of this core supports these following procedures: plastic processing/embedding/sectioning and staining, paraffin processing/embedding/sectioning and staining, and frozen sectioning. Discounts are provided primarily for plastic procedures as the prices for paraffin procedures are very competitive with other facilities on campus.

An advanced histology training program has been developed to provide for the safe and proficient use of histological equipment. In addition to the training, supervision of first-time use is provided to be sure that all safety measures are being followed and the equipment is being used in the proper manner.

Each training session also comes with future technical support, slide Q & A, staining advice, etc., as our goal is to have trainees not just know how to produce histology products, but how to do it well and to understand what they are doing on a scientific level. Trainees are encouraged to ask our Histologists anything about the process, suggested processing adaptations, how to better prepare samples the next time, etc. We also have a stock of control tissue that is open for anyone completing the training.

Existing Core Websites:

Dental School microCT core: https://dent.umich.edu/research/microct-core

ORL nanoCT core: https://nanoctcore.med.umich.edu

ORL Histology core: https://histologycore.med.umich.edu (this site is under construction)

Contact: Contact David Kohn, PhD when beginning a project and for general assistance with core access. He will provide guidance on experimental design and the appropriate Faculty and Core expert to contact next.

Core Leadership

Services Offered and Prices

1. ex vivo nanoCT and microCT: For P30 members, 20% of the cost for ex vivo nanoCT and microCT scanning is covered by the core center.

The cost structure allows P30 members to choose the system based on scientific need rather than price.

All rates shown below are for UofM faculty. For academic users outside of UofM or Industry users, please contact contact Andrea Clark (clarkand@med.umich.edu for nanoCT scans) or Michelle Lynch (mayln@umich.edu for microCT scans) for current rates. Prices shown are effective 8/1/2024.

2. Raman spectroscopy: The Composition Core provides faculty, students, and staff with training and access to research-grade Raman spectroscopy instruments for analyzing the matrix composition of soft and hard tissues, and synthetic materials. By examining the molecular composition and structure of tissues, Raman spectroscopy enables holistic characterization of their phenotype or pathology. The molecular composition of tissues, with varying proteins, amino acids, lipids, and/or sugar components, can be detected to yield relative quantitative insights. For hard tissues and mineralized biomaterials, Raman spectroscopy can also help identify the minerals present and offer insights into their crystalline state. For more information, contact Dr. Gurjit Mandair (gmandair@umich.edu) or Dr. David Kohn (dhkohn@umich.edu). Refer to this flyer and the SOP Raman section for details on our Raman instruments, protocols, and application notes.

3. See the Histology Workflow and Standard Operating Procedures (SOPs) for more information on the Cryosectioning, Paraffin and Plastic embedding and sectioning services. The various Workflow and SOPs describe the prep work, steps, and where each of the services listed below (items 3 & 4) would be involved in the process. Also available is a booklet containing all the protocols relative to plastic thin sectioning and histomorphometric analysis of the sections. Please note that plastic services extend the turnaround time due to extended processing times and the slow polymerization of the (poly) methyl methacrylate.

4. The Histology Core is using iLab to process histology requests. Requests for service may be submitted on the UMICH Orthopaedic Research Laboratories (ORL) Histology Core iLab page. Help or general information on using the iLab site can be found here.

NOTE: All rates shown below are for UofM faculty. For academic users outside of UofM or Industry users, please contact Carol Whitinger (whitinge@med.umich.edu) or Emma Snyder-White (eparrs@med.umich.edu) for current rates. Prices shown are effective 8/1/2024.

5. Labor Rates for Miscellaneous Services

Plastic Services $59.70 / hour
Paraffin Services $42.80 / hour

6. Full Service Histology (services provided byMiMHC Core personnel)

7. Self Service Histology (training provided by MiMHC Core personnel; only trained users can use sectioning equipment)

8. Advanced training (training provided by MiMHC Core personnel and includes the proper use of equipment, safety training, review of work, and quality assurance)

An advanced histological training program has been developed to provide for the safe and proficient use of histological equipment. In addition to the training, supervision of first-time use is provided to ensure that all safety measures are being followed and the equipment is being used properly. Each training session comes with future technical support, slide Q & A, staining advice, etc. Our goal is to have trainees and staff not just know how to produce high quality histological outcomes, but to also improve their understanding of what they are doing on a scientific level. Trainees are welcome to ask our Histologists anything about the process, how to better prepare samples, and how to improve sample processing, etc. We also have a stock of control tissues that is available to accelerate the training.

NOTE: All rates shown above are for UofM faculty. For academic users outside of UofM or Industry users, please contact Carol Whitinger (whitinge@med.umich.edu) or Emma Snyder-White (eparrs@med.umich.edu) for current rates. Prices shown are effective 8/1/2024.

9. Histological Staining Menu

Please look at this page for special stain offerings and sample images.

10. Additional equipment and services provided by the core:

Stratec XCT 2000 L peripheral quantitative computed tomography (pQCT) imaging system (training required)

Advice on use of Dragonfly software for image analysis, use of fully convolutional neural networks (FCNNs) for image segmentation, and development and validation of new FCNNs.

Advice on use of contrast agents and vascular perfusions to acquire 3D micro/nanoCT images of soft tissues

Access to Faxitron imaging in the Orthopaedic Research Laboratories

Referencing Core services in manuscripts

When referencing the use of the MiMHC Core services in your manuscripts, please use the following text:

"Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number P30 AR069620. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.”

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