From ulcer healing to remission: imaging and biomechanics of tissue properties in association with foot ulcer risk in diabetes

Background

The risk of developing a foot ulcer in people with diabetes increases when peripheral neuropathy, biomechanical abnormalities and peripheral vascular disease are present as complications of the disease. In particular when people have just healed from a foot ulcer, the risk of developing another one is high. In this high-risk group, we have an incomplete understanding of the pathogenesis of ulcer recurrence. Biomechanical factors are important, but there are gaps in our knowledge concerning the extent and exact mechanisms through which these factors contribute to foot ulceration. This is evident in the early stages of remission, the first months after healing of a foot ulcer.

In this DIALECT project we aim to go beyond the state-of-the-art and develop and validate comprehensive and novel biomechanical analyses and models of the foot in remission using advanced imaging, histological and biomechanical techniques, to better understand the complexity and severity of this condition and pave the way for more personalised medicine in ulcer and amputation prevention.

Approach

The properties of the skin and soft tissue underneath it likely contribute to the increased risk for renewed skin breakdown, with histological and biochemical changes of previously ulcerated tissue likely affecting the reparative response, and possibly further mediated by the severity of neuropathy and micro- and macrovascular disease in the leg. These changes affect the mechanical properties and loading capacity of the tissue, yet in-depth soft-tissue and biomechanical analyses are not yet available, maybe due to a lack of advanced imaging solutions to assess subtle changes in hard and soft tissue in relation to mechanical stress under dynamic conditions. These advanced imaging solutions include weight-bearing CT (WBCT), fat fraction assessment with MRI, MR and ultrasound elastography.

The doctoral candidate will explore, develop and apply these imaging  solutions together with histological and biomechanical techniques in people who have just healed from a plantar foot ulcer. The doctoral candidate will compare follow patients over time to associate tissue properties with biomechanical and clinical outcomes and with that develop a comprehensive biomechanical model of ulcer recurrence. These analyses are unprecedented in this field and expected to advance our understanding of diabetic foot disease in remission.

Secondments will take place at IOR for training in lower-extremity biomechanics, tissue properties and engineering, and imaging (weight-bearing CT and dual energy CT) and data analysis; and at SDCC for training in foot biomechanics, cadaveric anatomical studies with hard and soft tissue analysis, orthopaedic foot surgery, and patient-related factors in ulcer recurrence. 

Our Research Team

Amsterdam UMC is a leading institute in the world on biomechanical, radiological and clinical research on diabetic foot disease, in particular on the prevention of foot ulceration and amputation. The candidate will learn from, and collaborate with a multidisciplinary team of clinicians, movement scientists and radiologists and also with two other DIALECT Doctoral Candidates in Amsterdam UMC who focus in their projects on specific deformities and footwear development for ulcer prevention.

The research group is embedded within the department of Rehabilitation Medicine that has high-class facilities for biomechanical research with a motion analysis laboratory, including plantar pressure measurements, and hosts the outpatient diabetic foot clinic; and also in the department of Radiology, which is equipped with high-end clinical and research techniques exploring both qualitative morphological and quantitative biomarker development: high field MRI (3T, 7T), WBCT. Dual-energy CT, ultrasound. The new technique of elastography can be used with MR and US; it’s use needs exploration and development. The RICC (Research Imaging Core Center) and the Imaging groups of prof. Nederveen and prof. Strijker focus on biomarker development, both qualitative and quantitative. The research group is also embedded in the Amsterdam Movement Sciences research institute, within which collaboration exists with partners in the field of movement sciences, tissue engineering, musculoskeletal disease, and sports, as part of the Faculty of Behavioural and Movement Sciences of the Vrije Universiteit.

Amsterdam University Medical Centers

The Amsterdam UMC is the largest hospital and foremost medical research institution in the Netherlands with over 13,000 employees, combining what were previously the Academic Medical Center and Vrije Universiteit Medical Center. The location of Amsterdam UMC at Meibergdreef is part of the University of Amsterdam. Some 2500 staff members are fully or partially employed in medical research. Amsterdam Movement Sciences is one of the 8 research institutes of Amsterdam UMC that conducts world-class research on many different aspects of movement, both fundamental and clinical (see here for more info). Amsterdam UMC houses high quality core facilities including a movement analysis lab, advanced imaging techniques, medical physics department.