Dr. Amit Gefen’s Deformation and Deep Tissue Injury Work
The ROHO Group Research Department
Dr. Amit Gefen is an Associate Professor in the Department of Biomedical Engineering at Tel Aviv
University and Supervisor of the Musculoskeletal Biomechanics Laboratory. The prolific work of
Dr. Gefen and his team from 2006-present has focussed on studying the mechanisms of DTI and
the effects of tissue deformation. The severity and life-threatening nature of DTIs, as well as the
difficulty in visually detecting them, is shifting the focus of the research world from superficial
ulcers to this more life-threatening, and more difficult to detect, mode of injury. DTI awareness
is being actively promoted by EPUAP, and Dr. Gefen is an executive board member of the
organization.
This appears to be the first time a research team has been able to link real-world human, organ,
tissue, and cellular studies to a finite element model that can predict mechanical strains
beneath the ITs and ultimately cell death rates based on strain.
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Finite Element models (FEMs) were developed from human, seated MRIs, and from
experimentation with living animal tissues and BioArtificial Muscle (BAM). The models
can predict the muscle stresses and strains under the ischial tuberosities (ITs), which can
lead to DTI. (Appendix 1)
Living animal tissue and BAM studies were conducted to undestand the stiffening effects
under load and further validate the mechanical properties of muscle tissue. He has also
proven that DTI originates in the muscle tissues, with deformation being the primary
mechanism of death, accelerated by ischemia. (Appendix 2)
Cellular level studies were conducted. Cell death mechanisms of deformation, ischemia,
and membrane stretch were examined and modeled. The result was a strain-time / cell
death mathematical curve that can predict how quickly cells will die under a given
percentage of strain. (Appendix 3)
Linking the understanding of cells and tissues, and the effects of deformation and
ischemia, with FEMs that have been validated to human subjects and through other
means, allows for the opportunity to understand how a cushion design can reduce or
accelerate the time to cell death that can initiate the death spiral mechanisms of
potentially life-threatening DTIs.
ROHO Research Department Summary (Kopplin, Woods, Parsons), edited and approved by Dr. Gefen
December 12, 2011
APPENDIX I
FEM Development and Validation
Gefen’s team took seated MRI scans of multiple people, loaded (deformed) and unloaded.
These overall shapes, along with IT drops, formed boundary conditions that were put into
the subject-specific FEMs, (MRI-FEM) along with tissue mechanical properties (from
previous studies).
Healthy, spinal cord injury (SCI) and obese subjects all underwent patient-specific analysis
with seated MRIs, along with subjects sitting in varying positions/angle/sitting postures.
Static and dynamic studies were also conducted. Their data has further refined the model
for determining %-Strain (compression, tension, von Mises, and shear ) and Stress
(compression, von Mises, shear) at the deep tissues beneath the ITs.
The resulting FEM includes distinct muscle, fat, and skin properties, and can be adjusted
for levels of muscle atrophy and sharpness of the ITs. The FEM can calculate distributions
of stresses and strains in muscle tissues beneath the ITs, which have been found by
Gefen’s work to be adequate predictors of DTI.
Results were validated by comparing FEM deformation predictions and actual subject MRI
measurements of skin, fat, and muscle deformations (tissue contours). Further validation
was done with pressure maps, comparing predicted and actual surface pressure readings.
Tissue mechanical property calculations were fine-tuned (based on tissue studies) to
create agreement and refine the modeling. Model deformation predictions were further
validated against physical phantom models (e.g. including real bovine muscle tissue,
human geometry), as well as against predictions of commecial, non-real-time FE models.
A specific, real-life human injury validation was conducted (a case study of a cell phone
induced DTI in an unconscious patient). Actual DTI at the hip injury site was compared to
predictions by the FEM, which was found to reasonably predict the size and shape of the
DTI, and the strains and stresses in the muscles and fat which led to the injury outcome
(as validated by MRI).
ROHO Research Department Summary (Kopplin, Woods, Parsons), edited and approved by Dr. Gefen
December 12, 2011
Real-Time detection of DTI - Possible Clinical Tool
Real-time analysis model (based on the Hertz contact theory) is a simplified, analytical
model that defines fat and muscle more simply and utilizes a rigid spherical indenter to
represent a bony prominence. This allows the computing to be done by a PDA instead of
a larger computer, for portability, speed and cost-effectiveness. This model was validated
by the MRI-FE, and hopes are that it can be developed into a clinical tool. Device
envisioned would require a one-time ulstrasound or MRI scan, and entry of basic
characteristics of the individual. Device could then accompany person all day, constantly
checking and warning user. 2009 refinement enhanced the model to represent fat and
muscle more realistically.
By coupling the FEM with the Stress-time/cell-death curve, the effects of body type,
position, muscle atrophy, and sitting surface have been evaluated and translated into
predicted “safe sitting” times according to each variable.
ROHO Research Department Summary (Kopplin, Woods, Parsons), edited and approved by Dr. Gefen
December 12, 2011
The work of Dr. Gefen and others has determined and highlighted the factors that lead to
this injury, and the FEMs and detection systems proposed have the potential to
dramatically improve the quality of preventive care for SCI individuals.
Portnoy S, V. N., Payan Y, Gefen A. (2011). "Clinically oriented real-time monitoring of the
individual's risk for deep tissue injury." Med Biol Eng Comput. 49(4):473-83.
Shabshin, N., G. Zoizner, et al. (2010). "Use of weight-bearing MRI for evaluating wheelchair
cushions based on internal soft-tissue deformations under ischial tuberosities." The Journal of
Rehabilitation Research and Development 47(1): 31.
Linder-Ganz, E., G. Yarnitzky, et al. (2009). "Real-Time Finite Element Monitoring of SubDermal Tissue Stresses in Individuals with Spinal Cord Injury: Toward Prevention of Pressure
Ulcers." Annals of Biomedical Engineering 37(2): 387-400.
Linder-Ganz, E., Shabshin, N., and gefen, A. (2009). “Patient –specific Modeling of Deep tissue
Injury Biomechanics in an Unconscious Patient who Developed Myonecrosis after Prolonged
Lying.” Journal of Tissue Viability 18: 62-71
Agam, L. and A. Gefen (2008). "Toward real-time detection of deep tissue injury risk in
wheelchair users using Hertz contact theory." J Rehabil Res Dev 45(4): 537-550.
Gefen, A. (2007). "Pressure-Sensing Devices for Assessment of Soft Tissue Loading Under Bony
Prominences: Technological Concepts and Clinical Utilization." Wounds 19(12): 350.
Linder-Ganz E, S. N., Itzchak Y, Gefen A (2007). "Assessment of mechanical conditions in subdermal tissues during sitting: a combined experimental-MRI and finite element approach." J
Biomech. 40(7):1443-54.
ROHO Research Department Summary (Kopplin, Woods, Parsons), edited and approved by Dr. Gefen
December 12, 2011
APPENDIX 2
Organ and Tissue Testing
Porcine, bovine and ovine muscle and fat tissue properties were experimentally
determined and incorporated in the FEM. The gluteal muscle tissues were identified as
the most susceptible sites for DTI, not fat or skin (muscle tissues are directly loaded by
bony prominences, as opposed to fat and skin which also contain less vascularization).
Rat muscle tissues were subjected to compressive loading and shear, and values were
used to refine the FEM. Studies revealed stiffening of rat muscle tissue when injured (up
to 3 times depending on load – “local rigor mortis”), which was incorporated as damage
laws within the FEM, to modify the stress calculations of the regions in the boundaries of
the injury site. BAMs were created using tissue engineering methods to analyze the
effects of loading on cell death rates, in the absence of a vascular system so that the
contribution of deformation to cell death could be tested in isolation from ischemic
factors.
In human studies conducted by the Gefen group using MRI-FE and real-time FE patientspecific analyses, patients with a SCI experienced peak stress dose values beneath the ITs
that were 35-50 times higher than in healthy individuals. In these patients, 12-24%
smaller cross-sectional areas of the muscle tissues were observed as soon as 6 months
post-injury. It was concluded that loss of muscle mass per se is a major DTI risk factor,
and IT geometries change post-injury as well through shape adaptation responses of the
cortical bone.
A word on the contribution of ischemia to DTI: tissue-engineered BAM studies illustrated
the effects of load/deformation on diffusivity of metabolites and cell death without a
vascular system. This and other studies clearly indicated a damage spiral which is not just
due to ischemia – tissue and cell deformation is a critical factor, particularly at the onset
of the injury. Unloaded muscle has high tolerance for ischemia, but death accelerates
with compressive deformations, at even low shear strains (partial blood flow exists even
at high compressive loads as confirmed by infrared thermography). Presence of abovecritical mechanical loading is a direct cause of tissue damage – ischemia accelerates it
(this has been confirmed by Eindhoven research as well, Oomens et al.) Tissue can live
with only ischemia for up to 22 hrs , but almost instant cell death can occur if there is
sufficient deformation, e.g. damage can occur within 4 hours if <25% deformation.
ROHO Research Department Summary (Kopplin, Woods, Parsons), edited and approved by Dr. Gefen
December 12, 2011
Gefen A. (2007) The biomechanics of sitting-acquired pressure ulcers in patients with spinal
cord injury or lesions. Int Wound J.4(3):222-31.
Linder-Ganz, E. and A. Gefen (2009). "Stress analyses coupled with damage laws to
determine biomechanical risk factors for deep tissue injury during sitting." Journal of
Biomechanical Engineering 131: 011003.
Gefen, A. (2009). "Deep Tissue Injury from a B
Management 55(4): 26-36.
Linder-Ganz E, S. N., Itzchak Y, Yizhar Z, Siev-Ner I, Gefen A (2008). "Strains and stresses in
sub-dermal tissues of the buttocks are greater in paraplegics than in healthy during sitting." J
Biomech. 41(3):567-80.
Gefen A, van Nierop B, Bader DL, Oomens CW. (2008) Strain-time cell-death threshold for
skeletal muscle in a tissue-engineered model system for deep tissue injury. J. Biomech.
41:2003-2012.
Linder-Ganz, E. and A. Gefen (2007). "The Effects of Pressure and Shear on Capillary Closure in
the Microstructure of Skeletal Muscles." Annals of Biomedical Engineering 35(12): 2095-2107.
Gefen, A., N. Gefen, et al. (2005). "In Vivo Muscle Stiffening Under Bone Compression
Promotes Deep Pressure Sores." Journal of Biomechanical Engineering 127(3): 512-524.
Palevski A, Glaich I, Portnoy S, Linder-Ganz E, Gefen A. (2006) Stress relaxation of
porcine gluteus muscle subjected to sudden transverse deformation as related to
pressure sore modeling. J Biomech Eng. 128(5):782-7.
Gefen A, Haberman E. (2007) Viscoelastic properties of ovine adipose tissue covering the
gluteus muscles. J Biomech Eng. 129(6):924-30.
ROHO Research Department Summary (Kopplin, Woods, Parsons), edited and approved by Dr. Gefen
December 12, 2011
APPENDIX 3
Histology / Cell Testing
Mechanisms of cell death as a result of deformation were explored with tissueengineered BioArtificial Muscle (BAM), rat muscle tissue histology (using stains) as well as
in cell culture experiments. Specific cell FEM were created, simulating how deformation
stretches the cellular plasma membrane and affects diffusivity of oxygen and other
metabolites, calcium ions, hormones, etc., which can lead to cytotoxicity as the cell-scale
mechanism of cell death, relating deformation and transport. This mechanism of
increased permeability of the plasma membrane was recently confirmed experimentally
by the Gefen group using a device which allows deforming cells in a controlled manner
and monitoring the uptake of fluorescent biomolecules by the distorted cells (Slomka et
al., Leopold and Gefen). Similar studies of the influx and efflux of dextran were conducted
to measure the effect of temperature drops on cell death in BAMs (to simulate ischemia
since the BAMs have no vascular system).
Gefen’s cellular studies, along with work he has done in collaboration with Oomens and
Bader, resulted in the stress-time/cell-death curve that can be used to take measured or
modeled internal strains/stresses and translate these data into predicted “safe” sitting
times.
ROHO Research Department Summary (Kopplin, Woods, Parsons), edited and approved by Dr. Gefen
December 12, 2011
Leopold E, Sopher R, Gefen A. (2011) The effect of compressive deformations on the rate of
build-up of oxygen in isolated skeletal muscle cells. Med Eng Phys;33:1072-1078.
Leopold E, Gefen A. (2011) A simple stochastic model to explain the sigmoid nature of the
strain-time cellular tolerance curve. J Tissue Viability, in press (available online),
doi:10.1016/j.jtv.2011.11.002.
Slomka N, Gefen A. (2011) Relationship between strain levels and permeability of the plasma
membrane in statically stretched myoblasts. Annals of Biomedical Engineering, in press
(available online), doi: 10.1007/s10439-011-0423-1.
Slomka N, Or-Tzadikario S, Sassun S, Gefen A. (2009) Membrane-stretch-induced cell death in
deep tissue injury: computer model studies. Cellular and Molecular Bioengineering 2:118-132.
Gefen A, van Nierop B, Bader DL, Oomens CW. (2008) Strain-time cell-death threshold for
skeletal muscle in a tissue-engineered model system for deep tissue injury. J. Biomech.
41:2003-2012.
ROHO Research Department Summary (Kopplin, Woods, Parsons), edited and approved by Dr. Gefen
December 12, 2011