Magnetic resonance elastography of skeletal muscle deep tissue injury

The underlying mechanisms leading to deep tissue injury after sustained compressive loading are not well understood. It is hypothesized that initial damage to muscle fibers is induced mechanically by local excessive deformation. Therefore, in this study, an animal model was used to study early damage after compressive loading to elucidate on the damage mechanisms leading to deep pressure ulcers. The tibialis anterior of Brown-Norway rats was loaded for 2 h by means of an indenter. Experiments were performed in a magnetic resonance (MR)-compatible loading device. Muscle tissue was evaluated with transverse relaxation time (T2)-weighted MRI both during loading and up to 20 h after load removal. In addition, a detailed examination of the histopathology was performed at several time points (1, 4, and 20 h) after unloading. Results demonstrated that, immediately after unloading, T2-weighted MR images showed localized areas with increased signal intensity. Histological examination at 1 and 4 h after unloading showed large necrotic regions with complete disorganization of the internal structure of the muscle fibers. Hypercontraction zones were found bilateral to the necrotic zone. Twenty hours after unloading, an extensive inflammatory response was observed. The proposed relevance of large deformation was demonstrated by the location of damage indicated by T2-weighted MRI and the histological appearance of the compressed tissues. Differences in damage development distal and proximal to the indenter position suggested a contribution of perfusion status in the measured tissue changes that, however, appeared be to reversible.

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Serum and Urine Biomarker Elevation Indicating the Onset of Deep Tissue Injury as Examined on a Rat Model

ASME 2010 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2010-19313 ◽

2010 ◽

Author(s):

Mohsen Makhsous ◽

Atek Pandya ◽

Mauli Modi ◽

Briana Reprogle ◽

Christopher C. Chadwick ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Damage ◽

Rat Model ◽

Tissue Injury ◽

Muscle Layer ◽

Release Time ◽

Deep Tissue ◽

Fatty Acid Binding ◽

Deep Tissue Injury ◽

Serum And Urine

Deep tissue injury (DTI) is a serious pressure ulcer (PU) which initiates in deep tissue, mainly muscle, and progresses rapidly to a full-thickness wound [1, 2]. Therefore, an early indication should help in increasing awareness and providing prompt intervention to prevent it from progressing to an open wound, which is susceptible to infection and typically needs prolonged and aggressive care. However, the diagnosis of DTI is currently still vague at best[2] with only subjective tools. This situation calls for tools for objectively sensing the tissue changes while the skin is still intact, to allow development of evidence-based protocols for early diagnosis and treatment. Since DTI initiates from deep muscle layer around a bony prominence, a tool that sensitive to muscle damage may have the potential to objectively sense the onset of a DTI in clinical application. A number of molecular biomarkers have been reported in the literature as suitable for indicating muscle damage. Some of the most promising biomarkers are myoglobin and heart-type fatty acid binding protein (H-FABP). Myoglobin and H-FABP are two relatively small muscle proteins that show a very fast release time after skeletal muscle damage/necrosis when no myocardial infarction or damage is present; therefore, they may be used to identify skeletal muscle injury in DTI formation. The objective of this study was to initially test whether myoglobin and H-FABP in serum and urine respond quickly to pressure induced deep tissue injury on a rat model. It is expected that knowledge gained from this study may lead to a promising new methodology to sense the visually invisible DTI.

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Myoprotective effects of bFGF on skeletal muscle injury in pressure-related deep tissue injury in rats

Burns & Trauma ◽

10.1186/s41038-016-0051-y ◽

2016 ◽

Vol 4 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Hongxue Shi ◽

Haohuang Xie ◽

Yan Zhao ◽

Cai Lin ◽

Feifei Cui ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Regeneration ◽

Muscle Injury ◽

Muscle Development ◽

Tissue Injury ◽

Skeletal Muscle Regeneration ◽

Deep Tissue ◽

External Compression ◽

Deep Tissue Injury ◽

Skeletal Muscle Injury

Abstract Background Pressure ulcers (PUs) are a major clinical problem that constitutes a tremendous economic burden on healthcare systems. Deep tissue injury (DTI) is a unique serious type of pressure ulcer that arises in skeletal muscle tissue. DTI arises in part because skeletal muscle tissues are more susceptible than skin to external compression. Unfortunately, few effective therapies are currently available for muscle injury. Basic fibroblast growth factor (bFGF), a potent mitogen and survival factor for various cells, plays a crucial role in the regulation of muscle development and homeostasis. The main purpose of this study was to test whether local administration of bFGF could accelerate muscle regeneration in a rat DTI model. Methods Male Sprague Dawley (SD) rats (age 12 weeks) were individually housed in plastic cages and a DTI PU model was induced according to methods described before. Animals were randomly divided into three groups: a normal group, a PU group treated with saline, and a PU group treated with bFGF (10 μg/0.1 ml) subcutaneously near the wound. Results We found that application of bFGF accelerated the rate of wound closure and promoted cell proliferation and tissue angiogenesis. In addition, compared to saline administration, bFGF treatment prevented collagen deposition, a measure of fibrosis, and up-regulated the myogenic marker proteins MyHC and myogenin, suggesting bFGF promoted injured muscle regeneration. Moreover, bFGF treatment increased levels of myogenesis-related proteins p-Akt and p-mTOR. Conclusions Our findings show that bFGF accelerated injured skeletal muscle regeneration through activation of the PI3K/Akt/mTOR signaling pathway and suggest that administration of bFGF is a potential therapeutic strategy for the treatment of skeletal muscle injury in PUs.

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Temporal differences in the influence of ischemic factors and deformation on the metabolism of engineered skeletal muscle

Journal of Applied Physiology ◽

10.1152/japplphysiol.01374.2006 ◽

2007 ◽

Vol 103 (2) ◽

pp. 464-473 ◽

Cited By ~ 68

Author(s):

Debby Gawlitta ◽

Cees W. J. Oomens ◽

Dan L. Bader ◽

Frank P. T. Baaijens ◽

Carlijn V. C. Bouten

Keyword(s):

Skeletal Muscle ◽

Cell Death ◽

Muscle Tissue ◽

Tissue Injury ◽

Glucose Deprivation ◽

Tissue Response ◽

Deep Tissue ◽

Deep Tissue Injury ◽

Tissue Metabolism ◽

Glucose Levels

Prolonged periods of tissue compression may lead to the development of pressure ulcers, some of which may originate in, for example, skeletal muscle tissue and progress underneath intact skin, representing deep tissue injury. Their etiology is multifactorial and the interaction between individual causal factors and their relative importance remain unknown. The present study addressed the relative contributions of deformation and ischemic factors to altered metabolism and viability. Engineered muscle tissue was prepared as previously detailed ( 14 ) and subjected to a combination of factors including 0% oxygen, lactic acid concentrations resulting in pH from 5.3 to 7.4, 34% compression, and low glucose levels. Deformation had an immediate effect on tissue viability {[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay}, which increased with time. By contrast, hypoxia evoked metabolic responses (glucose and lactate levels) within 24 h, but viability was only reduced after 48 h. In addition, lactic acidification downregulated tissue metabolism up to an acid concentration (∼23 mM) where metabolism was arrested and cell death enhanced. A similar tissue response was observed during glucose deprivation, which, at negligible concentration, resulted in both a cessation of metabolic activity and a reduction in cell viability. The combination of results suggests that in a short-term (<24 h) deformation, extreme acidification and glucose deprivation increased the level of cell death. By contrast, nonextreme acidification and hypoxia influenced tissue metabolism, but not the development of cell death. These data provide more insight into how compression-induced factors can lead to the onset of deep tissue injury.

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Strain-time cell-death threshold for skeletal muscle in a tissue-engineered model system for deep tissue injury

Journal of Biomechanics ◽

10.1016/j.jbiomech.2008.03.039 ◽

2008 ◽

Vol 41 (9) ◽

pp. 2003-2012 ◽

Cited By ~ 118

Author(s):

Amit Gefen ◽

Bastiaan van Nierop ◽

Dan L. Bader ◽

Cees W. Oomens

Keyword(s):

Skeletal Muscle ◽

Cell Death ◽

Tissue Injury ◽

Model System ◽

Deep Tissue ◽

Deep Tissue Injury

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Modelling the effect of repositioning on the evolution of skeletal muscle damage in deep tissue injury

Biomechanics and Modeling in Mechanobiology ◽

10.1007/s10237-012-0397-4 ◽

2012 ◽

Vol 12 (2) ◽

pp. 267-279 ◽

Cited By ~ 5

Author(s):

Jan Demol ◽

Dorien Van Deun ◽

Bart Haex ◽

Hans Van Oosterwyck ◽

Jos Vander Sloten

Keyword(s):

Skeletal Muscle ◽

Muscle Damage ◽

Tissue Injury ◽

Deep Tissue ◽

Deep Tissue Injury ◽

Skeletal Muscle Damage

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Cell-level temperature distributions in skeletal muscle post spinal cord injury as related to deep tissue injury

Medical & Biological Engineering & Computing ◽

10.1007/s11517-009-0566-5 ◽

2009 ◽

Vol 48 (2) ◽

pp. 113-122 ◽

Cited By ~ 15

Author(s):

Yael Ruschkewitz ◽

Amit Gefen

Keyword(s):

Skeletal Muscle ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Tissue Injury ◽

Cell Level ◽

Deep Tissue ◽

Deep Tissue Injury ◽

Temperature Distributions ◽

Cord Injury

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The Relative Contributions of Muscle Deformation and Ischemia to Pressure Ulcer Development

ASME 2012 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2012-80239 ◽

2012 ◽

Cited By ~ 1

Author(s):

Sandra Loerakker ◽

Gustav J. Strijkers ◽

Klaas Nicolay ◽

Frank P. T. Baaijens ◽

Dan L. Bader ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Tissue ◽

Pressure Ulcer ◽

Soft Tissues ◽

Tissue Injury ◽

Skeletal Muscle Tissue ◽

Ischemia And Reperfusion ◽

Deep Tissue ◽

Deep Tissue Injury ◽

Damage Process

Sustained mechanical loading of soft tissues covering bony prominences may lead to degeneration of skeletal muscle tissue. This can result in a condition termed deep tissue injury (DTI), a severe kind of pressure ulcer that initiates in deep tissue layers, and progresses towards the skin. Previously, we have provided evidence that in a controlled animal model, deformation is the main trigger for damage within a 2 h loading period [1,2]. Recently, we also showed that ischemia and reperfusion may contribute to the damage process during prolonged loading [3]. In the present study, we investigated the relative effects of deformation, ischemia, and reperfusion on the temporal and spatial damage process of skeletal muscle tissue during a 6 h period using magnetic resonance imaging (MRI) techniques.

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An advanced magnetic resonance imaging perspective on the etiology of deep tissue injury

Journal of Applied Physiology ◽

10.1152/japplphysiol.00891.2017 ◽

2018 ◽

Vol 124 (6) ◽

pp. 1580-1596 ◽

Cited By ~ 10

Author(s):

Jules L. Nelissen ◽

Willeke A. Traa ◽

Hans H. de Boer ◽

Larry de Graaf ◽

Valentina Mazzoli ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Rat Model ◽

Tissue Injury ◽

Tissue Response ◽

Resonance Imaging ◽

Complementary Information ◽

Damage Development ◽

Deep Tissue ◽

Deep Tissue Injury

Early diagnosis of deep tissue injury remains problematic due to the complicated and multifactorial nature of damage induction and the many processes involved in damage development and recovery. In this paper, we present a comprehensive assessment of deep tissue injury development and remodeling in a rat model by multiparametric magnetic resonance imaging (MRI) and histopathology. The tibialis anterior muscle of rats was subjected to mechanical deformation for 2 h. Multiparametric in vivo MRI, consisting of T2, T2*, mean diffusivity (MD), and angiography measurements, was applied before, during, and directly after indentation as well as at several time points during a 14-day follow-up. MRI readouts were linked to histological analyses of the damaged tissue. The results showed dynamic change in various MRI parameters, reflecting the histopathological status of the tissue during damage induction and repair. Increased T2 corresponded with edema, muscle cell damage, and inflammation. T2* was related to tissue perfusion, hemorrhage, and inflammation. MD increase and decrease was reported on the tissue’s microstructural integrity and reflected muscle degeneration and edema as well as fibrosis. Angiography provided information on blockage of blood flow during deformation. Our results indicate that the effects of a single damage-causing event of only 2 h of deformation were present up to 14 days. The initial tissue response to deformation, as observed by MRI, starts at the edge of the indentation. The quantitative MRI readouts provided distinct and complementary information on the extent, temporal evolution, and microstructural basis of deep tissue injury-related muscle damage. NEW & NOTEWORTHY We have applied a multiparametric MRI approach linked to histopathology to characterize damage development and remodeling in a rat model of deep tissue injury. Our approach provided several relevant insights in deep tissue injury. Response to damage, as observed by MRI, started at some distance from the deformation. Damage after a single indentation period persisted up to 14 days. The MRI parameters provided distinct and complementary information on the microstructural basis of the damage.

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