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An advanced magnetic resonance imaging perspective on the etiology of deep tissue injury
Abstract
Early diagnosis of deep tissue injury remains problematic due to the complicated and multi-factorial 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 multi-parametric magnetic resonance imaging (MRI) and histopathology. The tibialis anterior muscle of rats was subjected to mechanical deformation for 2 h. Multi-parametric 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 days 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 T2corresponded with edema, muscle cell damage, and inflammation. T2∗ was related to tissue perfusion, hemorrhage, and inflammation. MD increase and decrease reported on the tissue's microstructural integrity and reflected muscle degeneration, 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 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.
... More recent studies have adopted other methodologies to demonstrate the aetiology of DTI. These include the use of magnetic resonance imaging (MRI) (Nelissen et al, 2018) and biomarkers to indicate the source and magnitude of tissue damage (Traa et al, 2019). ...
... Notably, Nelissen et al (2018) demonstrated that damage to deep muscle is visible on an MRI scan for up to 2 weeks following mechanical deformation periods of only 2 hours. This was later supported by a study by Traa et al (2019), who demonstrated that concentrations of myoglobin and troponin in blood and urine samples rise following mechanical compression, which provides strong evidence of damage to muscle tissues even in the absence of clinically visible tissue damage at the skin surface. ...
... Solmos et al (2019) concluded that lesions caused by non-pressure related pathologies may frequently be confused with DTI as there is a lack of effective assessment methods to differentiate between DTI and other lesions because DTI aetiology is poorly understood. This reflects current methodologies adopted to investigate DTI; these rely on FEM or animal models and seek to demonstrate damage in deep tissues caused by mechanical deformation, vascular shearing or metabolic stresses but do not demonstrate any clear differences in aetiology between 'normal' PI and DTI because of a lack of concurrent observations of changes in the skin or use of human subjects (Nelissen et al, 2018;Traa et al, 2019). ...
Deep tissue injuries (DTIs) were added to pressure ulcer grading systems in 2009. Since then, they have been associated with the same aetiological processes as other forms of pressure injury (PI). This is despite notable clinical differences in their presentation along with variations in natural history that suggest they are the consequence of processes distinct from those that cause other PIs. Understanding the aetiology of DTIs is essential to guide prevention and treatment in addition to ensuring healthcare governance processes deeply tied to pressure injury are effective and efficient. Current understanding of the aetiology of DTI has significant gaps, with several key challenges impeding progress in this area of PI research, including inconsistent reporting by healthcare services and the limitations of animal and computer models in addition to the ethical barriers to conducting studies on human subjects. Synthesis of early studies with studies undertaken before 2009 is also limited by the variety in definitions of DTI used before that published by the European Pressure Ulcer Advisory Panel, the National Pressure Injury Advisory Panel and the Pan Pacific Pressure Injury Alliance in 2009. To date, few prospective clinical studies have been conducted. This article presents a narrative review on the clinical and animal study evidence indicating contemporary understanding of DTI.
... 22 Concerning pressure ulcers, two main physiological processes, described in histological studies, are inflammation and edema (or interstitial fluid accumulation). [41][42][43][44][45][46][47][48] One study has demonstrated the potential of C-reactive protein (CRP) levels in blood samples as a chemical biomarker of inflammation associated with muscle damage in deep tissue injury. 49 In contrast, biomarkers sampled from the skin surface (e.g., sweat lactate) were not able to reflect damage to the subcutaneous tissue and muscle tissue. ...
... Most included studies (n = 8) used a quasi-experimental design. 34,48,[58][59][60][61][62][63] From the other studies, two used an observational design, 40,64 one combined an observational design with a quasi-experimental design, 65 and one was a nonsystematic review with an educational purpose. 28 The quasiexperimental studies were mostly performed in an animal model (mouse, rat, pig). ...
... In most studies, mechanical loads were applied for 2 hours. 34,48,[58][59][60]62,63 The development of inflammation and associated edema were described using various methods: histology, 48,58-63 biochemistry, 34,59-61 high-resolution ultrasonography, 40,64,65 magnetic resonance imaging, 48,62,63 or immunohistochemistry. 59 To study the effect of ischemia-reperfusion, measurements were performed at time-frames varying between 1 day or less 34,58-60,62,63 till 14 days. 48 One study compared varying number of ischemiareperfusion cycles. ...
Deep tissue injuries are pressure ulcers which initiate in the subcutaneous tissues and extend through a bottom‐up pathway. Once deep tissue injuries are visual at skin level, serious irreversible tissue damage has already occurred. In pressure ulcer development, inflammation and oedema are coupled physiological processes associated with tissue damage arising due to sustained mechanical loading. This study aimed to provide an in‐depth overview of the physiological processes of inflammation and oedema initiated by sustained mechanical loading in subcutaneous tissues, in the context of pressure ulceration. A scoping review was performed according to the framework by Arksey and O'Malley. The databases MEDLINE, EMBASE, Web of Science, and Scopus, and the reference lists of included studies were searched for in vivo (animal, human), and in vitro studies matching the study objectives (from inception to 28 May 2018). No restrictions for inclusion were applied for study design, setting, participants, and year of publication. A total of 12 studies were included, varying in study design, sample characteristics, amount and duration of mechanical loads that were applied, follow‐up time, and assessment methods. Neutrophil infiltration and oedema occur in the subcutaneous tissues nearly immediately after the application of load on soft tissues. The amount of neutrophils and oedema increase in the first days after the mechanical insult and decrease once healing has been initiated and no supplementary mechanical load was applied. One study indicated that oedema may extend up to the level of the dermo‐epidermal junction. Further research should focus on how deep tissue inflammation and oedema are reflected into unique tissue changes at skin level, and how abnormal inflammatory responses manifest (e.g. when the nervous system is not functioning normally). This article is protected by copyright. All rights reserved.
... 19,27 Several MRI and histopathologic readouts were employed to provide a comprehensive understanding of the damage development, recovery, and regeneration in this model. 18,21,25,28,29 It was found that the initial tissue response to deformation started at some distance from the center of indentation, affecting a relatively large area. Secondly, a single indentation of the TA muscle resulted in muscle damage that required at least two weeks to recover. ...
... Time of flight MR angiography provided information on occlusion of blood flow during the indentation period. 29 Furthermore, the use of an animal-specific FEA model, for which the geometry and loading conditions were derived from MRI, supplied estimations of the local tissue deformations. 30 This combined experimental-numerical approach resulted in new understandings of the biomechanical conditions that contribute to the development of deep tissue injury. ...
... The response of skeletal muscle deep tissue injury is known to follow a well-known pathway with multiple overlapping pathological processes. 29 Several studies have concluded that a single MRI contrast cannot capture all of the pathological processes involved in skeletal muscle damage, 22,25,28,[41][42][43][44][45][46][47][48][49][50][51][52][53] which therefore warrants a multi-parametric approach using several complementary MRI readouts to characterize different aspects of injury and recovery. Furthermore, thus far there is limited knowledge on the spatio-temporal changes in the biomechanical properties of the muscle tissue following deformation-induced muscle damage. ...
The current state‐of‐the‐art diagnosis method for deep tissue injury in muscle, a subcategory of pressure ulcers, is palpation. It is recognized that deep tissue injury is frequently preceded by altered biomechanical properties. A quantitative understanding of the changes in biomechanical properties preceding and during deep tissue injury development is therefore highly desired. In this paper we quantified the spatial–temporal changes in mechanical properties upon damage development and recovery in a rat model of deep tissue injury.
Deep tissue injury was induced in nine rats by two hours of sustained deformation of the tibialis anterior muscle. Magnetic resonance elastography (MRE), T2‐weighted, and T2‐mapping measurements were performed before, directly after indentation, and at several timepoints during a 14‐day follow‐up.
The results revealed a local hotspot of elevated shear modulus (from 3.30 ± 0.14 kPa before to 4.22 ± 0.90 kPa after) near the center of deformation at Day 0, whereas the T2 was elevated in a larger area. During recovery there was a clear difference in the time course of the shear modulus and T2. Whereas T2 showed a gradual normalization towards baseline, the shear modulus dropped below baseline from Day 3 up to Day 10 (from 3.29 ± 0.07 kPa before to 2.68 ± 0.23 kPa at Day 10, P < 0.001), followed by a normalization at Day 14.
In conclusion, we found an initial increase in shear modulus directly after two hours of damage‐inducing deformation, which was followed by decreased shear modulus from Day 3 up to Day 10, and subsequent normalization. The lower shear modulus originates from the moderate to severe degeneration of the muscle. MRE stiffness values were affected in a smaller area as compared with T2. Since T2 elevation is related to edema, distributing along the muscle fibers proximally and distally from the injury, we suggest that MRE is more specific than T2 for localization of the actual damaged area.
... Female Sprague-Dawley rats (n = 25, 14 weeks old) were obtained from Charles River, Paris, France. These animals were part of a much larger study on DTI damage development in rats (Nelissen et al., 2018). During the acclimatisation period (minimal 7 days) animals were socially housed under controlled laboratory conditions (12 h light/dark cycles) with standard food and water provided ad libitum. ...
... The experimental setup and protocol have been detailed elsewhere (Nelissen et al., 2018). Briefly, anaesthesia as described above was maintained for 6 h to allow for the MR measurements. ...
... We therefore hypothesize that increases in troponin levels coincide with structural damage. A previous study demonstrated that increased T 2 values correlate to signs of muscle damage on histology over 14 day period (Nelissen et al., 2018). Indeed the animals that initially demonstrated an increase in troponin levels still reveal a marked increase in T 2 value in 19-60% of the volume of the leg (data not shown). ...
Pressure-induced deep tissue injury is a form of pressure ulcer which is difficult to detect and diagnose at an early stage, before the wound has severely progressed and becomes visible at the skin surface. At the present time, no such detection technique is available. To test the hypothesis that muscle damage biomarkers can be indicative of the development of deep tissue injury after sustained mechanical loading, an indentation test was performed for 2 h on the tibialis anterior muscle of rats. Myoglobin and troponin were analysed in blood plasma and urine over a period of 5 days. The damage as detected by the biomarkers was compared to damage as observed with T2 MRI to validate the response. We found that myoglobin and troponin levels in blood increased due to the damage. Myoglobin was also increased in urine. The amount of damage observed with MRI immediately after loading had a strong correlation with the maximal biomarker levels: troponin in blood rs = 0.94; myoglobin in blood rs = 0.75; and myoglobin in urine rs = 0.57. This study suggests that muscle damage markers measured in blood and urine could serve as early diagnosis for pressure induced deep tissue injury.
... The ADC can be estimated easily and fast using one image without diffusion weighting and three images with orthogonal gradient directions in order to get the trace image. Prior studies in pathological human skeletal muscle have demonstrated a change in ADC due to muscle denervation (24% increase) [55], in inflammatory myopathies (17% increase) [56], and deformation-induced injury (between 16% increase and 10% decrease, depending on time after injury) [57] -hence the ADC could serve as a biomarker in muscular disorders. However, analysis of ADC in resting healthy human muscles has yielded a broad range of normal values between 1.26 × 10 -3 and 1.99 × 10 -3 mm 2 /s [54][55][56][58][59][60][61], i.e. a 58% difference between the lowest and the highest values. ...
... Due to the close association between muscle damage (loss of sarcoplasm integrity), inflammation, and edema, it is often difficult to separate these individual components from net changes in MRI signal. Despite this, careful animal studies along with detailed histological analysis at specific time points [93,186] and multimodal MR acquisitions are providing insight into sources of the different contrast mechanisms [57,93,184,186]. Often in these analyses it is necessary to take into account the multicomponent nature of relaxation or diffusion that are occurring on the subpixel scale [186]. ...
Neuromuscular diseases are characterized by progressive muscle degeneration and muscle weakness resulting in functional disabilities. While each of these diseases is individually rare, they are common as a group, and a large majority lacks effective treatment with fully market approved drugs. Magnetic resonance imaging and spectroscopy techniques (MRI and MRS) are showing increasing promise as an outcome measure in clinical trials for these diseases. In 2013, the European Union funded the COST (co-operation in science and technology) action BM1304 called MYO-MRI (www.myo-mri.eu), with the overall aim to advance novel MRI and MRS techniques for both diagnosis and quantitative monitoring of neuromuscular diseases through sharing of expertise and data, joint development of protocols, opportunities for young researchers and creation of an online atlas of muscle MRI and MRS. In this report, the topics that were discussed in the framework of working group 3, which had the objective to: Explore new contrasts, new targets and new imaging techniques for NMD are described. The report is written by the scientists who attended the meetings and presented their data. An overview is given on the different contrasts that MRI can generate and their application, clinical needs and desired readouts, and emerging methods.
... In order to facilitate the use of 2D FE modelling techniques an oblong rounded bar-shaped indenter, with its long axis parallel to the target muscle, was used in all these studies since this provided approximate plane stress conditions. Recent MR data obtained from a similar experiment, showed that muscle damage extends along the muscle fibres, beyond the local indentation site (Nelissen et al. 2018). Since damage evolution was demonstrated to be a more complex 3D phenomenon, analysis of such experimental findings requires an extension of the existing 2D methods to 3D FE investigations. ...
... Analysis was performed on Sprague-Dawley rats that were part of a larger study on damage development in rats (Nelissen et al. 2018(Nelissen et al. , 2017. For the study described in this paper, data of 10 female rats (11-14 weeks, Charles River, Paris, France) were used. ...
Pressure ulcers occur due to sustained mechanical loading. Deep tissue injury is a severe type of pressure ulcer, which is believed to originate in subcutaneous tissues adjacent to bony prominences. In previous experimental-numerical studies the relationship between internal tissue state and damage development was investigated using a 2D analysis. However, recent studies suggest that a local analysis is not sufficient. In the present study we developed a method to create animal-specific 3D finite element models of an indentation test on the tibialis anterior muscle of rats based on MRI data. A detailed description on how the animal specific models are created is given. Furthermore, two indenter geometries are compared and the influence of errors in determining the indenter orientation on the resulting internal strain distribution in a defined volume of tissue was investigated. We conclude that with a spherically-shaped indenter errors in estimating the indenter orientation do not unduly influence the results of the simulation.
... Age, impaired mobility, continence, temperature and nutrition are all factors that can contribute to the onset of DTI (Linder-Ganz et al., 2007;Westby et al., 2017;Oomens et al., 2003). However, the relatively large mechanical deformation of soft tissue seems to be the dominant initiating factor (Linder-Ganz et al., 2007;Bouten et al., 2003;Nelissen et al., 2018). ...
Advancements in systems for prevention and management of pressure ulcers require a more detailed
understanding of the complex response of soft tissues to compressive loads. This study aimed at quantifying
the progressive deformation of the buttock based on 3D measurements of soft tissue displacements from MR
scans of 10 healthy subjects in a semi-recumbent position. Measurements were obtained using digital volume
correlation (DVC) and released as a public dataset. A first parametric optimisation of the global registration
step aimed at aligning skeletal elements showed acceptable values of Dice coefficient (around 80%). A second
parametric optimisation on the deformable registration method showed errors of 0.99 mm and 1.78 mm against
two simulated fields with magnitude 7.30 ± 3.15 mm and 19.37 ± 9.58 mm, respectively, generated with a finite
element model of the buttock under sitting loads. Measurements allowed the quantification of the slide of the
gluteus maximus away from the ischial tuberosity (IT, average 13.74 mm) that was only qualitatively identified
in the literature, highlighting the importance of the ischial bursa in allowing sliding. Spatial evolution of the
maximus shear strain on a path from the IT to the seating interface showed a peak of compression in the fat,
close to the interface with the muscle. Obtained peak values were above the proposed damage threshold in
the literature. Results in the study showed the complexity of the deformation of the soft tissues in the buttock
and the need for further investigations aimed at isolating factors such as tissue geometry, duration and extent
of load, sitting posture and tissue properties.
... Cell and tissue deformation -tissue deformation triggers a variety of effects, which may be involved in early cell damage, such as local stresses leading to buckling and rupture of the membrane (Loerakker et al. 2011). This loss of membrane integrity will lead to altered transport of biomolecules and ions, volume changes and modifications of cytoskeletal organisation, all of which can affect cell viability and limit the remodelling capacity of the tissues (Nelissen et al. 2018). ...
It is well established that persons with Spinal Cord Injury (SCI) are at considerable risk of developing a Pressure ulcer (PU) at all times in their life following injury. This risk is associated with limited mobility coupled with impaired sensation leading to prolonged periods of support in bed or in a wheelchair. Monitoring has traditionally involved short term mapping of pressures on different support surfaces. More recently, pressure mapping systems have been adapted to acquire data over prolonged periods in lying and sitting postures. By identifying sharp transitions in the temporal profiles of selected pressure-related parameters and verifying these with customised software, a comprehensive analysis of posture and mobility can be achieved during each monitoring period. This approach was adopted with a heterogeneous cohort of SCI persons (n=12), who were in-patients at the Duke of Cornwall Spinal Centre and had been judged to be capable of “sitting out” in their wheelchair for at least four hours per day. This represented phase 3 of their rehabilitation, which had been identified in a retrospective analysis to represent a period in which individuals were particularly vulnerable of developing a pressure ulcer. The first in-patient analysis revealed considerable variation in movement behaviour in both bed and sitting across the cohort. Movements to offload vulnerable areas (MOVA) were explored. Closer examination revealed that two parameters, namely, average number of MOVAs per hour and maximum time between MOVAs. Notable trends were discovered when analysing the aforementioned parameters against the individual SCI level and ASIA score. There were, however, a few outliers to these general trends, which could be associated with specific co-morbidities. The initial analysis motivated an Individualized Pressure Ulcer Prevention Plan (IPUPP) which was examined with a small proportion (33%) of the cohort who remained as in-patients. This revealed considerable diversity in the second analysis of movement behaviour. In particular, a general improvement was only evident with those individuals who had experienced a previous history of bed rest of skin damage, as confirmed in their associated interviews. The analysis following discharge to the community, revealed some marked changes to the individual movement behaviour, which could be attributed to a number of factors, including differences in support surfaces to match community settings, carer capacities and individual functional potential following their injury. This bioengineering approach needs to be extended to accommodate a larger SCI population. This will enable a generalisation of the findings to ensure informed education and training of pressure ulcer prevention for the individual and their carer.
... Skeletal muscle tissues are more susceptible to PU/PI damage than skin, likely due to the greater capillary and mitochondrial volume density in muscles, which is associated with their greater metabolic demand. 43,44,61,62,106 Skin is also considerably stiffer than muscle or adipose tissues and therefore deforms to a lesser extent in most clinically relevant scenarios, which in turn makes it less susceptible to ischaemic damage. In animal experiments, the first signs of ischaemic damage are found in skeletal muscle after 2 to 4 hours of sustained deformations. ...
In 2019, the third and updated edition of the Clinical Practice Guideline (CPG) on Prevention and Treatment of Pressure Ulcers/Injuries has been published. In addition to this most up-to-date evidence-based guidance for clinicians, related topics such as pressure ulcers (PUs)/pressure injuries (PIs) aetiology, classification, and future research needs were considered by the teams of experts. To elaborate on these topics, this is the third paper of a series of the CPG articles, which summarises the latest understanding of the aetiology of PUs/PIs with a special focus on the effects of soft tissue deformation. Sustained deformations of soft tissues cause initial cell death and tissue damage that ultimately may result in the formation of PUs/PIs. High tissue deformations result in cell damage on a microscopic level within just a few minutes, although it may take hours of sustained loading for the damage to become clinically visible. Superficial skin damage seems to be primarily caused by excessive shear strain/stress exposures, deeper PUs/PIs predominantly result from high pressures in combination with shear at the surface over bony prominences, or under stiff medical devices. Therefore, primary PU/PI prevention should aim for minimising deformations by either reducing the peak strain/stress values in tissues or decreasing the exposure time.
... • The investigational compound is administered to the animals for 14 or 21 days and the wound healing effect is assessed by measuring wound area (Shi et al. 2016). • At the end of the study, rats are euthanized and tibialis anterior muscles are dissected and stored for histopathological analysis (Nelissen et al. 2018). ...
The process of drug discovery and development is divided into three major phases viz, discovery, preclinical development (including formulation development, compatibility studies, in vitro and in vivo drug efficacy studies, and toxicological studies), and clinical trial. Preclinical evaluation is part of the preclinical development phases and this part is an essential component aimed to assess the safety and efficacy of the investigational compound prior to the clinical trials. Preclinical evaluations/studies are an essential part of the process of drug discovery and to study the effect of investigational drugs/compounds on the living system (cell culture and animal models) before a series of human clinical trials. The preclinical studies include pharmacokinetic studies, pharmacodynamics, and toxicological studies where a safe dose for the first-in-man study is determined. In preclinical studies, cell culture and animal models are commonly used. The objective of this chapter is to summarize preclinical models for wound healing and repair studies.
... Given a lack of supporting tissue structures, supply of metabolites, and waste clearance through these structures, skin breakdown follows within hours to days. 3,4 Despite this progression, clinicians still depend primarily on routine visual skin assessments to identify injuries and intervene when symptoms appear. 5 Even when well conducted, a visual assessment is always subjective, qualitative, and subject to interrater variability. ...
This article is a review of the work conducted and published to date in employing computer finite element (FE) modeling for efficacy research of prophylactic dressings in the context of preventing pressure injuries. The authors strive to explain why FE modeling is essential in establishing the efficacy of prophylactic dressings, as it is in the development and evaluation of any other preventive intervention. In particular, FE modeling provides insights into the interactions between dressing structures and weight-bearing body tissues (including susceptible anatomical locations such as the sacrum and heels of supine patients). Modeling further facilitates reliable visualization and quantification of the mechanical loads that develop in superficial and deep tissues as a result of body weight or external forces based on known physical principles. The modeling then helps to determine how these tissue loads are mitigated using prophylactic dressings of different designs, structures, and material compositions and rate performances of existing or new products.
All of the work published so far on modeling the modes of action of prophylactic dressings has focused on the Mepilex Border dressing (Mölnlycke Health Care AB, Gothenburg, Sweden). Published work has revealed several key design features that are pivotal for obtaining successful clinical outcomes, namely, (1) a multilayered alternating-stiffness structure with embedded anisotropy; (2) a minimal friction coefficient at the external surface of the dressing; and (3) low impact of fluid retention on the mechanical behavior of the dressing. These features, their importance, and the methods of identifying their roles in the modes of action of effective prophylactic dressings are detailed here.
Computer models clearly inform the process of engineering prophylactic dressings, but they may also provide guidance in clinical use, contribute to assessing technologies and products, support purchasing, and describe product endurance. As the methods of FE modeling of dressings improve, simulations may soon incorporate the simultaneous complex interactions among tissue distortion, heat transfer in tissue, and prophylactic dressings to inform patient care.
Superoxide, an anionic dioxygen molecule, plays a crucial role in redox regulation within the body but is implicated in various pathological conditions when produced excessively. Efforts to develop superoxide detection...
Background:
Subepidermal moisture (SEM) changes may detect early tissue injury and enhance pressure injury risk assessments. However, little is known how modifiable factors, like head of bed elevation (HOBE), affect SEM.
Aim:
This study investigated the influence of HOBE on sacral and heel SEM, using the Provizio ® SEM Scanner.
Method:
A 2 × 2 randomised crossover study compared the effects of 30-min of 30⁰ versus 60⁰ HOBE on sacral and heel SEM in healthy adults.
Results:
48 participants were randomly allocated to 30⁰ or 60⁰ HOBE and crossed over after a 60-min washout period. The mean age was 40.6 years (SD = 18.3). The study found the sacral and heel SEM values were not statistically different at 30⁰ versus 60⁰ HOBE. No clinically relevant association between SEM and characteristics of age, sex, body mass index and skin type were found. Baseline sacral and heel SEM values recovered after a 60-min washout period. Notably, half of the initial baseline measures suggested pressure injury risk.
Conclusion:
The HOBE may not influence SEM at the sacrum and heels, in healthy adults after 30 min of loading. Standard operating procedures for measuring SEM for pressure injury risk assessment require a stronger body of evidence in varied populations and timeframes before this technology is widely adopted.
Trial registration:
Australian and New Zealand Clinical Trials Registry ACTRN12622001456741.
Objective:
To establish a preoperative evaluation procedure by measuring the volume of dead space using MRI in patients with ischial pressure injuries.
Methods:
Patients with spinal cord injury and ischial pressure injuries who underwent treatment between August 2016 and November 2019 were included in the study. Preoperative MRI scan was conducted on all patients. The volume estimation and three-dimensional (3D) reconstruction were performed based on MRI data using a 3D Slicer. Based on the resulting volume, a muscle flap that could fit the dead space was selected. Surgery was performed with the selected muscle flap, and a fasciocutaneous flap was added, if necessary.
Results:
A total of eight patients with ischial pressure injuries were included in the study. The mean patient age was 59.0 ± 11.0 years. The mean body mass index was 26.62 ± 3.89 kg/m2. The mean volume of dead space was 104.75 ± 81.05 cm3. The gracilis muscle was the most selected muscle flap and was used in four patients. In five of eight cases, a fasciocutaneous flap was used as well. The mean follow-up period was 16 months, and by that point, none of the patients evinced complications that required surgery.
Conclusions:
To the authors' knowledge, this is the first report on volumetric evaluation of dead space in ischial pressure injuries. The authors believe that the 3D reconstruction process would enable adequate dead space obliteration in ischial pressure injuries. The authors propose that preoperative MRI scans in patients with ischial pressure injury should become an essential part of the process.
We investigated the efficacy and molecular mechanisms of tazarotene gel for healing deep tissue injury (DTI). We used male C57BL/6J mice to establish a DTI model. Animals were divided randomly into control, tazarotene gel and purilon gel groups. We injected 100 ul tazarotene gel, purilon gel or saline every 48 h for 20 days. Hematoxylin and eosin staining was used to observe pathological changes on days 14 and 21. The mRNA and protein expression of VEGF-α, TGF-β1 and HIF-1α were detected by qRT-PCR and western blot, respectively. Wound sites exhibited accelerated healing by 20 days in the tazarotene gel group. Fewer inflammatory cells and more granulation tissue were found in both experimental groups compared to controls. The mRNA and protein expression of VEGF-α and TGF-β1 in the experimental groups were increased compared to the control group by day 14. Expression of HIF-1α in the experimental groups was significantly less than in the controls. Tazarotene gel promoted wound healing independent of the HIF-1α/VEGF signalling pathway during tissue repair of DTI. Tazarotene and purilon gels exhibited similar macroscopic healing of wounds and expression of genes and proteins.
Background and purpose
New capillaries are essential for deep tissue pressure injury wound healing. Tazarotene is a recently discovered small molecule drug and functions to promote neovascularization and tissue repair. At present, the application of tazarotene in the repair of pressure injuries has not previously been investigated. This study used poly (lactic-co-glycolic acid) (PLGA) as nanoparticle carriers loaded with tazarotene (Ta/PLGA NPs) for drug delivery and to overcome shortcomings associated with the low water solubility, short half-life, easy photolysis and low bioavailability of tazarotene itself.
Methods
The physicochemical properties, drug release and bioactivity of Ta/PLGA NPs were examined in vitro by transmission electron microscope, spectrophotometry and cell assays. Mouse models of deep tissue pressure injuries (DTPI) were established and the therapeutic effects and mechanisms of Ta/PLGA NPs in local wound repair were studied.
Results
The results showed that Ta/PLGA NPs were of uniform size and distribution and were non-toxic both in vitro and in vivo. In vivo experiments suggested that Ta/PLGA NPs significantly promoted DTPI wound repair through activation of the VEGF/VEGFR-Notch1/DLL4 signaling pathway.
Conclusion
This study highlights the potential clinical significance of implementation of tazarotene small molecule drugs in combination with effective biomaterial carriers for the treatment of chronic refractory wounds, such as DTPI.
Objectives
Peripheral arterial disease (PAD) is characterised by arterial occlusion and fibrosis in the lower extremities. Extracellular volume matrix fraction (ECV) is a biomarker of skeletal muscle fibrosis, but has not been applied to the lower extremities with PAD. This study investigated the clinical feasibility of using ECV for calf muscle fibrosis quantification by comparing normal controls (NC) and PAD patients.Methods
From October 2016 to December 2017, we recruited patients with PAD, and patients with head and neck cancer receiving fibular flap as NC group. All participants underwent magnetic resonance imaging (MRI) to determine the ECV of the calves and the differences between the NC and PAD groups. ECV was calculated from T1 values at steady-state equilibrium, defined as the point in time after contrast agent injection when the variance of T1 relaxation time in blood and muscle becomes less than 5%.ResultsA total of 46 patients (18 in the NC group and 28 in the PAD group) were recruited. Steady-state equilibrium was reached at 11–12 min after contrast agent injection. The NC group had significantly lower mean ECV than the PAD group (12.71% vs. 31.92%, respectively, p < 0.001). In the PAD group, the mean ECV was slightly lower in patients with collateral vessels than in those without (26.58% vs. 34.88%, respectively, p = 0.047).Conclusion
Evaluation of skeletal fibrosis in PAD using ECV is feasible. ECV can help identify PAD patients with collateral vessel formation and lay the foundation for future research in PAD management.Key Points
• Steady-state equilibrium for ECV measurement of the lower limbs can be reached at around 11–12 min.
• Quantification of lower limb muscle fibrosis by measuring ECV is clinically feasible and can be used to differentiate between patients with PAD and histologically proven normal controls.
• ECV can differentiate PAD patients with or without visible collateral vessels, further expanding its role in identifying the presence of collateral supply in clinical decision-making.
Background:
Internal soft tissue strains have been shown to be one of the main factors responsible for the onset of Pressure Ulcers and to be representative of its risk of development. However, the estimation of this parameter using Finite Element (FE) analysis in clinical setups is currently hindered by costly acquisition, reconstruction and computation times. Ultrasound (US) imaging is a promising candidate for the clinical assessment of both morphological and material parameters.
Method:
The aim of this study was to investigate the ability of a local FE model of the region beneath the ischium with a limited number of parameters to capture the internal response of the gluteus region predicted by a complete 3D FE model. 26 local FE models were developed, and their predictions were compared to those of the patient-specific reference FE models in sitting position.
Findings:
A high correlation was observed (R = 0.90, p-value < 0.01). A sensitivity analysis showed that the most influent parameters were the mechanical behaviour of the muscle tissues, the ischium morphology and the external mechanical loading.
Interpretation:
Given the progress of US for capturing both morphological and material parameters, these results are promising because they open up the possibility to use personalised simplified FE models for risk estimation in daily clinical routine.
p>Background: deep tissue injury is a type of pressure ulcer which originates subcutaneously due to sustained mechanical loading. The relationship between mechanical compression and damage development has been extensively studied in 2D. However, recent studies have suggested that damage develops beyond the site of indentation. The objective of this study was to compare mechanical loading conditions to the associated damage in 3D.
Methods: an indentation test was performed on the tibialis anterior muscle of rats (n = 39). Changes in the form of oedema and structural damage were monitored with MRI in an extensive region. The internal deformations were evaluated using MRI based 3D finite element models.
Findings: damage propagates away from the loaded region. The 3D analysis indicates that there is a subject specific tolerance to compression induced deep tissue injury. Interpretation: Individual tolerance is an important factor when considering the mechanical loading conditions which induce damage.</p
Cardiovascular magnetic resonance imaging (CMR) has become an indispensable clinical tool for the assessment of morphology, function and structure of the heart muscle. By exploiting quantification of the effective transverse relaxation time (T2*) CMR also affords myocardial tissue characterization and probing of cardiac physiology, both being in the focus of ongoing research. These developments are fueled by the move to ultrahigh magnetic field strengths, which permits enhanced sensitivity and spatial resolution that help to overcome limitations of current clinical MR systems with the goal to contribute to a better understanding of myocardial (patho)physiology in vivo. In this context, the aim of this report is to introduce myocardial T2* mapping at ultrahigh magnetic fields as a promising technique to non-invasively assess myocardial (patho)physiology. For this purpose the basic principles of T2* assessment, the biophysical mechanisms determining T2* and (pre)clinical applications of myocardial T2* mapping are presented. Technological challenges and solutions for T2* sensitized CMR at ultrahigh magnetic field strengths are discussed followed by a review of acquisition techniques and post-processing approaches. Preliminary results derived from myocardial T2* mapping in healthy subjects and cardiac patients at 7.0 T are presented. A concluding section discusses remaining questions and challenges and provides an outlook on future developments and potential clinical applications.
Deformation of skeletal muscle in the proximity of bony structures may lead to deep tissue injury category of pressure ulcers. Changes in mechanical properties have been proposed as a risk factor in the development of deep tissue injury and may be useful as a diagnostic tool for early detection. MRE allows for the estimation of mechanical properties of soft tissue through analysis of shear wave data. The shear waves originate from vibrations induced by an external actuator placed on the tissue surface. In this study a combined Magnetic Resonance (MR) compatible indentation and MR Elastography (MRE) setup is presented to study mechanical properties associated with deep tissue injury in rats. The proposed setup allows for MRE investigations combined with damage-inducing large strain indentation of the Tibialis Anterior muscle in the rat hind leg inside a small animal MR scanner. An alginate cast allowed proper fixation of the animal leg with anatomical perfect fit, provided boundary condition information for FEA and provided good susceptibility matching. MR Elastography data could be recorded for the Tibialis Anterior muscle prior to, during, and after indentation. A decaying shear wave with an average amplitude of approximately 2 μm propagated in the whole muscle. MRE elastograms representing local tissue shear storage modulus Gd showed significant increased mean values due to damage-inducing indentation (from 4.2 ± 0.1 kPa before to 5.1 ± 0.6 kPa after, p<0.05). The proposed setup enables controlled deformation under MRI-guidance, monitoring of the wound development by MRI, and quantification of tissue mechanical properties by MRE. We expect that improved knowledge of changes in soft tissue mechanical properties due to deep tissue injury, will provide new insights in the etiology of deep tissue injuries, skeletal muscle damage and other related muscle pathologies.
Our understanding of pressure injury etiology and development has grown in recent years through research, clinical expertise, and global interdisciplinary expert collaboration. Therefore, the National Pressure Ulcer Advisory Panel (NPUAP) has revised the definition and stages of pressure injury. The revision was undertaken to incorporate the current understanding of the etiology of pressure injuries, as well as to clarify the anatomical features present or absent in each stage of injury. An NPUAP-appointed Task Force reviewed the literature and created drafts of definitions, which were then reviewed by stakeholders and the public, including clinicians, educators, and researchers around the world. Using a consensus-building methodology, these revised definitions were the focus of a multidisciplinary consensus conference held in April 2016. As a result of stakeholder and public input, along with the consensus conference, important changes were made and incorporated into the new staging definitions. The revised staging system uses the term injury instead of ulcer and denotes stages using Arabic numerals rather than Roman numerals. The revised definition of a pressure injury now describes the injuries as usually occurring over a bony prominence or under a medical or other device. The revised definition of a Stage 2 pressure injury seeks to clarify the difference between moisture-associated skin damage and injury caused by pressure and/or shear. The term suspected has been removed from the Deep Tissue Pressure Injury diagnostic label. Each definition now describes the extent of tissue loss present and the anatomical features that may or may not be present in the stage of injury. These important revisions reflect the methodical and collaborative approach used to examine the available evidence and incorporate current interdisciplinary clinical expertise into better defining the important phenomenon of pressure injury etiology and development.
The objective of this study was to investigate the efficacy of using quantitative magnetic resonance imaging (MRI) as a non-invasive tool for the monitoring of gene therapy for muscular dystrophy. The clinical investigations for this family of diseases often involve surgical biopsy which limits the amount of information that can be obtained due to the invasive nature of the procedure. Thus, other non-invasive tools may provide more opportunities for disease assessment and treatment responses. In order to explore this, dystrophic mdx4cv mice were systemically treated with a recombinant adeno-associated viral (AAV) vector containing a codon-optimized micro-dystrophin gene. Multi-parametric MRI of T2, magnetization transfer, and diffusion effects alongside 3-D volume measurements were then utilized to monitor disease/treatment progression. Mice were imaged at 10 weeks of age for pre-treatment, then again post-treatment at 8, 16, and 24 week time points. The efficacy of treatment was assessed by physiological assays for improvements in function and quantification of expression. Tissues from the hindlimbs were collected for histological analysis after the final time point for comparison with MRI results. We found that introduction of the micro-dystrophin gene restored some aspects of normal muscle histology and pathology such as decreased necrosis and resistance to contraction-induced injury. T2 relaxation values showed percentage decreases across all muscle types measured (tibialis anterior, gastrocnemius, and soleus) when treated groups were compared to untreated groups. Additionally, the differences between groups were statistically significant for the tibialis anterior as well. The diffusion measurements showed a wider range of percentage changes and less statistical significance while the magnetization transfer effect measurements showed minimal change. MR images displayed hyper-intense regions of muscle that correlated with muscle pathology in histological sections. T2 relaxation, alongside diffusion and magnetization transfer effects provides useful data towards the goal of non-invasively monitoring the treatment of muscular dystrophy.
Recent years have seen tremendous progress towards therapy of many previously incurable neuromuscular diseases. This new context has acted as a driving force for the development of novel non-invasive outcome measures. These can be organized in three main categories: functional tools, fluid biomarkers and imagery. In the latest category, nuclear magnetic resonance imaging (NMRI) offers a considerable range of possibilities for the characterization of skeletal muscle composition, function and metabolism. Nowadays, three NMR outcome measures are frequently integrated in clinical research protocols. They are: 1/ the muscle cross sectional area or volume, 2/ the percentage of intramuscular fat and 3/ the muscle water T2, which quantity muscle trophicity, chronic fatty degenerative changes and oedema (or more broadly, “disease activity”), respectively. A fourth biomarker, the contractile tissue volume is easily derived from the first two ones. The fat fraction maps most often acquired with Dixon sequences have proven their capability to detect small changes in muscle composition and have repeatedly shown superior sensitivity over standard functional evaluation. This outcome measure will more than likely be the first of the series to be validated as an endpoint by regulatory agencies. The versatility of contrast generated by NMR has opened many additional possibilities for characterization of the skeletal muscle and will result in the proposal of more NMR biomarkers. Ultra-short TE (UTE) sequences, late gadolinium enhancement and NMR elastography are being investigated as candidates to evaluate skeletal muscle interstitial fibrosis. Many options exist to measure muscle perfusion and oxygenation by NMR. Diffusion NMR as well as texture analysis algorithms could generate complementary information on muscle organization at microscopic and mesoscopic scales, respectively. ³¹P NMR spectroscopy is the reference technique to assess muscle energetics non-invasively during and after exercise. In dystrophic muscle, ³¹P NMR spectrum at rest is profoundly perturbed, and several resonances inform on cell membrane integrity. Considerable efforts are being directed towards acceleration of image acquisitions using a variety of approaches, from the extraction of fat content and water T2 maps from one single acquisition to partial matrices acquisition schemes. Spectacular decreases in examination time are expected in the near future. They will reinforce the attractiveness of NMR outcome measures and will further facilitate their integration in clinical research trials.
Magnetic resonance imaging (MRI) provides non-invasive, repetitive measures in the same individual, allowing the study of a physio-pathological event over time. In this study, we tested the performance of 7 Tesla multi-parametric MRI to monitor the dynamic changes of mouse skeletal muscle injury and regeneration upon acute ischemia induced by femoral artery dissection. T2-mapping (T2 relaxation time), diffusion-tensor imaging (Fractional Anisotropy) and perfusion by Dynamic Contrast-Enhanced MRI (K-trans) were measured and imaging results were correlated with histological morphometric analysis in both Gastrocnemius and Tibialis anterior muscles. We found that tissue damage positively correlated with T2-relaxation time, while myofiber regeneration and capillary density positively correlated with Fractional Anisotropy. Interestingly, K-trans positively correlated with capillary density. Accordingly, repeated MRI measurements between day 1 and day 28 after surgery in ischemic muscles showed that: 1) T2-relaxation time rapidly increased upon ischemia and then gradually declined, returning almost to basal level in the last phases of the regeneration process; 2) Fractional Anisotropy dropped upon ischemic damage induction and then recovered along with muscle regeneration and neoangiogenesis; 3) K-trans reached a minimum upon ischemia, then progressively recovered. Overall, Gastrocnemius and Tibialis anterior muscles displayed similar patterns of MRI parameters dynamic, with more marked responses and less variability in Tibialis anterior. We conclude that MRI provides quantitative information about both tissue damage after ischemia and the subsequent vascular and muscle regeneration, accounting for the differences between subjects and, within the same individual, between different muscles.
Background:
A substantial impediment to progress in trials of new therapies in neuromuscular disorders is the absence of responsive outcome measures that correlate with patient functional deficits and are sensitive to early disease processes. Irrespective of the primary molecular defect, neuromuscular disorder pathological processes include disturbance of intramuscular water distribution followed by intramuscular fat accumulation, both quantifiable by MRI. In pathologically distinct neuromuscular disorders, we aimed to determine the comparative responsiveness of MRI outcome measures over 1 year, the validity of MRI outcome measures by cross-sectional correlation against functionally relevant clinical measures, and the sensitivity of specific MRI indices to early muscle water changes before intramuscular fat accumulation beyond the healthy control range.
Methods:
We did a prospective observational cohort study of patients with either Charcot-Marie-Tooth disease 1A or inclusion body myositis who were attending the inherited neuropathy or muscle clinics at the Medical Research Council (MRC) Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery, London, UK. Genetic confirmation of the chromosome 17p11.2 duplication was required for Charcot-Marie-Tooth disease 1A, and classification as pathologically or clinically definite by MRC criteria was required for inclusion body myositis. Exclusion criteria were concomitant diseases and safety-related MRI contraindications. Healthy age-matched and sex-matched controls were also recruited. Assessments were done at baseline and 1 year. The MRI outcomes-fat fraction, transverse relaxation time (T2), and magnetisation transfer ratio (MTR)-were analysed during the 12-month follow-up, by measuring correlation with functionally relevant clinical measures, and for T2 and MTR, sensitivity in muscles with fat fraction less than the 95th percentile of the control group.
Findings:
Between Jan 19, 2010, and July 7, 2011, we recruited 20 patients with Charcot-Marie-Tooth disease 1A, 20 patients with inclusion body myositis, and 29 healthy controls (allocated to one or both of the 20-participant matched-control subgroups). Whole muscle fat fraction increased significantly during the 12-month follow-up at calf level (mean absolute change 1.2%, 95% CI 0.5-1.9, p=0.002) but not thigh level (0.2%, -0.2 to 0.6, p=0.38) in patients with Charcot-Marie-Tooth disease 1A, and at calf level (2.6%, 1.3-4.0, p=0.002) and thigh level (3.3%, 1.8-4.9, p=0.0007) in patients with inclusion body myositis. Fat fraction correlated with the lower limb components of the inclusion body myositis functional rating score (ρ=-0.64, p=0.002) and the Charcot-Marie-Tooth examination score (ρ=0.63, p=0.003). Longitudinal T2 and MTR changed consistently with fat fraction but more variably. In muscles with a fat fraction lower than the control group 95th percentile, T2 was increased in patients compared with controls (regression coefficients: inclusion body myositis thigh 4.0 ms [SE 0.5], calf 3.5 ms [0.6]; Charcot-Marie-Tooth 1A thigh 1.0 ms [0.3], calf 2.0 ms [0.3]) and MTR reduced compared with controls (inclusion body myositis thigh -1.5 percentage units [pu; 0.2], calf -1.1 pu [0.2]; Charcot-Marie-Tooth 1A thigh -0.3 pu [0.1], calf -0.7 pu [0.1]).
Interpretation:
MRI outcome measures can monitor intramuscular fat accumulation with high responsiveness, show validity by correlation with conventional functional measures, and detect muscle water changes preceding marked intramuscular fat accumulation. Confirmation of our results in further cohorts with these and other muscle-wasting disorders would suggest that MRI biomarkers might prove valuable in experimental trials.
Funding:
Medical Research Council UK.
We report the case of a 46-year-old female who presented with a category IV pressure ulcer (PU) in the sacral region. Undermining of the PU was assessed with the aid of two-dimensional and three-dimensional ultrasound (3D-US).3D-US clearly visualized the wound in three directions and allowed determination of its volume. Our results show that volumetric analysis carried out with 3D-US enables the evaluation of wound morphology and thus better treatment of patients with PUs. The technique is simple and can be used routinely in daily wound management to assess the volume of the undermined wound.
Background
Myocardial fibrosis is a common hallmark of many diseases of the heart. Late gadolinium enhanced MRI is a powerful tool to image replacement fibrosis after myocardial infarction (MI). Interstitial fibrosis can be assessed indirectly from an extracellular volume fraction measurement using contrast-enhanced T1 mapping. Detection of short T2* species resulting from fibrotic tissue may provide an attractive non-contrast-enhanced alternative to directly visualize the presence of both replacement and interstitial fibrosis.
Objective
To goal of this paper was to explore the use of a T2*-weighted radial sequence for the visualization of fibrosis in mouse heart.
Methods
C57BL/6 mice were studied with MI (n = 20, replacement fibrosis), transverse aortic constriction (TAC) (n = 18, diffuse fibrosis), and as control (n = 10). 3D center-out radial T2*-weighted images with vary
Deep tissue injury (DTI) can be difficult to diagnose because many other skin and wound problems can appear as purple skin or rapidly appearing eschar. The diagnosis of DTI begins with a thorough history to account for times of exposure to pressure, such as 'time down' at the scene or time during which the patient was flat and could not respond. Patients with light skin tones present with classic skin discolouration of purple or maroon tissue, a defined border around the area of injury, and often surrounding erythema is evident. Persistent erythema and hyperpigmentation, rather than blanching, should be used to determine pressure injury in dark skin tone patients. Differential diagnosis includes stage 2 pressure ulcers, incontinence-associated dermatitis, skin tears, bruising, haematoma, venous engorgement, arterial insufficiency, necrotising fasciitis and terminal skin ulcers. Many skin problems can also have a purple hue or rapidly developing eschar, and a working knowledge of dermatology is needed.
© 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.
This paper discusses the critical determinants of pressure ulcer development and proposes a new pressure ulcer conceptual framework.
Recent work to develop and validate a new evidence-based pressure ulcer risk assessment framework was undertaken. This formed part of a Pressure UlceR Programme Of reSEarch (RP-PG-0407-10056), funded by the National Institute for Health Research. The foundation for the risk assessment component incorporated a systematic review and a consensus study that highlighted the need to propose a new conceptual framework.
Discussion Paper.
The new conceptual framework links evidence from biomechanical, physiological and epidemiological evidence, through use of data from a systematic review (search conducted March 2010), a consensus study (conducted December 2010-2011) and an international expert group meeting (conducted December 2011).
A new pressure ulcer conceptual framework incorporating key physiological and biomechanical components and their impact on internal strains, stresses and damage thresholds is proposed. Direct and key indirect causal factors suggested in a theoretical causal pathway are mapped to the physiological and biomechanical components of the framework. The new proposed conceptual framework provides the basis for understanding the critical determinants of pressure ulcer development and has the potential to influence risk assessment guidance and practice. It could also be used to underpin future research to explore the role of individual risk factors conceptually and operationally.
By integrating existing knowledge from epidemiological, physiological and biomechanical evidence, a theoretical causal pathway and new conceptual framework are proposed with potential implications for practice and research.
Satellite cells, the quintessential skeletal muscle stem cells, reside in a specialized local environment whose anatomy changes dynamically during tissue regeneration. The plasticity of this niche is attributable to regulation by the stem cells themselves and to a multitude of functionally diverse cell types. In particular, immune cells, fibrogenic cells, vessel-associated cells and committed and differentiated cells of the myogenic lineage have emerged as important constituents of the satellite cell niche. Here, we discuss the cellular dynamics during muscle regeneration and how disease can lead to perturbation of these mechanisms. To define the role of cellular components in the muscle stem cell niche is imperative for the development of cell-based therapies, as well as to better understand the pathobiology of degenerative conditions of the skeletal musculature.
Skeletal muscle remodeling in response to various noxae physiologically includes structural changes and inflammatory events. The possibility to study those phenomena in-vivo has been hampered by the lack of validated imaging tools. In our study, we have relied on multiparametric magnetic resonance imaging for quantitative monitoring of muscle changes in mice experiencing age-related sarcopenia or active regeneration after sterile acute injury of tibialis anterior muscle induced by cardiotoxin (CTX) injection. The extent of myofibrils' necrosis, leukocyte infiltration, and regeneration have been evaluated and compared with parameters from magnetic resonance imaging: T2-mapping (T2 relaxation time; T2-rt), diffusion-tensor imaging (fractional anisotropy, F.A.) and diffusion weighted imaging (apparent diffusion coefficient, ADC). Inflammatory leukocytes within the perimysium and heterogeneous size of fibers characterized aged muscles. They displayed significantly increased T2-rt (P
Pressure ulcer grading is a useful tool for defining the severity of pressure ulcers. However, it is obvious that education
is essential in order to ensure that grades are correctly identified and that incontinence lesions are not mistaken for pressure
ulcers. The EPUAP provides access to a very useful educational program via its website (www.epuap.org.uk). The PUCLAS program
was developed at the University of Ghent, Belgium. It provides both educational material and a self-assessment quiz. It is
currently available in nine languages—English, Dutch, Finnish, French, German, Italian, Portuguese, Spanish, and Swedish—and
may be freely used for personal or educational purposes. This is a great opportunity for individuals to improve their own
assessment skills. Wide use of such educational tools could substantially improve the accuracy of pressure ulcer grading in
the clinical area.
Deep tissue injury (DTI) is a severe form of pressure ulcer where tissue damage starts in deep tissues underneath intact skin. Tissue deformation may play an important role in the aetiology, which can be investigated using an experimental-numerical approach. Recently, an animal-specific finite element model has been developed to simulate experiments in which muscle tissue was compressed with an indenter. In this study, the material behaviour and boundary conditions were adapted to improve the agreement between model and experiment and to investigate the influence of these adaptations on the predicted strain distribution. The use of a highly nonlinear material law and including friction between the indenter and the muscle both improved the quality of the model and considerably influenced the estimated strain distribution. With the improved model, the required sample size to detect significant differences between loading conditions can be diminished, which is clearly relevant in experiments involving animals.
The repair process of damaged tissue involves the coordinated activities of several cell types in response to local and systemic signals. Following acute tissue injury, infiltrating inflammatory cells and resident stem cells orchestrate their activities to restore tissue homeostasis. However, during chronic tissue damage, such as in muscular dystrophies, the inflammatory-cell infiltration and fibroblast activation persists, while the reparative capacity of stem cells (satellite cells) is attenuated. Abnormal dystrophic muscle repair and its end stage, fibrosis, represent the final common pathway of virtually all chronic neurodegenerative muscular diseases. As our understanding of the pathogenesis of muscle fibrosis has progressed, it has become evident that the muscle provides a useful model for the regulation of tissue repair by the local microenvironment, showing interplay among muscle-specific stem cells, inflammatory cells, fibroblasts and extracellular matrix components of the mammalian wound-healing response. This article reviews the emerging findings of the mechanisms that underlie normal versus aberrant muscle-tissue repair.
Animal models of skeletal muscle injury should be thoroughly described and should mimic the clinical situation. We established a model of a critical size crush injury of the soleus muscle in rats. The aim was to describe the time course of skeletal muscle regeneration using mechanical, histological, and magnetic resonance (MR) tomographic methods.
Left soleus muscles of 36 Sprague-Dawley rats were crushed in situ in a standardized manner. We scanned the lower legs of 6 animals by 7-tesla MR one week, 4 weeks, and 8 weeks after trauma. Regeneration was evaluated at these times by in vivo measurement of muscle contraction forces after fast-twitch and tetanic stimulation (groups 1W, 4W, 8W; 6 per group). Histological and immunohistological analysis was performed and the amount of fibrosis within the injured muscles was determined histomorphologically.
MR signals of the traumatized soleus muscles showed a clear time course concerning microstructure and T1 and T2 signal intensity. Newly developed neural endplates and myotendinous junctions could be seen in the injured zones of the soleus. Tetanic force increased continuously, starting at 23% (SD 4) of the control side (p < 0.001) 1 week after trauma and recovering to 55% (SD 23) after 8 weeks. Fibrotic tissue occupied 40% (SD 4) of the traumatized muscles after the first week, decreased to approximately 25% after 4 weeks, and remained at this value until 8 weeks.
At both the functional level and the morphological level, skeletal muscle regeneration follows a distinct time course. Our trauma model allows investigation of muscle regeneration after a standardized injury to muscle fibers.
Previous studies report that pressure ulcer classification and differentiation from incontinence associated dermatitis are difficult. Incorrect classification and differentiation result in incorrect prevention and treatment. Education is important to spread evidence-based insights about this topic and to improve classification skills.
To assess the effectiveness of the Pressure Ulcer Classification (PUCLAS) education tool. PUCLAS was developed by the PUCLAS Workgroup of the European Pressure Ulcer Advisory Panel.
Randomised controlled trial.
A convenience sample of 1217 Belgian, Dutch, British and Portuguese nurses.
Correct classification of pressure ulcer photographs and differentiation from photographs of incontinence-associated dermatitis.
Baseline, 44.5% of the photographs were classified correctly. In the post-test, the results in the intervention group were significantly higher (63.2%) compared with the control group (53.1%; p<0.001). The percentage of correct assessments of incontinence associated dermatitis (IAD) was 70.7% in the intervention group and 35.6% in the control group (p<0.001). The skill to differentiate IAD from pressure ulcers was significantly associated with the experimental intervention (OR 4.07, 95% CI 3.21 to 5.15, p<0.001).
The PUCLAS tool improved pressure ulcer classification and IAD differentiation significantly.
Mechanical loading of soft tissues covering bony prominences can cause skeletal muscle damage, ultimately resulting in a severe pressure ulcer termed deep tissue injury. Recently, by means of an experimental-numerical approach, it was shown that local tissue deformations cause tissue damage once a deformation threshold is exceeded. In the present study, the effects of load exposure time and intermittent load relief on the development of deformation-induced muscle damage were investigated. The data showed that a 2 h loading period caused more damage than 10 min loading. Intermittent load reliefs of 2 min during a 2 h loading period had minimal effect on the evolution of skeletal muscle damage. In addition, a local deformation threshold for damage was found, which was similar for each of the loading regimes applied in this study. For short loading periods, these results imply that local tissue deformations determine whether muscle damage will develop and the exposure time influences the amount of tissue damage. Temporary load reliefs were inefficient in reducing deformation-induced damage, but may still influence the development of ischemia-induced damage during longer loading periods.
This book provides an up-to-date scientific account of all aspects related to pressure ulcers and pressure ulcer research, as well as evidence-based knowledge of pressure ulcer aetiology. Further, it describes current and future tools for evaluating patients at risk. It comprises 20 chapters by renowned international experts in the field of pressure ulcer research. Among them are representatives of the European and American Pressure Ulcer Advisory Panels, basic researchers, clinicians and tissue viability nurses. Topics range from economic and legal aspects to evidence-based knowledge on prevention and treatment, aetiology, risk assessment and future aspects of pressure ulcer management.
Diffusion tensor imaging (DTI) is increasingly applied to study skeletal muscle physiology, anatomy, and pathology. The reason for this growing interest is that DTI offers unique, noninvasive, and potentially diagnostically relevant imaging readouts of skeletal muscle structure that are difficult or impossible to obtain otherwise. DTI has been shown to be feasible within most skeletal muscles. DTI parameters are highly sensitive to patient-specific properties such as age, body mass index (BMI), and gender, but also to more transient factors such as exercise, rest, pressure, temperature, and relative joint position. However, when designing a DTI study one should not only be aware of sensitivity to the above-mentioned factors but also the fact that the DTI parameters are dependent on several acquisition parameters such as echo time, b-value, and diffusion mixing time. The purpose of this review is to provide an overview of DTI studies covering the technical, demographic, and clinical aspects of DTI in skeletal muscles. First we will focus on the critical aspects of the acquisition protocol. Second, we will cover the reported normal variance in skeletal muscle diffusion parameters, and finally we provide an overview of clinical studies and reported parameter changes due to several (patho-)physiological conditions. J. Magn. Reson. Imaging 2015.
© 2015 Wiley Periodicals, Inc.
The paper describes the current views on the cause of a sub-class of pressure ulcers known as pressure induced deep tissue injury (DTI). A multi-scale approach was adopted using model systems ranging from single cells in culture, tissue engineered muscle to animal studies with small animals. This has led to a clear understanding on two damage mechanisms associated with the development of DTI. Direct deformation results from high, but physiologically relevant, strains and is a process that leads to the first signs of cell damage within minutes. Ischaemic damage is caused by occlusion of blood vessels, but takes several hours to develop. The paper ends with some clinical consequences.
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.
Muscle diseases commonly have clinical presentations of inflammation, fat infiltration, fibrosis, and atrophy. However, the results of existing laboratory tests and clinical presentations are not well correlated. Advanced quantitative MRI techniques may allow the assessment of myo-pathological changes in a sensitive and objective manner. To progress towards this goal, an array of quantitative MRI protocols was implemented for human thigh muscles; their reproducibility was assessed; and the statistical relationships among parameters were determined. These quantitative methods included fat/water imaging, multiple spin-echo T2 imaging (with and without fat signal suppression, FS), selective inversion recovery for T1 and quantitative magnetization transfer (qMT) imaging (with and without FS), and diffusion tensor imaging. Data were acquired at 3.0 T from nine healthy subjects. To assess the repeatability of each method, the subjects were re-imaged an average of 35 days later. Pre-testing lifestyle restrictions were applied to standardize physiological conditions across scans. Strong between-day intra-class correlations were observed in all quantitative indices except for the macromolecular-to-free water pool size ratio (PSR) with FS, a metric derived from qMT data. Two-way analysis of variance revealed no significant between-day differences in the mean values for any parameter estimate. The repeatability was further assessed with Bland–Altman plots, and low repeatability coefficients were obtained for all parameters. Among-muscle differences in the quantitative MRI indices and inter-class correlations among the parameters were identified. There were inverse relationships between fractional anisotropy (FA) and the second eigenvalue, the third eigenvalue, and the standard deviation of the first eigenvector. The FA was positively related to the PSR, while the other diffusion indices were inversely related to the PSR. These findings support the use of these T1, T2, fat/water, and DTI protocols for characterizing skeletal muscle using MRI. Moreover, the data support the existence of a common biophysical mechanism, water content, as a source of variation in these parameters. Copyright © 2014 John Wiley & Sons, Ltd.
Purpose:
To test the ability of different magnetic resonance imaging (MRI) modalities to discriminate the time course of damage and regeneration in a model of acute, toxin-induced muscle damage.
Materials and methods:
We analyzed the time course of tissue and cellular changes in mouse lower limb musculature following localized injection of myotoxin by T2 , magnetization transfer (MT), and diffusion-weighted MRI. We also used T1 -weighted imaging to measure leg muscle volume. In addition, postmortem histological analysis of toxin-injected muscles was compared to uninjected controls.
Results:
The damages detected by the MRI modalities are transient and recover within 3 weeks. Muscle water diffusivity and edema measured by leg volume increased within the first hours after injection of the toxin. The rate constant for volume increase was 0.65 ± 0.11 hr(-1) , larger than the increase in T2 (0.045 ± 0.013 hr(-1) ) and change in MT ratio (0.028 ± 0.021 hr(-1) ). During repair phase, the rate constants were much smaller: 0.022 ± 0.004 hr(-1) , 0.013 ± 0.0019 hr(-1) and 0.0042 ± 0.0016 hr(-1) for volume, T2 , and MT ratio, respectively. Histological analyses confirmed the underlying cellular changes that matched the progression of MR images.
Conclusion:
The kinetics of change in the MRI measurements during the progression of damage and repair shows MRI modalities can be used to distinguish these processes.
We have designed and constructed an experimental set-up allowing electrical stimulation of hindlimb mouse muscles and the corresponding force measurements at high-field (11.75T). We performed high-resolution multimodal MRI (including T2-weighted imaging, angiography and diffusion) and analysed the corresponding MRI changes in response to a stimulation protocol. Mice were tested twice over a 1-week period to investigate the reliability of mechanical measurements and T2 changes associated with the stimulation protocol. Additionally, angiographic images were obtained before and immediately after the stimulation protocol. Finally, multislice diffusion imaging was performed before, during and immediately after the stimulation session. Apparent diffusion coefficient (ADC) maps were calculated on the basis of diffusion weighted images (DWI). Both force production and T2 values were highly reproducible as illustrated by the low coefficient of variation (<8%) and high intraclass correlation coefficient (≥0.75) values. Maximum intensity projection angiographic images clearly showed a strong vascular effect resulting from the stimulation protocol. Although a motion sensitive imaging sequence was used (echo planar imaging) and in spite of the strong muscle contractions, motion artifacts were minimal for DWI recorded under exercising conditions, thereby underlining the robustness of the measurements. Mean ADC values increased under exercising conditions and were higher during the recovery period as compared with the corresponding control values. The proposed experimental approach demonstrates accurate high-field multimodal MRI muscle investigations at a preclinical level which is of interest for monitoring the severity and/or the progression of neuromuscular diseases but also for assessing the efficacy of potential therapeutic interventions. Copyright © 2014 John Wiley & Sons, Ltd.
Myopathies often display a common set of complex pathologies that include muscle weakness, inflammation, compromised membrane integrity, fat deposition, and fibrosis. Multi-parametric, quantitative, non-invasive imaging approaches may be able to resolve these individual pathological components. The goal of this study was to use multi-parametric MRI to investigate inflammation as an isolated pathological feature. Proton relaxation, diffusion tensor imaging (DTI), quantitative magnetization transfer (qMT-MRI), and dynamic contrast enhanced (DCE-MRI) parameters were calculated from data acquired in a single imaging session conducted 6–8 hours following the injection of λ-carrageenan, a local inflammatory agent. T2 increased in the inflamed muscle and transitioned to bi-exponential behavior. In diffusion measurements, all three eigenvalues and the apparent diffusion coefficient increased, but λ3 had the largest relative change. Analysis of the qMT data revealed that the T1 of the free pool and the observed T1 both increased in the inflamed tissue, while the ratio of exchanging spins in the solid pool to those in the free water pool (the pool size ratio) significantly decreased. DCE-MRI data also supported observations of an increase in extracellular volume. These findings enriched the understanding of the relation between multiple quantitative MRI parameters and an isolated inflammatory pathology, and may potentially be employed for other single or complex myopathy models. Copyright © 2014 John Wiley & Sons, Ltd.
Aims To develop and validate a non-invasive method for measuring myocardial iron in order to allow diagnosis and treatment before overt cardiomyopathy and failure develops.
Methods and Results We have developed a new magnetic resonance T2-star (T2*) technique for the measurement of tissue iron, with validation to chemical estimation of iron in patients undergoing liver biopsy. To assess the clinical value of this technique, we subsequently correlated myocardial iron measured by this T2* technique with ventricular function in 106 patients with thalassaemia major. There was a significant, curvilinear, inverse correlation between iron concentration by biopsy and liver T2* (r=0·93,P <0·0001). Inter-study cardiac reproducibility was 5·0%. As myocardial iron increased, there was a progressive decline in ejection fraction (r=0·61, P<0·001). All patients with ventricular dysfunction had a myocardial T2* of <20ms. There was no significant correlation between myocardial T2* and the conventional parameters of iron status, serum ferritin and liver iron. Multivariate analysis of clinical parameters to predict the requirement for cardiac medication identified myocardial T2* as the most significant variable (odds ratio 0·79,P <0·002).
Conclusions Myocardial iron deposition can be reproducibly quantified using myocardial T2* and this is the most significant variable for predicting the need for ventricular dysfunction treatment. Myocardial iron content cannot be predicted from serum ferritin or liver iron, and conventional assessments of cardiac function can only detect those with advanced disease. Early intensification of iron chelation therapy, guided by this technique, should reduce mortality from this reversible cardiomyopathy.
Abnormal signal intensity within skeletal muscle is frequently encountered at magnetic resonance (MR) imaging. Potential causes are diverse, including traumatic, infectious, autoimmune, inflammatory, neoplastic, neurologic, and iatrogenic conditions. Alterations in muscle signal intensity seen in pathologic conditions usually fall into one of three recognizable patterns: muscle edema, fatty infiltration, and mass lesion. Muscle edema may be seen in polymyositis and dermatomyositis, mild injuries, infectious myositis, radiation therapy, subacute denervation, compartment syndrome, early myositis ossificans, rhabdomyolysis, and sickle cell crisis. Fatty infiltration may be seen in chronic denervation, in chronic disuse, as a late finding after a severe muscle injury or chronic tendon tear, and in corticosteroid use. The mass lesion pattern may be seen in neoplasms, intramuscular abscess, myonecrosis, traumatic injury, myositis ossificans, muscular sarcoidosis, and parasitic infection. Some of these conditions require prompt medical or surgical management, whereas others do not benefit from medical intervention. The ability to accurately diagnose these conditions is therefore necessary, and biopsy may be required to establish the correct diagnosis. Clues to the correct diagnosis and whether biopsy is necessary or appropriate are often present on the MR images, especially when they are correlated with clinical features and the findings from other imaging modalities.
Pressure ulcer prevention strategies include the prevention, and early recognition, of deep tissue injury (DTI), which can evolve into a Stage III or Stage IV pressure ulcer. In addition to their role in pressure-induced ischemia, shearing forces are believed to contribute substantially to the risk of DTI. Because the visual manifestation of a DTI may not occur until many hours after tissues were damaged, research to explore methods for early detection is on-going. For example, rhabdomyolysis is a common complication of deep tissue damage; its detection via blood chemistry and urinalysis is explored as a possible diagnostic tool of early DTI in anatomical areas where muscle is present. Substances released from injured muscle cells have a predictable time frame for detection in blood and urine, possibly enabling the clinician to estimate the time of the tissue death. Several small case studies suggest the potential validity and reliability of ultrasoun for visualizing soft tissue damage also deserve further research. While recommendations to reduce mechanical pressure and shearing damage in high-risk patients remain unchanged, their implementation is not always practical, feasible, or congruent with the overall plan of patient care. Early detection of existing tissue damage will help clinicians implement appropriate care plans that also may prevent further damage. Research to evaluate the validity, reliability, sensitivity, and specificity of diagnostic studies to detect pressure-related tissue death is warranted.
To provide an estimate of the costs of treating pressure ulcers in the UK at August 2011 prices, as a means of highlighting the importance of pressure ulcer prevention.
Resource use was derived from a bottom-up methodology, based on the daily resources required to deliver protocols of care reflecting good clinical practice, with prices reflecting costs to the health and social care system in the UK. This approach was used to estimate treatment costs per episode of care and per patient for ulcers of different severity and level of complications.
The cost of treating a pressure ulcer varies from £1,214 (category 1) to £14,108 (category IV). Costs increase with ulcer severity because the time to heal is longer and the incidence of complications is higher in more severe cases.
Pressure ulcers represent a significant cost burden in the UK, both to patients and to health-care providers. Without concerted effort, this cost is likely to increase in the future as the population ages. The estimates reported here provide a basis for assessment of the cost-effectiveness of measures to reduce the incidence of hospital-acquired ulcers.
Heron Evidence Development Ltd. was funded for this work by Mölnlycke Health Care (UK). The authors have no other conflicts of interest to declare.
Deep pressure ulcers represent a major problem for individuals with spinal cord injury (SCI), with the initial damage often hidden underneath intact skin. Accordingly, early detection is difficult and treatment is problematic. In the present study, circulatory levels of biomarkers for muscle damage were investigated to explore their potential in the early detection of deep pressure ulcers. Baseline concentrations of creatine kinase, myoglobin (Mb), heart-type fatty acid binding protein (H-FABP), and C-reactive protein (CRP) were measured in small groups of nondisabled (age 39-66 yr) subjects and subjects with SCI (age 40-68 yr, American Spinal Injury Association grade A-B, level of injury thoracic 11 to lumbar 3) over a period of 5 days. Each subject exhibited a unique concentration profile for all markers, although some correlations were observed; for example, Mb and H-FABP were correlated for both subject groups. No significant differences were found in marker concentrations between the two subject groups, although a trend toward higher CRP levels was observed in the SCI subjects. Furthermore, one SCI subject with a category II pressure ulcer exhibited higher H-FABP and CRP concentrations than all other subjects. Because the variations in each of the marker concentrations were smaller than the predicted increases after pressure ulcers, this combination of plasma markers may prove appropriate for the early detection of deep pressure ulcers.
To design a time-efficient patient-friendly clinical diffusion tensor MRI protocol and postprocessing tool to study the complex muscle architecture of the human forearm.
The 15-minute examination was done using a 3 T system and consisted of: T(1) -weighted imaging, dual echo gradient echo imaging, single-shot spin-echo echo-planar imaging (EPI) diffusion tensor MRI. Postprocessing comprised of signal-to-noise improvement by a Rician noise suppression algorithm, image registration to correct for motion and eddy currents, and correction of susceptibility-induced deformations using magnetic field inhomogeneity maps. Per muscle one to five regions of interest were used for fiber tractography seeding. To validate our approach, the reconstructions of individual muscles from the in vivo scans were compared to photographs of those dissected from a human cadaver forearm.
Postprocessing proved essential to allow muscle segmentation based on combined T(1) -weighted and diffusion tensor data. The protocol can be applied more generally to study human muscle architecture in other parts of the body.
The proposed protocol was able to visualize the muscle architecture of the human forearm in great detail and showed excellent agreement with the dissected cadaver muscles.
The purpose of this prospective exploratory study was to determine the percentage of suspected deep tissue injuries (sDTI) that evolve into full-thickness skin loss, to describe the progression from sDTI to full-thickness skin loss, and to explore associated conditions.
The study was conducted by WOC nurses at 6 acute care medical facilities in North Carolina. Inclusion criteria were age 21 years or older and presence of an sDTI lesion. Participating members of the North Carolina WOC Nurse's Group identified 40 patients with a total of 45 sDTI.
A 2-part data collection tool was developed by 1 of the investigators and validated by members of the North Carolina WOC Nurse Group; data were collected at the time of initial consult and at a follow-up visit that occurred 1 to 20 days later (average 6 days). Data collected included description of wound appearance as well as information about comorbid and potential risk factors.
The sample comprised 40 subjects with 45 sDTI; 3 were lost to follow-up, resulting in a total of 37 subjects with 42 sDTI at the second assessment. Eleven (26%) sDTI developed into full-thickness skin loss, and 7 (17%) evolved from purple/maroon discoloration to thin blisters over dark wound beds. Twenty (48%) did not change between the time of initial consult and the follow-up visit up between 1 and 20 days later. Two lesions healed (1 at 6 days and the other at 8 days).
Despite preventive care, 26% of the sDTI evolved into full-thickness lesions at follow-up visit, and 17% evolved into unstageable pressure ulcers. However, 5% healed and 48% remained the same, suggesting that preventive care may be effective for many sDTI lesions.
PURPOSE: To enhance the learner's competence with information about heel pressure ulcers. TARGET AUDIENCE: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. OBJECTIVES: After participating in this educational activity, the participant should be better able to: 1. Interpret factors contributing to potential pressure ulcers (PrUs). 2. Apply knowledge gained on risk factors, prevention and treatment of heel PrUs, suspected deep tissue injuries, and "purple heel" to patient care scenarios. ABSTRACT: The heel is a frequent site of pressure ulcer formation, in particular, the development of suspected deep tissue injury. This article reviews the epidemiology, pathophysiology and prevention of heel pressure ulcers. Also, the related concept of purple heel, a not-well-recognized entity, is introduced.
Deep tissue injury (DTI) is a severe form of pressure ulcer where tissue damage starts in deep tissues underneath intact skin. In the present study, the contributions of deformation, ischemia, and reperfusion to skeletal muscle damage development were examined in a rat model during a 6-h period. Magnetic resonance imaging (MRI) was used to study perfusion (contrast-enhanced MRI) and tissue integrity (T2-weighted MRI). The levels of tissue deformation were estimated using finite element models. Complete ischemia caused a gradual homogeneous increase in T2 (∼20% during the 6-h period). The effect of reperfusion on T2 was highly variable, depending on the anatomical location. In experiments involving deformation, inevitably associated with partial ischemia, a variable T2 increase (17-66% during the 6-h period) was observed reflecting the significant variation in deformation (with two-dimensional strain energies of 0.60-1.51 J/mm) and ischemia (50.8-99.8% of the leg) between experiments. These results imply that deformation, ischemia, and reperfusion all contribute to the damage process during prolonged loading, although their importance varies with time. The critical deformation threshold and period of ischemia that cause muscle damage will certainly vary between individuals. These variations are related to intrinsic factors, such as pathological state, which partly explain the individual susceptibility to the development of DTI and highlight the need for regular assessments of individual subjects.
Pressure ulcers are localized areas of soft tissue breakdown due to mechanical loading. Susceptible individuals are subjected to pressure relief strategies to prevent long loading periods. Therefore, ischemia-reperfusion injury may play an important role in the etiology of pressure ulcers. To investigate the inter-relation between postischemic perfusion and changes in skeletal muscle integrity, the hindlimbs of Brown Norway rats were subjected to 4-h ischemia followed by 2-h reperfusion. Dynamic contrast-enhanced MRI was used to examine perfusion, and changes in skeletal muscle integrity were monitored with T2-weighted MRI. The dynamic contrast-enhanced MRI data showed a heterogeneous postischemic profile in the hindlimb, consisting of areas with increased contrast enhancement (14-76% of the hindlimb) and regions with no-reflow (5-77%). For T2, a gradual increase in the complete leg was observed during the 4-h ischemic period (from 34 to 41 msec). During the reperfusion phase, a heterogeneous distribution of T2 was observed. Areas with increased contrast enhancement were associated with a decrease in T2 (to 38 msec) toward preischemic levels, whereas no-reflow areas exhibited a further increase in T2 (to 42 msec). These results show that reperfusion after prolonged ischemia may not be complete, thereby continuing the ischemic condition and aggravating tissue damage.
The diagnosis of deep tissue injury (DTI) is currently still vague [1], with only subjective methods available for quantification. Tools are missing for clinicians to objectively sense DTI under the intact skin, which hampers the development of evidence-based practice for early diagnosis and treatment. Several molecules [2–9] have been reported as indicating muscle injury because they are released during skeletal muscle damage and subsequent inflammation [10]. Myoglobin (MB) [2,6], heart-type fatty acid binding protein (H-FABP) [2,8,9], myosin [4], and troponin-I (TnI) [6] have shown significant increases after severe skeletal muscle injury, whereas hydroxyproline (HP) is released during collagen breakdown in tissue damage [9]. Common biomarkers for tissue injury–related inflammation are creatine kinase (CK) [7,8,11], and α1-acid glycoprotein (α1-AGP) [12]. The objective of this study was to examine the concentration of these molecules in blood and/or urine on a spinal cord injury (SCI)-DTI rat model [13] during DTI formation to initially assess their potential as the biomarkers indicating the onset of a DTI.
Suspected deep tissue injury (sDTI) was identified in 2001 and added as a staging definition by the National Pressure Ulcer Advisory Panel in 2007. Clinical data on sDTI are sparse. This article reports the overall prevalence data and describes the demographics of subjects with sDTI from the International Pressure Ulcer Prevalence survey 2006-2009.
Participating healthcare facilities performed prevalence surveys in their facility during a pre-determined 24-hour period within a pre-selected 2- to 3-day window. All generated data was incorporated into the database, even if specific data fields were absent.
Approximately 79,000 to 92,000 patients were surveyed each year from 2006 to 2009. The overall and nosocomial pressure ulcer (PrU) prevalence decreased by approximately 1% in 2009 (P < .001), after remaining fairly constant in the years 2006-2008. The proportion of ulcers identified as sDTI has increased 3 fold, to 9% of all observed ulcers in 2009 and is more prevalent than either Stage III or IV ulcers. Over the same period, the proportion of Stage I and II ulcers have decreased, and the proportion of Stage III and IV ulcers has remained nearly constant. Patients with sDTIs are older than patients with Stage III, IV, and Unstageable ulcers. The anatomic location of sDTIs are more commonly found at the heel (41%), the sacrum (19%), or the buttocks (13%). Compared with other staged ulcers, sDTIs are significantly more prevalent at the heel (P < .001) and the ankle and foot (P < .001) and less prevalent at the sacrum and coccyx (P < .001) and at the buttocks and ischial tuberosities (P < 0.001).
The survey data indicate that a decrease in overall prevalence of PrUs, as well as hospital-acquired PrUs, may have occurred in 2009. Suspected deep tissue injuries have become more commonly identified, which may be secondary to education of staging definitions.
For pressure ulcer prevention an ambitious goal would be the establishment of a mechanical threshold for tissue damage. In the past, several researchers have sought to establish such a threshold often involving the loading time. However, they have not resulted in a unique reliable value that could be used in practice. This limitation is probably due to the focus on interface pressure. The objective of this paper is to clarify to an audience with no conventional background in mechanics, why interface pressure is not the appropriate parameter to define a damage threshold, whereas internal local deformations (strains) may prove more suitable. The paper reveals that it may be possible to identify a damage threshold for healthy skeletal muscle tissue based on local internal deformations.
Sustained mechanical loading of skeletal muscle may result in the development of a severe type of pressure ulcer, referred to as deep tissue injury. Recently it was shown that the diffusion of large molecules (10-150kDa) is impaired during deformation of tissue-engineered skeletal muscle, suggesting a role for impaired diffusion in the aetiology of deep tissue injury. However, the influence of deformation on diffusion of smaller molecules on its aetiology is less clear. This motivated the present study designed to investigate the influence of deformation of skeletal muscle on the diffusion of water, which can be measured with diffusion tensor magnetic resonance imaging (MRI). It could be predicted that this approach will provide valuable information on the diffusion of small molecules. Additionally the relationship between muscle temperature and diffusion was investigated. During deformation of the tibialis anterior a decrease of the apparent diffusion coefficient (ADC) was observed (7.2+/-3.9%). The use of a finite element model showed that no correlation existed between the maximum shear strain and the decrease of the ADC. The ADC in the uncompressed gastrocnemius muscle decreased with 5.9+/-3.7%. In an additional experiment a clear correlation was obtained between the decrease of the ADC and the relative temperature change of skeletal muscle tissue as measured by MRI. Taken together, it was concluded that (1) the decreased diffusion of water was not a direct effect of tissue deformation and (2) that it is likely that the observed decreased ADC during deformation was a result of a decreased muscle temperature. The present study therefore provides evidence that diffusion of small molecules, particularly oxygen and carbon dioxide, is not impaired during deformation of skeletal muscle tissue.
High-force lengthening contractions are associated with muscle damage and pain, and the muscle-tendon junction is commonly cited as the primary area where myofiber damage occurs. We induced injury in the rat tibialis anterior muscle and acquired magnetic resonance imaging (MRI) images postinjury. We also assayed membrane damage and quantified the number of centrally nucleated myofibers throughout the injured muscles. Results suggest that myofiber injury occurs primarily in the middle portion of the muscle, with interstitial edema in the middle and distal portions.