Timeline of the longitudinal study. Magnetic resonance Elastography measurements are indicated by MRE in the timeline, and T 2 -

Timeline of the longitudinal study. Magnetic resonance Elastography measurements are indicated by MRE in the timeline, and T 2 -

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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 developme...

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... animal experiments were approved by the Animal Care and Use Committee of Maastricht University (protocol 2013-047, Maastricht University, Maastricht, The Netherlands) and performed in accordance with Directive 2010/63/EU for animal experiments in the European Union. Figure 1 shows the timeline of the longitudinal study. MRE, T 2 -weighted, and T 2 -mapping measurements were performed pre and post-2 h damage-inducing deformation of the TA muscle at Day 0, as well as at Day 3, 5, 7, 10, and 14. ...

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... First and foremost, objective muscle tone data can help the health care professional determine the lesion or other deviation from the physiological norm, its extent and degree, and possibly its nature or cause. For example, using both USE (ultrasound elastography) [91] and MRE, it has been possible to detect changes in various myopathies [92], conditions preceding pressure ulcers [93], and other muscle pathologies. Furthermore, these methods or Myoton can be used to detect stiff fascicles characteristic of myofascial trigger points [66,94,95], to assess rigidity [96][97][98][99][100] or spasticity [101]. ...
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“Muscle tone” is a clinically important and widely used term and palpation is a crucial skill for its diagnosis. However, the term is defined rather vaguely, and palpation is not measurable objectively. Therefore, several methods have been developed to measure muscle tone objectively, in terms of biomechanical properties of the muscle. This article aims to summarize these approaches. Through database searches, we identified those studies related to objective muscle tone measurement in vivo, in situ. Based on them, we described existing methods and devices and compared their reliability. Furthermore, we presented an extensive list of the use of these methods in different fields of research. Although it is believed by some authors that palpation cannot be replaced by a mechanical device, several methods have already proved their utility in muscle biomechanical property diagnosis. There appear to be two issues preventing wider usage of these objective methods in clinical practice. Firstly, a high variability of their reliability, and secondly, a lack of valid mathematical models that would provide the observed mechanical characteristics with a clear physical significance and allow the results to be compared with each other.
... Biomarkers relevant to dermal white adipose tissue (dWAT) or muscle associated with a deep tissue injury (DTI) were not within the scope of this study, where imaging biomarkers may be a better reflection of tissue status. 47 It is important to further investigate the predictive and prognostic capability of the panel of cytokines in a longitudinal clinical study, in which Stage I PU sites may heal or progress to wounds. ...
Article
Pressure Ulcers (PU) are a major burden for affected patients and healthcare providers. Current detection methods involve visual assessments of the skin by healthcare professionals. This has been shown to be subjective and unreliable, with challenges associated with identifying erythema in darker colour skin. Although there exists a number of promising non‐invasive biophysical techniques such as ultrasound, capacitance measurements, and thermography, the present study focuses on directly measuring the changes in the inflammatory status of the skin and underlying tissues. Therefore, in this study, we aim to analyse inflammatory cytokines collected through non‐invasive sampling techniques to detect early signs of skin damage. Thirty hospitalised patients presenting with Stage I PU were recruited to evaluate the inflammatory response of skin at the site of damage and an adjacent healthy control site. Sebutapes were collected over three sessions to investigate the temporal changes in the inflammatory response. The panel of cytokines investigated included high‐abundance cytokines, namely, IL‐1α and IL‐1RA, and low abundance cytokines; IL‐6, IL‐8, TNF‐α, INF‐γ, IL‐33, IL‐1β and G‐CSF. Spatial and temporal differences between sites were assessed and thresholds were used to determine the sensitivity and specificity of each biomarker. The results suggest significant (P < .05) spatial changes in the inflammatory response, with upregulation of IL‐1α, IL‐8, and G‐CSF as well as down‐regulation of IL‐1RA over the Stage I PU compared with the adjacent control site. There were no significant temporal differences between the three sessions. Selected cytokines, namely, IL‐1α, IL‐1RA, IL‐8, G‐CSF, and the ratio IL‐1α/IL‐1RA offered clear delineation in the classification of healthy and Stage‐I PU skin sites, with receiver operating characteristic curves demonstrating high sensitivity and specificity. There were limited influences of intrinsic and extrinsic factors on the biomarker response. Inflammatory markers provided a high level of discrimination between the sites presenting with Stage I PU and an adjacent healthy skin site, in a cohort of elderly inpatients. Indeed, the ratio of IL‐1α to IL‐1RA provided the highest sensitivity and specificity, indicative that inflammatory homeostasis is affected at the PU site. There was a marginal influence of intrinsic and extrinsic factors, demonstrating the localised effects of the inflammation. Further studies are required to investigate the potential of inflammatory cytokines incorporated within Point of Care technologies, to support routine clinical use.
... As it stands, the direct measurement of overload thresholds in the context of occipital ulceration would involve applying and sustaining pressure until the development of an overload injury in the soft tissues at the back of the head. Similar methodologies have been successfully used in literature to study overload injury in the muscle of animal models of pressure ulceration [24][25][26] or in in vitro tissue engineering models. 27 However, this invasive approach is not applicable for human in vivo testing. ...
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Introduction The high prevalence of occipital ulcers in UK military casualties observed during the conflict in Afghanistan is a multifactorial phenomenon. However, the consensus is that ulceration is triggered by excessive pressure that is maintained for too long during the use of the general service military stretcher. Thresholds for capillary occlusion are accepted benchmarks to define excessive pressure, but similar thresholds for safe/excessive duration of pressure application do not exist. To address this gap in knowledge, we propose to use the time it takes for a healthy person to feel pain at the back of the head as an initial indication of safe exposure to pressure. Methods Healthy military personnel (16 male/10 female) were asked to lie motionless on a typical general service stretcher until they felt pain. Time-to-pain and the location of pain were recorded. To support the interpretation of results, baseline sensitivity to pain and pressure distribution at the back of the head were also measured. Independent samples t-test was used to assess differences between genders. Results Twenty participants felt pressure-induced soft-tissue pain at the back of the head. The remaining six participants terminated the test due to musculoskeletal pain caused by poor ergonomic positioning. On average, pain at the occiput developed after 31 min (±14 min). Female participants were significantly more sensitive to pain (t(24)=3.038,p=0.006), but time-to-pain did not differ significantly between genders (p>0.05). Conclusions When people lie motionless on a typical military stretcher, the back of the head is the first area of the body that becomes painful due to pressure. The fact that pain develops in ≈30 min can help healthcare providers decide how frequently to reposition their patients who are unable to do this on their own. More research is still needed to directly link time-to-pain with time-to-injury.
... S. Loerakker et al. 2010;S. Loerakker et al. 2011;Nelissen et al. 2019;Stekelenburg et al. 2006;Traa et al. 2018;van Nierop et al. 2010). Based on the results obtained on N=11 female Brown-Norway rats, Ceelen et al. established that tissue damage could be measured using T2-weighted MRI when the maximum shear strain in the tissues and the compressive strain were in excess of 75% and 45 % respectively (Ceelen et al. 2008). ...
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OBJECTIVE: 2D Ultrasound (US) imaging has been recently investigated as a more accessible alternative to 3D Magnetic Resonance Imaging (MRI) for the estimation of soft issue motion under external mechanical loading. In the context of pressure ulcer prevention, the aim of this pilot MRI study was to design an experiment to characterize the sacral soft tissue motion under a controlled mechanical loading. Such an experiment targeted the estimation of the discrepancy between tissue motion assessed using a 2D imaging modality (echography) versus tissue motion assessed using a (reference) 3D imaging modality (MRI).METHODS: One healthy male volunteer participated in the study. An MRI-compatible custom-made setup was designed and used to load the top region of the sacrum with a 3D-printed copy of the US transducer. Five MR images were collected, one in the unloaded and four in the different loaded configurations (400-1200 [g]). Then, a 3D displacement field for each loading configuration was extracted based on the results of digital volume correlation. Tissue motion was separated into the X, Y, Z directions of the MRI coordinate system and the ratios between the out-of-plane and in-plane components were assessed for each voxel of the selected region of interest.RESULTS: Ratios between the out-of-plane and in-plane displacement components were higher than 0.6 for more than half of the voxels in the region of interest for all load cases and higher than 1 for at least quarter of the voxels when loads of 400-800 [g] were used.CONCLUSION: The out-of-ultrasound-plane tissue displacement was not negligible, therefore 2D US imaging should be used with caution for the evaluation of the tissue motion in the sacrum region. The 3D US modality should be further investigated for this application.
... S. Loerakker et al. 2010;S. Loerakker et al. 2011;Nelissen et al. 2019;Stekelenburg et al. 2006;Traa et al. 2018;van Nierop et al. 2010). Based on the results obtained on N=11 female Brown-Norway rats, Ceelen et al. established that tissue damage could be measured using T2-weighted MRI when the maximum shear strain in the tissues and the compressive strain were in excess of 75% and 45 % respectively (Ceelen et al. 2008). ...
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Objective 2D Ultrasound (US) imaging has been recently investigated as a more accessible alternative to 3D Magnetic Resonance Imaging (MRI) for the estimation of soft issue motion under external mechanical loading. In the context of pressure ulcer prevention, the aim of this pilot MRI study was to design an experiment to characterize the sacral soft tissue motion under a controlled mechanical loading. Such an experiment targeted the estimation of the discrepancy between tissue motion assessed using a 2D imaging modality (echography) versus tissue motion assessed using a (reference) 3D imaging modality (MRI). Methods One healthy male volunteer participated in the study. An MRI-compatible custom-made setup was designed and used to load the top region of the sacrum with a 3D-printed copy of the US transducer. Five MR images were collected, one in the unloaded and four in the different loaded configurations (400–1200 [g]). Then, a 3D displacement field for each loading configuration was extracted based on the results of digital volume correlation. Tissue motion was separated into the X, Y, Z directions of the MRI coordinate system and the ratios between the out-of-plane and in-plane components were assessed for each voxel of the selected region of interest. Results Ratios between the out-of-plane and in-plane displacement components were higher than 0.6 for more than half of the voxels in the region of interest for all load cases and higher than 1 for at least quarter of the voxels when loads of 400–800 [g] were used. Conclusion The out-of-ultrasound-plane tissue displacement was not negligible, therefore 2D US imaging should be used with caution for the evaluation of the tissue motion in the sacrum region. The 3D US modality should be further investigated for this application.
... The link between tissue damage and altered mechanical properties was previously demonstrated for muscle tissue using an animal model 9,10 . Nelissen et al. induced deep-tissue injury by applying large-strain indentation for two hours in the tibialis anterior muscle of anaesthetised rats 9 . ...
... The link between tissue damage and altered mechanical properties was previously demonstrated for muscle tissue using an animal model 9,10 . Nelissen et al. induced deep-tissue injury by applying large-strain indentation for two hours in the tibialis anterior muscle of anaesthetised rats 9 . Measurement of the tissue's mechanical behaviour before and after overloading revealed significant localised stiffening following overload injury. ...
... Measurement of the tissue's mechanical behaviour before and after overloading revealed significant localised stiffening following overload injury. Even though the methods for overloading-induced tissue damage presented by Nelissen et al. are not transferable to in vivo human testing, their findings highlight tissue stiffening as a potential marker for soft tissue overloading 9,10 . ...
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This proof-of-concept study demonstrates that repetitive loading to the pain threshold can safely recreate overloading-induced soft tissue damage and that localised tissue stiffening can be a potential marker for injury. This concept was demonstrated here for the soft tissue of the sole of the foot where it was found that repeated loading to the pain threshold led to long-lasting statistically significant stiffening in the overloaded areas. Loading at lower magnitudes did not have the same effect. This method can shed new light on the aetiology of overloading injury in the foot to improve the management of conditions such as diabetic foot ulceration and heel pain syndrome. Moreover, the link between overloading and tissue stiffening, which was demonstrated here for the first time for the plantar soft tissue, opens the way for an assessment of overloading thresholds that is not based on the subjective measurement of pain thresholds.
... Recent studies have evaluated spasticity (Beattie et al. 2016;Marinelli et al. 2017;Carlyle and Mochizuki 2018;Chen et al. 2018) using electromyography (Cram and Steger 1983) and imaging techniques that quantify muscle spasticity in clinical practice (Illomei et al. 2017). New technologies including magnetic resonance elastography (Creze et al. 2018;Tan et al. 2018;Nelissen et al. 2019;Wang et al. 2019) and USE show promising findings for the direct measurement of the mechanical properties of muscles (Brandenburg et al. 2014). Furthermore, some studies reported that the symptoms of spasticity gradually develop after a stroke (Burke et al. 2013), mainly between 1 and 6 wk after the ictus (Lundstr€ om et al. 2010;Balakrishnan and Ward 2013). ...
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The incidence of muscle spasticity is high in patients with diseases of the central nervous system. This condition leads to significant limitations in movement and impaired functional capacities. Muscle spasticity manifests as changes in the mechanical properties of the muscles. This muscle disorder is generally assessed using qualitative methods, whose validity, reliability and sensitivity are questionable. In recent years, ultrasound elastography (USE) has been used as a non-invasive technique for characterizing the stress response and mechanical properties of individual muscles in the evaluation of spasticity. This article presents a systematic review of the USE techniques, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) declaration guidelines, used for the evaluation of muscle stiffness caused by spasticity. The articles selected in this study were evaluated using the Quality Appraisal of Diagnostic Reliability (QAREL) tool. Mainly, studies on the assessment of spasticity involving the evaluation of muscle stiffness with USE techniques (i.e., shear-wave elastography [SWE] or compression elastography [CE]) were selected. Then, common topics related to the assessment of spastic muscles and the statistical results of these studies were classified. Of 21 articles, nine used only CE, 10 used only SWE and two used both techniques. In the studies, statistically significant differences were observed in the measurements of muscle stiffness between the paretic and non-paretic sides as well as between patients and healthy patients. The clinical measurements obtained, devices used and assessment and probe positions for both techniques were discussed. The most frequently studied muscles were the biceps (n = 7) and gastrocnemius (n = 11). On applying the QAREL tool, we found that only two studies showed compliance at 80%–90%, seven studies at 50%–70% and the remaining 12 at 10%–40%. The results showed that USE techniques have limitations in spasticity assessment, such as subjectivity because of the lack of standardized protocols. A deficit of studies on intra-operator and inter-operator measurements indicates that this technique is not yet mature for spasticity diagnosis, although it is a promising diagnostic tool for designing treatment plans and monitoring the effectiveness of therapeutic modalities.
... Connecting macroscopic mechanical response to microscopic cellular organization of tissue, MRE opens up new avenues for assessing the etiology of tissue pathology. The modality has been implemented to varying degrees of success on skeletal muscle [1][2][3][4][5][6][7][8][9], breast [10][11][12][13][14][15][16][17], liver [18][19][20][21][22][23][24], and brain [25,26]. ...
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Magnetic Resonance Elastography allows noninvasive visualization of tissue mechanical properties by measuring the displacements resulting from applied stresses, and fitting a mechanical model. Poroelasticity naturally lends itself to describing tissue - a biphasic medium, consisting of both solid and fluid components. This article reviews the theory of poroelasticity, and shows that the spatial distribution of hydraulic permeability, the ease with which the solid matrix permits the flow of fluid under a pressure gradient, can be faithfully reconstructed without spatial priors in simulated environments. The paper describes an in-house MRE computational platform - a multi-mesh, finite element poroelastic solver coupled to an artificial epistemic agent capable of running Bayesian inference to reconstruct inhomogenous model mechanical property images from measured displacement fields. Building on prior work, the domain of convergence for inference is explored, showing that hydraulic permeabilities over several orders of magnitude can be reconstructed given very little prior knowledge of the true spatial distribution.
... Connecting macroscopic mechanical response to microscopic cellular organization of tissue, MRE opens up new avenues for assessing the etiology of tissue pathology. The modality has been implemented to varying degrees of success on skeletal muscle [1][2][3][4][5][6][7][8][9], breast [10][11][12][13][14][15][16][17], liver [18][19][20][21][22][23][24], and brain [25,26]. ...
... The shear modulus did not show this behavior, with image reconstruction recovering inclusion geometry and relative distribution very well by the 50 th iteration, although different initial conditions are seen to lead to different final absolute values -a peculiarity noted in prior work [106]. The lower panels of Fig. [5,6,8,9] show the inference trajectories, with initial estimates noted by an asterisk and changes in descent strategy indicated by red markers. ...
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Full-text available
Magnetic Resonance Elastography allows noninvasive visualization of tissue mechanical properties by measuring the displacements resulting from applied stresses, and fitting a mechanical model. Poroelasticity naturally lends itself to describing tissue -- a biphasic medium, consisting of both solid and fluid components. This article reviews the theory of poroelasticity, and shows that the spatial distribution of hydraulic permeability, the ease with which the solid matrix permits the flow of fluid under a pressure gradient, can be faithfully reconstructed without spatial priors in simulated environments. The paper describes an in-house MRE computational platform -- a multi-mesh, finite element poroelastic solver coupled to an artificial epistemic agent capable of running Bayesian inference to reconstruct inhomogenous model mechanical property images from measured displacement fields. Building on prior work, the domain of convergence for inference is explored, showing that hydraulic permeabilities over several orders of magnitude can be reconstructed given very little prior knowledge of the true spatial distribution.
Article
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Pressure injuries (PIs) are localized tissue damage resulting from prolonged compression or shear forces on the skin or underlying tissue, or both. Different stages of PIs share common features include intense oxidative stress, abnormal inflammatory response, cell death, and subdued tissue remodeling. Despite various clinical interventions, stage 1 or stage 2 PIs are hard to monitor for the changes of skin or identify from other disease, whereas stage 3 or stage 4 PIs are challenging to heal, painful, expensive to manage, and have a negative impact on quality of life. Here, we review the underlying pathogenesis and the current advances of biochemicals in PIs. We first discuss the crucial events involved in the pathogenesis of PIs and key biochemical pathways lead to wound delay. Then, we examine the recent progress of biomaterials-assisted wound prevention and healing and their prospects.