Optical Coherence Tomography Reveals Self-Organizing Di-Fork Architecture of Mice Cutaneous Scars

AbstractScientific studies report crucial impacts of biomechanical effectors to modulate wound healing either by scarring or regeneration. Further, the biological decision to predominantly favor the former is still cryptic. Real-time visualization of biomechanical manifestations in situ in scarring is hence necessary. Endorsed by nanostructural testing, synthetic phantom analysis, and computational simulations, we found strong mechanobiological correlates for Swept Source Optical Coherence Tomography (SS-OCT) speckles in mice cutaneous repair (full-thickness) up to 10 months. The theoretical basis of the optomechanics to provide insights into scar form-factor and evolution is proposed. Optomechanical changes have been considered as the resultant of intrinsic (e.g. fiber elastic modulus) and gross tissue mechanics (extracellular matrix (ECM)) in maturing scars. Non-invasive optomechanics supported with microscopic findings reveal scar’s cross-sectional self-organizing di-fork architecture. Dual-compartment heterogeneity of di-fork exhibits stress-evading features with a dichotomy in inhabitant cellular stress-fiber distributions. This differential interactivity of scar with adjoining tissues reflects its architectural intelligence to compensate tissue loss (hypodermis/muscle) by assembling into a di-fork. Gradual establishment of baseline shifted lasting mechanobiological steady-state, later in scarring, expose scar as an alternate stable state within the skin.Significance StatementWound repair in mammals, predominantly culminates into function compromising scar that is occasionally fatal in vital organs. How the biological system often adopts scarring over a restorative regeneration is yet a conundrum. Wound and ambient mechanics play a pivotal role in deciding the healing fate. SS-OCT is hence demonstrated here as a non-invasive window to such mechanical manifestations during skin wound healing. This exposed gradual emergence of temporally maintained and stress-resilient di-fork architecture of the scar with differential neighborhood interfaces. Accommodation of such an alternate self-organizing steady-state of scar sheds light on its sustenance and paradoxical selection.

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Evaluation of optical coherence tomography as a non-invasive diagnostic tool in cutaneous wound healing

Skin Research and Technology ◽

10.1111/srt.12077 ◽

2013 ◽

Vol 20 (1) ◽

pp. 1-7 ◽

Cited By ~ 19

Author(s):

Monika Kuck ◽

Helene Strese ◽

Seyed Arash Alawi ◽

Martina C. Meinke ◽

Joachim W. Fluhr ◽

...

Keyword(s):

Wound Healing ◽

Optical Coherence Tomography ◽

Diagnostic Tool ◽

Optical Coherence ◽

Cutaneous Wound Healing ◽

Cutaneous Wound ◽

Non Invasive

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Volumetric quantification of wound healing by machine learning and optical coherence tomography in adults with type 2 diabetes: the GC-SHEALD RCT

10.1101/2021.06.30.21259754 ◽

2021 ◽

Author(s):

Yinhai Wang ◽

Ramzi Ajjan ◽

Adrian Freeman ◽

Paul M Stewart ◽

Francesco Del Galdo ◽

...

Keyword(s):

Machine Learning ◽

Type 2 Diabetes ◽

Wound Healing ◽

Optical Coherence Tomography ◽

Granulation Tissue ◽

Wound Repair ◽

Optical Coherence ◽

Impaired Wound Healing ◽

Volumetric Quantification

Type 2 diabetes mellitus is associated with impaired wound healing, which contributes substantially to patient morbidity and mortality. Glucocorticoid (stress hormone) excess is also known to delay wound repair. Optical coherence tomography (OCT) is an emerging tool for monitoring healing by 'virtual biopsy', but largely requires manual analysis, which is labour-intensive and restricts data volume processing. This limits the capability of OCT in clinical research. Using OCT data from the GC-SHEALD trial, we developed a novel machine learning algorithm for automated volumetric quantification of discrete morphological elements of wound healing (by 3mm punch biopsy) in patients with type 2 diabetes. This was able to differentiate between early / late granulation tissue, neo-epidermis and clot structural features and quantify their volumetric transition between day 2 and day 7 wounds. Using OCT, we were able to visualize differences in wound re-epithelialisation and re-modelling otherwise indistinguishable by gross wound morphology between these time points. Automated quantification of maximal early granulation tissue showed a strong correlation with corresponding (manual) GC-SHEALD data. Further, % re-epithelialisation was improved in patients treated with oral AZD4017, an inhibitor of systemic glucocorticoid-activating 11β-hydroxysteroid dehydrogenase type 1 enzyme action, with a similar trend in neo-epidermis volume. Through the combination of machine learning and OCT, we have developed a highly sensitive and reproducible method of automated volumetric quantification of wound healing. This novel approach could be further developed as a future clinical tool for the assessment of wound healing e.g. diabetic foot ulcers and pressure ulcers.

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Optical Coherence Tomography: A Non-Invasive Method to Assess Wound Healing

Annals of Emergency Medicine ◽

10.1016/j.annemergmed.2005.06.254 ◽

2005 ◽

Vol 46 (3) ◽

pp. 68

Author(s):

A.J. Singer ◽

Z. Wang ◽

S.A. McClain ◽

Y. Pan

Keyword(s):

Wound Healing ◽

Optical Coherence Tomography ◽

Optical Coherence ◽

Non Invasive ◽

Invasive Method

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Optical coherence tomography angiography monitors human cutaneous wound healing over time

Quantitative Imaging in Medicine and Surgery ◽

10.21037/qims.2018.02.07 ◽

2018 ◽

Vol 8 (2) ◽

pp. 135-150 ◽

Cited By ~ 9

Author(s):

Anthony J. Deegan ◽

Wendy Wang ◽

Shaojie Men ◽

Yuandong Li ◽

Shaozhen Song ◽

...

Keyword(s):

Wound Healing ◽

Optical Coherence Tomography ◽

Optical Coherence Tomography Angiography ◽

Optical Coherence ◽

Cutaneous Wound Healing ◽

Cutaneous Wound ◽

Over Time

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Non-invasive three-dimensional thickness analysis of oral epithelium based on optical coherence tomography—development and diagnostic performance

Heliyon ◽

10.1016/j.heliyon.2021.e06645 ◽

2021 ◽

Vol 7 (4) ◽

pp. e06645

Author(s):

Charlotte Theresa Trebing ◽

Sinan Sen ◽

Stefan Rues ◽

Christopher Herpel ◽

Maria Schöllhorn ◽

...

Keyword(s):

Optical Coherence Tomography ◽

Diagnostic Performance ◽

Three Dimensional ◽

Oral Epithelium ◽

Optical Coherence ◽

Non Invasive

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Label-free non-invasive classification of rice seeds using optical coherence tomography assisted with deep neural network

Optics & Laser Technology ◽

10.1016/j.optlastec.2020.106861 ◽

2021 ◽

Vol 137 ◽

pp. 106861

Author(s):

Deepa Joshi ◽

Ankit Butola ◽

Sheetal Raosaheb Kanade ◽

Dilip K. Prasad ◽

S.V. Amitha Mithra ◽

...

Keyword(s):

Neural Network ◽

Optical Coherence Tomography ◽

Deep Neural Network ◽

Optical Coherence ◽

Label Free ◽

Non Invasive ◽

Rice Seeds

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Monitoring New Long-Lasting Intravitreal Formulation for Glaucoma with Vitreous Images Using Optical Coherence Tomography

Pharmaceutics ◽

10.3390/pharmaceutics13020217 ◽

2021 ◽

Vol 13 (2) ◽

pp. 217

Author(s):

Maria Jesus Rodrigo ◽

Amaya Pérez del Palomar ◽

Alberto Montolío ◽

Silvia Mendez-Martinez ◽

Manuel Subias ◽

...

Keyword(s):

Optical Coherence Tomography ◽

Relative Intensity ◽

Therapeutic Option ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Aggregate Size ◽

Daily Practice ◽

Optical Coherence ◽

Non Invasive ◽

Invasive Method

Intravitreal injection is the gold standard therapeutic option for posterior segment pathologies, and long-lasting release is necessary to avoid reinjections. There is no effective intravitreal treatment for glaucoma or other optic neuropathies in daily practice, nor is there a non-invasive method to monitor drug levels in the vitreous. Here we show that a glaucoma treatment combining a hypotensive and neuroprotective intravitreal formulation (IF) of brimonidine–Laponite (BRI/LAP) can be monitored non-invasively using vitreoretinal interface imaging captured with optical coherence tomography (OCT) over 24 weeks of follow-up. Qualitative and quantitative characterisation was achieved by analysing the changes in vitreous (VIT) signal intensity, expressed as a ratio of retinal pigment epithelium (RPE) intensity. Vitreous hyperreflective aggregates mixed in the vitreous and tended to settle on the retinal surface. Relative intensity and aggregate size progressively decreased over 24 weeks in treated rat eyes as the BRI/LAP IF degraded. VIT/RPE relative intensity and total aggregate area correlated with brimonidine levels measured in the eye. The OCT-derived VIT/RPE relative intensity may be a useful and objective marker for non-invasive monitoring of BRI/LAP IF.

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