Photoacoustic and High-Frequency Ultrasound Imaging of Systemic Sclerosis Patients

Abstract Introduction: Systemic sclerosis starts with an early phase characterized by Raynauds phenomenon, puffy fingers/hands, autoantibodies and a scleroderma nailfoldmicroscopic pattern. Alterations in the nailfoldmicroscopic pattern are not evident in all early SSc patients. Photoacoustics(PA) and high-frequency ultrasound (HFUS) could fulfill this need. The former can measure oxygen saturation while the latter can measure skin thickening. We hypothesize that photoacoustics and high-frequency ultrasound can distinguish (early) SSc patients from individuals with primary Raynaud's phenomenon (PRP) by measuring oxygenation of the fingertip and skin thickening.Methods: We compared measurements of the third finger in (early)SSc patients to healthy and PRP individuals. The level of oxygenation and skin thickness were compared between groups. Nailfoldcapillaroscopy was performed on all subjects.Results: Thirty-one adult subjects participated in this study: twelve patients with SSc, 5 patients with early SSc, 5 volunteers with PR and 9 healthy controls. We found a significant difference in oxygen saturation between (early) SSc patients (80.8% ± 8.1 and 77,9% ± 10.5 ) and individuals with PRP (93.9% ± 1.1). Measurements of skin thickening showed a significant difference in (early) SSc patients compared to individuals with PRP (0.48 ± 0.06 mm and 0.51 ±0.16 mm vs. 0.27 ± 0.01 mm). There was no significant difference between healthy and PRP individuals in oxygenation or skin thickening.Conclusion: Photoacoustic and high-frequency ultrasound can distinguish between (early)SSc, PRP and healthy individuals in both oxygenation and skin thickening.

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AB0582 DIAGNOSING SYSTEMIC SCLEROSIS WITH PHOTOACOUSTIC AND HIGH-FREQUENCY ULTRASOUND IMAGING

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1388 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1588.1-1588

Author(s):

B. Kersten ◽

K. Daoudi ◽

C. H. M. Van den Ende ◽

F. Van den Hoogen ◽

C. De Korte ◽

...

Keyword(s):

Systemic Sclerosis ◽

Early Diagnosis ◽

Oxygen Saturation ◽

High Frequency ◽

Raynaud’S Phenomenon ◽

Raynaud's Phenomenon ◽

Skin Thickness ◽

High Frequency Ultrasound ◽

Significant Difference ◽

Frequency Ultrasound

Background:Vasculopathy is already evident in early systemic sclerosis (SSc); Raynaud’s phenomenon and typical nailfoldcapillaroscopic findings are part of the criteria of very early diagnosis of SSc (VEDOSs) (1). As not all early SSc patients have alterations in their nailfoldcapillaries, there is need for other diagnostic tools. Photoacoustics(PA) and high-frequency ultrasound (HFUS) might be able to fulfill this need (2). The former can measure the oxygen saturation of hemoglobin by using short pulsed laser light while the latter can provide high-resolution images that allow measuring skin thickening distal from DIP joint, which could be used to determine skin involvement early.Objectives:We hypothesize that photoacoustics and high-frequency ultrasound can distinguish (early) SSc patients from individuals with primary Raynaud’s phenomenon (PR) by measuring the oxygenation (by PA) of the fingertip and skin thickening (by HFUS).Methods:In our cross-sectional study, we compared measurements of the third finger in (early)SSc patients with individuals with PR and healthy volunteers. Smoking and beta-blockage were exclusion criteria. The level of oxygenation (by PA) and skin thickness (by HFUS) were compared between groups. Nailfoldcapillaroscopy was performed on all subjects and analyzed for the pattern.Results:Thirty-one adult subjects participated in this study: twelve patients with SSc, 5 patients with early SSc, 5 volunteers with PR and 9 healthy controls.We found a significant difference in median (IQR) oxygen saturation between earlySSc patients 75.9% (IQR 75.1%-86.6%) and subjects with PR 94.1% (IQR 93.1%-94.5%) (p=0.0002) using the Wilcoxon rank-sum test (figure 1).Figure 1.Boxplot of saturation (%) per group.Measurements of skin thickening also showed a significant difference in early SSc patients compared to subjects with PR, respectively 0.5mm (IQR 0.4mm-0.5mm) vs. 0.3mm (IQR 0.3mm-0.3mm), P=0.0002 (figure 2).Figure 2.Boxplot of skin thickness (mm) per group.Conclusion:Our results demonstrate that photoacoustic and high-frequency ultrasound can distinguish between (early)SSc and PR in both oxygenation saturation and skin thickening. In a larger prognostic study we want to determine the value of photoacoustic and high frequency ultrasound in diagnosing earlySSc.References:[1]Minier T, Guiducci S, Bellando-Randone S, Bruni C, Lepri G, Czirjak L, et al. Preliminary analysis of the very early diagnosis of systemic sclerosis (VEDOSS) EUSTAR multicentre study: evidence for puffy fingers as a pivotal sign for suspicion of systemic sclerosis. Annals of the rheumatic diseases. 2014;73(12):2087-93.[2]Wang LV, Yao J. A practical guide to photoacoustic tomography in the life sciences. Nature methods. 2016;13(8):627-38Disclosure of Interests:Brigit Kersten: None declared, Khalid Daoudi: None declared, C.H.M. van den Ende: None declared, FHJ van den Hoogen Consultant of: AbbVie, Actelion, Biogen, BMS, Celltrion, Corbus, Eli-Lilly, Mundipharma, Pfizer, Sanofi-Genzyme, Speakers bureau: Amgen, Boehringer-Ingelheim, Novartis, CL de Korte: None declared, Madelon Vonk Grant/research support from: Janssen and Ferrer, Consultant of: Boehringer Ingelheim, Janssen and GSK, Speakers bureau: Boehringer Ingelheim, BMS and Roche

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Photoacoustic and high-frequency ultrasound imaging of systemic sclerosis patients

Arthritis Research & Therapy ◽

10.1186/s13075-020-02400-y ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Khalid Daoudi ◽

Brigit E. Kersten ◽

Cornelia H. M. van den Ende ◽

Frank H. J. van den Hoogen ◽

Madelon C. Vonk ◽

...

Keyword(s):

Systemic Sclerosis ◽

Oxygen Saturation ◽

High Frequency ◽

Raynaud’S Phenomenon ◽

Raynaud's Phenomenon ◽

Skin Thickness ◽

Healthy Controls ◽

High Frequency Ultrasound ◽

Significant Difference ◽

Frequency Ultrasound

Abstract Introduction Systemic sclerosis starts with an early phase characterized by Raynaud’s phenomenon, puffy fingers/hands, autoantibodies, and a scleroderma nailfold microscopic pattern. Alterations in the nailfold microscopic pattern are not evident in all early SSc patients. Photoacoustics (PA) and high-frequency ultrasound (HFUS) could fulfill this need. The former can measure oxygen saturation while the latter can measure skin thickening. We hypothesize that photoacoustics and high-frequency ultrasound can distinguish (early) SSc patients from individuals with primary Raynaud’s phenomenon (PRP) by measuring oxygenation of the fingertip and skin thickening. Methods We compared measurements of oxygenation and skin thickness of the third finger between (early) SSc patients and PRP individuals and healthy controls. The spearman rank correlation was used to analyze an association between capillary density and oxygen saturation of the fingers. Results Thirty-one adult subjects participated in this study: twelve patients with SSc, 5 patients with early SSc, 5 volunteers with PR, and 9 healthy controls. We found a significant difference in oxygen saturation between (early) SSc patients (80.8% ± 8.1 and 77.9% ± 10.5) and individuals with PRP (93.9% ± 1.1). Measurements of skin thickening showed a significant difference in (early) SSc patients compared to individuals with PRP (0.48 ± 0.06 mm and 0.51 ± 0.16 mm vs. 0.27 ± 0.01 mm). There was no significant difference between healthy and PRP individuals in oxygenation or skin thickening. Conclusion Photoacoustic and high-frequency ultrasound could help to distinguish between (early) SSc, PRP, and healthy individuals in both oxygenation and skin thickening.

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SAT0305 PERFORMANCE OF HIGH FREQUENCY ULTRASOUND IN THE ASSESSMENT OF SKIN INVOLVEMENT IN SYSTEMIC SCLEROSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.6373 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1097.3-1098

Author(s):

G. Lettieri ◽

V. Picerno ◽

D. Temiz Karadağ ◽

M. C. Padula ◽

G. A. Mennillo ◽

...

Keyword(s):

Systemic Sclerosis ◽

High Frequency ◽

Disease Duration ◽

Skin Thickness ◽

Skin Involvement ◽

High Frequency Ultrasound ◽

Upper Arm ◽

Significant Difference ◽

Disease Stages ◽

Frequency Ultrasound

Background:The modified Rodnan skin score (mRSS) is the current gold standard for skin assessment in systemic sclerosis (SSc) both in clinical trials and practice. High frequency ultrasound (HFUS) has been suggested to offer a quantitative assessment of skin thickness in SSc by several studies, however results are inhomogeneous with regards to the machine used, number of imaged sites, as well as the various stages of skin involvement.Objectives:Aim of this cross-sectional study was to compare performance of HFUS in the assessment of skin involvement in diffuse cutaneous SSc (dcSSc) patients, at different disease stages, as compared with healthy controls (HC).Methods:Dorsal finger, hand, forearm and upper arm skin of consecutive dcSSc patients, at different disease stages, and of matched-HC were scanned bilaterally using HFUS. Two investigators, expert in MSK ultrasound, blinded to the clinical details, measured skin thickness using Esaote MyLab70 equipped with a 22 MHZ probe. Clinical involvement was assessed by a blinded operator using the mRSS and results were compared with imaging data. Statistical analysis was performed using GraphPad Prism software V.7.0.Results:A total of 704 HFUS images were obtained from 22 dcSSc patients [20 Female, mean age 49 (±11) years, 12 with ≤ 5 years disease duration] and 22 HC [20 Female, mean age 50.7 (±6.7) years]. Skin thickness was significantly higher in SSc patients than in HC at fingers (p<0.0001) and hands (p<0.0001), while no significant difference was found at the forearms and upper arms (p>0.05). HFUS showed a good discriminative ability between SSc and HC skin at fingers and hands (AUC 0.91, 0.81, 0.6 and 0.65 for fingers, hands, forearms and upper arms respectively). When analysing the subgroup of SSc patients with ≤5 years disease duration, HFUS showed a slightly lower performance in discriminating between SSc without clinical skin involvement (site mRSS=0) and HC (AUC 0.68, 0.57, 0.68 for hands, forearms and upper arms respectively). Mean HFUS skin thickness significantly correlated with mRSS at site of analysis (hand: r=0.78, p=<0.0001; forearm: r=0.47, p=0.0013; upper arm: r=0.52, p=0.0003) and total mRSS (hand: r=0.53, p=0.0002; forearm: r=0.63, p<0.0001; upper arm: r=0.63, p<0.0001). No significant correlation was found between finger skin thickness and mRSS (both local and total, p>0.05). Interobserver reliability for skin thickness was good to excellent at all sites with intraclass correlation coefficient ranging between 0.79 and 0.94.Conclusion:HFUS of the skin is a reliable measure of skin involvement in SSc. Studies with higher number of patients with different clinical features are needed to explore the potential of HFUS to discriminate between healthy and SSc skin, including sites at a preclinical stage of involvement.Disclosure of Interests:None declared

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High frequency ultrasound assessment of systemic sclerosis skin involvement: intra-observer repeatability and relationship with clinician assessment and dermal collagen content

The Journal of Rheumatology ◽

10.3899/jrheum.200234 ◽

2020 ◽

pp. jrheum.200234

Author(s):

Victoria A. Flower ◽

Shaney L. Barratt ◽

Darren J. Hart ◽

Amanda B. Mackenzie ◽

Jacqueline A. Shipley ◽

...

Keyword(s):

Systemic Sclerosis ◽

High Frequency ◽

Convergent Validity ◽

Objective Assessment ◽

Collagen Content ◽

Skin Thickness ◽

High Frequency Ultrasound ◽

Dermal Collagen ◽

The Relationship ◽

Frequency Ultrasound

Objective The modified Rodnan skin score (mRSS) remains the preferred method for skin assessment in systemic sclerosis (SSc). There are concerns regarding high inter-observer variability of mRSS and negative clinical trials utilising mRSS as the primary endpoint. High frequency ultrasound (HFUS) allows objective assessment of cutaneous fibrosis in SSc. We investigated the relationship between HFUS with both mRSS and dermal collagen. Methods Skin thickness (ST), echogenicity and novel Shear wave elastography (SWE) were assessed in 53 SSc patients and 15 healthy controls (HC) at the finger, hand, forearm and abdomen. The relationship between HFUS parameters with mRSS (n=53) and dermal collagen (10 SSc patients and 10 HC) was investigated. Intra-observer repeatability of HFUS was calculated using intra-class correlation coefficients (ICCs). Results HFUS assessment of ST (hand/forearm) and SWE (finger/hand) correlated with local mRSS at some sites. Subclinical abnormalities in ST, echogenicity and SWE were present in clinically uninvolved SSc skin. Additionally, changes in echogenicity and SWE were sometimes apparent despite objectively normal ST on HFUS. ST, SWE and local mRSS correlated strongly with collagen quantification (rho 0.697, 0.709, 0.649 respectively). Intra-observer repeatability was high for all HFUS parameters (ICCs for ST 0.946-0.978, echogenicity 0.648- 0.865 and SWE 0.953-0.973). Conclusion Our data demonstrates excellent reproducibility and reassuring convergent validity with dermal collagen content. Detection of subclinical abnormalities is an additional benefit of HFUS. The observed correlations with collagen quantification support further investigation of HFUS as an alternative to mRSS in clinical trial settings.

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P162 Cross-validation and complementary value of optical coherence tomography and high frequency ultrasound for the assessment of skin disease in systemic sclerosis

Rheumatology ◽

10.1093/rheumatology/keaa111.157 ◽

2020 ◽

Vol 59 (Supplement_2) ◽

Author(s):

Duygu Temiz Karadag ◽

Giovanni Lettieri ◽

Valentina Picerno ◽

Ozcan Gundogdu ◽

Maria Carmela Padula ◽

...

Keyword(s):

Optical Coherence Tomography ◽

Systemic Sclerosis ◽

Skin Disease ◽

High Frequency ◽

Skin Thickness ◽

Optical Coherence ◽

Skin Involvement ◽

High Frequency Ultrasound ◽

Complementary Value ◽

Frequency Ultrasound

Abstract Background The modified Rodnan skin score (mRSS) is the current gold standard for skin assessment in systemic sclerosis (SSc) both in clinical trials and practice. Several studies have reported that skin high frequency ultrasound (HFUS) and, more recently, optical coherence tomography (OCT) are able to reflect the severity of the skin disease in SSc. Aim of the study was to compare OCT and HFUS in the assessment of skin involvement in SSc. Methods Dorsal forearm skin of consecutive diffuse cutaneous SSc (dcSSc) patients and matched-healthy controls (HC) were scanned using OCT and HFUS by investigators blinded to the clinical details using Vivosight scanner (1 assessor) and Esaote MyLab70 equipped with a 22 MHZ probe (2 assessors) respectively. Minimum Optical Density (MinOD), Maximum OD (MaxOD) and OD at 300 micron-depth (OD300) (OCT) and skin thickness (HFUS) were measured. Clinical involvement was assessed by a blinded operator using the mRSS and results were cross matched with imaging data. Statistical analysis was performed using GraphPad Prism software V.7.0. Results A total of 88 OCT images and 176 HFUS images were obtained from 22 dcSSc patients [20 Female, mean age 49 (±11) years, 12 with < 5 years disease duration) and 22 HC (20 Female, mean age 50.7 (±6.7) years]. All OCT measures (MinOD, MaxOD and OD300) were significantly lower in SSc patients than in HC (p = 0.011, p < 0.0001, p < 0.0001 respectively). HFUS showed a lower performance in discriminating SSc skin vs HC compared to OCT (overall AUC 0.6 vs 0.72, 0.8 and 0.89 for MinOD, MaxOD and OD300 respectively). Nevertheless, mean HFUS skin thickness significantly correlated with mRSS at site of analysis (r = 0.47, p = 0.0013) and showed overall excellent interobserver reliability between assessors (ICC >0.8). Importantly, MaxOD and OD300 negatively correlated with HFUS skin thickness (r=-0.32, p = 0.035; r=-0.31, p = 0.039). Conclusion OCT of the skin has been previously validated against skin biopsy in SSc. Our results validate HFUS against OCT and indicate that HFUS of the skin is a reliable measure of skin involvement. Further, here we show that HFUS and OCT outperform each other in measuring different aspects of skin involvement in SSc and they offer complementary surrogate outcome measures of disease. Disclosures D. Temiz Karadag None. G. Lettieri None. V. Picerno None. O. Gundogdu None. M. Padula None. G.A. Mennillo None. A.A. Padula None. F. Del Galdo None. S. D'Angelo None. G. Abignano None.

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High frequency ultrasound measurement of digital dermal thickness in systemic sclerosis

Annals of the Rheumatic Diseases ◽

10.1136/ard.2009.114843 ◽

2009 ◽

Vol 69 (6) ◽

pp. 1140-1143 ◽

Cited By ~ 48

Author(s):

Olga Kaloudi ◽

Francesca Bandinelli ◽

Emilio Filippucci ◽

Maria Letizia Conforti ◽

Irene Miniati ◽

...

Keyword(s):

Systemic Sclerosis ◽

High Frequency ◽

Interobserver Variability ◽

Ultrasound Measurement ◽

Skin Thickness ◽

Intraobserver Variability ◽

High Frequency Ultrasound ◽

Dermal Thickness ◽

Dermal Thickening ◽

Frequency Ultrasound

BackgroundCurrently, assessment of dermal thickness in systemic sclerosis (SSc) is performed by palpation and assessment using the modified Rodnan skin score (mRSS).ObjectiveTo verify whether high frequency ultrasound (US) may be a reliable and a reproducible method to measure digital dermal thickness.MethodsIn 70 patients with SSc, skin thickness was evaluated with US by 2 observers at 2 different sites on the second digit of the dominant limb to determine the interobserver variability. Patients and controls were examined twice by the first observer for intraobserver variability. Patients were divided into three subgroups according to the phase of the disease (oedematous, fibrotic or atrophic).ResultsAt both examined areas, US showed a significant dermal thickening (p<0.001) in the whole group of patients with SSc. A low intraobserver and interobserver variability was found. A highly significant correlation between the global mRSS and the local dermal thickness at the two examined sites (p=0.032, p=0.021) was detected. Skin thickness was significantly higher in the oedematous than in the fibrotic group (p<0.001) and significantly higher in the fibrotic and the oedematous group (p<0.001) than in the atrophic group (p<0.002).ConclusionsUS is a reliable tool giving reproducible results, and is able to detect digital dermal thickening in SSc.

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Morphologic Features of Cutaneous T-Cell Lymphomas Using Dermoscopy and High Frequency Ultrasound

Journal of Clinical Medicine ◽

10.3390/jcm10010017 ◽

2020 ◽

Vol 10 (1) ◽

pp. 17

Author(s):

Iris Wohlmuth-Wieser ◽

Joel M. Ramjist ◽

Neil Shear ◽

Raed Alhusayen

Keyword(s):

T Cell ◽

High Frequency ◽

Early Stage ◽

Skin Lesions ◽

Diagnostic Tools ◽

Skin Thickness ◽

High Frequency Ultrasound ◽

T Cell Lymphomas ◽

Standardized Parameters ◽

Frequency Ultrasound

The diagnosis of cutaneous T-cell lymphomas (CTCL) is frequently delayed by a median of three years and requires the clinical evaluation of an experienced dermatologist and a confirmatory skin biopsy. Dermoscopy and high-frequency ultrasound (HFUS) represent two non-invasive diagnostic tools. While dermoscopy is inexpensive and widely used for the diagnosis of melanoma and non-melanoma skin cancers, HFUS of skin lymphomas represents a novel diagnostic approach that is not yet implemented in the routine dermatologic practice. The aim of our study was to prospectively assess skin lesions of patients with either CTCL patches or plaques with dermoscopy and HFUS and to compare the findings with atopic dermatitis (AD) and psoriasis. Thirteen patients with an established diagnosis of CTCL, psoriasis, or AD were studied: Dermoscopy features including spermatozoa-like structures and the presence of white scales could assist in differentiating between early-stage CTCL and AD. HFUS measurements of the skin thickness indicated increased epidermal-, thickness in CTCL, and psoriasis compared with AD. Our results support the use of dermoscopy as a useful tool to diagnose CTCL. HFUS could augment the dermatologic assessment, but further studies will be needed to define standardized parameters.

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