Applications of Laser Speckle Contrast Imaging Technology in Dermatology

Abstract

Laser speckle contrast imaging, or laser speckle imaging (LSI), is a noninvasive imaging technology that can detect areas of dynamic perfusion or vascular flow. Thus, LSI has demonstrated increasing diagnostic utility in various pathologies and has been employed for intraoperative, postoperative, and long-term monitoring in many medical specialties. Recently, LSI has gained traction in clinical dermatology, as it can be effective in the assessment of pathologies that are associated with increased perfusion and hypervascularity as compared to normal tissue. To date, LSI has been found to be highly accurate in monitoring skin graft reperfusion, determining severity of burns, evaluating neurosurgical revascularization, assessing persistent perfusion in capillary malformations post-laser therapy, and differentiating malignant and benign skin lesions. LSI affords the advantage of non-invasively assessing lesions prior to more invasive methods of diagnosis, such as tissue biopsy, while remaining inexpensive and exhibiting no adverse events to date. However, potential obstacles to its clinical use include tissue movement artifact, primarily qualitative data, and unclear impact on clinical practice given lack of superiority data compared to current standard of care (SOC) diagnostic methods. In this review, we discuss the clinical applications of LSI in dermatology for use in the diagnosis and monitoring of vascular, neoplastic, and inflammatory skin conditions. Laser speckle contrast imaging, or laser speckle imaging (LSI), is a noninvasive imaging technology that can detect areas of dynamic perfusion or vascular flow. Thus, LSI has demonstrated increasing diagnostic utility in various pathologies and has been employed for intraoperative, postoperative, and long-term monitoring in many medical specialties. Recently, LSI has gained traction in clinical dermatology, as it can be effective in the assessment of pathologies that are associated with increased perfusion and hypervascularity as compared to normal tissue. To date, LSI has been found to be highly accurate in monitoring skin graft reperfusion, determining severity of burns, evaluating neurosurgical revascularization, assessing persistent perfusion in capillary malformations post-laser therapy, and differentiating malignant and benign skin lesions. LSI affords the advantage of non-invasively assessing lesions prior to more invasive methods of diagnosis, such as tissue biopsy, while remaining inexpensive and exhibiting no adverse events to date. However, potential obstacles to its clinical use include tissue movement artifact, primarily qualitative data, and unclear impact on clinical practice given lack of superiority data compared to current standard of care (SOC) diagnostic methods. In this review, we discuss the clinical applications of LSI in dermatology for use in the diagnosis and monitoring of vascular, neoplastic, and inflammatory skin conditions. Laser speckle imaging (LSI), first introduced in 1981, is recognized as a convenient method for visualizing blood flow within vessels. LSI often utilizes a low-intensity near-infrared laser, a low-power and long-wavelength light source, to illuminate the skin. Light is reflected towards the device’s sensor to provide information about blood flow over time, which is then captured by a camera. The image’s resulting pixel pattern, known as speckles, is subsequently analyzed by computer software to quantify movement of these pixels. Laser speckles occur when a coherent light illuminates a surface, producing random interference effects. Such light is often from a laser beam of a particular wavelength. In the LSI skin imaging, the light source is often a continuous wave laser running at near-infrared region (e.g., 785 nm), the so-called therapeutic window, where light can penetrate better and dispose less energy to tissue compared with visible or infrared light. The resulting laser speckle interference effect is displayed visually as a granular pattern consisting of dark and bright spots. When the speckle pattern is illuminated on a moving object, such as in-transit intravascular fluid, the flow disturbs the speckle pattern causing blurriness of laser speckles, causing partial or complete disappearance of speckles in the image of the flow related region. LSI captures this speckle displacement, creating a quasi-real time blood flow imaging system [Figure 1] (Aminfar et al., 2019Aminfar A. Davoodzadeh N. Aguilar G. Princevac M. Application of optical flow algorithms to laser speckle imaging.Microvasc Res. 2019; 122: 52-59Crossref PubMed Scopus (11) Google Scholar). LSI images can be analyzed using spatial and temporal analysis, both of which are demonstated in Figures 2 and 3. Spatial analysis, or laser speckle contrast analysis (LASCA), requires only one image and measures contrast in that image over pixels. Temporal analysis requies a series of multiple images and measures contrast in one pixel over the sequential images. The temporal method affords better spatial resolution, as it uses single-pixel intensity over a period of time.(Draijer et al., 2009Draijer M. Hondebrink E. van Leeuwen T. Steenbergen W. Review of laser speckle contrast techniques for visualizing tissue perfusion.Lasers Med Sci. 2009; 24: 639-651Crossref PubMed Scopus (261) Google Scholar). LSI has been effectively translated into medicine for the purpose of monitoring revascularization, particularly in the fields of neurosurgery and ophthalmology (Boas and Dunn, 2010Boas D.A. Dunn A.K. Laser speckle contrast imaging in biomedical optics.J Biomed Opt. 2010; 15011109Crossref Scopus (784) Google Scholar). In a recent review of all clinical applications of the technology, no adverse events were reported, most likely due to LSI’s low photon energy and illumination power (Heeman et al., 2019Heeman W. Steenbergen W. van Dam G. Boerma E.C. Clinical applications of laser speckle contrast imaging: a review.J Biomed Opt. 2019; 24: 1-11Crossref PubMed Scopus (113) Google Scholar).Figure 2Laser speckle images in “normal” versus lesional skin in a patient with biopsy-proven melanoma. The x- and y-axes represent pixel positions, and the color maps indicate the value of K, the local spatial variance or speckle contrast. Areas with higher blood flow have a lower contrast, or K. All images were captured with a laser wavelength of 785 nanometers and a circular aperature 2 centimeters in diameter. Spatial correlation was captured over 7 x 7 pixels, and temporal correlation was analyzed over 49 images. (a) Left panel: Laser speckle images captured over “normal” skin in a patient seen in a dermatology clinic at the Medical University of South Carolina. Imaging of normal skin resulted in homogenous laser speckle pattern. (b) Right panel: Laser speckle images captured in the same patient over a lesion concerning for cancer, confirmed with biopsy to be malignant melanoma. Imaging of melanoma demonstrates higher blood flow around the lesion periphery compared to the center of the lesion in temporal correlation, as well as compared to the control skin in (a). Spatial and temporal images are similar with improved spatial resolution reflected in the temporal correlation.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3Laser speckle images in “normal” versus lesional skin in a patient with a cherry angioma. As in Figure 2, the x- and y-axes represent pixel positions, and the color maps indicate the value of K, the local spatial variance or speckle contrast. Areas with higher blood flow have a lower contrast, or K. All images were captured with a laser wavelength of 785 nanometers and a circular aperature 2 centimeters in diameter. Spatial correlation was captured over 7 x 7 pixels, and temporal correlation was analyzed over 49 images. (a) Left panel: Laser speckle images captured over “normal” skin. Again, imaging of normal skin resulted in homogenous laser speckle pattern. (b) Right panel: Laser speckle images captured in the same patient over a stable cherry angioma. Imaging of cherry angioma demonstrates overall higher blood flow compared to control skin, with pinpoint areas of highest blood flow within clumped lesional blood vessels, best appreciated in spatial correlation. Temporal correlation depicts less change in speckle contrast over time compared to the contrast over one image using spatial correlation.View Large Image Figure ViewerDownload Hi-res image Download (PPT) LSI is a technology with both clinical and surgical dermatologic utility. LSI is effective for evaluating vascular anomalies, cutaneous neoplasms, inflammatory dermatoses, autoimmune conditions, and dermal and subcutaneous growths through detection of perfusion differences in lesional versus perilesional skin. This imaging method has also proven to be an effective surgical tool for the planning of skin graft dissections, as well as the assessment of revascularization of skin grafts and flaps after surgery (Berggren et al., 2021Berggren J. Castelo N. Tenland K. Dahlstrand U. Engelsberg K. Lindstedt S. et al.Reperfusion of Free Full-Thickness Skin Grafts in Periocular Reconstructive Surgery Monitored Using Laser Speckle Contrast Imaging.Ophthalmic Plast Reconstr Surg. 2021; 37: 324-328PubMed Google Scholar, Brinca et al., 2020Brinca A. Pinho A. Vieira R. Laser speckle contrast imaging for assessment of human skin graft microcirculation.J Eur Acad Dermatol Venereol. 2020; 34: e491-e493Crossref PubMed Scopus (2) Google Scholar, Carvalho Brinca et al., 2021Carvalho Brinca A.M. de Castro Pinho A. Costa Vieira R.J.D. Blood Perfusion of Random Skin Flaps in Humans-In Vivo Assessment by Laser Speckle Contrast Imaging.Dermatol Surg. 2021; 47: 1421-1426Crossref PubMed Scopus (3) Google Scholar). Dermatologic advantages of LSI include its noninvasive nature, low cost, rapid results, and ability to produce accurate data when used simultaneously with dermoscopy (Tkaczyk, 2017Tkaczyk E. Innovations and Developments in Dermatologic Non-invasive Optical Imaging and Potential Clinical Applications.Acta Derm Venereol. 2017; Suppl 218: 5-13PubMed Google Scholar, White et al., 2018White S.M. Valdebran M. Kelly K.M. Choi B. Simultaneous Blood Flow Measurement and Dermoscopy of Skin Lesions Using Dual-Mode Dermascope.Sci Rep. 2018; 816941Crossref Scopus (4) Google Scholar). The purpose of this review is to highlight applications of LSI in clinical dermatology. Selected studies involve investigation of the utility and efficacy of LSI for diagnostic or management purposes of three major categories of dermatologic lesions: vascular, neoplastic, and inflammatory. A capillary malformation, known as a nevus flammeus or port wine stain (PWS), appears clinically as a red-purple patch present from birth. Port wine stains are often benign birthmarks but have recently been found to be associated with high-morbidity genetic syndromes such as Sturge-Weber and Klippel-Trénaunay-Weber when present with more widespread vascular malformations (Fitzpatrick, 2018, Gangopadhyay and Tiwari, 2021Gangopadhyay AN, Tiwari P. Capillary Malformation. In: Khanna AK, Tiwary SK, editors. Vascular Malformations. Singapore: Springer Singapore; 2021. p. 73-82.Google Scholar). Treatment with pulsed dye laser (PDL) is the SOC approach to these congenital lesions; however, complete resolution with PDL is not commonly achieved. Huang, et al. were the first to describe the use of LSI as a tool for assessment of perfusion changes during and after treatment of port wine stains with PDL. Though the study showed an overall decrease in perfusion of lesions after treatment, and many speckle maps indicated areas within lesions that maintained some degree of persistent perfusion. The authors hypothesized that this persistent, undesired blood flow represented regions that received incomplete PDL therapy and suggested that increased use of real-time LSI during laser treatments could result in more thorough treatment and improved removal of PWS lesions in the future (Huang et al., 2009Huang Y.C. Tran N. Shumaker P.R. Kelly K. Ross E.V. Nelson J.S. et al.Blood flow dynamics after laser therapy of port wine stain birthmarks.Lasers Surg Med. 2009; 41: 563-571Crossref PubMed Scopus (44) Google Scholar). Additional studies have since drawn similar conclusions and shown the efficacy of LSI as a noninvasive method of post-treatment monitoring of PWS birthmarks. Qiu, et al., noted that the superior ability of LSI to detect microvascular blood flow changes over both space and time is a feature not afforded with lesional biopsies (Qiu et al., 2012Qiu H. Zhou Y. Gu Y. Ang Q. Zhao S. Wang Y. et al.Monitoring microcirculation changes in port wine stains during vascular targeted photodynamic therapy by laser speckle imaging.Photochem Photobiol. 2012; 88: 978-984Crossref PubMed Scopus (31) Google Scholar). In a report of a 7-month-old infant with a magnetic resonance imaging (MRI)-confirmed arteriovenous malformation (AVM), LSI technology was used to further characterize the lesion. The authors found that LSI accurately highlighted the lesion in a similar pattern as MRI. They suggest that LSI could be preferable for initial AVM assessment in patients with contraindications to MRI or in pediatric patients due to the lack of anesthesia required to obtain imaging (Humeau-Heurtier et al., 2017Humeau-Heurtier A. Martin L. Bazeries P. Abraham P. Henni S. Laser Speckle Contrast Imaging of Skin Changes in Arteriovenous Malformation.Circ Cardiovasc Imaging. 2017; 10Crossref PubMed Scopus (1) Google Scholar). Literature detailing use of LSI for assessment of other vascular anomalies, such as venous or lymphatic malformations, is scarce, and thus further studies are required to assess efficacy of LSI as a diagnostic and post-treatment monitoring tool of vascular malformations as compared with current SOC imaging modalities. Tissue biopsy is the gold standard of diagnosis for skin malignancies, but this can occasionally result in unnecessary, invasive diagnostic measures in patients who are ultimately proven to have a benign skin condition (Agnew et al., 2005Agnew KL, Gilchrest BA, Bunker CB. Fast Facts : Skin Cancer. Abingdon, UNITED KINGDOM: Health Press Limited; 2005.Google Scholar). Biopsy procedures have inherent risks of bleeding, infection, scarring, and disfiguration, thus assessment of suspicious skin lesions with a noninvasive modality prior to skin biopsy might decrease the rate of unnecessary procedures, as well as procedure-related complications. LSI has been shown to be an accurate tool in differentiating benign and malignant skin lesions. Tchvialeva, et al., utilized LSI to assess five different types of benign and malignant skin lesions in vivo: basal cell carcinoma (BCC), squamous cell carcinoma (SCC), malignant melanoma (MM), seborrheic keratosis (SK), and melanocytic nevus (Tchvialeva et al., 2013Tchvialeva L. Dhadwal G. Lui H. Kalia S. Zeng H. McLean D.I. et al.Polarization speckle imaging as a potential technique for in vivo skin cancer detection.J Biomed Opt. 2013; PubMed Scopus Google Scholar). were confirmed with tissue A of skin lesions were analyzed using different laser nm), which from and and laser nm), which the speckle pattern of from SK, and was using analysis compared to other diagnostic imaging, and LSI was shown to have similar as and and higher as compared to and When on a of the the for and were and (Tchvialeva et al., 2013Tchvialeva L. Dhadwal G. Lui H. Kalia S. Zeng H. McLean D.I. et al.Polarization speckle imaging as a potential technique for in vivo skin cancer detection.J Biomed Opt. 2013; PubMed Scopus Google Scholar). This study that LSI is a for assessing skin lesions suspicious for prior to invasive tissue study was by et al., in which patients with were with LSI to microvascular blood from that of the perilesional skin. Speckle were by speckle speckle contrast, and showed that using region of and speckle demonstrated differences in lesional blood flow as compared to perilesional skin for speckle contrast nm), for speckle nm), for no for data at This study demonstrated that LSI is a method for assessing of compared to normal skin in a The authors suggest that also be using LSI technology et al., M. M. Springer S. R. A. M. et laser speckle imaging for skin 2021; PubMed Scopus (2) Google which could be utilized during future surgical the Medical University of South a LSI has been and used for lesions concerning skin cancer prior to tissue The initial demonstrated increased perfusion in lesional skin of as well as vascular lesions 2 and the of LSI’s efficacy in the diagnosis of skin malignancies, further studies are to LSI for this Blood flow imaging by LSI can be used to and by the and in of the skin (Tkaczyk, 2017Tkaczyk E. Innovations and Developments in Dermatologic Non-invasive Optical Imaging and Potential Clinical Applications.Acta Derm Venereol. 2017; Suppl 218: 5-13PubMed Google Scholar). LSI is of skin vascular et al., A. Y. A. laser speckle imaging and for monitoring vascular Biomed Opt. 2019; 24: PubMed Scopus Google by This be translated to characterize inflammatory dermatologic associated with increased blood flow or et al., S. E. K. J. M. M. et but 2020; PubMed Scopus (1) Google or to assess the of treatment that have on blood such as and et al., L. L. de J. Laser speckle contrast imaging, the future imaging technique for Res. 2020; PubMed Scopus (3) Google Scholar, et al., J. A.M. N. M. Nelson et cell vascular changes associated with an to in 2013; Scopus Google Scholar). these studies suggested LSI potential to assess of and on the skin surface, such as in and other inflammatory Skin changes are in the of and with increased lesion perfusion. In a et al. utilized the Perfusion a by to microvascular skin perfusion in patients with as by recent of In a of the LSI was employed to perilesional perfusion and perfusion as a of lesion et al., A. T. van de E. et by laser speckle contrast imaging as a for of PubMed Scopus (1) Google Scholar). of a demonstrated increased perilesional perfusion was of after as compared to lesion and lesion Perfusion was a but of lesion at as compared to these it was that LSI has potential applications in assessing or in patients with However, further studies are required to uses in clinical practice et al., A. T. van de E. et by laser speckle contrast imaging as a for of PubMed Scopus (1) Google Scholar). LSI are found to be in using both and et al., A. T. Steenbergen W. versus laser speckle contrast perfusion imaging demonstrated in Rep. 2021; Scopus (3) Google Scholar). with are known to have in both and a study skin microvascular in patients with using The found that patients with microvascular during as compared with in the of or et al., N. E. A. A. P. P. et microvascular in patients with and 2021; PubMed Scopus Google Scholar). suggest skin microvascular is present in of et al., N. E. A. A. P. P. et microvascular in patients with and 2021; PubMed Scopus Google Scholar). In the LSI be used as an noninvasive method of evaluating of vascular in cutaneous lesions. in skin have been shown to with cutaneous et al., M. and analysis of of the of benign and malignant lesions of the skin by Med PubMed Scopus Google Scholar). In to the dermatologic uses afforded by of increased perfusion as LSI has also been shown to differences in skin it a potential tool in the assessment of skin In a study with skin of normal skin was with LSI and the which a and image of the skin The study demonstrated that LSI was to detect a in skin not to the degree of the The authors that the ability of LSI to skin have clinical such as skin which are often associated with increased skin et al., M. M. Springer S. R. A. M. et laser speckle imaging for skin 2021; PubMed Scopus (2) Google Scholar). has been suggested that LSI is of producing of in patch (Tkaczyk, 2017Tkaczyk E. Innovations and Developments in Dermatologic Non-invasive Optical Imaging and Potential Clinical Applications.Acta Derm Venereol. 2017; Suppl 218: 5-13PubMed Google Scholar). In the LSI be used for the assessment of cutaneous LSI has also been shown to detect perfusion in of patients et al., E. G. S. et a study of cutaneous and 2020; PubMed Scopus (1) Google and increased in lesions of et al., et al. in the microvascular and dermal in A Suppl et al., H. A. S. M. E. et with 2021; Scopus Google Scholar, et al., T. R. measures in in and Clinical 2018; PubMed Scopus (3) Google and et al., M. N. W. Wang Y. et of by Laser Speckle Contrast A in Surgery and 2021; PubMed Scopus Google Scholar, et al., S. M. Wang perfusion and noninvasive method for evaluating the severity of Surg Med. Scopus Google Scholar, et al., Q. Wang Y. N. Wang Y. et blood flow in and skin by laser speckle contrast Surg Med. PubMed Scopus Google Scholar, et al., Y. L. R. Y. H. et al.Blood perfusion in and by laser speckle contrast 2021; PubMed Scopus Google Scholar). Additional is to these represent areas of future clinical utility for LSI an tool for the assessment of skin lesions with increased to its clinical use The technology can have movement artifact, particularly when used which et al., A. T. Steenbergen W. versus laser speckle contrast perfusion imaging demonstrated in Rep. 2021; Scopus (3) Google Scholar, et al., 2019Heeman W. Steenbergen W. van Dam G. Boerma E.C. Clinical applications of laser speckle contrast imaging: a review.J Biomed Opt. 2019; 24: 1-11Crossref PubMed Scopus (113) Google This could use of the imaging in or other that have remaining during is also of multiple of speckles with which et al., E. S. M. Steenbergen W. et speckle contrast imaging: and of 2013; PubMed Scopus Google the speckle pattern data is qualitative (Heeman et al., 2019Heeman W. Steenbergen W. van Dam G. Boerma E.C. Clinical applications of laser speckle contrast imaging: a review.J Biomed Opt. 2019; 24: 1-11Crossref PubMed Scopus (113) Google and have used different algorithms or to assess speckle pattern changes within the A on the most accurate method of image differences be given that many of the dermatologic are clinically or with SOC diagnostic it is unclear LSI change the of clinical practice for the management of these conditions, particularly diagnostic superiority data compared to current is the that LSI’s utility in a of monitoring lesions during or after treatment is a of the LSI has shown as a accurate method of and monitoring multiple dermatologic vascular, neoplastic, and inflammatory skin Additional of the imaging modality include low and lack of adverse effects. However, some of the technology and most clinical studies of LSI in dermatology are to lesion types with patient studies with are to further assess the clinical utility of this of potential clinical uses of laser speckle imaging in uses of wine of treatment in lesions after pulsed dye laser (PDL) assessment of lesions during PDL imaging for anesthesia in and lymphatic for initial imaging for anesthesia in further studies imaging assessment of lesions concerning for prior to invasive tissue biopsy, differentiating malignant melanoma from other benign or skin assessment during surgical of or of of microvascular in a

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