Mapping port wine stain in vivo by optical coherence tomography angiography and multi-metric characterization.

Port wine stain (PWS) is a congenital cutaneous capillary malformation composed of ecstatic vessels, while the microstructure of these vessels remains largely unknown. Optical coherence tomography angiography (OCTA) serves as a non-invasive, label-free and high-resolution tool to visualize the 3D tissue microvasculature. However, even as the 3D vessel images of PWS become readily accessible, quantitative analysis algorithms for their organization have mainly remained limited to analysis of 2D images. Especially, 3D orientations of vasculature in PWS have not yet been resolved at a voxel-wise basis. In this study, we employed the inverse signal-to-noise ratio (iSNR)-decorrelation (D) OCTA (ID-OCTA) to acquire 3D blood vessel images in vivo from PWS patients, and used the mean-subtraction method for de-shadowing to correct the tail artifacts. We developed algorithms which mapped blood vessels in spatial-angular hyperspace in a 3D context, and obtained orientation-derived metrics including directional variance and waviness for the characterization of vessel alignment and crimping level, respectively. Combining with thickness and local density measures, our method served as a multi-parametric analysis platform which covered a variety of morphological and organizational characteristics at a voxel-wise basis. We found that blood vessels were thicker, denser and less aligned in lesion skin in contrast to normal skin (symmetrical parts of skin lesions on the cheek), and complementary insights from these metrics led to a classification accuracy of ∼90% in identifying PWS. An improvement in sensitivity of 3D analysis was validated over 2D analysis. Our imaging and analysis system provides a clear picture of the microstructure of blood vessels within PWS tissues, which leads to a better understanding of this capillary malformation disease and facilitates improvements in diagnosis and treatment of PWS.

Feasibility of photoacoustic-guided ultrasound treatment for port wine stains.

BACKGROUND AND OBJECTIVES: Port wine birthmark, also known as port wine stain (PWS) is a skin discoloration characterized by red/purple patches caused by vascular malformation. PWS is typically treated by using lasers to destroy abnormal blood vessels. The laser heating facilitates selective photothermolysis of the vessels and attenuates quickly in the tissue due to high optical scattering. Therefore, residual abnormal capillaries deep in the tissue survive and often lead to the resurgence of PWS. Ultrasound (US) has also been proposed to treat PWS, however, it is nonselective with respect to the vasculature but penetrates deeper into the tissue. We aim to study the feasibility of a hybrid PWS treatment modality combining the advantages of both modalities. MATERIALS AND METHODS: In this manuscript, we propose a photoacoustic (PA) guided US focusing methodology for PWS treatment which combines the optical contrast-based selectivity with US penetration to focus the US energy onto the vasculature. The PA signals collected by the transducers, when time-reversed, amplified, and transmitted, converge onto the PWS, thus minimally affecting the neighboring tissue. We performed two- and three-dimensional simulations that mimic realistic transducers and medium properties in this proof of concept study. RESULTS: The time-reversed PA signals when transmitted from the transducers converged onto the vasculature, as expected, thus reducing the heating of the neighboring tissue. We observed that while the US focus is indeed affected due to experimental factors such as limited-view, large detector separation and finite detection bandwidth, and so forth, the US did focus completely or partially onto the vasculature demonstrating the feasibility of the proposed methodology. CONCLUSION: The results demonstrate the potential of the proposed methodology for PWS treatment. This treatment method can destroy the deeper capillaries while minimally heating the neighboring tissue, thus reducing the chances of the resurgence of PWS and as well as cosmetic scarring.

Analysis of port-wine birthmark vascular characteristics by location: Utility of optical coherence tomography mapping.

INTRODUCTION: Port-wine birthmarks (PWBs) are congenital capillary malformations that can be located on any area of the body. Vascular features include vessel size, depth, and density, which can greatly differ between patients, individual lesions, and even sites within the same lesion. Previous studies have determined that the location of PWB lesions has impacted their clinical response to laser treatment. OBJECTIVE: We utilized dynamic optical coherence tomography (D-OCT) to measure in vivo vessel diameter, density, and superficial plexus depth in patients of all ages with PWB on various sites of the body. We hypothesized that these vascular characteristics would differ according to body location. MATERIALS AND METHODS: Patients who had a PWB and presented to clinic at three sites for treatment with the pulsed dye laser (PDL) were enrolled into the study. A D-OCT scanner was utilized for noninvasive, in vivo imaging of PWB lesions. The depth of the top portion of the superficial vascular plexus was estimated as the depth at which the vessel density reaches 50% of the maximum. Vessel diameter and density were calculated by incorporated software algorithm. RESULTS: A total of 108 patients were enrolled into the study. There was a total of 204 measurements of PWB lesions. Of all patients, 56.5% (n = 61) reported having a previous treatment with PDL. Of all D-OCT scans, 62.3% (n = 127) were located on the head, 14.2% (n = 29) the upper extremities, 8.3% (n = 17) the lower extremities, 7.8% (n = 16) the trunk, and 7.8% (n = 15) the neck. All locations were compared for each vascular characteristic. For superficial plexus depth, lesions on the head were significantly shallower than those on the upper extremities (217 vs. 284 µm; p < 0.001) and lower extremities (217 vs. 309 µm; p < 0.001). For vessel diameter, lesions on the head had significantly larger vessels than those on the upper extremities (100 vs. 72 µm; p = 0.001). For vessel density, lesions on the head had significantly denser vessels than those on the trunk (19% vs. 9.6%; p = 0.039) and upper extremities (19% vs. 9.3%; p < 0.001) CONCLUSIONS: PWB lesions have distinct vascular characteristics, which can be associated with their body location. This includes superficial vascular plexus depth as well as vessel diameter and density.

Quantitative assessment of vascular features in port wine stains through optical coherence tomography angiography.

BACKGROUND: Vascular lesions such as port wine stains (PWS) lead to facial and psychological problems, which require careful and precise treatments. The key point of treating PWS is to selectively destroy the abnormal blood vessels. Hence, the in vivo monitoring of targeted vessels is crucial. Optical coherence tomography angiography (OCTA), an emerging label-free imaging tool, facilitates the evaluation of skin structure and vasculature at a high resolution. In this study, we utilised OCTA to capture the structural and vascular morphology in patients with PWS. Moreover, we quantitatively characterised the morphological features of different types of PWS. METHODS: This observational clinical study was conducted on 3 patients with flat PWS and 3 patients with thickened PWS. The age range was 4-27 years, and all of them had not received any treatment before this study. The OCTA images of the PWS lesions and contralateral skin were compared. Vascular morphology was characterized, and ectatic vessel depth was quantified according to the OCTA images. RESULTS: The blood vessels of the PWS lesions tend to had larger diameters and higher densities than those in the contralateral normal skin. The vessel diameters of PWS lesions were 73 ± 14 µm, with high heterogeneity ranging from 10 to >150 µm, however, the vessel diameters of normal skin were 28 ± 2 µm, ranging from 10 µm to 60 µm. In terms of different PWS lesions, the thickened type showed a trend of larger vessel diameter and higher density than those of the purplish red type. The ectatic vessels were located at the depth of 216 ± 13 µm in the PWS skin. CONCLUSIONS: OCTA can facilitate the in vivo three-dimensional visualization of structure and vasculature for PWS lesions. Various quantitative analysis parameters, such as vessel diameter, density, and depth, are typically measured using OCTA. This fact demonstrates the superior capability of OCTA for the precise and comprehensive assessment of PWS lesions.

Imaging and Pathological Characteristics of Port-Wine Stain Patients with Tissue Hypertrophy Before Laser Therapy: Retrospective Data.

Background: Port-wine stain (PWS) patients may simultaneously have accompanied soft tissue hypertrophy. The outcome of laser therapy can be poor. Objective: To study the imaging and histopathological characteristics of PWS patients with facial overgrowth. Materials and methods: We retrospectively assessed the effect of therapy on a subset of PWS patients with facial overgrowth. The degree of hypertrophy and the density of enhanced signals on T1-weighted magnetic resonance imaging (MRI) were independently graded by two radiologists using a quartile scale. Biopsies/resection of tissue deep to the facial muscle was reviewed and compared with flat PWS. Results: Thirty-two PWS patients with facial hypertrophy and 15 patients with flat PWS were included. MRI revealed a statistically significant correlation between the degree of hypertrophy and the density of enhanced signals (3.02 ± 0.92 vs. 2.47 ± 0.69; p < 0.01). Histological features of a subset of patients showed that vascular malformations existed in the dermis and also in the subcutaneous fat and muscle with much larger vessel diameters (fat, 0.048 vs. 0.020; muscle, 0.035 vs. 0.017) and thicker vessel walls (fat, 0.014 vs. 0.006; muscle, 0.010 vs. 0.006) (both p < 0.05). Conclusions: The imaging and pathological findings indicate that capillary malformation in subcutaneous tissue might be a major cause of poor therapeutic effect of laser therapy for PWS. Clinical trial registration no.: ChiCTR1800014278.

A neonate with Klippel-Trénaunay syndrome: a case report.

BACKGROUND: Klippel-Trénaunay syndrome is a rare congenital capillary-lymphatic-venous condition characterized by the clinical triad of capillary malformations (port wine stains), varicose veins with or without venous malformations, and bony and/or soft-tissue hypertrophy. It has a very low incidence of about 1:100,000. CASE PRESENTATION: We report the case of 21-day-old neonate Black African female (born in Uganda) with Klippel-Trénaunay syndrome who presented with macrodactyly and ectrodactyly on the left foot, as well as numerous port wine stains on the left thoracoabdominal region and anteroposterior left lower limb. Color Doppler ultrasound examination of the left lower limb and abdomen revealed varicose veins without signs of arteriovenous fistula. CONCLUSION: The report presents the case of a neonate with a rare congenital vascular disorder type Klippel-Trénaunay syndrome.

Vascular characteristics of port wine birthmarks as measured by dynamic optical coherence tomography.

BACKGROUND: Port wine birthmarks (PWBs) are congenital capillary malformations. Vessel characteristics, such as diameter and depth, may impact presentation and outcomes. They can be imaged using dynamic optical coherence tomography, a high-resolution, noninvasive imaging method. PURPOSE: We conducted a cross-sectional observational study to measure in vivo vascular characteristics as a function of PWB color. METHODS: Patients undergoing treatment for PWB were recruited from 3 sites. PWBs were classified by color. Dynamic optical coherence tomography images with calculations were obtained. RESULTS: One hundred eight patients were enrolled. Mean age correlated with PWB color, with birthmarks being lighter in younger patients and darker in older patients (P < .01). Mean superficial plexus depth was significantly shallower in purple PWBs than in pink PWBs. Color was not associated with significant differences in mean superficial vessel density or diameter. Among pink PWBs, each 10-year increase in age was associated with a 10.6-µm increase in superficial plexus depth. Among purple PWBs, each 10-year increase in age was associated with a 16.2-µm reduction in superficial plexus depth. In lesions without prior treatment, vessel density was 12.7% lower in purple PWBs than in pink PWBs. CONCLUSION: Superficial vessels of purple PWBs were significantly closer to the epidermis than those of pink PWBs, which might impact optimal laser parameters.

Cutaneous Stigmata of the Spine: A Review of Indications for Imaging and Referral.

Cutaneous stigmata of the midline spine are a common question in pediatrics. They are known to be related to a higher likelihood of underlying dysraphic spinal abnormalities. Clear understanding of different types of cutaneous stigmata and correlating dysraphic findings can aid in appropriate imaging workup and timely management of patient pathology. In this article, the authors review midline spinal cutaneous findings in the pediatric population with occult spinal dysraphism.

CM-AVM syndrome - A prospective observational study of unrelated paediatric cases.

OBJECTIVE: The main objective of this study is to describe the clinical spectrum of CM-AVM syndrome as well as radiological and genetic findings. METHODS: This is a single-centre prospective observational study performed at Sydney Children's Hospital. Patients under the age of 18 years that presented to our paediatric dermatology clinic or vascular birthmark clinic between January 2015 and September 2020 with one or more geometric shaped pink/ red/ brown macule with a peripheral pallor characteristic of a high-flow vascular stain were included. Children subsequently diagnosed with other diagnosis or family members with CM-AVM syndrome were excluded. RESULTS: Sixty children were included, with two subsequently excluded. A third of patients (n = 22, 38%) presented with a single characteristic HFVS, whereas the remaining two thirds (n = 36; 62%) had multiple HFVS. In children with multiple HFVS, one notably larger HFVS was detected in the majority of children (n = 32, 88%). In 33 patients, a brain and spine MRI was performed, which detected a spine AVM in one symptomatic patient with sensorimotor deficits. No cerebral AVM or AVF was picked up in the cohort. A RASA 1 result was available for evaluation in 24, of which 16 (67%) were positive. An EPHB4 result was available in eight, two (25%) of which were positive. CONCLUSIONS: One large HFVS often accompanied by multiple small HFVS can be seen in most patients. Despite of the lack of genetic confirmation of diagnosis in single lesions, this phenotype might be of interest and warrants further investigation.

Coexistence of RASA1 and COL4A2 variants caused pial arteriovenous fistula (AVF) in a patient with capillary malformation-arteriovenous malformation.

Pial arteriovenous fistulas (AVFs) are rare vascular lesions; their exact pathophysiology is largely unknown. Pial AVFs have been reported to develop within capillary malformation-arteriovenous malformation (CM-AVM); however, only a few cases have been reported. Variants in the RASA1 gene have been reported as a cause of CM-AVM. We report the case of an adult patient with pial AVF, who carried variants in the RASA1 and COL4A2 genes. The patient in the current report was likely to have been affected by CM-AVM and the RASA1 variant seemed to be the primary factor in the pathogenesis of pial AVF. However, COL4A2 may have also contributed to the development of pial AVF because the COL4A2 and RASA1 variants have a common pathophysiology, wherein the patient develops lesions due to collagen type IV deficiency.

Noninvasive diagnostic techniques of port wine stain.

Port-wine stain (PWS) is a benign capillary malformation that most commonly occurs in the head and neck. It is present at birth and progresses over time. It is formed by progressive dilatation of post-capillary venules and is associated with hypertrophy and nodularity with increasing age, leading to cosmetic disfigurement and psychological aggravation. It is caused by genetic mosaicism in GNAQ and GNA11 genes. Histopathology is the gold standard for assessment of PWS but it is invasive and may cause scarring. Inadequate characterization of the lesions may predispose to inadequate treatment protocols as well as higher treatment dosages. Clinical evaluation of treatment efficacy is subjective and may not be a representative of actual results. Therefore, an objective visualization modality is required. With evolving technology, numerous optical instruments have been developed for objective evaluation and visualization of subsurface structures. These include VISIA-CR™ system, videodermoscopy, high-frequency ultrasound (HFUS), laser speckle contrast imaging (LSCI), reflectance spectrophotometers and tristimulus colorimeter, laser Doppler flowmetry (LDF), cross-polarized diffuse reflectance imaging system (CDR), reflectance confocal microscopy (RCM), optical coherence tomography (OCT), and spatial frequency domain imaging (SFDI). These semi-quantitative modes of diagnosis are complementary to each other. Some can be used in the clinical setting while others, due to high instrument cost, are limited to the research settings. In this review, we bring to you a brief overview of noninvasive diagnostic modalities in PWS.

Capillaroscopy and reflectance confocal microscopy characterization of refractory port-wine stains.

Port-wine stains (PWS) are frequently refractory to laser treatments. Although previous data highlight prognostic factors and biological events related to poor outcomes, no previous publications correlate their capillaroscopic and architectural features. The aim of the present study is to describe refractory port-wine stains performing capillaroscopy and reflectance confocal microscopy (RCM) to describe their morphological and microscopic aspects. This is a prospective cohort study. All the consecutive patients with PWS poor responsive to previous treatment were included. Clinical assessment, capillaroscopy, and reflectance confocal microscopy were performed. A total of 65 patients were included, 12 with a capillaroscopic Type II pattern patients and 53 with Type III. At RCM examination, PWS with a capillaroscopic Type III pattern showed deeper-located blood vessels (p < 0.001) with a higher diameter (p < 0.042) compared with Type II. At the dynamic evaluation, 3 RCM patterns can be distinguished: Subset A, characterized by linear vessels with reduced diameter; Subset B, formed by enlarged vessels; and Subset C, characterized by deep and large aneurysmatic dilatation connected to small vessels. We defined 3 RCM patterns of refractory PWS.

Photodynamic Therapy Using HMME for Port-Wine Stains: Clinical Effectiveness and Sonographic Appearance.

This study aims at exploring the clinical efficacy and sonographic changes of photodynamic therapy (PDT) using Hematoporphyrin Monomethyl Ether (HMME) for the treatment of port-wine stains (PWS). Forty-five patients with PWS were recruited between March 2017 and June 2018 from the Department of Dermatology of The Third Affiliated Hospital of Soochow University. Five cases were of the pink type, thirty-nine cases were of the purple-red type, and one case was of the thickened type. All patients received three treatment sessions of PDT. After covering normal skin outside the treated area, patients received an intravenous injection of 5 mg/kg HMME within 20 minutes. The affected areas were exposed to a 532 nm LED light and were kept vertically at a distance of 10 cm. The irradiation energy density was set between 80 and 110 J/cm2 in 15-minute sessions. Intermittent power density adjustment was performed at a rate of 5 mW/cm2, and the treatment was withheld when the endpoint reaction appeared. Three follow-ups were performed before and after treatment, respectively, and the efficacy, thickness, and density of skin before and after treatment were evaluated with high-frequency ultrasound. The overall efficacy rate was 97.78% in forty-five cases after treatment for three sessions. Efficacy was related to age (P = 0.029) and lesion severity (P < 0.001). There were significant differences in the efficacy between the groups of <18 years old, 18-29 years old, and >29 years old (P = 0.029). A marked decrease in the numbers of distorted enlarged blood vessels per unit of the lesion was observed under high-frequency ultrasound. There were significant differences in skin thickness and skin density before and after treatment (F = 14.528, 5.428, P < 0.001). The swelling was reported to varying degrees in the treated areas in 23 patients with cheek lesion and in 6 frontal lesions. Hyperpigmentation after inflammation was observed in four patients that faded spontaneously after two months. In conclusion, photodynamic therapy for the treatment of PWS using HMME is effective and safe with few adverse reactions. Moreover, monitoring the changes in skin thickness and density of lesion tissue using high-frequency ultrasound can objectively evaluate the clinical efficacy of HMME photodynamic therapy and provide the basis for the formulation of individualized photodynamic therapy.

[Clinical and Neuroimaging Analysis of 24 Cases of Sturge-Weber Syndrome].

OBJECTIVE: To analyze the clinical manifestations and neuroimaging characteristics of Sturge-Weber syndrome (SWS), to describe the manifestations of facial port-wine stains (PWS) of SWS, and to explore the screening opinions for SWS. METHODS: A retrospective analysis was performed on the general condition, clinical manifestations, and neuroimaging results of 24 SWS patients from the dermatology department of West China Hospital of Sichuan University between 2017 and 2019. Three different facial PWS distribution methods (traditional anatomical distribution, facial trigeminal nerve distribution, and facial embryological vasculature distribution) in SWS patients were Analysed. RESULTS: Among the 24 patients, 50% were male and 50% were female, with an average age of (18.9±14.0) years (range 1 to 54 years old). 12 cases were SWS type Ⅰ, and the other 12 cases were type Ⅱ. All patients had facial PWS at birth, and the facial PWS of 13 cases (54.2%) were thickened. According to the anatomical division, all the PWS involved the upper and middle face (above the oral commissure); according to the trigeminal nerve distribution, 100% (24/24) patients involve the V2 area; according to the distribution of facial embryological vasculature, 95.8% (23/24) of the patients involved frontal region. 22 patients had ophthalmic abnormalities, the most common was glaucoma (70.8%), and 4 patients had a history of epilepsy. The typical neuroimaging presentations of SWS include leptomeningeal enhancement, cortical calcification, enlarged choroid plexus, focal cerebral atrophy, abnormal intracranial vessels, and local thickening of the skull. CONCLUSION: Early intervention is recommended for facial PWS in patients with SWS , and ophthalmological screening should be performed on children with PWS found in any part of the upper and middle face after birth. Moreover, neuroimaging examination (MRI) for patients with high suspicion of SWS should be performed after 1 year old, and regular ophthalmological examination and intraocular pressure measurement is necessary.