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Article ; Online: Automated Segmentation of Skin Strata in Reflectance Confocal Microscopy Depth Stacks.

Samuel C Hames / Marco Ardigò / H Peter Soyer / Andrew P Bradley / Tarl W Prow

PLoS ONE, Vol 11, Iss 4, p e

2016 Volume 0153208

Abstract: Reflectance confocal microscopy (RCM) is a powerful tool for in-vivo examination of a variety of skin diseases. However, current use of RCM depends on qualitative examination by a human expert to look for specific features in the different strata of the ... ...

Abstract	Reflectance confocal microscopy (RCM) is a powerful tool for in-vivo examination of a variety of skin diseases. However, current use of RCM depends on qualitative examination by a human expert to look for specific features in the different strata of the skin. Developing approaches to quantify features in RCM imagery requires an automated understanding of what anatomical strata is present in a given en-face section. This work presents an automated approach using a bag of features approach to represent en-face sections and a logistic regression classifier to classify sections into one of four classes (stratum corneum, viable epidermis, dermal-epidermal junction and papillary dermis). This approach was developed and tested using a dataset of 308 depth stacks from 54 volunteers in two age groups (20-30 and 50-70 years of age). The classification accuracy on the test set was 85.6%. The mean absolute error in determining the interface depth for each of the stratum corneum/viable epidermis, viable epidermis/dermal-epidermal junction and dermal-epidermal junction/papillary dermis interfaces were 3.1 μm, 6.0 μm and 5.5 μm respectively. The probabilities predicted by the classifier in the test set showed that the classifier learned an effective model of the anatomy of human skin.
Keywords	Medicine ; R ; Science ; Q
Subject code	571
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A first-in-human study of BLZ-100 (tozuleristide) demonstrates tolerability and safety in skin cancer patients

Miko Yamada / Dennis M. Miller / Melinda Lowe / Casey Rowe / Dominic Wood / H. Peter Soyer / Kelly Byrnes-Blake / Julia Parrish-Novak / Laura Ishak / James M. Olson / Gordon Brandt / Paul Griffin / Lynda Spelman / Tarl W. Prow

Contemporary Clinical Trials Communications, Vol 23, Iss , Pp 100830- (2021)

2021

Abstract: BLZ-100 (tozuleristide) is an intraoperative fluorescent imaging agent that selectively detects malignant tissue and can be used in real time to guide tumor resection. The purpose of this study was to assess the safety, tolerability, and pharmacokinetics ...

Abstract	BLZ-100 (tozuleristide) is an intraoperative fluorescent imaging agent that selectively detects malignant tissue and can be used in real time to guide tumor resection. The purpose of this study was to assess the safety, tolerability, and pharmacokinetics of BLZ-100 and to explore the pharmacodynamics of fluorescence imaging of skin tumors. In this first-in-human study, BLZ-100 was administered intravenously to 21 adult patients 2 days before excising known or suspected skin cancers. Doses were 1, 3, 6, 12, and 18 mg, with 3–6 patients/cohort. Fluorescence imaging was conducted before and up to 48 h after dosing. BLZ-100 was well tolerated. There were no serious adverse events, deaths, or discontinuations due to adverse events, and no maximum tolerated dose (MTD) was identified. Headache (n = 2) and nausea (n = 2) were the only BLZ-100 treatment-related adverse events reported for >1 patient. Median time to maximal serum concentration was <0.5 h. Exposure based on maximal serum concentrations increased in a greater than dose-proportional manner. For intermediate dose-levels (3–12 mg), 4 of 5 basal cell carcinomas and 4 of 4 melanomas were considered positive for BLZ-100 fluorescence. BLZ-100 was well tolerated at all dose levels tested and these results support further clinical testing of this imaging agent in surgical oncology settings. Clinicaltrials.gov: NCT02097875.
Keywords	Skin neoplasms ; Fluorescent dyes ; Cystine-knot miniproteins ; Medicine (General) ; R5-920
Subject code	616 ; 610
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Non-Invasive Nanoparticle Imaging Technologies for Cosmetic and Skin Care Products

Lynlee L. Lin / Kaitlin L. Nufer / Shoko Tomihara / Tarl W. Prow

Cosmetics, Vol 2, Iss 3, Pp 196-

2015 Volume 210

Abstract: The nanotechnology field is growing at an unprecedented rate. This is resulting in significant benefits in skin care products and formulations. Likewise, imaging technology is also advancing. The convergence of these fields offers a unique opportunity to ...

Abstract	The nanotechnology field is growing at an unprecedented rate. This is resulting in significant benefits in skin care products and formulations. Likewise, imaging technology is also advancing. The convergence of these fields offers a unique opportunity to observe and quantify the interactions of nanoparticles within cosmetic and skin care formulations. More importantly, imaging technology holds tremendous promise for understanding how formulated nanoparticles interact with our skin. Imaging technologies can be broken into two major groups that include those that require invasive sample collection and processing (e.g., electron microscopy, mass spectrometry, and super-resolution structured illumination microscopy) and those that can be used in non-invasive data collection settings. Fluorescence microscopy, confocal microscopy, coherent anti-Stokes Raman scattering spectroscopy and optical coherence tomography fall into the latter category and are the focus of this review in the context of skin care product and cosmetics testing. Cosmetic and skin care product testing is most informative when carried out in volunteers. This makes invasive or disruptive analysis techniques unfeasible and supports the use of non-invasive imaging technologies. The combination of non-invasive imaging and minimally invasive microbiopsy sampling for combined imaging and molecular data is the future of skin care product testing.
Keywords	non-invasive ; imaging ; nanoparticles ; in vivo ; human volunteers ; cosmetic testing ; Chemistry ; QD1-999
Subject code	571
Language	English
Publishing date	2015-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Automated detection of actinic keratoses in clinical photographs.

Samuel C Hames / Sudipta Sinnya / Jean-Marie Tan / Conrad Morze / Azadeh Sahebian / H Peter Soyer / Tarl W Prow

PLoS ONE, Vol 10, Iss 1, p e

2015 Volume 0112447

Abstract: BACKGROUND:Clinical diagnosis of actinic keratosis is known to have intra- and inter-observer variability, and there is currently no non-invasive and objective measure to diagnose these lesions. OBJECTIVE:The aim of this pilot study was to determine if ... ...

Abstract	BACKGROUND:Clinical diagnosis of actinic keratosis is known to have intra- and inter-observer variability, and there is currently no non-invasive and objective measure to diagnose these lesions. OBJECTIVE:The aim of this pilot study was to determine if automatically detecting and circumscribing actinic keratoses in clinical photographs is feasible. METHODS:Photographs of the face and dorsal forearms were acquired in 20 volunteers from two groups: the first with at least on actinic keratosis present on the face and each arm, the second with no actinic keratoses. The photographs were automatically analysed using colour space transforms and morphological features to detect erythema. The automated output was compared with a senior consultant dermatologist's assessment of the photographs, including the intra-observer variability. Performance was assessed by the correlation between total lesions detected by automated method and dermatologist, and whether the individual lesions detected were in the same location as the dermatologist identified lesions. Additionally, the ability to limit false positives was assessed by automatic assessment of the photographs from the no actinic keratosis group in comparison to the high actinic keratosis group. RESULTS:The correlation between the automatic and dermatologist counts was 0.62 on the face and 0.51 on the arms, compared to the dermatologist's intra-observer variation of 0.83 and 0.93 for the same. Sensitivity of automatic detection was 39.5% on the face, 53.1% on the arms. Positive predictive values were 13.9% on the face and 39.8% on the arms. Significantly more lesions (p<0.0001) were detected in the high actinic keratosis group compared to the no actinic keratosis group. CONCLUSIONS:The proposed method was inferior to assessment by the dermatologist in terms of sensitivity and positive predictive value. However, this pilot study used only a single simple feature and was still able to achieve sensitivity of detection of 53.1% on the arms.This suggests that image analysis ...
Keywords	Medicine ; R ; Science ; Q
Subject code	630
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Minimally invasive microbiopsies: a novel sampling method for identifying asymptomatic, potentially infectious carriers of Leishmania donovani

Kirstein, Oscar David / Alon Warburg / Asrat Hailu / Ben Zion Horwitz / Charles Jaffe / Ibrahim Abbasi / Laura Skrip / Lynlee L. Li / Tarl W. Prow

International journal for parasitology. 2017 Sept., v. 47, no. 10-11

2017

Abstract: Visceral leishmaniasis (VL) is a potentially lethal, sand fly-borne disease caused by protozoan parasites belonging to the Leishmania donovani species complex. There are several adequate methods for diagnosing VL, but the majority of infected individuals ...

Abstract	Visceral leishmaniasis (VL) is a potentially lethal, sand fly-borne disease caused by protozoan parasites belonging to the Leishmania donovani species complex. There are several adequate methods for diagnosing VL, but the majority of infected individuals remain asymptomatic, comprising potential parasite reservoirs for transmission of the disease. The gold standard for assessing host infectiousness to biting vector insects is xenodiagnosis (i.e. scoring infection rates among insectary-reared insects that had fed on humans suspected of being infected). However, when it comes to sand flies and leishmaniasis, xenodiagnosis is an intricate operation burdened by logistical hurdles and ethical concerns that prevent its effective application for mass screening of widely dispersed communities, particularly in rural regions of underdeveloped countries. Minimally invasive microbiopsy (MB) devices were designed to penetrate the skin to a depth of ∼200μm and absorb blood as well as skin cell lysates, mimicking the mode by which phlebotomine sand flies acquire blood meals, as well as their composition. MBs taken from 137 of 262 volunteers, living in endemic VL foci in Ethiopia, detected Leishmania parasites that could potentially be imbibed by feeding sand flies. Although the volume of MBs was 10-fold smaller than finger-prick blood samples, Leishmania DNA detection rates from MBs were significantly higher, implying that skin, more often than blood, was the source of parasites. Volunteers with histories of VL were almost as likely as healthy volunteers to test positive by MBs (southern Ethiopian focus: 95% CI: 0.35–2.59, P=1.0. northern Ethiopian focus 0.87: 95% CI: 0.22–3.76, P=1), suggesting the importance of asymptomatic patients as reservoirs of L. donovani. Minimally invasive, painless MBs should be considered for reliably and efficiently evaluating both L. donovani infection rates among large numbers of asymptomatic carriers and their infectiousness to blood-feeding sand flies.
Keywords	blood ; blood meal ; blood sampling ; carrier state ; developing countries ; DNA ; ethics ; humans ; insects ; Leishmania donovani ; parasites ; patients ; Phlebotominae ; rural areas ; screening ; visceral leishmaniasis ; xenodiagnosis ; Ethiopia
Language	English
Dates of publication	2017-09
Size	p. 609-616.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	120518-3
ISSN	1879-0135 ; 0020-7519
ISSN (online)	1879-0135
ISSN	0020-7519
DOI	10.1016/j.ijpara.2017.02.005
Database	NAL-Catalogue (AGRICOLA)

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Zs.A 789: Show issues

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Article ; Online: Concurrent Reflectance Confocal Microscopy and Laser Doppler Flowmetry to Improve Skin Cancer Imaging

Alireza Mowla / Thomas Taimre / Yah Leng Lim / Karl Bertling / Stephen J. Wilson / Tarl W. Prow / H. Peter Soyer / Aleksandar D. Rakić

Sensors, Vol 16, Iss 9, p

A Monte Carlo Model and Experimental Validation

2016 Volume 1411

Abstract: Optical interrogation of suspicious skin lesions is standard care in the management of skin cancer worldwide. Morphological and functional markers of malignancy are often combined to improve expert human diagnostic power. We propose the evaluation of the ...

Abstract	Optical interrogation of suspicious skin lesions is standard care in the management of skin cancer worldwide. Morphological and functional markers of malignancy are often combined to improve expert human diagnostic power. We propose the evaluation of the combination of two independent optical biomarkers of skin tumours concurrently. The morphological modality of reflectance confocal microscopy (RCM) is combined with the functional modality of laser Doppler flowmetry, which is capable of quantifying tissue perfusion. To realize the idea, we propose laser feedback interferometry as an implementation of RCM, which is able to detect the Doppler signal in addition to the confocal reflectance signal. Based on the proposed technique, we study numerical models of skin tissue incorporating two optical biomarkers of malignancy: (i) abnormal red blood cell velocities and concentrations and (ii) anomalous optical properties manifested through tissue confocal reflectance, using Monte Carlo simulation. We also conduct a laboratory experiment on a microfluidic channel containing a dynamic turbid medium, to validate the efficacy of the technique. We quantify the performance of the technique by examining a signal to background ratio (SBR) in both the numerical and experimental models, and it is shown that both simulated and experimental SBRs improve consistently using this technique. This work indicates the feasibility of an optical instrument, which may have a role in enhanced imaging of skin malignancies.
Keywords	skin cancer detection ; Monte Carlo modelling ; laser feedback interferometry ; reflectance confocal microscopy ; laser Doppler flowmetry ; Technology (General) ; T1-995 ; Technology ; T ; Analytical chemistry ; QD71-142 ; Chemistry ; QD1-999 ; Science ; Q ; Chemical technology ; TP1-1185
Language	English
Publishing date	2016-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: RNA-seq reveals more consistent reference genes for gene expression studies in human non-melanoma skin cancers

Van L.T. Hoang / Lisa N. Tom / Xiu-Cheng Quek / Jean-Marie Tan / Elizabeth J. Payne / Lynlee L. Lin / Sudipta Sinnya / Anthony P. Raphael / Duncan Lambie / Ian H. Frazer / Marcel E. Dinger / H. Peter Soyer / Tarl W. Prow

PeerJ, Vol 5, p e

2017 Volume 3631

Abstract: Identification of appropriate reference genes (RGs) is critical to accurate data interpretation in quantitative real-time PCR (qPCR) experiments. In this study, we have utilised next generation RNA sequencing (RNA-seq) to analyse the transcriptome of a ... ...

Abstract	Identification of appropriate reference genes (RGs) is critical to accurate data interpretation in quantitative real-time PCR (qPCR) experiments. In this study, we have utilised next generation RNA sequencing (RNA-seq) to analyse the transcriptome of a panel of non-melanoma skin cancer lesions, identifying genes that are consistently expressed across all samples. Genes encoding ribosomal proteins were amongst the most stable in this dataset. Validation of this RNA-seq data was examined using qPCR to confirm the suitability of a set of highly stable genes for use as qPCR RGs. These genes will provide a valuable resource for the normalisation of qPCR data for the analysis of non-melanoma skin cancer.
Keywords	RNA-seq ; Reference gene ; qPCR ; Non-melanoma skin cancer ; Medicine ; R ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2017-08-01T00:00:00Z
Publisher	PeerJ Inc.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Microneedle enhanced delivery of cosmeceutically relevant peptides in human skin.

Yousuf H Mohammed / Miko Yamada / Lynlee L Lin / Jeffrey E Grice / Michael S Roberts / Anthony P Raphael / Heather A E Benson / Tarl W Prow

PLoS ONE, Vol 9, Iss 7, p e

2014 Volume 101956

Abstract: Peptides and proteins play an important role in skin health and well-being. They are also found to contribute to skin aging and melanogenesis. Microneedles have been shown to substantially enhance skin penetration and may offer an effective means of ... ...

Abstract	Peptides and proteins play an important role in skin health and well-being. They are also found to contribute to skin aging and melanogenesis. Microneedles have been shown to substantially enhance skin penetration and may offer an effective means of peptide delivery enhancement. The aim of this investigation was to assess the influence of microneedles on the skin penetration of peptides using fluorescence imaging to determine skin distribution. In particular the effect of peptide chain length (3, 4, 5 amino acid chain length) on passive and MN facilitated skin penetration was investigated. Confocal laser scanning microscopy was used to image fluorescence intensity and the area of penetration of fluorescently tagged peptides. Penetration studies were conducted on excised full thickness human skin in Franz type diffusion cells for 1 and 24 hours. A 2 to 22 fold signal improvement in microneedle enhanced delivery of melanostatin, rigin and pal-KTTKS was observed. To our knowledge this is the first description of microneedle enhanced skin permeation studies on these peptides.
Keywords	Medicine ; R ; Science ; Q
Subject code	571
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comparative immune phenotypic analysis of cutaneous Squamous Cell Carcinoma and Intraepidermal Carcinoma in immune-competent individuals

Andrew Freeman / Jennifer A Bridge / Pirashanthini Maruthayanar / Nana H Overgaard / Ji-Won Jung / Fiona Simpson / Tarl W Prow / H Peter Soyer / Ian H Frazer / Michael Freeman / James W Wells

PLoS ONE, Vol 9, Iss 10, p e

proportional representation of CD8+ T-cells but not FoxP3+ Regulatory T-cells is associated with disease stage.

2014 Volume 110928

Abstract: Squamous Cell Carcinoma (SCC) is a type of non-melanoma skin cancer prevalent in immune-suppressed transplant recipients and older individuals with a history of chronic sun-exposure. SCC itself is believed to be a late-stage manifestation that can ... ...

Abstract	Squamous Cell Carcinoma (SCC) is a type of non-melanoma skin cancer prevalent in immune-suppressed transplant recipients and older individuals with a history of chronic sun-exposure. SCC itself is believed to be a late-stage manifestation that can develop from premalignant lesions including Intraepidermal Carcinoma (IEC). Notably, while SCC regression is rare, IEC typically regresses in response to immune modifying topical treatments, however the underlying immunological reasons for these differential responses remain unclear. This study aimed to define whether IEC and SCC are associated with distinct immune profiles. We investigated the immune cell infiltrate of photo-damaged skin, IEC, and SCC tissue using 10-colour flow cytometry following fresh lesion digest. We found that IEC lesions contain higher percentages of CD3+ T-cells than photo-damaged skin, however, the abundance of CD3-CD56+ Natural Killer (NK) cells, CD11c+HLA-DR+ conventional Dendritic Cells (cDC), BDCA-2+HLA-DR+ plasmacytoid DC (pDC), FoxP3+ Regulatory T-cells (T-reg), Vα24+Vβ11+ invariant NKT-cells, and γδ Tcells did not alter with disease stage. Within the total T-cell population, high percentages of CD4+ T-cells were associated with SCC, yet CD8+ T-cells were less abundant in SCC compared with IEC. Our study demonstrates that while IEC lesions contain a higher proportion of T-cells than SCC lesions in general, SCC lesions specifically display a lower abundance of CD8+ T-cells than IEC. We propose that differences in CD8+ T-cell abundance contribute critically to the different capacity of SCC and IEC to regress in response to immune modifying topical treatments. Our study also suggests that a high ratio of CD4+ T-cells to CD8+ T-cells may be a immunological diagnostic indicator of late-stage SCC development in immune-competent patients.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Effective cutaneous vaccination using an inactivated chikungunya virus vaccine delivered by Foroderm

Rudd, Penny A / Andreas Suhrbier / Anthony P. Raphael / Joy Gardner / Kaitlin L. Nufer / Miko Yamada / Natalie A. Prow / Nhung Dang / Tarl W. Prow / Thuy T.T. Le / Wayne A. Schroder

Vaccine. 2015 Sept. 22, v. 33, no. 39

2015

Abstract: Foroderm is a new cutaneous delivery technology that uses high-aspect ratio, cylindrical silica microparticles, that are massaged into the skin using a 3D-printed microtextured applicator, in order to deliver payloads across the epidermis. Herein we show ...

Abstract	Foroderm is a new cutaneous delivery technology that uses high-aspect ratio, cylindrical silica microparticles, that are massaged into the skin using a 3D-printed microtextured applicator, in order to deliver payloads across the epidermis. Herein we show that this technology is effective for delivery of a non-adjuvanted, inactivated, whole-virus chikungunya virus vaccine in mice, with minimal post-vaccination skin reactions. A single topical Foroderm-based vaccination induced T cell, Th1 cytokine and antibody responses, which provided complete protection against viraemia and disease after challenge with chikungunya virus. Foroderm vaccination was shown to deliver fluorescent, virus-sized beads across the epidermis, with beads subsequently detected in draining lymph nodes. Foroderm vaccination also stimulated the egress of MHC II+ antigen presenting cells from the skin. Foroderm thus has potential as a simple, cheap, effective, generic, needle-free technology for topical delivery of vaccines.
Keywords	antibodies ; antigen-presenting cells ; Chikungunya virus ; cytokines ; lymph nodes ; mice ; silica ; T-lymphocytes ; vaccination ; vaccines ; viremia
Language	English
Dates of publication	2015-0922
Size	p. 5172-5180.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2015.07.099
Database	NAL-Catalogue (AGRICOLA)

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