Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Melanoma

Pigmentation Disorders

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

* fPAM imaging will be performed prior to scheduled excision. The time to excision will not be extended longer than 2 weeks for imaging purposes.
* When the participant presents for imaging, the area of the thickest lesion depth will be determined by fPAM. The area of deepest thickness will be marked perpendicular to the longest axis of the lesions and a clinical photo will be taken and placed in the image storage database.
* Surgical excision will be performed as standard of care and fPAM depth will be compared with histological examination.
* To image CTCs in cutaneous blood vessels, a small cuticle area on a finger will be imaged (Single cell PAM imaging) and the most distal cutaneous metastasis or metastasis of largest diameter will be imaged

-Hybrid imaging technique that detects absorbed diffusive protons ultrasonically through the photoacoustic effect.

Functional photoacoustic microscopy

Standard of care surgical excision

Single cell photoacoustic microscopy

Lynn Cornelius, M.D.

The investigators propose the use of functional photoacoustic microscopy (fPAM) to evaluate both benign and malignant pigmented lesions for tumor depth. Through fPAM analysis followed by histological examination, the investigators anticipate that they will be able to non-invasively determine tumor depth of pigmented lesions (moles and melanoma). In melanoma, tumor depth (Breslow's depth) is not only an important prognostic indicator, but also directs surgical treatment. The ultimate goal is to develop a sensitive clinical tool that will allow non-surgical evaluation of pigmented lesions, which eventually, will aid in melanoma diagnosis and management - potentially an earlier and more definitive surgical management.

In addition, the investigators propose to use the combination of fPAM and single-cell PAM to respectively image CTCs in trunk vessels and cuticle capillaries. Based on the investigators' murine models, the investigators anticipate that they will be able to differentiate CTCs from other blood cells and reliably calculate CTC concentration in a non-invasive manner. CTC concentration has been demonstrated to be a valuable indicator of a melanoma's metastatic potential and a potential tool in evaluating treatment efficacy. The ultimate goal is to develop a sensitive imaging device that will allow accurate evaluation of the risk of melanoma recurrence and metastases, that may facilitate treatment monitoring.

fPAM for the in Vivo Depth Measurement of Pigmented Lesions and Melanoma Depth

Pilot Study to Determine the Feasibility and Functionality of fPAM Imaging for the in Vivo Depth Measurement of Pigmented Lesions and Melanoma Depth

-The thickness as measured by fPAM will be compared with the thickness of the formalin fixed excised lesion.

Washington University School of Medicine

Diseases and Abnormalities at or Before Birth

Syndrome

Dysplastic Nevus Syndrome

Neoplastic Syndromes, Hereditary

Genetic Diseases, Inborn

Dermoscopic imaging of a lesion decided to be biopsied

Solely after the dermatologist has decided to biopsy a lesion and sent the patient to biopsy, a dermoscopic image is captured by a camera attached to a dermoscope.

dermoscopy

Avi Dascalu, MD, Ph.D.

Robert Raleigh, MBA

Avi Dascalu, MD

Avi Dascalu, MD. Ph.D.

Malignant melanoma (MM) is a deadly cancer, claiming globally about 160000 new cases per year and 48000 deaths at a 1:28 lifetime incidence (2016).

The golden standard, dermoscopy, enables Dermatologists to diagnose with a sensitivity of 40%, and a 8-12% specificity, approximately. Additional diagnostic abilities are restricted to devices which are either unproved or experimental.

A new technology of Neuronal Network Clinical Decision Support (NNCD) was developed. It uses a dermoscopic imaging device and a camera able to capture an image. The photo is transferred to a Cloud Server and further analyzed by a trained classifier. Classifier training is aimed at a high accuracy diagnosis of Dysplastic Nevi (DN), Spitz Nevi and Malignant Melanoma detection with assistance from a Deep Neuronal Learning network (DLN). Diagnosis output is an excise or do not excise recommendation for pigmented skin lesions.

A total of 80 subjects already referred to biopsy pigmented skin lesions will be examined by dermoscopy imaging in a non interventional study. Artificial Intelligence output results, as measured by 2 different dermoscopes, to be compared to ground truth biopsies, by either classifier decisions or a novel Modified Classifier Technology output decisions.

Primary endpoints are sensitivity and specificity detection of the NNCD techniques. Secondary endpoints are the positive and negative prediction ratios of NNCD techniques.

Background

Malignant melanoma (MM) is a deadly cancer, claiming globally about 160000 new cases per year and 48000 deaths \[1\]. The incidence rate for MM ascended between 1950 and 2007 more than 17-fold in men (1.9 to 33.5 per 100,000) and more than 9-fold in women (2.6 to 25.3 per 100,000) \[2\]. It is estimated that 76000 new cases and 9000 deaths are diagnosed/ year (US, only, 2017) \[3\]. European Countries yield 22000/yr. stage 4 melanomas.

MM starts de novo in about 70% of subjects, with a small 2 millimeters or more superficial skin lesion which, if left undiagnosed, might develop into a more advanced stage cancer, followed by silent lymph node spreading and invasion of vital organs such as liver and brain. MM is staged by either direct invasion into the skin, the Breslow scale in mm, or by its skin level involvement, a Clark 1-5 structural skin level of involvement. Both methods of assessment are predictors of long term survival, which is almost unchanged at a Breslow depth beneath 1 mm and much decreased beyond Clark III stage. Therefore early detection of melanoma, generally tagged as small melanoma, is critical.

Present Methodologies of MM detection

The following different methods and diagnostic means for detection of the cutaneous melanoma are currently employed as a means of diagnosis:

1. Visual recognition by an Asymmetry, Border, Color, Diameter and Evolvement (ABCDE rule). A 30 year old methodology and still running, assessing: ABCDE. It is used by part of US dermatologists who trust their clinical skills and instincts \[4\]. Due to its innate complexity and myriad of recognition patterns, dermoscopy by epiluminescence microscopy is considered as ineffective by 60% of the non users dermatologists and 30% report it as time consuming, rendering it impracticable. The abovementioned rule was reviewed in 2015 \[5\] and teaches the use of a diameter greater than 6 mm as a criteria for melanoma recognition. Consequently, it does not contribute to early detection of a melanoma, which might be life saving, since 70-80% of melanomas start de novo as small melanomas. An attempt to change the Diameter criteria, i.e. a decrease in the postulated 6 mm Diameter, leads to a major decrease in sensitivity and specificity, rendering the ABCDE ineffective for early melanoma detection. It is concluded that these basic visual criteria, although widely used, are a non effective prevention method due to their innate criteria which misses the evolving melanomas, since all melanomas start as small melanomas.
2. Epiluminescence microscopy is a 65 years old art, which is considered the golden standard of evaluation. It is highly dependent on the skills and knowledge of the diagnostician. Epiluminescence microscopy is a the bridge between clinical observation and histopathological diagnosis. It allows visualization of skin pigments up to the papillary dermis and improves detection sensitivity and specificity. Analysis is made by a clinician based on dermoscopy rules \[6\], which are based on a complicated dermoscopic pattern analysis.

   Complete dermoscopic pattern analysis of a lesion is the mainstream of diagnosis. Each of the dermoscopic patterns can diverge in extent, diameter, general or local appearance, or evolve as multi patterns with various area of expression on the same lesion and rendering the diagnosis beyond an encyclopedic task.

   Due to the complexity of the dermoscopic pattern analysis method, different modifications were proposed, such as a simplified ABCD rule, an intermediate 7 rules assessment and a 11 rules checklist. The myriad of data and its interpretation render even experts in dermoscopy to identify melanomas with a relative low ratio from 5:1 to 15:1, i.e. the number of biopsies of benign lesions performed in order to make the diagnosis of one skin melanoma.

   Furthermore, there are claims that one diagnostic sign might be more sensitive that other signs, alike the criteria of a light brown structureless area. Dermatologists commonly fail in diagnosing early small melanoma which is the critical period of growth of the tumor and most efficacious prevention.
3. Visual recognition by temporal total body photography is yet non standardized methodology, a time consuming and patient expensive procedure. It uses the human comparison assessment and is subjected to biases of pixel photo during performance of the measurement, due to lighting, background and camera position. Addition of patient assessment by artificial intelligence, an analysis based on computer evaluation of different colorimetric and geometric parameters of a lesion in real time, confer a limited advantage only, yielding sometimes more false positives compared to inexperienced or even experienced clinicians.
4. Multi Spectrometry devices, which provide measurements of melanin, collagen and hemoglobin with further use of image analysis, do not confer any advantage to epiluminescence microscopy. Although displaying a higher sensitivity, these methodologies specificity are considerably below that of simple epiluminescence microscopy in melanoma identification rate .
5. Confocal scanning microscopy, a procedure which uses a low power laser for a 3D imaging. An effective means of diagnosis. However, the use of this methodology is limited by its high cost, a prolonged (6 mo) learning curve of 2000-4000 images, and the requirement for a highly specialized and trained personal, since this methodology is highly subjected to artifacts.
6. Experimental under development methods: alike Electrical impedance spectroscopy, Optical coherence tomography, High frequency ultrasound, Laser doppler perfusion imaging, Dynamic thermal imaging, Photoacoustic microscopy, to be further developed and proved.

Clinical Requirements

It is desirable to identify a new non invasive methodology which will

1. Improve Sensitivity of diagnosis of pigmented skin lesions, alike dysplastic nevi, Spitz nevi and MM
2. Identify small MM,
3. Increase Specificity of lesions to be biopsied
4. Non invasive fast technology.

Common Practice

Commonly, a patient is evaluated by a physician due to either a skin lesion complaint or, with high risk patients, a summon to visit on a regular basis.

Only some of the dermatologists employ dermoscopy or are skilled to use it since it may seem to be time consuming. There is no international standard of degree of skill. Even a golden standard textbook of dermoscopy is not existent.

Upon recognition of suspicious lesion, patient is referred to a surgeon for biopsy.

As recently reviewed and in view of the above-mentioned, the incidence of melanoma is continuing to increase. All present methods commonly do not diagnose melanoma at an early stage and epiluminescence microscopy is highly user dependant and commonly misses the diagnosis . Early excision is the only strategy to reduce the death toll associated with melanoma. Unnecessary excision of benign lesions increases morbidity and raise healthcare costs associated with melanoma screening, resulting in recommended restrictions to a total body screening by Surgeon General (2016) and questioning the efficacy of such a screening.

The requirement for a more systemized methodology and system is obvious in view of the expected increase in melanoma incidence to a 1:15 within the next 15 years. A new device able to capture the window of opportunity of Dysplastic Nevus to small melanoma is highly useful for today healthcare systems.

Primary Study Objectives

* A Sensitivity of at least 75% for Classifier results as compared to biopsy Sensitivity is the percentage of correctly diagnosed dysplastic nevi, Spitz nevi or melanomas. \[ Designated as safety issue: No \].
* A Sensitivity of at least 85% for an Modified Classifier Technology (MCT) results as compared to biopsy. Sensitivity is the percentage of correctly diagnosed dysplastic nevi, Spitz nevi or melanomas. \[ Designated as safety issue: No \]
* A Specificity of at least 33% for Classifier results as compared to biopsy. Specificity is the percentage of correctly identified dysplastic nevi, Spitz nevi or melanomas. \[ Designated as safety issue: No \]
* A Specificity of at least 33% for MCT results as compared to biopsy. Specificity is the percentage of correctly identified dysplastic nevi, Spitz nevi or melanomas. \[ Designated as safety issue: No \]

Secondary Study Objectives

* The positive predictive value of MCT, compared to the biopsy result \[ Designated as safety issue: No \]
* The negative predictive value of MCT, \[ Designated as safety issue: No \]
* The false positive rate of MCT, \[ Designated as safety issue: No \]
* The false negative rate of MCT, \[ Designated as safety issue: No \]
* The difference between two dermoscopes, \[ Designated as safety issue: No \]
* The positive predictive value of Classifier, compared to the biopsy result \[ Designated as safety issue: No \]
* The negative predictive value of Classifier, \[ Designated as safety issue: No \]
* The false positive rate of Classifier, \[ Designated as safety issue: No \]
* The false negative rate of Classifier, \[ Designated as safety issue: No \]
* Clinical decision Sensitivity and Specificity rates.

Artificial Intelligence-assisted Evaluation of Pigmented Skin Lesions

Dermoscopy Evaluation of Pigmented Skin Lesions by a Neuronal Network Clinical Decision Support: an Open Prospective Non Interventional Study

A Sensitivity of at least 75% for Classifier results as compared to biopsy

A Sensitivity of at least 85% for Classifier results as compared to biopsy

The positive predictive value of MCT, compared to the biopsy result

The negative predictive value of MCT, compared to the biopsy result

Assuta Hospital Systems

The SECM skin imaging procedure will be very similar to that by the FDA approved RCM devices. First, the skin lesion (such as a mole) will be identified on a forearm of the subject. The lesion will be imaged first with a dermatoscope, and then with the SECM device. A dermatoscope is a hand-held device used for the visual observation of the epidermis. It is a superior surface contact microscope used to examine skin lesions.

Consented Participants will be asked to allow their forearm to be imaged by the dermatoscope on the same skin/lesions as a control comparison. We will be trying to image pigmented skin/lesions present on the forearm. This will be followed by imaging using the SECM Skin imaging device

SECM Skin Imaging

Guillermo Tearney, M.D, PhD.

The aim of this study is to evaluate the imaging performance of Spectrally Encoded Confocal Microscopy (SECM) for imaging human skin and skin diseases.

SECM provides an order of magnitude faster imaging speed than conventional confocal microscopy devices. The investigators have previously utilized the SECM technology for imaging large area of human esophagus in vivo. They have also developed endoscopic capsule devices which have been used to safely image over 60 human subjects, healthy volunteers and subjects with eosinophilic esophagitis, using SECM technology, rapidly.

When used for skin imaging, SECM can provide real-time three-dimensional confocal imaging and significantly reduce the imaging time. While SECM has been successfully used for imaging human esophagus in vivo, its utility in skin imaging needs to be tested in a new pilot study. The investigators will be taking images with a dermatoscope as well. This will the control to compare the experimental images to, as the dermatoscope is the standard of care diagnostic tool for dermatologists.

Pilot Study of Imaging Human Skin With High-Speed Spectrally Encoded Confocal Microscopy

The quality, resolution and depth of the images will be reviewed by the PI. This is a qualitative analysis to determine the feasibility of the device, the parameters mentioned will be compared to correlative data obtained from the dermatoscope control. Unit measurements are not available.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
fPAM for the in Vivo Depth Measurement of Pigmented Lesions and Melanoma Depth	NCT02613325	Pigmented Skin ... Melanoma	Functional phot... Standard of car... Single cell pho...	18 Years -	Washington University School of Medicine
fPAM for the in Vivo Depth Measurement of Pigmented Lesions and Melanoma Depth	NCT02613325	Pigmented Skin ... Melanoma	Functional phot... Standard of car... Single cell pho...	18 Years -	Washington University School of Medicine
Artificial Intelligence-assisted Evaluation of Pigmented Skin Lesions	NCT03362138	Melanoma Pigmented Skin ... Dysplastic Nevi	dermoscopy	18 Years - 90 Years	Assuta Hospital Systems
Pilot Study of Imaging Human Skin With High-Speed Spectrally Encoded Confocal Microscopy	NCT04566302	Pigmented Lesio... Pigmented Skin ... Pigmented Moles Skin Lesion	SECM Skin Imagi...	18 Years -	Massachusetts General Hospital
Artificial Intelligence-assisted Evaluation of Pigmented Skin Lesions	NCT03362138	Melanoma Pigmented Skin ... Dysplastic Nevi	dermoscopy	18 Years - 90 Years	Assuta Hospital Systems
Artificial Intelligence-assisted Evaluation of Pigmented Skin Lesions	NCT03362138	Melanoma Pigmented Skin ... Dysplastic Nevi	dermoscopy	18 Years - 90 Years	Assuta Hospital Systems

Spots Global Cancer Trial Database for pigmented skin lesion