SBIR-STTR Award

Nonmelanoma skin cancer (NMSC) represents the most common form of cancer in the human body. The method for diagnosing and treating NMSCs requires removal of a biopsy that is prepared and stained for analysis on a standard optical microscope. This process is painful for patients, introduces a substantial delay into the flow of care, and represents a considerable cost to healthcare ($6.5B/yr) due to the large number of unnecessary biopsies. Zebra Medical Technologies (ZMT) aims to address the need for a better method to diagnose NMSCs by creating a noninvasive imaging technology capable of displaying histology like images of skin cellular structure in real time. In this project, ZMT will construct a portable, skin-imaging microscope for human clinical studies (Aim 1), develop software for data acquisition, image processing, and improved user interface (Aim 2), and demonstrate in 5 human subjects with basal cell carcinoma (BCC) the ability to detect pathologic features of BCC (Aim 3). ZMT is the creator of the only commercially available fiber coupled multiphoton microscopy (MPM) system for in vivo imaging of skeletal muscle cellular structures and contractile dynamics, the Zebrascope, which has been sold to three universities and one hospital to date. ZMT will adapt and optimize technologies invented for the Zebrascope to specifically visualize cellular structures in skin. The ZMT team possesses expertise in miniaturizing optical systems, designing disposable optical probes with highly repeatable alignment, imaging deep into living tissue, and conducting human studies with MPM under IRB oversight. ZMT has already proven feasibility of this concept with a bench top prototype that successfully imaged subcellular structures in the epidermis and dermis in living human skin and in excised tumor samples. Success in this project will lead to a larger clinical study in Phase II. ZMT views NMSC as a natural first target for real time diagnosis that paves the way for applications in melanoma diagnosis followed by other epithelial cancers such as oral, esophageal, and cervical.

Public Health Relevance Statement:
Zebra Medical Technologies is developing a noninvasive microscopy system to provide images of suspected nonmelanoma skin cancer with subcellular resolution to aid in the diagnosis and treatment of this most common form of cancer. This technology will reduce the number of patient incisions, increase the speed and efficiency of diagnosis and treatment, and reduce the cost of unnecessary biopsies.

Project Terms:
Biopsy; neoplasm/cancer; malignancy; Malignant Tumor; Cancers; Malignant Neoplasms; epithelial carcinoma; Malignant Epithelial Tumors; Malignant Epithelial Neoplasms; Epithelial cancer; Carcinoma; malignant skin tumor; Malignant Skin Neoplasm; Skin Cancer; Rodent Ulcer; Basiloma; Basal Cell Epithelioma; Basal cell carcinoma; Nucleus; Cell Nucleus; Cell Body; Cells; Clinical Study; Clinical Research; Clinical Trials; Collagen; Color; Cytoplasm; Cutis; Corium; Dermis; Diagnosis; Cognitive Discrimination; Discrimination; Coloring Agents; Dyes; Epidermis; Feedback; Histology; Hospitals; Modern Man; Human; Lasers; Laser Radiation; Laser Electromagnetic; Light; Photoradiation; Literature; melanoma; Malignant Melanoma; Methods; Microscopy; Miniaturization; Miniaturisations; Motion; Muscle; muscular; Muscle Tissue; Noise; Optics; optical; Pain; Painful; Patients; Recruitment Activity; recruit; active recruitment; Computer software; Software; Stains; Technology; Medical Technology; Testing; Time; Tissues; Body Tissues; Universities; Artifacts; Morphologic artifacts; health care; Healthcare; Blinded; Caring; Custom; Tube; base; human subject; image processing; Microscope; improved; incision; Otomy; Surgical incisions; Cervical; Surface; Clinical; Phase; Ensure; Training; Lesion; Epithelial; Stratum Germinativum; Rete Malpighii; Basal Layer; Stratum Basale; Fiber; Lens Fiber; Voluntary Muscle; Skeletal Muscle; Human Figure; Human body; Cell Structure; Cell Components; Cellular Structures; Oncology Cancer; oncology; Solid Tumor; Solid Neoplasm; Intellectual Property; Zebra; Complex; Scanning; Oral; Clinic; System; Staining method; Stainings; Nuclear; Operative Surgical Procedures; surgery; Surgical Procedure; Surgical Interventions; Surgical; Operative Procedures; experience; neoplastic cell; Tumor Cell; photomultiplier; success; Sterility; sterile; Speed; Structure; Skin Carcinoma; nonmelanoma skin cancer; Non-Melanoma Skin Cancer; Excision; resection; Surgical Removal; Removal; Extirpation; Abscission; Subcellular structure; Intracellular Structure; Sampling; software development; developing computer software; develop software; miniaturize; portability; Skin; imaging modality; imaging method; image-based method; Address; Data; Economic Burden; Motor; Resolution; in vivo; Pathologic; Characteristics; Process; Esophageal; developmental; Development; imaging; Image; cost; rapid detection; designing; design; Imaging technology; Coupled; innovation; innovative; innovate; Cancerous; data acquisition; prototype; tumor; motor control; minimally invasive; in vivo imaging; non-invasive imaging; noninvasive imaging; optical spectra; optical spectrum; emission spectrum; emission spectra; microscopic imaging; microscopy imaging; microscope imaging; multiphoton imaging; multi-photon imaging; in vivo imaging system; IVIS system; IVIS spectrum; IVIS spectral imaging; IVIS optical imaging; IVIS imaging; IVIS SpectrumCT

Nonmelanoma skin cancer (NMSC) represents the most common form of cancer in the human body. The method for diagnosing and treating NMSCs requires a skin biopsy that is processed and stained for analysis on a standard optical microscope. This process is painful for patients, and the invasiveness of biopsy introduces a delay into NMSC detection, which contributes to patient morbidity and adds substantial cost to the healthcare system. Zebra Medical Technologies (ZMT) aims to address the unmet clinical need for a better method to detect NMSCs earlier. In Phase I of this grant, ZMT demonstrated the feasibility of a portable, skin- imaging microscope for human clinical studies (Aim 1), developed software for data acquisition, image processing, and improved user interface (Aim 2), and demonstrated in 5 human subjects with basal cell carcinoma (BCC) the ability to detect pathologic features of BCC (Aim 3). ZMT has created the first fiber coupled multiphoton microscopy (MPM) system for in vivo imaging of skin cellular anatomy. Building on this success, ZMT will build clinical evidence in Phase II to support a 510(k) submission for United States Food & Drug Administration (FDA) clearance. This is a necessary and valuable step towards bringing this technology into regular clinical practice. In this proposal we will accomplish three aims: Aim 1) Advance development of the portable, skin-imaging microscope for a clinical trial, Aim 2) Develop library of slide images of targeted skin diseases comparing MPM to traditional histology, and Aim 3) Conduct in vivo human performance testing to support FDA clearance.

Public Health Relevance Statement:
Zebra Medical Technologies is continuing to develop its noninvasive cellular imaging system to aid in the early detection of nonmelanoma skin cancers, the most common form of malignancy. We will begin collecting clinical evidence to support submission for United States Food & Drug Administration clearance and bring this technology into clinical practice. Our innovation will provide point-of-care clinicians with unprecedented rapid access to cellular histology, ensuring potential cancers are discovered as soon as possible.

Project Terms:
System; H and E; Hematoxylin and Eosin; Hematoxylin and Eosin Staining Method; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; Operative Surgical Procedures; early detection; Early Diagnosis; Performance; success; Speed; Devices; Non-Melanoma Skin Cancer; nonmelanoma skin cancer; Skin Carcinoma; Intracellular Structure; Subcellular structure; Sampling; performance tests; develop software; developing computer software; software development; portability; Skin; Address; Defect; Data; Imaging Instrument; Imaging Tool; Imaging Device; Cell Anatomy; Cellular Anatomy; Subcellular Anatomy; in vivo; Cancer Detection; Cancer Cause; Cancer Etiology; Validation; Pathologic; Process; developmental; Development; cell imaging; cellular imaging; point of care; imaging; Image; cost; Advanced Development; rapid detection; designing; design; new approaches; novel approaches; novel strategy; novel strategies; Coupled; innovate; innovative; innovation; data acquisition; Image data archive; image archive; image library; picture archive; image archival system; usability; prototype; clinical practice; risk minimization; imaging in vivo; in vivo imaging; noninvasive imaging; non-invasive imaging; imaging system; targeted imaging; microscope imaging; microscopy imaging; microscopic imaging; multi-photon imaging; multiphoton imaging; IVIS SpectrumCT; IVIS imaging; IVIS optical imaging; IVIS spectral imaging; IVIS spectrum; IVIS system; in vivo imaging system; multiphoton excitation microscopy; multiphoton microscopy; Adoption; Age; ages; Anatomy; Anatomic; Anatomic Sites; Anatomic structures; Anatomical Sciences; Biopsy; Malignant Neoplasms; Cancers; Malignant Tumor; malignancy; neoplasm/cancer; Skin Cancer; Malignant Skin Neoplasm; malignant skin tumor; Basal cell carcinoma; Basal Cell Epithelioma; Basiloma; Rodent Ulcer; Clinical Research; Clinical Study; Clinical Trials; Color; Diagnosis; Female; Freezing; Future; Goals; Gold; Grant; Healthcare Systems; Health Care Systems; Histology; Human; Modern Man; Incidence; Libraries; Methods; Morbidity - disease rate; Morbidity; Optics; optical; Pain; Painful; Pathology; Patients; Research; Safety; skin disorder; Cutaneous Disorder; Dermatoses; Skin Diseases; Skin Diseases and Manifestations; cutaneous disease; skin lesion; Computer software; Software; Specificity; Stains; Staining method; Technology; Medical Technology; Testing; Tissues; Body Tissues; United States Food and Drug Administration; Food and Drug Administration; USFDA; Blinded; Custom; human subject; image processing; Microscope; improved; Image Analyses; image evaluation; image interpretation; Image Analysis; Left; Area; Benign; Clinical; Malignant; Malignant - descriptor; Phase; Ensure; Training; Lesion; Fiber; Human Figure; Human body; Dermatologist; Zebra; Consensus; Catalogs; Clinic; Slide