SBIR-STTR Award

Every year in the US, 650,000 cancer patients are treated with chemotherapy. As a side effect, their neutrophil counts (number of white blood cells that aid in fighting infections) become low (referred to as neutropenia) and expose them to febrile neutropenia (FN) which are episodes of serious infection that entail costly hospitalization and sometimes death. If neutropenia is detected early, FN can be avoided through timely delivery of prophylactic antibiotics or growth stimulating factors. Currently, neutrophil measurements require visits to healthcare centers. This increases infection risk (as measurements are taken infrequently and low counts may not be detected before infections ensue) and reduces chemotherapy efficacy (as chemotherapy levels are kept at the lower end of frequency and dose for safety). We aim to overcome this limitation with PointCheck, a noninvasive neutrophil test that can be used frequently in local health centers or at home, enabling physicians to minimize infections and personalize chemotherapy planning. The basis for our technology is noninvasive optical imaging of microcirculation in nailfold capillaries. We conducted a pilot clinical study where trained nurses used PointCheck to acquire data from 46 chemotherapy patients. By manually analyzing a training dataset (N=38 measurements from 16 patients), we built a labeled dataset of flow gaps in the microcirculation that can be considered proxies of neutrophils and demonstrated their number can be used to distinguish baseline patients (>500 neutrophils/mm3) from grade IV neutropenic ones (<500/mm3). However, the need for manual analysis makes the technology inaccessible to patients on its current status. With support from SBIR Phase I, we will (a) develop algorithms that automatize the manual data processing workflow employed on our training set, (b) test those algorithms on our acquired and unanalyzed testing database (N=103 measurements from 30 patients) and (c) generate additional performance data including further intermediate neutrophil ranges (>500 and <1,500 neutrophils/mm3), thus fulfilling the requirements for a minimum viable product. The consecution of these milestones will enable, in Phase II, using PointCheck in a multi-site diagnostic validation trial to confirm, under clinical conditions, that the management of FN can be improved with this new paradigm.

Public Health Relevance Statement:
Development of a portable optical imaging device that can noninvasively detect neutropenia-related immunosuppression, to enable more frequent monitoring of chemotherapy patients so that timely medical interventions can be staged before life-threatening infections develop.

Project Terms:
Accident and Emergency department; Adverse effects; Algorithms; Antibiotics; Area; Autologous Stem Cell Transplantation; base; Blinded; Blood capillaries; Blood specimen; Cancer Patient; Cells; Cessation of life; chemotherapy; Classification; Clinic; Clinical; Clinical Research; cohort; Colony-Stimulating Factors; Computer Vision Systems; computerized data processing; cost; Data; Data Analyses; Data Set; Databases; deep learning; Detection; Development; Devices; Diagnostic; Dose; experience; Fever; fighting; Fingers; FPS-FES Oncogene; Frequencies; Generations; Goals; Grant; Growth; Health; Healthcare; Healthcare Systems; Hematology; Home environment; Hospital Costs; Hospitalization; Hospitals; Hour; Human; Imaging Device; Immunosuppression; improved; Incidence; Infection; Intervention; Interview; Label; learning strategy; Letters; Leukocytes; Life; Malignant Neoplasms; man; Manuals; Measurement; Medical; Microcirculation; Monitor; mortality; movie; Neutropenia; neutrophil; non-invasive optical imaging; Nurses; oncology; optical imaging; Patients; Performance; personalized chemotherapy; Phase; Physicians; Pilot Projects; point of care; portability; Process; prophylactic; prototype; Proxy; Risk; ROC Curve; Safety; Sample Size; Sampling; Sensitivity and Specificity; Site; Small Business Innovation Research Grant; System; Systems Analysis; Technology; Testing; Time; Training; Triage; Validation; Visit

The goal of this Phase II SBIR project is to optimize and validate PointCheck, the first non-invasive point-of-care (POC) device that identifies patients undergoing cancer chemotherapy who have early- stage febrile neutropenia and need immediate treatment to prevent serious infections. Every year in the US, 650,000 cancer patients are treated with chemotherapy. One side effect of treatment is neutropenia, a life- threatening condition caused by low levels of neutrophils that leads to hospitalization, increased risk of mortality and total associated costs of $2.7B annually. PointCheck uses noninvasive optical imaging of microcirculation in nailfold capillaries to detect severe neutropenia without the need for a blood sample. It is intended for use by cancer patients undergoing chemotherapy, in order to identify patients with neutropenia who require prompt treatment to avoid serious infections, hospital readmission costs and morbidity. Because it is self-contained and does not require blood sampling or reagents, it ultimately may be used by patients at home to monitor blood counts between chemotherapy sessions. In Phase I of this project, Leuko Labs successfully: (1) automated the selection of suitable capillaries from raw videos; (2) automated the detection of flow gaps that indicate passage of neutrophils in nail-fold capillaries; and (3) automatically analyzed manually-collected 1-min videos of nailfold capillaries from 44 cancer chemotherapy patients and identified those with grade IV neutropenia (<500 neutrophils/mm3) with an excellent classification performance (AUC=0.95). The objective of this Phase II project is to complete the next steps to bring PointCheck to market by designing a production-ready PointCheck device and validating it in a clinical study to support the filing of a Class II De Novo approval to the FDA. Aim 1 is to design a production-ready PointCheck hardware prototype for unsupervised use by patients by miniaturizing the optical components. Aim 2 is to develop and integrate the image analysis software pipeline to the production-ready unit. Aim 3 is to complete an initial pilot usability study performed in 3 cohorts of 30 patients (n=90 total) as the device is optimized in Aims 1 and 2; this study will also confirm that PointCheck is ready for the pivotal clinical study in Aim 4. Aim 4 is to complete a pivotal clinical study to validate PointCheck in a clinical diagnostic study (n=100) to confirm that grade IV neutropenia can be identified safely and effectively. Aim 5 is to submit a Class II De Novo approval package to the FDA. Successful completion of this Phase II project will fulfill the requirements for a minimum viable product and enable initial commercialization of this first-in-kind technology to improve the management of febrile neutropenia in cancer patients undergoing chemotherapy.

Public Health Relevance Statement:
PROJECT NARRATIVE PointCheck is a self-administered portable point-of-care optical imaging device that noninvasively detects immunosuppression resulting from cancer chemotherapy, without the need for a blood sample. Use of PointCheck in outpatient cancer clinics, and ultimately in patients' homes, will provide early detection and enable prompt medical care to prevent life-threatening infections in cancer patients undergoing chemotherapy.

Project Terms:
Accident and Emergency department; Algorithms; Anti-Infective Agents; automated analysis; base; Biological Assay; Blood; Blood capillaries; Blood specimen; Cancer Patient; Caring; Cells; chemotherapy; Chemotherapy-Oncologic Procedure; Classification; Clinic; Clinical; clinical diagnostics; Clinical Research; cohort; Colony-Stimulating Factors; commercialization; Computer software; cost; Data; data acquisition; data exchange; data quality; design; Detection; Development; Devices; Early Diagnosis; Early treatment; Evaluation; experience; Feedback; Fever; fighting; Fingers; Goals; Gold; Growth; Healthcare; Home environment; hospital readmission; Hospitalization; Hospitals; Image Analysis; Imaging Device; Immunosuppression; improved; improved outcome; Incidence; Infection; Infection prevention; Intervention; Interview; Leukocytes; Life; Malignant Neoplasms; Manuals; Measurement; Medical; meetings; Microcirculation; miniaturize; Monitor; Morbidity - disease rate; mortality; mortality risk; Nail Fold; Neutropenia; neutrophil; non-invasive optical imaging; Notification; Oncology; optical imaging; Optics; Outpatients; Participant; Pathway interactions; Patients; Performance; Phase; Physicians; Pilot Projects; point of care; portability; prevent; Process; Production; Protocols documentation; prototype; Quality Control; Reagent; Reproducibility; research clinical testing; Risk; Safety; Sampling; Self Administration; Sensitivity and Specificity; Serious Adverse Event; Small Business Innovation Research Grant; software systems; Structure of nail of finger; success; System; Technology; Testing; Time; Treatment Side Effects; Triage; usability; validation studies; Video Microscopy; Visit