PV[O]H: Noninvasive Enabling Technology, New Physiological Monitoring, and Big Data.

INTRODUCTION: Measures of normal and abnormal physiology are interrelated and vary continuously. Our ability to detect and predict changes in physiology in real time has been limited in part by the requirement for blood sampling and the lack of a continuous data stream of various "signals", i.e., measurements of vital signs. It is important to determine which signals are most revealing for detection and treatment of, e.g., internal bleeding, managing fluid balance for mission/combat readiness, and hydration. Although our current algorithm for PV[O]H reflects changes in hematocrit and blood and plasma volumes, additional algorithms utilizing the whole raw PV[O]H data stream, along with other variables, can be constructed. We present a working prototype demonstrating that acceptable size, power, and complexity footprints for military needs can be achieved. Results of previous studies involving humans have demonstrated that PV[O]H can provide simultaneous, noninvasive, in vivo continuous monitoring of hematocrit, vascular volume, hemoglobin oxygen saturation, pulse rate, and breathing rate using a single light source with a reporting frequency of every 3 seconds. MATERIALS AND METHODS: We have engineered an instrument implementing the PV[O]H algorithm in which (1) single channel photodetectors replace multichannel detection; (2) optical filters replace gratings; (3) battery power is used; and (4) sufficient computation with input/output capability moderated by application specific graphical user interfaces, and compatible with all cloud, wireless environment, and local protocols is implemented. RESULTS: We have engineered a complete version of a two-probe PV[O]H system meeting military needs and have fabricated a first version. Testing of subsystems, calibration, and optical characterization of the optical probes are underway. CONCLUSIONS: Simultaneous noninvasive continuous monitoring of peripheral vessels using a previous PV[O]H system demonstrates large, physiology revealing data sets. The technologies enable the methodical search for relevant physiological signals allowing the use of discriminant analysis, Bayesian approaches, and artificial intelligence to create predictive algorithms enabling timely interventions in medical care and troop training.

Noninvasive Blood and Tissue Analysis: Raman Spectroscopy, One Perspective for Monitoring of Glucose and Beyond.

Noninvasive in vivo blood and tissue analysis remains a challenge to medical technology epitomized by the ongoing quest to replace fingerstick self-monitoring of blood glucose. Recent developments warrant comment on near-term prospects for using Raman spectroscopy to meet that challenge. These developments combined with 20 years of experimentation with noninvasive blood and tissue analysis suggest that it may be possible and practical to perform noninvasive in vivo glucose analysis with improvements in (1) the enabling technologies for making Raman measurements and (2) an underlying anatomical-physiological model of how in vivo spectroscopic measurements are made and interpreted. We review the substantial progress made toward meeting the challenge and the personal, public health, and economic implications of these ongoing efforts.

In vivo, noncontact, real-time, PV[O]H imaging of the immediate local physiological response to spinal cord injury in a rat model.

We report a small exploratory study of a methodology for real-time imaging of chemical and physical changes in spinal cords in the immediate aftermath of a localized contusive injury. One hundred separate experiments involving scanning NIR images, one-dimensional, two-dimensional (2-D), and point measurements, obtained in vivo, within a 3 × 7 mm field, on spinal cords surgically exposed between T9 and T10 revealed differences between injured and healthy cords. The collected raw data, i.e., elastic and inelastic emission from the laser probed tissues, combined via the PV[O]H algorithm, allow construction of five images over the first 5 h post injury. Within the larger study, a total of 13 rats were studied using 2-D images, i.e., injured and control. A single 830-nm laser (100-µm diameter round spot) was spatially line-scanned across the cord to reveal photobleaching effects and surface profiles possibly locating a near surface longitudinal artery/vein. In separate experiments, the laser was scanned in two dimensions across the exposed cord surface relative to the injury in a specific pattern to avoid uneven photobleaching of the imaged tissue. The 2-D scanning produced elastic and inelastic emission that allowed construction of PV[O]H images that had good fidelity with the visually observed surfaces and separate line scans and suggested differences between the volume fractions of fluid and turbidity of injured and healthy cord tissue.

Virtual reality technologies for research and education in obesity and diabetes: research needs and opportunities.

The rising rates, high prevalence, and adverse consequences of obesity and diabetes call for new approaches to the complex behaviors needed to prevent and manage these conditions. Virtual reality (VR) technologies, which provide controllable, multisensory, interactive three-dimensional (3D) stimulus environments, are a potentially valuable means of engaging patients in interventions that foster more healthful eating and physical activity patterns. Furthermore, the capacity of VR technologies to motivate, record, and measure human performance represents a novel and useful modality for conducting research. This article summarizes background information and discussions for a joint July 2010 National Institutes of Health - Department of Defense workshop entitled Virtual Reality Technologies for Research and Education in Obesity and Diabetes. The workshop explored the research potential of VR technologies as tools for behavioral and neuroscience studies in diabetes and obesity, and the practical potential of VR in fostering more effective utilization of diabetes- and obesity-related nutrition and lifestyle information. Virtual reality technologies were considered especially relevant for fostering desirable health-related behaviors through motivational reinforcement, personalized teaching approaches, and social networking. Virtual reality might also be a means of extending the availability and capacity of health care providers. Progress in the field will be enhanced by further developing available platforms and taking advantage of VR's capabilities as a research tool for well-designed hypothesis-testing behavioral science. Multidisciplinary collaborations are needed between the technology industry and academia, and among researchers in biomedical, behavioral, pedagogical, and computer science disciplines. Research priorities and funding opportunities for use of VR to improve prevention and management of obesity and diabetes can be found at agency websites (National Institutes of Health: http://grants.nih.gov/grants/guide/index.html; Department of Defense: www.tatrc.org).

Consensus recommendations for advancing breast cancer: risk identification and screening in ethnically diverse younger women.

A need exists for a breast cancer risk identification paradigm that utilizes relevant demographic, clinical, and other readily obtainable patient-specific data in order to provide individualized cancer risk assessment, direct screening efforts, and detect breast cancer at an early disease stage in historically underserved populations, such as younger women (under age 40) and minority populations, who represent a disproportionate number of military beneficiaries. Recognizing this unique need for military beneficiaries, a consensus panel was convened by the USA TATRC to review available evidence for individualized breast cancer risk assessment and screening in young (< 40), ethnically diverse women with an overall goal of improving care for military beneficiaries. In the process of review and discussion, it was determined to publish our findings as the panel believes that our recommendations have the potential to reduce health disparities in risk assessment, health promotion, disease prevention, and early cancer detection within and in other underserved populations outside of the military. This paper aims to provide clinicians with an overview of the clinical factors, evidence and recommendations that are being used to advance risk assessment and screening for breast cancer in the military.

Nanotechnology research: applications in nutritional sciences.

The tantalizing potential of nanotechnology is to fabricate and combine nanoscale approaches and building blocks to make useful tools and, ultimately, interventions for medical science, including nutritional science, at the scale of approximately 1-100 nm. In the past few years, tools and techniques that facilitate studies and interventions in the nanoscale range have become widely available and have drawn widespread attention. Recently, investigators in the food and nutrition sciences have been applying the tools of nanotechnology in their research. The Experimental Biology 2009 symposium entitled "Nanotechnology Research: Applications in Nutritional Sciences" was organized to highlight emerging applications of nanotechnology to the food and nutrition sciences, as well as to suggest ways for further integration of these emerging technologies into nutrition research. Speakers focused on topics that included the problems and possibilities of introducing nanoparticles in clinical or nutrition settings, nanotechnology applications for increasing bioavailability of bioactive food components in new food products, nanotechnology opportunities in food science, as well as emerging safety and regulatory issues in this area, and the basic research applications such as the use of quantum dots to visualize cellular processes and protein-protein interactions. The session highlighted several emerging areas of potential utility in nutrition research. Nutrition scientists are encouraged to leverage ongoing efforts in nanomedicine through collaborations. These efforts could facilitate exploration of previously inaccessible cellular compartments and intracellular pathways and thus uncover strategies for new prevention and therapeutic modalities.

Differences in the prevalence of growth, endocrine and vitamin D abnormalities among the various thalassaemia syndromes in North America.

This study aimed to determine differences in the rates of growth, endocrine- and calcium-related abnormalities in the various thalassemia syndromes in North America treated with current therapies. Medical history, physical examinations and blood and urine collections were obtained from patients with all thalassemia syndromes age 6 years and older in the Thalassemia Clinical Research Network. 361 subjects, 49% male, mean age 23.2 years (range 6.1-75 years) were studied. Approximately 25% of children and adults, regardless of the thalassemia syndrome, had short stature. Overall growth in children was mildly affected. Final height was close to midparental height (z = -0.73 +/- 1.24). Patients with beta thalassemia major (TM) had higher rates of hypogonadism, multiple endocrinopathies, worse hyperglycaemia, subclinical hypoparathyroidism and hypercalciuria. Hypogonadism remained the most frequent endocrinopathy and was frequently under-treated. 12.8% of the subjects had 25 vitamin D concentrations less than 27 nmol/l and 82% less than 75 nmol/l, regardless of the thalassemia syndrome. Adolescents had lower 25 vitamin D levels than children and adults. Compared to patients with other thalassemia syndromes, those with beta TM suffered from higher rates of multiple endocrinopathies, abnormal calcium metabolism and hypercalciuria. Vitamin D abnormalities were high among adolescents.

Effect of hemoglobin concentration variation on the accuracy and precision of glucose analysis using tissue modulated, noninvasive, in vivo Raman spectroscopy of human blood: a small clinical study.

Tissue modulated Raman spectroscopy was used noninvasively to measure blood glucose concentration in people with type I and type II diabetes with HemoCue fingerstick measurements being used as reference. Including all of the 49 measurements, a Clarke error grid analysis of the noninvasive measurements showed that 72% were A range, i.e., clinically accurate, 20% were B range, i.e., clinically benign, with the remaining 8% of measurements being essentially erroneous, i.e., C, D, or E range. Rejection of 11 outliers gave a correlation coefficient of 0.80, a standard deviation of 22 mg/dL with p<0.0001 for N=38 and places all but one of the measurements in the A and B ranges. The distribution of deviations of the noninvasive glucose measurements from the fingerstick glucose measurements is consistent with the suggestion that there are at least two systematic components in addition to the random noise associated with shot noise, charge coupled device spiking, and human factors. One component is consistent with the known variation of fingerstick glucose concentration measurements from laboratory reference measurements made using plasma or whole blood. A weak but significant correlation between the deviations of noninvasive measurements from fingerstick glucose measurements and the test subject's hemoglobin concentration was also observed.

Current and future commitment to hematology research.

This article provides an overview of the National Heart Lung and Blood Institute's (NHLBI) current and future commitment to hematology research. The paper comprises nine sections: (1) a brief history of how NHLBI incorporated blood research in its mission; (2) a summary of the traditional areas of research interest for blood diseases and resources; (3) a description of how NHLBI has assured and continues to assure a safe blood supply; (4) the current and future plans for transfusion medicine and cellular therapy research; (5) research support for hemoglobinopathies and red cell disorders; (6) research support for thrombosis and hemostatic disorders; (7) current and future research of hematopoietic stem cell biology, and aplastic and preneoplastic conditions; (8) future training for hematologists, and (9) a concluding summary.