Method for the discovery, validation and clinical application of multiplex biomarker algorithms based on optical, physical and/or electromagnetic patterns

Abstract

A method for diagnosing or predicting the risk of shock, the method incorporating an algorithmic combination of optical, electromagnetic, and other sensors, along with their anatomic and temporal patterns. A method for developing the algorithms through iterative optimization using machine learning.

What is claimed is: 
     
         1 . A medical device system for assisting in the diagnosis of a systemic medical condition of a patient, the medical device system comprising:
 a plurality of sensors configured to be placed at multiple physiologically distinct locations of the patient and to measure one or more optical or electromagnetic properties at the respective multiple physiologically distinct locations;   at least one computational device; and   an output of the at least one computational device for displaying medical information of the patient;   wherein the at least one computational device is configured to:   store at least one predetermined anatomic pattern between the multiple physiologically distinct locations;   receive signals from the plurality of sensors based on the measured optical or electromagnetic tissue properties,   estimate at least one physiologic variable based on the received signals,   determine a temporal pattern between estimated physiologic variables corresponding to at least two of the plurality of sensors,   estimate a current or future probability of shock in the patient based on the anatomic and temporal patterns,   determine a scale or index that provides an indication of the current or future probability of shock in the patient, and   visually display on the output the scale or index that provides the indication of the current or future probability of shock in the patient.   
     
     
         2 . The medical device system of  claim 1 , wherein the estimation of the current or future probability of shock in the patient comprises an optimization of a combination of sensitivity, specificity, positive predictive value, negative predictive value, receiver operator characteristic curves, or time before shock. 
     
     
         3 . The medical device system of  claim 1 , wherein the plurality of sensors are configured to measure one or more physical properties of tissue comprising at least one of temperature, density, weight, hydration state, and transmission of sound. 
     
     
         4 . The medical device system of  claim 1 , wherein the measured optical or electromagnetic properties includes properties measured via at least one of pulse oximetry, ECG, impedance, near infra-red spectroscopy (NIRS), Raman spectroscopy, speckle, and surface plasmon resonance. 
     
     
         5 . The medical device system of  claim 1 , wherein the at least one physiologic variable includes at least one of cardiac function, electrocardiogram, heart rate, blood pressure, cardiac output, stroke volume, tissue oxygenation, tissue pH, hemoglobin, cytochrome oxygenation reduction status or other cellular energy status, hematocrit, lactate level, cephalic oxygenation, central oxygenation, deep visceral oxygenation, extremity oxygenation, cephalic energetics, central energetics, deep visceral energetics, extremity energetics, cephalic perfusion, central perfusion, deep visceral perfusion, and extremity perfusion. 
     
     
         6 . The medical device system of  claim 5 , wherein the estimated current or future probability of shock is based on a comparison between oxygenation in deep visceral, cephalic and/or central tissue regions and oxygenation in extremity tissue regions. 
     
     
         7 . The medical device system of  claim 5 , wherein the estimated current or future probability of shock is based on a comparison between energetics in deep visceral, cephalic and/or central tissue regions and oxygenation in extremity tissue regions. 
     
     
         8 . The medical device system of  claim 5 , wherein the estimated current or future probability of shock is based on a comparison between perfusion in deep visceral, cephalic and/or central tissue regions and oxygenation in extremity tissue regions. 
     
     
         9 . The medical device system of  claim 5 , wherein the anatomic and temporal patterns are indicative of one or more organs being spared in comparison to axial musculature or skin. 
     
     
         10 . The medical device system of  claim 1 , wherein the physiologically distinct locations of the patient comprise at least one of the cranium, the neck, the thorax, the abdomen, one or more extremities, axial, extremities, oral, conjunctiva, rectal, nasal, needle intra-tissue, and intravascular catheter based locations. 
     
     
         11 . The medical device system of  claim 1 , wherein the anatomic pattern comprises at least one of craniosacral, axial-appendicular, skeletal-visceral, cranial-skeletal, cranial-visceral, axial-acral, depth below the skin, or distance from the sensor, and on or within the body. 
     
     
         12 . The medical device system of  claim 11 , wherein the anatomic pattern comprises an axial-acral distribution of measurements. 
     
     
         13 . The medical device system of  claim 1 , wherein the temporal pattern comprises at least one of stable and unchanged, baseline to present, increasing or decreasing instability, accelerating deterioration, stabilizing deterioration, improvement, and changes in measurements over time. 
     
     
         14 . The medical device system of  claim 1 , wherein the estimated current or future probability of shock is based on changes in measurements over time. 
     
     
         15 . The medical device system of  claim 1 , wherein the at least one computational device is configured to estimate a current or future probability of sepsis, congestive heart failure, hypoxia and/or other perfusion-threatening pathologic process. 
     
     
         16 . The medical device system of  claim 5 , wherein one or more of the variables includes variation in physiologic variable a differing depths below the skin at two or more times and locations. 
     
     
         17 . The medical device system of  claim 5  wherein one or more of the sensors are inside of the patient in a location or locations selected from the group consisting of a hollow viscous organ, the gastrointestinal tract, the respiratory tract or the ear canal. 
     
     
         18 . The medical device system of  claim 5  wherein one or more of the sensors measures optical or electromagnetic energy whose source is outside of the patient's body. 
     
     
         19 . The medical device system of  claim 5  wherein one or more of the sensors measures optical or electromagnetic energy whose source is within the patient's body. 
     
     
         20 . The medical device system of  claim 5  wherein one or more of the measurements is obtained after administration of a systemic or local physical or pharmacologic agent or combination of agents. 
     
     
         21 . The medical device system of  claim 1  wherein the computational device incorporates data selected from a list including patient demographics, age, or sex vital signs, in-vitro diagnostics, or elements within the electronic medical record.