System for assessing tissue substance extraction

1. A system for measuring a micro-vascular flow distribution of a tissue portion of a mammal, the system comprises:

a measuring unit for measuring a first indicator of blood flow through a capillary bed;

a measuring unit for measuring a second indicator of heterogeneity of the blood flow in said capillary bed;

a first processor operatively connected to the measuring unit for measuring the first indicator, wherein the first processor is arranged for using the measured first and the measured second indicators to estimate an extraction capacity (EC) of a substance from blood in said capillary bed, wherein the estimate includes uptake and diffusion of the substance that is relevant for metabolism;

wherein the first processor applies a model connecting the measured first and the measured second indicators to the extraction capacity (EC) of the substance from the blood in said capillary bed, the model comprising a transfer rate of total substance concentration (CT) across the capillaries being linearly dependent on a plasma concentration of the substance (CP), the model further comprising a non-vanishing back flow of the substance from tissue into capillaries, wherein the first processor is configured to detect a previously undiagnosed disease based on the heterogeneity of the blood;

a display operatively connected to the first processor, wherein the display is configured to display images related to the blood flow;

wherein the measured first indicator is a mean transit time (MTT) of the blood flow, and the measured second indicator is a standard deviation (σ) of the mean transit time of the blood flow;

wherein the substance is oxygen and an extraction capacity is the oxygen extraction capacity (OEC);

wherein the first processor is further arranged for assessing one, or more, of the first indicator, the second indicator, or the extraction capacity with a database comprising reference values thereof; and

wherein the reference values in the database include threshold values for the first indicator and the second indicator that classify whether the mammal likely has the previously undiagnosed disease.

2. The system according to claim 1 , wherein the model is based on at least one rate constant, k, related to a permeability of a capillary wall to the substance.

3. The system according to claim 1 , wherein the model applies a variable shift to a rate constant for diffusion of the substance across the capillary (k), the mean transit time (r), and a fractional distance of the capillary (x) to enable an averaging over a transit time distribution to be performed from one capillary.

4. The system according to claim 1 , wherein the model further comprises the substance cooperativity due to a non-linear binding of the substance with a protein in blood.

5. The system according to claim 4 , wherein the model comprises the oxygen cooperativity due to the non-linear binding of the oxygen with haemoglobin.

6. The system according to claim 1 , wherein a first measuring unit for measuring the first indicator for the blood flow through a capillary bed and/or for measuring the second indicator of the heterogeneity of the blood flow in said capillary bed are measurement units based on direct in vivo measurement of a distribution of particle velocities, particle flux, and/or particle transit times.

7. The system according to claim 1 , wherein the measuring unit for measuring the first indicator for the blood flow through a capillary bed and/or for measuring the second indicator of the heterogeneity of the blood flow in said capillary bed are measurement units configured for indirect in vivo measurement of distribution of particle velocities, particle flux, and/or particle transit times.

8. The system according to claim 1 , wherein the system further comprises the database with reference levels of one, or more, of the first indicator, the second indicator or the extraction capacity for one or more subjects having shock, circulatory shock, septic shock, stroke, hypoxia, ischemia, myocardial ischemia, renal ischemia, reperfusion injury of an organ, an hypoperfusional state, Sickle cell disease, hypotension, hemorrhagic hypotension, cancer, a malignant tumour, diabetes, obesity, hypertension, a systemic autoimmune disease, a systemic sclerosis, a viral encephalopathy, a psychiatric disorder associated with chronic inflammation, depression, schizophrenia, ADHD, autism, aging, a neurodegenerative disease, Alzheimer's disease, dementia, Parkinson's disease, Huntington's Disease, or multiple sclerosis.

9. The system according to claim 1 , wherein the threshold values are determined through receiver operating characteristic (ROC) curve analysis.