Spectroscopic method for quantitatively determining the change of concentration of a light or other radiation absorbing compound in a medium which is interrogated through an intervening medium
First Claim
1. A method of determining a change in concentration of at least one subject substance in one region of a plurality of regions of a medium, the one region being adaptable to both absorb and scatter radiation, substantially all of the change in concentration of the at least one subject substance in the medium occurring in the one region of the plurality of regions, said method comprising:
- introducing into and propagating through the medium first interrogating radiation which is penetrative of the medium;
detecting the first interrogating radiation which has propagated through the medium and determining a total differential pathlength traversed by the first interrogating radiation in the medium;
identifying a plurality of reference substances, each of which possesses a sufficiently distinct specific absorption coefficient to interrogating radiation and a known concentration in each region of the plurality of regions of the medium, the concentration of each of the plurality of reference substances in the one region being different from the concentration of the same reference substance in each of the other regions of the plurality of regions of the medium;
for each reference substance of the plurality of reference substances, introducing into and propagating through the medium second interrogating radiation which is penetrative of the medium, detecting and spectrometrically analyzing the second interrogating radiation which has propagated through the medium, and determining an intensity of a spectral absorption feature of the reference substance;
determining a partial differential pathlength of the one region by simultaneously solving a first linearly independent equation for each reference substance and a second equation, the first and second equations respectively being expressed as follows;
##EQU5## where ai is the intensity of the spectral absorption feature of the reference substance;
Cij is the known concentration of the reference substance in the region j of the plurality of regions;
.di-elect cons.i is the absorption coefficient of the reference substance;
ZT is the total differential pathlength;
Zj is a partial differential pathlength of the radiation in the region j of the plurality of regions; and
n is a total number of regions in the plurality of regions;
introducing into and propagating through the medium third interrogating radiation which is penetrative of the medium;
detecting and spectrometrically analyzing the third interrogating radiation which has propagated through the medium and determining a change in an intensity of a spectral feature of the at least one subject substance; and
obtaining the change in concentration of the at least one subject substance in the one region of the plurality of regions of the medium by solving a third equation, the third equation being expressed as follows;
space="preserve" listing-type="equation">C=A/(.di-elect cons.·
Z)whereC is the change in concentration of the at least one subject substance in the one region of the plurality of regions of the mediumA is the change in the intensity of the spectral feature of the at least one subject substance;
.di-elect cons. is an absorption coefficient of the at least subject substance; and
Z is the partial differential pathlength of the one region.
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Abstract
A spectrometric technique is described for quantitatively determining the change in concentration of a substance which is contained in a medium which both absorbs and scatters spectroscopically interrogated radiation, and in particular to the specific case in which the change in concentration of the substance occurs in one spatially distinct region of the medium. The medium includes a plurality of such regions displaying potentially different absorption and scattering properties to the radiation. Specific applications are disclosed involving the noninvasive determination of changes in concentration of the substances oxyhemoglobin and deoxyhemoglobin and/or changes in the redox state of the substance cytochrome oxidase within the brain or skeletal muscle, and in cases where the brain or skeletal muscle is interrogated by radiation in the near-infrared part of the electromagnetic spectrum through intervening surface tissues, i.e., cortical bone or adipose tissue, where it may be assumed that no changes of concentration of said substances occur within said surface tissues.
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Citations
33 Claims
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1. A method of determining a change in concentration of at least one subject substance in one region of a plurality of regions of a medium, the one region being adaptable to both absorb and scatter radiation, substantially all of the change in concentration of the at least one subject substance in the medium occurring in the one region of the plurality of regions, said method comprising:
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introducing into and propagating through the medium first interrogating radiation which is penetrative of the medium; detecting the first interrogating radiation which has propagated through the medium and determining a total differential pathlength traversed by the first interrogating radiation in the medium; identifying a plurality of reference substances, each of which possesses a sufficiently distinct specific absorption coefficient to interrogating radiation and a known concentration in each region of the plurality of regions of the medium, the concentration of each of the plurality of reference substances in the one region being different from the concentration of the same reference substance in each of the other regions of the plurality of regions of the medium; for each reference substance of the plurality of reference substances, introducing into and propagating through the medium second interrogating radiation which is penetrative of the medium, detecting and spectrometrically analyzing the second interrogating radiation which has propagated through the medium, and determining an intensity of a spectral absorption feature of the reference substance; determining a partial differential pathlength of the one region by simultaneously solving a first linearly independent equation for each reference substance and a second equation, the first and second equations respectively being expressed as follows;
##EQU5## where ai is the intensity of the spectral absorption feature of the reference substance;Cij is the known concentration of the reference substance in the region j of the plurality of regions; .di-elect cons.i is the absorption coefficient of the reference substance; ZT is the total differential pathlength; Zj is a partial differential pathlength of the radiation in the region j of the plurality of regions; and n is a total number of regions in the plurality of regions; introducing into and propagating through the medium third interrogating radiation which is penetrative of the medium; detecting and spectrometrically analyzing the third interrogating radiation which has propagated through the medium and determining a change in an intensity of a spectral feature of the at least one subject substance; and obtaining the change in concentration of the at least one subject substance in the one region of the plurality of regions of the medium by solving a third equation, the third equation being expressed as follows;
space="preserve" listing-type="equation">C=A/(.di-elect cons.·
Z)where C is the change in concentration of the at least one subject substance in the one region of the plurality of regions of the medium A is the change in the intensity of the spectral feature of the at least one subject substance; .di-elect cons. is an absorption coefficient of the at least subject substance; and Z is the partial differential pathlength of the one region. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9)
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10. A method of determining a change in concentration of at least one subject substance in one region of a plurality of regions of a medium, the one region being adaptable to both absorb and scatter radiation, substantially all of the change in concentration of the at least one subject substance in the medium occurring in the one region of the plurality of regions, said method comprising:
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introducing into and propagating through the medium first interrogating radiation which is penetrative of the medium; detecting the first interrogating radiation which has propagated through the medium and determining a total differential pathlength traversed by the first interrogating radiation in the medium; identifying at least one reference substance, the at least one reference substance possessing a sufficiently distinct specific absorption coefficient to the first interrogating radiation and a known concentration in each region of the plurality of regions of the medium; introducing into and propagating through the medium second interrogating radiation which is penetrative of the medium, detecting and spectrometrically analyzing the second interrogating radiation which has propagated through the medium, and determining an intensity of a spectral feature of the at least one reference substance; introducing into and propagating through the medium third interrogating radiation which is penetrative of the medium; detecting and spectrometrically analyzing the third interrogating radiation which has propagated through the medium and determining a change in an intensity of a spectral feature of the at least one subject substance; determining a partial differential pathlength of the one region by simultaneously solving first and second equations, the first and second equations respectively being expressed as follows;
##EQU6## where aref is the intensity of the spectral feature of the at least one reference substance;Cj is the known concentration of the at least one reference substance in region j of the plurality of regions; .di-elect cons.ref is the absorption coefficient of the at least one reference substance; Zj is a partial differential pathlength in the region j; and ZT is the total differential pathlength; n is a total number of regions in the plurality of regions; and obtaining the change in concentration of the at least one subject substance in the one region of the plurality of regions of the medium by solving a third equation, the third equation being expressed as follows;
space="preserve" listing-type="equation">C=A/(.di-elect cons.·
Z)where A is the change in the intensity of the spectral feature of the at least one subject substance; C is the change in concentration of the at least one subject substance in the one region of the plurality of regions of the medium; .di-elect cons. is an absorption coefficient of the at least subject substance; and Z is the partial differential pathlength of the one region. - View Dependent Claims (11, 12, 13, 14, 15, 16, 17, 18, 19)
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20. An apparatus for determining a change in concentration of at least one subject substance in one region of a plurality of regions of a medium, the one region being adaptable to both absorb and scatter radiation, substantially all of the change in concentration of the at least one subject substance in the medium occurring in the one region of the plurality of regions, the plurality of regions each comprising at least one reference substance possessing a distinct specific absorption coefficient to a specific radiation and a known concentration, said apparatus comprising:
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a first light source for introducing into and propagating through the medium first interrogating radiation which is penetrative of the medium; a first photodetecting unit for detecting the first interrogating radiation which has propagated through the medium to measure an intensity of a spectral feature of the at least one subject substance or the at least one reference substance; a second light source for introducing into and propagating through the medium second interrogating radiation which is penetrative of the medium; a second photodetecting unit for detecting the second interrogating radiation which has propagated through the medium to measure a total differential pathlength traversed by the second interrogating radiation in the medium; a first processing unit for receiving the intensity of the spectral feature of the at least one subject substance or at least one reference substance from said first photodetecting unit, for receiving the total differential pathlength from said second photodetecting unit, and for determining the partial differential pathlength of the one region by solving first and second equations, the first and second equations being expressed as follows;
##EQU7## where aref is said intensity of said spectral feature of the at least one reference substance;Cj is the known concentration of the at least one reference substance in region j of the plurality of regions; .di-elect cons.ref is the absorption coefficient of said at least one reference substance; Zj is a partial differential pathlength in the region j; and ZT is the total differential pathlength; n is a total number of regions in the plurality of regions; and a second processing unit for determining the change in concentration of the at least one substance in the one region of the plurality of regions of the medium by a third equation, the third equation being expressed as follows;
space="preserve" listing-type="equation">C=A/(.di-elect cons.·
Z)where A is the change in the intensity of the spectral feature of the at least one subject substance; C is the change in concentration of the at least one subject substance in the one region of the plurality of regions of the medium; .di-elect cons. is an absorption coefficient of the at least subject substance; and Z is the partial differential pathlength of the one region. - View Dependent Claims (21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33)
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Specification