Methods of and apparatus for measuring the concentration of a gaseous component of exhaled gases

Abstract: In the method and apparatus, a patient breathing through a mask (34) receives breathing air from a breathing air system (A). A xenon gas supply (12) selectively supplies xenon or other enhancement gases into the breathing air. During each exhalation portion of a respiratory cycle, a portion of the exhaled gas passes through a narrow tube (40) to a xenon concentration detector (44) and a carbon dioxide concentration detector (46). A carbon dioxide concentration comparing circuit (54) compares the carbon dioxide concentration values with characteristics (56) of carbon dioxide concentration during a end-tidal portion of the exhalation respiratory cycle. Xenon concentrations read during the end-tidal portion of the respiratory cycle (62) are utilized to project a blood absorption curve (64). In the application of the method and apparatus in a medical diagnostic imaging system including a computed tomography (CT) scanner, a plurality of CT images are generated by the CT scanner (B) as the blood xenon concentration increases. A look-up table array (90) preprogrammed in accordance with the Kety equations is addressed by the blood xenon concentration curve and the pixel values of the CT images to generate partition coefficient and flow values.

Description: This invention relates to methods of and apparatus for measuring the concentration of a gaseous component of exhaled gases. The invention finds particular application in the art of medical diagnostic imaging in conjunction with measuring xenon concentration in end-tidal gases. However, it is to be appreciated that the invention will also find application in conjunction with measuring concentrations of other gases. Many medical diagnostic techniques call for a measurement of an absorbed gas in the patient's blood. Arterial blood gas concentration are in equilibrium with lung gases that are in intimate contact with the alveoles. These lung gases, denoted as end-tidal gases, are found at the end of the tide of the exhaled breath. By measuring the concentration of the gas in question in these last bits of the exhaled gas, the concentration of the gas in the blood can be determined. The xenon concentration in the end-tidal gas can be measured by placing a thermoconductivity detector in the exhalation line, as disclosed in US-A-4,622,976 which describes the measurement of xenon concentration, carbon dioxide concentration, or the like. Because the thermoconductivity detector will indicate xenon concentration continuously, it was necessary to determine which reading represents the end-tidal gases. In one end tidal identifying technique, a chamber or reservoir was formed in the exhaled gas line leading from the breathing mask to hold exhaled gas. A mechanical system determined when the patient started to inhale fresh gas from a supply line. The thermoconductivity of the gas retained in the exhale chamber was measured. Such a technique is disclosed in US-A-4,535,780. One of the problems of this technique is that the apparatus is expensive. Another problem is that the mechanical means for determining the changeover point between inhaling and exhaling tends to be relatively unreliable. Another disadvantage is that exhaled gases intermix in the chamber diluting the end-tidal gases with earlier exhaled gases. Another technique for determining the end-tidal gas was to monitor the xenon concentration continuously and assume that the xenon concentration minima were attributable to the end-tidal gases. However, when the patient began breathing rapidly, the minimum xenon concentrations did not correspond to end-tidal gas. Further, after the first few patient breaths, the magnitudes of the minima increased sufficiently close to the breathing gas xenon concentration that they were difficult to identify. Commonly, the end-tidal gas minimum values became substantially indistinguishable from the exhaled xenon concentration in the rest of the exhaled gas after the first minute of a five to seven minute xenon protocol. It is an object of the present invention to provide a method of and apparatus for measuring the concentration of a gaseous component of exhaled gases wherein the above problems are overcome. According to a first aspect of the present invention there is provided a method of measuring the concentration of a preselected gaseous component other than carbon dioxide of end-tidal gases from a patient, the method comprising: (a) providing a patient with breathing gases; and (b) measuring carbon dioxide concentrations in exhaled gas during at least exhalation portions of a respiratory cycle, characterised in that the method comprises: (c) monitoring carbon dioxide concentration in exhaled gases for a preselected criteria indicative of a decrease from a respiratory cycle carbon dioxide concentration maximum, which decrease is indicative of when end-tidal gases are exhaled; and (d) measuring the concentration of the preselected gaseous component in direct response to the monitoring of the preselected criteria indicating the end-tidal gas exhalation point of the respiratory cycle such that the concentration of the preselected gaseous component in the end-tidal gases is measured. According to a second aspect of the present invention there is provided an apparatus for measuring the concentration of an exhancement gas of end-tidal gases comprising: a breathing mask means through which a patient inhales breathing gas and exhales exhalation gases; a breathing gas supply means for supplying breathing gas to the mask means; an enhancement gas introduction means for selectively introducing an enhancement gas into the breathing gas; a carbon dioxide analyzing means for measuring carbon dioxide concentration, the carbon dioxide analyzing means being operatively connected with the mask means to receive at least exhalation gases therefrom; and an enhancement gas analyzing means for measuring enhancement gas concentration, the enhancement gas analyzing means being operatively connected with the mask means to receive at least exhalation gases therefrom, characterised in that said apparatus comprises: a carbon dioxide concentration comparing means for comparing the measured carbon dioxide concentration with characteristics of a decrease from a carbon dioxide concentration maximum, said decrease being indicative of end-tidal gases; and end-tidal enhancement gas concentration record means operatively connected with the enhancement gas analyzing means and the comparing means for providing a record of end-tidal enhancement gas concentrations, said enhancement gas analyzing means, said comparing means and said record means being directly responsive to said carbon dioxide concentration decrease. US-A-3 890 959 discloses a method of determining cerebral blood flow in a discrete region of a patient's brain wherein the radioactive gas xenon¹³³ is inhaled by the patient over a data collection period during which the concentration of the gas in the blood is increased. The local cerebral blood flow is determined from determinations of arterial blood and tissue radiation concentrations made during the data collection period. The arterial blood radiation concentration is determined by measuring the radiation concentration of the gas in the last part of an exhalation. The tissue radiation concentration is determined from detected brain radiation emissions. The concentration of carbon dioxide and oxygen in the exhaled gases is monitored so that such can be taken into consideration in the determination of cerebral blood flow. EP-A-269 280 discloses a method of determining the partition coefficient and fluid flow rate of each of a plurality of sub-regions of a region of interest of a patient. Xenon gas is inhaled by the patient. At the end of each respiratory cycle the concentration of xenon in the patient's blood is determined by measuring the xenon concentration in the breath exhaled at the end of the respiratory cycle. A curve indicative of the absorption of xenon in the patient's blood is derived using the xenon concentration measurements. The absorption curve is used to select one of a plurality of look-up tables. During the period over which the xenon concentration measurements are made a plurality of images of the region of interest of the patient are generated. Xenon concentration values from pixels of each image corresponding the sub-regions of the region of interest are utilised to address the selected look-up table to retrieve precalculated partition coefficient and fluid flow rate values. One method of and apparatus for measuring the concentration of a gaseous component of exhaled gases will now be described, by way of example, with reference to the accompanying drawings, in which: Figures 1A and 1B together constitute a diagrammatic illustration of a computed tomography (CT) scanner in combination with a blood xenon gas concentration measuring apparatus in accordance with the present invention; Figure 2 illustrates typical CO₂ concentration vs. time for a single breathing cycle with a trigger point for a xenon gas concentration reading indicated; and Figure 3 illustrates exhaled gas xenon concentration vs. time over multiple breathing cycles following initiation of xenon delivery to a patient. Referring to Figures 1A and 1B, a gas supply means A supplies breathing gas to a medical diagnostic CT scanner B. A processing system or means C processes data from the CT scanner and the breathing gas supply system to produce images and other diagnostic information. The breathing gas supply means A includes a breathing air or oxygen supply 10 and a xenon gas supply 12. Preferably, the xenon gas supply means provides a mixture of 80% xenon and 20% oxygen to guarantee that the patient receives at least 20% oxygen even during a malfunction. A first blower 14 supplies recirculated breathing gases along with added xenon for mixture with additional oxygen from the oxygen supply means 10. Most of the mixture passes to a breathing bag 16 with the exception of a small fraction that is pumped by a pump 18 through a xenon detector 20. The xenon detector 20 determines the concentration of xenon in the gaseous breathing mixture and controls a xenon control valve 22 to maintain the xenon concentration substantially constant. Typically, the xenon concentration is selected to be about 30%. A carbon dioxide absorber 30 removes carbon dioxide from the breathing gases that are supplied to an outlet port check valve 32. When the patient inhales through a breathing mask 34, the patient draws the breathing gases through the outlet check valve 32. When the patient exhales, the exhaled gases are returned through an exhaust gas path or tube 36 and a return check valve 38. The exhaust gases passing through the return check valve 38 are returned to the blower 14 and recirculated through the system. The exhaust gas analysis is performed periodically, e.g. every 0.25 seconds, on gases passing through a small diameter line 40 extending parallel to the exhaust gas path to reduce the dilution effects. In the much larger diameter exhaust gas path, the exhaust gases tend to tumble and mix which dilutes end-tidal gases with other exhaust gases. The narrow diameter line inhibits the swirling and countercurrent flow patterns that tend to intermix the gases and enables a more nearly instantaneous reading of the gases to be made. The gases drawn through the small diameter line by a pump or blower 42 are analyzed by a xenon detector 44 and a carbon dioxide detector 46. The xenon detector measures the xenon concentration of the exhaled gases and the carbon dioxide detector measures the carbon dioxide concentration of the exhaled gases. With particular reference to FIGURE 2, as the patient starts to exhale, the concentration of carbon dioxide gas increases generally exponentially and logarithmically to a plateau 50. The carbon dioxide concentration remains relatively constant through a significant portion of the exhalation portion of the respiratory cycle. Just after the end-tidal gases are exhaled, the patient inhales CO₂ free gas through check valve 32 and the CO₂ concentration drops rapidly 52. A carbon dioxide level comparing means 54 compares the carbon dioxide level with preselected characteristics, specifically, a preselected drop 56 from the plateau 50. In response to the preselected carbon dioxide concentration drop, the comparing means 54 triggers the selection of a previously taken end-tidal xenon concentration reading by the xenon detector 11 a fixed, preselected time earlier 58, e.g. a 0.5 sec. With continuing reference to FIGURE 2, when the patient is panting rapidly, end-tidal gas is not reliably discharged at the end of the exhalation cycle. Accordingly, it may be advantageous not to sample the xenon concentration detector 44 in a panting respiratory cycle. However, the partial pressure of CO₂ during panting does not rise to the plateau concentration 50. Hence, the measured drop 56 from the plateau does not occur and the sampling of blood xenon concentration is not triggered. With reference to FIGURE 3, in each respiratory cycle, the concentration of xenon gas peaks 60 at the xenon concentration in the breathing air. In an exhale cycle portion in which the patient's lungs are fully evacuated such that end-tidal gas is expelled, the xenon concentration reaches a minimum value 62 at the end-tidal portion of each breath. The blood xenon concentration and the corresponding end-tidal xenon concentration increase along a blood xenon absorption curve 64. However, with several respiratory cycles, the concentration of xenon in the patient's blood approaches the concentration of xenon in the breathing gas. After a half dozen or a dozen breaths, the differences in height between the xenon concentration peaks and valleys becomes so small that the random noise fluctuations cannot reliably be differentiated from the true xenon concentration minimum. The end-tidal xenon concentrations 62 are conveyed to a blood xenon concentration curve memory means 66. A blood xenon concentration display means 68 is connected with the blood xenon concentration memory means to provide the physician with a continuous indication of blood xenon concentrations. The output of this memory means may also be displayed as a graph of xenon or blood xenon concentration vs. time. The CT medical diagnostic scanner B of the preferred embodiment includes an x-ray source 70 for projecting a fan beam of radiation through an image region 72. The patient is supported on a patient table 74 with tissue to be examined, typically the head or brain tissue, disposed in the image region. An array of x-ray detectors 76 receives the fan beam of radiation from the x-ray source including the radiation which has traversed the portion of the patient from the image region. An image reconstruction means 78 reconstructs CT image representations from the x-ray data collected by the radiation detectors as the radiation source is rotated about the region of interest. The processing circuitry C includes a reference image means 80 for storing an image representation of the tissue of interest of the patient without xenon gas absorbed in the patient's blood. As the patient starts inhaling xenon containing gas and the patient's blood xenon concentration increases, several additional CT images are taken, each being stored temporarily in an image memory 82. Each image can be considered as the sum of a patient tissue image and a xenon image. A subtraction means 84 subtracts the reference image from each subsequent image to produce a difference image indicative of xenon concentrations. More specifically, each difference image includes an array of pixel values, each pixel value corresponding to a preselected volume cell (voxel) or subregion of the portion of the patient disposed in the image region. A partition coefficient and blood flow rate determining means 90 utilizes known relationships, such as the relationships set forth in the Kety equation, to determine a partition coefficient and blood flow rate for each image voxel. These calculations are based on the blood xenon concentration curve stored in the blood xenon concentration in memory 66 and the increase in xenon concentration in subsequent corresponding pixels of the difference image. In the preferred embodiment, the partition coefficient and blood flow values are determined on a pixel by pixel basis from a look-up table means 92. The look-up table means is addressed by the relative times t₁, t₂, t n of the CT scans, corresponding pixel values of a plurality of CT scans as stored in difference scan memories 94, and by blood xenon concentration curve parameters. More specifically, a blood xenon concentration parameter determining means 96 determines conformity of the actual blood xenon concentration curve to preselected concentration curve characteristics, such as saturation concentration, slope, exponential time constants, and the like. In one embodiment, the look-up table means includes an array of look-up tables. The blood xenon concentration curve characteristics determine which look-up table(s) conforms best to the patient blood xenon concentration curve. The selected look-up table(s) is then addressed by the corresponding pixel values from each image in the difference image memory means 94. The relative times at which the images were collected in the preferred embodiment are preset. However, if the times are to be variable, these times are also utilized to select among a larger plurality of look-up tables. Digital look-up tables can only be addressed by preselected addresses. The actual pixel values may fall between these addresses. Each of the two closest addresses are accessed and an interpolating means 98 performs a weighted interpolation of the retrieved partition coefficient and flow values. Analogously, the absorption curve characteristics may fall between two or more look-up tables of the array. An interpolation means 98 performs a weighted interpretation of the partition coefficient and flow values retrieved by the closest difference image pixel values and the closest time or xenon curve addressed look-up tables. The procedure is repeated for each pixel of the images to build a partition coefficient image for storage in a partition coefficient image memory 100 and a flow image for storage in a flow image memory means 102. The partition coefficient and flow images may be selectively displayed on a display means 96. Optionally, other parameters may also be displayed, such as a confidence or fit value which is indicative of how closely each partition coefficient and flow value conforms with the normal statistical deviation from the actual value, i.e. reliability or confidence that one may have in each pixel value.

Claims: A method of measuring the concentration of a preselected gaseous component other than carbon dioxide of end-tidal gases from a patient, the method comprising: (a) providing a patient with breathing gases; and (b) measuring carbon dioxide concentrations in exhaled gas during at least exhalation portions of a respiratory cycle, characterised in that the method comprises: (c) monitoring carbon dioxide concentration in exhaled gases for preselected criteria indicative of a decrease (56) from a respiratory cycle carbon dioxide concentration maximum (50), which decrease (56) is indicative of when end-tidal gases are exhaled; and (d) measuring the concentration of the preselected gaseous component in direct response to the monitoring of the preselected criteria indicating the end-tidal gas exhalation point of the respiratory cycle such that the concentration of the preselected gaseous component in the end-tidal gases is measured. A method according to Claim 1 further including repeating the carbon dioxide measuring, comparing, and preselected gaseous component measuring steps over each of a plurality of respiratory cycles as a concentration of the preselected gaseous component in a patient's blood increases to generate points (62) of a curve (64) indicative of changes in the preselected gaseous component in the patient's blood over time. A method according to Claim 1 wherein during an exhalation portion of each respiratory cycle, the monitored carbon dioxide concentration increases to a plateau (50) concentration and decreases rapidly (52) from the plateau (50) at the end-tidal portion of the respiratory cycle and wherein the comparing step includes determining a preselected fall-off (56) from the plateau (50) and selecting a measurement of the preselected gaseous component taken a preselected duration prior to the occurrence of the preselected fall-off (56). A method according to Claim 1 or Claim 2 or Claim 3 wherein the preselected gaseous component is xenon. A method according to Claim 4 further including storing each measured end-tidal xenon concentration and determining characteristics of at least one curve (64) which describes variations in the measured xenon concentration with time. A method according to Claim 1 further comprising: repeating steps (b) to (d) over a plurality of respiratory cycles, as the concentration of the preselected gaseous component in the patient's blood increases with time, to generate a blood preselected gaseous component concentration curve (64); also over the plurality of respiratory cycles, generating a plurality of diagnostic scanner images of the patient in which the preselected gaseous component concentration changes from image to image, each diagnostic image including a plurality of pixel values; and, calculating partition coefficient and blood flow values of the patient from the blood preselected gaseous component concentration curve (64) and at least selected corresponding pixel values of the series of images. A method according to Claim 6 wherein during an exhalation portion of each respiratory cycle, the measured carbon dioxide concentration increases to a plateau (50) and decreases rapidly (52) from the plateau (50) at the end-tidal portion of the respiratory cycle and wherein the monitoring step includes determining a preselected fall-off (56) from the plateau (50), the occurrence of the preselelected fall-off (56) triggering the preselected gaseous component measuring. A method according to Claim 6 or Claim 7 wherein the preselected gaseous component is xenon. A method according to Claim 8 further including storing each measured end-tidal xenon concentration and determining characteristics of at least one curve (64) which describes variations in the measured xenon concentration with time. An apparatus for measuring the concentration of an enhancement gas of end-tidal gases comprising: a breathing mask means (34) through which a patient inhales breathing gas and exhales exhalation gases; a breathing gas supply means (A) for supplying breathing gas to the mask means (34); an enchancement gas introduction means (12) for selectively introducing an enhancement gas into the breathing gas; a carbon dioxide analyzing means (46) for measuring carbon dioxide concentration, the carbon dioxide analyzing means (46) being operatively connected with the mask means (34) to receive at least exhalation gases therefrom; and an enhancement gas analyzing means (44) for measuring enhancement gas concentration, the enhancement gas analyzing means (44) being operatively connected with the mask means (34) to receive at least exhalation gases therefrom, characterised in that said apparatus comprises: a carbon dioxide concentration comparing means (54) for comparing the measured carbon dioxide concentration with characteristics of a decrease (56) from a carbon dioxide concentration maximum (50), said decrease (56) being indicative of end-tidal gases; and end-tidal enhancement gas concentration record means (66) operatively connected with the enhancement gas analyzing means (44) and the comparing means (54) for providing a record of end-tidal enhancement gas concentrations, said enhancement gas analyzing means (44), said comparing means (54) and said record means (66) being directly responsive to said carbon dioxide concentration decrease (56). An apparatus according to Claim 10 wherein the breathing gas supply means (A) receives the exhalation gases from the breathing mask (34) through an exhalation gas outlet port (36, 38) and further including gas conditioning means (20, 30) for conditioning the exhalation gases before being supplied to the breathing mask (34) with the breathing gases. An apparatus according to Claim 11 further including a further breathing gas return passage (40) extending from the breathing mask (34) to the breathing gas supply means (A), the enhancement gas (44) and carbon dioxide (46) analyzing means being connected along the return passage (40), the return passage (40) being smaller in diameter than the exhalation outlet port (36, 38), whereby mixing and dilution of gases monitored by the carbon dioxide (46) and enhancement gas (44) analyzing means is inhibited. An apparatus according to any one of Claims 10 to 12 wherein the enhancement gas is xenon. A medical diagnostic imaging apparatus for taking a plurality of medical diagnostic images through a region of interest of a patient including an apparatus for measuring the concentration of an enhancement gas of end-tidal gases according to any one of Claims 10 to 13 with the patient breathing through said breathing mask (34) as a concentration of the enhancement gas increases. A medical diagnostic imaging apparatus comprising: an apparatus for measuring the concentration of an enhancement gas of end-tidal gases according to any one of Claims 10 to 13; a computed tomography scanner means (B) for generating a plurality of diagnostic images through a region of interest of a patient breathing through the breathing mask (34); and a partition coefficient and blood flow rate determining means (90) for determining partition coefficient and blood flow rates for subregions of the region of interest from the computed tomography images and the end-tidal xenon concentrations.

Inventors: LINDSTROM WALTER W, LINDSTROM, WALTER W.
Applicants: PICKER INT INC, PICKER INTERNATIONAL, INC.
Application year: 1989
Main classification: A61B5
IPC codes: A61B5, A61B6, G01N33