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Publication numberUS3769966 A
Publication typeGrant
Publication dateNov 6, 1973
Filing dateMar 22, 1971
Priority dateMar 22, 1971
Publication numberUS 3769966 A, US 3769966A, US-A-3769966, US3769966 A, US3769966A
InventorsJ Barker, M Youdin
Original AssigneeYork University
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Apparatus for determining local cerebral blood flow
US 3769966 A
Abstract
An apparatus for determining local cerebral blood flow in a discrete radiation emission detection zone of a patient's brain. The brain is subdivided into a plurality of detection zones, such as 144, by means of a headgear apparatus which defines these detection zones by means of a multiplanar array of an equal number of detectors, each detector having an associated collimator to limit the field of view of the detector. A radioactive gas such as Xe133, is inhaled by the patient, such as in a closed inhalation-exhalation breathing system, over a predetermined data collection period during which the concentration of the gas in the blood is periodically increased. Determinations of arterial blood radiation concentration and tissue radiation concentration are made during this period, and the local cerebral blood flow is subsequently determined from these determinations. The arterial blood radiation concentration is preferably determined by determining the radiation concentration of the gas in the last part of an exhalation, while the tissue radiation concentration is preferably determined from the radiation emissions quantified by the detector array.
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Youdin et al.

[ 1 Nov. 6, 1973 [54] APPARATUS FOR DETERMINING LOCAL CEREBRAL. BLOOD FLOW [75] Inventors: Myron Youdin, Flushing; June N.

Barker, New York, both of N.Y.

[73] Assignee: New York University, New York,

221 Filed: Mar.22,197l

[21] Appl.No.: 126,770

[52] U.S. Cl. 128/2.05 F, 128/2 A, 250/71.5 S [51] Int. Cl. A611) 5/02, A6lb 6/00 [58] Field of Search 128/2.05 F, 2.05 R, 128/2.05 A, 2.05 V, 2 A, 2 G, 2 R; 250/715 S [56] References Cited UNITED STATES PATENTS 3,658,054 4/1972 lberall l28/2.05 R 3,418,471 12/1968 Gydesen 128/2 A X 3,268,728 8/1966 Stoddart et al. 128/2 A X 3,591,806 7/1971 Brill et al 250/71.5 S 3,432,660 3/1969 Anger 250/71.5 S 3,405,233 10/1968 Anger 250/715 S X OTHER PUBLICATIONS Reid, W. B. et al., lnt. Journ. of Applied Radiation & Isotopes, 1958, Vol. 3, pp.1-7.

Miraldi, F. et al., Radiology, Vol. 94, March 1970, pp. 513-520.

Hindel, R. et al., Nucleonics, 1947, March, Vol. 25,

No.3, pp- 52-57. Bender, M. A. et al., Int. .lourn. of Applied Radiation & Isotopes, 1959, V01. 4, pp. 154-161 Primary Examiner-Kyle L. Howell Attorney-Hubbell, Cohen & S tiefel [57] ABSTRACT An apparatus for determining local cerebral blood flow in a discrete radiation emission detection zone of a patients brain. The brain is subdivided into a plurality of detection zones, such as 144, by means of a headgear apparatus which defines these detection zones by means of a multiplanar array of an equal number of detectors, each detector having an associated collimator to limit the field of view of the detector. A radioactive gas such as Xe is inhaled by the patient, such as in a closed inhalation-exhalation breathing system, over a predetermined data collection period during which the concentration of the gas in the blood is periodically increased. Determinations of arterial blood radiation concentration and tissue radiation concentration are made during this period, and the local cerebral blood flow is subsequently determined from these determinations. The arterial blood' radiation concentration is preferably determined by determining the radiation concentration of the gas in the last part of an exhalation, while the tissue radiation concentration is preferably determined from the radiation emissions quantified by the detector array.

37 Claims, 10 Drawing Figures TO RADIATION DETECTION T0 RADIATION DETECTION SIGNAL PROCESSING CIRCUIT 57 GLABELLAR-SELLAR PLANE TO R'ADIATION DETECTION SIGNAL PROCESS" ING ClRCUlT(67) PAIENIEUHUV 6I9I5 3.769.666 SHEET 1 UF 4 I, RADIATION DETECTION "67 A SIGNAL PROCESSING v CIRCUIT RADIATION DETECTION /74 SIGNAL PROCESSING CIRCUIT TO EXHAUST HOOD I m" 7Z HEADGEAR I fi 7 APPARATUS 02 GAS ANALYZER I 80 EXHAUST END'TIDAL HOOD M r SAMPLER \62 N-.. t 6-O-':MINICOMPUTERI -2 BUFFER I I I 3:- TO EXHAUST HOOD I I 1 J I GENERAL INHALATION 1 GAS PURI- L XENON' GAS PURPOSE CHAMBER FICATION INJECTION COMPUTER UNIT SYSTEM k pw I I LOCAL CEREBRAL BLOOD FLOW DATA OUTPUT I 2 I To RADIATION I DETECTION x '0 SIGNAL PROCESS- I G CIRCUIT (67) TO RADIATION DETECTION SIGNAL PROCESSING INvENTORS EE MYRON YOUDIN JUNE N. BARKER THEOBALD REICH ATTORNEYS- PATENTEDIIIIII. 6 I975 3.769.966 SHEET 3 [.F 4

4 J/ MID-SAGGITAL PLANE GLABELLAR- SELLAR PLAN E GLABELLA OCCIPITAL BONE MANDIBL HIGH VOLTAGE POWER SUPPLY- r THALL|UM- TEN STAGE I73 ACTIVATED PHOTOMULTI' SODIUM DLIER WITH SQ IXQ W IODIDE INDIVIDUAL CRYSTAL VOLTAGE DETECTOR DIVIDING ASSEMBLY NETWORK 1Z8 I8(0 '3 VARIABLE SUMMING PULSE GATE RRE- HEIGHT AND AMPLIFIER DETECTOR UL E STRETCI-IER THRESHOLD TO LEVEL MINICOMPUTER CONTROL BDEFERIOD) NVENTORS MYRON YOUDIN JUNE N. BARKER THEOBALD REICH BY '1' I ,7

ATTORN EYS.

PATENTED UV 6 I973 SHEET C PLANE Z C PLANE CLT COT CRT f B PLANE BLT BOT BRT FIG. 7

4 2 6 6 6 2 O 6 8 unm 6 6 6 6 6 6 6 2 2 2 W Z w H 2 66 6 2 6 6 6m 2 z m z 7. Z 8 4 6 a 6 6 6 z z z u 7 3 9 Mn 2 6 5 5 LL 2 Z Z 6 6 6 Z 6 6 6 M 9'5 I 7 m 6 1 6 Z Z Z Z Z Z Z 6 a 0 f MW E W M E f 2 F W. A N .E rWL H A A D. C L E A F D. N L T 0 6 B A P .E R SO L B N E A R P M N O .O B D. T 0C 0 A U L O O R X U B U C A J. O R B C U A w 1 6 A 8 w 8 w C W A U L A A PLANE 1 DIRECTION VIEW BACKGROUND OF INVENTION 1. Field of the Invention The present invention relates to an apparatus for determining local cerebral blood flow.

2. Description of the Prior Art The ability to measure cerebral blood flow within the human brain is an important medical diagnostic tool as variations in a normal flow can indicate actual, probable, or impending cerebral medical deficiencies, such as possible stroke or brain trauma. Since the human brain is the vital command center for the body, it is important that any possible malfunctions which effect the brain be discovered as rapidly as possible. Prior art diagnostic techniques for determining total or regional cerebral blood flow have involved the use of a radioactive diagnostic agent dissolved in the blood. However, such prior art techniques have only been able to determine a total or regional blood flow,- which is a mean rate of blood flow through a region, such region normally being defined by a large cone of tissue. One such prior art device which might provide a means of estimating a qualitative indication of regional blood flow utilizes a uniplanar detector array. However, such a device has a poor energy and spatial resolution and cannot detect small blockages of blood flow within the brain; even large reductions in local flow are not easily discernible.

Other prior art techniques of this type utilize a multition, and provide only generalized regional mean rate blood flow data as opposed to localized, or direct discrete measurements of cerebral blood flow in a defined discrete localized portion of the brain, these techniques have not gained wide acceptance for other than cases in which such generalized data is acceptable.

These disadvantages of the prior art are overcome by the present invention.

SUMMARY OF THE INVENTION A system is provided for determining local cerebral blood flow in a discrete defined radiation emission detection zone of a patients brain. The brain is subdivided into a plurality of detection zones, which are preferably identical, by means of a headgear apparatus which defines these detection zones. The headgear apparatus ispreferably aligned on the patients head with respect to three mutually perpendicular reference planes; namely, the glabellar-sellar plane as a reproducible basal plane, the mid-saggital plane as a zero reference plane, and a reference plane tangent at the forehead. This headgear apparatus preferably includes an array of 144 or more radiation emission detectors arranged in a multiplanar array about the brain so as to provide an equal number of defined viewing or detection zones in the brain. The detectors, such as semiconductors, thallium-activated sodium iodide crystals, or

proportional counter tubes each have associated there- 9 with a collimator which has a lumen of predetermined configuration, preferably square, in order to present a plicity of probes in a random array to view a large;

randomly located cone shaped region in the brain for determining a mean rate of cerebral blood flow in this single random location. However, no provision is made for compensating for the effects of the radiation which emanates from the surrounding areas of the brain during this measurement. In addition, if there is a variation in cerebral blood flow from that of a previous measurement, there is no way of pinpointing the exact location predetermined portion of the plurality of detection (zones to the associated detector.

tration of this gas in the blood is increased due to periof the flow reduction other than that there is one in the overall region.

Some of these prior art techniques have utilized the inhalation or intra arterial injection of a radioisotopic gas as'the diagnostic agent in conjunction with a regional blood flow measurement. However, the prior art inhalation technique requires the patient to breathe the radioactive gas until equilibration and subsequent elimination occurs. The equilibration period is normally seven to ten minutes using a closed breathing circuit of a device such as a basal metabolism or anesthesia machine followed by a washout period of greater than 20 minutes. The washout of the radioisotopic gas is then measured with an external radiation detector directed toward the region. However, once again, only a mean rate of blood flow, or regional blood flow, through the region, or cone of tissue if that is the defined region, is provided.

The technique wherein the radioactive diagnostic agent is injected into the internal carotid artery is considerably more dangerous to the patient and cannot be used except under serious medical indications for the test. While this latter technique obviates the contribution of extracerebral radioisotope, the time limitations for measurement are equally long and the method still only provides a regional blood flow measurement. Since these prior art techniques are slow, of low resoluodic injection of a specified additional amount of the 40' gas into the breathing system. Measurements are made of the arterial blood radioisotope concentration, such as by a means separate from the 144 detectors, which determines the radioisotope concentration of the gas in the last part of an exhalation of the patient during the data collection period. A determination is also preferably made of the quantity of radioisotope concentration associated with each discrete detection zone based upon measurements of resultant radiation emission by the detector array and a predetermined relationship between the plurality of detection zones which provides a plurality of solvable simultaneous equations relating the contributions of various detection zones in the plurality to each quantified resultant radiation emission.

These equations are solved to provide the tissue radioisotope concentration for each discrete detection zone. The local cerebral blood flow for a discrete detection zone is provided from the tissue and arterial radioisotope concentrations for the zone, which concentrations are preferably repeatedly determined at 10 second intervals during the 1 minute data collection period, in accordance with another predetermined relationship between these factors and cerebral blood flow, such as by applying the well known Fick-Kety expression.

BRIEF DESCRIPTION OF DRAWINGS FIG. 1 is a diagrammatic illustration of the preferred system of the present invention;

FIGS. 2A and 2B are diagrammatic illustrations of the headgear apparatus portion of the system of the present invention;

FIG. 3 is a block diagram of the radiation detection signal processing circuitry portion for one detection channel of the headgear apparatus;

FIG. 4 is a graphical illustration of isotopic concentration utilized in describing the method of the present invention;

FIG. 5 is a diagrammatic illustration of the human skull from the side utilized in explaining the preferred orientation of the headgear apparatus of the present invention;

FIG. 6 is a block diagram partially in schematic, similar to FIG. 3, of an alternative embodiment of the signal processing circuitry for one detection channel;

FIG. 7A is an exploded perspective view of a mathematical model utilized in describing the present invention;

FIG. 7B is an exploded perspective view of a mathematical model, similar to FIG. 7A, utilized in describing the present invention; and

FIG. 8 is a diagrammatic illustration utilized in explaining the preferred field of view of a single detector.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS General Description Referring now to the drawings in detail and especially to FIG. 1 thereof, the system of the present invention, generally referred to by reference numeral 10 is shown. System 10 is for determining local cerebral blood flow, which is the blood flow within a discrete preselected portion of a patients brain. It should be understood that FIG. I is merely a diagrammatic illustration of the system 10 for purposes of explanation, and is not meant to indicate the critical dimensions of the system, such as a preferred requirement of minimum dead space in the closed breathing system. The system 10 of the present invention preferably includes a breathing mask 12 which is preferably removably mounted on the face of the patient during the performance of the local cerebral blood flow determination so as to isolate the breathing passages of the patient from the surrounding environment and provide a closed inhalationexhalation breathing system, which will be described in greater detail hereinafter. The mask 12, which is preferably a conventional breathing mask, is preferably formed of a material which is pliable enough to provide a comfortable but close fit on the face of the patient in the mounted position so as to reduce apprehension during a data collection period which is associated with the local cerebral blood flow determination.

The mask 12 includes a conventional type of mouthpiece breathing port 14 which is provided with an inlet or inhalation conduit 16 and an outlet or exhalation conduit 18. Conduits 16 and 18, respectively, supply the substance or gas to be inhaled to the mask 12 and remove the substance exhaled from the mask 12. Preferably, the inhalation conduit 16 and the exhalation conduit 18 each include a conventional demand valve 20 and 22, respectively, disposed within the conduit flow path so as to close off the respective associated conduits 16 or 18 unless the patient is either demanding the next breath (inhalation) or exhaling his previous breath (exhalation).

Inhalation demand valve 20 is preferably interposed in inhalation conduit 16 between the mouthpiece breathing port 14 and a small gas reservoir radiationshieded spirometer or inhalation chamber 28 from which the substance or gas to be breathed by the patient is provided. Exhalation demand valve 22 is preferably interposed in exhalation conduit 18 between the mouthpiece breathing port 14 and an exhalation chamber 30 which is preferably equal in volume to the inhalation chamber 28. The inhalation chamber 28 and the exhalation chamber 30 are preferably connected together in the closed inhalation-exhalation breathing system through a conventional gas purification unit 32 having an inlet conduit 34 connected to the exhalation chamber 30 outlet, and an outlet conduit 36 connected to the inhalation chamber 28 inlet. The gas purification unit 32 operates in a conventional manner to remove excess carbon dioxide from the breathing system, add oxygen to the breathing system, and filter the air passing therethrough. The gas purification unit 32 is preferably operated responsive to the beginning of a breath by the patient in a manner to be described in greater detail hereinafter.

In the preferred embodiment of the present invention, as will be explained in greater detail hereinafter, in order to introduce a diagnostic agent into the cerebral blood, the patient breathes a radioactive gas which is preferably the radioisotopic gas Xenon which is the preferred diagnostic agent. As will also be explained in greater detail hereinafter, a high concentration of this gas is desirable during the performance of the local cerebral blood flow determination and, most preferably, this concentration increases during the quantification of the data necessary for the local cerebral blood flow determination. In order to accomplish this desired condition, a radioactive gas injection system 40 is connected through a valve 42 via a conduit 44 to the inlet of the exhalation chamber 30 for injecting a predetermined quantity of the radioactive Xenon gas into the exhalation chamber 30 each time valve 42 is opened. In addition, gas injector 40 also preferably includes a conduit 48 which is connected to the inlet of the inhalation chamber 28 via another valve 50 which is preferably only opened at the end of the patients next breath after the beginning of the data collection period so as to also inject this predetermined quantity of radioactive gas into inhalation chamber 28 as well as exhalation chamber 30 at this time. Preferably, valve 50 remains closed throughout the remainder of the data collection period and gas injector 40 only injects the radioactive gas into the exhalation chamber 30 where it is mixed, such as by an impeller (not shown), with the gas contained therein and passed through the gas purification unit 32 to the inlet of the inhalation chamber 28. If desired, other variations of this system may be utilized, such as by locating the purifier 32 between valve 22 and chamber 30, so that fresh radioisotope need not pass through purifier 32.

Preferably, for purposes of gas evacuation at the completion of the data collection period, another valve 52 is interposed in inhalation conduit 16 between demand valve 20 and the mouthpiece breathing port 14, and another valve 54 is interposed in conduit 18 between the exhalation demand valve 22 and the mouthpiece breathing port 14. Vavles 52 and 54 are each, respectively, connected to conduits 56 and 58. Conduit 56 is preferably open to the surrounding environment to provide room air therethrough, and conduit 58 preferably opens to an exhaust hood (not shown) for evacuating the gas from the system 10. Valve 52 preferably blocks conduit 56 during the data collection period while leaving conduit 16 open to demand valve and, similarly, valve 54 blocks conduit 58 during this period while leaving conduit 18 open to demand valve 22. As will be explained in greater detail hereinafter, at the conclusion of this period, valves 52 and 54 are operated, such as electrically via a signal from a conventional programmable minicomputer 60, such as a Honeywell 316, which may be utilized to coordinate the data collection and the resultant cerebral blood flow determination. The actuation of valves 52 and 54 changes them from their normal mode to the gas evacuation mode wherein conduits l6 and 18 are closed off to demand valves 20 and 22 and inhalation chamber 28 and exhalation chamber 30, respectively, and open to conduits 56 and 58, respectively.

In this manner, a closed inhalation-exhalation breathing system is provided during the data collection period for the local cerebral blood flow determination from inhalation chamber 28, via inhalation conduit 16 to mouthpiece breathing port 14 of the mask 12, via mouthpiece breathing port 14 to exhalation conduit 18, via exhalation conduit 18 to the exhalation chamber 30, via exhalation chamber 30 to the gas purification unit 32, and via gas purification unit 32 back to the inhalation chamber 28; with the radioactive gas being injected periodically during this period into the closed inhalation-exhalation breathing system from gas injector 40.

The portion of the system utilized in making a quantitative local cerebral blood flow determination will now be described. As will be explained in greater detail hereinafter, a conventional general purpose computer 61, such as an IBM 360, may preferably be utilized in conjunction with, or in place of, the minicomputer 60 in order to process the data collected during the data collection period, if desired, in order to enhance the speed in which results are obtained. However, if desired, any other conventional method of processing such data may be utilized. For purposes of illustration, it shall be assumed that the general purpose computer 61 is utilized in conjunction with minicomputer 60 to process this data.

A conventional end-tidal sampler 62, such as a Falk- Kupferman end-tidal sampler, preferably has an inlet which is connected to exhalation conduit 18 for sampling the alveolar or end-tidal gas concentrations at the end of each breath, and an outlet which is connected to a radioactive gas analyzer 63, to be described in greater detail hereinafter, which preferably includes a coiled passageway 64 of known volume and a radiation emission detector assembly 65. As will be described in greater detail hereinafter, the end-tidal sampler 62 contains a relay mechanism (not shown) which is normally actuated at the beginning and end of each breath in a conventional manner. This relay is preferably utilized to activate the gas injector 40 at the end of each breath and the gas purification unit 32 at the beginning of each breath in a manner to be described in greater detail hereinafter.

The end-tidal samples passed through end-tidal sampler 62 are preferably drawn through the coiled passageway 64, or another type of sampling chamber if desired, of analyzer 63, which is preferably shielded against external radiation. For efficiency and convenience, the coiled passageway 64 and detector assembly 65 are preferably located near the patients head adjacent a headgear apparatus 66 which is mounted in a predetermined position on the patients head preferably by means of a universal mounting means 68. A more detailed description of headgear apparatus 66 will be presented hereinafter in connection with FIGS. 2A and 2B.

Suffice it to say at this point that the headgear apparatus 66 preferably provides radiation emission detection signals which are each fed through an associated radiation detection signal processing circuit 67, one circuit being provided for each detector although only one such circuit and signal path are shown for purposes of clarity. Circuit 67 will be described in greater detail hereinafter. The output of circuit 67 is in turn preferably fed to the minicomputer 60, which, preferably acts as a buffer in order to more efficiently handle the data collected during the data collection period as considerable expense is involved in utilizing a large scale general purpose computer 60 such as the IBM 360 online throughout the data collection period. However, if this is not a consideration, the minicomputer buffer 60 may be omitted and the data fed directly to the general purpose computer 61.

The radiation emission detector assembly 65, which is to be described in greater detail with reference to the headgear apparatus 66 which preferably contains similar assemblies, is mounted in analyzer 63 in relation to coiled passageway 64 so as to quantify the radiation emission associated with the sampled gas contained in the coiled passageway 64. Detector assembly 65, which preferably provides a signal output in response to a gamma radiation input, is connected to a radiation detection signal processing circuit 74, which is preferably similar to detection circuit 67, whose output is in turn also preferably connected to the minicomputer buffer 60.

Preferably, the gas analyzer coiled passageway 64 is also operatively connected, in a manner to be described in greater detail hereinafter, to an end-tidal sample analyzer system 75, to be described in greater detail hereinafter, in order to determine the concentrations of carbon dioxide and oxygen in the patients breath. Both of these substances, and especially carbon dioxide, are influential upon the rate at which the blood flows through the human brain and should, therefore, preferably be taken into consideration. Normally the patients respiration is adjusted to maintain these gases at fairly constant levels. However, some patients may have additional diseases which may influence the level of these gases; while other patients may over-breathe during the data collection period because of tension or apprehension induced by the data collection procedure. If the patient over-breathes during this period and thus reduces his carbon dioxide pressure, his cerebral blood flow will be slowed and of an altered pattern even though his cerebrovascular system is normal. However, the relationship between the reduction in this blood flow for a given reduction in carbon dioxide pressure is known and can be easily compensated for in the final determination of cerebral blood flow if this reduction is known. Similarly, a patient having impaired ventilation may have a higher rate of cerebral blood flow which can also be predicted from the elevated carbon dioxide pressure if it is known. In addition, low arterial oxygen tension during impaired ventilation/profusion can also cause a faster rate of cerebral blood flow. It is therefore both preferable and desirable to know the carbon dioxide and oxygen pressures in order to compensate for their effects on the cerebral blood flow determination or errors may be introduced in the final determination.

The end-tidal sample analyzer system 75, preferably includes a conventional through-flow carbon dioxide gas analyzer 76, such as a Capnograph which is an infrared carbon dioxide gas analyzer, and a conventional through-flow oxygen analyzer 77, such as a Rappox manufactured by Instrumentation Associates, which analyzers 76 and 77 are preferably connected together in a serial through-flow path, although they may be connected in parallel through-flow paths if desired. The inlet to the carbon dioxide gas analyzer 76 is preferably connected to the coiled passageway 64 outlet via a conduit 78 having a valve 79 disposed therein for preferably directing the end-tidal sampled gas leaving the coiled passageway 64 either through conduit 78, from which it is drawn through the carbon dioxide analyzer 76 and therefrom through the oxygen analyzer 77 from where it is exhausted to the closed circuit breathing system or through another conduit 80, through which it is exhausted directly to the exhaust hood. Preferably, the valve 79 only passes the end-tidal sampled gas through the analyzer system 75 prior to the initiation of the actual data collection period associated with the local cerebral blood flow determination, the valve 79 directing the gas through conduit 80 during this period, in order to quantify or measure the oxygen and carbon dioxide gas pressures present in the end-tidal sample as well as the period of time in which the carbon dioxide gas present in the end-tidal sample is on the plateau portion of its exhalation curve, which curve is similar to that for Xenon gas. The end-tidal sampler 62 may then preferably be normalized or calibrated to operate on this portion of the exhalation curve during the data collection period.

Furthermore, the oxygen and carbon dioxide pressure information may be utilized to determine the time at which the actual data collection period is to commence, which is preferably when these pressures are stabilized. At that time, the data collection may proceed without introduction of any significant errors in the cerebral blood flow determination due to carbon dioxide or oxygen gas pressure variations. If desired, these measurements may be displayed visually and the data collection begun manually by an operator by actuation of a start switch (not shown) when these pressures are stabilized, or in the alternative, these values may generate corresponding electrical signals which when fed to a comparator (not shown) may provide a begin data collection signal to the minicomputer 60 at stabilization if the minicomputer 60 is utilized as an overall control mechanism for the data collection procedure.

As will be explained in greater detail hereinafter, the normalized end-tidal sampler 62 is preferably initially activated from minicomputer 60 at the time when the actual data collection period is to commence so as to synchronize the selection and radiation emission detection times of the end-tidal gas samples with the radiation emission detection times of the headgear apparatus 66, the end-tidal sampler 62 being activated in a conventional manner thereafter. If the start signal is manually initiated, then this signal merely puts the minicomputer 60 on-line so that it may provide the end-tidal sampler 62 synchronization signal; whereas, if the minicomputer 60 is utilized as an overall control, then it can be programmed to only provide this synchronization signal after it has received the start signal from the comparator.

If desired, the carbon dioxide and oxygen gas analyzers 76 and 77, respectively, may be electrically connected to the minicomputer 60 in order to provide dynamic pressure information during the data collection period instead of, for example, merely providing a start signal and, in this instance, the computer 61 may then be preferably programmed to compensate for pressure aberrations in the resultant local cerebral blood flow determination. In such instance, the valve 79 would be open so as to direct the end-tidal gas sample to the calibration systen throughout the actual data collection period, as opposed to only prior thereto.

Headgear Apparatus Now referring to FIGS. 2A and 2B and describing the headgear apparatus 66 in greater detail, the system 10 of the present invention, as will be explained in greater detail hereinafter, preferably subdivides the patients brain into a predetermined plurality of discrete detection zones for purposes of determining the rate of cerebral blood flow in each of these zones, although, if desired, the final determination may be limited to any number of zones in the plurality, such as one. These detection zones, which are shown by way of example by dotted lines in FIGS. 2A and 2B are preferably represented by three-dimensional cubes 81-81 which are each of equal volume and dimensions. It should be noted that these detection zones 81 are merely mathematical models of sub-volumes defined within the overall brain volume by means of the headgear apparatus 66 and are preferably correlated to a brain map" so as to pinpoint their exact location within the brain. Most preferably, 144 such detection zones are utilized to define the overall brain volume, although other numbers might be employed. As will be explained in greater detail hereinafter, during the data collection period, each of these zones 81 will be provided with an associated radioisotope concentration and corresponding radiation emission due to the presence of the radioactive gas in the cerebral blood.

In order to define these detection zones 81 in the brain, which are termed radiation emission detection zones for purposes of the local cerebral blood flow determination, the headgear apparatus 66 preferably includes a substantially rectangular hollow helmet housing 82 having a front portion 84, a rear portion 86, a top portion 88, side portions and 92, and a bottom portion 94 through which the head of the patient is inserted. Preferably, a plurality of substantially identical individual detector assemblies 95, equal in number to the plurality of radiation emission detection zones 81, which in the preferred embodiment is 144, are arrayed in parallel and angular 83 modular banks on the front 84, rear 86, top 88, and sides 90 and 92 of the helmet housing 82, along edges, and in a pair of modular banks 96 and 98 of these individual detector assemblies 95 as required to yield independent linear equations. Each of the detector assemblies 95 is preferably arrayed along an axis normal to the plane in which the respective associated modular bank 83, 84, 86, 88, 90, 92, 96 and 98 lies. Modular banks 96 and 98 are preferably angularly related to the side portions of the helmet housing, respectively, at an angle of 135 degrees with the cube diagonals. For purposes of illustration, modular banks 96 and 98 are shown rotated 90 in to the plane of view with respect to their actual preferred positions. One of the detector assemblies 95a and 95b is shown in crosssection in FIGS. 2a and 2b, respectively, for purposes of explanation, the field of view of assemblies 95a and 95b being preferably identical in volume.

As shown in FIG. 2B, the top portion 88 of the helmet housing 82 preferably includes six modular banks or columns of detector assemblies 95, columns 102, 104, 106, 108, 110 and 111, each of the detector assemblies 95 being preferably located in the center of the zone 81 being defined thereby. Similarly, the six columns 102 through 111, inclusive, of detectors 95 are preferably arrayed on the top portion 88 of the he]- met housing 82 so as to also provide six rows 112, 114, 116, 118, 120 and 122 of detector assemblies 95, each detector assembly 95, once again, being preferably located in the center of the detection zone 81 defined thereby. In this manner a six-by-six array of detector assemblies 95 is provided so as to provide thirty-six radiation emission viewing surfaces for the detection zones 81 in the plane of the top portion 88 of housing 82, each of such surfaces being the associated detection zone surface of entry of view into the brain volume for the associated detector assembly 95. Similarly, front and rear portions 84 and 86 and side portions 90 and 92 each are preferably shown as having four rows of six detector assemblies 95 each, although other arrangements may be utilized, each detector assembly 95 also preferably being located in the center of the detection zone 81 defined thereby, so as to provide a fourby-six array of 24 detector assemblies 95 in the plane of the respective helmet portion 84, 86, 90 and 92 so as to provide 24 such viewing surfaces for the detection zones 81 in each of these planes. This provides 132 of such radiation emission viewing surfaces for the preferred 144 detection zones 81. The additional twelve detector assemblies 95 which are required so as to provide the preferred equal plurality of 144 detector assemblies 95 are provided by means of modular banks 96 and 98 which each include a row of six detector assemblies 95. It should be understood that many of the detectors as enumerated may, if desired, be relocated along edges of the housing 82, as required, to yield the preferred 144 independent linear equations.

Preferably, the headgear apparatus 66 is designed for the largest head likely to be encountered and, therefore, variations in the air space between the detector assemblies 95 and the scalp of the patient may occur. This variable air space is due to variable cranial curvatures associated with different patients as well as variations in the size of the head. In order to compensate for these variations in air space, which variations affect the quantity of the radiation emissions detected by detector assemblies 95, a gauge-type means may preferably be included in the helmet housing 82 substantially at the position of each of the detector assemblies 95 which measures the size of the air space between the associated detector assembly 95 and the scalp of the patient. These gauges 130, 132, 134, 136, and 138, only one of which is shown'in each of the portions 84, 86, 88, 90, and 92 of the helmet housing 82 for purposes of clarity, may be calibrated rods or, if desired, may be conventional position transducers so as to provide a contemporaneous measurement of the air space between the associated detector assembly 95 and the scalp of the patient during the data collection period. If desired, a separate head-gauge, comprising solely position trnasducers or calibrated rods located at each of the detector assembly positions in an identical array with that of the helmet housing 82, may be utilized prior to the use of the headgear apparatus 66 so as to provide these air space measurements prior to the actual data collection period. In this instance, the headgear apparatus 66 is preferably not provided with a gauge at each detector assembly 95 position, but rather is preferably merely provided with only one calibrated rod or position transducer gauge in an identical position with that of such gauge in the head-gauge in each of the portions or planes of the helmet housing 84 through 92, inclusive, illustratively shown by gauges 130 through 138, inclusive, so as to insure that the helmet housing 82 is aligned in the identical position in which the head-gauge was aligned when the air space measurements were made. The universal mounting means 68, as was previously mentioned, is preferably capable of aligning the headgear apparatus 66 in this desired alignment or orientation position and preferably includes locking means (not shown) for retaining it in this position during the data collection period.

As will be explained in greater detail hereinafter, the headgear apparatus 66 should preferably bear a specific and reproducible relationship to the patients brain. Therefore, in aligning the headgear apparatus 66, a reproducible basal plane, which defines the angle of viewing to which all other planes will be parallel, perpendicular, or angulated at 45, must be chosen. In the preferred system 10 of the present invention the gIabellar-sellar plane (see FIG. 5), which is the plane which delimits the lower surface of the human brain, is preferably chosen as the basal plane. The mid-saggital plane (see FIG. 5), which is the plane perpendicular to the basal plane and midway between its lateral limits, is preferably chosen as the second plane of orientation or reference in the preferred alignment position of the headgear apparatus 66. The third plane of orientation or reference for the headgear apparatus 66, which thereby defines the exact alignment or orientation of the headgear apparatus 66 with respect to the brain of the patient, is the plane perpendicular to the basal plane and the mid-saggital plane and tangent to the forehead (see FIG. 5). When the head-gear apparatus 66 is aligned in these three planes, with the mid-saggital plane preferably being the zero reference plane, the patients brain volume is subdivided into the plurality of detection zones 81, which are preferably cubic in volume, arranged in a rectangular six-by-six array in the glabellar-sellar plane and four cubes high in the midsaggital plane, as shown in FIG. 5 by the dotted lines. If a separate headgauge device is utilized to measure the variable air space, as was previously mentioned, then this device too should be similarly oriented prior to the taking of these measurements.

Detector Assembly Now describing the radiation emission detector assembly in greater detail, detector assembly 95 preferably being identical with detector assembly 65 of the Xenon gas analyzer 63 as was previously mentioned. A typical preferred detector assembly 95a and 95b is shown in FIGS. 2A and 28, respectively, detector assembly 95b being a plan view of a different detector assembly from that of detector assembly 95a. However, this plan view is preferably identical with that of one for detector assembly 95a which view is omitted in FIG. 2B for purposes of clarity. Accordingly, for purposes of explanation, the structural details of the preferred detector assemblies 95, all of which are preferably identical, will be described hereinafter only with reference to detector assembly 950. The detector assembly 950 preferably includes a collimator portion 140 made of radiation absorbing material cooperatively associated with a radiation emission detector 142. Preferably, the collimator portion 140 of the detector assembly 95a is a tube of specific length and cross-sectional lumen area whose function is to limit the direction from which radiation may enter the detector 142. It should be noted that it is the collimator 140 which primarily determines the degree of spatial resolution of the system of the present invention. In the preferred system 10 of the present invention, the shape of the collimator lumen 144 is preferably square so as to define the preferred cubic detection zone 81 into which the patients brain is preferably subdivided and to maximize the area of the detector 142 utilized for viewing, although other shapes, such as circular, may be utilized therefor if desired. The collimator tubing 140 is formed of a material which has a high radiation absorption characteristic, such as a composite material composed of 90 percent tungsten plus 10 percent nickel and copper (e.g., Kullite l 12 or Mallory 1,000), so as to sharply restrict the radiation emission to the lumen-area of the detector 142.

The length of the collimator 140 determines the volume of tissue observed at the detector 142 through the lumen 144 of a given cross-sectional area and, therefore, determines the number of detection zones 81 observed by the detector 142 in its direction of view. The preferred square collimator lumen 144 provides a square prism field of view for the detector 142, each detector 142 arrayed about the helmet housing 82 preferably looking into the face of the cubic detection zone 81 associated therewith and seeing its own prism of tissue. The collimator 140 length is preferably chosen so that the prismatic base of the field of view, as shown illustratively in FIGS. 2A and 28 by the shaded areas, is only slightly larger than the cube face of the detection zone 81 at the distal side of the third detection zone 81 in depth in a straight line based from the detector assembly 95a in that direction or field of view. In addition, with the preferred collimator 140 of the present invention, the square prism field of view for the associated detector 142 preferably includes portions of the detection zones 81 in a three-by-three, nine-zone matrix array about both the second and third detection zones 81 in depth in a straight line based from detector assembly 95a in the direction of view (entering the brain volume) in the plane of the respective second and third detection zones normal to the direction of view, with these second and third zones being at the center of the respective nine-zone matrix array in its respective plane. The preferred collimator 140, therefore, provides a preferred effective field of view three detection zones in depth, and a proportionate amount of such zones 81 which are in a three-by-three matrix array in the plane normal to the direction of view for both the second and third zones in depth in a straight line with these zones being at the center of each threeby-three matrix array. Therefore, as will be explained in greater detail hereinafter, the radiation emission quantified or detected by a given detector assembly will be a resultant value dependent on the contributions to this resultant provided by the respective radiation concentrations of the radioactive gas in the portions of the detection zones 81 contained within the preferred effective field of view This preferred optimal choice for the collimator 140 is based upon the useful depth of view; that is, beyond a given depth of tissue, for the gamma energy of the preferred radioisotope Xe', the tissue attenuation and dispersion of radiation emission according to the inverse-square law only allows a negligible fraction of radiation emission to actually arrive at the detector 142 from these depths. Therefore, radiation emissions from beyond three detection zones 81 in depth are outside this effective field of view as they do not significantly affect the determinations of local cerebral blood flow. If it is desired to take these negligible amounts into consideration, the collimator 140 may be designed so as to include these additional detection zones in its effective field of view.

The detector 142 of the detector assembly 95a is preferably a semiconductor such as ultra high purity germanium. Such a solid-state detector 142 is particularly applicable to the detection of gamma radiation of relatively low energy, such as the gamma radiation associated with the preferred gas Xenon (81 Kev) with high energy resolution. This is of particular concern since gamma radiation is the preferred radiation emission to be detected, beta radiation not penetrating the skull of the patient. Such a preferred solid-state detector 142 absorbs the gamma radiation and generates secondary electrons in response thereto which signal is processed in the radiation detection signal processing circuit 67 associated with each of the detector assemblies 95. If desired, a crystal detector, such as a crystal of thallium-activated sodium iodide may be utilized in place of the solid-state detector. However, as shown and preferred in FIG. 6, when such a crystal is utilized, a photomultiplier 146 should preferably be utilized therewith due to the fact that such a crystal emits a very weak light photon when an energy quantum of the gamma radiation is absorbed by the crystal, the photomultiplier 146 converting this light photon into electrical energy and amplifying it to a transmittable level in the form of electrical pulses. The crystal detector 142, in such an instance, is preferably interposed between the collimator 140 and the photomultiplier tube 146 so as to receive a gamma radiation emission input from the collimator 140 and provide an output to the photomultiplier tube 146 in response thereto.

SOLID STATE DETECTOR Referring now to FIG. 3, the output of the solid-state detector assembly 95 for a typical detection channel or processing circuit 67 is preferably operatively connected through a conventional charge sensitive preamplifier stage 148 and conventional linear amplifier stage 150 to a conventional single channel analyzer or pulse height detector stage 152, such as a circuit comprising transistomransistor logic (TTL), to preferably provide a TTL type output signal to the minicomputer buffer 60 which is indicative of the detected count in that detection channel, which signal 'is subsequently preferably fed to the general purpose computer 61. Since the three stages 148, 150 and 152 comprising the preferred radiation detection signal processing circuit 67 are preferably conventional, a detailed description is deemed unnecessary.

CRYSTAL DETECTOR RADIATION DETECTION SIGNAL PROCESSING CIRCUIT If a crystal detector 142 fabricated of thalliumactivated sodium iodide is utilized in place of the preferred solid-state detector then the radiation detection signal processing circuit configuration shown in FIG. 6 is preferably utilized for each of the detection channels in place of the detection signal processing circuit 67 configuration previously described with reference to FIG. 3.

Referring now to FIG. 6, the photomultiplier tube 146 for a typical detection channel in which a thalliumactivated sodium iodide crystal is utilized as the detector 142 is preferably a conventional ten-stage photomultiplier having an individual voltage dividing network, such as is provided by an RCA type 7767 multiplier phototube which has ten electrostatically focused dynode stages with in-line arrangement thereof. In the system of the present invention, such a tube 146 .is preferably magnetically shielded. A conventional high voltage power supply 170 is connected to the photomultiplier tube 146 via a conventional gain adjustment potentiometer 172 having an adjustable wiper arm 173 so as to supply the required voltage necessary to excite the photo-cathode to its range of sensitivity to light. If desired, a single high voltage power supply 170 may be utilized to supply power to any number of photomultiplier tubes 146 in the detector assembly array. In such instance, a different gain adjustment potentiometer 172 is preferably provided for each tube 146 so as to properly adjust the voltage for each of the individual detectors 142. The output of the photomultiplier tube 146 is connected through a conventional pre-amplifier 174 and amplifier 176 to a conventional discriminator stage or variable pulse height detector stage 178 whose function is to eliminate all pulses or voltages below and above a specified level so as to eliminate low voltage electrical noise and background counts or emissions outside of the energies to be detected. In addition the discriminator stage I78 preferably is provided with conventional means 179, such as a variable potentiometer, for shifting the discriminator to another threshold level which would be appropriate for a different radioisotopic gas as well as to the optimal level for the preferred radioisotopic gas Xenon The output of the discriminator stage 178 is preferably fed through a conventional summing gate and pulse stretcher network 180 whose output is preferably fed to the general purpose computer 61 via the minicomputer buffer 60, if desired.

LOCAL CEREBRAL BLOOD FLOW DETERMINATION SYSTEM METHOD OF OPER- ATION General Description Now generally describing the preferred method of operation of the present invention in accordance with which the local cerebral blood flow determination system 10 previously described is preferably utilized. In any local cerebral blood flow determination there are significant physical factors which affect this determination but which may be considered to be constants for a given patient whose local cerebral blood flow is being determined. However, these significant constants must preferably be initially determined for the patient. In utilizing the system 10 in accordance with the preferred method of the present invention, the local cerebral blood flow is ultimately determined in accordance with the well known Fick-Kety expression of which one form is where C, equals the brain tissue radioisotope concentration preferably in microcuries per gram; (C,,-C,,) equals the arterial-venous blood radioisotope concentration difference, preferably in microcuries per gram; m equals the starting time of the local cerebral blood flow determination, preferably in seconds, F equals the local cerebral blood flow, preferably in microliters per gram per minute; W equals the weight of the tissue comprising the detection zone for which the local cerebral blood flow is being determined; and m equals the number of seconds after the beginning of the first inhalation by the patient during the data collection period.

As will be explained in greater detail hereinafter, this Fick-Kety expression-is preferably utilized for each of the detection zones 81 in which it is desired to determine the local cerebral blood flow therefor. Furthermore, it should be noted that the local cerebral blood flow determined in accordance with the preferred method of the present invention is preferably a quantitative determination of cerebral blood flow for that detection zone 81 for which the Fick-Kety expression is utilized (as opposed to a mean rate of flow for a region) which, as will be explained in greater detail hereinafter, is possible because the various factors in the Fick-Kety expression can be localized for each detection zone 81 in accordance with the preferred method of the present invention. C,, and C4 are related by the expression C,, (venous concentration)= C (brain tissue concentration 7(tissue/blood partition coefficient for the gas), and the value of 'r can be determined. Furthermore, since the specific gravity of brain tissue is approximately equal to one, the weight of the tissue W is approximately equal to the volume of the detection zone 81, which is also a known factor as it is predetermined by the structure which defines each of the detection zones 81. Therefore, the only unknowns involved in applying this Fick-Kety expression to the determination of a local cerebral blood flow is the tissue radiation concentration quantity C and the arterial blood radiation concentration quantity C It is in determining these quentities for the preselected discrete detection zone 81 that the preferred method of the present invention is most useful.

DETAILED DESCRIPTION Now describing the preferred method of operation of the present invention in greater detail. In utilizing the system of the present invention, the headgear apparatus 66 is preferably aligned on the patients head so as to provide a specific and reproducible relationship to the patients brain. As was previously mentioned, the headgear apparatus 66 is preferably aligned so as to be oriented as shown in FIG. 5 with the glabellar-sellar plane being the basal plane for the detector array of the rectangular helmet 82, the plane of detectors 95 in the top portion 88 of the helmet 82 preferably being parallel thereto. When the headgear apparatus 66 is so aligned, the other two preferred reference planes of the three reference planes which define the orientation or alignment of the head-gear apparatus 66 are, as was previously mentioned, the mid-saggital plane and the plane perpendicular to the basal plane and the midsaggital plane and tangent to the forehead, and the detection zones 81 of the patients brain are defined as shown in FIG. 5 by the dotted lines.

As was also previously mentioned, the length of air space between the associated detector assembly 95 and the portion of the patients scalp opposite that detector assembly 95 affects the radiation emission detected thereby. Therefore, it is both preferable and desirable that the length of air space between a particular detector assembly 95 and the skull of the patient be known for purposes of the local cerebral blood flow determination. Accordingly, if a separate head-guage is utilized to measure the lengths of these air spaces, as was previously mentioned, the gauges 130 through 138, inclusive, located in the helmet housing 82 must be checked to insure that the patients head retains exactly the same position during the actual data collection period as during the time when the air space measurements were made.

In addition, compensation should also preferably be made for the thickness of the patients skull and the degree of bone mineralization as these factors may introduce errors in the measurements of radiation emission by the detector assemblies 95. These factors may be determined by ultrasonic techniques such as are employed for neurologic echo-scanning. However, if the errors introduced by variations in bone mineralization are tolerable, then no additional compensation need be made for this factor. If the errors introduced by variations in skull thickness can be tolerated, no additional compensation need be made for this factor either. Corrections for mean skull thickness and density are then sufficient.

Once the headgear apparatus 66 is aligned in the preferred predetermined orientation or alignment position, the balance of the local cerebral blood flow determination may be performed in accordance with the the present invention. The radioactive gas, which is preferably xenon, although other gases such as Krypton 85 may be utilized if desired, is then dissolved in the patients blood by means of the closed inhalationexhalation breathing system associated with the mask 12. Throughout the actual data collection period, the patient receives his air supply through this closed inhalation-exhalation breathing system. When the actual data collection is to commence, that is preferably when the patients breathing conditions, such as oxygen and carbon dioxide pressure, are stabilized as indicated by the carbon dioxide and oxygen analyzers 76 and 77, the minicomputer buffer 60 preferably sends a signal to the end-tidal sampler 62 which activates the sampler 62 to turn it ON so as to preferably synchronize the initiation of end-tidal sampling and the resultant radiation emission detection or counting times in the Xenon gas analyzer detector assembly 65 with that of the detector assemblies associated with the headgear apparatus 66 detector array. After this initial activation, the endtidal sampler 62 functions in a conventional manner throughout the duration of the data collection period, and its operation will not be described in greater detail hereinafter. Suffice it to say that the endtidal sampler 62 relay mechanism (not shown) is actuated at the beginning and end of each breath by airway pressure changes within the closed breathing system resulting from these conditions; the end-tidal sampler 62 functioning to extract end-tidal samples when activated by the gas pressure within the mask 12 reaching a given pressure at the end of the breath and continuing to sample until negative pressure arises at the beginning of the next breath.

Subsequent to the initial turning ON of the end-tidal sampler 62, signifying the beginning of the actual data collection period, the actuation of the end-tidal sampler 62 relay at the end of the patients next breath actuates the Xenon gas injector 40 solenoids (not shown) associated with valves 42 and 50. Gas injector 40 thereafter injects a predetermined amount of the radioisotopic Xenon gas into both the inhalation and the exhalation chambers 28 and 30, respectively, through the respective intermittently opened valves 42 and 50, which thereafter close, and associated conduits 44 and 48, respectively. The injected radioisotopic gas mixes with the air already contained in the chambers 28 and 30.

As the patient continues to breath normally, the airway pressure in inhalation conduit 16, and the closed breathing system as a whole, changes and demand valve 20 opens at the beginning of the next breath. The end-tidal sampler 62 relay is again actuated in response to this initial pressure change, which preferably sends an initial signal to the minicomputer 60, or if desired, directly to the measuring devices; namely, the radiation detection signal processing circuits 67 and 74, placing them in the data collection mode. This signal is preferably only sent at this initial time, the circuits 67 and 74 remaining in this mode throughout the balance of the data collection period. In addition, a signal is also sent to the gas purification unit 32 which signal activates the unit 32 so as to refill the inhalation chamber 28 from the exhalation chamber 30 via the gas purification unit 32 which removes excess carbon dioxide, adds oxygen to the closed breathing system, and filters the air contained thereon.

Each subsequent breath of the pateint during the data collection period causes the actuation of the endtidal sampler 62 relay mechanism at the beginning of the breath; the resultant operation of gas injector 40 to inject a predetermined quantity of radioisotopic Xenon gas only into the exhalation chamber 30, valve 50 preferably remaining closed throughout the balance of the data collection period; the actuation again of the end-tidal sampler 62 relay mechanism at the end of the breath; and the resultant operation of gas purification unit 32 to return the injected gas well mixed to the inhalation chamber 28 to be breathed by the patient. In this manner, the radioisotopic gas concentration in the blood is cuased to rise steeply since each breath contains a still higher concentration of the radioisotopic gas.

Arterial Blood Radiation Concentration Determination Preferably, as was previously mentioned, in order to determine the arterial blood radiation concentration quantity C in accordance with the present invention, the alveolar or end-tidal gas concentration at the end of each breath is sampled in the manner previously described above. This end-tidal gas sample is drawn through the coiled passageway 64 which, as was previously mentioned, contains a known total volume of the sampled gas. Detector assembly 65 looks at the coiled passageway 64 and preferably measures the gamma radiation emission emanating therefrom, which is equivalent to the gamma radiation emission in that known sample volume. The gamma radiation emission entering collimator 140 which is incident on detector 142 is absorbed and causes the generation of secondary electrons which are amplified in the radiation detection signal processing circuit 74 to provide a pulse or signal which is the equivalent of the resultant radiation emission count of detector assembly 65. Since the lung gas in contact with the blood has essentially the same partial pressure as-the gas contained in arterial blood, and since it is this equilibrated gas which appears in the last part of each breath, the gas concentration in the last part of each breath is essentially equivalent to the concentration of the radioisotopic gas in arterial blood. This signal, which therefore is representative of the arterial blood radiation concentration, is then preferably fed to the minicomputer buffer 60 for temporary storage before being passed to the general purpose computer 61 for processing along with the other collected data.

As will be explained 1 in greater detail hereinafter, each time an end-tidal sample is taken and the resultant arterial blood radiation concentration signal produced in accordance therewith, a point on an arterial concentrationcurve is created. Most preferably, the data collection period duration is one minute and six determinations at ten second intervals m and m m m m and m,, as shown in FIG. 4, are made so as to construct" an arterial concentration curve for purposes of the local cerebral blood flow determination in accordance with the Fick-Kety expression, this arterial blood radiation concentration quantity being represented by the term C BRAIN TISSUE RADIATION CONCENTRATION DETERMINATION Now referring to the operation of the system in accordance with the preferred method of the present invention so as to provide the brain tissue radioisotope concentration quantity C, for, preferably, each of the detection zones 81 so that this data may be processed in accordance with the previously stated FicIc-Kety expression. The radioactive gas, which as was previously mentioned dissolves in the blood passing through the lungs, is delivered to the brain parts or detection zones 81 in proportion to the local rate of blood flow. The resultant gamma radiation emissions detected by the various detector assemblies 95 included in the headgear 1 apparatus 66 detector array are a function of the amount of radioactive gas deposited, or radioisotope concentration, in the various detection zones 81 and the effective field of view associated with a given detector assembly 95.

As was previously described, in the preferred system 10 of the present invention the detector assemblies look at the brain from one hundred forty-four different positions (or locations), and the degree of resolution or localization observed by each detector assembly 95, that is, its effective field of view, is determined by the collimator associated with the particular detector 142. In order to properly determine the rate of local cerebral blood flow, the radioactive gas must be administered to the patient in sufficiently high concentration to provide a statistically acceptable counting rate, or quantity of detectable radiation emission, in the preferred sampling interval which is 10 seconds, but not so high that the patient is endangered by the radiation. As was previously mentioned, the preferred square lumen collimator 140 has a length which provides the preferred three detection zone 81 useful depth of view for the preferred effective field of view, which field of view includes a proportionate amount of such zones 81 which are in a three-by-three matrix array in the plane normal to the direction of view for both the second and third zones in depth in a straight line, with these zones being at the center of each three-by-three matrix array. This preferred collimator 140 represents the optimal compromise between an acceptable level of radioactive gas isotope administration and the collimator size suitable for localization. Each preferred detector 142, therefore, sees this preferred effective field of view of three detection zones in depth, the total or resultant radiation emission observed by each detector 142, as was previously mentioned, being due to the radioisotope concentration present in the portions of each of the detection zones 81 contained within the effective field of view of the particular detector 142.

This relationship between the resultant radiation emission detected or observed by a given detector 142 and the radioisotope concentration present in the portions of each of the detection zones 81 contained within the preferred effective field of view of the detector 142 may be preferably defined by the following general expression in which we have assumed, for purposes of explanation, that all the detection zones 81 are included within the bone surrounding the patients brain, although it would be obvious to one of ordinary skill how to readily modify the following expression to take into account the surrounding bone if the detection zones were defined so as to include this bone which, in such instance, could be considered as non-radioactive source bearing material. Before defining this expression, however, a nomenclature for the detection zones 81 including the effective field of view, preferably must first be established so that this general expression may be preferably defined for a typical detection zone 810. The general expression may be rewritten for each of the other 143 detection zones 81 in the array.

For purposes of explanation, based upon the preferred effective field of view, and the preferred planes of orientation of the headgear apparatus 66, the given detector assembly 950, for which the expression is defined, shall be assumed to be located, in the most general case, adjacent the center of the three-by-three zone effective matrix array in the plane normal to the direction of view, which array is three zones in depth from that plane so as to provide a three-by-three-bythree matrix array effective volume comprising 27 detection zones 81. Such an array is shown in FIG. 7A which is an exploded perspective view of this mathematical model matrix array, the letter X designating the center detection zone 81c associated with this detector assembly 950. Each detection zone within this effective matrix array will be defined by three coordinates of position in the direction of view these coordinates being depth, row, and column, in that order, where the column is in a vertical direction normal to the direction of view and the row is in a horizontal direction normal to the direction of view; wherein A represents the designator for the plane of the first zone in depth; B represents the designator for the parallel plane of the second zone in depth; C represents the designator for the parallel plane of the third zone in depth; represents the designator for the center row in each of the parallel planes (A, B, C) of the zones in depth; T represents the designator for each of the zones in the row above the center row in each of these planes (A, B, C) in depth; U represents the designator for each of the zones in the row below the center row in each of these planes (A, B, C) in depth; 0 represents the designator for the center column in each of these planes (A, B, C) in depth; R represents the designator for each of the zones in the column to the right of the center column in each of these planes (A, B, C) in depth; and L represents the designator for each of the zones in the column to the left of the center column of each of these planes (A, B, C) in depth. Utilizing this labeling system or nomenclature of designators, the zones 81 in the effective matrix array are designated as shown in FIG. 7A, with A00 being the designation or coordinates describing the center detection zone 81c labeled X for the general case.

In addition, as shown in FIG. 8, which is a diagrammatic view of the useful depth of view in the efi'ective field of view for the typical detector assembly 950 having a collimator 1400 and a detector 1420, each detection zone 81 is preferably further subdivided in depth in the direction of view 200 into equal volume thirds designated 1, 2 and 3 for the first zone in depth (bracket A); 4, 5 and 6 for the second zone in depth (bracket B) in the direction or axis of view 200; and 7, 8 and 9 for the third zone in depth (bracket C) in the direction of view 200. For purpsoes of explanation, it shall be assumed that the radiation concentration contained in each third of a detection zone 1 through 9, inclusive, may be represented by a point source at the center of each of the detection zone thirds 1 through v 9, inclusive, along the direction or axis of view 200, the effective field of view preferably being symmetrical about this axis 200. These central point source locations are designated a, b, 0, e, f, g, h, j, and k, for detection zone thirds 1 through 9, inclusive, respectively.

Since, as was previously mentioned, the effective field of view is preferably symmetrical about the axis of view 200, utilizing the above defined nomenclature, we can thereby define the following equalities with respect to the geometric proportionate amount of the various detection zones contained within the effective field of view of zone X 810 which zone X 810 has coordinates A00: BRO=BOT=BLO=BOU; BRU==A BLU=BRT=BLT; CRO=COT=CLO==COU; and

CRU=CLU=CRT=CLT. It should be noted that these equalities relate only to the geometric proportionate amounts of these zones which are present and not to the various radiation concentrations which are present in these zones, which concentrations may differ. In addition, the preferred collimator 1400 is designed so that the effective field of view does not include ARO, ALO, ART, AOT, ALT, ARU, AOU and ALU; in other words it includes no other zones than A00 in plane A.

Now that we have defined our nomenclature, and taking into account the above identified equalities and the previously mentioned assumptions, the general expression defining the relationship between the resultant radiation emission detected by a given detector 1420 at position AOO, which is the starting zone or point of entry of its effective field of view into the array, and the radiation concentration present in the portions of each of the detection zones 81 contained within the preferred effective field of view of detector 1420 is as follows, letting P represents the detected resultant radiation emission or counting rate resulting from the contributions of all the detection zones 81 within the effective field of view; e represents the efficiency of the detection system; 8 represent the fraction of radioisotope remaining since its original assay at the time of the data collection for the local cerebral blood flow determination (loss due to radioactive decay); s represent the factor expressing the attenuation of radiation by the scalp and skull; A represent the area of the detector 1420; K represent the dimensional constant; p represent the total attenuation constant for gamma radiation of a specific energy (in square centimeters/gram); 1 represent the thickness of brain tissue through which the radiation is attenuated (in grams/square centimeter) in multiples of one-sixth of a zone; I represent the distance from the center of each one-third of a zone to the detector 1420 along the axis of view 200; V represent the volume of each one-third of a zone; VPOsmoN represent the effective pyramidal intercept of volume for one-third of a zone whose positional coordinates are represented by the three proper coordinates for a given POSITION (see FIG. 7), vposn' o v, in-

- cluding compensation for the collimatr factor, which is K A1658 'r g-I- o-a [IAIOOVAIOO 0-1 o-b 0" o-c a oo n oo T -l- IA3OOVA3OOT 6TH o-o -11 t -l P 13 00 B OO 3 00 va oo "A a +VBGLT B L'r'l B nn-ln ram-P a ar) l e-k Vmh ic Lr (IC9LT+IC9RU 0 111 IC9RT)] When all the constants for the system at the time of the data collection are solved for the appropriate terms combined, and letting C, through C represent these constants, this expression may be reduced to:

T,A00 CIIAOO 2 B00 s coo 4( B0T IBRO IBLO 3011) 5( 'coT+ I 0120 cLo+ 0011) C6(IBRT BLT'i IBRU+ IBLU) C1( cm'+ ICLT+ am/f ow) The above preferred expanded general expression for P as can be observed, includes corrections for tissue attenuation of the gamma radiation originating at various depths within the brain; i.e., in other detection zones, as well as for the inverse square relationship between counts detected and distance.

It should be noted that taking the above general expression, in conjunction with FIGS. 7A, 7B and 8 and providing each actual detection zone with a unique identifier, such as 2-1 through Z-144, inclusive (FIG. 78), this expression can then be readily rewritten by inspection by anyone with ordinary mathematical skill for any one of the 144 detection zones 81 in the array by assuming it to be located at this cenler position relative to its effective field of view and substituting the equivalent identifiers Z-l through 2-144, inclusive,

which correspond to the above subscripts which relate to the position of this zone and the portions of the zones contained within its effective field of view, the

effective fields of view being identical for each detector 142. For example, if the detection zones 81 are uniquely identified by numbering consecutively left-toright, row-by-row starting at the top row as shown in FIG. 7B, and a given detector is located by position adjacent the zone designated 2-8, where AOO=Z8, ALO=Z7, ARO=Z9, ALU=Z13, AOU=Z14,

ARU=Z-15, ALT= Z-l, AOT=Z-2, ART=Z-3,

BOO=Z32, BLO=Z-31, BRO=Z33, BLUZ-37,

BOU=Z38, BRU =Z-39, BLT Z-25, BOT=Z26,

CLU =Z-61, COU =Z-62, CRU =Z-63, GL1" Z -49,, COT=ZS0, and CRT=Z-51, the above described general expression for P the detected resultant radiation emission, assuming the constants for the system 10 at the time of the data collection to have been solved for and appropriate terms combined, for the detector 142 adjacent zone Z-8, would be rewritten as:

It should further be noted that some of the terms in the general expression may be zero when this expression is written for a detector 142 whose effective field of view contains a portion or portions which fall outside the 144 detection zone array into which the brain is preferably subdivided, such as a detector which is located at a corner or along the outer periphery of the array (such as at position 2-1 in FIG. 7B in the example given). In such instance the effective twenty-seven zone matrix array, only 19 of which are seen, will have portions or zones that do not exist as actual predefined detection zones within the effective field of view' within the subdivided brain volume. For example, utili'zing the same numbering system (FIG. 78) as in the previous example, if the given detector is located by position adjacent the zone designated 2-1, which is a corner, where the following equivalents now exist, the numeral 0 indicating that the zone does not exist, AO0= Z-l, ALO= 0, ARO 2-2, ALU 0, AOU 2-7, ARU Z-8, ALT== 0, AOT= 0, AOT= 0, ART= 0, B00 Z-25, BLO= 0, BRO= Z-26, BLU 0, BOU Z-31, BRU Z32, BLT= 0, BOT 0, BRT-0, COO 2-49, CLO 0, CR0 Z-50, CLU 0, COU 2-55, CRU Z-56, CLT== ,C,0 =.9,.,ad C ?0 he... bqxq described general expression for P for the detector 142 adjacent zone Z-ll would be rewritten as:

Tz-1 1 z-1 2 z-2s+ a z-49+ 4( z-2e z-a1) s- (0+I ,,+0-l-I )+C (0+0+I +0)+C (0+0+I +0) which reduces to Similarly, after a system of providing each detection zone 81 with a unique identifier Zll through 2-144, in-

clusive, is established, the expression for P can therefore, as was previously mentioned, be rewritten by inspection for each detector 142 in the array thereby preferably providing 144 counting expressions F for the various parts of the same tissue volume. Since, as can be observed from the foregoing general expression for P the quantity of detected radiation emission is directly related to the tissue radioisotope concentrations in the portions of the detection zones contained within the effective field of view, the tissue radioisotope concentration quantity C which is equivalent to I for a given detection zone, for each of the individual detection zones can be determined from the actual resultant radiation emissions observed by the detector array of the helmet housing 82, by solving these 144 equations or expressions for P simultaneously.

As was previously mentioned, the minicomputer buf' fer 60 preferably collects the counted radiation emissions which have been processed by the radiation detection signal processing circuitry 67, preferably completing a full-scan cycle for all of the detectors in the array before the last pulse or signal from the array has decayed, so as to provide tissue radiation emission sig nals from each of the 144 detectors associated with the helmet housing 82 every 10 seconds for the preferred 1 minute data collection period during which the blood radioisotope concentration is raised by breathing the Xenon gas. At the end of the preferred one minute data collection period, the minicomputer buffer 60 then preferably transfers this data to the general purpose computer 61, if it is available, which is programmed in conventional fashion to solve the 144 simultaneous equations for each l-second period. The mini-computer 60, then preferably goes OFF-line and this computer-OFF signal is utilized to operate valves 52 and 54 so as to change the mask 12 intake from the inhalation chamber 28 to room air, and the mask 12 has outflow to the exhaust hood instead of the exhalation chamber 30. Thereafter in a few breaths, most of the radioisotopic gas will have been breathed out of the patient and into the exhaust hood. If desired, if the general purpose computer 61 is not available at this time, the minicomputer 60 may go OFF-line so as to operate valves 52 and 54 and store the collected data for processing at a later time by the general purpose computer 61. In any event, if desired, at the completion of the data collection period, when the minicomputer 60 has collected all the data, it may transmit a signal which can be utilized to operate valves 52 and 54.

After the collected resultant radiation emission data has been transferred to the general purpose computer 61, the computer 61 then preferably constructs a curve of the rate of change in tissue radioisotope concentration I or C, in each brain part or detection zone, utilizing the six tissue radioisotope concentrations I quantified for each brain part or detection zone at the IO-second sampling intervals. Such a representative curve is shown by way of example in FIG. 4 by curve 210, the sampling intervals being represented by m m,, m,, m m and m As was previously mentioned, the computer 61 also constructs a curve for the rate of change of radioisotope concentration C, in arterial blood for these time intervals m through m inclusive, which curve is represented by the curve 212 in FIG. 4. Curve 210 provides the tissue radioisotope concentration characteristic C, for the detection zone while curve 202 provides the arterial blood radioisotope concentration characteristic C The computer 61 thereafter preferably determines the rate of local cerebral blood flow for each of the 144 detection zones or brain parts utilizing these characteristics or curves 210 and 212 in accordance wih the previously described Fick-Kety expression, the shaded area in FIG. 4 between curves 210 and 212 illustratively representing the integral portion of this Fick-Kety expression.

When utilizing the system of the present invention, if desired, the computer 61 may be programmed in a conventional manner to determine cerebral blood flow differences above and below a normal level and only to provide a print-out of the data within specific levels of abnormality, such as a print-out of all detection zones in which the blood flow is 20 to 40 percent below normal. Furthermore, if desired, the computer 61 may be programmed in a conventional manner to provide a printout of the local cerebral blood flow in each of the detection zones irrespective of whether such blood flow is normal or abnormal or, if desired, the computer 60 may be programmed in a conventional manner to write the local cerebral blood flows on a brain map. It will become apparent to one of ordinary skill in the art, that the local cerebral blood flow data may be utilized in a multiplicity of fashions depending on the desired diagnostic use of this information.

Summarizing the preferred method of operation of the present invention, the headgear apparatus is aligned in the predetermined position on the head of the patient; the patient then inhales the radioactive gas in a closed inhalation exhalation breathing system; the last part of the patients breath is end-tidal sampled at IO-second intervals during a 1 minute data collection period to provide an arterial blood radiation concentration characteristic; the headgear apparatus detector array, which has subdivided or defined I44 detection zones in the brain, quantifies the resultant radiation emission at each detector at the lO-second sampling intervals, which information is processed in accordance with the counting expression P for each detection zone to provide 144 simultaneous equations to the computer which solves these equations to provide a tissue radiation concentration characteristic; and the computer processes the tissue radiation concentration characteristic and the arterial blood radiation concentration characteristic in accordance with the Fick-Kety expression to provide a local cerebral blood flow for one or more of the 144 detection zones.

By utilizing the apparatus of the present invention local cerebral blood flow can be determined in a rapid and efficient manner with minimal discomfort to the patient. Furthermore, this information can be provided in any desired format which will enhance its usefulness as a valuable diagnostic tool for the physician.

It is to be understood that the above described embodiment of the invention is merely illustrative of the principles thereof and that numerous modifications and embodiments of the invention may be derived within the spirit and scope thereof, such as by dissolving the concentration of a radioactive substance in the blood by other than inhalation of a radioactive gas or by utilizing arterial catheterization, such as of the carotid artery, to determine the arterial blood radioisotope concentration, although these alternatives are not as desirable. In addition, it should be understood that an exact integration may be substituted for the approximations utilized in the counting expression without departing from the present invention.

What is claimed is:

1. An apparatus for use in quantitative localized cerebral blood flow analysis of a patients brain having irradiated cerebral blood flowing therethrough comprising headgear means, said headgear means including a housing, said headgear housing including means for mounting said headgear on said patients head in a predetermined position with respect to the brain, said headgear means further including a plurality of radiation emission detection means mounted in said housing in a multiplanar array comprising a plurality of substantially mutually perpendicular planes with respect to said brain, said mounted array being cooperatively associated with said headgear mounting means for defining a plurality of quantitative radiation emission detection zones for said brain for quantitatively localizing said irradiated cerebral blood flow when said headgear means is mounted in said predetermined position, each of said zones having an associated radiation concentration and resultant radiation emission dependent on said irradiated cerebral blood flow, each of said detection means having an associated effective field of view which includes an associated intercepted volume of said brain comprising at least a portion of one or more other zones of said plurality of quantitative radiation emission detection zones, said detection means being mounted in said mutually perpendicular planes with said associated intercepted volumes being spatially related to each other, whereby the radiation concentration in each detection zone due to said irradiated cerebral blood blow is resolvable in three dimensions from said detected radiation emissions.

2. An apparatus in accordance with claim 1 wherein said plurality of radiation emission detection means is equal to said plurality of quantitative radiation emission detection zones.

3. An apparatus in accordance with claim 2 wherein said plurality of radiation emission detection means comprises at least 144 of said detection means.

4. An apparatus in accordance with claim 1 wherein said multiplanar array of radiation emission detection means comprises a substantialy rectangular array comprising five planes, a portion of said plurality of detection means being arranged in each of said planes, said five planes including two pair of substantially parallel spaced apart planes, each of said parallel pairs of planes being substantially perpendicular to the other, and another plane which is substantially mutually perpendicular to each of said parallel pairs of planes, each of said spaced apart parallel pair of planes being on opposite sides of said patients head when said headgear is in said predetermined position.

5. An apparatus in accordance with claim 4 wherein each of said portions of radiation emission detection means are arranged in plurality of rows and columns in an associated plane.

6. An apparatus in accordance with claim 5 wherein each row in each of said parallel pairs of planes contains an equal quantity of radiation emission detection means.

7. An apparatus in accordance with claim 5 wherein said quantity of radiation emission detection means in each of said rows of each of said parallel pairs of planes and said other plane comprises at least six detection means.

I 8. An apparatus in accordance with claim 7 wherein said quantity of detection means in each column of said parallel pairs of planes and said other plane comprises four detection means, and said plurality of detection means comprises at least 144 of said detection means.

9. An apparatus in accordance with claim 8 wherein said multiplanar array further comprises six radiation emission detection means arranged in a row in each of a different pair of mutually perpendicular planes, each plane of said different pair intersecting one parallel plane of one of said parallel plane pairs at an angle of 45 to a normal to said said intersected plane.

10. An apparatus in accordance with claim 5 wherein said quantity of radiation emission detection means in each of said columns of each of said parallel pairs of planes comprises at least four detection means.

1 1. An apparatus in accordance with claim 4 wherein said multiplanar array further comprises a portion of said radiation emission detection means arranged in a different pair of substantially mutually perpendicular planes with respect to said brain, one of said planes of said different pair of planes intersecting one parallel plane of one of said parallel pairs of planes at a predetermined angle with respect to a normal to said intersected plane, the other of said planes of said different pair of planes intersecting said other parallel plane of said one pair at a predetermined angle with respect to a normal to said plane, said predetermined angles being equal.

12. An apparatus in accordance with claim ll wherein said plurality of radiation emission detection means comprises at least 144 of said detection means.

13. An apparatus in accordance with claim 1 wherein at least one of said radiation emission detection means includes collimator means fordefining said associated effective field of view for said detection means.

14. An apparatus in accordance with claim 13 wherein said radiation emission detection means including said collimator means further includes a means responsive to radiation emission cooperatively associated with said collimator means for quantifying said 10- calized cerebral blood flow.

15. An apparatus in accordance with claim 14 wherein said collimator means has a radiation emission inlet end and a radiation emission outlet end, said inlet end being adjacent to said patients head and said outlet-end being adjacent to a portion of said responsive means when said hadgear is in said predetermined position, one of said collimator ends comprising a lumen of predetermined configuration, said effective field of view being dependent on said lumen configuration.

16. An apparatus in accordance with claim 15 wherein one of said collimator ends comprises a lumen of substantially square configuration.

17. An apparatus in accordance with claim 14 wherein said responsive means includes means for providing a quantitative photoelectric response in response to a resultant radiation emission from said portion of quantitative radiation emission detection zones within said efiective field of view.

18. An apparatus in accordance with claim 14 wherein said responsive means includes crystal means having a lumen area for providing a quantitative photon emission in response to a resultant radiation emission from said portions of quantitative radiation emission detection zones within said effective field of view, said collimator means substantially limiting said response to said radiation emission from within said effective field of view.

19. An apparatus in accordance with claim 18 wherein said crystal includes thallium-activated sodium iodide.

20. An apparatus in accordance with claim 18 wherein said crystal comprises a semiconductor means.

21. An apparatus in accordance with claim 20 wherein said semiconductor means is a silicon semiconductor means.

22. An apparatus in accordance with claim 20 wherein said semiconductor means is a germanium semiconductor means. 7

23. An apparatus in accordance with claim 14 wherein said collimator means has dimensions for providing optimal localization of said cerebral blood flow, said optimal localization being dependent upon a predetermined quantity of radiation emission to be detected and a predetermined degree of spatial resolution with respect to said patients brain when said headgear is in said predetermined position.

24. An apparatus in accordance with claim 14 wherein said responsive means includes means for providing a quantitative electrical response in response to a resultant radiation emission from said portions of quantitative radiation emission detection zones within said effective field of view.

25. An apparatus in accordance with claim 24 wherein said responsive means includes means for providing secondary electrons in response to said radiation emission.

26. An apparatus in accordance with claim 1 wherein said radiation emission detection means includes a means responsive to radiation emission for quantifying said localized cerebral blood flow.

27. An apparatus in accordance with claim 26 wherein said responsive means includes means for providing a quantative electrical response in response to a resultant radiation emission from at least a portion of a portion of said plurality of quantitative radiation emission detection zones.

28. An apparatus in accordance with claim 27 wherein said responsive means further includes means for processing said electrical response to provide said quantified localized cerebral blood flow.

29. An apparatus in accordance with claim 28 wherein said processing means includes discriminator means having a preselected electrical value corresponding to a predetermined electrical equivalent value of radiation emission.

30. An apparatus in accordance with claim 29 wherein said discriminator means includes means for providing a new preselected value in accordance with a new corresponding electrical equivalent value of radiation emission.

31. An apparatus in accordance with claim 27 wherein said responsive means includes photomultiplier means for providing said electrical response in response to said radiation emission.

32. An apparatus in accordance with claim 1 wherein said mounting means includes means for aligning the headgear in said predetermined position.

33. An apparatus in accordance with claim 32 wherein said alignment means includes means for contacting the patients head in an alignment position when said headgear is in said predetermined position.

34. An apparatus in accordance with claim 32 wherein said alignment means includes a plurality of means for providing an alignment position of said headgear, said alignment position corresponding to said predetermined position, at least one of said plurality of position providing means being associated with a different plane of said multiplanar array.

35. An apparatus in accordance with claim 1 wherein said headgear housing comprises a helmet housing.

36. An apparatus in accordance with claim 1 wherein said mounted multiplanar array comprises a plurality of removably mountable radiation emission detection modular means.

37. An apparatus in accordance with claim 1 wherein each of said radiation emission detection means includes an associated collimator means for defining said associated effective field of view for said associated detection means.

' UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3 ,769 ,966 Dated Novembfil" 6 973 Inventor(s) MyTon n et al.

It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

On the cover sheet, in the heading, itemfZE] Inventors:

"Myron Youdin, Flushing; June N. Barker, New York, both of N..Y. should read Myron Youdin, Flushing; June N.

Barker; Theobald Reich, New York, all of N.Y.

Column 21, 7 line 66, "oenler" should read center Signed and sealed this 25th day of June 197L (SEAL) Attest:

EDWARD M.FLETCHER,JR. C. MARSHALL DANN Commissioner of Patents Attesting Officer FORM po'mso (169) uscoMM-oc 60376-P69 '15. GOVERNMENT PRINTING OFFICE I969 0366'334,

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Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US3976051 *Aug 5, 1975Aug 24, 1976Kay Thomas DHead-positioning scintillation camera and head holder therefor
US4033335 *Jun 12, 1975Jul 5, 1977Wisconsin Alumni Research FoundationMethod and apparatus for multiplexing of physiological sensor signals with gamma ray camera data signals
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US4111191 *Jul 10, 1974Sep 5, 1978Shaw Robert FApparatus and method for examining blood vessels of interest by tracking position with respect to time of particles introduced therein
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US4793358 *Feb 20, 1987Dec 27, 1988Kabushiki Kaisha ToshibaApparatus for measuring local cerebral blood flow
US4930510 *Nov 23, 1988Jun 5, 1990Picker International, Inc.Parameterization for CT blood flow mapping with xenon gas enhancement
US5458128 *Jun 17, 1994Oct 17, 1995Polanyi; MichaelMethod and apparatus for noninvasively measuring concentration of a dye in arterial blood
US8336549 *Jun 1, 2007Dec 25, 2012Ramses NashedDisposable anesthesia face mask
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Classifications
U.S. Classification600/431, 250/380
International ClassificationA61B6/00, A61B5/08, G01T1/161, A61B5/0275, G01T1/164, G01T1/29
Cooperative ClassificationG01T1/161, G01T1/1644, A61B5/0813, A61B6/501, A61B5/02755, A61B5/6803, G01T1/2928, G01T1/2985
European ClassificationA61B5/68B1B, A61B6/50B, G01T1/164B2, A61B5/0275B, G01T1/161, A61B5/08N, G01T1/29D1C, G01T1/29D4