CT blood flow mapping with xenon gas enhancement

A xenon gas system (B) introduces xenon gas into a patients's blood. The xenon gas concentration in the patient's blood is monitored and the characteristics of the patient's blood absorption curve are determined (34). A look-up table array (60) includes a plurality of look-up tables, each look-up table corresponding to one of a plurality of preselected blood absorption curves. A look-up table selection circuit (36) selects the look-up table which most closely corresponds to the projected blood absorption curve. A CT scanner (A) generates a plurality of image representations at preselected intervals after commencement of xenon gas interpolation, which images are stored in an image memory array (44). Xenon gas concentration values from corresponding pixels of each image representation are utilized to address the look-up table corresponding most closely to the patient's blood absorption curve in order to retrieve precalculated partition coefficient, blood flow rate, and confidence values. The retrieved values may be interpolated (80, 82) to compensate for a patient's blood absorption curve falling among a plurality of curves or the measured xenon concentration values falling between the preselected addressable values of the look-up tables. A display (96) displays images indicative of the partition coefficient, the blood flow rate, and the confidence value.

BACKGROUND OF THE INVENTION 
The present invention relates to the art of medical diagnostics. It finds 
particular application in conjunction with CT blood flow mapping of the 
brain and will be described with particular reference thereto. However, it 
is to be appreciated that the present invention will also find utility in 
conjunction with other imaging modalities, such as digital x-ray, magnetic 
resonance, radiation and positron emission, ultrasound, and the like. The 
present invention is further applicable to imaging other regions of human 
and veterinary patients, inanimate objects, and other subjects. 
In the human brain, blood reaches the tissue in two modes, directly through 
the arteries and indirectly through other tissue. In normal, healthy brain 
tissue, blood reaches gray matter at 40 to 140 ml per 100 ml per minute. 
Gray matter tissue which receives less than 30 ml per 100 ml per minute 
is not adequately fed for proper functioning and may suffer irrepairable 
damage. In white matter, cerebral blood flows are typically about one 
third of those for gray matter, with flows under about 10 ml per 100 ml 
per minute being considered inadequate. The early detection of brain 
regions with subnormal blood flows enables corrective action to be taken 
before the blood tissue is irreversibly damaged. 
One of the most common causes of insufficient feeding of the tissue is a 
blockage in the arterial blood flow. In the past, iodine was utilized as 
an enhancement agent injected into the blood to facilitate the location of 
arterial blockages. However, brain tissue membrane blocked the iodine 
enhancement agent from permeating the tissue. Because the iodine was 
unable to pass from the blood flow into the tissue, iodine was only able 
to enhance images of blood in arteries, capillaries, and veins. Iodine was 
unable to enhance representations of the actual profusion of blood into 
the tissues. 
Unlike iodine, xenon passes from the blood into the brain tissue. Thus, 
utilizing the xenon as an enhancement agent facilitates the imaging and 
measurement of blood profusion into the tissue. As the concentration of 
xenon gas in the patient's blood rises, the concentration of xenon gas in 
the brain tissue increases, asymptotically approaching an equilibrium 
concentration. The rate of the exponential xenon gas concentration 
increase in the tissue is indicative of the blood flow rate. The 
equilibrium concentration which is asymptotically approached is indicative 
of a partition coefficient, .lambda.. The partition coefficient, which is 
different for different kinds of tissue, is defined as the ratio of the 
quantity of xenon in each unit volume or voxel of tissue to the quantity 
of xenon per like volume in blood. For gray matter, the partition 
coefficient is typically about 0.95 and for white matter is typically 
about 1.35. Partition coefficients which differ significantly from these 
values are indicative of sick or dying tissue. 
The xenon concentration in the tissue of the ith unit volume or voxel at a 
time t is described by a formula known as the Kety equation: 
##EQU1## 
where C is the tissue xenon concentration, C.sub.a is the blood xenon 
concentration, K is the tissue clearance or build-up rate, and f is the 
flow rate. The partition coefficient, .lambda., is related to the flow 
rate and the clearance or build-up rate by the equation: 
EQU f=.lambda.K (2), 
where .lambda. is the tissue-blood partition coefficient. 
The blood xenon concentration is readily monitorable. The tissue xenon 
concentration for a tissue in a given voxel can be calculated from the CT 
number or other data value of a pixel of a CT image corresponding to the 
given voxel. By taking several CT images at different times, with the 
blood xenon concentration known for times preceeding each image, one can 
theoretically solve the Kety equation to determine the partition 
coefficient and blood flow for the tissue compartment corresponding to 
each pixel. Typically, three to six images were taken. More particularly, 
the values or CT numbers from the corresponding pixels of each of the 
three to six images were iteratively fit to the "best" flow f and 
partition coefficient which, with the known C.sub.a (w), allowed 
comparative C(t) to be calculated using any of various conventional curve 
fitting techniques. Perhaps the most common approximation implemented was 
the "minimum chi-square" curve fitting criterion which required extended 
and time consuming calculations. The chi-square curve fitting technique 
determined a best fit flow, a best fit partition coefficient, and a fit or 
confidence value indicative of the closeness of the best fit. The curve 
fitting technique was repeated for each pixel of the images. 
It is to be appreciated that chi-square and other curve fitting techniques 
for fitting three to six data points with a curve, then deriving the 
slope, the end point which the curve is asymptotically approaching, and 
the degree of conformity to the curve or best fit was a time consuming 
operation. When this operation was repeated over 65,000 times to fit the 
CT numbers of corresponding pixels of a conventional 256.times.256 image 
to corresponding curves, the computational time became excessive, even on 
a high speed computer. To reduce the computation to an acceptable time, 
the image resolution was commonly reduced from 256.times.256 pixels to as 
little as 32.times.32. However, calculating the flow, partition 
coefficient, and fit for each of the over 1000 pixels of a 32.times.32 
image still required up to ten minutes. 
The present invention contemplates a new and improved technique for more 
rapidly and more accurately determining the flow, the partition 
coefficient, and the fit or confidence value from CT or other image data. 
SUMMARY OF THE INVENTION 
In accordance with the present invention, precalculated flow, partition 
coefficient, and confidence values are stored for each combination of a 
plurality of possible sets of image data and arterial blood xenon 
concentration or absorption curves. When actual image data is collected, 
the most nearly corresponding precalculated flow, partition, and 
confidence values are retrieved from memory. 
In accordance with a more limited aspect of the present invention, the 
retrieved flow, partition coefficient, and confidence values are 
interpolated from the closely corresponding stored memory data. 
In accordance with a still more limited aspect of the present invention, a 
method of determining at least partition coefficient and flow values 
corresponding to each of a plurality of voxels of a region of interest is 
provided. After starting to introduce an enhancement agent into the 
patient, a concentration of the enhancement agent in a preselected patient 
tissue, e.g. blood, is measured. An absorption curve is projected from the 
measured enhancement agent concentrations. Also, after starting to 
introduce the enhancement agent into the patient, a plurality of image 
representations are generated. Each image representation is defined by a 
plurality of pixels which correspond to voxels of the region of interest. 
Each image representation includes a pixel value for each pixel, which 
pixel value is indicative of enhancement agent concentration in the 
corresponding voxel. A look-up table array is accessed with at least the 
projected absorption curve and corresponding pixel values of each of the 
plurality of image representations generated at different intervals to 
retrieve the precalculated partition coefficient and flow values. 
In accordance with another more limited aspect of the present invention, an 
apparatus for determining partition coefficients and blood flow rates in a 
region of interest is provided. An enhancement agent means introduces an 
enhancement agent into the patient's blood and provides an indication of 
the enhancement agent concentration within the blood. An absorption curve 
projecting means projects an absorption curve which is indicative of 
enhancement agent absorption by the blood from the provided indications of 
enhancement agent concentration in the blood over time. A look-up table 
means is preprogrammed with at least precalculated blood flow and 
partition coefficient values which have been previously calculated in 
accordance with preselected sampling intervals, pixel values, and 
preselected absorption curves. The look-up table means is addressed by at 
least the pixel values and absorption curve values to retrieve at least 
the corresponding precalculated blood flow and partition coefficient 
values. An imaging means generates electronic image representations of the 
region of interest. Each image representation includes a plurality of 
pixel values, each of which is indicative of enhancement agent 
concentration in the corresponding voxel of the region of interest. A 
plurality of image representations are generated, each at a selected 
sampling interval. A look-up table access means selectively accesses the 
look-up table means with one or more of the absorption curve, the image 
pixel values, and the sampling intervals to retrieve at least the most 
nearly corresponding stored partition coefficient and blood flow values 
for each of the image pixels. 
In accordance with a yet more limited aspect of the present invention, an 
apparatus is provided for determining partition coefficient, blood flow, 
and confidence values of each voxel of a region of interest of a patient. 
A xenon means introduces xenon into the patient's blood and produces a 
xenon gas concentration signal indicative of xenon concentration in the 
blood. An absorption curve projecting means projects at least one 
absorption curve which is indictive of absorption of xenon gas in the 
blood from the xenon concentration signals. Each of a plurality of look-up 
tables corresponds to a preselected absorption curve. Each of the look-up 
tables is preprogrammed with precalculated blood flow, partition 
coefficient, and confidence values which have been precalculated in 
accordance with the corresponding absorption curve, pixel values, and 
preselected sampling intervals. Each look-up table is addressable at least 
by a xenon gas concentration value to retrieve corresponding precalculated 
blood flow, partition coefficient, and confidence values. A scanner 
generates a plurality of image representations. Each image representation 
is defined by pixels that correspond to preselected voxels of the region 
of interest and includes a plurality of pixel values that are indicative 
of radiation altering properties of substances in the corresponding 
voxels. A reference image memory means stores a reference image 
representation generated prior to introducing xenon into the patient's 
blood. A subtraction means subtracts pixel values of the corresponding 
pixels of the reference image representations and image representations 
generated at the preselected sampling intervals. In this manner, 
difference pixel values are created corresponding to each voxel of the 
region of interest, which difference pixel value is indicative of xenon 
concentration in the corresponding voxel. A difference image memory means 
stores a plurality of difference image representations, each corresponding 
to one of the preselected sampling intervals. The look-up tables are 
operatively connected with the difference image memory means such that the 
look-up table corresponding to the projected blood absorption curve is 
addressed by the corresponding pixel values from each of the plurality of 
difference images to retrieve the precalculated blood flow, partition 
coefficient, and confidence values for the corresponding pixel. A 
partition coefficient memory means stores each retrieved partition 
coefficient value in a corresponding pixel of a partition coefficient 
image representation. A blood flow image memory means stores each 
retrieved blood flow value in a corresponding blood flow image pixel. A 
confidence image memory means stores each retrieved confidence value in a 
corresponding confidence image pixel. A display means is operatively 
connected with the partition coefficient, blood flow, and confidence image 
memory means for selectively displaying the partition coefficient, blood 
flow, and confidence images. 
A primary advantage of the present invention is that it generates flow, 
partition coefficient, and confidence images quickly. 
Another advantage of the present invention is that it generates flow, 
partition coefficient, and confidence images with full, detailed 
resolution. In particular, flow, partition coefficient, and confidence 
images for 256.times.256 pixel images can be done in as little as seven 
seconds as compared to ten minutes for 32.times.32 pixel images of the 
prior art curve fitting techniques. 
Another advantage of the present invention is that it enables interpolated 
and data improved images of 256.times.256 pixel images to be generated in 
less than four minutes as compared to 646 minutes to calculate 
256.times.256 pixel images using a chi-square curve fitting technique. 
Still further advantages will become apparent to those skilled in the art 
upon reading and understanding the following detailed description of the 
preferred embodiment.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
With reference to FIG. 1, an imaging means A, such as an axial tomographic 
scanner, selectively examines a subject and reconstructs image 
representations depicting properties of each voxel or subregion within an 
examined region of interest. An enhancement agent system B introduces 
selected amounts of an enhancement agent into the subject and derives an 
indication of the concentration of the enhancement agent in at least 
selected portions of the patient. The enhancement agent is selected such 
that its concentration or presence in the subject alters the image 
representations. In the preferred embodiment, the enhancement region is 
xenon gas whose concentration is reflected in the reconstructed image 
representations. The resultant image representations are essentially the 
sum of two images--an image depicting the xenon gas in the voxels of the 
region of interest and an image of the tissue in the region of interest. A 
processing means C processes the image data from the scanner A collected 
with varying concentrations of the enhancement agent and processes the 
enhancement agent concentrations from the enhancement agent system B to 
derive images representing the partition coefficient or permeability, 
blood or other fluid flow rates, and a confidence value or degree of fit. 
The imaging means A may be a CT scanner, a digital x-ray scanner, a 
magnetic resonance imager, or other diagnostic scanning device which 
generates data which can be reconstructed into a representation of an 
image of a region of interest. In the CT scanner embodiment, the scanner 
includes a gantry 10 which houses a rotating x-ray source and radiation 
detectors. Images from a CT scanner are indicative of x-ray 
absorption/transmission properties of tissue in each voxel of a planar 
region of interest or slice. In a magnetic resonance scanner, the gantry 
10 houses appropriate electromagnetic coils and antennae. A patient 
supporting couch 12 selectively indexes a patient through the gantry such 
that one or more planar slices are selectively imageable. 
The enhancement agent supply system B includes a source 20 of the 
enhancement agent, such as a tank of xenon gas. A flow or pressure 
regulator 22 controls the supply rate of the xenon gas to a breathing mask 
24 or other means for introducing the enhancement agent into the patient. 
An enhancement agent concentration means 26 determines concentrations of 
the enhancement agent within the patient. It is well known that there is a 
linear relationship between the xenon concentration in exhaled breath at 
the end of an exhalation cycle and the concentration of xenon gas in a 
patient's blood. In the preferred embodiment, the enhancement agent 
concentration means 26 measures the concentration of xenon gas at the end 
of a respiratory cycle and provides an output signal indicative thereof. 
Before the xenon gas or other enhancement agent is introduced to the 
patient, a reference scan is conducted to generate an image representation 
depicting the imaged region without the enhancement agent. The reference 
image is stored in a reference image memory 30. Upon completion of the 
reference image at a time t, the enhancement agent system B starts 
supplying xenon gas to the patient. For example, xenon may be substituted 
for 30% of the gases breathed by the patient. At the end of each 
respiratory cycle, generally every few seconds, the breath analyzer means 
26 determines the concentration of xenon gas in the patient's blood. The 
increase in xenon concentration in the blood with time normally increases 
exponentially as illustrated in curve 32 of FIG. 2. 
Generally, the data acquisition period lasts for several minutes, e.g. five 
to seven minutes. During this time, some 50 or more xenon concentration 
readings are commonly made by the breath analyzer means 26. A curve 
fitting means 34 utilizes known curve fitting techniques to project an 
absorption curve which is indicative of the absorption of xenon in the 
patient's blood. That is, the curve fitting means generates equations 
which describe the parameters of a curve 32 that most closely fits the 
discrete data points from the breath analyzer 26. Various conventional 
curve fitting techniques may be implemented. In a preferred embodiment, 
the curve fitting technique implements a double exponential fit. That is, 
from the breath analyzer data points, two exponential curves are 
determined, which two curves sum to produce a curve which follows the 
actual blood flow concentration. The double exponential fit technique 
requires the determination of three variables: a scaler multiplier f and 
two exponential values, a, b. That is: 
EQU f(1-e.sup.-at)+(1-f)(1-e.sup.-bt) (3). 
Optionally, other curve fitting techniques may be implemented. However, 
more precise curve fitting techniques, such as those that describe the 
curve in terms of three or more parameters are preferred. The values of 
the three or other number of parameters which describe the absorption 
curve are used to address a blood curve selection means 36 such as a three 
dimensional look-up table. 
The three dimensional blood curve selection look-up table 36 is addressable 
only by preselected values of the three parameters. Normally, each of the 
three calculated parameter values falls between two preselected address 
values. In one embodiment, the preselected address value that is closest 
to the calculated value is used as the address. In another embodiment, 
each of the eight combinations of adjoining preselected address values are 
used to retrieve eight blood curves, which may all be the same. 
As the xenon concentration in the patient's blood is building, a plurality 
of images of the planar region are generated at preselected sampling 
intervals or times. As each image is reconstructed, it is stored in a 
temporary memory 40. A subtraction means 42 subtracts the xenon image from 
the reference image stored in the reference image memory means 30 to 
produce a difference or xenon concentration image representative only of 
xenon concentration. A difference image memory 44 stores a plurality of 
difference images, each corresponding to a different sampling interval. 
A first xenon enhanced scan is conducted a first preselected sampling 
interval t1 after the patient commences breathing xenon gas. This first 
produces a first image from which the reference image is subtracted to 
produce a first difference image that is stored in a first difference 
image memory 46. At a second preselected sampling interval or time after 
the patient starts breathing the xenon gas, t2, a second scan generates a 
second image from which the reference image is subtracted to produce a 
second difference image that is stored in a second image memory 48. In the 
preferred embodiment, a third difference image memory 50 stores a third 
difference image which is generated from a scan at a third sampling 
interval t3. Fourth and additional image memories are contemplated as may 
be appropriate to the degree of precision required. In the preferred 
embodiment, the first sampling interval is 11/2 minutes after t.sub.o, the 
second sampling interval t2 is 3 minutes after t.sub.o, and the third 
sampling interval t3 is 5 minutes after t.sub.o. Optionally, a fourth 
image may be taken at a fourth sampling interval of 7 minutes. 
Each difference image is defined by an array of pixels which each 
correspond to a voxel of the region of interest. Corresponding pixels of 
each difference image stored are those that depict the same voxel but at a 
different sampling interval or time. The concentration of xenon in the 
corresponding pixels can be expected to increase logarithmically with 
time, analogous to curve 32. The CT number or other value stored for the 
corresponding pixel of each difference memories 46, 48, 50 is proportional 
to the concentration of xenon gas in the corresponding voxel at the 
sampling interval t1, t2, t3, etc. If a voxel is totally within an 
unblocked artery, the concentration would be expected to follow the 
blood-xenon absorption curve 32 exactly. If the pixel is in tissue, the 
increase in xenon concentration might be expected to somewhat less. The 
exact concentration is determined by the Kety equation (1) discussed 
above. 
A look-up table means 60 is preprogrammed with a blood flow value and 
partition coefficient stored in each memory element. Each memory element 
is addressed by a corresponding combination of preselected addressing 
absorption curves, pixel values, and sampling times. By addressing the 
look-up table means with the preselected addressing absorption curve, 
pixel values, and sampling times that are closest to the absorption curve 
projected by the curve projecting means 34, the corresponding pixel values 
of difference memory means 44, and the actual sampling interval, 
corresponding blood flow, and partition coefficient values are retrieved. 
Various techniques may be utilized to calculate the correspondence of the 
flow values and partition coefficients stored in the look-up table with 
the addressing values. 
In the preferred method for loading the look-up table, partition 
coefficients, blood flow rates, and absorption curves are selected which 
span the range normally encountered in human patients. The number of 
partition coefficients, blood flow rates, and absorption curves selected 
determines the precision with which the final answer is reached but 
increases the size of the look up table and the complexity of the 
calculations to fill it. For a given blood flow rate, partition 
coefficient and absorption curve, xenon concentration curves are 
calculated from the Kety equation. The calculated xenon concentration 
curves give the exact concentration at each of the preselected sampling 
intervals or times t1, t2, and t3, i.e. the concentration or pixel values 
which address each stored blood flow value and partition coefficient. 
Because all possible concentrations which might be measured at t1, t2, and 
t3, will not fall exactly on a theoretically calculated xenon 
concentration curve, many of the look-up table entries will remain 
unfilled. To fill these remaining look-up table entries, the CT number 
values theoretically predicted at each sampling time are varied randomly a 
small amount. These stochastic variations generate additional look-up 
table entries with varying likelihoods. The most likely flow and lambda 
values are then used to fill this matrix value and the degree of 
likelihood or "confidence" value is also stored. 
It is to be appreciated that the reliability of flow and partition 
coefficient values generated by large deviations in observed CT absorption 
are less reliable than flow and lambda data which corresponds precisely to 
one of the theoretical curves. To advise the viewer of the degree of fit 
to the theoretical curves, the confidence value is stored in the 
corresponding memory element along with the stored partition coefficient 
and flow rate. 
Looking now to a preferred organization of the look-up table means 60, a 
plurality of look-up tables are provided, each look-up table corresponding 
to one of a plurality of preselected blood curves, i.e. C.sub.a (w) in 
Equation (1), and xenon enhanced measurement times t1, t2, t3. The look-up 
table selection means 36 selects at least the look-up table which was 
precalculated in accordance with the absorption curve which is most like 
the patient's blood curve C.sub.a (w) and the selected sampling times t1, 
t2, t3. Each of the look-up tables is an n dimensional look-up table, 
where n is the number of difference images generated and stored in the 
image memory means 44 during a single examination. 
For simplicity of illustration, the organization of each individual look-up 
table is described in conjunction with three images per study, i.e. a 
three dimensional look-up table. As illustrated in FIG. 3, t1, t2, and t3 
are the coordinates of a three dimensional look-up table. The magnitude of 
the preselected addressing xenon concentrations, CT numbers, or pixel 
values along each axis function as the look-up table. It is to be 
appreciated that additional sampling intervals e.g., t4, may also be 
accomodated. Further, additional look-up tables may be provided for 
different sampling intervals or numbers of sampling intervals. 
During a patient scan, a read control means 62 causes the pixel value or CT 
number corresponding to the same pixel in each image to be read from the 
difference images taken at sampling intervals t1, t2, and t3. As 
illustrated in FIG. 3, the pixel value from the pixel of the t1 image 
which normally falls between two precalculated xenon concentration values 
defines a planar region of possible solutions 64. The thickness of the 
planar region is determined by the distance between adjacent precalculated 
addressing xenon concentrations or pixel values. The data value from the 
t2 image similarly defines a planar region 66 and the data value taken 
from the t3 image determines a planar region of possible solutions 68. 
With reference to FIGS. 3 and 4, the intersection of these three planar 
regions defines a volume or cube 70 within which point 72 defined by the 
three actual pixel values falls. The precalculated blood flow, partition 
coefficient and confidence values are stored in memory elements 
corresponding to each corner of the volume. The partition coefficient, 
flow value, and confidence values at the closest corner are retrieved and 
read out of the look-up tables 60. 
For greater accuracy, the partition coefficient, flow rate, and fit may be 
interpolated from values stored in the eight memory elements at the 
corners of the volume 70 by interpolating means 80. In a preferred 
embodiment, the distance between the point 72 and each corner is 
calculated. The partition coefficient, flow rate, confidence value from 
the memory element at each corner is weighted in inverse proportion to the 
calculated distance. The weighted retrieved values are summed. 
As indicated above, the theoretical blood-xenon absorption curve projected 
by absorption curve calculating means 34 in many instances will not 
describe one of the preselected addressing absorption curves precisely. 
Rather, the value may tend to fall between two or more of the 
precalculated absorption curves. Because the absorption curve is described 
by three variables in the preferred embodiment, variables may address a 
point within a volume defined by eight corners as discussed above in 
conjunction with FIG. 4. In the preferred embodiment, the look-up tables 
corresponding to each of the eight corners absorption curves are also 
addressed by each pixel value to generate eight sets of partition 
coefficients, flow rates, and fit values. Each of the eight sets is 
interpolated by the first interpolating means 80. A second interpolating 
means 82 performs a weighted averaging of eight partition coefficients, 
flow rates, and confidence values from the first interpolating means. The 
weighting is again in inverse proportion to the distance between 72 and 
the corners. It is to be appreciated that the processing may be simplified 
when several corners of absorption curve look-up table 36 define the same 
absorption curve. 
The sampling times t1, t2, and t3 may also be varied. To vary the sampling 
times, additional sets of look-up tables are provided for each additional 
sampling time combination. A third interpolating means may be provided to 
adjust for differences between the actual sampling time and the look-up 
tables actually provided. The interpolated partition coefficient values 
corresponding each pixel are stored in corresponding pixels of a partition 
coefficient image memory means 90. Analogously, the blood flow rates 
retrieved for each pixel are stored in a flow image memory means 92 and 
the retrieved fit or confidence values are stored in a fit or confidence 
image memory means 94. A display means 96 displays partition coefficient, 
flow rate, and fit or confidence images. 
The look-up tables 60, as well as the absorption curve select look-up table 
36, are all described as three dimensional look-up tables. Optionally, 
other dimensions may be provided. Single dimensional look-up tables could 
be utilized but may produce suspect partition coefficients, flow values, 
and confidence value images. Dimensions higher than those can produce 
greater accuracy and higher confidence values. 
The invention has been described with reference to the preferred 
embodiment. Obviously, modifications and alterations will occur to others 
upon reading and understanding the preceding specification. It is intended 
that the invention include all such alterations and modifications insofar 
as they come within the scope of the appended claims or the equivalents 
thereof.