WO1990015575A1

WO1990015575A1 - Statistical based display for positron emission tomography scans

Info

Publication number: WO1990015575A1
Application number: PCT/US1990/003650
Authority: WO
Inventors: Roy John Erwin
Original assignee: New York University
Priority date: 1989-06-22
Filing date: 1990-06-21
Publication date: 1990-12-27
Also published as: US5027817A

Abstract

In medical imaging system a patient is injected with a radiopharmaceutical spontaneously emitting positrons and a PET (Positron Emission Tomography) scan is taken along parallel planes of a portion of the subject's body to produce a slice image composed of pixels arranged in a pattern. The intensity of each pixel is automatically, in a computer system, converted to digital data. The computer system then normalizes the pixels of the slice as to location by calculating the location of each pixel in an ideal or normal slice. The computer system then calculates a Z transform, on a pixel-by-pixel basis, compared to the slices from a normal group to obtain a topographic color-coded map showing the degree of abnormality at each pixel location.

Description

i

STATISTICAL BASED DISPLAY FOR POSITRON EMISSION TOMOGRAPHY SCANS

Background of the Invention

1 . Field of the Invention

The present invention relates to medical imaging systems and more particularly to Positron Emission Tomography ( PET) scan systems and methods.

2. Related Art

Medical imaging systems are used in the diagnosis and treatment of patients. They are non- invasive and therefore are considered safer tha surgical procedures to examine internal body tissue.

Positron Emission Tomography ( PET) is an imaging technique which enables visualizing the three-dimensional distribution of radionuciides in the human body. For example, a radiopharmaceutical containing suitable short-lived cyclotron-produced radionuciides, such as carbon eleven or nitrogen thirteen in a glucose solution, is injected into the subject to determine varying metabolic rates in the different areas of the subject's brain . The subject is placed in a PET scanner. The radionuciides underg decay with spontaneous emission of positrons. The positrons combine with nearby electron to simultaneously generate two photons, by annihilation, which travel in opposite directions along a line; i .e. , anti-parallel . The two photons are detected as light flashes by two scintillation detectors positioned on opposite sides of the patient. The number of coincidences of detection (electronic collimation ) by the detectors may be viewed as the degree of intensity at each pixel of images constructed by a computer syste associated with the PET scanner. Generally, the PET scanner produces a series of images corresponding to parallel planes ( "slices" ) through a portion of the patient's body, for example, 14 slices of the brain. The physician may view the slice images, for example, to determine areas of abnormal metabolic activity.

However, the amount and accuracy of the information obtained by the physician depends upon his training, ability and attention. Some of the information content present in the PET scans may be missed, even by experienced personnel, because the image intensity variations are too slight or too gradual to be detected by eyesight, or lie within the statistical variability of the counting rate of the radioactive decay (approximately 1 /«/ where n is the number of radioactive disintegrations per pixel per unit time) or lie within the normal variability encountered from individual to individual.

β Objectives and Features of the Invention It is an objective of the present invention to provide a PET scan system and method in which a patient's PET scan images may be objectively analyzed on a statistical basis. It is a further objective of the present invention to provide a

PET display which appears in shape like a portion of the patient's human body and which vividly and accurately shows regions which are abnormal and the degree of abnormality compared to a similar body portion of a normal group. It is a further objective of the present invention to provide a

PET display which shows, on an objective statistical basis, the comparison between the patient's PET scan at one time compared to a PET scan of the same body portion at a different time, treating one or a series of the scans as a self -norm for comparison purposes. It is a further objective of the present invention to provide a

PET display which more clearly delineates body areas showing abnormal activity, even though the delineation and/or the areas are too faint to be seen visually in the raw data of a PET scan image.

It is a feature of the present invention to provide a method and system for the production of a Positron Emission Tomography ( PET ) image display. The method includes administering a radiopharmaceutical radioactive material which spontaneously emits positrons from a patient; for example, the material may be an injected glucose solution to test metabolism. The patient is positioned in a PET scanner and at least one PET scan is taken of a body plane of the subject's body to produce a PET slice image comprising a plurality of image pixels arranged in a pattern on an image plane. The intensity of each pixel represents the positron emission from the area on the patient body plane corresponding to the pixel . The pixel intensities are converted into subject pixel digital data representing the intensity of each pixel and that data is input to a computer system. That computer system stores normative digital data representing the siice-by-slice and pixel-by-pixel intensities of PET scans of a reference or normal sample, for example, prior scans of the patient or scans of a healthy group of subjects. The location of each pixel of each individual scan is normalized in location based on anatomical features of that subject's PET scan . The computer system automatically calculates the normalized location of each pixel in the subject's slice image based on some anatomical feature of that image and produces a pixel-by-pixei normal ized-as-to- location set of subject data. The computer system then computes, on a pixel-by- pizel basis, a statistical comparison between the mean value of each pixel in the normal group and the digital value of each corresponding subject pixel, dividing by the pixel variance, to provide the degree of abnormality of the subject at each normalized-as-to-location pixel as a Z-score. The degree of abnormality of the subject at each pixel, calculated from the Z-score, is displayed in a topographic map, color-coded to reflect the significance of deviations from the normative values.

Further features of the present invention are that the administrat of the radiopharmaceutical is by injection, inhalation or ingestion of a labele substance such as a sugar solution; the PET image is of the distribution of brain neural activity showing brain region variations in the metabolic rates of sugar consumption or the uptake of the labeled substance; the degree of abnormality is expressed in standard deviation units; and the normalization of the pixels as to location is by expanding outwardly or contracting inwardl in relationship to a center point of the body portion. The labeled substanc includes radioieptic drugs, radio transmitters, radioiigands, precursors of metabolism, and other substances present in the brain or other body organ of interest.

Summary of the Invention In accordance with the present invention there is provided a method and system to present a statistically evaluated display which is obtained from PET scan data. A group of healthy, normal subjects provide the basis for comparison to a patient. The normal data is assembled by taking PET scan images on parallel planes (slices) with each image consistin of a portion ( rows and columns) of pixels. Each normal group image and patient image is automatically, in a computer system, normalized by being transformed as to shape and size so that, in computer, each of the transfor pixels are aligned. An average and standard deviation are obtained, on a pixel-by-pixel basis, for the normal group and that average is used, in a Z transformation, which evaluates absolute intensity data on a pixel-by-pixel basis. The degree of intensity data abnormality is displayed in a topographic color-coded map of the slice. Similarly, the same method can be used to evaluate relating intensity, that is, the percentage of the total body portion utilization of any radionuclide labeled substance represented by each pixel in the image.

Brief Description of the Drawings Other objectives and features of the present invention will be apparent from the following detailed description, taken in conjunction with the accompanying drawings. In the drawings:

Figure 1 is a block flow diagram of the absolute Z transform; Figure 2 is a block flow diagram of the relative Z transform; Figure 3 illustrates the conversion of a PET scan to a normalize PET scan; and Figure 4 illustrates the pixels in a PET scan image.

Detailed Description of the Invention Metabolic processes in the human body may be detected by injecting radiopharmaceuticais into a subject and subsequently scanning the subject with a positron emission tomographic ( PET ) image. The localized radiopharmaceutical spontaneously emits positrons at a rate corresponding to the local concentration of the labeled material .

The emitted positron interacts with a nearby electron, annihilating both particles to produce a pair of photons. These photons travel in anti-parallel directions (along the same line but in opposite directions ) at equal velocities.

When the subject is positioned in a PET scanner, simultaneously emitted photons are detected by scintillators located on opposite sides of the subject. The detection system may be rotated around the subject or may be constructed around the subject in order to obtain sufficient data to process a tomographic image for a particular plane.

The tomographically processed data is converted to a pixel space where the data for each pixel corresponds to the total number of photons emitted from the corresponding area on the imaged plane.

The present invention describes a method for statistical evaluation of the pixelized metabolic image of a test individual or group relative to a pixelized image of the normative metabolic rate of a reference group or prior state .

The first step in this process involves the selection of subjects who will comprise the normative population. This population would exclude subjects with a history of pathology within the region of interest. Each subject would then be given a radiopharmaceutical and scanned on the PET camera. ( An analogous procedure could be used to evaluate data relative to some reference state of an individual . ) i⁷

In order to obtain a normative value for each pixel across this normative group of subjects, variation in slice location during imaging and variation in individual subject morphology must be normalized. This normalization assures that pixel comparison among subjects represents the same anatomical region.

The pixel pattern on the original image, as shown in Figure 4, consists of rows 20 and columns 21 of pixels, for example, an image typicall consists of 10,000 pixels.

Normalization may be performed through a transformation that relates the tomographic coordinate system to an anatomical coordinate system based on the center of mass. The distance between the center of mass and a particular pixel is related to the dimensions of a standardized body in the tomographic coordinate system by a translational, rotational and proportional transformation. Slice normalization involves only translational transformation with a scaling factor calculated according to

( ^Xanat ) ^Xtomog ⁼ < ^T _x anat ^{} ( T} x tomog * ^{+ A X}'

where X t. o _mog is the total distance across all the slices of the individual subject, X_anat is the distance across each individual slice, T_χ is the distance across each standardized slice, T to oα '^{s tne tota}' ^'^stance across all the slices of the standardized body of the tomograph and _<Δ. X is the difference between the centers of mass of the two coordinate systems Normalization of morphology requires rotation of the imaged plan around the longitudinal axis in order to align the subject structure with th standardized structure. In addition, the coordinates of the subject pixels must be multiplied by the degree of magnification or shrinkage necessary to have a one-to-one correspondence between the pixelized image of the subjec and the pixelized image of the standardized body. This transformation may be stated as:

^T Y tomog ^{sin Θ}

-tomog

| ^Z anat cos Θ

( ^TZ anat j Z tomog

Z] } > Mag

tomog ^TY tomog ^{cos Θ "}I

J T_£

t ^T Z anat tomog si

- Δ Y] > Ma

where Θ is the angle of rotation around the axis perpendicular to the plane of the slice, T is the total distance across the subject image in the

Y anat

Y-direction, T_γ is the total distance across the standardized image in the Y-direction, T-, is the total distance across the Z-direction of the subject image and T_?. is the total distance across the Z-direction of the standardized image.

As shown in Figure 3, in a cross-section PET slice 10 of a brain, the center 11 is used to normalize the slice 10, which is small compared to the standard slice 12. The pixel location 13a of slice 10 is moved outwardly, by computer calculation, relative to center 11 to reach the normalized pixel location 13b.

After each subject's image in the normal group is normalized as to position and size, an average for the intensity of each pixel across all 1° subjects of the normal group is found. This pixel data is the absolute mean shape average of the normal group.

Next, a test group, comprised of subjects who have undergone prior pathological screening, is given a PET scan. The data for each subjec is normalized to the same coordinate system as the normal group by the equations above. The "shape" normalized value for each member of the test group is then compared to the average of the normal group according to the equation : „_.

Z . ^PH - ^{' ■}„^' °~ii where P.. is the shape normalized pixel value of the test subject. P.. Is the shape normalized average of P.. in the normal group and (7~. is the standar deviation of the value of P.. in the normal group. The resulting set of data is the absolute Z transformation that represents the probability of pathologic deviation of the test group from the norm in standard deviation units of the normal group. The set of data obtained from the Z-transformation is then displayed on a CRT color monitor according to a color coding. Red represen significant positive Z value or deviation of increased absolute metabolic rate, green represents Z values not significantly different from zero or normal metabolic rate, and blue represents significant negative Z values or deviations of decreased absolute metabolic rate. This is the "heat scale" color code. // This invention also introduces the relative Z transformation into the data analysis of the individual subject's PET scan. In this transformation, each pixel value is divided by the sum of all pixel values for that subject. The relative Z transformation equation may be written:

Z =

where P.. is the value of the particular pixel, ^T Σ^' Σ. P..„ is the total of 'J i j IT 'J* all pixel values. P.. is the average pixel value as percent of total, and CT~ is the standard deviation of pixel P.. as percent of total activity.

The resulting data for each pixel is then displayed according to the red, green and blue color code, in which red represents the probability of higher than average relative metabolic activity, green represents average relative metabolic activity and blue represents lower than average relative metabolic activity within the particular subject image.

Modifications may be made in the above-described invention within the scope of the subjoined claims. For example, preferably the normative and subject data is corrected for age, on an age regression basis, as well as for gaussian distribution. One type of age regression system is described in Science, Dec 12, 1980, Vol . 210, pgs. 1255-1258. incorporated by reference herei In addition, the computer system may analyze the normal ized-as- to-location subject images by factor analysis and discriminating variables.

A slice, having, for example, a 100 x 100 matrix providing 10,000 points, forms a vector or a series of slices, for example, 14, from vectors which are linked head-to-tail . In either case, the vectors form a factor structure in space. IZL

The general subjects of factor analysis and discriminating variables is dealt with in a publication "Neurometric Topographic Mapping of EEG and EP Features: Application To Clinical Diagnostic and Cognitive Evaluation", John, Prichep, Freedman S Easton, in Topographic Brain Mapping of EEG and EP, Ed. K, Maurer, Springer-Berlin, incorporated by reference herein.

Claims

CLAIMS: 1 . A method for the production of a Positron Emission Tomography ( PET ) image display, including the steps, in order, of: ( a ) administering a radiopharmaceutical material, which spontaneously emits positrons, to a patient; ( b) positioning the patient in a PET scan device; (c) taking at least one PET scan on a body plane of the subject's body to produce a PET slice image comprising a plurality of image pixels arranged in a pattern on an image plane with the intensity of each pixel representing the positron emission from the area on the patient body plane corresponding to the pixel; ( d ) converting the pixel intensities into subject pixel digital data representing the absolute or relative (%) intensity of each pixel; ( e) in a computer system, storing normative digital data representing the mean values and standard deviations of the absolute or relative intensities of each pixel in a normal group of PET scans, with each pixel in the normativ group being normalized in location based on an anatomical feature of that PET scan; (f ) in said computer system, automatically calculating the normalized location of each pixel in the subject's slice image based on an anatomical feature found in that image; to produce a pixel-by-pixel normalized-as-to- location set of subject data; (g) automatically computing in said computer system, on a pixel-by-pixel basis, a statistical comparison between said normal group pixel data and said subject pixel digital data using the Z— transformation to provide the degree of abnormality of the subject at each normalized as-to- location pixel compared to said normative group; and ( h ) displaying in a color-coded topographic map display the degree of abnormality of the subject at each pixel .

2. A method as in claim 1 wherein the administration of the radiopharmaceutical is by injection of a radioactively labeled sugar solution, neuroleptic drug, neurotransmi ter or iiςand; the PET image is of the distribution of brain neucefl activity showing brain region variations in the metabolic rates of sugar consumption or uptake or bonding of the labeled materials, and .the degree of abnormality is expressed in standard deviation units of tlpxt. normative group.

3. A method as in claim 2 wherein the patient may have schizophrenia and the analysis is to determine the presence or absence of a hypometabolic pattern of sugar utilization in the cortex.

4. A method as in claim 1 wherein the step (f ) utilizes the shape of the patient body Dortion in which the normalization of the pixels as to location is by expanding outwardly or contracting inwardly in relationship to a center point of the body portion.

5. A method as in claim 4 wherein the body portion is the brain and the center is found in relationship to the scalp, I^s"

6. A method as in claim 2 wherein the Z transformation on a pixei-by-pixel basis is given by the equation:

Z = (Y - Y) ιc- wherein Y is the value of the uptake in the subject, Y is the average value of the uptake in the normal group after transformation to yield a gaussian distribution, and 0~ is the standard deviation of the uptak the normal group after transformation to yield a gaussian distribution.

7. A method as in claim 1 in which the color code i≤ the heat scale in which red represents positive_* greeh represents zerQ, and blue represents negative.

8. A method as in claim 1 wherein the normative group is a group of healthy normal subjects.

9. A method as in claim 1 wherein the normative group of PET scans is obtained from the same patient at a different time.

ι

10. A system for medical imaging including: (a) a Positron Emission Tomography (PET) scan means to produce an image of a body portion of a patient administered with a radiopharmaeutical material which spontaneously emits positrons; (b) means for taking at least one PET scan on a body plane of a portion of the subject's body to produce a PET patient image comprising a plurality of image pixels arranged in a pattern with the intensity at each pixel representing the positron emission from a corresponding area on the body plane; (c) means for converting the pixel intensities into patient pixel digit data; (d) normalizing computer means for automatically computing the norm location of each pixel of the patient image based on an anatomical feature of the PET patient image to produce a set of normalized digital data representi a normalized pixel pattern; (e) Z transform computer means, including computer memory, for automatically computing, on a slice-by-slice and pixel-by-pixel basis, a Z transformation statistical comparison with a set of normative data stored i computer memory to provide the degree of abnormality of the subject at each normalized pixel; and (f) means for displaying a color-coded topographic map showing th degree of abnormality of the subject at each pixel.

11 . A system as in claim 10 wherein the administration is an injectio of a radioactive substance selected from the group of a radioactive drug, neurotransmitter or ligand; the PET image is of the distribution of brain neural activity showing brain region variations in uptake; and the abnormality is expressed in standard deviation units of a reference sample. if

12. A system as in claim 11 wherein the patient may have schizophr and the PET scan is to determine the presence or absence of a hypometabol pattern of sugar utilization in the frontal cortex.

13. A system as in claim 10 wherein the normalized pixel pattern is based upon the size and shape of the patient body portion in which the normalizing computer means calculates the pixels either expanded outwardly or contracted inwardly in relationship to a center point of the body portion

14. A system as in claim 13 wherein the body portion is the brain and the center is found in relationship to the scalp.

15. A system as in claim 11 wherein the Z -transformation on a pixel-by-pixel basis is given by the equation :

Z = (Y - Y) / σ~ wherein Y is the value of the metabolic rate or uptake in the subject, Y is the value of the metabolic rate or uptake in the norm group after transformation to yield' an age regression correction and gaussi distribution , and T~ is the standard deviation of the metabolic rate or uptake in the normative gpoup after transformation to yield an age regression correction and gaussian distribution .

16. A system as in claim 10 in which the color code is the heat scale in which red represents positive, green represents zero, and blue represen negative.