CN105816197A - SPECT dopamine development quantitative analysis technique and application thereof in brain dopamine assessment - Google Patents
SPECT dopamine development quantitative analysis technique and application thereof in brain dopamine assessment Download PDFInfo
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Abstract
The invention relates to an absolute quantitative technique of brain dopamine images, in particular to a technique method for dopamine absolute uptake value measurement in SPECT or SPECT-CT brain dopamine images and application of the technique method in dopamine activity assessment. The technique method comprises the implementation steps of nuclide physical decay correcting, patient motion correcting during scanning, scattering correcting, tissue attenuation figure generating, tissue attenuation correcting, image spatial resolution recovering, noise removing, quantitative index calculating and dopamine activity assessing. Through the technique means, absolute quantitative images and quantitative indexes of the SPECT brain dopamine images can be generated, the problem of conducting brain dopamine quantitative analysis through SPECT and SPECT-CT development is solved, and the technique can be applied to brain dopamine quantity assessment.
Description
[technical field]
The present invention is the quantitative analysis tech about a kind of brain image, especially with regard to a kind of Single photon emission computer tomography imaging (singlephotonemissioncomputedtomography, or the brain image treatment technology of Single photon emission computer tomography imaging/x-ray computer tomography (SPECT/CT) SPECT), can measure for the nuclear medicine single photon dopamine imaging medicament absolute picked-up degree in brain, and carry out the calculating of quantitative target, including: the special picked-up ratio of striatum (striatum), tail (caudate) shell (putamen) ratio and the symmetry value of left and right brain, and the purposes that this technical method is in terms of brain dopamine activity assessment.
[background technology]
Parkinsonism (Parkinson ' sdisease, or Ba Jinsen syndrome (Parkinsonism PD), PM) it is dopamine (dopamine) neurotransmitter hyposecretion or the abnormal caused a kind of nervus centralis type disease of conduction operation in nervus centralis, dyskinesia problems such as the most independently shaking, slow in action and stiff can be caused, according to the statistics defending planning commission, the most every 10 people there is 130-140 people to suffer from PD/PM, is consequently belonging to the high cranial nerve of prevalence rate and degenerates or damage disease.But the PD/PM that is not easily distinguishable clinically trembles the caused dyskinesia with other originality, needs the assistance by nuclear medicine molecular imaging could effectively differentiate both.In recent years with99mThe dopamine SPECT imaging medicament of Tc labelling has been actually applied, but dopamine SPECT imaging now yet suffers from shortcomings, including: imaging medicament injection dosage is relatively low causes picture noise height and other physical factors for the interference of image, the accuracy variation that dopamine SPECT is imaged is big, often cannot effectively the dopamine activity in brain striatum (striatum) accurately be measured, thus reduce the actual application value of dopamine SPECT imaging, and serious obstruction is produced for popularization and application development.
Given this, there is a need to develop the image quantitative analysis technical method of a kind of dopamine SPECT and SPECT/CT imaging, to realize the measurement of dopamine absolute intake and special picked-up ratio (specificbindingratio), tail (caudate) shell (putamen) ratio (caudate-to-putamenratio) and left and right brain symmetry value (SBRsymmetry, the assay method of quantitative target such as SBR-sym), and quantitative target can be actually used in the assessment of brain dopamine activity.
[summary of the invention]
It is an object of the invention to provide the quantitative analysis method that the absolute intake of dopamine of a kind of SPECT or SPECT/CT brain calculates with SBR, CPR and SBR-sym, with overcome tradition SPECT and SPECT/CT technology can only qualitative and cannot the defect of quantitative analysis, and by this New technical use in the assessment of brain dopamine activity.
The technology used in the present invention means are the absolute quantitation image of a kind of SPECT or SPECT/CT brain, intake absolute to the dopamine in brain can accurately measure the calculating with SBR, CPR and SBR-sym quantitative target, novel technical method comprises altogether: (1)99mTc nucleic physical decay aligning step, for being equipped with mental retardation high-res (low-energyhigh-resolution) or SPECT or the SPECT/CT equipment of fan (fan-beam) collimator, the rotation time popped one's head according to SPECT and the Physical Attenuation (isotopedecay) of the half-life compensation image of nucleic;(2) patient's shift calibrating step in scanning: project (forward-projection) before including using iterative and maximal relevance carries out the estimation of patient's motion-vector between each angle and moves with patient between correct scan;(3) scatter correction step, utilizes scattering energy window, calculates scattering (scatter) component in image, and deduct scattering component image and obtain scatter correction image;(4) tissue attenuation image generation step, produces the tissue attenuation image of brain position by the dopamine uptake SPECT image of brain;(5) tissue attenuation aligning step, sets up tissue attenuation matrix by tissue attenuation image, rebuilds removal SPECT image with iterative method and is underestimated dopamine imaging medicament intake because brain tissue's decay causes;(6) image spatial resolution recovering step, by transfer point spacing from the change of collimator surface, measure in projects images and apart from relevant point spread function (pointspreadfunction, PSF), and set up point spread function matrix number, and point spread function matrix number is used for iterative image reconstruction and again recovers spatial resolution;(7) noise remove step, is used in iterative image reconstruction by analyzing (analytic) or small echo (wavelet) wave filter, to remove the noise in image;(8) striatum definitely absorbs concentration recovering step, tested by brain prosthese, obtain partial volume effect (partialvolumeeffect) coefficient of (tail, shell) in striatum and the relation of background ratio through graphical analysis respectively, and then calculate the recovery coefficient matrix of the absolute activity concentration of tail shell;(9) quantitative target calculation procedure, through image alignment, rotate, adjust shape with adjust curvature the SPECT image of absolute quantitation is normalized (normalization), by standardized magnetic resonance brain image and standardized tail, shell and pillow brain " perception interest district " 3D template, measure the uptake values in each district, by recovery coefficient matrix recover tail shell definitely absorb concentration, and carry out the calculating of quantitative target, and including: special picked-up ratio, tail shell ratio and bilateral symmetry value;(10) appraisal procedure, measures the activity height of brain dopamine by quantitative target.
Through the technology used in the present invention means, solve and utilize SPECT and SPECT/CT carry out dopamine image absolute quantitation and accurately measure a difficult problem for quantitative target, and this technology can be made for the assessment of brain dopamine activity height.
[accompanying drawing explanation]
Fig. 1 shows the flow chart moved according to present invention enforcement with patient in automatic correct scan.
Fig. 2 shows according to present invention enforcement to produce the flow chart of tissue attenuation image.
Fig. 3 shows according to present invention enforcement to produce the flow chart of tissue attenuation matrix.
During Fig. 4 A display present invention implements, without the image of timing.
During Fig. 4 B display present invention implements, through the image of noise remove.
During Fig. 4 C display present invention implements, the image of patient's shift calibrating in noise remove, scanning.
During Fig. 4 D display present invention implements, patient's shift calibrating, the image of tissue attenuation correction in noise remove, scanning.
During Fig. 4 E display present invention implements, patient's shift calibrating, tissue attenuation correction, the image of scatter correction in noise remove, scanning.
During Fig. 4 F display present invention implements, patient's shift calibrating, tissue attenuation correction, scatter correction, spatial resolution correction, the image of nucleic physical decay correction in noise remove, scanning.
Fig. 5 shows the absolute uptake values curve implementing to obtain recovery tail shell according to the present invention.
Fig. 6 shows the normalization step implementing SPECT image according to the present invention.
Fig. 7 shows that the foundation present invention implements to obtain two different clinical symptoms showers, by the absolute quantitation SPECT image (left side) after the obtained normalization of this technical method, normalization absolute quantitation SPECT image and standardization 3D magnetic resonance image (MRI) and the fusion image (middle) of region of interest template, by measuring tail, shell calculates left and right SBR with resting the head on definitely absorbing of brain, left and right CPR and SBR-sym value (right table), the SBR quantitative target that display clinical symptoms shows more apparent person is relatively low, CPR quantitative target is relatively low relatively low with SBR-sym quantitative target, therefore the technical method of the present invention can assess brain dopamine activity height.
[detailed description of the invention]
The present invention provides the image quantitative analysis technology that a kind of SPECT Yu SPECT/CT brain dopamine images, it is possible to obtains brain and carries out absolute quantitation for the picked-up of dopamine activity, and carries out the calculating of quantitative target, including SBR, CPR and SBR-sym.Physical correction step is to obtain to determine the essential condition that image is quantitative, it is possible to obtain the lifting of picture quality.
First, nucleic physical decay aligning step, the time point rotated according to the SPECT probe being equipped with mental retardation high-res or fan collimator with99mThe half-life of Tc nucleic, the physical decay of correction chart picture.When SPECT probe is surrounded on patient, the time point in corresponding rotational angle calculates, and calculates correction coefficient with exponential disintegration module (exponentialdecaymodel), thus readjusts the radiocounting in original projection image.
Patient's shift calibrating step in scanning, the patient in correct scan moves (Intra-scanpatientmotion).Patient in scanning moves and is moved between SPECT image acquisition the brain dislocation that position caused by patient, thus affect the accuracy of subsequent images reconstruction.In scanning, the original image of patient is carried out rebuilding acquisition SPECT image by patient's shift calibrating, projects images before front projection (forward-projection) obtains, and and compare original image translation with front projects images in each angle, shift calibrating vector is obtained with maximal relevance, by the iterative process of (reconstruction-front projection-comparison), move with the patient in correct scan.Fig. 1 represents the flow chart that in automatic correct scan, patient moves.
Scatter correction step, utilize the original image of main peak energy window (140 ± 10%keV or 126-154keV) and the dispersion image of scattering energy window (118 ± 12%keV or 110-125keV), by scattering component and the scattering component in the triangle approximation relation estimation original image of main peak energy window, and deduct scattering component from original image and be scattered correction.
Tissue attenuation image generation step, SPECT image after rebuilding is changed to spherical coordinates from rectangular coordinate, the border of brain is found out by ray tracing (raytracing), the position of estimation skull bone, and the region in skull bone is converted to soft tissue position, region outside skull bone is converted to air position, will represent trizonal 140keV attenuation quotient (skull bone: 0.25cm respectively-1, brain soft tissue: 0.154cm-1, air: 0.0cm-1) insert, and image is gone back to rectangular coordinate and obtains tissue attenuation image, Fig. 2 shows the flow chart producing tissue attenuation figure.
Tissue attenuation aligning step, the position rotated by tissue attenuation image correspondence probe, the pad value of the corresponding probe of each pixel cell is calculated with line integral (linearintegration) and the damping matrix that founds an organization with exponential model (exponentialmodel), and in iterative approximation, use tissue attenuation matrix correction tissue attenuation, wherein tissue attenuation matrix records the amplitude of every homologous pair photon attenuation with 4 parameters (x, y, z, θ), and Fig. 3 shows the flow chart producing tissue attenuation matrix.As above-mentioned, before tissue attenuation correction, patient in scanning room has been needed to move, to improve the accuracy of tissue attenuation correction.
Image spatial resolution recovering step, utilize halfwidth (fullwidthofhalfmax) change in Raw projection data of the mobile point source, obtain the point spread function (pointspreadfunction relevant to collimator distance, PSF) set up point spread function matrix number, and point spread function matrix number is used for iterative approximation and again recovers the spatial resolution of image.For SPECT and SPECT/CT of differently configured model, one group of PSF matrix can be measured respectively.PSF can model by analytic function (analyticfunctions).PSF matrix can be subsequently used to the front projection step in iterative approximation, by the spatial resolution of Iterative restoration image.
Noise remove step, will analyze (analytic) or small echo (wavelet) wave filter gives the implantation integrated reconstruction of iteration, to remove the noise in image.The noise of image utilizes in the step of the filtered original image of equivalent analysis wave filter (equivalentanalyticfilter) comparison in iterative approximation and front projects images and gave noise filtering.Alternatively, original image also can use wavelet filter with the noise of front projects images in iterative reconstruction process, in the step of the filtered original image of comparison and front projects images, noise filtering was given equally in iterative approximation, wherein wavelet filter carries out substrate expansion with fixed model (stationarymode) to image, get rid of the expansion coefficient of high frequency again with fixing window width in the expansion coefficient rectangular histogram of different estate (order), and use analytic function that expansion coefficient is filtered, carry out image reorganization the most again.Fig. 4 A to Fig. 4 F represents patient's image (Fig. 4 A) without physical correction respectively;Through the image (Fig. 4 B) of noise remove, picture noise is effectively removed in display;In noise remove, scanning, patient moves the image (Fig. 4 C) of removal, and display is effectively removed because in scanning, patient moves caused scalloping;In noise remove, scanning, patient moves removal, tissue attenuation correction chart picture, (Fig. 4 D), and display image is more uniform and background is relatively low;In noise remove, scanning, patient moves removal, tissue attenuation correction chart picture, scatter correction image (Fig. 4 E), and display promotes the contrast of image further;In noise remove, scanning, patient moves the image (Fig. 4 F) of the complete physical correction that removal, tissue attenuation correction chart picture, tissue attenuation correction chart picture, scatter correction image, spatial resolution recovery and nucleic physical decay are removed, display picture contrast obtains with resolution and improves, overall image quality obtains significantly to be improved, it is often more important that image clump non-quantitation form is converted to quantitative form (pixel value unit: Bq/ml).
Striatum absolute uptake values recovering step, by the brain prosthese of standard, prosthese simulation human brain comprises the positions such as tail, shell, pillow brain and brain bone shell, is respectively filled in, at tail, shell, many groups tallied with the actual situation from pillow brain different99mTc nuclide concentration, gathers through SPECT Yu CT imaging, and SPECT carries out Quantitative Reconstruction with abovementioned steps, to produce the image (pixel value unit: Bq/ml) of quantitative form.SPECT with CT is accurately merged, tail is sketched out with CT, shell and the 3D region, perception interest district resting the head on brain, analyze tail in image, shell uptake values and true nuclide concentration underestimate degree, calculate tail in SPECT image, shell uptake values and the target ratio (target-to-backgroundratio) resting the head on brain capture value, degree and target ratio two parameter will be underestimated and carry out the curvilinear regression of analytical type function (analyticalfunction), obtain the recovery coefficient curve with target ratio as function, tail is caused because of part volume effect with correction, underestimating of the absolute uptake values of shell, thus recover tail, the absolute uptake values of shell, Fig. 5 shows the curve recovering the absolute uptake values of tail shell.
Quantitative target calculation procedure, use magnetic resonance and the tissue attenuation image of a standardization and coupling, standardization tail, shell and the pillow brain masterplate that one group mates with magnetic resonance image (MRI), by the tissue attenuation image of patient with standardization body's decay pattern picture with 12 parameter modules, it is respectively as follows: para-position (x, y, z), rotatesAdjust shape (a, b, c) and tune curvature (i, j, k) to carry out minimizing the difference of two squares to calculate and set up normalization matrix, and normalization matrix set is used for SPECT image and produces the normalization SPECT image that mates with magnetic resonance, overlap for normalization SPECT image by standardization tail, shell and pillow brain masterplate, thus measuring tail, shell and the uptake values of pillow brain, Fig. 6 shows the step of SPECT image normalization.
Dopamine activity appraisal procedure, by testing the recovery coefficient curve obtained from brain prosthese, recover tail, the absolute uptake values of shell, and formula calculates SBR quantitative target, [tail/shell] formula calculates CPR quantitative target and [1-| the right SBR of left SBR-|/average (the right SBR of left SBR+)] calculates SBR-sym index, by the dopamine activity of SBR, CPR with SBR-sym assessment brain with [(tail-pillow brain)/pillow brain].
Illustration one
Fig. 7 A shows that a clinical sports impairment property shows less obvious patient, by the absolute quantitation SPECT image (left side) after the obtained normalization of this technical method, normalization absolute quantitation SPECT image and standardization 3D magnetic resonance image (MRI) and the fusion image (middle) of region of interest template, measure the definitely picked-up of tail, shell and pillow brain and calculate left and right SBR, left and right CPR and SBR-sym value (right table).
Illustration two
Fig. 7 B shows that a clinical sports impairment property shows more apparent patient, again by the absolute quantitation SPECT image (left side) after the obtained normalization of this technical method, normalization absolute quantitation SPECT image and standardization 3D magnetic resonance image (MRI) and the fusion image of region of interest template, measure tail equally, shell calculates left and right SBR with resting the head on definitely absorbing of brain, left and right CPR and SBR-sym value (right table), by can learn after two comparisons clinical symptoms show more apparent patient SBR quantitative target relatively low, CPR quantitative target is relatively low relatively low with SBR-sym quantitative target, therefore the technical method of the present invention can assess brain dopamine activity height.
Claims (10)
1. the absolute quantitation of a brain image measures technology, brain dopamine image processing techniques especially with regard to SPECT or the SPECT/CT camera being equipped with mental retardation high-res or fan-shaped collimator, image absolute quantitation can measure absolute intake and the calculating quantitative target of brain dopamine imaging medicament, definitely intake represents with radiation activity concentration Bq/ml, quantitative target calculates and includes calculating striatal special picked-up ratio by the image of Absolute quantification, tail (caudate) shell (putamen) ratio and the symmetry of left and right brain, and the purposes that the technology of the present invention is in terms of brain dopamine activity assessment, the technology of the present invention comprises:
Nucleic physical decay aligning step, the rotation time popped one's head according to SPECT and the Physical Attenuation of the half-life compensation image of nucleic;
Patient's shift calibrating step in scanning, by iteration comparison process, the patient in correct scan moves and obtains the SPECT image of shift calibrating;
Scatter correction step, utilizes scattering energy window, calculates the scattering component in image, and deduct scattering component image and obtain scatter correction image;
Tissue attenuation image generation step, is changed the flow process specified with tissue attenuation coefficient by the SPECT image after rebuilding, Coordinate Conversion, ray tracing, brain area, thus is obtained tissue attenuation image;
Tissue attenuation aligning step, sets up tissue attenuation matrix by tissue attenuation image, rebuilds removal SPECT image with iterative method and is underestimated dopamine imaging medicament intake because the decay of human body brain tissue causes;
Image spatial resolution recovering step, by transfer point spacing from the change of collimator surface, measure in projects images and apart from relevant point spread function, and set up point spread function matrix number, and point spread function matrix number is used for iterative image reconstruction and again recovers spatial resolution;
Noise remove step, is used in iterative image reconstruction by analysis or wavelet filter, to remove the noise in SPECT image;
Striatum absolute uptake values recovering step, the partial volume effect coefficient of (tail, shell) and the relation of target ratio in striatum is obtained respectively by the experiment of stricture of vagina shape brain prosthese and graphical analysis, and then the recovery coefficient curve of the absolute uptake values of generation tail shell, and it is applied to recover the absolute uptake values of tail shell;
Quantitative target calculation procedure, use standardization magnetic resonance and tissue attenuation figure, calculate generation normalization SPECT image by minimizing the difference of two squares, merged with magnetic resonance and normalization SPECT image by standardization 3D tail, shell and pillow brain masterplate, thus measure tail, shell and the uptake values of pillow brain;
Dopamine activity appraisal procedure, calculates quantitative target with normalized absolute quantitation SPECT image, including: special picked-up ratio, tail shell ratio and bilateral symmetry, and by the dopamine activity of these quantitative targets assessment brain.
2. such as patient's shift calibrating step in the scanning in claim 1, carry out the original image of patient rebuilding and obtain SPECT image, projects images before front projection obtains, and and compare original image translation with front projects images in each angle, shift calibrating vector is obtained with maximal relevance, by the iterative process of (reconstruction-front projection-comparison), move with the patient in correct scan.
3. produce step such as the tissue attenuation figure in claim 1, SPECT image after rebuilding is changed to spherical coordinates from rectangular coordinate, the border of brain is found out by ray tracing, and the region in skull bone is converted to soft tissue position, region outside skull bone is converted to air position, insert representing trizonal 140keV attenuation quotient respectively, and image is gone back to rectangular coordinate and obtains tissue attenuation figure.
4. such as the tissue attenuation aligning step in claim 1, the 140keV attenuation quotient of each pixel cell in SPECT image is calculated by tissue attenuation image, position by SPECT image correspondence probe, a damping matrix is created so that exponential model calculates the pad value of the corresponding probe of each pixel cell with line integral, and in iterative approximation, use damping matrix correction tissue attenuation, wherein damping matrix is with the amplitude of the homologous pair photon attenuation of multiple reference records every.
5. such as the image spatial resolution recovering step in claim 1, utilize the halfwidth change in Raw projection data of the mobile point source, obtain the point spread function relevant to collimator distance and set up point spread function matrix number, and point spread function matrix number is used for iterative approximation and again recovers the spatial resolution of image, point spread function models by analytic function, the front projection step that point spread function matrix number is subsequently used in iterative approximation, by the spatial resolution of Iterative restoration image.
6. such as the noise remove step in claim 1, analysis or wavelet filter are given the implantation integrated reconstruction of iteration, to remove the noise in image, utilize and the step of the equivalent analysis wave filter filtered original image of comparison in iterative approximation and front projects images gave noise filtering, wherein wavelet filter carries out substrate expansion with fixed model to image, get rid of the expansion coefficient of high frequency again with fixing window width in the expansion coefficient rectangular histogram of different estate, and use analytic function that expansion coefficient is filtered, carry out image reorganization the most again, to remove picture noise.
7. uptake values recovering step as absolute in the striatum in claim 1, prosthese experiment need to be first passed through the absolute uptake values of tail, shell is underestimated degree and target ratio two parameter carry out the curvilinear regression of analytical type function, obtain the absolute uptake values recovery coefficient curve with target ratio as function, cause underestimating of the absolute uptake values of tail, shell with correction because of part volume effect, thus recover the absolute uptake values of striatum (tail, shell).
8. definitely absorbing such as the recovery striatum in claim 7, the brain prosthese simulation human brain that need to first pass through use standard comprises the positions such as tail, shell, pillow brain and brain bone shell, is respectively filled in, at tail, shell, many groups tallied with the actual situation from pillow brain different99mTc nuclide concentration, then carry out Quantitative Reconstruction by the image processing step in claim 1, to obtain the SPECT image (pixel value unit: Bq/ml) of quantitative form.
9. such as the quantitative target calculation procedure in claim 1, magnetic resonance and the tissue attenuation figure of a standardization and coupling need to be used, the standardization 3D tail that one group mates with magnetic resonance image (MRI), shell and pillow brain masterplate, the tissue attenuation figure of patient and standardization body's decay pattern are respectively with para-position, rotate, adjust shape and tune curvature to carry out minimizing the difference of two squares to calculate and set up normalization matrix, and normalization matrix is produced with applying mechanically back SPECT image the normalization SPECT image mated with magnetic resonance, by standardization tail, shell and pillow brain masterplate set are for normalization SPECT image, thus measure tail, shell and the uptake values of pillow brain.
10., as in claim 1~9, this quantitative analysis method is applicable to any use99mSPECT or the SPECT/CT imaging of Tc Labeled Dopamine imaging medicament.
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