CN108982557A - Radiobiological experiment radiation pneumonitis CT quantitative detecting method - Google Patents
Radiobiological experiment radiation pneumonitis CT quantitative detecting method Download PDFInfo
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Abstract
The present invention provides a kind of radiobiological experiment radiation pneumonitis CT quantitative detecting method, pass through the low-dose scanning parameter of CT, scan image grows lung images matrix three-dimensional segmentation technology based on automated regional after three-dimensional reconstruction, obtain CT three-dimensional segmentation image pixel histogram, pneumonia exponentiation algorithm is used through pneumonia degree quantitative criterion, mouse pneumonia index is obtained and completes non-invasive quantitative detection.This method has effectively filled up the blank for being directed to mouse radiation pneumonitis model non-invasive quantitative detection method both at home and abroad, it is a kind of experiment detection method that can objective, real-time, precisely quantify the generation of mouse pneumonia, development, accuracy, simplification, stability and the high efficiency of radiation-induced mouse radiation pneumonitis detection can be dramatically increased.Substantially lower experimental cost and while energy, decrease dependence to toy minitype CT, reduce experimental cost, have that noninvasive, quick scanning, precision is high, the significant advantages such as reproducible.
Description
Technical field
The technology of the present invention belongs to experimental method, is related to CT quantitative detecting method more particularly to a kind of radioecology (mouse
Class) experiment radiation pneumonitis CT quantitative detecting method.
Background technique
Mouse radiation pneumonitis model is research normal tissue radioreaction, respiratory disease and immune response machine
The important tool of system has irreplaceable role in radioecology, radiotherapeutics and anti-injury of lungs medicament research and development.It puts
Penetrating property injury of lungs early stage is mainly shown as radiation pneumonitis (the 1-3 month after usual secondary radiotherapy), due to a large amount of T lymphocytes by
Activation generates immune response, a kind of lymphatic pulmonary alveolitis;Advanced stage can develop as interstitial pulmonary fibrosis (6 after irradiation
A month or so).Once it is serious dysfunction of ventilation or respiratory failure that its consequence, which occurs, for pulmonary fibrosis, cause chronic pulmonary source therewith
Property heart disease, eventually leads to the vicious circle of cardio-pulmonary function obstacle (cardiopulmonary syndrome).
However, the generation of face mouse radiation pneumonitis at present both at home and abroad, that development there is no is objective, noninvasive, accurately quantitative
Detection technique, this greatlys restrict the development of this important research field.In the past few decades, in the world still using more
Kind of invasive and/or noninvasive technology reacts to quantify experiment mice pulmonary toxicity after irradiation, including lethality, respiratory rate or
Lung compliance, Histological change, and carry out testing and evaluation radiotoxicity effect with high resolution ct and micro-CT.However,
These check and evaluation means still have many technological deficiencies.
First, physiologic parameters (i.e. respiratory rate, lung compliance, lethality or weight) can more objective reaction lung limit
Abnormal gas caused by property dysfunction of ventilation processed, diffusivity interstitial inflammation or scar exchanges, but these parameters be easy by it is many other
The interference of factor, such as temperature, infection, merging cardiac toxic.
Second, using can only be in lung tissue section it is observed that a small amount of pneumonia, these physiologic index when low dose exposure
Lesion degree is relatively light or the self-healing stage can not actual response pulmonary lesion: also do not observe apparent respiratory rate change,
Individual death or weight loss (when such as x-ray dosage < 10.5Gy), are easy to appear false negative situation.However this false negative situation,
Graded doses (from low to high) measured value is usually required in mathematical modeling carries out operation and simulation, i.e. low dose group detected value spirit
Sensitivity will directly affect the accuracy and reliability of model.
Third, since lung function has larger compensatory capacity, the assessment for early stage injury of lungs (i.e. inflammation phase), tissue
Learn interstitial lung thicken that evidence, inflammatory cell hyperplasia or infiltration and individual mice be dead or respiratory rate increase have no it is directly related
Property, this influences the accuracy of result to a certain extent.
4th, from statistical angle, these methods measurement acquisition data belong to ordinal number variable (ordinal data)
Or quantitative response data (graded response data), before carrying out Probit or Logistic model analysis, it is necessary to root
It factually tests animal number amount and carries out quantization reaction (quantal response) conversion.This usually requires that test different experiments every time
Group is required to keep sizable initial sample size, it is especially desirable in view of the radioactive poison side effect of middle and advanced stage is (as seriously put
Penetrating property dermatitis) and the individual death that dramatically increases of high dose group.
5th, although noninvasive high resolution ct or micro-CT have some superiority on identifying advanced stage lung fiber, this
Advantage is generated dependent on excessive collagen albumen and cicatrization.And radiation pneumonitis does not have the change of this fibrosis, because
This is only difficult to realize the detection to mouse initial lung inflammation with high resolution ct or micro-CT image itself.In addition, radioactivity
Injury of lungs is closely related with dose of radiation, and risk caused by additional x-ray dose commitment caused by long-term CT follow-up can not be ignored.One
As CT picture noise (noise propagation) and (dosage Dose)-1/2(Pixel Dimensions isotropic voxel
size)-2It is directly proportional.In CT image, every n times of the raising of intrinsic resolution, the dose of radiation that mouse receives needs to improve this meaning
n4Times.Briefly, it needs to transport to reduce image motion artifact (such as breathing, heartbeat) in micro-CT or high-resolution ct
With relatively long sweep time and respiratory gating technology, for the x-ray dosage of scanning exposure up to 100-300 mGy, this will every time
The test of direct interference radioactive dosage.
Clinically CT or X-ray examination rabat are the common methods of diagnosis of pneumonia.But due to the small (adult mice of individual mice
Lung's transverse diameter only about 1-1.5cm) it is restricted by CT scan resolution ratio, even high-resolution or profession micro-CT image all can not standards
Make a definite diagnosis disconnected mouse radiation pneumonitis.Have the defects that in view of current induced lung injury mouse experiment above-mentioned, it is objective to be unable to reach
The purpose of accurate quantitative analysis assessment, detection method use area of computer aided diagnostic imaging (computer-assisted
Radiology) technology, to realize a kind of easy, accurate and method that pneumonia development degree can be quantitatively evaluated.Area of computer aided shadow
As diagnostic techniques refers to by iconography, Medical Image Processing and other possible physiology, biochemical apparatus, in conjunction with calculating
The analytical calculation of machine, auxiliary discovery lesion, improves the accuracy rate technology of diagnosis.
Summary of the invention
It is tested the object of the present invention is to provide a kind of radioecology (muroid) and uses radiation pneumonitis CT quantitative detecting method,
It is realized by following steps:
(1) the low-dose scanning parameter of CT includes: 80kV, 80mAs, spacing 0.6mm, thickness 0.6mm, and acquisition time is
32s;The parameter can be applied to the clinical CT equipment of the different manufacturers such as Siemens, Toshiba, Philip, GE, compatible.
(2) scan image grows lung images matrix three-dimensional segmentation technology based on automated regional after three-dimensional reconstruction, includes
(a) 3-dimensional reconstruction and (b) automated regional growth segmentation two parts;
Wherein (a) 3-dimensional reconstruction: by image reconstruction being 138 × 138mm using filter kernel H50s, H60s2Cross
To FOV as 512 × 512 matrixes;
(b) automated regional growth segmentation: using in image post processing software (such as OsiriX) manually shearing CT image
After tracheae, lung tissue window is defined between (- 1000,0), and it is raw that input two above extreme value (maximum and minimum) carries out automated regional
Long segmentation extracts the histogram of the identical lung areas merged in the section of 10HU to obtain CT lung three-dimensional matrice,
The negative exponent of oversampling ratio in SUMO software using 0.2 further smooths histogram;
(3) pneumonia degree quantitative criterion uses pneumonia index (pneumonitis index, PI) algorithm, sweeps through above-mentioned CT
It retouches imaging, three-dimensional image reconstruction and automated regional growth to divide, can be obtained CT three-dimensional segmentation image pixel histogram, meet pool
Lung tissue window (- 900,0) after segmentation is divided into gassiness area (- 900, -450) and interstitial lung area (- 450,0) two by pine distribution
Point, HU absolute value is taken according to pixel histogram:
HUi=HU+1000 (1)
Calculate gray-value pixel distribution weighting (HU weighted):
Histo′i=Histoi × HO 'i (2)
It calculates gray value weighted average (averaged weighted HU):
Therefore, mouse interstitial lung index (P) isSection summation:
According to irradiation group and blank control group interstitial lung index ratio, pneumonia index can be obtained are as follows:
Thus, it is possible to the numerical value for being defined as pneumonia index (PI) is calculated, the bigger i.e. objective reaction mouse of the numerical value
Radiation pneumonitis degree is higher;The numerical value is smaller, i.e. pneumonia degree is lower, and definition Normal healthy mice pneumonia index is 1 (PI=
1)。
It is restricted by image resolution ratio, CT image is to mouse radiation pneumonitis without value of clarifying a diagnosis.Detection method
Using three-dimensional image pixel histogram, by mathematical algorithm to realize area of computer aided diagnostic imaging, essence this is improved
Method sensibility, the further investigation to be suitable for radioactivity murine pneumonia model.Pixel histogram to lung tissue density, including
Gassiness area of lung and interstitial lung area have accurately reflection.The change that the present invention is exactly conceived to pixel histogram interstitial lung area is looked for
To " breach ".Using similar to molecular biology polymerase chain reaction (Polymerase chain reaction, PCR)
Thinking, that is, copy archaeal dna polymerase to expand the mode of specific DNA fragmentation, attempt that histogram will be hidden in by mathematical operation
" password (code) " in figure interstitial lung area is amplified to relatively apparent range.And it is finally realized in the way of gray value weighting
This purpose, establish can non-invasive quantitative assessment mouse radiation pneumonitis method, have noninvasive, quick scanning, precision high, again
Renaturation waits well significant advantages.With stronger research application and actual promotional value.
This method has effectively filled up the blank for being directed to mouse radiation pneumonitis model non-invasive quantitative detection method both at home and abroad, mentions
Detection method objective, real-time, that precisely quantitatively mouse pneumonia occurs, develops can be realized for the first time for a kind of.The technology can significantly increase
Add accuracy, simplification, stability and the high efficiency of radiation-induced mouse radiation pneumonitis detection.Substantially lower experimental cost with
While energy, dependence to toy minitype CT (expensive and cannot quantify) is decreased, by Clinical CT energy
Independent development high-precision, the detection of high-volume mouse radiation pneumonitis and tracking are quantitatively.
Detailed description of the invention
Image three-dimensional divides schematic diagram after Fig. 1 clinic CT scan mouse lung and reconstruction.
Fig. 2 CT non-invasive quantitative detection technique of the present invention and conventional method contrast schematic diagram.
Fig. 3 pixel histogram thermal map dynamic tracing analyzes mouse radiation pneumonitis.
Fig. 4 mouse radiation pneumonitis histopathology verifies (12 weeks).
Under Fig. 5 difference chest dose of radiation, the occurrence and development degree (HE dyeing) of mouse radiation pneumonitis.
Quantitative and modeling of Fig. 6 the method for the present invention for mouse radiation pneumonitis experimental model.
Specific embodiment
The present invention is further described with reference to the drawings and specific embodiments.
1 radioecology of embodiment (muroid) experiment radiation pneumonitis CT quantitative detecting method
The full lung field of mouse is carried out using conventional clinac to irradiate, and completes the model modeling of mouse radiation pneumonitis.
Mouse is in narcosis, is fixed well.
Referring to Fig.1, different time points after the full lung field irradiation of mouse, use medical conventional computer tomoscan (CT) equipment
Image Acquisition is carried out using low-dose scanning parameter;Subsequent row three-dimensional image reconstruction, the lung based on automated regional growth are three-dimensional
Segmentation.
Referring to Fig. 2, the intuitively comparing of CT non-invasive quantitative detection technique and conventional method of the present invention.Previous conventional CT image is commented
Valence generallys use region of interest back-and-forth method (Regions of interests, ROIs), and major defect includes: that subjectivity is big
(sketching the contours range by the subjectivity of experimenter), to pneumonia without x-ray reconditioning in diagnostic value, scanning process larger, cost performance
It is lower.And low-dose scanning parameter of (I) that the present invention initiates based on Clinical CT, (II) scan image are based on after three-dimensional reconstruction
The combination of both automated regional growth lung images matrix three-dimensional segmentations can directly obtain the quantitive CT based on full lung field and change, and turn
Chemical conversion pixel histogram is analysed in depth.
Referring to Fig. 3, lung tissue after irradiation is taken to carry out histopathology verifying mouse lung inflammation.To make alveolar be in expansion
State, the inflammatory cell infiltration state for preferably observing lung tissue carry out paraffin after generalling use 4% formalin perfusion lung cavity
Embed stained slice analysis.
Referring to Fig. 4, CT pixel histogram and thermal map dynamic tracing analyze mouse radiation pneumonitis development, and acquisition group
Knit pathology verifying.Early stage CT follow-up scan image (upper left), correspondence after radiation-induced murine pneumonia model 20Gy roentgen radiation x
Pixel histogram (left) and mean pixel histogram thermal map analysis (lower-left, n=6) and inflammatory phase Histological change (right side).By
This as it can be seen that after the irradiation of full lung equal no significant difference in the 4th, 8,12 week mouse follow-up micro-CT image, radiation pneumonitis
Radiologic imaging presents negative.And pixel histogram thermal map follow-up analysis is utilized, the hot-zone occurred for the 12nd week after display irradiation is " right
Move " phenomenon (arrow), prompt pneumonia lesion.
Referring to Fig. 5, under different chest dose of radiations, the occurrence and development degree (HE dyeing) of mouse radiation pneumonitis.The group
It knits pathology slice analysis and shows that generation, development degree and the dose of radiation size of mouse radiation pneumonitis have direct close
Connection.
Referring to Fig. 6, for the quantitative of mouse radiation pneumonitis experimental model and modeled using quantitative detecting method of the present invention,
Radiation pneumonitis caused by different dose of radiations can be distinguished.It is to be given using two positive control mice experimental models in figure
Wild type C57BL6 mouse DNA dependent protein kinase inhibitor MS-3814 (MS promotees radiation pneumonitis) or DNA dependence egg
White kinases knocks out C57BL6 mouse (DNA-PKcs K.O.) after the full lung irradiation of x-ray graded doses, square frame-shaped: graded doses x-ray
Irradiation mouse gives pneumonia generation, development degree after DNA dependent protein kinase (DNA-PKcs) inhibitor MS-3814 simultaneously;
Triangle: DNA dependent protein kinase knock-out mice gives rear pneumonia generation, development degree after graded doses roentgen radiation x, then base
In effect-dose curve that CT three-dimensional segmentation pixel histogram " pneumonia index " calculates.
Embodiment 2: received after full lung field irradiates 12 weeks using 8-10 week old C57BL6, carry out the quantitative detection of pneumonia, had
Body method is described below:
1. zoopery irradiation and grouping: 8-10 week old C57BL6 female mice is used, SPF grade are raised, and rearing conditions are,
Temperature (23 ± 1) DEG C, relative humidity 55% ± 5%, pressure difference≤10Pa, daily illumination 12h, drinking-water of freely ingesting.
2. being transferred to dedicated mouse chest irradiation device after isoflurane induced anesthesia before irradiation and properly fixing.Using
Conventional clinac carries out full lung field irradiation.
3. giving single 20Gy exposure dose.
4. blank control group does not receive roentgen radiation x (0Gy).Control group and every group of each dosage experiments group are randomly assigned 12
Mouse;
5. (respectively 0,4,8,12 week point) is imaged before irradiation and every 4 weeks row CT scan after irradiation;Low dosage is swept
Retouch technical parameter: 80kV, 80mAs, spacing 0.6mm, thickness 0.6mm, acquisition time 32s;
6. image reconstruction is 138 × 138mm after scanning2Lateral FOV as 512 × 512 matrixes;
Divide after 7.CT 3-dimensional reconstruction through automated regional growing three-dimensional, extraction merges identical in the section of 10HU
The histogram of lung areas further smooths histogram using the negative exponent of 0.2 oversampling ratio;
8. carrying out the calculating of pneumonia index based on CT three-dimensional segmentation lung images matrix, pneumonia generation, development degree are determined;
9. fresh lung tissue is extracted: putting to death mouse using cervical dislocation within the 24th week after irradiation, extract fresh lung tissue
Freeze for further histology and molecular biology research, including the fixed paraffin-embedded tissue of formalin, mRNA and protein
It deposits;
10. histopathology is verified: specimens paraffin embedding slices h and E (HE) dyeing, collagen dyeing are to examine
Look into form and fibrin deposition.The infiltration of inflammatory cell and alveolar septum thickness will be scored using sxemiquantitative;
11. statistical procedures: carrying out data analysis using 7 software of GraphPad Prism.All data meet normal state
Distribution, data indicate that two comparison among groups use independent samples t test with x ± s.P < 0.05 is that difference is statistically significant.
Claims (3)
1. a kind of radiobiological experiment radiation pneumonitis CT quantitative detecting method, which is characterized in that pass through following steps reality
It is existing:
(1) the low-dose scanning parameter of CT includes: 80kV, 80mAs, spacing 0.6mm, thickness 0.6mm, acquisition time 32s;
(2) scan image grows lung images matrix three-dimensional segmentation technology based on automated regional after three-dimensional reconstruction, contains (a)
3-dimensional reconstruction and (b) automated regional growth segmentation two parts;
(3) pneumonia degree quantitative criterion uses pneumonia indices P I algorithm, through the imaging of above-mentioned CT scan, three-dimensional image reconstruction and automatic
Region growing segmentation can be obtained CT three-dimensional segmentation image pixel histogram, meet Poisson distribution, by the lung tissue after segmentation
Window -900,0 point is gassiness area -900, -450 and interstitial lung area -450,0 two parts, HU absolute value is taken according to pixel histogram:
HU '=HU+1000 (1)
It calculates gray-value pixel and is distributed Weighted H U:
Histo’i=Histoi×HU′i (2)
Calculate gray value weighted average HU:
Therefore, mouse interstitial lung indices P is Histo 'i∈ (450,900) section summation:
According to irradiation group and blank control group interstitial lung index ratio, pneumonia index can be obtained are as follows:
Thus, it is possible to the numerical value for being defined as pneumonia indices P I is calculated, the bigger i.e. objective reaction mouse radioactivity of the numerical value
Pneumonia degree is higher;The numerical value is smaller, i.e. pneumonia degree is lower, and defining Normal healthy mice pneumonia index is 1.
2. a kind of radiobiological experiment according to claim 1 radiation pneumonitis CT quantitative detecting method, feature
It is, (a) 3-dimensional reconstruction described in step (2): the use of filter kernel H50s, H60s by image reconstruction is 138 × 138mm2
Lateral FOV as 512 × 512 matrixes;
(b) automated regional growth segmentation: after shearing the tracheae in CT image manually using image post processing software, lung tissue window is fixed
Justice inputs the above maximum with minimum two extreme values and carries out automated regional growth segmentation, to obtain CT lung between -1000,0
Three-dimensional matrice extracts the histogram of identical lung areas merged in the section of 10HU, adopts in SUMO software using 0.2
The negative exponent of sample ratio further smooths histogram.
3. a kind of radiobiological experiment according to claim 1 radiation pneumonitis CT quantitative detecting method, feature
Be, step (1) sweep parameter and Siemens, Toshiba, Philip, GE different manufacturers Clinical CT hardware compatibility.
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
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CN111462097A (en) * | 2020-04-03 | 2020-07-28 | 深圳前海微众银行股份有限公司 | Image processing method, device, equipment and storage medium based on federal learning |
CN111544026A (en) * | 2020-06-02 | 2020-08-18 | 陈强 | Pneumonia index calculating device |
CN111583252A (en) * | 2020-05-15 | 2020-08-25 | 宁波威联生物科技有限公司 | Analysis evaluation device and evaluation system for lung tomography image based on electric field CT |
-
2018
- 2018-07-23 CN CN201810811453.0A patent/CN108982557A/en active Pending
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111462097A (en) * | 2020-04-03 | 2020-07-28 | 深圳前海微众银行股份有限公司 | Image processing method, device, equipment and storage medium based on federal learning |
CN111583252A (en) * | 2020-05-15 | 2020-08-25 | 宁波威联生物科技有限公司 | Analysis evaluation device and evaluation system for lung tomography image based on electric field CT |
CN111544026A (en) * | 2020-06-02 | 2020-08-18 | 陈强 | Pneumonia index calculating device |
CN111544026B (en) * | 2020-06-02 | 2023-04-07 | 陈强 | Pneumonia index calculating device |
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