包尚聯(lián)ICMIP-XXXX全體會議的發(fā)言ppt課件

1、Present and Future of Medical Imaging Physics包尚聯(lián)Shanglian Bao北京大學(xué)醫(yī)學(xué)物理和工程北京市重點實驗室 Key Lab of Medical Physics & Engineering北京大學(xué)腫瘤物理診療技術(shù)研討中心The Research Center of Tumor Diagnosis and Therapeutical P .Basic disciplines of health protectionPhysics，Chemistry & informatics Safeguard human h

2、ealthSolve problem from original requirementGoal: get enough Vivo state information by Non-invasive medical imaging means including molecular，cell，organ and system for morphological, physiological and psychological information in precise, accuracy.Physics & Engineering of Medical Imaging Medical Ima

3、ging PhysicsPrinciple and prototype deviceMedical Imaging EngineeringIndustry device and productionBoth do application in clinical disease Diagnosisdisease therapeuticsData treatment and analysisVerification and guarantee .4 Major ModalitiesX-ray Imaging (animal & human imaging)Planer: DR, CRTomogra

4、phy: spiral CT, Cone Bean CT NMI (animal & human imaging)SPECT: combining with CTPET: combining with CTMRI (animal & human imaging)Middle，high & Extra high field system;Ultrasound I3D, 4D imagingGeneral and special.Essential TaskAll places & times need to extend the human eye capability，Accompanying

5、 human developmentAfter Macroscopic information，Microscopic information more important； After morphology，physiology more important；After eye visible information, eye invisible information is more important, including physiology and psychology.Front Direction: Molecular ImagingPermanent topic：New gen

6、etic material and proteinsAccompanying the progress of mankindRevealing essential pathological reasonVery earlier (sufficient time to adjust and treatment).mRNADNARNA酶的合成和活性調(diào)控物轉(zhuǎn)運蛋白 RNA結(jié)合物報告探針報告基因DNAAATglut 4代謝產(chǎn)物MAb激素配體縮氨酸DNA合成物+ other moleculesAll in dynamical and 3D distribution.Two most important

7、moleculesNew genetic materialHuman evolution faster than before (natural and artificial)Nature：changes on biodiversity, climatic conditions, food chain, speed of mixed race geneArtificial：New genetic modification of plants and animals，even humanProteinsHuman Progress rely on proteins and new protein

8、s .Gene MutationGood gene mutationPromoting human progressBad gene mutationCause diseases, such as cancerVarious diseases, e.g. cancer，cardiovascular & brain diseases increasing Every Individual：progressive disease，which is genetically determined .突變, 超量表達基因, 抗原產(chǎn)生抗體生物標志物 遺傳 病毒感染 化學(xué)致癌物 輻射致癌物 老化 其他血液中

9、相應(yīng)抗體Cancer genetic material encoding the protein markers用載體克隆基因克隆表達, 基因和載體蛋白克隆挑選得到癌癥相關(guān)克隆.Other MoleculesSuch as Metabolites，Hormones，NeurotransmittersMainly determined by acquired environmentalWhich were worse than before in China, which dependence on health carenew challenges for health workersMedi

10、cal physicists & physiciansEngineers and others.Complexity & huge numberMolecules in vivoHuge numbers：constructor body, keep stable running, maintain vitality of cells and humanComplexityMultiple Structures & multiple functionsDifferent roles in different processDynamical changes.New Tasks on Device

11、s and ProbesDevicesCreative new measuring imaging devices Multiple modality integrationComprehensive data analysis and processingProbesCovering all kind of moleculesMethodologies on Synthesis, labeling and testingProbes for new modalities，e.g. for MRI .Molecular Nuclear Medical ImagingTraditional mo

12、lecular imagingPET，SPECT & their combination with CT, MRIDeveloped a sufficient number of biological probesRoutine clinical diagnostic toolDisadvantage Poor space and time resolutionsTake them as anatomic source only using their WeaknessWhy no dynamical analysis in ChinaNo time to satisfy so many pa

13、tientsNo specialist to do the analysisNo original creative research (including the drug D).2001，first Inter. Conference in molecular imaging in Boston2002, May, Nature: Vasilis Ntziachristos et al: Fluorescence molecular tomography resolves protease activity in vivo2002, October Mr. Tang Xiaowei hol

14、d the Xiangshan Science Symposium in Hang Zhou, Title: Molecular medical imaging.End of 2002，Based imaging measurements (including optical imaging) of the dynamics of molecular and cellular events Visualization, Science: One of the top ten breakthroughs2006, 973 subject on molecular iamging set up,

15、Tian Jie, Bai Jing and Bao Shanglian 2021, continued 分子影像學(xué)國內(nèi)外研討現(xiàn)狀和開展趨勢綜述.Diagnosis in earlier stage, distinguish Benign and malignant tumors；Develop new drugs：Pharmacology, toxicity, and in vivo stability, including the probesTesting the dynamical analysis modelQuantitative parameters in parameter i

16、magingSignificant of Dynamical Molecular Imaging.inputoutputAuthentic tracerconcentrationavailable inarterial bloodConcentrationin tissuemeasured byPET scannerPerfusionEndothelial permeabilityVascular volume fractionTransport across cell membranesSpecific binding to receptorsNon-specific bindingEnzy

17、me activityPrinciple parametric image：Perfusion (mL blood)/(min x mL tissue)Glucose uptake rate (mol glucose) / (min x mL tissue)Binding potential (Bmax/Kd).BLOODorPLASMATACTISSUE TAC-sinogram or-image or-regionalRESULTS(model parameters)MODELModel .TAC:時間活度曲線分類流出型平臺型流入型 parameters：time-to-peakSlope

18、SER.GlucoseGlucose-6-PhosphateGlucoseK1k3k2k418FFDG18FFDG -6-Phosphate18FFDGK*1k*3k*2k*4Lumped constant (LC) correctsfor the different affinities oftransporters and hexokinaseto glucose and FDGInflux rate constant:Linear & Non- Linear models，here FDG Three compartment model.PET 3D Dynamic Data clust

19、ering results byK-means and hierarchical clustering combined.運用LLS第一行所示和cLLS第二行所示方法分析3D PET FDG臨床動態(tài)數(shù)據(jù)得到的第12層參數(shù)圖像結(jié)果 Parameter images of FDG PET.MRI & fMRIAdvantagesOnly modality can simultaneously measure anatomical, physiological and psychological imaging data;Without radiation damage;disadvantages

20、Complex and expensivefMRI dose not spread in clinical (re-training physicians, phyicists)FutureClinical regulation of Neurology & psychological Develop and practice more reliable analyzing softwareAdd more position in radiology Dept.Condition is Ripe Whatever physiology or psychology，the application

21、 in clinical is Progressively ripeFacilities of MRI Improve faster； Physiological parameter measuring is accurate enough for clinical testSports, and ear, nose and eye-related functions are enough precisely measured in some degree.e.g. Quantitative DEC-MRIMethodology TAC Characterization analysisAna

22、lysis of hemodynamic parametersDWI to determine ADC valueslower in tumor areaEnhanced morphological tumor areaEasy to be used by radilogists .TAC:時間活度曲線分類流出型平臺型流入型 parameters：time-to-peakSlopeSER.DCE-MRI 藥代分析評價化療效果的研討病人化療前情況 左乳浸潤性導(dǎo)管癌，部分呈導(dǎo)管內(nèi)癌，局灶區(qū)域見淋巴細胞聚集invasive ductal carcinoma with ductal carcinoma

23、 in situ and lymphocytes aggregation病人化療后情況 化療后乳腺改良根治本本：乳腺浸潤性導(dǎo)管癌invasive ductal carcinoma，腫瘤組織伴壞死、退變及鈣化，肉眼未見明確腫塊，鏡下可見腫瘤浸潤范圍約2x2cm。余乳腺組織內(nèi)可見纖維腺瘤構(gòu)成。乳頭、基底及切緣凈。淋巴結(jié)：腋窩3/8可見癌轉(zhuǎn)移；另送腋窩0/3未見癌轉(zhuǎn)移。.化療前 Ktrans 三維分布.Typical output curves.Evaluation after Chemotherapy for G4.Overview.BREAST IMAGING REPORTING AND DAT

24、A SYSTEM: BI RADS American College of Radiology. Illustrated Breast Imaging Reporting and Data System (BI-RADS), 3rd ed. Reston, VA: American College of Radiology, 1998Fig 57-year-old woman with lesion variably termed focal asymmetric density versus indistinct mass. Bilateral routine craniocaudal (A

25、) and mediolateral oblique (B) mammograms show focal normal variant asymmetric parenchyma (arrows) that was unchanged for 5 years.THE SHORTAGE OF CHARACTERISTIC KINETIC CURVE (CKC)Katja C. Siegmann, Markus Mller-Schimpfle, Fritz Schick, Christopher T. Remy et al, “MR ImagingDetected Breast Lesions:

26、Histopathologic Correlation of Lesion Characteristics and Signal Intensity Data, AJR. 178, 14031409 (2002).Neoadjuvant chemotherapy for locally advanced breast cancer.TWO-COMPARTMENT REFERENCE REGION PHARMACOKINETIC ANALYSISKtrans (volume transfer constant) Ve (extravascular extracellular volume).Th

27、e Ktrans is always believed to correlated to angiogenesis and Ve may increase in the case of edema or necrosis. Ktrans 與血管生成有關(guān)Ve 與水腫或壞死有關(guān).TRADITIONAL QUANTITATIVE TWO-COMPARTMENT REFERENCE REGION PHARMACOKINETIC ANALYSISChallenge 1: 3D T1 map of the whole imaging volume With gradient echo multi-angl

28、e approach used, it take more than ten minutes for the measurement.Challenge 2: AIF (Artery input function: the concentration of contrast agent in the vascular) It is difficult to get AIF through direct measurement.Traditional solution Population-based (cause significant errors in the calculation)Mo

29、re than conventional DCE-MRI 3D dataset acquisitions .Our solutionFixed T1 value for contrast agent concentration deriving.Reference region model instead of conventionalA empirical formula and fuzzy-cluster are adopted for conventional DCE-MRI data points deficiency.results a slice of breast 3D DCE-

30、MRI dataset, the tumor in the left is selected for segmented and further.3D Ktrans maps show the proliferation area in the periphery with the increased Ktrans value in this area.For 3D Ve map, the malignant area (defined by the Ktrans map) still has increased values in the rim where tumor locates. I

31、n the center of the tumor, the Ve value is still relatively low.a benign example (one slice of the 3D DCE-MRI dataset).the 3D Ktrans map of the tumor, some relative high voxel of the Ktrans map may be caused by the exchange between the normal vessel and tissue.the 3D Ktrans map of the tumor region.C

32、linical available softwareAfter several PhD thesisIt has been developed as clinical usable softwareBut, been introduced to Top Grade company, but not been approve by CFDA.New Requirements Need put is into a special designed MRI facilityTest for more tumors Further improve the accuracy Practice in wi

33、de clinical application.Brain imaging & Its ApplicationUSA, Europe start the new projects on brain imaging and more challenge research goal Main task is Connections between individual nerve fibers, too difficult non-invasivelyHuman has about 1.5 X 1012 neuronsEach neuron has about 103-105 Synapses.U

34、SA going on plan：HCPNIH：2021-2021;Derive the connection between main brain region to reveal the difference at 1mm space resolutionUndertakerUniversity of Washington, $ 30 million;Harvard University and the Massachusetts General Hospital and other institutions, $ 8.5 million TasksScan 1200 brain of h

35、ealth adultsincluding 300 pairs of twins) compare their difference of connectivity, Cognitive and behavioral，Eventually all depict the human brain neural connectionsThey published the results by MGH firstThe previous results are at 2-3 mm space resulution.European Brain ProjectFeb of 2021，CEC JRC de

36、clared: HumanBrainProject in 1 billion euros in 10 years to simulate whole brainFirst step is also 1mm space resolution simulation with real time requirement, This is an Infinite, no end plan both of USA and Europe.About the applications Create an artificial brain, know how to improve the connectivi

37、ty to increase the efficiencyUnderstand how the disease is formed and the onset via comparison with patients such as Schizophrenia, clinical depression or autism (精神分裂癥、臨床抑郁癥或自閉癥)Human can do it at different space resolution level and at Different stages of the process.北大正在開展的研討簡介北京大學(xué)高家紅教授來了之后，正在組建一

38、個有3臺3T和1臺9.4T動物成像系統(tǒng)的MRI中心在神經(jīng)科學(xué)中的運用是高家紅教授的專長直接丈量神經(jīng)元的電磁活動產(chǎn)生的信號并成像動態(tài)銜接度的研討基于解剖學(xué)構(gòu)造，尤其是纖維束的銜接基于功能的虛擬的銜接靜息態(tài)的銜接問題.MRI設(shè)備的關(guān)鍵技術(shù)研討開發(fā)0.7T C型超導(dǎo)MRI系統(tǒng)，實現(xiàn)產(chǎn)業(yè)化梯度線圈、屏蔽線圈和勻場線圈的設(shè)計；RF線圈的設(shè)計和制造譜儀的研發(fā)系統(tǒng)軟件的開發(fā).我的研討小組正在開展立體視覺方面的任務(wù)三維立體視覺fMRI研討順應(yīng)三維立體影視節(jié)目觀看、顯示器的立體化以及其他三維、四維影視節(jié)目的添加三維立體視覺盲的存在，基于雙眼視覺差的三維立體視覺功能丈量立體視覺盲的鑒別觀看三維立體視覺溫馨度問題的

39、研討.V1-V4解剖學(xué)構(gòu)呵斥像和定位研討人腦視覺皮層區(qū)域特性分析視網(wǎng)膜映射腦功能實驗第二部分解剖圖像信息處置 & 可視化 第一部分 第三部分.解剖圖像信息處置 & 可視化 第一部分notice針對人類大腦皮層數(shù)據(jù)的二維平面化分析方法，可以提高解剖學(xué)信息的縱向?qū)Ρ确治霾鸥珊途?(Anticevic et al., 2021; Van Essen et al., 1998) ，提高功能數(shù)據(jù)分析結(jié)果的顯著性和可信度 (Argall et al., 2006; Hagler et al., 2006; Jo et al., 2007; Van Essen, 2005).結(jié)合FreeSurfer和MW

40、 投影的平面分析處置，引入大腦皮層的多層面劃分，對五種掃描的數(shù)據(jù)進展了高分辨率重采樣、配準和參數(shù)計算。掃描序列和參數(shù)計算得到多個參數(shù)掃描膨脹的球體空間& 2D 一致空間第四類 Mollweide 投影圖大腦皮層的多層細分研討內(nèi)容 第一部分.(A) 其中一個被試的鼓起的左半腦 (LH) 。(B) 球面坐標系下，經(jīng)過配準的左半腦。(C) Mollweide 投影平面圖。.第四類 Mollweide 投影圖(MW4)枕極 Occipital pole (黃色標志點) 在投影平面圖中心. 根據(jù)投影平面中心的位置不同，還有另外三類顯示See also: /hcnlab/cortical

41、-mapping/.大腦皮質(zhì)周圍多個層面Cortical surface S0: 白質(zhì)WM/灰質(zhì)GM交界面;Pial surface S1: 白質(zhì)GM/腦脊液CSF交界面; Surface S0.5: S0 and S1中間的一層面;Surfaces S-1 and S-2: S0向內(nèi)白質(zhì)中的1 mm and 2 mm 位置的層面. .Scan:(1) 兩組高分辨率的MPRage T1加權(quán)像 (TR = 3000 ms, TE = 1.62 ms, flip angle = 9o, voxel size 1 1 1 mm); (2) 高分辨率T2加權(quán)像 (TR = 2000 ms, TE =

42、409 ms, variable flip angle, voxel size 1 1 1 mm); (3) 兩組 DTI 掃描 (TR = 10700 ms, TE = 95 ms, flip angle = 15o, b = 1500 s/mm2, 30 個方向, voxel size 2 2 2 mm)， 其中第二次DTI掃描的分散梯度方向與第一次相反，以減少圖像平面內(nèi)的非仿射幾何失真 (Shen et al., 2004); (4) 兩組MT掃描，其中一組不加MT脈沖。 (TR = 2600 ms, TE = 13.3 ms, flip angle = 70o, voxels size

43、 2 2 2 mm); (5) 四組EPI掃描，伴隨四組視覺刺激 (TR = 2510 ms, TE = 30 ms, flip angle = 90o, voxels size 3 3 4 mm). 數(shù)據(jù)采集參數(shù) 第一部分.Parameters：FA: DTI中所運用的各向異性參數(shù)可以很好的反映神經(jīng)纖維的組織構(gòu)造和完好性。 (Le Bihan, 2003).MTR: Magnetization Transfer Ratio ，磁化率轉(zhuǎn)移成像MTI運用MTR參數(shù)，表征細胞膜和髓磷脂的分布情況(Bastin et al., 2021; Schiavone et al., 2021; Vrenke

44、n et al., 2021). MTR = (Ms M0) / M0 x100%T1/T2: T1加權(quán)像 (我們運用的序列稱號為MPrage) 和T2加權(quán)像的比值也能從一定程度反映髓磷脂分布和大腦皮層區(qū)域的分界限 (Glasser and Van Essen, 2021). 圖像處置獲得的參數(shù) 第一部分.視網(wǎng)膜映射腦功能實驗第二部分 第三部分.視網(wǎng)膜映射腦功能實驗的流程第二部分旋轉(zhuǎn)楔形縮放圓環(huán)刺激圖01FFT 分析02呼應(yīng)強度F-統(tǒng)計過濾相位編碼定位偽彩色標志顯示視網(wǎng)膜映射03程度和垂直刺激對應(yīng)區(qū)域分界限參考前人研討成果04劃分區(qū)域激活信號 相位圖 確定邊境.刺激圖及其條件第二部分.sign

45、al信號時間序列( 上圖)頻譜分析(以下圖)信號時序圖第二部分.相位編碼視網(wǎng)膜映射定位圖結(jié)果.實驗結(jié)果顯示第二部分.上頁圖(A) and (B) 中的黃色矩形框區(qū)域放大圖.處置結(jié)果顯示(放大)第二部分.根據(jù)多個被試平均結(jié)果所劃分的感興趣區(qū)域(ROI)，同時與白色線條顯示的Van Essen小組研討結(jié)果進展對比印證. 視網(wǎng)膜映射腦功能實驗第二部分.人腦視覺皮層區(qū)域特性分析 第三部分.不同ROI內(nèi)在五層平面上的EAR (左)FA (右)平均值及其規(guī)范誤差各向異性的分布 第三部分.不同ROI內(nèi)在五層平面上的MTR平均值及其規(guī)范誤差分層顯示MTR值 第三部分.不同ROI內(nèi)在五層平面上的T1/T2平均值

46、及其規(guī)范誤差顯示T1/T2平均值及其規(guī)范誤差.結(jié)果的圖標顯示 第三部分.結(jié)論1對解剖學(xué)圖像的高精度配準，可以減少多個被試之間高階視覺區(qū)域(V2, V3 et al.)位置的差別.2多個解剖學(xué)參數(shù)在不同視覺功能區(qū)域內(nèi)都表達一定拓撲分布規(guī)律.3白質(zhì)和灰質(zhì)內(nèi)不同的變化趨勢.4ROI內(nèi)上述參數(shù)的左右大腦不對稱性.關(guān)于立體圖像中的雙眼視差引起的腦激活差別的功能磁共振研討立體圖像中的雙眼視差引起的腦激活差別。經(jīng)過向察看者展現(xiàn)消除了外形要素差別的立體圖，幾個與立體視覺相關(guān)的腦區(qū)被鑒別出來，它們主要分布在背側(cè)視覺通路上。在視差幅度和符號方面，信號強度和平面刺激相應(yīng)之間都表現(xiàn)出了明顯差別。.立體刺激片源的設(shè)計技

47、術(shù)道路通常運用的隨機點立體圖這種立體圖在二維情況下是一群沒有意義的隨機點，而在三維情況下卻表現(xiàn)出了一定的外形，因此三維與二維對比的差別不僅僅表現(xiàn)為平面與立體差別，還具有物體的外形。.立體片源的設(shè)計改良后的隨機點立體圖采用黑白棋盤格規(guī)劃的方式，使得二維和三維情況下具有一樣的外形特征，從而消除了外形要素呵斥的對比差別，只存在立體差別。左右眼子圖交融后的紅藍立體圖二維和三維效果圖.數(shù)據(jù)采集方法6種視差block隨機展現(xiàn)一個block群8個block，每個block繼續(xù)20s)Block實驗設(shè)計方式，包含8種實驗條件1個控制條件，1個平面刺激條件，6個立體刺激條件.結(jié)果統(tǒng)計參數(shù)圖譜3對主要的區(qū)域得到了

48、明顯的激活，它們分布在背側(cè)視覺通路V2，V3A，hMT/V5)及頂葉(DIPSM, DIPSA)上。沒有明顯的腹側(cè)腦區(qū)被激活。而其他運用隨機點構(gòu)成的立體圖的研討者在實驗中卻發(fā)現(xiàn)了相關(guān)的腹側(cè)激活腦區(qū)。.激活圖譜的闡明激活簇T得分峰值MNI 坐標/mmBrodmann 腦區(qū)(體素數(shù)目a)功能腦區(qū)19.04(-18, -90, 30)BA18(33), BA19(133)V2, V3A27.03(21, -93, 24)37.38(-39, -81, 6)BA18(13), BA19(46), BA39(14)hMT/V545.63(39, -81, 3)55.58(-24, -57, 60)BA7

49、(99)DIPSM, DIPSA66.74(24, -63, 66)a 體素數(shù)目本質(zhì)包含在對應(yīng)Brodmann腦區(qū)內(nèi)的 激活體素數(shù)目。體素大小為333mm。.統(tǒng)計學(xué)直方圖分析結(jié)果3對激活簇的視差-激活圖一切背側(cè)通路腦區(qū)的激活強度都隨視差幅度添加而添加在一樣視差幅度下，正視差近視差要比負視差遠視差引起更劇烈的腦激活.結(jié)論運用靜態(tài)立體圖的實驗發(fā)現(xiàn)了腹側(cè)區(qū)域的激活，而我們改良后的圖片沒有引起腹側(cè)區(qū)域激活。因此我們推斷：背側(cè)視覺通路或許在立體視覺處置中發(fā)揚著主要的作用，而腹側(cè)視覺通路僅僅抽取了立體圖中的外形信息。我們的被試普遍反映正視差要比負視差的立體圖難感知，大視差要比小視差難感知。因此我們推斷：兩

50、幅視網(wǎng)膜圖像越難以被感知，大腦激活區(qū)顯示出越強的呼應(yīng)。.察看立體影視刺激的銜接度問題經(jīng)過比較不同腦區(qū)之間的神經(jīng)活動的時間相關(guān)性，得到功能性腦網(wǎng)絡(luò)銜接，而腦區(qū)之間的時間相關(guān)性強弱表示了腦功能區(qū)之間銜接的強弱。經(jīng)過解剖學(xué)構(gòu)造之間的銜接(DTI和DSI)研討搞清楚神經(jīng)系統(tǒng)在銜接過程中如何任務(wù)的。在很高空間分辨率條件下，兩種有能夠一致。.用fMRI開展的功能性銜接采用fMRI手段獲得腦區(qū)的神經(jīng)活動信號，相比其它方法它有更好的空間定位性。對于靜息形狀和義務(wù)形狀下的BOLD信號的數(shù)據(jù)采集，都是經(jīng)過EPI序列做延續(xù)掃描。然后構(gòu)建出不同腦區(qū)之間的功能銜接。有兩種方法來分析功能數(shù)據(jù)1.用 Independent component analysis等統(tǒng)計學(xué)方法，在數(shù)據(jù)驅(qū)動條件下分析時空信號，確定功能網(wǎng)絡(luò)。2. Seed-based/Region of interest 分析感興趣區(qū)和其它區(qū)域之間的關(guān)系，提示這個功能區(qū)相關(guān)性質(zhì)。.功能性銜接和疾病的關(guān)系目前處理的只是粗銜接上出問題的疾病，例如：老年癡呆癥：銜接會減弱 Li, R (2021) AJNR Am J Neuroradiol.自閉癥：銜接會加強 Hulvershorn (2021) Brain Imaging Behav.精神分裂癥：銜接網(wǎng)絡(luò)紊亂 Venkataraman (20