包尚联ICMIP-全体会议的发言

1、Present and Future of Medical Imaging Physics包尚联Shanglian Bao北京大学医学物理和工程北京市重点实验室Beijing Key Lab of Medical Physics & Engineering北京大学肿瘤物理诊疗技术研究中心The Research Center of Tumor Diagnosis and Therapeutical Physicsbao 2022/8/281ICMIP-2013 沈阳南京Basic disciplines of health protectionPhysics，Chemistry & infor

2、matics Safeguard human healthSolve 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, accuracy2022/8/282ICMIP-2009 沈阳Physic

3、s & Engineering of Medical Imaging Medical Imaging PhysicsPrinciple and prototype deviceMedical Imaging EngineeringIndustry device and productionBoth do application in clinical disease Diagnosisdisease therapeuticsData treatment and analysisVerification and guarantee 2022/8/283ICMIP-2013 沈阳南京4 Major

4、 ModalitiesX-ray Imaging (animal & human imaging)Planer: DR, CRTomography: 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 special2022/8/284ICMIP-

5、2013 沈阳Essential TaskAll places & times need to extend the human eye capability，Accompanying human developmentAfter Macroscopic information，Microscopic information more important； After morphology，physiology more important；After eye visible information, eye invisible information is more important, i

6、ncluding physiology and psychology.2022/8/285ICMIP-2013 沈阳南京Front Direction: Molecular ImagingPermanent topic：New genetic material and proteinsAccompanying the progress of mankindRevealing essential pathological reasonVery earlier (sufficient time to adjust and treatment)2022/8/286ICMIP-2013 沈阳南京mRN

7、ADNARNA酶的合成和活性调控物转运蛋白 RNA结合物报告探针报告基因DNAAATglut 4代谢产物MAb激素配体缩氨酸DNA合成物+ other moleculesAll in dynamical and 3D distribution2022/8/287ICMIP-2013 沈阳南京Two most important moleculesNew genetic materialHuman evolution faster than before (natural and artificial)Nature：changes on biodiversity, climatic condit

8、ions, food chain, speed of mixed race geneArtificial：New genetic modification of plants and animals，even humanProteinsHuman Progress rely on proteins and new proteins 2022/8/288ICMIP-20139 沈阳Gene MutationGood gene mutationPromoting human progressBad gene mutationCause diseases, such as cancerVarious

9、 diseases, e.g. cancer，cardiovascular & brain diseases increasing Every Individual：progressive disease，which is genetically determined 2022/8/289ICMIP-2013 沈阳南京突变, 超量表达基因, 抗原产生抗体生物标志物 遗传 病毒感染 化学致癌物 辐射致癌物 老化 其他血液中相应抗体Cancer genetic material encoding the protein markers用载体克隆基因克隆表达, 基因和载体蛋白克隆筛选得到癌症相关克隆

10、Other MoleculesSuch as Metabolites，Hormones，NeurotransmittersMainly determined by acquired environmentalWhich were worse than before in China, which dependence on health carenew challenges for health workersMedical physicists & physiciansEngineers and others2022/8/2811ICMIP-2013 沈阳南京Complexity & hug

11、e numberMolecules in vivoHuge numbers：constructor body, keep stable running, maintain vitality of cells and humanComplexityMultiple Structures & multiple functionsDifferent roles in different processDynamical changes2022/8/2812ICMIP-2013 沈阳南京New Tasks on Devices and ProbesDevicesCreative new measuri

12、ng 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 2022/8/2813ICMIP-2013 沈阳南京Molecular Nuclear Medical ImagingTraditional molecular imagin

13、gPET，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 patientsNo speci

14、alist to do the analysisNo original creative research (including the drug D)2022/8/2814ICMIP-2013 沈阳南京2001，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

15、Xiaowei hold 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 iamgi

16、ng set up, Tian Jie, Bai Jing and Bao Shanglian 2011, continued 分子影像学国内外研究现状和发展趋势综述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 p

17、arameter imagingSignificant of Dynamical Molecular Imaging”input”output”Authentic tracerconcentrationavailable inarterial bloodConcentrationin tissuemeasured byPET scannerPerfusionEndothelial permeabilityVascular volume fractionTransport across cell membranesSpecific binding to receptorsNon-specific

18、 bindingEnzyme 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:时间活度曲线分类流出型平台型流入型 parameters：time-to

19、-peakSlopeSERGlucoseGlucose-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 modelPET 3D Dynamic Da

20、ta clustering results byK-means and hierarchical clustering combined使用LLS（第一行所示）和cLLS（第二行所示）方法分析3D PET FDG临床动态数据得到的第12层参数图像结果 Parameter images of FDG PETMRI & fMRIAdvantagesOnly modality can simultaneously measure anatomical, physiological and psychological imaging data;Without radiation damage;disa

21、dvantages 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.2022/8/2823ICMIP-2013 沈阳南京Condition is Ripe Whatever phys

22、iology or psychology，the application 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 degree2022/8/2824ICMIP-2013 沈阳南京e.g. Qua

23、ntitative DEC-MRIMethodology TAC Characterization analysisAnalysis of hemodynamic parametersDWI to determine ADC valueslower in tumor areaEnhanced morphological tumor areaEasy to be used by radilogists TAC:时间活度曲线分类流出型平台型流入型 parameters：time-to-peakSlopeSERDCE-MRI 药代分析评估化疗效果的研究病人化疗前情况 （左乳）浸润性导管癌，部分呈导管

24、内癌，局灶区域见淋巴细胞聚集（invasive ductal carcinoma with ductal carcinoma in situ and lymphocytes aggregation病人化疗后情况 化疗后乳腺改良根治标本：乳腺浸润性导管癌（invasive ductal carcinoma），肿瘤组织伴坏死、退变及钙化，肉眼未见明确肿块，镜下可见肿瘤浸润范围约2x2cm。余乳腺组织内可见纤维腺瘤形成。乳头、基底及切缘净。淋巴结：腋窝3/8可见癌转移；另送（腋窝）0/3未见癌转移。化疗前 Ktrans 三维分布Typical output curvesEvaluation afte

25、r Chemotherapy for G4OverviewBREAST IMAGING REPORTING AND DATA 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 dens

26、ity versus indistinct mass. Bilateral routine craniocaudal (A) 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, Ch

27、ristopher T. Remy et al, “MR ImagingDetected Breast Lesions: Histopathologic Correlation of Lesion Characteristics and Signal Intensity Data,” AJR. 178, 14031409 (2002).Neoadjuvant chemotherapy for locally advanced breast cancerTWO-COMPARTMENT REFERENCE REGION PHARMACOKINETIC ANALYSISKtrans (volume

28、transfer constant) Ve (extravascular extracellular volume).The Ktrans is always believed to correlated to angiogenesis and Ve may increase in the case of edema or necrosis. Ktrans 与血管生成有关Ve 与水肿或坏死有关TRADITIONAL QUANTITATIVE TWO-COMPARTMENT REFERENCE REGION PHARMACOKINETIC ANALYSISChallenge 1: 3D T1 m

29、ap of the whole imaging volume With gradient echo multi-angle 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 Popu

30、lation-based (cause significant errors in the calculation)More 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-M

31、RI data points deficiency.results a slice of breast 3D DCE-MRI dataset, the tumor in the left is selected for segmented and further3D 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) st

32、ill has increased values in the rim where tumor locates. In 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

33、vessel and tissue.the 3D Ktrans map of the tumor regionClinical available softwareAfter several PhD thesisIt has been developed as clinical usable softwareBut, been introduced to Top Grade company, but not been approve by CFDA2022/8/2844ICMIP-2013 沈阳南京New Requirements Need put is into a special desi

34、gned MRI facilityTest for more tumors Further improve the accuracy Practice in wide clinical application2022/8/2845ICMIP-2013 沈阳南京Brain imaging & Its ApplicationUSA, Europe start the new projects on brain imaging and more challenge research goal Main task is Connections between individual nerve fibe

35、rs, too difficult non-invasivelyHuman has about 1.5 X 1012 neuronsEach neuron has about 103-105 SynapsesUSA going on plan：HCPNIH：2010-2015;Derive the connection between main brain region to reveal the difference at 1mm space resolutionUndertakerUniversity of Washington, $ 30 million;Harvard Universi

36、ty and the Massachusetts General Hospital and other institutions, $ 8.5 million TasksScan 1200 brain of health adults（including 300 pairs of twins) compare their difference of connectivity, Cognitive and behavioral，Eventually all depict the human brain neural connectionsThey published the results by

37、 MGH firstThe previous results are at 2-3 mm space resulutionEuropean Brain ProjectFeb of 2013，CEC JRC declared: 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 bot

38、h of USA and EuropeAbout the applications Create an artificial brain, know how to improve the connectivity to increase the efficiencyUnderstand how the disease is formed and the onset via comparison with patients such as Schizophrenia, clinical depression or autism (精神分裂症、临床抑郁症或自闭症)Human can do it a

39、t different space resolution level and at Different stages of the process北大正在开展的研究简介北京大学高家红教授来了之后，正在组建一个有3台3T和1台9.4T动物成像系统的MRI中心在神经科学中的应用是高家红教授的专长直接测量神经元的电磁活动产生的信号并成像动态连接度的研究基于解剖学结构，尤其是纤维束的连接基于功能的虚拟的连接静息态的连接问题MRI设备的关键技术研究开发0.7T C型超导MRI系统，实现产业化梯度线圈、屏蔽线圈和匀场线圈的设计；RF线圈的设计和制造谱仪的研发系统软件的开发我的研究小组正在开展立体视觉方面的

40、工作三维立体视觉fMRI研究适应三维立体影视节目观看、显示器的立体化以及其他三维、四维影视节目的增加三维立体视觉盲的存在，基于双眼视觉差的三维立体视觉功能测量立体视觉盲的鉴别观看三维立体视觉舒适度问题的研究V1-V4解剖学结构成像和定位研究人脑视觉皮层区域特性分析视网膜映射脑功能实验第二部分解剖图像信息处理 & 可视化 第一部分 第三部分解剖图像信息处理 & 可视化 第一部分notice针对人类大脑皮层数据的二维平面化分析方法，能够提高解剖学信息的纵向对比分析能力和精度 (Anticevic et al., 2008; Van Essen et al., 1998) ，提高功能数据分析结果的显

41、著性和可信度 (Argall et al., 2006; Hagler et al., 2006; Jo et al., 2007; Van Essen, 2005).结合FreeSurfer和MW 投影的平面分析处理，引入大脑皮层的多层面划分，对五种扫描的数据进行了高分辨率重采样、配准和参数计算。扫描序列和参数计算得到多个参数扫描膨胀的球体空间& 2D 统一空间第四类 Mollweide 投影图大脑皮层的多层细分研究内容 第一部分(A) 其中一个被试的鼓起的左半脑 (LH) 。(B) 球面坐标系下，经过配准的左半脑。(C) Mollweide 投影平面图。第四类 Mollweide 投影图(

42、MW4)枕极 Occipital pole (黄色标记点) 在投影平面图中心. 根据投影平面中心的位置不同，还有另外三类显示See also: /hcnlab/cortical-mapping/57大脑皮质周围多个层面Cortical surface S0: 白质WM/灰质GM交界面;Pial surface S1: 白质GM/脑脊液CSF交界面; Surface S0.5: S0 and S1中间的一层面;Surfaces S-1 and S-2: S0向内白质中的1 mm and 2 mm 位置的层面. 58Scan:(1) 两组高分辨率的MPRage T1加权像 (TR = 3000 m

43、s, TE = 1.62 ms, flip angle = 9o, voxel size 1 1 1 mm); (2) 高分辨率T2加权像 (TR = 2000 ms, TE = 409 ms, variable flip angle, voxel size 1 1 1 mm); (3) 两组 DTI 扫描 (TR = 10700 ms, TE = 95 ms, flip angle = 15o, b = 1500 s/mm2, 30 个方向, voxel size 2 2 2 mm)， 其中第二次DTI扫描的扩散梯度方向与第一次相反，以减少图像平面内的非仿射几何失真 (Shen et al.

44、, 2004); (4) 两组MT扫描，其中一组不加MT脉冲。 (TR = 2600 ms, TE = 13.3 ms, flip angle = 70o, voxels size 2 2 2 mm); (5) 四组EPI扫描，伴随四组视觉刺激 (TR = 2510 ms, TE = 30 ms, flip angle = 90o, voxels size 3 3 4 mm). 数据采集参数 第一部分Parameters：FA: DTI中所使用的各向异性参数能够很好的反映神经纤维的组织结构和完整性。 (Le Bihan, 2003).MTR: Magnetization Transfer Ra

45、tio ，磁化率转移成像（MTI）使用MTR参数，表征细胞膜和髓磷脂的分布情况(Bastin et al., 2009; Schiavone et al., 2009; Vrenken et al., 2010). MTR = (Ms M0) / M0 x100%T1/T2: T1加权像 (我们使用的序列名称为MPrage) 和T2加权像的比值也能从一定程度反映髓磷脂分布和大脑皮层区域的分界线 (Glasser and Van Essen, 2011). 图像处理获得的参数 第一部分视网膜映射脑功能实验第二部分 第三部分视网膜映射脑功能实验的流程第二部分旋转楔形缩放圆环刺激图01FFT 分析0

46、2响应强度F-统计过滤相位编码定位伪彩色标记显示视网膜映射03水平和垂直刺激对应区域分界线参考前人研究成果04划分区域激活信号 相位图 确定边界刺激图及其条件第二部分signal信号时间序列( 上图)频谱分析(下图)信号时序图第二部分相位编码视网膜映射定位图结果.实验结果显示第二部分上页图(A) and (B) 中的黄色矩形框区域放大图.处理结果显示(放大)第二部分依据多个被试平均结果所划分的感兴趣区域(ROI)，同时与白色线条显示的Van Essen小组研究结果进行对比印证. 视网膜映射脑功能实验第二部分人脑视觉皮层区域特性分析 第三部分不同ROI内在五层平面上的EAR (左)FA (右)平

47、均值及其标准误差各向异性的分布 第三部分不同ROI内在五层平面上的MTR平均值及其标准误差分层显示MTR值 第三部分不同ROI内在五层平面上的T1/T2平均值及其标准误差显示T1/T2平均值及其标准误差结果的图标显示 第三部分结论1对解剖学图像的高精度配准，能够减少多个被试之间高阶视觉区域(V2, V3 et al.)位置的差异.2多个解剖学参数在不同视觉功能区域内都体现一定拓扑分布规律.3白质和灰质内不同的变化趋势.4ROI内上述参数的左右大脑不对称性.关于立体图像中的双眼视差引起的脑激活差异的功能磁共振研究立体图像中的双眼视差引起的脑激活差异。通过向观察者展示消除了形状因素差异的立体图，几

48、个与立体视觉相关的脑区被鉴别出来，它们主要分布在背侧视觉通路上。在视差幅度和符号方面，信号强度和平面刺激相应之间都表现出了明显差异。.立体刺激片源的设计技术路线通常使用的随机点立体图这种立体图在二维情况下是一群没有意义的随机点，而在三维情况下却表现出了一定的形状，因此三维与二维对比的差异不仅仅表现为平面与立体差异，还具有物体的形状。立体片源的设计改进后的随机点立体图采用黑白棋盘格布局的方式，使得二维和三维情况下具有相同的形状特征，从而消除了形状因素造成的对比差异，只存在立体差异。左右眼子图融合后的红蓝立体图二维和三维效果图数据采集方法6种视差block（随机展示）一个block群（8个bloc

49、k，每个block持续20s)Block实验设计方式，包含8种实验条件（1个控制条件，1个平面刺激条件，6个立体刺激条件）结果统计参数图谱3对主要的区域得到了明显的激活，它们分布在背侧视觉通路（V2，V3A，hMT/V5)及顶叶(DIPSM, DIPSA)上。没有明显的腹侧脑区被激活。而其他使用随机点形成的立体图的研究者在实验中却发现了相关的腹侧激活脑区。激活图谱的说明激活簇T得分峰值MNI 坐标/mmBrodmann 脑区(体素数目a)功能脑区19.04(-18, -90, 30)BA18(33), BA19(133)V2, V3A27.03(21, -93, 24)37.38(-39, -

50、81, 6)BA18(13), BA19(46), BA39(14)hMT/V545.63(39, -81, 3)55.58(-24, -57, 60)BA7(99)DIPSM, DIPSA66.74(24, -63, 66)a 体素数目实质包含在对应Brodmann脑区内的 激活体素数目。体素大小为333mm。统计学直方图分析结果3对激活簇的视差-激活图所有背侧通路脑区的激活强度都随视差幅度增加而增加在相同视差幅度下，正视差（近视差）要比负视差（远视差）引起更强烈的脑激活结论使用静态立体图的实验发现了腹侧区域的激活，而我们改进后的图片没有引起腹侧区域激活。因此我们推断：背侧视觉通路或许在立体

51、视觉处理中发挥着主要的作用，而腹侧视觉通路仅仅抽取了立体图中的形状信息。我们的被试普遍反映正视差要比负视差的立体图难感知，大视差要比小视差难感知。因此我们推断：两幅视网膜图像越难以被感知，大脑激活区显示出越强的响应。观察立体影视刺激的连接度问题通过比较不同脑区之间的神经活动的时间相关性，得到功能性脑网络连接，而脑区之间的时间相关性强弱表示了脑功能区之间连接的强弱。通过解剖学结构之间的连接(DTI和DSI)研究搞清楚神经系统在连接过程中如何工作的。在很高空间分辨率条件下，两种有可能一致。用fMRI开展的功能性连接采用fMRI手段获得脑区的神经活动信号，相比其它方法它有更好的空间定位性。对于静息状

52、态和任务状态下的BOLD信号的数据采集，都是通过EPI序列做连续扫描。然后构建出不同脑区之间的功能连接。有两种方法来分析功能数据1.用 Independent component analysis等统计学方法，在数据驱动条件下分析时空信号，确定功能网络。2. Seed-based/Region of interest 分析感兴趣区和其它区域之间的关系，揭示这个功能区相关性质。功能性连接和疾病的关系目前解决的只是粗连接上出问题的疾病，例如：老年痴呆症：连接会减弱 Li, R (2012) AJNR Am J Neuroradiol.自闭症：连接会增强 Hulvershorn (2011) Brain Imaging Behav.精神分裂症：连接网络紊乱 Venkatara