016 2012MR elastography of the in vivo abdominal aorta：a feasibility study for comparing

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超声弹性成像在乳腺疾病诊断中的仿真分析

超声弹性成像在乳腺疾病诊断中的仿真分析赵婷婷;严碧歌【摘要】乳腺疾病是当今女性的常见病,由于超声检查简单易行,已成为乳腺疾病中良恶性肿块鉴别的常用方法.本研究借助于MATLAB软件下的PDE工具箱,利用有限元分析方法,结合弹性力学理论计算得到良恶性乳腺肿块在不同情况下的应变分布图.仿真结果表明,对于弹性模量较大的肿块,其x方向应变和切应变图像在鉴别诊断上都具有较高的临床应用价值,但是对于一些硬度较大的良性病变和一些硬度较小的恶性病变,其准确性不是很高,为后续研究提供了依据.【期刊名称】《中国生物医学工程学报》【年(卷),期】2011(030)001【总页数】6页(P140-145)【关键词】乳腺肿瘤;超声弹性成像;应变【作者】赵婷婷;严碧歌【作者单位】陕西师范大学物理学与信息技术学院,西安,710062;陕西师范大学物理学与信息技术学院,西安,710062【正文语种】中文【中图分类】R318引言乳腺疾病是一种常见病，多发病，是危害妇女身心健康的主要疾病，其致病因素较复杂，如不及时治疗，将可能发生病变，随时导致生命危险。

近年来，我国的乳腺疾病发病率有明显上升趋势，其中乳腺癌发病率居女性恶性肿瘤首位［1］。

乳腺肿块的良恶性鉴别成为医学诊断的焦点。

在乳腺实性肿块中，乳腺纤维腺瘤和乳腺癌最为常见。

乳腺纤维腺瘤是常见的乳腺良性肿瘤，其典型表现为:形态呈规则圆形或椭圆形。

而乳腺癌为恶性肿瘤，其典型的特征为:呈毛刺状、蟹足状或分叶状改变，无明显边界［2］。

乳腺肿块的软硬或弹性，反映其本身的特性。

对于这些信息的检测，往往有助于良、恶性的鉴别。

传统医学诊断中的触诊是取得这些信息的常用简便方法，但这种方法具有很多局限性，一方面它受医生主观经验的影响较大，另一方面，当肿块太小或者埋藏得太深时，这种方法就无能为力了。

弹性成像则是通过不同组织间的硬度差别进行成像的，而且超声检查简单易行，所以超声弹性成像现已成为诊断乳腺疾病的常用检查方法之一。

达托霉素

(IIb-B) ✓ DAP可用于耐青霉素、氨基糖苷类和VAN肠球菌属引起的NVE或PVE的治疗，剂量为
10~12mg/kg/24h，疗程为﹥6周(IIb-C)；当DAP用于上述感染治疗时，可考虑与头孢他洛林或氨苄西林合用，特别是在持续菌血症或肠球菌对DAP的MIC值位于敏感折点内但较高时(如 3μg/mL，敏感折点为≦4μg/mL)(IIb-C)。但在体外试验中庆大霉素、利福平和替加环素与DAP 合用不具协同效应，应避免选用
[3] Habib G, Lancellotti P, Antunes MJ, et al. 2015 ESC Guidelines for the management of infective endocarditis. European Heart Journal, 2015
英国抗菌化疗协会(BSAC)和中华医学会指南
①经验性治疗
②葡萄球菌NVE
9
③葡萄球菌PVE
[4] Gould FK, Denning DW, Elliott TS, et al. Guidelines for the diagnosis and antibiotic treatment of endocarditis in adults: a report of the Working Party of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother 2012; 67: 269–289
手工筛选标准： DAP疗程≥3d，基线CPK正常、至少1次CPK随访、开始DAP治疗后的7d内无手术史、无
其他引起CPK ↑原因
无任何肌病相关证据
1:1匹配，匹配原则：DAP疗程相等，整个疗程无CPK增高及肌病相关症状

21版：(步步高) (辽鲁琼) Unit 4 Astronomy：the science of th

Ⅰ.阅读理解A(2020·四川检测)Imagine a small group of people with a shared passion for the same craft.They all have different skills and approaches，but they come together to share skills，share stories，and share in the joy of making something.Modern maker culture is filling headlines and lab spaces all over the world.The way makers communicate with each other has changed over time.In the past，skills mainly came from personal sit-downs with members of the group.But sometimes a teacher wasn’t available，or the one available didn’t know how to do the skill others wanted to learn.Today a teacher doesn’t even have to be in the same country or occupy the same decade as the students.Thanks to the work of people who take the time to break down and share the details of their craft，an interested individual can learn anything.Guides may range from videos to diagrams and text.Regardless of the media，maker resources are meant to be shared.One of the features of the maker movement is the crossover between different interests.Perhaps a passion for cars and for leathercraft can result in a truly custom interior (定制的内饰)．Perhaps a love of knitting(编织) and robotics will result in a tiny—but very mobile—robotic furry cat.And once you have started your creation，finding a community to share with is no longer limited to the people nearby.Modern makers have been sharing videos of their progress online for years，contributing greatly to the rapid spread of the maker movement.As different as the participants might be，they share enthusiasm，support，and a willingness to try.Imagine making a ping-pong table together with your makers’team.One group builds the basic frame.Another group takes on the responsibility of painting.You knit the net.There is joy in just giving it a try.It will remind you of childhood creations.Whether you are an experienced programmer or just picking up a hammer for the first time，it is never a bad time to come up with an idea，try something，and share the results.1．How did makers communicate with each other in the past?A．By meeting face to face.B．By asking personal questions.C．By visiting a teacher together.D．By sitting together in a classroom.答案 A解析细节理解题。

超声弹性成像在肝脏病变中的应用

超声弹性成像在肝脏病变中的应用蒋孝鸣【摘要】Ultrasound elastography is a new type of ultrasonic diagnosis technology.At present,it is extensively used in the small organs,such as breast,thyroid and prostate.But in the liver lesions,its application is less.Medical researchers have been trying achieve accurate and non-invasive diagnosis of hepatic lesions,and elastography makes it possible.Here is to make a review of the literature about elastic imaging to improve the cognition about ultrasound elastography in liver diseases.%超声弹性成像是近些年发展起来的一种新型超声诊断技术,目前在乳腺、甲状腺、前列腺等小器官中应用较广泛,但在肝脏病变方面应用不多.医学研究者们一直在为如何做到无创、准确地检查肝脏病变而努力,而超声弹性成像使之成为可能,以下主要复习超声弹性成像在肝脏方面的文献报道,提高对超声弹性成像在肝脏疾病应用中的认识.【期刊名称】《医学综述》【年(卷),期】2013(019)012【总页数】3页(P2213-2215)【关键词】弹性成像;超声检查;脂肪肝;肝纤维化;肝硬化;恶性肿瘤【作者】蒋孝鸣【作者单位】安徽医科大学解放军174临床学院,福建厦门361000【正文语种】中文【中图分类】R445.1超声弹性成像技术于 1991年由 Ophir等［1］提出，随后逐渐发展为一种实时超声成像工具。

In-vivo_Degradation_Kinetic_of

In-vivo Degradation Kinetic of Magnesium ImplantsF. Witte, H.-A. Crostack1, J. Nellesen1, J. Fischer and F. Beckmann2,3Dept.. of Orthopaedic Surgery of Medical School Hannover, Anna-von-Borries-Str. 1-7,30625 Hannover,Germany1Lehrstuhl für Qualitätswesen of University Dortmund, Joseph-von-Fraunhofer Str. 20,44227 Dortmund,Germany2GKSS-Forschungszentrum Geesthacht, Max-Planck-Straße 1, 21502 Geesthacht, Germany3Hamburger Synchrotronstrahlungslabor at Deutschen Elektronensynchrotron, Notkestr. 85,22603 Hamburg,GermanyTemporary bone implants made of magnesium alloys degrade in bone [1]. This degradation is predicted to be a corrosion process. The corrosion of magnesium alloys is depending on its environment, the elemental composition of the magnesium alloy and its processing treatment. The corrosion can also be controlled by surface coating. Basic principles of magnesium corrosion in bone could be demonstrated in animal studies [2].In preliminary studies casted magnesium alloys were used that were chilled to pins and were applied as bone implants [2]. These implants showed a local and high corrosion attack at the implant surface. In a new approach to more corrosion resistant magnesium alloys the base material was extruded and chilled to little cylinders. The extrusion process provide a more homogenous magnesium alloy.To observe the corrosion process in the bone histological sections are commonly used to determine the bone-implant interphase. These destructive methods effect the magnesium alloys because of its soluble nature. Therefore, the bone-implant interphase was studied by microcomputed tomography as a non-destructive method with a high spatial resolution.In order to get an degradation kinetic of the magnesium alloy we had to determine magnesium samples postoperatively after various time intervals. Magnesium implant degradation was observed over a total postoperative time of 12 weeks, scanned in intervals of 2, 4, 6 and 12 weeks.Bone healing and bone remodelling processes provide a high interindividual variety. Therefore, at least 5 animals at each time interval had to be studied. The magnesium cylinders were implanted in the femur condyls of the rabbits (New Zealand White Rabbits).The micro-tomography measurements (XTM) were carried out at beamline W2 using a photon energy of 31.0 keV. The projection data contain radioscopic images consisting of 1536x692 pixels acquired at 720 rotation angles for one sample. The observation area was kept to the center of the bone specimen.In total, 40 bone-implant samples were scanned each in two different levels. So, 80 tomograms were performed and have to be reconstructed and analyzed. The tomograms of each level were stacked together after reconstruction to observe the whole implantation site.First results of the reconstructed data show that extruded magnesium alloys corrode at a slower rate and more homogeneously than casted magnesium alloys. Extruded magnesium alloys corrode in direct contact to the surrounding bone.Further evaluation and complete reconstructed data are going to provide the first detailed information about the in-vivo degradation rate of magnesium alloys in bone.weeks after operation.Figure 2: 3D view of corroding magnesium implant in rabbit condyl 12 weeks after operation. Red dyedgrey values represent corroded magnesium alloy.The authors acknowledge the financial support of Medical School Hannover,DFG Sonderforschungsbereich 599 and HASYLAB (II-01-078). References[1] McBride, JAMA, Vol. 111: 508-515 (1938)[2] F. Witte, H.-A. Crostack, J. Nellesen and F. Beckmann, Hasylab Annual Report, 954-6 (2002)。

Synthesis and spectroluminescence properties of lithium aluminosilicate glass–ceramics

OPTICAL MATERIAL SCIENCE AND TECHNOLOGYSynthesis and spectroluminescence properties of lithium aluminosilicate glass–ceramics containing Er x Yb2−x Ti2O7nanocrystalsO.Dymshits,a),b)A.Zhilin,and I.AlekseevaScientiﬁc Research and Technological Institute of Optical Material Science,VNTs S.I.Vavilov State Optical Institute,St.PetersburgN.Skoptsov,A.Malyarevich,and K.YumashevScientiﬁc Research Center of Optical Materials and Technologies,Belarusan National Technical University,Minsk,Belarus(Submitted December7,2011)Opticheski˘ıZhurnal79,45–57(July2012)Transparent glass–ceramics in the lithium aluminosilicate system with nanosize crystals oferbium and ytterbium titanates having defect-ﬂuorite and pyrochlore structures have beensynthesized for theﬁrst time,and the structural transformations that accompany their formationhave been investigated.The absorption and the luminescence spectra and kinetics in the near IRregion of the erbium and ytterbium ions have been investigated,along with the up-conversionluminescence of erbium ions in glasses and glass–ceramics obtained at various heat-treatmenttemperatures.c 2012Optical Society of America.INTRODUCTIONMaterials doped with erbium ions Er3+are used in various optoelectronic devices,because the radiation of these materials in the1.5-µm region is comparatively safe for the organs of vision,since it is fairly strongly absorbed by the outer coatings of the eye(the cornea and the sclera),and only a small fraction of the irradiation energy reaches its retina. Moreover,the radiation of the1.5–1.6-µm region falls into the so-called second window of transparency of the atmosphere, since the losses when it passes through the atmosphere are small.Finally,quartzﬁbers,which are the basis of modern optical communication networks,are characterized by low absorption and dispersion in this spectral region.Materials doped with Er3+possess good up-conversion properties,and this allows them to be used as active media in up-conversion lasers,as well as in various optoelectronic devices based on the up-conversion of IR radiation into radiation of the visible region.1–3Pyrochlores,with the common formula A2B2O7,where A is a divalent or trivalent cation—in particular,a rare-earth ion—while B is a tetravalent or pentavalent cation with a large ionic radius,are widely used structures.More than 450compounds with this structure are known.In these compounds,all the cations are ordered,with cations A lying in eight-coordinated surroundings(A A),while cations B lie in octahedral surroundings(B B).The degree of ordering of the pyrochlore structure is determined by the ratio of the radii of cations A and B:The greater the difference of these radii,the more ordered the pyrochlore structure of the compound.The pyrochlore structure(space group Fd3m) is closely associated with theﬂuorite structure AO2,where cation A is eight-coordinated(space group Fm3m)and is regarded as the superlattice of the defect-ﬂuorite,disordered (A,B)O2structure,in which the two cation positions differ, and one eighth of all the anions are absent.When cations A and B in compounds with the pyrochlore structure have similar ionic radii,structural disordering is observed;as a result,compounds with the defect-ﬂuorite structure are formed,in which cations A and B are located randomly,A A+ B B→A B+B A,where A A are cations A in eight-coordinated surroundings,B B are cations B in octahedral surroundings,A B are cations A in octahedral surroundings,and B A are cations B in eight-coordinated surroundings.This is accompanied by disordering of the cation sublattice,with the formation of Frenkel defects,and this in turn results in disordering of the anion sublattice.4In compounds with the defect-ﬂuorite structure,the mean coordination number of the A and B ions with respect to oxygen lies between6and8.5Ytterbium titanate Yb2Ti2O7,which has the pyrochlore structure,is a promising matrix for Er3+ions.Crystals of Yb2Ti2O7and Er2Ti2O7have the same crystal structure and a similar crystal-lattice parameter.Therefore,the Yb3+and Er3+ions,which have similar ionic radii[r(Er3+)c.n.8= 1.004˚A,r(Yb3+)c.n.8=0.985˚A,Ref.6]will be structurallyindistinguishable from each other in an Er x Yb2−x Ti2O7 crystal.This reduces the effect of concentration quenching of the luminescence of the Er3+ions.7The titanates of yttrium and the rare-earth(RE)elements,with the pyrochlore structure,possess relatively low phonon energy of the crystal lattice(in particular,<712cm−1in Yb2Ti2O7,<695cm−1 in Gd2Ti2O7,and<717cm−1in Dy2Ti2O7,Ref.8),and this reduces the probability of nonradiative relaxation of the electron excitation and thereby increases the quantum yield of the IR luminescence and the up-conversion luminescence intensity of the Er3+ions.There are data in the literature on producing and studying the luminescence properties ofTABLE1.Characteristics of the crystalline phases precipitated by heat-treating glasses of the lithium aluminosilicate system,from XPA data.(D is the diameter of the nanocrystals,a is the unit-cell parameter,and I is the relative amount of the crystal phase).single-crystal Yb2Ti2O7and Yb x Y2−x Ti2O7,9,10thin-ﬁlm Er x Y2−x Ti2O7,11–13,nanocrystals of Y2Ti2O7:Er3+,7and Er x Yb2−x Ti2O7ﬁlms14with the pyrochlore structure obtained by the sol–gel method.However,the authors of this article know of no papers in which the spectroluminescence properties of similar crystals with theﬂuorite structure were studied.This paper discusses the phase transformations that accompany sitallization and the absorption spectra,as well as the Stokes luminescence spectra and kinetics in the near-IR region and the up-conversion luminescence of erbium ions in the original glasses and glass–ceramics of the lithium aluminosilicate system containing nanocrystals of Er x Yb2−x Ti2O7that have various degrees of ordering and were obtained under various regimes of secondary heat treatment.As far as the authors of this article know,no transparent glass–crystal materials with nanocrystals of such a composition were synthesized earlier.OBJECTS OF STUDY AND EXPERIMENTAL TECHNIQUE The original glasses of mass400g were synthesized from“very high purity”and“chemically pure”reagents in quartz ceramic crucibles,with mixing at a temperature of 1580◦C for4h and with ebullition with oxygen for1h to dewater the glass melt,were cast on a metal plate,and were annealed at a temperature of660◦C.The glasses were subjected to differential–thermal analysis and heat treatment under a temperature gradient,followed by x-ray phase analysis (XPA)of the materials obtained under various heat-treatment temperatures.Based on these results,the presitallization and sitallization temperatures were selected(Table1).The original glasses were heat-treated in a shaft furnace.Titanium dioxide was introduced into the lithium alu-minosilicate glasses as a crystallization catalyst.The glasses were doped with0.14mol%erbium oxide and/or4.11mol% ytterbium oxide,and this corresponded to erbium-and ytterbium-ion concentrations of0.56×1020cm−3and16×1020cm−3,respectively.The original lithium aluminosilicate glass doped with erbium and ytterbium oxides is designated as1-Er,Yb,while that heat-treated according to various regimes is designated as2-Er,Yb–6-Er,Yb(Table1).The original lithium aluminosilicate glass doped with ytterbium oxide is designated as1-Yb,while that heat-treated according to various regimes is known as2-Yb–6-Yb(Table1).The original ytterbium-containing glasses and the glasses codoped with erbium and ytterbium were simultaneously subjected to heat treatment under the same regimes in one furnace.The crystalline phases precipitated when the original glasses were heat-treated were identiﬁed on the basis of XPA by means of a Shimadzu XRD6000diffractometer using CuKαradiationﬁltered by Ni.The mean size of the crystals was determined from the broadening of the x-ray lines,using Scherrer’s formula D=Kλ/ (2θ)cosθ,where λis the wavelength of the x-rays,θis the diffraction angle, (2θ)is the half-width of the peak,and K is a constant,which was taken to be equal to unity in the calculations.15The absorption spectra of the test samples were recorded by means of a Cary Varian5000spectrophotometer.The luminescence was excited by the continuous radiation of a semiconductor laser lasing at962nm.The luminescence-damping kinetics at wavelengths1.03and1.53µm and the luminescenceﬂareup at1.53µm were recorded with excitation by25-ns laser pulses with wavelength976nm.The exciting radiation was formed by an optical parametric generator based on a beta-barium borate crystal,which was pumped with the third-harmonic radiation of a laser based on a Y AG:Nd crystal operating in the Q-switched regime.The time response of the photodetector that records the luminescence signal was0.6µs. RESULTS AND DISCUSSIONStudy of the crystallization and nature of the precipitatedcrystal phasesFigure1shows x-ray patterns of the original glasses and of the glasses subjected to heat treatment,while Table1shows the sizes of the crystals,the unit-cell parameters,and theFPP PP P P P PPFFF FFFFFFF 643265432115FF11131140033122240044062244451144062244471122210103030505070702θ, deg2θ, degI n t e n s i t y , r e l . u n i t sI n t e n s i t y , r e l . u n i t s(a)(b)FIG.1.X-ray patterns of the original (1)and heat-treated (2–6)lithium aluminosilicate glasses doped with 0.14mol%Er 2O 3and 4.11mol%Yb 2O 3(a),and doped with 4.11mol%Yb 2O 3(b).The heat-treatment regimes are as follows:2—770◦C,12h;3—785◦C,12h;4—770◦C,12h +800◦C,6h;5—785◦C,12h +800◦C,6h;6—785◦C,12h +900◦C,6h.Conventional notation:F —Er x Yb 2−x Ti 2O 7with the defect-ﬂuorite structure,P —Er x Yb 2−x Ti 2O 7with the disordered-pyrochlore structure,∗—β-quartz solid solution.relative number of crystal phases precipitated under various heat treatments (determined from the overall intensity of the most intense peak of this phase on the diffractogram).The hkl indices of the crystals with the defect-ﬂuorite structure are given only in Fig.1(a),curve 5,while those of the crystals with the pyrochlore structure are given in Fig.1(a),curve 6.The transition from the ﬂuorite structure to the pyrochlore structure is accompanied by the appearance of superlattice diffraction spots on the x-ray patterns of the samples.6The original glasses are transparent,and their x-ray patterns are typical of amorphous materials (Figs.1(a)and 1(b),curves 1).As follows from Fig.1and Table 1,cubic crys-tals of erbium–ytterbium titanate Er x Yb 2−x Ti 2O 7(Fig.1(a))and ytterbium titanate Yb 2Ti 2O 7(Fig.1(b))with the defect-ﬂuorite structure begin to precipitate in the glasses at a temperature of 770◦C.The materials remain transparent after the crystalline phase precipitates.Increasing the temperature to 800◦C increases the amount of precipitated crystalline phase while maintaining its structure and the transparency of the material.After the samples are heat-treated at 900◦C,peaks appear on their x-ray patterns that serve as distinctive signs of Er 2Ti 2O 7and Yb 2Ti 2O 7crystals with the pyrochlore structure,with their large half-width (the peaks with odd hkl indices)indicating structural imperfection of this phase and indicating that it is disordered.Increasing the temperature above 1000◦C causes crystals with the ordered pyrochlore structure to form;however,such materials are opaque,and their spectral properties were not investigated in this paper.The size of the crystals that precipitate at 770◦C in Er,Yb-containing glass–ceramics is about 7nm and increases to 13nm as the crystallization temperature is increased from 770to 900◦C.In the Yb-containing glass–ceramics,crystals with a size of 8.5nm precipitate at 770◦C (Table 1);as the crystallization temperature increases,they reach somewhat greater sizes than the crystals of erbium–ytterbium titanate (14.5–15.5nm).The unit-cell parameters of the crystals increase with increasing processing temperature but remain appreciably less in this case than in single crystals of er-bium titanate (10.076˚A[JCPDS card 18-499])and ytterbium titanate (10.030˚A[JCPDS card 17-454])with the pyrochlore structure.The reduction of the unit-cell parameters of the crystals that precipitate in the glass by comparison with the parameters of the corresponding single crystals can be associated with the interaction at the crystal–glass phase interface,while the increase of the parameters as the heat-treatment temperature increases can be explained by the growth of the size of the crystals,which reduces the relative contribution of the interphase interactions to the value of the lattice parameter of the nanocrystal.The transparent erbium–ytterbium-and ytterbium-containing glass–ceramics obtained at heat-treatment temper-atures 770–800◦C have a single crystalline phase,consisting of erbium–ytterbium titanate or erbium titanate,respectively,with the ﬂuorite structure.In Er,Yb-containing material processed at 900◦C,besides erbium–ytterbium titanate with the disordered pyrochlore structure,traces are detected of β-quartz solid solution;at the same time,in Yb-containing glass–ceramic obtained at this temperature,besides ytterbium titanate with the disordered pyrochlore structure,an appre-ciable amount of solid solution with the β-quartz structure also crystallizes (Fig.1(b)).It should be pointed out that,in glasses of this composition that contain no RE-oxide additives,solid solutions with the β-quartz structure precipitate at temperatures of 750–800◦C,depending on its duration.The increase detected in this paper of the temperature at which this crystalline phase precipitates when RE ions are introduced and their total amount is increased agrees with earlier data 16concerning the gradual increase of the temperature at which solid solutions with the β-quartz structure precipitate when another RE oxide (neodymium)is introduced into this glass and its concentration is increased.Glass–ceramics obtained by crystallization at 900◦C opalesce,with an increase of the light scattering in Er,Yb-containing glass–ceramics being associated with an increase of the number and size of crystals with a high refractive index (n =2.47in Er 2Ti 2O 7and n =2.51in Yb 2Ti 2O 7,Ref.17).In the Yb-containing glass–ceramics,besides the causes mentioned above,the precipitation of large crystals of β-quartz solid solution apparently also affects the increase of the light scattering.SPECTRAL PROPERTIESFigures2(a)and2(b)show the absorption spectra of glasses and glass–ceramics of the lithium aluminosilicate system in the near-IR region.The absorption spectra of the original glasses(Figs.2(a)and2(b),curves1)includes a band characteristic of the Yb3+ions in the wavelengthregion0.9–1.0µm,caused by electron transitions from the ground Stark sublevel of the2F7/2multiplet to the Stark sublevels of the2F5/2multiplet of the Yb3+ions(Fig.3). There is also an absorption band caused by4I15/2→4I11/2 transitions in the region of these wavelengths in the Er3+ions. However,the absorption cross section and concentration of erbium ions is much less than the absorption cross section and concentration of ytterbium ions,and,in samples that contain Yb3+and Er3+,the contribution of Er3+to the overall absorption in the0.95-µm wavelength region is negligible by comparison with the contribution of Yb3+(Fig.2).An absorption band is observed in ytterbium–erbium-containing samples in the1.5-µm region related to the4I15/2→4I13/2 electron transitions in the Er3+ions(Fig.2(a)).Processing the original glasses at temperatures of 770–800◦C changes the shape,position,and intensity of the absorption bands of the Yb3+ions—they have greater structuring,and the position of the absorption peak is changed (Figs.2(a)and2(b),curves2).Thus,during the subsequent transition from the original glass to a glass–ceramic,as the heat-treatment temperature increases,the position of the absorption peak gradually shifts from976to974nm,and its intensity decreases;in the0.85–0.95-µm interval,peaks in the914-and943-nm wavelength region appear and become more and more distinct;and the intensity also falls off at the maximum of the long-wavelength part of the absorption band around1.0µm.An especially strong intensity decrease of the absorption bands of the Yb3+ions while conserving their shape is observed after the glasses are heat-treated at 900◦C,when structural ordering occurs in the crystals,with the formation of the defect-pyrochlore structure(Figs.2(a)and 2(b),curves3and the inset to Fig.2(b),where the absorption spectra of glass–ceramic samples5-Yb and6-Yb are shown).A similar shape of the absorption band of the Yb3+ions was observed in the spectrum of single-crystal Yb2Ti2O7with the pyrochlore structure(maxima appear at971,924,and 909nm).9,10A small change of the shape of the absorption band of the Er3+ions is also observed in the1.5-µm region when the processing temperature is increased—the short-wavelength wing of the band shifts from1489to1477nm and its long-wavelength maximum shifts from1557to1560nm (Fig.2(a)and the inset to thatﬁgure).The intensity of the absorption band of Er3+,like that of the absorption band of Yb3+,sharply falls off after the sample is heat-treated at 900◦C(Fig.2(a),curve3).The indicated changes in the absorption spectra of samples1-Er,Yb–6-Er,Yb can be unambiguously associated with the formation of the crystalline phase of Er x Yb2−x Ti2O7 with the defect-ﬂuorite structure at temperatures770–800◦C (Fig.1(a),curves2–5)and with the subsequent appearance of elements of the ordered pyrochlore structure in this phase at900◦C(Fig.1(a),curve2).The ytterbium ions in the311227501000140015001600125015001750 011020313229009501000 0510151020Wavelength, nmWavelength, nmAbsorptioncoefficient,cm–1Absorptioncoefficient,cm–1850900950100010501100(a)(b)FIG.2.Absorption spectra of glasses(1)and glass–ceramics(2and3) of the lithium aluminosilicate system.The heat-treatment regimes of the glass–ceramics are as follows:2—785◦C,12h+800◦C,6h;3—785◦C, 12h+900◦C,6h.(a)Samples that contain Er3+and Yb3∗ions.Inset: Absorption spectra of the original glass(1)and of glass–ceramic(2)in the 1400–1600-nm region.(b)Samples that contain Yb3∗ions.Inset:Absorption spectra of glass–ceramic samples(2and3)put side by side for convenience of comparison.4FH7/2211/24S3/24F9/22F5/22F7/2Yb3+Er3+4I9/24I11/24I13/24I15/2.98µm.98µm.98µm.98µm.52µm.55µm.65µm1.5µmFIG.3.Energy-level diagrams of Er3+and Yb3+ions.The straight arrows denote some transitions with energy absorption or emission,the wavy arrows denote nonradiative relaxation,and the two-headed arrow shows the direction of energy transport between the ions.pyrochlore structure occupy positions with local symmetry D3d.9,10In the crystalﬁeld of this symmetry,the2F7/24, 564511222541331500500600160070040008000Wavelength, nmWavelength, nm300002000010000I n t e n s i t y , r e l . u n i t sI n t e n s i t y , r e l . u n i t s(a)(b)FIG.4.Stokes spectra (a)and up-conversion spectra (b)of the luminescence of samples codoped with erbium and ytterbium oxides.1—Original glass.The heat-treatment regimes of the glass–ceramic are as follows:2—770◦C,12h;3—785◦C,12h;4—770◦C,12h +800◦C,6h;5—785◦C,12h +800◦C,6h;6—785◦C,12h +900◦C,6h.The excitation wavelength is 962nm.ground state of the ytterbium ions splits into four sublevels,while the 2F 5/2excited state splits into three sublevels,and three maxima will accordingly be observed in the absorption spectra,caused by electron transitions from the ground Stark sublevel of the 2F 7/2multiplet to the Stark sublevels of the 2F 5/2multiplet.The abrupt intensity attenuation of the Er 3+absorption bands detected in this paper accompanying the appearance of elements of the pyrochlore superlattice is in accordance with the data of Ref.18,in which a gradual decrease was observed in the intensity of the coloration of Er 2Ti 2O 7obtained by the sol–gel method in the process of the ﬂuorite–pyrochlore structural transition.This paper is apparently the ﬁrst to report the intensity attenuation of the components of the Yb 3+absorption band that accompanies the reconstruction of Yb 2Ti 2O 7in samples 1-Yb–6-Yb.The luminescence spectra of the samples doped with Yb 3+and Er 3+are shown in Fig.4.The Stokes luminescence in the 1.5-µm region is caused by radiative transitions of electrons from the 4I 13/2level to the 4I 15/2ground state of the Er 3+ions (Fig.4(a)).No appreciable changes were observed in the position and shape of the luminescence band123456Time, mse –11e –9e –7e –5I n t e n s i t y , r e l . u n i t sFIG.5.Luminescence-damping kinetics of Er 3+at λ=1.53µm in glass (1)and glass–ceramics (2–6)of the lithium aluminosilicate system.The heat-treatment regimes are as follows:2—770◦C,12h;3—785◦C,12h;4—770◦C,12h +800◦C,6h;5—785◦C,12h +800◦C,6h;6—785◦C,12h +900◦C,6h.as the heat-treatment temperature increases.The shapes of the luminescence bands of the original glass and of the glass–ceramics obtained by processing at 770–800◦C are similar to the shape of the luminescence band of the Er 3+ions in an amorphous ytterbium titanate ﬁlm.14The luminescence intensity is greater in the original glass than in the glass–ceramics.This agrees with the intensity decrease of the absorption band of Er 3+in the 1.5-µm region as the heat-treatment temperature increases (Fig.2(a))and is associated with the formation of the crystalline phase of Er x Yb 2−x Ti 2O 7with the defect-ﬂuorite structure (samples 2-Er,Yb–5-Er,Yb)and then the disordered-pyrochlore structure (sample 6-Er,Yb,Fig.1(a)).The local surroundings of the erbium ions in this case become more and more symmetric than in the original glass,and this can reduce the probability of the f –f transitions in the Er 3+ions and the luminescence intensity.The absence of structuring of the luminescence band that characterizes the Er x Yb 2−x Ti 2O 7crystals with the ordered pyrochlore structure 14is in accordance with the XPA data concerning the high defect level of the pyrochlore structure of the Er x Yb 2−x Ti 2O 7crystals (Figs.1(a)and 1(b),curves 6,Table 1).Figure 5shows the luminescence damping kinetics of the Er 3+ions at wavelength 1.53µm in the glasses and glass–ceramics of the lithium aluminosilicate system (samples 1-Er,Yb–6-Er,Yb).The exciting radiation with wavelength 962nm falls into the absorption bands caused by the 4I 15/2→4I 11/2electron transitions in the Er 3+ions and the 2F 7/2→2F 5/2transitions in the Yb3+ions (Fig.3);however,as noted above,it is predominantly absorbed by the Yb 3+ions.Excitation is followed by the process of resonance energy transport from the 2F 5/2level of the Yb 3+ions to the 4I 11/2level of the Er 3ions and then the process of rapid nonradiative relaxation 4I 11/2→4I 13/2,with subsequent accumulation of the electrons on the long-lived 4I 13/2level of the Er 3+ions and relaxation to the ground state with emission of photons with wavelength about 1.53µm.The characteristic damping time of the Er 3+luminescence at wavelength 1.53µm is thus determined by the lifetime on the 4I 13/2level.TheTABLE2.Damping times of Stokes luminescence of Er3+(τEr)and Yb3+(τYb)∗eff,(τYb)eff,radiative lifetime(τYb)rad of2F5/2excited state of the Yb3+ion and energy-transport efﬁciencyηfrom the ytterbium ions to the erbium ions in glasses and glass–ceramics of the lithium aluminosilicate system.luminescence signal in this case has aﬂareup section whose characteristic time(determined by the energy-transport times from Yb3+to Er3+and the4I11/2→4I13/2relaxation)is more than an order of magnitude less than the damping time.The luminescence damping of the erbium ions in all the samples has a monoexponential character(Fig.5).The measured damping times are given in Table2.In a multiphase system in which each of the phases(both the residual glass and the crystalline phase)contains erbium ions,it would be hard to expect a monoexponential character of their luminescence damping.However,this character of the damping can be associated with the fact that the lifetime of the Er3+ions in the4I13/2state,τEr,is virtually identical in the glass and the crystalline phases that are formed and is independent of the heat-treatment temperature of the glass–ceramic.It equals about6.6ms.Therefore,it is not possible to separate the luminescence of the erbium ions in the crystalline phase and the residual glass.It should be pointed out that this timeτEr agrees fairly well with the data on the concentration dependences of the luminescence-damping time determined by the4I13/2→4I15/2electronic transitions and measured for thinﬁlms of Er x Y2−x Ti2O7and nanocrystals of Y2Ti2O7:Er3+with the pyrochlore structure,obtained using sol–gel technology.7,11–13The radiative lifetime(τEr)rad(the lifetime when the only mechanism for depleting the level is spontaneous radiative relaxation)of the4I13/2excited state of the Er3+ ions,calculated by means of Judd–Ofelt theory from the absorption spectrum,19is virtually identical in the various existing structures of the samples1-Er,Yb–6-Er,Yb and equals about9.1ms.The luminescence quantum yield from the4I13/2level of the Er3+ions,deﬁned as the ratio of timesτEr/(τEr)rad,can thus be estimated asϕ=70–77% in the glass and glass–ceramics obtained using various heat-treatment regimes and possessing various structures(both theﬂuorite structure and the disordered-pyrochlore structure). The shorter luminescence-damping time by comparison with the radiative lifetime of the4I13/2state of the Er3+ions is caused by quenching of the excitation by the OH groups and by nonlinear up-conversion luminescence quenching.The process of nonradiative relaxation in the4I13/2→4I15/2 channel evidently does not substantially reduce the quantum yield of the luminescence as a consequence of the low phonon energy of the crystal lattice of the Re2Ti2O7crystal(as pointed out above,the RE titanates with a pyrochlore structure are characterized by a phonon energy of about700cm−1).Figure6(a)shows the luminescence-damping kinetics of the Yb3+ions at a wavelength of1.03µm in samples1-Yb–6-Yb,which contain no Er3+.The characteristic damping time of this luminescence is determined by the lifetime of Yb3+on the2F5/2level.The luminescence-damping kinetics of all the samples is characterized by a nonmonoexponential shape with rapid quenching(20–50µs)at the initial stage(Fig.6(c)).The effective damping time of the luminescence I(t)in these cases was calculated from the formulaτeff=tI(t)dt/I(t)dt.The times(τYb)eff for samples1-Yb–6-Yb are shown in Table2. The lifetime on the2F5/2level of the Yb3+ions in the original glass(260µs)is less than in the glass–ceramics (520–630µs,Table2).In this case,the given time increases with increasing processing temperature.That is,crystallization of the ytterbium-containing phase and structural ordering in this phase increases the lifetime of Yb3+in the2F5/2state.The radiative lifetime(τYb)rad of the excited2F5/2state of the Yb3+ion,calculated from the absorption spectrum by means of Judd–Ofelt theory,19increases from about0.95 (in the original glass1-Yb)to1.5ms(in material6-Yb, Table2).Thus,the behavior of the times(τYb)rad and (τYb)eff is qualitatively identical when there is a change of the heat-treatment temperature.Consequently,the increase of the time(τYb)rad can also be explained by the formation of a more and more ordered crystalline phase Yb2Ti2O7as the processing temperature of the material is increased.The luminescence quantum yield from the2F5/2level of the Yb3+ ion,estimated asϕ=(τYb)eff/(τYb)rad,is appreciably less than100%and equals about30%in the original glass1-Yb and46%in the glass–ceramics(2-Yb–6-Yb).Such lowϕvalues are hard to explain,keeping in mind the comparatively small phonon energy in the Yb2Ti2O7crystal.The rapid initial luminescence damping of the ytterbium ions in samples1-Yb–6-Yb in their time constant is not characteristic of ytterbium ions20and cannot be associated with these ions,when they occur in glass or in any crystalline phase.On the other hand,the low luminescence quantum yield of the Yb3+ions in combination with the nonmonoexponential quenching of their luminescence is characteristic of an additional relaxation channel associated with the transport of energy to other centers,and this makes it possible to speak of the presence of a certain luminescence quenching in the。

2012届步步高高考英语大二轮专题复习与增分策略训练：活页练(18)

活页练(十八)Test 1Dear Laura，I just heard you tell an old story of gift giving and unselfish love in your program．You doubted that such unselfish love would happen in today’s world．Well，I’m here to give you __1__．I wanted to do something very __2__ for my fifteen-year-old son，who has always been the perfect child．He __3__ all summer to earn enough money to buy a used motorcycle．Then，he spent hours and hours on it __4__ it looked almost new．I was so __5__ of him that I bought him the shiniest helmet and a riding outfit．I could __6__ wait for him to open up his gift．In fact，I barely slept the night before．Upon awakening，I went to the kitchen to __7__ the coffee，tea，and morning goodies．In the living room was a beautiful keyboard with a __8__：“To my wonderful mother，all my love，your son．”I was so __9__．It had been a long-standing joke in our family that I wanted a piano so that I could __10__ lessons．“Learn to play the piano，and I’ll get you one” was my husband’s __11__．I stood there shocked，crying a river，asking myself how my son could __12__ this expensive gift．Of course，the __13__ awoke，and my son was thrilled with my reaction．Many kisses were __14__，and I immediately wanted him to __15__ my gift．As he saw the helmet and outfit，the look on his face was not __16__what I was expecting．Then I __17__ that he has sold the motorcycle to get me the keyboard．Of course I was the proudest mother __18__ on that day，and my feet never hit the ground for a month．So I wanted you to know，that kind of love still __19__ and lives even in the ever-changing world of me，me，me!I thought you’d love to __20__ this story．Yours，Hilary P．S．The next day，my husband and I bought him a new “used” already shiny motorcycle．1．A．hope B．adviceC．support D．courage2．A．polite B．similarC．special D．private3．A．played B．studiedC．traveled D．worked4．A．after B．beforeC．unless D．until 5．A．sure B．fondC．proud D．confident 6．A．perhaps B．reallyC．almost D．hardly 7．A．start B．cookC．set D．serve 8．A．note B．noticeC．word D．sign 9．A．disturbed B．confused C．astonished D．inspired 10．A．give B．takeC．draw D．teach 11．A．reason B．requestC．comment D．response 12．A．present B．affordC．find D．order 13．A．neighbor B．buildingC．home D．house 14．A．exchanged B．experienced C．expected D．exhibited 15．A．tear B．openC．check D．receive 16．A．purely B．basically C．obviously D．exactly 17．A．realized B．remembered C．imagined D．supposed 18．A．only B．stillC．ever D．even 19．A．works B．existsC．matters D．counts 20．A．send B．publishC．share D．write211工程(优秀生选做题)2．vocabulary：(1)gift n．礼物；天赋；天才；才能gift ________ sth．/for doing sth．拥有某方面/做某事的天赋(2)reaction n．反应；回应reaction ________ sb．/sth．对某人/某事的反应1．翻译句子It had been a long-standing joke in our family that I wanted a piano so that I could take lessons．________________________________________________________________________________________________________________________________________________ 1．根据下句的划线部分仿写句子In_the_living_room_was_a beautiful keyboard with a note．________________________________________________________________________Test 2When I was about 12，I had an enemy，a girl who liked to point out my shortcomings．Week by week her list __1__：I was very thin；I wasn’t a __2__ student；I talked too much；I was too __3__，always feeling superior to(胜过)others，and so on．I tried to hear all these as long as I could．__4__，I became very angry．I ran to my father with __5__ in my eyes．He listened to me __6__，and then he asked，“Are the things she says true or not? Janet，didn’t you ever wonder __7__you’re really like? Well，you now have that girl’s __8__．Go and __9__ a list of everything she said and mark the points that are __10__．Pay no attention to the other things she said．”I did __11__ he told me．To my great __12__，I discovered that about half the things were true．Some of them I couldn’t __13__(like being very thin)，but a good number I could and suddenly I wanted to change．For the first time I went to a fairly __14__ picture of myself．I brought the list back to Daddy．He __15__ to take it．“That’s just for you，”he said．“You know __16__ than anyone else the truth about yourself．But you have to __17__，not just close your ears in anger，feeling __18__ when something said about you is true，you’ll find it of help to you．Our world is full of people who think they know your affairs．Don’t shut your __19__．Listen to them all，but hear the truth and do what you know is the right thing to do．”Daddy’s advice has always __20__ to me at many important moments．In my life，I’ve never had a better piece of advice．1．A．collected B．addedC．grew D．continued2．A．good B．badC．short D．greedy3．A．silly B．friendlyC．dull D．proud4．A．In other words B．Above allC．As a result D．At last5．A．tears B．happinessC．promises D．wishes6．A．coldly B．quietlyC．eagerly D．happily7．A．who B．howC．what D．that8．A．excuse B．opinionC．talk D．advice9．A．take B．makeC．create D．receive10．A．wrong B．correctC．big D．true11．A．as B．soC．before D．till12．A．joy B．pleasureC．surprise D．anger13．A．say B．likeC．do D．change14．A．wonderful B．clearC．interesting D．beautiful15．A．promised B．refusedC．expected D．agreed16．A．wider B．higherC．better D．worse17．A．listen B．standC．speak D．share18．A．hurt B．sadC．shy D．excited19．A．words B．mouthsC．eyes D．ears20．A．returned B．goneC．appeared D．happened211工程(优秀生选做题)2．vocabulary：(1)in anger＝________in surprise＝________；in shame＝________；in excitement＝________(2)(be) of help＝helpfulbe of importance＝be ________；be of value＝be ________；be of no use＝be ________；be of an age＝be ________________1．翻译句子Listen to them all，but hear the truth and do what you know is the right thing to do．________________________________________________________________________________________________________________________________________________ 1．What does the underlined word “it” refer to?________________________________________________________________________答案Test 11．A2．C3．D4．D5．C6．D7．A8．A9．C10．B11．D12．B 13．D14．A15．B16．D17．A18．C19．B20．C211工程(优秀生选做题)2．(1)for(2)to1．我想要一架钢琴以便我能上课，这是一个在我们家里存在已久的笑话。

Hematology-2012-450-4

The conundrum of neonatal coagulopathyShoshana Revel-Vilk11Hadassah Hebrew-University Hospital,Jerusalem,IsraelThe maturation and postnatal development of the human coagulation system wasﬁrst studied and described more than20years ago.These older studies,supported by more recent data,conﬁrm the signiﬁcant and important differences in the physiology of coagulation andﬁbrinolysis in neonates and young children compared with older children and adults.Subsequently,signiﬁcant differences were also described in the physiology of primary hemostasis and in global in vitro tests for hemostasis.These differences,which mostly reﬂect the immaturity of the neonatal hemostasis system,are functionally balanced.Healthy neonates show no signs of easy bruising or other bleeding diathesis and no increased tendency to thrombosis for any given stimulus compared with adults.Systemic diseases may affect hemostasis,predisposing ill neonates to increased hemorrhagic or thrombotic complications.The immaturity of the hemostasis system in preterm and very-low-birth-weight neonates may contribute to a higher risk for intraventricular hemorrhage.Therapies targeting the hemostasis system can be effective for preventing and treating these events.The concept of“neonatal coagulopathy”has an important impact on both the diagnosis and management of hemorrhagic or thrombotic events in neonates.For diagnosis of hemostasis disorders,diagnostic laboratories processing pediatric samples should use age-,analyzer-,and reagent-appropriate reference ranges.Age-speciﬁc guidelines should be followed for the management of neonates with hemostatic disorders.IntroductionHemostasis is a complex process that balances pro-and anticoagu-lant forces to protect the organism from uncontrolled bleeding secondary to vessel injury while at the same time preventing excessive clotting.At the site of vessel wall injury,adhesion, activation,and aggregation of platelets result in the formation of a platelet plug(primary hemostasis).Activation of the coagulation pathway results in the formation of covalently cross-linkedﬁbrin that stabilizes the platelet plug(secondary hemostasis).Inhibitors of the coagulation cascade limit and conﬁne the coagulation response, and activation of theﬁbrinolysis pathway results in the dissolution ofﬁbrin clots to maintain and/or restore blood vessel patency.The term“developmental hemostasis”was coined to reﬂect the fact that the hemostasis system is incompletely developed at birth and matures throughout infancy until adulthood.The aim of this review is to summarize our knowledge on the neonatal hemostasis system and to delineate the implications of age-related changes on the risk of thrombosis or bleeding in neonates.The approach to the diagnosis of coagulopathy in neonates is also reviewed. Developmental hemostasisAlthough the key components of the hemostasis system are present at birth,important quantitative and qualitative differences exist among preterm neonates,full-term neonates,children,and adults (Table1).It has been thought that these age-related changes are not related to coagulation,but rather are part of normal physiological development.1Platelet number and volume are relatively similar in neonates compared with adult values.Samples from more than 47000neonates demonstrated that the platelet count increases with gestational age(GA)from a lower-limit(5th percentile)platelet count of104200ϫ109/L for those at32weeks GA to a platelet count of123100ϫ109/L for late preterm and term neonates.2In the same study,the platelet count normally increased during theﬁrst 9weeks after birth up to750000ϫ109/L.2Differences were described in the kinetics of thrombopoiesis between preterm neonates,term neonates,and adults.3,4Platelet ultrastructure in neonates does not differ from that in adults. Platelet surface glycoproteins are present on neonatal platelets,but their expression and response to agonists are different from those of adults.5Neonatal platelets have a decreased response to agonists, decreased granule secretion,and decreased expression ofﬁbrinogen-binding sites.The decreased platelet response persists for theﬁrst 2-4weeks after delivery.6Despite platelet hyporeactivity in neonates,in vivo global assays of platelet function,such as bleeding time and the platelet function analyzer(PFA-100),do not show platelet dysfunction.6-8Further-more,global in vitro testing for hemostasis using thromboelastogra-phy and rotating thromboelastometry show accelerated coagulation and strong clotﬁrmness9,10(Table2).This inconsistency may be explained by the role of the VWF in neonatal hemostasis.Neonates have a higher concentration of plasma VWF levels and a greater percentage of large VWF multimers.11,12The higher hematocrit levels in neonates may also explain this inconsistency,because a higher hematocrit level is associated with a shorter bleeding time.7 For the procoagulant factors,the differences in neonates are mainly quantitative(Table1).11,13,14Both full-term and preterm neonates are born with low levels of most procoagulant factors,including all of the contact activation factors and vitamin K–dependent factors. The reduced plasma concentration of coagulation factors in neo-nates may be the result of decreased production and/or accelerated clearance15and are probably explained by reasons unrelated to hemostasis,such as the function of these proteins in angiogenesis, inﬂammation,and wound repair.16Low levels of factor II(FII), FVII,FIX,and FX could not be explained solely by vitamin KN OT S O‘B ENIGN’H EMATOLOGIC I SSUES IN C HILDRENdeﬁciency,because low levels were also measured in neonates who received vitamin K prophylaxis at birth.The low levels of contact activation factors contribute to the normally prolonged activated partial thromboplastin time(aPTT)in neonates(Table2).Levels of the major anticoagulant proteins are also low at birth. Antithrombin levels in theﬁrst3months of life are lower than those observed in many adults with antithrombin deﬁciency and recurrent thrombosis.Furthermore,plasma concentrations of protein C and protein S at birth are very low.However,because protein S in neonates is completely present in the free,active form,the functional activity of protein S in neonates is similar to that in adults.1Conversely,alpha2macroglobulin(␣2M),an important inhibitor of thrombin in neonatal plasma,is elevated in neonates, being up to twice the level in adults.It is suggested that␣2M in neonates partly compensates for the low levels of antithrombin and may increase the interaction of protein S with activated protein C.17The qualitative differences in neonatal procoagulant and anticoagu-lant factors were reviewed recently.15Posttranslational modiﬁca-tions affect the structure of hemostatic proteins and most probably affect the function of these proteins.18Fetalﬁbrinogen was shown to have fewer fractions of high-molecular-weightﬁbrinogen and decreased content of sialic acid and phosphorus compared with adultﬁbrinogen.These biochemical differences may explain the slower polymerization ofﬁbrin clot from fetalﬁbrinogen compared with that ofﬁbrin from adultﬁbrinogen.19Although no human studies are yet available,neonatal forms of protein C and antithrom-bin have been described in animal fetuses.15Table1.Neonatal hemostasis versus older children/adult hemostasisPreterm neonates vs term neonates Neonates vs olderchildren/adultsApproximate ageof adult values*Primary hemostasisPlatelet count Decreased(Ͻ32w)SamePlatelet function Decreased Decreased†2-4wk %of reticulated platelets Higher Higher NA VWF level NA Higher3mo VWF large multimers NA Higher3mo Coagulation factorsFII,FVII,FIX,FX Lower Lower16y FV Lower Same or lower16y FVIII Higher Same or higher1mo‡FXI Lower Lower1y FXII Lower Lower16y Fibrinogen level Same SameFibrinogen function NA Decreased5y Regulation of coagulationAntithrombin Lower Lower3mo Protein C Lower Lower16y Total protein S Lower Lower1mo Free protein S NA Higher NA APCR generation NA Reduced NA Free TFPI NA Lower Adult FibrinolysisPlasminogen level Lower Lower6mo Plasminogen function NA Decreased NA tPA Same§Higher5d␣2antiplasmin Lower Lower5d␣2M Same Higher Adult PAI Same§Same or higher5d NA indicates not available;APCR,activated protein C resistance;and TFPI,tissue factor pathway inhibitor.For reference values of coagulation and regulation of coagulation factors,see Monagle et al,2006.14*Maximum age reported.†Decreased response was reported to agonists such as thrombin,collagen,epinephrine,and thrombin activation peptide as tested byﬂow cytometry.‡Lower levels compared with adults are reported from1mo to16y of age.§Higher levels in extremely preterm neonates on d10of life compared with older preterm or term neonates.Table2.Screening laboratory tests for hemostasis:neonatesversus adultsPreterm neonates vs term neonates Neonatesvs olderchildren/adultsApproximateage ofadult value*aPTT Longer Longer16y Prothrombin time Longer Same or longer16y INR Higher Same or higher16y Thrombin time Longer Same or longer5y Bleeding time Longer†Shorter1mo PFA-100Longer†Shorter1mo ROTEM/TEGClotting time Same Shorter3mo Clot formation time Same Shorter3mo Maximal clotﬁrmness Stronger Stronger3mo INR indicates International Normalized Ratio;ROTEM,rotating thromboelastometry; and TEG,thromboelastography.*Maximum age reported.†In samples drawn in theﬁrst7-10d of life.Plasminogen,the major protein inﬁbrinolysis,has both lower levels and decreased activity in neonates compared with adults.In neonates,5times the amount of tissue plasminogen activator(tPA) is required to activate plasminogen compared with activation of plasminogen in adults.20Elevated plasma levels of tPA and plasminogen activator inhibitor(PAI)also reﬂect the reduced ﬁbrinolytic activity in neonates.The increased levels of tPA and PAI found on theﬁrst day of life contrast markedly with values obtained from cord blood,which are signiﬁcantly lower than adults levels.Indeed,samples from cord plasma show an increased ﬁbrinolytic index,as measured by the clot formation and lysis assay (CloFAL).21The change inﬁbrinolytic activity immediately after birth may depend on circulatory and respiratory adaptation to extrauterine life.The maturation of the hemostasis system in utero is reﬂected in hemostatic differences between preterm and term neonates(Tables 1and2).1,9,22-24The differences in platelet activity and in global assays of platelet function are detected in samples drawn in theﬁrst week to10days of life.3,7,25,26Coagulation andﬁbrinolysis differ-ences have also been found between small-for-GA and appropriate-for-GA term and preterm neonates.27,28Clinical implications of developmental hemostasis Despite the quantitative and qualitative deﬁciencies of multiple hemostatic factors,healthy neonates have normal hemostasis. Although often characterized as“immature,”the neonatal hemo-static system is nevertheless functionally balanced with no tendency toward coagulopathy or thrombosis.Healthy neonates show no signs of easy bruising or other bleeding diathesis,and no increased tendency to thrombosis for any given stimulus compared with adults.Illnesses that disrupt the hemostatic system may predispose neonates to hemorrhagic or thrombotic complications.Studying the effects of neonatal illness on hemostasis values is important both for understanding the risk for thrombosis/bleeding events in ill neonates and for exploring the most effective intervention that may be used to treat or prevent these events.Neonatal thrombosisNeonates have the highest risk of developing thrombosis compared with infants and children,likely promoted by sepsis,inﬂammation, hypotension,hypoxia,and the use of intravascular catheters in small-caliber and umbilical vessels.29,30Deﬁciency of␣2M,protein C,protein S,and antithrombin in ill neonates may explain their increased risk of thrombotic events.31Nevertheless,because most cases of neonatal thrombosis occur with normal age-appropriate levels of inhibitors of coagulation proteins,the indication for measuring plasma levels of protein C,protein S,and/or antithrom-bin should be discussed on a case-by-case basis.In vitro data suggest that transfusion of adult platelets into neonatal blood results in stronger clotﬁrmness and shorter clotting,potentially increasing the thrombosis risk.32Currently,this in vitro observation has not been tested in vivo and thus cannot be translated into practical recommendations.The impact of developmental hemostasis on antithrombotic therapy should also be considered.18For example,neonates may require a higher concentration of tPA to successfully induce ﬁbrinolysis and lower doses of antiﬁbrinolytics to prevent ﬁbrinolysis.33The poor correlation between the aPTT test and anti-Xa levels in neonates and infants treated with unfractionated heparin(UFH)may imply that the anti-Xa level and not the aPTT test should be used to monitor UFH therapy in childrenϽ1year of age.34A recent study showing high thrombus resolution in neonates and infantsϽ6months of age treated with UFH, despite the delay in attaining therapeutic anti-Xa levels questions this recommendation and raises a question on the required therapeutic dose of UFH in this age group.35These examples and others highlight the importance of using age-speciﬁc guidelines for the management of neonatal thrombosis.34Neonatal bleedingNeonates with severe congenital bleeding disorders are more vulnerable for bleeding,especially intracranial hemorrhage,com-pared with older children and adults.36Asphyxiated neonates develop thrombocytopenia,decreased platelet survival,decreased platelet function,and an increased risk for disseminated intravascu-lar coagulation.37Septic neonates may develop thrombocytopenia and coagulopathy secondary to liver failure and/or disseminated intravascular coagulation.It is speculated that the deﬁciency in the ability of neonates to increase their megakaryocyte size may contribute to the predisposition of sick neonates to develop pro-longed and severe thrombocytopenia.4Prolonged clotting time and reduced clotﬁrmness in neonates with complex congenital heart disease38and prolonged bleeding times in those with low hematocrit and those receiving ampicillin7,39,40may increase bleeding risk in these children.Bleeding time was shown to be increased by 3.6seconds for every1%decrease in hematocrit in these neonates.7 The contribution of the immaturity of the hemostasis system to the occurrence of intraventricular hemorrhage(IVH)in very-low-birth-weight(VLBW)neonates is unclear.Preterm and VLBW neonates are at increased risk for IVH,especially in theﬁrst week of life,as a result of immaturity of the cerebral circulatory system.41The higher bleeding tendency in preterm and VLBW neonates may also contribute to this risk.A higher bleeding tendency,found mostly in theﬁrst10days of life,is correlated with the risk period for IVH.7,23 The role of therapies targeting the hemostasis system for the prevention or the treatment of IVH in preterm and VLBW neonates is currently being debated.42Laboratory diagnosis of hemostatic disorders in neonatesLaboratory diagnosis of hemostatic disorders in neonates may be difﬁcult to establish because of the need to adapt laboratory tests to the smaller sample volumes obtained.Sample integrity is a major problem in pediatric coagulation studies,and attention to using repeat samples is important to avoid erroneous results.18Overdiag-nosis and misdiagnosis are both common when age-,analyzer-,and reagent-speciﬁc reference reagents are not used.Recently,the Perinatal and Pediatric Hemostasis Subcommittee (SCC)of the International Society on Thrombosis and Hemostasis (ISTH)published consensus recommendations for laboratories reporting pediatric samples for hemostasis tests.The main recom-mendation is that all diagnostic laboratories processing pediatric samples should use age-,analyzer-,and reagent-appropriate refer-ence ranges.43The following age-appropriate reference ranges were recommended;neonates,1month-1year of age,1-5years of age, 6-10years of age,and11-16years of age.Addressing the labor-intensive effort needed for development of local reference ranges,the committee stated that hemostasis test results can be compared across laboratories providing the population,reagents, and analyzer are identical.Currently,age-appropriate reference ranges have been established for platelet counts,coagulation screening tests,and coagulation and anticoagulation proteins in preterm and term neonates.2,11,13,14,24 Age-dependent references have also been established for global in vitro hemostasis testing such as PFA-100,thromboelastography, and rotating thromboelastometry.8,10,44Term and preterm neonatal reference ranges for the percentage of reticulated platelets were established and can be used for interpretation of this test in thrombocytopenic neonates.3The consensus paper pointed to the need for developing reference values in very young,VLBW,and extremely sick premature infants and for new devices and hemosta-sis assessment techniques.43Finally,the interpretation of diagnostic laboratory results in neonates may also be misleading and should be approached with caution.A laboratory test result outside of the95%conﬁdence limit of healthy neonates is not sufﬁcient to deﬁne a disease.The diagnosis of thrombophilia or of a bleeding disorder in neonates should be based on the presence of a positive clinical phenotype,family history,and of reproducible abnormal laboratory results.18Overdiagnosis and misdiag-nosis of hemostatic disorders in neonates may lead to the administra-tion of wrong and potentially harmful treatments for many years. Therefore,insisting on both clinical correlation and on repeated abnormal laboratory results is extremely important in this population. DisclosureConﬂict-of-interest disclosure:The author declares no competing ﬁnancial interests.Off-label drug use:None disclosed. CorrespondenceShoshana Revel-Vilk,MD,MSc,Pediatric Hematology/Oncology Department,Hadassah Hebrew-University Hospital,POB12000, Jerusalem,Israel91200;Phone:972-26777408;Fax:972-26777833; e-mail:shoshanav@.il.References1.Monagle P,Massicotte P.Developmental haemostasis:second-ary haemostasis.Semin Fetal Neonatal Med.2011;16(6):294-300.2.Wiedmeier SE,Henry E,Sola-Visner MC,Christensen RD.Platelet reference ranges for neonates,deﬁned using data from over47,000patients in a multihospital healthcare system.J Perinatol.2009;29(2):130-136.3.Saxonhouse MA,Sola MC,Pastos KM,et al.Reticulatedplatelet percentages in term and preterm neonates.J Pediatr Hematol Oncol.2004;26(12):797-802.4.Sola-Visner M,Sallmon H,Brown R.New insights into themechanisms of nonimmune thrombocytopenia in neonates.Semin Perinatol.2009;33(1):43-51.5.Strauss T,Sidlik-Muskatel R,Kenet G.Developmental hemo-stasis:primary hemostasis and evaluation of platelet function in neonates.Semin Fetal Neonatal Med.2011;16(6):301-304. 6.Israels SJ.Diagnostic evaluation of platelet function disordersin neonates and children:an update.Semin Thromb Hemost.2009;35(2):181-188.7.Del Vecchio A,Latini G,Henry E,Christensen RD.Templatebleeding times of240neonates born at24to41weeks gestation.J Perinatol.2008;28(6):427-431.8.Carcao MD,Blanchette VS,Dean JA,et al.The PlateletFunction Analyzer(PFA-100):a novel in vitro system for evaluation of primary haemostasis in children.Br J Haematol.1998;101(1):70-73.9.Strauss T,Levy-Shraga Y,Ravid B,et al.Clot formation ofneonates tested by thromboelastography correlates with gesta-tional age.Thromb Haemost.2010;103(2):344-350.10.Oswald E,Stalzer B,Heitz E,et al.Thromboelastometry(ROTEM)in children:age-related reference ranges and correla-tions with standard coagulation tests.Br J Anaesth.2010;105(6): 827-835.11.Andrew M,Paes B,Milner R,et al.Development of the humancoagulation system in the full-term infant.Blood.1987;70(1): 165-172.12.Katz JA,Moake JL,McPherson PD,et al.Relationship betweenhuman development and disappearance of unusually large von Willebrand factor multimers from plasma.Blood.1989;73(7): 1851-1858.13.Andrew M,Paes B,Milner R,et al.Development of the humancoagulation system in the healthy premature infant.Blood.1988;72(5):1651-1657.14.Monagle P,Barnes C,Ignjatovic V,et al.Developmentalhaemostasis.Impact for clinical haemostasis laboratories.Thromb Haemost.2006;95(2):362-372.15.Ignjatovic V,Mertyn E,Monagle P.The coagulation system inchildren:developmental and pathophysiological consider-ations.Semin Thromb Hemost.2011;37(7):723-729.16.Ignjatovic V,Lai C,Summerhayes R,et al.Age-relateddifferences in plasma proteins:how plasma proteins change from neonates to adults.PLoS One.2011;6(2):e17213.17.Guzzetta NA,Miller BE.Principles of hemostasis in children:models and maturation.Paediatr Anaesth.2011;21(1):3-9. 18.Monagle P,Ignjatovic V,Savoia H.Hemostasis in neonates andchildren:pitfalls and dilemmas.Blood Rev.2010;24(2):63-68.ler BE,Tosone SR,Guzzetta NA,Miller JL,Brosius KK.Fibrinogen in children undergoing cardiac surgery:is it effec-tive?Anesth Analg.2004;99(5):1341-1346.20.Parmar N,Albisetti M,Berry LR,Chan AK.Theﬁbrinolyticsystem in newborns and children.Clin Lab.2006;52(3-4):115-124.21.Goldenberg NA,Hathaway WE,Jacobson L,Manco-JohnsonMJ.A new global assay of coagulation andﬁbrinolysis.Thromb Res.2005;116(4):345-356.22.Barnard DR,Simmons MA,Hathaway WE.Coagulation stud-ies in extremely premature infants.Pediatr Res.1979;13(12): 1330-1335.23.Sentilhes L,Leroux P,Radi S,et al.Inﬂuence of gestational ageonﬁbrinolysis from birth to postnatal day10.J Pediatr.2011;158(3):377-382.24.Salonvaara M,Riikonen P,Kekomaki R,et al.Effects ofgestational age and prenatal and perinatal events on the coagulation status in premature infants.Arch Dis Child Fetal Neonatal Ed.2003;88(4):F319-323.25.Bednarek FJ,Bean S,Barnard MR,Frelinger AL,MichelsonAD.The platelet hyporeactivity of extremely low birth weight neonates is age-dependent.Thromb Res.2009;124(1):42-45. 26.Saxonhouse MA,Garner R,Mammel L,et al.Closure timesmeasured by the platelet function analyzer PFA-100are longer in neonatal blood compared to cord blood samples.Neonatol-ogy.2010;97(3):242-249.27.Mitsiakos G,Papaioannou G,Papadakis E,et al.Haemostaticproﬁle of full-term,healthy,small for gestational age neonates.Thromb Res.2009;124(3):288-291.28.Mitsiakos G,Giougi E,Chatziioannidis I,et al.Haemostaticproﬁle of healthy premature small for gestational age neonates.Thromb Res.2010;126(2):103-106.29.Saracco P,Parodi E,Fabris C,Cecinati V,Molinari AC,Giordano P.Management and investigation of neonatal throm-boembolic events:genetic and acquired risk factors.Thromb Res.2009;123(6):805-809.30.Trenor CC3rd.Thrombosis and thrombophilia:principles forpediatric patients.Blood Coagul Fibrinolysis.2010;21(Suppl1):S11-S15.31.El Beshlawy A,Alaraby I,Abou Hussein H,Abou-Elew HH,Mohamed Abdel Kader MS.Study of protein C,protein S,and antithrombin III in newborns with 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Magnetic resonance elastography (MRE) is a novel imaging technique that can image theresponse of the tissue to externally-generated acoustic waves to obtain the intrinsicmechanical properties of the tissue (16–22). A phase contrast MRE sequence is used tosynchronize external motion with motion sensitizing gradients in the phase of the MRimages to obtain propagating waves. These wave images are then converted to stiffness mapknown as inversion (23,24). MRE has been shown to be clinically valuable in diseases suchas liver cirrhosis where organ stiffness changes (16,25–27).Our hypothesis is that MRE can be used to image early hypertensive changes occurring inthe aorta which result in increased wall stiffness. The purpose of this study is to demonstratefeasibility of using MRE to identify hypertensive changes in the abdominal aorta whencompared to normotensives based on the stiffness measurements and these MRE-derivedstiffness measurements are not presented relative to a gold standard of direct mechanicalmeasurement of the tissue which was not possible in our subjects.MethodsExperiment Setup In vivo aortic MRE was performed on 4 normotensives (25–45 years old Male) and 4hypertensive (44 and 66 years old, 2 Females; 54 and 63 years old, 2 Males) volunteers with a long history of hypertension currently controlled on antihypertensive medications (Blood pressure in range of 118–127 systolic and 80–90 diastolic). Written consent was obtained from the volunteers with the permission of institutional review board. All imaging was performed in a 1.5-Tesla MRI scanner (Signa Excite, GE Health Care, Milwaukee, WI). The volunteers were positioned in the supine position and placed feet first into the scanner as shown in figure 1.Image AcquisitionSingle shot fast spin echo imaging was performed to obtain scout image in a sagittal plane.A gradient echo MRE sequence (28) was performed on this sagittal slice. Mechanical waveswere introduced into the abdominal aorta by a pneumatic driver system as shown in figure 1.The passive driver was placed just inferior to the xiphisternum. Imaging parameters includedTR/TE= 50,66,83/21,24,26 ms; FOV= 24,32,40 cm; α= 30°; slice thickness= 3,5,8 mm;acquisition matrix= 256x96; excitation frequency= 60 Hz (16.67 ms); 4 MRE phase offsets(i.e. the MRI acquisition is performed with multiple offsets of the phase of the externallyapplied wave to obtain images of the wave propagation over time; and the time shift for eachphase offset is 4.17 ms (16.67/4)); and 16.67 ms duration (60 Hz) motion encoding gradientswere applied separately in the x, y, and z directions to measure the in-plane and throughplane motion. Additionally, the wave images were acquired without applying externalmotion, to verify that the wave images observed were from externally applied and not fromphysiologic motion. All images were acquired in free breathing.Image AnalysisThe sagittal images in all the volunteers were masked to obtain abdominal aorta forprocessing as shown in figure 2 indicated by red line. The x, y and z components of motionwere first Fourier transformed in time to obtain the first harmonic displacement data andthen filtered using 4th order Butterworth band pass filter with cutoff values of 1 – 40 waves/FOV to remove longitudinal and high frequency displacements and additionallydirectionally filtered (23) in 8 directions to remove reflected waves. Then the filtereddisplacement data was analyzed using the phase gradient inversion algorithm (24) to obtaineffective stiffness maps.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptStatistical AnalysisStudent’s t-test was performed on MRE-derived stiffness measurements to determine thesignificant difference between normotensives and hypertensives. Values were shown asmean ± standard deviation.Results The experimental results demonstrated that propagating mechanical waves could be visualized in the abdominal aorta in all the volunteers examined as shown in figures 2.When no external motion is applied no discernible waves were imaged indicating MRE is insensitive to the physiological motion of the aorta (not shown).Figure 2 (a-e) shows an example of magnitude image of abdominal aorta with a red contour delineating aorta and the corresponding phase images of the in-plane component of propagating waves at four MRE phase offsets in one of the normotensive (i.e. normal)volunteer. Figure 2(f) shows the weighted stiffness map from 3 encoding directions using phase gradient inversion algorithm with a mean stiffness of 4.2 kPa.Figure 3 (a-f) shows the magnitude image and phase images of propagating waves in the controlled hypertensive volunteer and the corresponding weighted stiffness map from 3encoding directions using phase gradient inversion algorithm with a mean stiffness of 11.4kPa.MRE effective stiffness of abdominal aorta in hypertensives was significantly greater than that of normotensives (Figures 4a) with p=0.02. Figure 4b shows the plot of mean effective stiffness from all the volunteers in each group. The normotensive group demonstrated an average abdominal aortic stiffness of 3.7 ± 0.8 kPa, while the controlled-hypertensive demonstrated an average abdominal aortic stiffness of 9.3 ± 1.9kPa.DiscussionThis study demonstrated feasibility of using MRE to identify hypertensive changes in theabdominal aorta when compared to normotensives based on the stiffness measurements andshowed controlled hypertensives have significantly higher stiffness compared tonormotensives.In this study the external motion was applied to generate waves in the aorta. There was thepossibility that the MRE scan could detect interference motion from the heart and lungs.MRE wave images were acquired with no external motion applied. When no externalmotion was applied, no discernible waves were seen. When external motion was applied wecould observe discernible waves. This supports the fact that the motion sensitization of theMRE imaging filters out the extraneous motion noise.There was also the possibility that the aortic wall would be too thin to detect on the MREexamination. However, the wave propagation was observed in the aorta because of the waveguided effect (22,29). When an aorta is vibrated, the aortic wall and the adjacent bloodvibrate with the same frequency. Therefore, aortic wall and resulting motion of the adjacentblood in the lumen are used in the analysis of MRE to obtain the stiffness of aortic wall.MRE method used in this study is different from all previous methods, in particular PWV.PWV indirectly measures aortic stiffness by assuming the ratio of aortic wall thickness andradius remains constant based on the Moens-Korteweg equation (12). The Moens-Kortewegequation states that PWV is proportional to the square root of the incremental elasticmodulus of the vessel wall given constant ratio of the wall thickness to the vessel radiusNIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscript(30). Aortic wall thickness and radius varies from one location to the other in the aorta(31).However, clinically, PWV is measured how fast the wave travels a specified distance of the vascular bed, i.e. which requires measuring the length of the aorta and is subject to inter-observer variability, and is a limitation of PWV (7–10,31–33). The current study measures the stiffness based on the wavelengths of propagating waves without incorporating the thickness of the aorta. Other imaging strategies such as ultrasound (33,34) and MR (35,36)are in use to estimate the PWV to indirectly report the stiffness of the aorta. However, each technology applies completely different procedures to estimate the PWV and has its own limitations and therefore cannot be compared against each other and to the current study.The MRE method used in this study also is different from MRE methods used in previous studies (22,29). Previously, MRE stiffness measurements in ex vivo models were reported by expressing stiffness in terms of product of Young’s modulus and wall thickness of the aorta. Therefore, the effective aortic stiffness reported in this study cannot be compared against previous studies’ results, (7–10,22,29,32) as they have implemented completely different procedure to estimate stiffness of the aorta. However, our new noninvasive measure of effective aortic stiffness has the advantage of not requiring measurement of aortic wall thickness.There are several limitations to this study. First, the inversion used in this study is a two-dimensional (2D) inversion. Wave propagation within aorta is not planar and very complex associated with waveguide effects therefore a true three-dimensional (3D) inversion with the application of curl operator may offer further information to minimize the effects form waveguide. However, a 3D inversion requires a 3D volumetric data acquisition, which in turn requires a much longer scan time and becomes more difficult for the patient to tolerate.Therefore to incorporate a 3D inversion, data acquisition should be accelerated, so volumetric data can be obtained in a single breathhold. Furthermore, the obtained stiffness measurement for each volunteer is a measurement across the cardiac cycle, but it would beuseful to be able to measure the stiffness in systole and diastole which might be possiblewith cardiac gating. Additionally, our stiffness measurement is a combination of intrinsicproperties of the aorta plus luminal pressure, therefore the stiffness estimates are effective.The final limitation was that the patients were not age-matched in their comparison due tothe small sample size. Despite of these limitations, we have observed significant aorticstiffness differences between controlled hypertensives and normotensives volunteers.Future work will include implementation of 3D acquisition in the aorta during a singlebreathhold by applying parallel imaging acquisition strategies using gradient echo or echoplanar imaging, which is feasible to acquire wave information in one encoding direction.This strategy is currently being implemented in liver MRE scans in our research studies.Further, we will apply cardiac gated cine MRE sequence to determine the stiffness of theaorta across the cardiac cycle, as aorta is a non-linear viscoelastic material and has influenceof pressure (i.e. pressures changes from 80–120mmHg across the cardiac cycle) on stiffness.Future applications of in vivo aortic MRE will be investigated to diagnose different cardiacor aortic disease states, and more elaborate studies will be performed to attempt to separatethe influence of load in measuring stiffness.In conclusion, we have demonstrated feasibility of performing in vivo aortic MRE. 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Measurement of pulse wave velocity using magnetic resonance imaging. Conf ProcIEEE Eng Med Biol Soc. 2004; 5:3684–3687. [PubMed: 17271093] NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptFigure 1.Schematic showing MRE pneumatic passive driver placed on the abdomen of a volunteer.Sound waves are transmitted through a hollow plastic tube to the passive driver and into thevolunteer’s abdominal aorta. NIH-PA Author ManuscriptNIH-PA Author ManuscriptFigure 2. Normotensive Volunteera) Sagittal magnitude image of the abdominal aorta indicated with red contour. b-e) Snapshot of four phases of the in-plane component of the propagating waves and f) Weightedstiffness map from 3 encoding directions with a mean stiffness of 4.2 kPa. NIH-PA Author ManuscriptNIH-PA Author ManuscriptFigure 3. Controlled Hypertensive Volunteera) Sagittal magnitude image of the abdominal aorta indicated with red contour. b-e) Snapshot of four phases of the in-plane component of the propagating waves and f) Weightedstiffness map from 3 encoding directions with a mean stiffness of 11.4 kPa. NIH-PA Author ManuscriptNIH-PA Author ManuscriptFigure 4.a) Plot of MRE-derived aortic stiffness measurements for normotensives and hypertensives.Hypertensives have significantly stiffer aorta than normotensives. b) Plot of mean aorticstiffness measurement in normotensives and hypertensives. Normotensives have mean aortic stiffness of 3.7 ± 0.8 kPa, while controlled hypertensives have mean aortic stiffness of 9.4 ±1.9 kPa.Kolipaka et al.Page 11J Magn Reson Imaging . Author manuscript; available in PMC 2013 March 01.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscript。