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Ngokusekwe kwi-interdisciplinary intersection yefiziksi kunye nesayensi yobomi, iindlela zokuxilonga kunye nezonyango ezisekelwe kunyango oluchanekileyo kutshanje ziye zatsala ingqalelo enkulu ngenxa yokusetyenziswa kweendlela ezintsha zobunjineli kwiinkalo ezininzi zonyango, ngakumbi kwi-oncology.Ngaphakathi kwesi sikhokelo, ukusetyenziswa kwe-ultrasound ukuhlasela iiseli zomhlaza kumathumba ukuze kubangele umonakalo onokwenzeka koomatshini kwizikali ezahlukeneyo kutsala umdla okhulayo wezazinzulu kwihlabathi liphela.Ukuthathela ingqalelo ezi zinto, ngokusekwe kwizisombululo zexesha elastodynamic kunye nokulinganisa kwamanani, sibonisa isifundo sokuqala sokulinganisa ikhompyuter yokusasazwa kwe-ultrasound kwiithishu ukuze kukhethwe i-frequencies kunye namandla afanelekileyo nge-irradiation yendawo.Iqonga elitsha lokuxilonga elebhu ye-On-Fiber teknoloji, ebizwa ngokuba yinaliti yesibhedlele kwaye sele inelungelo elilodwa lomenzi wechiza.Kukholelwa ukuba iziphumo zokuhlalutya kunye nokuqonda okuhambelanayo kwe-biophysical kunokuvula indlela entsha yokuxilonga kunye neendlela zonyango ezidibeneyo ezinokudlala indima ephambili ekusebenziseni iyeza elichanekileyo kwixesha elizayo, ukutsala kwiinkalo ze-physics.Intsebenziswano ekhulayo phakathi kwebhayoloji iyaqala .
Ngokulungiswa kwenani elikhulu lezicelo zeklinikhi, isidingo sokunciphisa imiphumo emibi kwizigulane ngokuthe ngcembe yaqala ukuvela.Ukuza kuthi ga ngoku, iyeza elichanekileyo1, ​​2, 3, 4, 5 libe yinjongo yeqhinga lokunciphisa idosi yamachiza asiwe kwizigulane, ngokusisiseko kulandelwa iindlela ezimbini eziphambili.Eyokuqala isekelwe kunyango olulungiselelwe ngokweprofayili ye-genomic yesigulana.Okwesibini, okuba ngumgangatho wegolide kwi-oncology, ijolise ekuphepheni iinkqubo zokuhanjiswa kweziyobisi zenkqubo ngokuzama ukukhulula inani elincinci leziyobisi, ngelixa kwangaxeshanye ukwandisa ukuchaneka ngokusetyenziswa kwonyango lwendawo.Eyona njongo iphambili kukuphelisa okanye ubuncinci ukunciphisa iziphumo ezibi zeendlela ezininzi zonyango, ezinje ngechemotherapy okanye ulawulo lwenkqubo yeeradionuclides.Ngokuxhomekeke kuhlobo lomhlaza, indawo, idosi yemitha, kunye nezinye izinto, nonyango lwemitha lunokuba nomngcipheko omkhulu wendalo kwizicubu ezisempilweni.Kunyango lwe-glioblastoma6,7,8,9 utyando lususa ngempumelelo umhlaza osisiseko, kodwa nangona kungabikho metastases, uninzi oluncinci lomhlaza olungena ngaphakathi lunokubakho.Ukuba azisuswanga ngokupheleleyo, abantu abatsha abanomhlaza banokukhula ngexesha elifutshane.Kulo mongo, amaqhinga amayeza achanekileyo akhankanywe ngasentla kunzima ukuwasebenzisa kuba ezi zingeno zingena zinzima ukuzibona kwaye zisasazeke kwindawo enkulu.Ezi zithintelo zithintela iziphumo ezicacileyo ekuthinteleni naluphi na ukuphindaphinda ngamayeza achanekileyo, ngoko ke iindlela zokuhanjiswa kwenkqubo zikhethwa kwezinye iimeko, nangona amachiza asetyenziswayo anokuba namazinga aphezulu kakhulu etyhefu.Ukoyisa le ngxaki, indlela efanelekileyo yonyango iya kuba kukusebenzisa iindlela ezinokuthi zihlasele ngokukhetha iiseli zomhlaza ngaphandle kokuchaphazela izicubu ezisempilweni.Ngenxa yale ngxabano, ukusetyenziswa kwee-vibrations ze-ultrasonic, eziye zabonakaliswa ukuba zichaphazela umhlaza kunye neeseli ezinempilo ngokwahlukileyo, zombini kwiinkqubo ze-unicellular kunye ne-mesoscale heterogeneous clusters, kubonakala ngathi isisombululo esinokwenzeka.
Ngokwembono yomatshini, iiseli ezisempilweni kunye nomhlaza ngokwenene zinezandi ezahlukeneyo zendalo ezijikelezayo.Le propati inxulunyaniswa neenguqu ze-oncogenic kwiimpawu zomatshini zesakhiwo se-cytoskeletal yeeseli zomhlaza12,13, ngelixa iiseli ze-tumor, ngokomndilili, zikhubazeke ngaphezu kweeseli eziqhelekileyo.Ke, ngokhetho olufanelekileyo lwefrikhwensi ye-ultrasound yokuvuselela, ukungcangcazela okubangelwa kwiindawo ezikhethiweyo kunokubangela umonakalo kwizakhiwo ezinomhlaza ophilayo, ukunciphisa impembelelo kwimeko ephilileyo yomkhosi.Ezi ziphumo zingekaqondwa ngokupheleleyo zinokubandakanya ukutshatyalaliswa kwamacandelo athile okwakhiwa kweeseli ngenxa yokushukuma okuphezulu okubangelwa yi-ultrasound (ngokwemigaqo efana kakhulu ne-lithotripsy14) kunye nomonakalo weselula ngenxa yento efana nokudinwa komatshini, okunokuthi kutshintshe isakhiwo seselula. .inkqubo kunye ne-mechanobiology.Nangona esi sisombululo sethiyori sibonakala sifanelekile kakhulu, ngelishwa asikwazi ukusetyenziswa kwiimeko apho izakhiwo zebhayoloji ze-anechoic zithintela usetyenziso oluthe ngqo lwe-ultrasound, umzekelo, kwizicelo ze-intracranial ngenxa yobukho bethambo, kwaye ezinye izicubu zethumba zebele zifumaneka kwi-adipose. ithishu.Ukuhoywa kunokunciphisa indawo yempembelelo yonyango enokubakho.Ukoyisa ezi ngxaki, i-ultrasound kufuneka isetyenziswe ekuhlaleni kunye neetransducer eziyilwe ngokukodwa ezinokuthi zifikelele kwisiza esifakwe i-irradiation ngendlela ehlaselayo kangangoko.Ngale nto engqondweni, sithathele ingqalelo into enokwenzeka yokusebenzisa izimvo ezinxulumene nokuba nokwenzeka kokwenza iqonga lobuchule lobuchwephesha elibizwa ngokuba “sisibhedlele senaliti”15.Ingcamango "yeSibhedlele kwiNaliti" ibandakanya ukuphuhliswa kwesixhobo sonyango esincinci sokuxilonga kunye nezicelo zonyango, ngokusekelwe ekudityanisweni kwemisebenzi eyahlukeneyo kwinaliti enye yonyango.Njengoko kuxutyushwa ngokubanzi kwiCandelo leNaliti yeSibhedlele, esi sixhobo esidibeneyo sisekelwe ngokukodwa kwiinzuzo ze-16, 17, 18, 19, 20, 21 fiber optic probes, ezithi, ngenxa yeempawu zazo, zilungele ukufakwa kwi-standard 20 iinaliti zonyango, 22 lumens.Ukusebenzisa ukuguquguquka okubonelelwa yiTekhnoloji yeLab-on-Fiber (LOF) ye-23, i-fiber ngokufanelekileyo iba liqonga elikhethekileyo le-miniaturized kunye nelungele ukusetyenziswa kwezixhobo zokuxilonga kunye nezonyango, kubandakanywa ne-biopsy ye-fluid kunye nezixhobo ze-tissue biopsy.ekubhaqweni kwe-biomolecular24,25, ukuhanjiswa kweziyobisi zendawo ekhokelwa ukukhanya26,27, ukuchaneka okuphezulu kwendawo ye-ultrasound imaging28, unyango lwe-thermal29,30 kunye nokuchongwa kwezicubu zomhlaza ezisekelwe kwi-spectroscopy31.Ngaphakathi kolu luvo, kusetyenziswa indlela yendawo esekelwe kwisixhobo "senaliti esibhedlele", siphanda ithuba lokuphucula ukukhuthazwa kwendawo yokuhlala yezakhiwo zebhayoloji ngokusebenzisa ukusasazwa kwamaza e-ultrasound ngokusebenzisa iinaliti ukuvuyisa amaza e-ultrasound ngaphakathi kwendawo yomdla..Ngaloo ndlela, i-ultrasound ye-low-intensity therapeutic ultrasound inokusetyenziswa ngokuthe ngqo kwindawo yomngcipheko kunye nokuhlaselwa okuncinci kwiiseli ze-sonicating kunye nezakhiwo ezincinci eziqinileyo kwizicubu ezithambileyo, njengoko kwimeko yotyando olukhankanywe ngasentla, umngxuma omncinci kwi-skull kufuneka ufakwe kunye ne-skull. inaliti.Iphefumlelwe ziziphumo zamva nje zethiyori kunye novavanyo ezicebisa ukuba i-ultrasound inokumisa okanye ilibazise ukuphuhliswa kwee-cancer ezithile,32,33,34 indlela ecetywayo inokunceda ukujongana, ubuncinci, ukurhweba okuphambili phakathi kweziphumo ezinobundlobongela kunye nokunyanga.Ngolu qwalaselo engqondweni, kweli phepha langoku, siphanda ngamathuba okusebenzisa isixhobo senaliti esisesibhedlele kunyango olungephi lwe-ultrasound yomhlaza.Ngokuchanekileyo, kwi-Scattering Analysis of Spherical Tumor Masses for Estimating Growth-Dependent Ultrasound Frequency section, sisebenzisa iindlela ezisekelwe kakuhle ze-elastodynamic kunye ne-acoustic scattering theory ukuqikelela ubungakanani be-spherical tumors eqinile ekhulile kwi-elast medium.ukuqina okwenzeka phakathi kwe-tumor kunye ne-host tissue ngenxa yokukhula ngokutsha kwezinto eziphathekayo.Emva kokuchaza inkqubo yethu, esiyibiza ngokuba "Isibhedlele kwiNaliti", kwicandelo elithi "Isibhedlele kwiNaliti", sihlalutya ukusasazwa kwamaza e-ultrasonic ngokusebenzisa iinaliti zonyango kwiifrikhwensi eziqikelelweyo kunye nemodeli yabo yamanani ihlahlela indawo yokufunda. iiparitha eziphambili zejometri (i-diameter yangempela yangaphakathi, ubude kunye nobukhali benaliti), echaphazela ukuhanjiswa kwamandla omsindo wesixhobo.Ukunikezelwa kwesidingo sokuphuhlisa izicwangciso ezintsha zobunjineli zonyango oluchanekileyo, kukholelwa ukuba isifundo esicetywayo sinokunceda ukuphuhlisa isixhobo esitsha sonyango lomhlaza ngokusekelwe ekusebenziseni i-ultrasound ehanjiswa ngeqonga elidibeneyo le-theragnostic elidibanisa i-ultrasound kunye nezinye izisombululo.Idityanisiwe, njengokuhanjiswa kweziyobisi ekujoliswe kuzo kunye noxilongo lwexesha langempela ngaphakathi kwenaliti enye.
Ukusebenza kokubonelela ngezicwangciso ze-mechanistic kunyango lwe-tumor eqinileyo yendawo usebenzisa i-ultrasonic (i-ultrasound) ukuvuselela kuye kwaba yinjongo yamaphepha amaninzi asebenza ngethiyori kunye novavanyo kunye nefuthe le-low-intensity ultrasonic vibrations kwi-single-cell systems 10, 11, 12 ., 32, 33, 34, 35, 36 Ukusebenzisa iimodeli ze-viscoelastic, abaphandi abaninzi baye babonisa ngokuhlalutyayo ukuba ithumba kunye neeseli eziphilileyo zibonisa iimpendulo zamaxesha ahlukeneyo abonakaliswe ngeencopho ezivakalayo kwi-US 10,11,12.Esi siphumo sicebisa ukuba, ngokomgaqo, iiseli zethumba zinokuhlaselwa ngokukhethayo ngokuvuselela oomatshini abagcina indawo yomkhosi.Oku kuziphatha kusisiphumo esithe ngqo sobungqina obuphambili bokuba, kwiimeko ezininzi, iiseli zethumba zithambile ngakumbi kuneeseli ezisempilweni, zisenokwandisa amandla azo okwanda nokufuduka37,38,39,40.Ngokusekwe kwiziphumo ezifunyenwe ngeemodeli zeeseli enye, umz. kwi-microscale, ukukhethwa kweeseli zomhlaza kukwabonakalisiwe kwi-mesoscale ngezifundo zamanani zeempendulo ze-harmonic ze-heterogeneous cell aggregates.Ukubonelela ngepesenti eyahlukileyo yeeseli zomhlaza kunye neeseli ezinempilo, ii-multicellular aggregates amakhulu ee-micrometers ngobukhulu zakhiwe ngokoluhlu.Kwi-mesolevel yezi ngqungquthela, ezinye iimpawu ze-microscopic zomdla zigcinwa ngenxa yokuphunyezwa ngokuthe ngqo kwezinto eziphambili zesakhiwo ezibonisa ukuziphatha komatshini kwiiseli enye.Ngokukodwa, iseli nganye isebenzisa i-architecture esekelwe kwi-tensegrity ukulinganisa impendulo yezakhiwo ezahlukeneyo ze-cytoskeletal prestressed, ngaloo ndlela zichaphazela ukuqina kwazo zonke12,13.Uqikelelo lwethiyori kunye neemvavanyo ze-in vitro zolu ncwadi lungasentla lunike iziphumo ezikhuthazayo, ezibonisa imfuneko yokufunda ubuntununtunu be-tumor masses ukuya kwi-low-intensity therapeutic ultrasound (LITUS), kunye novavanyo lokuphindaphinda kwe-irradiation ye-tumor masses ibalulekile.beka LITUS kwisicelo kwisiza.
Nangona kunjalo, kwinqanaba le-tissue, inkcazo ye-submacroscopic yecandelo lomntu ilahlekile ngokungenakuphepheka, kwaye iipropati zezicubu ze-tumor zingalandelelwa ngokusebenzisa iindlela ezilandelelanayo zokulandelela ukukhula kobunzima kunye neenkqubo zokuhlengahlengisa ezibangelwa uxinzelelo, kuthathelwa ingqalelo imiphumo ye-macroscopic. ukukhula.-utshintsho olwenziwe kwi-tissue elasticity kwisikali se-41.42.Inene, ngokungafaniyo neenkqubo ezidityanisiweyo kunye ne-aggregate, i-tumor eqinile ikhula kwizihlunu ezithambileyo ngenxa yokuqokelelwa ngokuthe ngcembe koxinzelelo lwentsalela, olutshintsha iipropathi zendalo zoomatshini ngenxa yokwanda kokuqina kwe-intratumoral iyonke, kunye ne-tumor sclerosis ihlala iba yinto emiselayo. ukufumanisa ithumba.
Ngolu qwalaselo engqondweni, apha sihlalutya impendulo ye-sonodynamic ye-tumor spheroids emiliselwe njenge-elastic spherical inclusions ekhula kwindawo eqhelekileyo yethishu.Ngokuchanekileyo, iipropathi ezi-elastic ezinxulumene nesigaba se-tumor zinqunywe ngokusekelwe kwiziphumo zethiyori kunye novavanyo olufunyenwe ngababhali abathile kumsebenzi wangaphambili.Phakathi kwazo, ukuvela kwe-spheroids ye-tumor eqinile ekhule kwi-vivo kwimidiya ye-heterogeneous iye yaphononongwa ngokusebenzisa iimodeli ze-non-linear mechanical 41,43,44 ngokudibanisa ne-interspecies dynamics ukuqikelela uphuhliso lwe-tumor mass kunye noxinzelelo oluhambelana ne-intratumoral.Njengoko kukhankanyiwe ngasentla, ukukhula (umzekelo, ukunwebeka kwe-inelastic) kunye noxinzelelo olushiyekileyo kubangela uhlengahlengiso oluqhubekayo lweepropathi zemathiriyeli yethumba, ngaloo ndlela itshintsha impendulo yayo ye-acoustic.Kubalulekile ukuqaphela ukuba kwi-ref.I-41 i-co-evolution yokukhula kunye noxinzelelo oluqinileyo kwi-tumors ibonakaliswe kumaphulo okulinga kwiimodeli zezilwanyana.Ngokukodwa, uthelekiso lokuqina kobunzima bethumba lebele eliye laphinda lavela kumanqanaba ahlukeneyo kunye nokuqina okufunyenwe ngokuvelisa kwakhona iimeko ezifanayo kwi-silico kwimodeli yento engqukuva enemilinganiselo efanayo kwaye kuthathelwa ingqalelo indawo yoxinzelelo lwentsalela eqikelelweyo yaqinisekisa indlela ecetywayo yoxinzelelo. ubunyani bemodeli..Kulo msebenzi, iziphumo ezifunyenwe ngaphambili zethiyori kunye novavanyo zisetyenziselwa ukuphuhlisa isicwangciso esitsha sonyango esiphuhlisiwe.Ngokukodwa, ubungakanani obuqikelelweyo obuneempawu zokuxhathisa ezihambelanayo zabalwa apha, eziye zasetyenziselwa ukuqikelela uluhlu lwamaqhuqhuva apho inqwaba yethumba efakwe kwindawo yomkhosi inovakalelo ngakumbi.Ukuza kuthi ga ngoku, siphande ngokuziphatha okuguquguqukayo kobunzima bethumba kumanqanaba ahlukeneyo, athathwe kumanqanaba ahlukeneyo, sithathela ingqalelo izikhombisi ze-acoustic ngokuhambelana nomgaqo owamkelweyo wokusasaza ekuphenduleni i-ultrasonic stimuli kunye nokuqaqambisa i-resonant phenomena ye-spheroid. .ngokuxhomekeke kwithumba kunye nomkhosi Ukukhula-kuxhomekeke umahluko phakathi kokuqina phakathi kwezicubu.
Ke ngoko, ubuninzi betyhalarha balinganiswe njengee-elastic spheres of radius \(a\) kwindawo ejikelezileyo elastiki yenginginya esekwe kwidatha yovavanyo ebonisa indlela izakhiwo eziyingozi ezinkulu ezikhula ngayo kwi-situ kwiimilo ezingqukuva.Ukubhekisa kuMfanekiso 1, usebenzisa ulungelelwaniso olungqukuva \(\{r,\theta,\varphi \}\) (apho \(\theta\) kunye \(\varphi\) zimele i-engile engaqhelekanga kunye ne-azimuth engile ngokulandelelanayo), i idomeyini yethumba ithatha iNgingqi efakwe kwindawo esempilweni \({\mathcal {V}_{T}=\{ (r,\theta,\varphi ):r\le a\}\) ummandla ongamiselwanga \({\mathcal { V} }_{H} = \{(r,\theta,\varphi):r > a\}\).Ukubhekisa kwiNkcukacha eyoNgezelelweyo (SI) ngenkcazo epheleleyo yemodeli yezibalo esekelwe kwisiseko esisekwe kakuhle se-elastodynamic esichazwe kwiincwadi ezininzi45,46,47,48, siqwalasela apha ingxaki ebonakaliswe yi-axisymmetric oscillation mode.Le ngcinga ithetha ukuba zonke iinguqu ngaphakathi kwe-tumor kunye neendawo ezinempilo zizimeleyo kwi-azimuthal coordinate \ (\ varphi \) kwaye akukho kuphazamiseka okwenzekayo kweli cala.Ngenxa yoko, iindawo zokufuduka kunye noxinzelelo zinokufumaneka kwizinto ezimbini ezinokubakho \ (\ phi = \ hat {\ phi} \ ekhohlo ( {r, \ theta} \ ekunene) e^ {{ - i \ omega {\ kern 1pt } t }}\) kunye \(\chi = \ hat{\chi }\khohlo ( {r,\theta } \ ekunene) e^ {{ - i\omega {\ kern 1pt} t }}\) , ngokulandelelanayo inxulumene namaza obude kunye namaza okucheba, ixesha lokungqamana t phakathi kokunyuka \(\theta \) kunye ne-engile phakathi kwesalathiso sesiganeko kunye nevektha yendawo \({\mathbf {x))\) ( njengoko kubonisiwe kumfanekiso 1) kwaye \(\omega = 2\pi f\) imele i-angular frequency.Ngokukodwa, ummandla wesiganeko uhlaziywa nge-wave wave \ (\ phi_{H} ^ {(in)}\) (kwaye yaziswa kwinkqubo ye-SI, kwi-equation (A.9)) isasaza kumthamo womzimba ngokutsho komthetho
apho \(\phi_{0}\) yiparameter yeamplitude.Ukwandiswa okungqukuva kwesangqa senqwelomoya yesiganeko (1) kusetyenziswa umsebenzi wamaza ongqukuva yingxoxo eqhelekileyo:
Apho \(j_{n}\) ngumsebenzi weBessel ongqukuva wohlobo lokuqala lolandelelwano \(n\), kwaye \(P_{n}\) yiLegendre polynomial.Inxalenye yesiganeko somdlalo wotyalo-mali sisasazeke kumbindi ojikelezileyo kwaye sigqithe kwibala lesiganeko, ngelixa elinye icala lisasazeke ngaphakathi kwisphere, linegalelo ekungcangcazeleni kwayo.Ukwenza oku, izisombululo ze-harmonic ze-equation yamaza \(\nabla^{2} \hat{\phi } + k_{1}^{2} {\ mkern 1mu} \hat{\phi } = 0\,\ ) kunye \ (\ nabla^{2} {\mkern 1mu} \hat{\chi } + k_{2}^{2} \hat{\chi } = 0\), kubonelelwe ngomzekelo ngu-Eringen45 (bona kwakhona SI ) ingabonisa i-tumor kunye neendawo eziphilileyo.Ngokukodwa, amaza okwandisa asasazekileyo kunye namaza e-isovolumic aveliswa kwindawo yokusingatha \ (H \) avuma amandla abo afanelekileyo:
Phakathi kwabo, umsebenzi we-Hankel ongqukuva wohlobo lokuqala \(h_{n}^{(1)}\) isetyenziselwa ukuqwalasela igagasi eliphumayo elisasazekileyo, kunye \(\ alpha_{n}\) kunye \(\ beta_{ n}\ ) zii-coefficients ezingaziwayo.kwinxaki.Kwii-equations (2)–(4), amagama \(k_{H1}\) kunye \(k_{H2}\) abonisa amanani amaza okungaqhelekanga kunye namaza anqamlezayo kwindawo ephambili yomzimba, ngokulandelelanayo ( bona SI).Imimandla yoxinzelelo ngaphakathi kwethumba kunye nokutshintsha kunefom
Apho \(k_{T1}\) kunye \(k_{T2}\) imele amanani amaza obude kunye ne-transverse kwingingqi yethumba, kunye nee-coefficients ezingaziwayo \(\gamma_{n} {\mkern 1mu}\) , \(\ eta_{n} {\mkern 1mu}\).Ngokusekwe kwezi ziphumo, iinxalenye ze-non-zero radial kunye ne-circumferential displacement luphawu lwemimandla enempilo kwingxaki eqwalaselwayo, njenge \(u_{Hr}\) kunye \(u_{H\theta}\) (\(u_{ H\ varphi }\ ) i-symmetry assumption ayisafuneki) - inokufumaneka kubudlelwane \(u_{Hr} = \ partial_{r} \ left( {\ phi + \ partial_ {r} ) (r\ chi ) } \ekunene) + k_}^{2} {\mkern 1mu} r\chi\) kunye \(u_{H\theta} = r^{- 1} \inxenye_{\theta} \khohlo({\phi + \inxenye_{r } ( r\chi ) } \ekunene)\) ngokwenza \(\phi = \phi_{H}^{(in)} + \phi_{H}^{(s)}\) kunye \ (\ chi = \ chi_ {H} ^ {(s)}\) (jonga i-SI ngeenkcukacha zokutsalwa kwezibalo).Ngokufanayo, ukubuyisela \(\phi = \phi_{T}^{(s)}\) kunye \(\chi = \chi_{T}^{(s)}\) ibuyisela {Tr} = \inxenye_{r} \ekhohlo( {\phi + \inxenye_{r} (r\chi)} \ekunene) + k_{T2}^{2} {\mkern 1mu} r\chi\) kunye \(u_{T\theta} = r^{-1}\inxenye _{\theta}\khohlo({\phi +\inxenye_{r}(r\chi )}\ekunene)\).
(Ekhohlo) Ijiyometri yethumba elingqukuva elikhule kwindawo enempilo apho intsimi yesiganeko isasazeke, (ekunene) Indaleko ehambelanayo ye-tumor-host stiffness ratio njengomsebenzi weradius yethumba, ingxelo yedatha (ethathwe kwiCarotenuto et al. 41) ukusuka kwiimvavanyo zoxinzelelo lwevitro zifunyenwe kumathumba ebele aqinileyo atofelwe ngeeseli ze-MDA-MB-231.
Kucingelwa ukuba umgca weelastiki kunye nezixhobo ze-isotropic, amacandelo angengo-zero oxinzelelo kwimimandla esempilweni kunye nethumba, oko kukuthi \(\sigma_{Hpq}\) kunye \(\sigma_{Tpq}\) - thobela umthetho weHooke jikelele, unikwe ukuba kukho zahlukile Lamé moduli , ebonakalisa umamkeli kunye nokunwebeka kwethumba, kuchazwa njenge \(\{ \mu_{H},\,\lambda_{H} \}\) kunye \(\{ \mu_{T},\, \lambda_ {T} \ }\) (jonga i-Equation (A.11) yokubonakaliswa okupheleleyo kwamacandelo oxinzelelo amelwe kwi-SI).Ngokukodwa, ngokwedatha ekwireferensi ye-41 kwaye iboniswe kuMfanekiso 1, ukukhula kwamathumba kubonise utshintsho kwi-tissue elasticity constants.Ke, ukufuduswa kunye noxinzelelo kwindawo yomkhosi kunye nethumba zimiselwe ngokupheleleyo ukuya kuthi ga kwiseti yezinto ezingaziwayo \ ({{\varvec{\upxi}}}_{n} = \{ \alpha_{n} ,{\mkern 1mu } \ beta_{ n} {\ mkern 1mu} \gamma_{n} ,\eta_{n} \}\ ) inemilinganiselo engenasiphelo ngokwethiyori.Ukufumana ezi vectors ze-coefficient, i-interfaces efanelekileyo kunye neemeko zomda phakathi kwe-tumor kunye neendawo eziphilileyo ziyaziswa.Ukucinga ukubophelela okugqibeleleyo kwi-interface ye-tumor-host \ (r = a\), ukuqhubeka kokufuduswa kunye noxinzelelo kufuna ezi meko zilandelayo:
Inkqubo (7) yenza inkqubo yokulinganisa kunye nezisombululo ezingenasiphelo.Ukongeza, imeko yomda ngamnye iya kuxhomekeka kwi-anomaly \ (\ theta\).Ukunciphisa ingxaki yexabiso lomda kwingxaki epheleleyo yealgebra kunye \(N\) iiseti zeenkqubo ezivaliweyo, nganye kuzo engaziwayo \({{\varvec{\upxi}}}_{n} = \{ \ alpha_ {n}, {\mkern 1mu} \beta_{n} {\mkern1mu} \gamma_{n}, \eta_{n} \}_{n = 0,…,N}\) (nge \ ( N \ ukuya \ infty \), ngokwethiyori), kunye nokuphelisa ukuxhomekeka kwee-equations kwimigaqo yetrigonometric, iimeko zojongano zibhalwa ngendlela ebuthathaka kusetyenziswa i-orthogonality ye-Legendre polynomials.Ngokukodwa, i-equation (7)1,2 kunye no (7)3,4 ziphindaphindwe ngo \(P_{n} \ left( {\cos \theta} \right)\) kunye \(P_{n}^{ 1} \ ekhohlo ( { \ cos\ theta} \ ekunene) \) kwaye emva koko udibanise phakathi \(0\) kunye \(\pi\) usebenzisa isazisi zemathematika:
Ngaloo ndlela, imeko ye-interface (7) ibuyisela inkqubo ye-algebraic equation ye-quadratic, enokuthi ibonakaliswe kwifom ye-matrix njenge \ ({\ mathbb{D}}_{n} (a) \cdot {{\varvec{\upxi}} } _{ n} = {\ mathbf{q}}_{n} (a)\) kwaye ufumane okungaziwayo \({{\varvec{\upxi}}}_{n}\ ) ngokusombulula umthetho weCramer.
Ukuqikelela i-flux yamandla esasazwe yi-sphere kwaye ufumane ulwazi malunga nempendulo ye-acoustic esekelwe kwidatha kwintsimi esasazwayo esasaza kwindawo yokusingatha, ubuninzi be-acoustic bunomdla, oyinto eqhelekileyo ye-bistatic scattering cross section.Ngokukodwa, icandelo lomnqamlezo osasazwayo, elibonakaliswe \ (s), libonisa umlinganiselo phakathi kwamandla acoustic ahanjiswe ngumqondiso osasaziweyo kunye nokwahlula kwamandla aqhutywe ngamaza esiganeko.Kulo mba, ubukhulu bomsebenzi wemilo \(\ left| {F_{\infty} \left(\theta \right)} \right|^{2}\) sisixa esisetyenziswa rhoqo kuphononongo lweendlela ezivakalayo. efakwe kulwelo okanye oluqilima Ukusasazwa kwezinto kwintlenga.Ngokuchaneke ngakumbi, i-amplitude yomsebenzi wemilo ichazwa njengokwahluka kwecandelo lomnqamlezo wokusasaza \ (ds\) kwindawo nganye yeyunithi, eyahluke ngokwesiqhelo ukuya kwicala lokusasazwa kwamaza esiganeko:
apho \(f_{n}^{pp}\) kunye \(f_{n}^{ps}\) ibonisa umsebenzi we-modal, obhekiselele kumlinganiselo wamagunya e-longitudinal wave kunye namaza asasaziweyo ngokunxulumene Isiganeko se-P-wave kwindlela yokufumana, ngokulandelelana, inikwe ngolu hlobo lulandelayo:
Imisebenzi ye-wave wave (10) inokufundwa ngokuzimeleyo ngokuhambelana ne-resonant scattering theory (RST) 49,50,51,52, eyenza ukuba kube lula ukwahlula i-elasticity ejoliswe kuyo yonke intsimi elahlekileyo xa ufunda iindlela ezahlukeneyo.Ngokwale ndlela, umsebenzi we-modal form unokuboliswa ube sisixa samalungu amabini alinganayo, angala \(f_{n} = f_{n}^{(res)} + f_{n}^{(b)}\ ) zinxulumene nobubanzi obungasemva beresonant kunye ne-nonresonant, ngokulandelelanayo.Umsebenzi wemilo yemowudi ye-resonant inxulumene nempendulo ekujoliswe kuyo, ngelixa imvelaphi idla ngokuhambelana nokumila kwe-scatterer.Ukubona ifomati yokuqala yethagethi yendlela nganye, ubungakanani bemilo yemodal resonance umsebenzi \(\ left| {f_{n}^{(res)} \khohlo( \theta \ ekunene)} \ ekunene|\ ) ibalwa ngokucingela imvelaphi eqinileyo, equlathe iingqukuva ezingangenekiyo kwisixhobo sokusingathwa esielastiki.Le ngcamango ikhuthazwa yinto yokuba, ngokubanzi, zombini ukuqina kunye nokuxinana kwanda ngokukhula kobunzima be-tumor ngenxa yoxinzelelo olushiyekileyo.Ngoko ke, kwinqanaba elinzima lokukhula, umlinganiselo we-impedance \ (\rho_{T} c_{1T} /\rho_{H} c_{1H}\) kulindeleke ukuba ube mkhulu kune-1 kuninzi lwamathumba aqinileyo akhula ngokuthambileyo. izicubu.Ngokomzekelo, uKrouskop et al.I-53 ibike umlinganiselo womhlaza kwimodyuli eqhelekileyo malunga ne-4 yezicubu ze-prostate, ngelixa eli xabiso lenyuka ukuya kwi-20 kwiisampuli zezicubu zesifuba.Obu budlelwane butshintsha ngokungathintelekiyo i-acoustic impedance yethishu, njengoko kubonisiwe luhlalutyo lwe-elastography54,55,56, kwaye inokunxulumana nokutyeba kwendawo okubangelwa kukwanda kwethumba.Lo mahluko ubuye wabonwa ngovavanyo kunye novavanyo olulula lokucinezela iibhloko zethumba lebele ezikhule kwizigaba ezahlukeneyo32, kwaye ukulungiswa kwakhona kwezinto kunokulandelwa kakuhle kunye neemodeli ezixelwe kwangaphambili zeentlobo zeentlobo zamathumba ezingakhuli ngokulinganayo43,44.Idatha yokuqina efunyenweyo inxulumene ngokuthe ngqo nokuvela kwemodyuli yoMncinci yamathumba aqinileyo ngokwefomula \ (E_{T} = S\ left( {1 – \ nu ^ {2}} \ right)/a\ sqrt \ varepsilon\ )( iingqukuva ezineradiyasi \(a\), ukuqina \(S\) kunye nomlinganiselo wePoisson \(\nu\) phakathi kwamacwecwe amabini aqinileyo angama-57, njengoko kubonisiwe kuMfanekiso 1).Ke, kunokwenzeka ukufumana imilinganiselo ye-acoustic impedance ye-tumor kunye nomkhosi kumanqanaba ahlukeneyo okukhula.Ngokukodwa, xa kuthelekiswa nemodyuli yezicubu eziqhelekileyo ezilingana ne-2 kPa kwi-Fig. iyahambelana nedatha exeliweyo.kwiimbekiselo ezingama-58, i-59 kwafunyaniswa ukuba uxinzelelo kwiisampulu zezicubu zesifuba yi-0.25–4 kPa kunye noxinzelelo lwangaphambili olunyamalalayo.Kwakhona cinga ukuba umlinganiselo we-Poisson we-tissue ephantse incompressible yi-41.60, oku kuthetha ukuba ukuxinana kwezicubu akutshintshi kakhulu njengoko umthamo unyuka.Ngokukodwa, i-avareji yobuninzi bobuninzi babantu \(\rho = 945\,{\text{kg}}\,{\text{m}}^{ - 3}\)61 isetyenziswa.Ngolu qwalaselo, ukuqina kunokuthatha imo yangasemva usebenzisa le ntetho ilandelayo:
Apho into engaziwayo \(\widehat{{{\varvec{\upxi))))_{n} = \{\delta_{n} ,\upsilon_{n} \}\) ingabalwa kuthathelwa ingqalelo ukuqhubeka bias ( 7 )2,4, oko kukuthi, ngokusombulula inkqubo yealgebraic \(\widehat{{\mathbb{D}}}_{n} (a) \cdot \widehat{({\varvec{\upxi}} } } _{n } = \ububanzi{{\mathbf{q}}}_{n} (a)\) ebandakanya abantwana\(\widehat{{\mathbb{D}}}_{n} (a) = \ {{\ mathbb{D}}_{n} (a)\}_{{\{ (1,3),(1,3)\} }}\) kunye nevektha yekholamu eyenziwe lula ehambelanayo\(\widehat {\ mathbf {q}}}_{n} (а)\) Ibonelela ngolwazi olusisiseko kwi-equation (11), i-amplitudes ezimbini ze-backscattering mode yokusebenza \(\ left| {f_{n}^{{ \ ekhohlo ( {res} \ ekunene) \, pp}} \ ekhohlo ( \ theta \ ekunene)} \ ekunene = \ ekhohlo | {f_ {n} ^ {pp} \ ekhohlo ( \ theta \ ekunene) - f_{ n}^{pp(b)} \ekhohlo( \theta \ekunene)} \ekunene|\) kunye \( \ekhohlo|{f_{n}^{{\ ekhohlo( {res} \ekunene)\,ps} } \ekhohlo( \theta \ ekunene)} \ ekunene|= \ ekhohlo| {f_{n}^{ps} \ ekhohlo ( \theta \ ekunene) - f_{n}^{ps(b)} \khohlo( \ theta \ ekunene)} \ ekunene|\) ibhekisa kuvuselelo lwamaza e-P kunye ne-P- kunye nomboniso wamaza e-S, ngokulandelelanayo.Ngaphezu koko, i-amplitude yokuqala yaqikelelwa njenge \ (\ theta = \ pi \), kwaye i-amplitude yesibini yaqikelelwa njenge \ (\ theta = \ pi/4 \).Ngokulayisha iipropati ezahlukeneyo zokuqulunqa.Umzobo 2 ubonisa ukuba iimpawu resonant spheroids ithumba ukuya kuthi ga kwi-15 mm ububanzi zigxininiswe ikakhulu band frequency ka 50-400 kHz, nto leyo ebonisa ukuba kungenzeka ukusebenzisa low-frequency ultrasound ukuphembelela resonant ithumba excitation.iiseli.Ezininzi.Kule bhendi ye-frequency, uhlalutyo lwe-RST lubonise iifomati zemowudi enye kwiindlela ze-1 ukuya kwi-6, zigxininiswe kwi-Figure 3. Apha, zombini i-pp- kunye ne-ps-scattered waves ibonisa iifomati zohlobo lokuqala, ezenzeka kwii-frequencies eziphantsi kakhulu, ezinyuka ukusuka malunga ne-20 kHz kwimowudi ye-1 ukuya malunga ne-60 kHz ye-n = 6, ebonisa ukuba akukho mahluko ubalulekileyo kwi-sphere radius.Umsebenzi we-resonant ps uyabola, ngelixa indibaniselwano yeefomati ze-amplitude ezinkulu ze-pp zibonelela nge-periodicity malunga ne-60 kHz, ebonisa i-frequency shift ephezulu kunye nenani lemowudi eyonyukayo.Lonke uhlalutyo lwenziwa kusetyenziswa isoftware yekhompyutha yeMathematica®62.
Imisebenzi yefom ye-backscatter efunyenwe kwimodyuli ye-tumor yesifuba yobukhulu obuhlukeneyo iboniswe kwi-Fig.
I-resonances yeendlela ezikhethiweyo ukusuka \(n = 1\) ukuya \(n = 6\), zibalwe phezu kokuvuswa kunye nokubonakaliswa kwe-P-wave kwiisayizi ezahlukeneyo zethumba (iigophe ezimnyama ukusuka \(\ left | {f_{ n} ^ {{\ ekhohlo( {res} \ ekunene)\,pp}} \ ekhohlo( \ pi \ ekunene)} \ ekunene | {f_{n}^ {pp} \ ekhohlo ( \ pi \ ekunene) -. f_{n }^{pp(b)} \ ekhohlo( \pi \ ekunene)} \ ekunene|\)) kunye novuselelo lwamaza e-P kunye nomboniso wamaza e-S (iigophe ezingwevu zinikwe ngomsebenzi wemilo yemodal \( \ ekhohlo | { f_{n }^{{\ ekhohlo( {res} \ ekunene)\,ps}} \ ekhohlo ( {\ pi /4} \ ekunene)} \ ekunene = \ ekhohlo | \ ekhohlo ( {\ pi /4} \ ekunene) - f_ {n}^ {ps(b)} \ ekhohlo ( {\ pi /4} \ ekunene)} \ ekunene |\)).
Iziphumo zolu hlalutyo lwangaphambili kusetyenziswa iimeko ezikude zokusasaza zingakhokelela ekukhethweni kwe-drive-specific drive frequencies kule milinganiso yamanani alandelayo ukufunda umphumo woxinzelelo lwe-microvibration kubunzima.Iziphumo zibonisa ukuba ulungelelwaniso lwee-frequencies ezizezona zichanekileyo zinokuthi zichaneke kwinqanaba elithile ngexesha lokukhula kwe-tumor kwaye kunokumiselwa ngokusebenzisa iziphumo zemifuziselo yokukhula ukuseka izicwangciso ze-biomechanical ezisetyenziswa kunyango lwezifo ukuqikelela ngokuchanekileyo ukulungiswa ngokutsha kwezicubu.
Inkqubela phambili ebalulekileyo kwi-nanotechnology iqhuba uluntu lwezenzululwazi ukufumana izisombululo ezitsha kunye neendlela zokuphuhlisa izixhobo zonyango ezincinci kunye ne-invasive encinci kwizicelo ze-vivo.Kulo mxholo, iteknoloji ye-LOF ibonise isakhono esimangalisayo sokwandisa amandla e-fiber optic, eyenza ukuphuhliswa kwezixhobo ezitsha ze-fiber optic ezitsha ze-fiber optic kwizicelo zesayensi yobomi21, 63, 64, 65. Ingcamango yokudibanisa i-2D kunye ne-3D imathiriyeli. ngeekhemikhali ezifunwayo, i-biological, kunye ne-optical properties kumacala e-25 kunye / okanye iphela i-64 ye-fiber optic fibers kunye nolawulo olupheleleyo lwendawo kwi-nanoscale ikhokelela ekuveleni kweklasi entsha ye-fiber optic nanooptodes.inoluhlu olubanzi lwemisebenzi yokuxilonga kunye neyonyango.Okuthakazelisayo kukuba, ngenxa yeempawu zabo zejometri kunye nemishini (icandelo elincinci lomnqamlezo, umlinganiselo omkhulu, ukuguquguquka, ubunzima obuphantsi) kunye ne-biocompatibility yezinto eziphathekayo (ngokuqhelekileyo iglasi okanye iipolymers), iifiber zamehlo zilungele ukufakwa kwiinaliti kunye ne-catheters.Izicelo zonyango20, ukuvula indlela yombono omtsha “wesibhedlele senaliti” (jonga uMfanekiso 4).
Enyanisweni, ngenxa yeedigri zenkululeko ezinikezelwa yiteknoloji ye-LOF, ngokusebenzisa ukudityaniswa kwe-micro- kunye ne-nanostructures eyenziwe kwizinto ezahlukeneyo zetsimbi kunye / okanye ze-dielectric, ii-fibers ezibonakalayo zinokusebenza ngokufanelekileyo kwizicelo ezithile ezihlala zixhasa i-resonant mode excitation., Intsimi yokukhanya i-21 ibekwe ngokuqinileyo.Ukunyanzeliswa kokukhanya kwisikali se-subwavelength, ngokuqhelekileyo kudibaniswa nekhemikhali kunye / okanye i-biological processing63 kunye nokuhlanganiswa kwezinto ezinovakalelo ezifana ne-polymers ezihlakaniphile65,66 zinokuphucula ukulawula ukusebenzisana kokukhanya kunye nomcimbi, onokuba luncedo kwiinjongo ze-theranostic.Ukukhethwa kohlobo kunye nobukhulu bamacandelo / izinto ezidibeneyo ngokucacileyo kuxhomekeke kumzimba, i-biological okanye i-parameters yekhemikhali ukuba ifunyenwe21,63.
Ukudityaniswa kwe-LOF probes kwiinaliti zonyango ezijoliswe kwiindawo ezithile emzimbeni kuya kwenza ukuba ulwelo lwendawo kunye ne-biopsies ye-tissue kwi-vivo, ivumele unyango lwendawo ngaxeshanye, ukunciphisa imiphumo emibi kunye nokwandisa ukusebenza kakuhle.Amathuba anokwenzeka abandakanya ukufunyanwa kwee-biomolecules ezahlukeneyo ezijikelezayo, kubandakanywa nomhlaza.i-biomarkers okanye i-microRNAs (i-miRNAs) 67, ukuchongwa kwezicubu ezinomhlaza usebenzisa i-spectroscopy ecacileyo kunye ne-non-linear efana ne-Raman spectroscopy (SERS) 31, i-high-resolution photoacoustic imaging22,28,68, utyando lwe-laser kunye nokuchithwa kwe-69, kunye neziyobisi zokuhanjiswa kwendawo usebenzisa i-light27 kunye isikhokelo esizenzekelayo seenaliti emzimbeni womntu20.Kuyafaneleka ukuba uqaphele ukuba nangona ukusetyenziswa kwee-optical fibers kuthintela ukungalungi okuqhelekileyo kweendlela "zeklasikhi" ezisekwe kumacandelo e-elektroniki, njengesidingo soqhagamshelwano lombane kunye nobukho bokuphazamiseka kwe-electromagnetic, oku kuvumela ukuba ii-sensors ezahlukeneyo ze-LOF zihlanganiswe ngokufanelekileyo inkqubo.inaliti yonyango enye.Ingqwalasela ekhethekileyo kufuneka ihlawulwe ekunciphiseni iziphumo ezinobungozi ezifana nongcoliseko, ukuphazamiseka kwamehlo, izithintelo zomzimba ezibangela iziphumo ze-crosstalk phakathi kwemisebenzi eyahlukeneyo.Nangona kunjalo, kukwayinyani ukuba uninzi lwemisebenzi ekhankanyiweyo akufuneki ukuba isebenze ngexesha elinye.Lo mba wenza ukuba kwenzeke ukuba ubuncinane kuncitshiswe ukuphazamiseka, ngaloo ndlela kuthintelwe impembelelo embi ekusebenzeni kweprobe nganye kunye nokuchaneka kwenkqubo.Ezi ngqwalasela zisivumela ukuba sijonge ingcamango "yenaliti esibhedlele" njengombono olula wokubeka isiseko esiqinileyo kwisizukulwana esilandelayo seenaliti zonyango kwiisayensi zobomi.
Ngokubhekiselele kwisicelo esithile esixutyushwa kweli phepha, kwicandelo elilandelayo siya kuphanda ngamanani amandla enaliti yonyango ukuqondisa amaza e-ultrasonic kwiiscuphe zomntu usebenzisa ukusasazwa kwawo kwi-axis yayo.
Ukusasazwa kwamaza e-ultrasonic ngenaliti yonyango ezaliswe ngamanzi kwaye ifakwe kwizicubu ezithambileyo (jonga umzobo kwi-Fig. 5a) yahlaziywa kusetyenziswa i-software ye-Comsol Multiphysics yorhwebo esekelwe kwindlela ye-finite element (FEM) 70, apho inaliti kunye nezicubu zenziwa imodeli. njengokusingqongileyo kwelastiki yomgca.
Ngokubhekiselele kuMzobo we-5b, inaliti ibonakaliswe njenge-cylinder engenanto (eyaziwa nangokuthi "i-cannula") eyenziwe ngensimbi engenasici, into eqhelekileyo yeenaliti zonyango71.Ngokukodwa, imodyuli ye-Young's modulus E = 205 GPa, umlinganiselo wePoisson ν = 0.28, kunye nobuninzi ρ = ​​7850 kg m −372.73.I-geometrically, inaliti ibonakaliswe ngobude be-L, i-diameter yangaphakathi ye-D (ebizwa ngokuba "i-clearance") kunye nodonga lwe-t.Ukongezelela, incam yenaliti ithathwa njengethambekele kwi-angle α ngokubhekiselele kwi-longitudinal direction (z).Umthamo wamanzi ngokuyimfuneko uhambelana nokumila kommandla wangaphakathi wenaliti.Kulo hlalutyo lwangaphambili, inaliti yayicingelwa ukuba igxininiswe ngokupheleleyo kummandla wezicubu (kucingelwa ukuba zandiswe ngokungenasiphelo), imodeli njenge-sphere ye-radius rs, ehlala ihleli kwi-85 mm ngexesha lonke ukulinganisa.Ngeenkcukacha ezingakumbi, sigqiba ummandla we-spherical kunye nomgca ohambelana ngokugqibeleleyo (i-PML), ubuncinane ukunciphisa amaza angafunekiyo abonakaliswe kwimida "ecingelwayo".Emva koko sakhetha i-radius rs ukuze sibeke umda we-spherical domain kude ngokwaneleyo ukusuka kwinaliti ukuba ingachaphazeli isisombululo sokubala, kwaye incinci ngokwaneleyo ukuba ingachaphazeli indleko yokubala yokulinganisa.
I-harmonic longitudinal shift of frequency f kunye ne-amplitude A isetyenziswe kumda ophantsi we-stylus geometry;le meko imele i-input stimulus esetyenziswa kwi-geometry efanisiweyo.Kwimida eseleyo yenaliti (ukudibana nezicubu kunye namanzi), imodeli eyamkelweyo ithathwa njengebandakanya ubudlelwane phakathi kweziganeko ezibini zomzimba, enye yazo inxulumene nobuchwephesha besakhiwo (kwindawo yenaliti), kunye enye kubuchwephesha bolwakhiwo.(kummandla we-acicular), ngoko ke iimeko ezihambelanayo zibekwe kwi-acoustics (kumanzi kunye nommandla we-acicular)74.Ngokukodwa, ii-vibrations ezincinci ezifakwe kwisihlalo senaliti zibangela ukuphazamiseka kombane omncinci;Ngaloo ndlela, ukucinga ukuba inaliti iziphatha njenge-elastic medium, i-vector ye-displacement U inokuqikelelwa kwi-elastodynamic equilibrium equation (Navier)75.I-oscillations yesakhiwo senaliti ibangela utshintsho kuxinzelelo lwamanzi ngaphakathi kuyo (ithathwa njengento emileyo kwimodeli yethu), ngenxa yoko amaza omsindo asasazeka kwicala le-longitudinal yenaliti, ngokuyimfuneko ukuthobela i-Helmholtz equation76.Ekugqibeleni, kucingwa ukuba imiphumo engabonakaliyo kwii-tissue ayinanto kwaye i-amplitude yamaza e-shear incinci kakhulu kune-amplitude yamaza oxinzelelo, i-equation ye-Helmholtz ingasetyenziselwa ukulinganisa ukusabalalisa kwamaza e-acoustic kwizicubu ezithambileyo.Emva kolu qikelelo, i-tissue ithathwa njenge-liquid77 kunye nobuninzi be-1000 kg / m3 kunye nesantya sesandi se-1540 m / s (ukungahoywa kweempembelelo ezixhomekeke kwi-frequency-dependent damping).Ukudibanisa le mimandla mibini yomzimba, kuyimfuneko ukuqinisekisa ukuqhubeka kwentshukumo eqhelekileyo kumda wento eqinileyo kunye nolwelo, ukulingana kwe-static phakathi koxinzelelo kunye noxinzelelo oluxhomekeke kumda wesigxina, kunye noxinzelelo lwe-tangential kumda wendalo. ulwelo kufuneka lilingane no-zero.75 .
Kuhlalutyo lwethu, siphanda ukusasazwa kwamaza e-acoustic kunye nenaliti phantsi kweemeko ezimileyo, sigxile kwimpembelelo yejometri yenaliti ekuphumeni kwamaza ngaphakathi kwezicubu.Ngokukodwa, siye saphanda impembelelo ye-diameter yangaphakathi yenaliti D, ubude be-L kunye ne-angle ye-bevel α, ukugcina ubukhulu be-t bugxininiswe kwi-500 µm kuzo zonke iimeko ezifundwayo.Eli xabiso le-t likufutshane nomgangatho oqhelekileyo wodonga lwama-71 kwiinaliti zorhwebo.
Ngaphandle kokulahlekelwa ngokubanzi, i-frequency f ye-harmonic displacement esetyenziswe kwisiseko senaliti yathathwa ilingana ne-100 kHz, kwaye i-amplitude A yayiyi-1 μm.Ngokukodwa, i-frequency isethelwe kwi-100 kHz, ehambelana noqikelelo lohlalutyo olunikwe kwicandelo "Uhlalutyo olusasazwayo lwe-spherical tumor masses ukuqikelela ukukhula okuxhomekeke kwi-ultrasound frequencies", apho ukuziphatha okufana ne-resonance ye-tumor mass yafunyanwa uluhlu lwe-frequency ye-50-400 kHz, kunye ne-amplitude enkulu yokusabalalisa igxininise kwii-frequencies eziphantsi malunga ne-100-200 kHz (jonga umfanekiso 2).
Iparameter yokuqala efundwayo yayiyi-diameter yangaphakathi ye-D yenaliti.Ukuze kube lula, kuchazwa njengeqhezu elipheleleyo lobude be-acoustic wave kumgodi wenaliti (oko kukuthi, emanzini λW = 1.5 mm).Enyanisweni, i-phenomena ye-propagation ye-wave wave kwizixhobo ezibonakaliswe yijometri enikeziweyo (umzekelo, kwi-waveguide) ihlala ixhomekeke kubukhulu beempawu zejometri esetyenziswe xa kuthelekiswa nobude be-wave wave wave wave.Ukongezelela, kuhlalutyo lokuqala, ukwenzela ukuba kugxininiswe kakuhle umphumo we-diameter D ekusasazeni kwe-acoustic wave ngokusebenzisa inaliti, siqwalasela isicatshulwa esicaba, ukubeka i-angle α = 90 °.Ngethuba lolu hlalutyo, ubude benaliti L buqiniswe kwi-70 mm.
Kwikhiwane.I-6a ibonisa i-avareji yobukhulu besandi njengomsebenzi we-dimensionless scale parameter SD, okt D = λW / SD evandlakanywe kwi-sphere ene-radius ye-10 mm esekelwe kwincam yenaliti ehambelanayo.Iparamitha yokulinganisa i-SD iyatshintsha ukusuka kwi-2 ukuya kwi-6, oko kukuthi, siqwalasela amaxabiso e-D ukusuka kwi-7.5 mm ukuya kwi-2.5 mm (ku-f = 100 kHz).Uluhlu lukwabandakanya ixabiso eliqhelekileyo le-71 yeenaliti zonyango ezingenasici.Njengoko kulindelekile, ububanzi bangaphakathi benaliti buchaphazela ubunzima besandi esikhutshwa yinaliti, kunye nexabiso eliphezulu (1030 W / m2) elihambelana ne-D = λW / 3 (okt D = 5 mm) kunye nokunciphisa umgangatho kunye nokunciphisa. ububanzi.Kufuneka kuthathelwe ingqalelo ukuba i-diameter D yiparameter yejometri ekwachaphazela ukuhlaselwa kwesixhobo sonyango, ngoko ke le nkalo ebalulekileyo ayinakuhoywa xa ukhetha ixabiso elifanelekileyo.Ngoko ke, nangona ukuhla kwe-D kwenzeka ngenxa yokuhanjiswa okuphantsi kwe-acoustic intensity kwizicubu, kwizifundo ezilandelayo, ububanzi D = λW / 5, okt D = 3 mm (ihambelana nomgangatho we-11G71 kwi-f = 100 kHz) , ithathwa njengento efanelekileyo phakathi kokungena kwesixhobo kunye nokuhanjiswa kwesandi esinamandla (umyinge malunga ne-450 W / m2).
Umyinge wokuqina kwesandi esikhutshwa yincam yenaliti (ithathwa njengecaba), kuxhomekeke kububanzi bangaphakathi benaliti (a), ubude (b) kunye ne-bevel angle α (c).Ubude kwi (a, c) yi-90 mm, kwaye ububanzi kwi (b, c) yi-3 mm.
Iparamitha elandelayo ekufuneka ihlalutywe bubude benaliti L. Njengophononongo lwangaphambili, siqwalasela i-oblique angle α = 90 ° kwaye ubude bulinganiswe njenge-multiple of wavelength emanzini, okt cinga L = SL λW .Iparamitha ye-SL engenamda iguquliwe ukusuka kwi-3 nge-7, ngaloo ndlela iqikelela ukuqina okuphakathi kwesandi esikhutshwa yincam yenaliti kuluhlu lobude ukusuka kwi-4.5 ukuya kwi-10.5 mm.Olu luhlu lubandakanya amaxabiso aqhelekileyo kwiinaliti zorhwebo.Iziphumo ziboniswe kwifig.I-6b, ebonisa ukuba ubude benaliti, i-L, inempembelelo enkulu ekuhanjisweni kokuqina kwesandi kwiithishu.Ngokukodwa, ukulungiswa kwale parameter kwenza kube lula ukuphucula ukuhanjiswa malunga nomyalelo wobukhulu.Enyanisweni, kuluhlu lobude obuhlalutyiweyo, ubukhulu besandi besandi buthatha ubuninzi bendawo ye-3116 W / m2 kwi-SL = 4 (okt, L = 60 mm), kwaye enye ihambelana ne-SL = 6 (oko kukuthi, L = 90 mm).
Emva kokuhlalutya impembelelo yobubanzi kunye nobude benaliti ekusasazeni i-ultrasound kwi-geometry ye-cylindrical, sigxininise kwimpembelelo ye-angle ye-bevel ekuhanjisweni kokuqina kwesandi kwizicubu.Ubungakanani obuqhelekileyo besandi esiphuma kwi-fiber tip yavavanywa njengomsebenzi we-angle α, ukuguqula ixabiso layo ukusuka kwi-10 ° (i-tip ebukhali) ukuya kwi-90 ° (i-flat tip).Kule meko, i-radius ye-sphere yokudibanisa ejikeleze i-tip ecingelwayo yenaliti yayiyi-20 mm, ukwenzela ukuba kuwo onke amaxabiso e-α, incam yenaliti ifakwe kumthamo obalwa ukusuka kumyinge.
Njengoko kubonisiwe kwifig.I-6c, xa i-tip ibukhali, oko kukuthi, xa i-α iyancipha ukusuka kwi-90 °, ukuqina kwesandi esidlulisiweyo kwandisa, ukufikelela kwixabiso eliphezulu malunga ne-1.5 × 105 W / m2, ehambelana ne-α = 50 °, ie, 2 lulandelelwano lobungakanani obuphezulu xa kuthelekiswa nemo ecaba.Ngokulolwa ngakumbi kwencam (oko kukuthi, ku-α ngaphantsi kwe-50 °), ukuqina kwesandi kuthanda ukuhla, ukufikelela kumaxabiso athelekiseka nencam ethe tyaba.Nangona kunjalo, nangona sithathele ingqalelo uluhlu olubanzi lwee-engile ze-bevel kwimilinganiso yethu, kuyafaneleka ukuba sithathele ingqalelo ukuba ukulolwa kwencam kuyimfuneko ukuze kube lula ukufakwa kwenaliti kwithishu.Enyanisweni, i-angle ye-bevel encinci (malunga ne-10 °) inokunciphisa amandla angama-78 afunekayo ukungena kwizicubu.
Ukongeza kwixabiso lesandi somsindo ohanjiswe ngaphakathi kwezicubu, i-angle ye-bevel iphinda ichaphazele isalathiso sokusasaza kwamaza, njengoko kuboniswe kwigrafu yezinga loxinzelelo lwesandi esiboniswe kwi-Fig. 7a (kwi-flat tip) kunye ne-3b (ye-10 ° ).i-beveled incam), i-parallel Ulwalathiso lwe-longitudinal luvandlakanywa kwi-plane ye-symmetry (yz, cf. Umzobo 5).Kwiimeko ezigqithisileyo zezi ngqwalasela zimbini, inqanaba loxinzelelo lwesandi (ekubhekiswa kulo njenge-1 µPa) ligxininiswe ikakhulu kumngxuma yenaliti (okt emanzini) kwaye lisasazeke kwithishu.Kwiinkcukacha ezithe kratya, kwimeko yencam ecaba (umzobo 7a), ukuhanjiswa kwenqanaba loxinzelelo lwesandi kuhambelana ngokugqibeleleyo ngokubhekiselele kulwalathiso lwelongitudinal, kunye namaza amileyo anokuhlukaniswa emanzini azalise umzimba.I-wave i-oriented longitudinally (z-axis), i-amplitude ifikelela kwixabiso layo eliphezulu emanzini (malunga ne-240 dB) kwaye iyancipha ngokuphambeneyo, okukhokelela ekunciphiseni malunga ne-20 dB kumgama we-10 mm ukusuka kumbindi wenaliti.Njengoko kulindelwe, ukuqaliswa kwesicatshulwa esicacileyo (Umfanekiso we-7b) uphula le symmetry, kwaye i-antinodes yamaza amileyo "iphambuka" ngokwencam yenaliti.Kuyabonakala ukuba, le asymmetry ichaphazela ubushushu bemitha kwincam yenaliti, njengoko kuchaziwe ngaphambili (Umfanekiso 6c).Ukuze uqonde ngcono le nkalo, ukuqina kwe-acoustic kwavavanywa kunye nomgca osikiweyo we-orthogonal ukuya kwicala le-longitudinal yenaliti, eyayibekwe kwiplani ye-symmetry yenaliti kwaye ibekwe kumgama we-10 mm ukusuka kwincam yenaliti ( iziphumo kuMfanekiso 7c).Ngokuthe ngqo, ukuhanjiswa koxinzelelo lwesandi kuhlolwe kwi-10 °, 20 ° kunye ne-30 ° i-oblique angles (imigca eluhlaza okwesibhakabhaka, ebomvu kunye nohlaza oluqinileyo, ngokulandelanayo) yafaniswa nokusasazwa kufuphi nesiphelo seflethi (iigophe ezinamachaphaza amnyama).Ukwabiwa kokuqina okuhambelana neenaliti ezinencapha-mcaba kubonakala ngathi zilinganisa malunga nombindi wenaliti.Ngokukodwa, kuthatha ixabiso elimalunga ne-1420 W / m2 kwiziko, ukuphuphuma kwe-300 W / m2 kumgama we-~ 8 mm, kwaye emva koko kuncipha kwixabiso malunga ne-170 W / m2 kwi- ~ 30 mm. .Njengoko incam isiya yalathwa, i-lobe esembindini iyahlukana ibe yi-lobes yobukhulu obahlukeneyo.Ngokukodwa ngakumbi, xa i-α yayingama-30 °, iipetali ezintathu zinokuhlukaniswa ngokucacileyo kwiprofayili elinganiswe kwi-1 mm ukusuka kwincam yenaliti.Embindini iphantse ibe sembindini yenaliti kwaye inexabiso eliqikelelweyo le-1850 W / m2, kwaye iphezulu ngasekunene imalunga ne-19 mm ukusuka kwiziko kwaye ifikelela kwi-2625 W / m2.Kwi-α = 20 °, kukho ii-lobes ezi-2 eziphambili: enye nge--12 mm kwi-1785 W / m2 kunye ne-14 mm kwi-1524 W / m2.Xa i-tip iba bukhali kwaye i-angle ifikelela kwi-10 °, ubuninzi be-817 W / m2 bufikeleleka malunga ne--20 mm, kunye ne-lobes ezintathu ezinobunzima obuncinci bubonakala kunye neprofayili.
Inqanaba loxinzelelo lwesandi kwiplani ye-symmetry y–z yenaliti enesiphelo esicaba (a) kunye ne-10 ° bevel (b).(c) Ubukhulu be-acoustic usasazo oluqikelelwa ecaleni komgca osikiweyo ngokuthe ngqo ukuya kwicala le-longitudinal yenaliti, kumgama we-10 mm ukusuka kwincam yenaliti kwaye ilele kwindiza ye-symmetry yz.Ubude be-L bungama-70 mm kunye nobubanzi be-D yi-3 mm.
Zithathiwe kunye, ezi ziphumo zibonisa ukuba iinaliti zonyango zinokusetyenziswa ngokufanelekileyo ukuhambisa i-ultrasound kwi-100 kHz kwizicubu ezithambileyo.Ubukhulu besandi esikhutshwayo buxhomekeke kwijometri yenaliti kwaye inokuphuculwa (ngokuxhomekeke kwimida ebekwe yi-invasiveness yesixhobo sokugqibela) ukuya kumaxabiso kuluhlu lwe-1000 W / m2 (kwi-10 mm).isetyenziswe phantsi kwenaliti 1. Kwimeko ye-micrometer offset, inaliti ithathwa ukuba ifakwe ngokupheleleyo kwizicubu ezithambileyo ezingapheliyo.Ngokukodwa, i-angle ye-bevel ichaphazela kakhulu ukuqina kunye nolwalathiso lokusasazwa kwamaza omsindo kwi-tissue, eyona nto ikhokelela kwi-orthogonality yokusikwa kwencam yenaliti.
Ukuxhasa uphuhliso lweendlela ezintsha zonyango lwe-tumor olusekwe ekusebenziseni iindlela zonyango ezingathinteliyo, ukusasazwa kwe-ultrasound ye-low-frequency kwindawo ye-tumor kwahlalutywa ngokuhlalutya kunye nokubala.Ngokukodwa, kwinxalenye yokuqala yesifundo, isisombululo se-elastodynamic sexeshana savumela ukuba sifunde ukusasazeka kwamaza e-ultrasonic kwi-spheroids ye-tumor eqinile eyaziwayo kunye nokuqina ukuze sifunde ukuva ubunzima.Emva koko, iifrikhwensi zomyalelo wamakhulu ekhilohertz zakhethwa, kunye nokusetyenziswa kwendawo yoxinzelelo lokungcangcazela kwindawo yethumba kusetyenziswa inaliti yenaliti yonyango yenziwa imodeli ngokulinganisa amanani ngokufunda impembelelo yeeparamitha zoyilo eziphambili ezimisela ukuhanjiswa kwe-acoustic. amandla esixhobo kokusingqongileyo.Iziphumo zibonisa ukuba iinaliti zonyango zingasetyenziselwa ngokufanelekileyo ukukhupha izicubu nge-ultrasound, kwaye ukuqina kwayo kuhambelana ngokusondeleyo ne-geometrical parameter yenaliti, ebizwa ngokuba yi-acoustic wavelength esebenzayo.Enyanisweni, ubukhulu be-irradiation ngokusebenzisa i-tissue buyanda ngokunyuka kwe-diameter yangaphakathi yenaliti, ukufikelela kubuninzi xa ububanzi buphindwe kathathu ubude be-wavelength.Ubude benaliti bukwabonelela ngenqanaba elithile lenkululeko yokwandisa utyhileko.Isiphumo sokugqibela ngokwenene senziwa sikhulu xa ubude benaliti bubekwe kwi-multiple of wavelength yokusebenza (ngokukodwa i-4 kunye ne-6).Okubangel 'umdla kukuba, kuluhlu lwefrikhwensi yomdla, idiameter ephuculweyo kunye namaxabiso obude asondele kwezo ziqhele ukusetyenziswa kwiinaliti eziqhelekileyo zorhwebo.I-angle ye-bevel, echaza ubukhali benaliti, iphinda ithintele ukukhutshwa, ukunyuka malunga ne-50 ° kunye nokubonelela ngokusebenza kakuhle malunga ne-10 °, esetyenziswa ngokuqhelekileyo kwiinaliti zorhwebo..Iziphumo zokulinganisa ziya kusetyenziswa ukukhokela ukuphunyezwa kunye nokulungiswa kwe-platform ye-intraneedle yokuxilonga yesibhedlele, ukudibanisa i-diagnostic kunye ne-ultrasound yonyango kunye nezinye izisombululo zonyango ezingaphakathi kwesixhobo kunye nokuqonda ukungenelela kweyeza lokuchaneka ngokubambisana.
Koenig IR, Fuchs O, Hansen G, von Mutius E. kunye no-Kopp MV Yintoni amayeza achanekileyo?I-Eur, yangaphandle.Ijenali 50, 1700391 (2017).
Collins, FS kunye neVarmus, H. Amanyathelo amatsha kunyango oluchanekileyo.N. enge.J. Amayeza.372, 793-795 (2015).
Hsu, W., Markey, MK kunye noWang, MD.I-Biomedical Imaging Informatics kwi-Precision Medicine Era: Impumelelo, imingeni, kunye namathuba.IJam.iyeza.yazisa.Unjingalwazi oncedisayo.20(6), 1010–1013 (2013).
Garraway, LA, Verweij, J. & Ballman, KV Precision oncology: ukuhlaziywa.J. Kwezonyango.Oncol.31, 1803-1805 (2013).
Wiwatchaitawee, K., Quarterman, J., Geary, S., kunye neSalem, A. Ukuphuculwa kwe-glioblastoma (GBM) yonyango usebenzisa inkqubo yokuhanjiswa kwe-nanoparticle.I-AAPS PharmSciTech 22, 71 (2021).
Aldape K, Zadeh G, Mansouri S, Reifenberger G kunye no-von Daimling A. Glioblastoma: i-pathology, iindlela ze-molecular kunye namanqaku.I-Acta Neuropathology.129 (6), 829-848 (2015).
Bush, i-NAO, i-Chang, i-SM kunye ne-Berger, i-MS yangoku kunye neendlela ezizayo zonyango lwe-glioma.neurosurgery.U-Ed.40, 1-14 (2017).