iindaba

Isifo sika-Alzheimer, eyona meko ixhaphakileyo kubantu abadala, iye yathwaxa abantu abaninzi.

Omnye wemiceli mngeni kunyango lwe-Alzheimer's disease kukuba ukuhanjiswa kweziyobisi zonyango kwizicubu zobuchopho kuthintelwe ngumqobo wegazi-ubuchopho. Uphononongo lwafumanisa ukuba i-MRI ekhokelwa yi-MRI ephantsi kogxininiso obugxile kwi-ultrasound inokuphinda ivule umqobo wegazi-lobuchopho kwizigulana ezinesifo se-Alzheimer okanye ezinye iziphazamiso zemithambo-luvo, kubandakanya nesifo sikaParkinson, amathumba ebuchotsheni, kunye ne-amyotrophic lateral sclerosis.

Uvavanyo lwamva nje oluncinci lobungqina be-Rockefeller Institute for Neuroscience kwiYunivesithi yaseWest Virginia lubonise ukuba izigulane ezine-Alzheimer's disease ezifumene i-aducanumab infusion ngokudibanisa ne-ultrasound egxininisiweyo yavula okwethutyana umqobo wegazi-ubuchopho kunciphisa kakhulu umthwalo we-brain amyloid beta (Aβ) kwicala lovavanyo. Uphando lunokuvula iingcango ezintsha kunyango lokuphazamiseka kwengqondo.

Umqobo wegazi-ubuchopho ukhusela ingqondo kwizinto ezinobungozi ngelixa uvumela izondlo ezibalulekileyo ukuba zidlule. Kodwa isithintelo segazi-engqondo sikwathintela ukuhanjiswa kwamachiza onyango kwingqondo, umngeni onzima ngakumbi xa kunyangwa isifo sika-Alzheimer. Njengoko iminyaka yehlabathi, inani labantu abanesifo se-Alzheimer liyanda unyaka nonyaka, kwaye ukhetho lwayo lonyango lunqongophele, lubeka umthwalo onzima kukhathalelo lwezempilo. I-Aducanumab yi-amyloid beta (Aβ) -ibophelelayo i-antibody ye-monoclonal evunyiweyo yi-US Food and Drug Administration (FDA) yonyango lwe-Alzheimer's disease, kodwa ukungena kwayo kwisithintelo segazi-ingqondo silinganiselwe.

I-ultrasound egxininisiweyo ivelisa amaza omatshini abangela i-oscillations phakathi koxinzelelo kunye nokunciphisa. Xa ijojowe egazini kwaye ibonakaliswe kwintsimi ye-ultrasonic, i-bubbles compress kwaye yandisa ngaphezu kwezicubu ezijikelezayo kunye negazi. Ezi oscillations zidala uxinzelelo lomatshini kudonga lwemithambo yegazi, okubangela unxibelelwano oluqinileyo phakathi kweeseli ze-endothelial zolule kwaye zivuleke (Umfanekiso ongezantsi). Ngenxa yoko, ingqibelelo yesithintelo segazi-ingqondo iyancipha, ivumela iimolekyuli ukuba zisasazeke kwingqondo. Umqobo wegazi ebuchotsheni uziphilela ngokwawo malunga neeyure ezintandathu.

Umzobo ubonisa umphumo we-ultrasound ye-directional kwiindonga ze-capillary xa iibhubhu ezinobungakanani be-micrometer zikhona kwimithambo yegazi. Ngenxa yoxinzelelo oluphezulu lwegesi, i-bubbles inkontileka kwaye yandisa ngaphezu kwezicubu ezijikelezayo, ezibangela uxinzelelo lomatshini kwiiseli ze-endothelial. Le nkqubo ibangela ukuba uqhagamshelo oluluqilima luvuleke kwaye lunokubangela ukuba iziphelo ze-astrocyte ziwe eludongeni lomthambo wegazi, zibeke esichengeni isidima somqobo wegazi kunye nokukhuthaza ukusasazwa kwe-antibody. Ukongeza, iiseli ze-endothelial ezivezwe kwi-ultrasound ekugxilwe kuyo ziphucule umsebenzi wazo wothutho osebenzayo we-vacuolar kunye nokucinezela umsebenzi wempompo ye-efflux, ngaloo ndlela yehlisa ukucaciswa kwengqondo kwee-antibodies. Umzobo B ubonisa ishedyuli yonyango, ebandakanya i-computed tomography (CT) kunye ne-imaging magnetic resonance (MRI) ukuphuhlisa isicwangciso sonyango lwe-ultrasound, i-18F-flubitaban positron emission tomography (PET) kwisiseko, ukunyuswa kwe-antibody ngaphambi kokugxilwa kunyango lwe-ultrasound kunye ne-microvesicular infusion ngexesha lonyango, kunye nokubeka iliso kwi-acoustic ye-ultrasound yokulawula ukusasazeka kwe-microvesicular. Imifanekiso efunyenwe emva kokunyangwa kwe-ultrasound egxininisiweyo ibandakanya i-MRI enesisindo esine-T1, ebonisa ukuba umqobo wegazi-ubuchopho wawuvulekile kwindawo yonyango ye-ultrasound. Imifanekiso yendawo enye emva kwe-24 kwiiyure ze-48 zokugxila kunyango lwe-ultrasound yabonisa ukuphiliswa okupheleleyo komqobo wegazi-ubuchopho. I-18F-flubitaban PET scan ngexesha lokulandelwa kwesinye sezigulane iiveki ze-26 kamva yabonisa ukunciphisa amanqanaba e-Aβ kwingqondo emva kokunyanga. Umzobo C ubonisa ukusekwa kwe-ultrasound ekhokelwa yi-MRI ngexesha lonyango. Isigcina-ntloko se-hemispherical transducer siqukethe ngaphezulu kwe-1,000 yemithombo ye-ultrasound eguqukela kwindawo enye ekugxilwe kuyo ebuchotsheni isebenzisa isikhokelo sexesha langempela esivela kwi-MRI.

Ngo-2001, i-ultrasound egxininisiweyo yaqala yaboniswa ukuba ikhuthaze ukuvulwa kwesithintelo segazi-ingqondo kwizifundo zezilwanyana, kwaye izifundo ezalandelayo ze-preclinical zibonise ukuba i-ultrasound egxininisiweyo inokuphucula ukuhanjiswa kwechiza kunye nokusebenza kakuhle. Ukusukela ngoko, kufunyaniswe ukuba i-ultrasound egxilileyo inokusivula ngokukhuselekileyo isithintelo segazi-kwingqondo kwizigulana ezine-Alzheimer's ezingafumani mayeza, kwaye inokuhambisa amajoni omzimba kumhlaza wesifuba metastases.

Inkqubo yokuhanjiswa kweMicrobubble

I-Microbubbles yi-ejenti yokuchasa i-ultrasound edla ngokusetyenziswa ukujonga ukuhamba kwegazi kunye nemithambo yegazi kuxilongo lwe-ultrasound. Ngethuba lonyango lwe-ultrasound, i-phospholipid-coated non-pyrogenic bubble ukumiswa kwe-octafluoropropane yajojowe nge-intravenously (Figure 1B). I-Microbubbles i-polydispersed kakhulu, kunye nobubanzi obusuka ngaphantsi kwe-1 μm ukuya ngaphezu kwe-10 μm. I-Octafluoropropane yigesi ezinzileyo engenziwanga i-metabolized kwaye inokukhutshwa ngemiphunga. Igobolondo le-lipid elisonga kwaye lizinzise amaqamza liqulunqwe ziilipids zomntu ezintathu zendalo ezixutywe ngendlela efanayo ne-endogenous phospholipids.

Isizukulwana se-ultrasound egxininisiweyo

I-ultrasound egxininisiweyo yenziwa yi-helmet ye-hemispherical transducer ejikeleze intloko yesigulane (Umfanekiso 1C). Isigqoko sixhotyiswe nge-1024 ngokuzimeleyo elawulwa yimithombo ye-ultrasound, egxile ngokwemvelo kumbindi we-hemisphere. Le mithombo ye-ultrasound iqhutywa yi-sinusoidal radio-frequency voltages kwaye ikhupha amaza e-ultrasonic akhokelwa yi-imaging resonance magnetic. Isigulana sinxibe isigqoko kunye namanzi ahlanjululweyo ajikeleza entloko ukuququzelela ukuhanjiswa kwe-ultrasound. I-ultrasound ihamba ngesikhumba kunye nokakayi ukuya kwithagethi yengqondo.

Utshintsho kwi-skull thickness and density iya kuchaphazela i-ultrasound propagation, okukhokelela kwixesha elahluke kancinane lokuba i-ultrasound ifikelele kwisilonda. Oku kuphazamisa kunokulungiswa ngokufumana idatha ye-tomography ye-high-resolution ye-high-resolution ukufumana ulwazi malunga nokumila kokakayi, ubukhulu kunye nobuninzi. Imodeli yokulinganisa ikhomputha ingabala ukutshintshwa kwesigaba esihlawulelwayo somqondiso ngamnye wokuqhuba ukubuyisela ugxininiso olubukhali. Ngokulawula isigaba somqondiso we-RF, i-ultrasound inokujoliswa kwi-elektroniki kwaye ibekwe kwindawo yokugubungela izixa ezikhulu zeethishu ngaphandle kokuhambisa uluhlu lwemithombo ye-ultrasound. Indawo yethishu ekujoliswe kuyo igqitywe yi-imaging magnetic resonance yentloko ngelixa unxibe isigcina-ntloko. Umthamo ojoliswe kuyo uzaliswe ngegridi ye-three-dimensional ye-ultrasonic anchor points, ekhupha amaza e-ultrasonic kwindawo nganye ye-anchor ye-5-10 ms, iphinda iphindwe yonke imizuzwana emi-3. Amandla e-ultrasonic anyuswa ngokuthe ngcembe de kubonwe isignali ye-bubble efunwayo, kwaye emva koko ibanjwe imizuzwana eyi-120. Le nkqubo iphinda iphindwe kwamanye ama-meshes de kube umthamo ojoliswe kuyo ugutyungelwe ngokupheleleyo.

Ukuvula isithintelo segazi-ingqondo kufuna ukuba i-amplitude yamaza omsindo idlule umqobo othile, ngaphaya koko ukunyanzeliswa kwesithintelo kunyuka ngokunyuka koxinzelelo lwe-amplitude de kubekho umonakalo wezicubu, obonakaliswe njenge-erythrocyte exosmosis, ukopha, i-apoptosis, kunye ne-necrosis, yonke into ehlala idibene ne-bubble collapse (ebizwa ngokuba yi-inertial cavitation). Umda uxhomekeke kubukhulu be-microbubble kunye nemathiriyeli yeqokobhe. Ngokufumanisa kunye nokutolika izibonakaliso ze-ultrasonic ezihlakazwa yi-microbubbles, ukubonakaliswa kunokugcinwa ngaphakathi koluhlu olukhuselekileyo.

Emva kokunyangwa kwe-ultrasound, i-MRI enesisindo se-T1 kunye ne-agent echaseneyo yayisetyenziselwa ukufumanisa ukuba isithintelo segazi-ingqondo sivulekile kwindawo ekujoliswe kuyo, kwaye imifanekiso ye-T2-weighted isetyenziswe ukuqinisekisa ukuba i-extravasation okanye ukuphuma kwegazi kwenzeka. Olu qwalaselo lunika isikhokelo sokulungelelanisa olunye unyango, ukuba kuyimfuneko.

Uvavanyo kunye nethemba lesiphumo sonyango

Abaphandi balinganisa umphumo wonyango kwi-brain Aβ umthwalo ngokuthelekisa i-18F-flubitaban positron emission tomography ngaphambi nangemva konyango ukuvavanya umahluko kwivolumu ye-Aβ phakathi kwendawo ephathwayo kunye nommandla ofanayo kwelinye icala. Uphando lwangaphambili lweqela elifanayo lubonise ukuba ukugxila nje kwi-ultrasound kunokunciphisa amanqanaba e-Aβ. Ukuncipha okubonwe kolu lingo kwakukhulu ngakumbi kunezifundo zangaphambili.

Kwixesha elizayo, ukwandisa unyango kumacala omabini obuchopho kuya kuba yinto ebalulekileyo ekuvavanyeni ukusebenza kwayo ekubambezeleni ukuqhubela phambili kwesifo. Ukongezelela, uphando olongezelelweyo lufunekayo ukuze kuqinisekiswe ukhuseleko lwexesha elide kunye nokusebenza kakuhle, kunye nezixhobo zonyango ezingabizi kakhulu ezingathembeli kwi-intanethi ye-MRI isikhokelo kufuneka ziphuhliswe ukufumaneka ngokubanzi. Nangona kunjalo, iziphumo zibangele ithemba lokuba unyango kunye namachiza asusa i-Aβ angacothisa ukuqhubeka kwe-Alzheimer.