izindaba

Isifo i-Alzheimer’s, okuyisifo esivame kakhulu kubantu asebekhulile, siye sahlupha abantu abaningi.

Enye yezinselelo ekwelapheni isifo i-Alzheimer's ukuthi ukulethwa kwemithi yokwelapha ezicutshini zobuchopho kunqunyelwe umgoqo wegazi nobuchopho. Ucwaningo luthole ukuthi i-MRI eqondiswa yi-low-intensity focused ultrasound ingavula ngokuhlehla umgoqo wegazi nobuchopho ezigulini ezinesifo i-Alzheimer's noma ezinye iziyaluyalu zezinzwa, okuhlanganisa nesifo sika-Parkinson, izimila zobuchopho, kanye ne-amyotrophic lateral sclerosis.

Uhlolo oluncane lwakamuva lobufakazi be-concept e-Rockefeller Institute for Neuroscience e-West Virginia University lubonise ukuthi iziguli ezinesifo i-Alzheimer's ezathola ukumnika kwe-aducanumab zihlangene ne-ultrasound egxilile zavula okwesikhashana umgoqo wegazi-ubuchopho wehlisa kakhulu umthwalo we-brain amyloid beta (Aβ) ohlangothini lwesilingo. Ucwaningo lungavula iminyango emisha ekwelapheni ukuphazamiseka kwengqondo.

Umgoqo wegazi nobuchopho uvikela ubuchopho ezintweni eziyingozi kuyilapho uvumela imisoco ebalulekile ukuba idlule. Kodwa umgoqo wegazi nobuchopho futhi uvimbela ukulethwa kwemithi yokwelapha ebuchosheni, inselele enzima kakhulu lapho ukwelapha isifo i-Alzheimer's. Njengoba iminyaka yomhlaba, inani labantu abanesifo i-Alzheimer liyanda unyaka nonyaka, futhi izindlela zokwelapha ezikhethwa kuzo zilinganiselwe, okubeka umthwalo osindayo ekunakekelweni kwezempilo. I-Aducanumab iyi-amyloid beta (Aβ) -ebopha i-monoclonal antibody egunyazwe i-US Food and Drug Administration (FDA) yokwelapha isifo i-Alzheimer's, kodwa ukungena kwayo kwesithiyo sobuchopho begazi kunomkhawulo.

I-Ultrasound egxilile ikhiqiza amaza emishini adala ukuzungeza phakathi kokucindezelwa nokuhlanjululwa. Lapho ejova egazini futhi evezwe ensimini ye-ultrasonic, amagwebu acindezela futhi ande ngaphezu kwezicubu ezizungezile negazi. Lawa ma-oscillations adala ukucindezelwa kwemishini odongeni lomkhumbi wegazi, okubangela ukuxhumana okuqinile phakathi kwamaseli e-endothelial ukuthi anwebe futhi avuleke (Umfanekiso ongezansi). Ngenxa yalokho, ubuqotho bomgoqo wegazi nobuchopho buyancipha, okuvumela ama-molecule ukuba asakazeke ebuchosheni. Umgoqo wegazi ebuchosheni ululama wodwa emahoreni ayisithupha.

Isibalo sibonisa umphumela we-ultrasound eqondisayo ezindongeni ze-capillary lapho amabhamuza anosayizi we-micrometer ekhona emithanjeni yegazi. Ngenxa yokucindezelwa okuphezulu kwegesi, amabhamuza ayafinyela futhi anda ngaphezu kwezicubu ezizungezile, okubangela ukucindezeleka komshini kumaseli e-endothelial. Le nqubo ibangela ukuxhuma okuqinile ukuthi kuvuleke futhi ingase futhi ibangele ukuthi iziphetho ze-astrocyte ziwe obondeni lomkhumbi wegazi, okonakalise ubuqotho bomngcele wegazi nobuchopho futhi kukhuthaze ukusakazeka kwamasosha omzimba. Ngaphezu kwalokho, amangqamuzana e-endothelial avezwe ku-ultrasound egxilile athuthukisa umsebenzi wawo wokuthutha we-vacuolar osebenzayo futhi acindezela umsebenzi wepompo ye-efflux, ngaleyo ndlela ehlisa ukucaciswa kobuchopho kwamasosha omzimba. Umfanekiso B ubonisa ishejuli yokwelashwa, ehlanganisa i-computed tomography (CT) kanye ne-magnetic resonance imaging (MRI) ukuthuthukisa uhlelo lokwelashwa kwe-ultrasound, i-18F-flubitaban positron emission tomography (PET) ekuqaleni, ukufakwa kwe-antibody ngaphambi kokwelashwa okugxilwe kwe-ultrasound kanye nokufakwa kwe-microvesicular ngesikhathi sokwelashwa, kanye nokuqapha kwe-acoustic kwe-microvesicular signal scatter esetshenziselwa ukulawula ukusakazeka kwe-microvesicular yokwelashwa. Izithombe ezitholwe ngemva kokwelashwa okugxilisiwe kwe-ultrasound zihlanganisa i-MRI ethuthukisiwe enesisindo esinesisindo se-T1, ebonise ukuthi umgoqo wegazi nobuchopho wawuvulekile endaweni yokwelashwa nge-ultrasound. Izithombe zendawo efanayo ngemva kwamahora angu-24 kuya kwangu-48 okwelashwa okugxilisiwe kwe-ultrasound zibonise ukuphulukiswa okuphelele kwesithiyo segazi nobuchopho. Ukuskena kwe-PET kwe-18F-flubitaban ngesikhathi sokulandelela kwesinye seziguli emasontweni angu-26 kamuva kwabonisa amazinga e-Aβ ancishisiwe ebuchosheni ngemva kokwelashwa. Umfanekiso C ubonisa ukusethwa kwe-ultrasound eqondiswa yi-MRI ngesikhathi sokwelashwa. Isigqoko sokuzivikela se-hemispherical transducer siqukethe imithombo ye-ultrasound engaphezu kwe-1,000 ehlangana endaweni eyodwa ebuchosheni isebenzisa ukuqondiswa kwesikhathi sangempela kusuka ku-MRI.

Ngo-2001, i-ultrasound egxilile yaboniswa okokuqala ukuze ivule umgoqo wegazi nobuchopho ezifundweni zezilwane, futhi ucwaningo olwalandela lwabonisa ukuthi i-ultrasound egxilile ingathuthukisa ukulethwa kwezidakamizwa nokusebenza ngempumelelo. Kusukela lapho, kutholakale ukuthi i-ultrasound egxilile ingavula ngokuphephile umgoqo wegazi nobuchopho ezigulini ezine-Alzheimer's ezingatholi imithi, futhi ingaletha amasosha omzimba kumametastase obuchopho bomdlavuza webele.

Inqubo yokulethwa kwe-Microbubble

Ama-Microbubbles ayi-ejenti yokuqhathanisa ye-ultrasound evame ukusetshenziselwa ukubuka ukugeleza kwegazi nemithambo yegazi ekuxilongweni kwe-ultrasound. Ngesikhathi sokwelashwa kwe-ultrasound, i-phospholipid-coated non-pyrogenic bubble ukumiswa kwe-octafluoropropane yajova nge-intravenously (Figure 1B). Amabhamuza amancane ahlakazeke kakhulu, anobubanzi obusuka ngaphansi kuka-1 μm ukuya ngaphezu kuka-10 μm. I-Octafluoropropane igesi ezinzile engagayelwanga futhi ingakhishwa ngamaphaphu. Igobolondo le-lipid eligoqa futhi lizinzise amabhamuza lakhiwe ama-lipids emvelo abantu amathathu agaywa ngendlela efanayo nama-phospholipids angapheli.

Isizukulwane se-ultrasound egxilile

I-ultrasound egxilile yenziwa isigqoko se-hemispherical transducer esizungeza ikhanda lesiguli (Umfanekiso 1C). Isigqoko sokuzivikela sifakwe imithombo ye-ultrasound elawulwa ngokuzimela engu-1024, egxile ngokwemvelo enkabeni ye-hemisphere. Le mithombo ye-ultrasound iqhutshwa ama-voltage e-sinusoidal radio-frequency voltages futhi ikhipha amaza e-ultrasonic aqondiswa yi-imaging resonance magnetic. Isiguli sigqoka umakalabha futhi amanzi akhishwe umoya azungeza ikhanda ukuze kube lula ukudluliswa kwe-ultrasound. I-Ultrasound ihamba ngesikhumba nogebhezi iye endaweni okuqondiswe kuyo ebuchosheni.

Ukushintsha kogebhezi nokuqina kogebhezi kuzothinta ukusakazwa kwe-ultrasound, okuholela esikhathini esihluke kancane sokuthi i-ultrasound ifinyelele isilonda. Lokhu kuhlanekezela kungalungiswa ngokuthola idatha ye-computed tomography yokulungiswa okuphezulu ukuze kutholwe ulwazi mayelana nokuma kogebhezi, ukujiya, nokuminyana. Imodeli yokulingisa ikhompuyutha ingabala ukushintshwa kwesigaba esinxephezelwe sesiginali yedrayivu ngayinye ukuze kubuyiselwe ukugxila okucijile. Ngokulawula isigaba sesiginali ye-RF, i-ultrasound ingagxilwa ku-elekthronikhi futhi ibekwe endaweni ukuze imboze inani elikhulu lezicubu ngaphandle kokuhambisa uhlu lomthombo we-ultrasound. Indawo yethishu eqondiwe inqunywa ukuthwebula kwe-magnetic resonance yekhanda ngenkathi ugqoke isigqoko. Ivolumu eqondiwe igcwaliswa ngegridi enezinhlangothi ezintathu zamaphoyinti okusetshenzwa kwe-ultrasonic, akhipha amagagasi e-ultrasonic endaweni ngayinye yokunamathisela ngo-5-10 ms, ephindaphindwa njalo ngemizuzwana emi-3. Amandla e-ultrasonic akhula kancane kancane kuze kutholakale isignali yokuhlakazeka kwebhamuza oyifunayo, bese ibanjelwa imizuzwana engu-120. Le nqubo iphindaphindiwe kwamanye ama-meshes kuze kube yilapho umthamo ohlosiwe umbozwe ngokuphelele.

Ukuvula umgoqo wegazi-ubuchopho kudinga ukuphakama kwamagagasi omsindo ukuze kudlule umkhawulo othile, okungaphezu kwalokho ukuvuthwa kwesithiyo kukhuphuka ngokukhuphuka kwe-amplitude yokucindezela kuze kube yilapho kwenzeka umonakalo wezicubu, obonakala njenge-erythrocyte exosmosis, ukopha, i-apoptosis, ne-necrosis, konke okuvame ukuhlotshaniswa nokuwa kwe-bubble (okubizwa ngokuthi i-inertial cavitation). I-threshold incike kusayizi we-microbubble kanye nezinto zegobolondo. Ngokuthola nokuhumusha amasignali e-ultrasonic ahlakazwe amabhamuza amancane, ukuchayeka kungagcinwa ngaphakathi kwebanga eliphephile.

Ngemva kokwelashwa kwe-ultrasound, i-MRI enesisindo se-T1 ene-ejenti yokuqhathanisa yasetshenziswa ukuze kutholwe ukuthi umgoqo wegazi nobuchopho wawuvuliwe yini endaweni okuqondiwe kuyo, futhi izithombe ezinesisindo se-T2 zasetshenziswa ukuze kuqinisekiswe ukuthi ingabe i-extravasation noma ukopha kwenzeke. Lokhu kubuka kunikeza isiqondiso sokulungisa ezinye izindlela zokwelapha, uma kunesidingo.

Ukuhlola kanye nethemba lomphumela wokwelapha

Abacwaningi balinganise umphumela wokwelashwa ebuchosheni be-Aβ umthwalo ngokuqhathanisa i-18F-flubitaban positron emission tomography ngaphambi nangemuva kokwelashwa ukuze kuhlolwe umehluko wevolumu ye-Aβ phakathi kwendawo ephathwayo kanye nendawo efanayo ekolunye uhlangothi. Ucwaningo lwangaphambilini olwenziwa yithimba elifanayo lubonise ukuthi ukumane ugxile ku-ultrasound kungehlisa kancane amazinga e-Aβ. Ukwehliswa okubonwe kulolu cwaningo kwakukhulu nakakhulu kunezifundo zangaphambilini.

Ngokuzayo, ukwandisa ukwelashwa kuzo zombili izinhlangothi zobuchopho kuzobaluleka ekuhloleni ukusebenza kwayo ekubambezelekeni kokuqhubeka kwesifo. Ukwengeza, ucwaningo olwengeziwe luyadingeka ukuze kunqunywe ukuphepha nempumelelo yesikhathi eside, kanye nemishini yokwelapha engabizi kakhulu engancikile ekuqondisweni kwe-MRI eku-inthanethi kumele ithuthukiswe ukuze itholakale kabanzi. Noma kunjalo, okutholiwe kudale ithemba lokuthi ukwelashwa nezidakamizwa ezisula i-Aβ ekugcineni zingabambezela ukuqhubeka kwe-Alzheimer.