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Chirwere cheAlzheimer, chinowanzoitika kune vakwegura, chatambudza vanhu vakawanda.

Rimwe rematambudziko mukurapa kwechirwere cheAlzheimer nderekuti kuendeswa kwemishonga yekurapa kune matishu ehuropi kunoganhurwa neropa-brain barriers. Chidzidzo ichi chakawana kuti MRI-inotungamirwa yakaderera-yakanyanya kutarisisa Ultrasound inogona kuvhurazve ropa-brain barriers muvarwere vane chirwere cheAlzheimer kana zvimwe zvirwere zvetsinga, kusanganisira chirwere cheParkinson, mamota europi, uye amyotrophic lateral sclerosis.

A ichangobva diki proof-of-concept test paRockefeller Institute for Neuroscience paWest Virginia University yakaratidza kuti varwere vane chirwere cheAlzheimer vakagamuchira aducanumab infusion pamwe chete nefocused ultrasound vakavhura kwechinguva chivharo cheropa-brain chakanyanya kuderedza brain amyloid beta (Aβ) mutoro padivi rekuedzwa. Tsvagiridzo iyi inogona kuvhura mikova mitsva yekurapa kwehuropi kusagadzikana.

Ropa-brain chipingamupinyi chinodzivirira huropi kubva kuzvinhu zvinokuvadza uku ichibvumira chikafu chakakosha kupfuura. Asi chipingamupinyi cheropa-uropi chinodzivirirawo kuendeswa kwemishonga yekurapa kuuropi, dambudziko rinonyanya kuoma pakurapa chirwere cheAlzheimer. Sezvo makore epasirese, huwandu hwevanhu vane hosha yeAlzheimer huri kuwedzera gore negore, uye nzira dzayo dzekurapa dzakashomeka, zvichiisa mutoro unorema pahutano. Aducanumab is an amyloid beta (Aβ) -binding monoclonal antibody iyo yakatenderwa neUS Food and Drug Administration (FDA) yekurapa chirwere cheAlzheimer, asi kupinda kwayo kweropa-brain barriers kune zvishoma.

Focused ultrasound inogadzira masaisai emuchina anoita kuti oscillations pakati pekumanikidza uye dilution. Kana yaiswa muropa uye yakaratidzwa kune ultrasonic munda, mabhubhu anodzvanya uye anowedzera kupfuura yakatenderedza tishu neropa. Aya maoscillations anogadzira kushushikana kwemagetsi pamadziro emidziyo yeropa, zvichikonzera kubatana kwakasimba pakati pemaseru endothelial kutambanudza nekuvhura (Mufananidzo pazasi). Nekuda kweizvozvo, kuvimbika kweropa-brain barriers kunokanganiswa, zvichibvumira mamorekuru kupararira muuropi. Chidziviso cheropa-uropi chinopora choga mumaawa matanhatu.

Iyo nhamba inoratidza mhedzisiro yeinotungamira ultrasound pamadziro ecapillary apo mabhubhu akaenzana nema micrometer aripo mutsinga dzeropa. Nekuda kwekunyanya kusimba kwegasi, mabubbles anobvumirana uye anowedzera kupfuura matishu akatenderedza, zvichikonzera kushushikana kwemagetsi pamaseru endothelial. Kuita uku kunokonzeresa kuti kubatana kwakasimba kuvhure uye kunogonawo kukonzera magumo eastrocyte kudonha kubva pamadziro etsinga yeropa, kukanganisa kutendeseka kweropa-brain barriers uye kukurudzira kupararira kwemasoja. Pamusoro pezvo, masero endothelial akafumurwa kune yakatariswa ultrasound akasimudzira yavo inoshanda vacuolar yekufambisa basa uye yakadzvanya efflux pombi basa, nekudaro ichidzikisa kuchena kwehuropi kwemasoja ekudzivirira chirwere. Mufananidzo B unoratidza chirongwa chekurapa, icho chinosanganisira computed tomography (CT) uye magnetic resonance imaging (MRI) yekugadzira chirongwa che ultrasound chekurapa, 18F-flubitaban positron emission tomography (PET) pakutanga, infusion ye antibody isati yatarisa ultrasound kurapwa uye microvesicular infusion panguva yekurapa, uye acoustic monitoring ye microvesicular signal scatter inoshandiswa kudzora kupararira kwehutachiona hwehutachiona. Mifananidzo yakawanikwa mushure mekutarisisa kurapwa kwe ultrasound yaisanganisira T1-yakayereswa musiyano-yakakwidziridzwa MRI, iyo yairatidza kuti ropa-brain chipingamupinyi chakavhurika munzvimbo yakarapwa ultrasound. Mifananidzo yenzvimbo imwechete mushure memaawa makumi maviri nemana kusvika makumi mana nemasere ekutarisisa ultrasound kurapwa kwakaratidza kuporeswa kwakazara kweropa-brain barriers. An 18F-flubitaban PET scan panguva yekutevera mune imwe yevarwere mavhiki e26 gare gare yakaratidza kuderedzwa kweAβ mazinga muuropi mushure mekurapa. Mufananidzo C unoratidza iyo MRI-inotungamirwa yakatarisa ultrasound setup panguva yekurapa. Iyo hemispherical transducer helmet ine zvinopfuura 1,000 ultrasound masosi ayo anochinja kune imwechete inotarisisa muuropi uchishandisa chaiyo-nguva kutungamira kubva kuMRI.

Muna 2001, yakanangana neultrasound yakatanga kuratidzwa kuti ikonzere kuvhurwa kweropa-brain chipingamupinyi muzvidzidzo zvemhuka, uye zvakazotevera zvidzidzo zvekiriniki zvakaratidza kuti yakanangwa ultrasound inogona kusimudzira kuendesa zvinodhaka uye kushanda. Kubva ipapo, zvakaonekwa kuti yakanangwa ultrasound inogona kuvhura zvakachengeteka ropa-brain chipingamupinyi muvarwere vane Alzheimer's vasiri kuwana mushonga, uye zvakare inogona kuendesa masoja ekudzivirira chirwere kugomarara rezamu metastases.

Microbubble delivery process

Microbubbles ndeye Ultrasound musiyano mumiririri unowanzo shandiswa kuona kuyerera kweropa uye tsinga dzeropa mune ultrasound kuongororwa. Munguva ye ultrasound therapy, phospholipid-yakavharwa isina-pyrogenic bubble kuturika kwe octafluoropropane yakabayiwa intravenously (Mufananidzo 1B). Microbubbles ane polydispersed zvakanyanya, ane madhayamita kubva pasi pe1 μm kusvika kune anopfuura gumi μm. Octafluoropropane igasi rakagadzikana risina kugadzirwa uye rinogona kubudiswa kuburikidza nemapapu. Iyo lipid shell inoputira uye inodzikamisa mabhubhu inoumbwa neatatu echisikigo lipids emunhu anogadziriswa nenzira yakafanana kune endogenous phospholipids.

Chizvarwa chekutarisisa ultrasound

Focused ultrasound inogadzirwa nehemispherical transducer helmet inotenderedza musoro wemurwere (Mufananidzo 1C). Iyo ngowani inoshongedzerwa ne1024 yakazvimiririra inodzorwa ultrasound masosi, ayo anongogara akatarisa pakati pehemisphere. Aya ma ultrasound masosi anofambiswa ne sinusoidal radio-frequency voltages uye emit ultrasonic masaisai anotungamirwa nemagnetic resonance imaging. Murwere anopfeka ngowani uye mvura yakasvibiswa inotenderera mumusoro kuitira kufambisa kutapurirana kweultrasound. Iyo ultrasound inofamba nemuganda uye dehenya kuenda kuhuropi chinangwa.

Shanduko muhukobvu hwedehenya uye density inokanganisa kupararira kwe ultrasound, zvichikonzera nguva yakati siyanei yekuti Ultrasound isvike paronda. Kukanganiswa uku kunogona kugadziriswa nekuwana yakakwirira-resolution computed tomography data kuti uwane ruzivo nezve dehenya chimiro, ukobvu, uye density. Kombuta yekutevedzera modhi inogona kuverenga iyo yakabhadharwa chikamu chekuchinja chega yega chiratidzo chedhiraivha kudzoreredza kutarisa kwakapinza. Nekudzora chikamu cheiyo RF chiratidzo, iyo ultrasound inogona kutariswa nemagetsi uye kuiswa panzvimbo yekuvhara huwandu hwakakura hwematishu pasina kufambisa iyo ultrasound sosi array. Nzvimbo yetishu inotangwa inotarirwa nemagnetic resonance imaging yemusoro wakapfeka ngowani. Iyo vhoriyamu yakanangwa yakazadzwa neatatu-dimensional grid ye ultrasonic anchor point, iyo inoburitsa ultrasonic mafungu pane imwe neimwe anchor point for 5-10 ms, inodzokororwa ese matatu masekonzi. Iyo ultrasonic simba inowedzerwa zvishoma nezvishoma kusvika yaunoda bubble yekuparadzira chiratidzo yaonekwa, uye yozobatwa kwe120 seconds. Iyi nzira inodzokororwa kune mamwe meshes kusvika iyo inotarirwa vhoriyamu yakavharwa zvachose.

Kuvhura iyo yeropa-uropi chipingamupinyi kunoda amplitude yemafungu eruzha kuti ipfuure imwe chikumbaridzo, kupfuura iyo iyo permeability yemhinganidzo inowedzera nekuwedzera kudzvinyirira amplitude kusvikira kukuvara kwenyama kuchiitika, kuratidzwa se erythrocyte exosmosis, kubuda ropa, apoptosis, uye necrosis, izvo zvese zvinowanzobatanidzwa nekuputsika kwebubble (inonzi inertial cavitation). Chikumbaridzo chinoenderana nehukuru hwe microbubble uye iyo shell zvinhu. Nekuona uye kududzira ma ultrasonic masaini akaparadzirwa nema microbubbles, kuratidzwa kunogona kuchengetedzwa mukati meyakachengeteka renji.

Mushure mekurapa kwe ultrasound, T1-inorema MRI ine musiyano ajenti yakashandiswa kuona kana chipingamupinyi cheropa-uropi chaive chakavhurika panzvimbo yakatarwa, uye mifananidzo yeT2-inorema yakashandiswa kusimbisa kana kuwedzera kana kubuda ropa kwakaitika. Aya maonero anopa nhungamiro yekugadzirisa mamwe marapirwo, kana zvichidikanwa.

Kuongorora uye tarisiro yekurapa maitiro

Vatsvakurudzi vakatsanangura maitiro ekurapa pauropi Aβ mutoro nekuenzanisa 18F-flubitaban positron emission tomography vasati uye mushure mekurapa kuti vaongorore mutsauko weAβ vhoriyamu pakati penzvimbo yakarapwa uye A yakafanana nzvimbo kune rumwe rutivi. Ongororo yapfuura nechikwata chimwe chete yakaratidza kuti kungotarisa ultrasound kunogona kuderedza zvishoma mazinga eAβ. Kuderedzwa kwakaonekwa muchiyedzo ichi kwakatonyanya kudarika mune zvidzidzo zvekare.

Mune ramangwana, kuwedzera kurapwa kumativi ese ehuropi kuchave kwakakosha pakuongorora kushanda kwayo mukunonoka kufambira mberi kwechirwere. Mukuwedzera, kutsvakurudza kwakawanda kunodiwa kuti uone kuchengetedzwa kwenguva refu uye kushanda, uye michina yekurapa inodhura isingavimbi nehutungamiri hweMRI yepaIndaneti inofanira kugadzirwa kuti ivepo yakawanda. Zvakadaro, zvakawanikwa zvaunza tariro yekuti kurapwa nemishonga inojekesa Aβ inogona kupedzisira inonotsa kufambira mberi kweAlzheimer.