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Matenda a Alzheimer, omwe amafala kwambiri mwa okalamba, avutitsa anthu ambiri.

Chimodzi mwazovuta pochiza matenda a Alzheimer's ndikuti kupereka mankhwala ochizira ku minofu yaubongo kumachepa ndi chotchinga chamagazi-muubongo. Kafukufukuyu adapeza kuti MRI yotsogozedwa ndi ultrasound yoyang'ana pang'onopang'ono imatha kutsegulanso chotchinga chamagazi mwa odwala omwe ali ndi matenda a Alzheimer's kapena matenda ena amisempha, kuphatikiza matenda a Parkinson, zotupa muubongo, ndi amyotrophic lateral sclerosis.

Kafukufuku wochepa waposachedwa wa umboni ku Rockefeller Institute for Neuroscience ku West Virginia University adawonetsa kuti odwala omwe ali ndi matenda a Alzheimer's omwe adalandira kulowetsedwa kwa aducanumab kuphatikiza ndi kuyang'ana kwa ultrasound adatsegula kwakanthawi chotchinga chamagazi-ubongo kwambiri kuchepetsa ubongo amyloid beta (Aβ) katundu pa mbali yoyeserera. Kafukufukuyu atha kutsegulira zitseko zatsopano zochizira matenda aubongo.

Chotchinga chamagazi ndi ubongo chimateteza ubongo ku zinthu zovulaza ndikulola kuti zakudya zofunikira zidutse. Koma chotchinga cha magazi ndi ubongo chimalepheretsanso kutumiza mankhwala ochizira ku ubongo, vuto lomwe limakhala lovuta kwambiri pochiza matenda a Alzheimer's. M'zaka zapadziko lonse lapansi, chiwerengero cha anthu omwe ali ndi matenda a Alzheimer chikuwonjezeka chaka ndi chaka, ndipo njira zake zochiritsira zimakhala zochepa, zomwe zimayika katundu wolemera pa chithandizo chamankhwala. Aducanumab ndi amyloid beta (Aβ) -binding monoclonal antibody yomwe yavomerezedwa ndi US Food and Drug Administration (FDA) kuti athe kuchiza matenda a Alzheimer's, koma kulowa kwake kwa chotchinga chamagazi ndi ubongo kumakhala kochepa.

Focused ultrasound imapanga mafunde amakina omwe amapangitsa kusinthasintha pakati pa kuponderezana ndi dilution. Pamene jekeseni mu magazi ndi poyera kuti akupanga kumunda, thovu compress ndi kukulitsa kuposa ozungulira minofu ndi magazi. Ma oscillation awa amapanga kupsinjika kwamakina pakhoma la chotengera chamagazi, zomwe zimapangitsa kuti kulumikizana kolimba pakati pa ma cell a endothelial kutambasula ndikutsegula (Chithunzi pansipa). Zotsatira zake, kukhulupirika kwa chotchinga chamagazi-muubongo kumasokonekera, zomwe zimapangitsa kuti mamolekyu afalikire muubongo. Chotchinga mu ubongo wa magazi chimachira pachokha pafupifupi maola asanu ndi limodzi.

Chithunzichi chikuwonetsa zotsatira za ultrasound pamakoma a capillary pomwe thovu laling'ono la micrometer limapezeka m'mitsempha. Chifukwa cha kupsinjika kwakukulu kwa gasi, thovulo limalumikizana ndikukulitsa kuposa minofu yozungulira, zomwe zimapangitsa kupsinjika kwamakina pama cell endothelial. Izi zimapangitsa kuti zolumikizana zolimba zitseguke ndipo zimathanso kupangitsa kuti ma astrocyte agwe pakhoma la mitsempha yamagazi, kusokoneza kukhulupirika kwa chotchinga muubongo ndikulimbikitsa kufalikira kwa ma antibody. Kuphatikiza apo, ma cell a endothelial omwe amawonetsedwa ndi ultrasound amakulitsa ntchito yawo yoyendera vacuolar ndikuchepetsa ntchito ya mpope ya efflux, potero amachepetsa kuchotsedwa kwa ma antibodies muubongo. Chithunzi B chikuwonetsa ndandanda yamankhwala, yomwe imaphatikizapo computed tomography (CT) ndi maginito resonance imaging (MRI) kuti apange dongosolo la chithandizo cha ultrasound, 18F-flubitaban positron emission tomography (PET) poyambira, kulowetsedwa kwa antibody musanayambe kuyang'ana chithandizo cha ultrasound ndi kulowetsedwa kwa microvesicular panthawi ya chithandizo, ndi kuyang'anitsitsa kwamawu a ultrasound mankhwala obalalitsa. Zithunzi zomwe zidapezedwa pambuyo pochiza chithandizo cha ultrasound zidaphatikizanso MRI yolemetsa yolemetsa ya T1, yomwe idawonetsa kuti chotchinga chamagazi-muubongo chinali chotseguka pamalo opangira ma ultrasound. Zithunzi za dera lomwelo pambuyo pa maola 24 mpaka 48 a chithandizo cha ultrasound chinasonyeza kuchiritsa kwathunthu kwa chotchinga cha magazi ndi ubongo. Kujambula kwa 18F-flubitaban PET panthawi yotsatiridwa ndi mmodzi mwa odwala masabata 26 pambuyo pake kunawonetsa kuchepa kwa Aβ mu ubongo pambuyo pa chithandizo. Chithunzi C chikuwonetsa kukhazikitsidwa kwa ultrasound motsogozedwa ndi MRI panthawi ya chithandizo. Chisoti cha hemispherical transducer chili ndi magwero opitilira 1,000 a ultrasound omwe amatembenukira kumalo amodzi muubongo pogwiritsa ntchito chitsogozo chanthawi yeniyeni kuchokera ku MRI.

Mu 2001, kuyang'ana kwa ultrasound kunawonetsedwa koyamba kuti kupangitse kutseguka kwa chotchinga chamagazi muubongo m'maphunziro a nyama, ndipo kafukufuku wotsatira wachipatala awonetsa kuti kuyang'ana kwa ultrasound kumatha kupititsa patsogolo kuperekera kwamankhwala ndikuchita bwino. Kuyambira pamenepo, zapezeka kuti kuyang'ana kwa ultrasound kumatha kutsegulira bwino chotchinga chamagazi muubongo mwa odwala omwe ali ndi Alzheimer's omwe sakulandira mankhwala, komanso amatha kupereka ma antibodies ku metastases ya ubongo wa khansa ya m'mawere.

Njira yoperekera microbubble

Ma Microbubbles ndi njira ya ultrasound yosiyanitsa yomwe imagwiritsidwa ntchito kuyang'anira kuthamanga kwa magazi ndi mitsempha yamagazi pozindikira matenda a ultrasound. Pa ultrasound mankhwala, phospholipid TACHIMATA sanali pyrogenic kuwira kuwira kuyimitsidwa wa octafluoropropane anali jekeseni mtsempha wa magazi (Chithunzi 1B). Ma Microbubbles ndi opangidwa ndi polydispersed kwambiri, okhala ndi mainchesi kuyambira zosakwana 1 μm mpaka 10 μm. Octafluoropropane ndi mpweya wokhazikika womwe umakhala wosasunthika ndipo ukhoza kutulutsidwa kudzera m'mapapo. Chigoba cha lipid chomwe chimakulunga ndikukhazikika kwa thovulo chimapangidwa ndi ma lipids atatu achilengedwe aumunthu omwe amapangidwa molingana ndi ma phospholipids amkati.

Mbadwo wa focused ultrasound

Focused ultrasound imapangidwa ndi hemispherical transducer chisoti chomwe chimazungulira mutu wa wodwalayo (Chithunzi 1C). Chisoticho chili ndi magwero a 1024 oyendetsedwa ndi ultrasound, omwe mwachilengedwe amakhala pakatikati pa dziko lapansi. Ma ultrasound awa amayendetsedwa ndi sinusoidal radio-frequency voltages ndipo amatulutsa mafunde akupanga motsogozedwa ndi kujambula kwa maginito. Wodwala amavala chisoti ndipo madzi osungunuka amazungulira pamutu kuti athandizire kufala kwa ultrasound. Ultrasound imadutsa pakhungu ndi chigaza kupita ku ubongo.

Kusintha kwa makulidwe a chigaza ndi kachulukidwe kake kumakhudza kufalikira kwa ultrasound, zomwe zimapangitsa kuti pakhale nthawi yosiyana kwambiri kuti ultrasound ifike pachilondacho. Kupotoza kumeneku kungathe kukonzedwa mwa kupeza chidziwitso chapamwamba cha computed tomography kuti mudziwe zambiri za mawonekedwe a chigaza, makulidwe, ndi kachulukidwe. Makina oyerekeza a pakompyuta amatha kuwerengetsa kusintha komwe kwalipidwa kwa siginecha iliyonse yoyendetsa kuti abwezeretse kuyang'ana kwakuthwa. Pakuwongolera gawo la siginecha ya RF, ma ultrasound amatha kuyang'ana pamagetsi ndikuyikidwa kuti azitha kuphimba minofu yambiri popanda kusuntha magwero a ultrasound. Malo omwe minofu yomwe ikukhudzidwayo imatsimikiziridwa ndi kujambula kwa maginito kwa mutu pamene wavala chisoti. Chandamale voliyumu wodzazidwa ndi atatu azithunzithunzi gululi wa akupanga nangula mfundo, amene zimatulutsa akupanga mafunde pa aliyense nangula mfundo 5-10 ms, mobwerezabwereza aliyense 3 masekondi. Mphamvu ya akupanga imachulukitsidwa pang'onopang'ono mpaka chizindikiro chobalalitsa chomwe chimafunidwa chizindikirika, kenako chimachitika kwa masekondi 120. Izi zimabwerezedwa pa ma meshes ena mpaka voliyumu yomwe chandamale idaphimbidwa.

Kutsegula chotchinga cha magazi-ubongo kumafuna kuti matalikidwe a mafunde a phokoso apitirire malire ena, kupitirira kumene kutsekemera kwa chotchinga kumawonjezeka ndi kuwonjezereka kwamphamvu mpaka kuwonongeka kwa minofu, kuwonetseredwa ngati erythrocyte exosmosis, magazi, apoptosis, ndi necrosis, zomwe nthawi zambiri zimagwirizanitsidwa ndi kugwa kwa kuwira (kutchedwa inertial cavitation). Poyambira zimatengera kukula kwa microbubble ndi zinthu zipolopolo. Pozindikira ndi kutanthauzira ma ultrasound omwe amabalalika ndi ma microbubbles, mawonekedwewo amatha kusungidwa pamalo otetezeka.

Pambuyo pa chithandizo cha ultrasound, MRI yolemetsa ya T1 yokhala ndi wosiyanitsa idagwiritsidwa ntchito kuti adziwe ngati chotchinga chamagazi-muubongo chinali chotseguka pamalo omwe chandamale, ndipo zithunzi zolemera za T2 zidagwiritsidwa ntchito kutsimikizira ngati kutulutsa kapena kutuluka magazi kunachitika. Kuwona kumeneku kumapereka chitsogozo chosinthira chithandizo china, ngati kuli kofunikira.

Kuunika ndi chiyembekezo cha achire zotsatira

Ofufuzawo adawerengera zotsatira za chithandizo paubongo wa Aβ poyerekeza 18F-flubitaban positron emission tomography isanayambe komanso itatha chithandizo kuti awone kusiyana kwa voliyumu ya Aβ pakati pa malo ochiritsidwa ndi A ofanana mbali ina. Kafukufuku wam'mbuyomu wa gulu lomwelo wawonetsa kuti kungoyang'ana ma ultrasound kumatha kuchepetsa milingo ya Aβ. Kuchepetsa komwe kunachitika mu kuyesaku kunali kwakukulu kuposa maphunziro am'mbuyomu.

M'tsogolomu, kukulitsa chithandizo ku mbali zonse za ubongo kudzakhala kofunika kwambiri kuti tiwone momwe zimagwirira ntchito pochedwetsa kukula kwa matenda. Kuonjezera apo, kufufuza kwina kumafunika kuti mudziwe chitetezo cha nthawi yaitali komanso chogwira ntchito, komanso zipangizo zochiritsira zotsika mtengo zomwe sizidalira malangizo a MRI pa intaneti ziyenera kupangidwa kuti zikhalepo zambiri. Komabe, zomwe zapezazo zadzetsa chiyembekezo choti chithandizo ndi mankhwala omwe amachotsa Aβ atha kuchedwetsa kupita patsogolo kwa Alzheimer's.