| Abstract | Prenatalni razvoj ljudskog telencefalona je obilježen nizom dinamičnih promjena. Stijenka fetalnog telencefalona izgrađena je od prolaznih fetalnih zona u kojima se odvijaju najbitniji neurogenetski procesi. Kao rezultat složenih neurogenetskih zbivanja i procesa, morfološke i histološke karakteristike fetalnog telencefalona se neprekidno mijenjaju, ovisno o dobi fetusa te fazi razvoja. Oslikavanjem fetalnog telencefalona metodom magnetske rezonancije mogu se prikazati i kvalitativne i kvantitativne promjene izgleda i svojstava prolaznih fetalnih zona tijekom razvoja.
Da bismo istražili i opisali kvantitativne pokazatelje ključnih neurogenetskih procesa u odnosu na specifične faze razvoja telencefalona, analizirali smo i rekonstruirali kvantitativne promjene volumena i debljine prolaznih fetalnih zona, kako u cijelom telencefalonu, tako i u njegovim pojedinim područjima. Koristili smo Siemensov uređaj za magnetsku rezonanciju (snage polja 3 Tesla) te posebne programe izrađene na Sveučilištu McGill u Montrealu, za analizu trodimenzionalnih (3D) T1 snimaka dobivenih na devetnaest moždanih polutki fetalnih mozgova u dobi od 11 do 40 tjedana nakon začeća (TNZ).
Rezultati dobiveni izračunavanjem volumena prolaznih fetalnih zona pokazuju da je subplate zona najvažnija tijekom razvoja ljudskog telencefalona, budući da ona sve do 30. TNZ zauzima oko 40% ukupnog volumena stijenke telencefalona. Volumen proliferacijskih zona se povećava tijekom fetalne faze razvoja (od 13. do 23. TNZ) i doseže vrhunac tijekom 23. TNZ. Krivulja rasta volumena proliferacijskih zona se poklapa s krivuljom intenziteta migracije i proliferacije neurona; stoga tu krivulju možemo koristiti kao jedan od bioloških pokazatelja fetalne faze razvoja. Nadalje, međusobna ovisnost regionalnih volumena subplate zone (u odnosu na razvojnu dob), koji dosežu vrhunac tijekom 30. TNZ, te regionalnih volumena kortikalne ploče, čiji porast se eksponencijalno ubrzava nakon 30. TNZ, govori u prilog shvaćanju da ovisnost regionalnih promjena volumena subplate zone i kortikalne ploče odražavaju intenzitet neurogenetskih procesa ključnih za prenatalni razvoj moždane kore, kao što su urastanje i čekanje aksona u subplate zoni ili urastanje aksona u kortikalnu ploču. Regionalne razlike u debljini i volumenu subplate zone, ali i njihova snažna povezanost s regionalnim rastom kortikalne ploče nakon 24. TNZ, pokazuju da je subplate zona vrlo bitna za normalni razvoj moždane kore, zbog glavnih neurogenetskih procesa koji se u toj zoni odvijaju.
U zaključku, rezultati ovog istraživanja potvrđuju hipotezu da kvantitativni pokazatelji dobiveni analizom MR snimaka fetalnog telencefalona mogu služiti kao pokazatelji za praćenje intenziteta nekih ključnih neurogenetskih procesa koji se odvijaju u prolaznim fetalnim zonama. |
| Abstract (english) | Before the birth the human telencephalon undergoes dynamic changes. The fetal telencephalic wall is built of transient fetal zones. These transient fetal zones are sites of occurence of the most important neurogenetic and histogenetic processes. As a result of intertwined complex neurogenetic events, morphological characteristics of the fetal telencephalon change depending on the age and the stage of development. Imaging of fetal telencephalon using magnetic resonance imaging thus allows quantitative measurements of transient fetal zones of the developing brain. Moreover, as qualitative MRI reflects the microstructural content (cell volume, the amount of fibres and extracellular space), the qualitative MRI information can be used as a basis for quantitative analysis. To determine the most important quantitative indicators, depending on the stage of development, the dominant neurogenetic events are analyzed and reconstructed within the framework of dynamical change in volume of transient fetal zones and their regional three-dimensional changes in thickness.
Nineteen post-mortem fetal brains, aged 11 to 40 post-conceptional weeks (PCW), were obtained and scanned using the 3T Siemens MRI device. The MRI images were analyzed using programs developed at McGill University specifically designed for the analysis of postmortem fetal brains.
The results obtained by calculating the volume of transient fetal zones suggest that the subplate zone represents the most important zone during the development of human telencephalon. Up to 30 PCW, it occupies about 40% of the total volume of telencephalon. The volume of proliferative zones, during the fetal stage of development (13 - 23 PCW), increases and reaches its peak value at 23 PCW. The increase in the volume of proliferative zones coincides with the dynamics and the peak wave of migration and proliferation of neuronal precursors described in literature. Thus, it can be used as one of biomarkers for the fetal stage of development. Furthermore, correlation matrices derived from regional analysis of subplate zone volumes (reaching the total volume peak at 30 PCW), regional cortical plate volumes (the total volume accelerates and exponentially increases after the 30 PCW) and between them suggest that the interaction of histogenetic changes (indirectly seen as postive and negative correlation between regional volumes), such as the ingrowth of axons in the subplate zone and the ingrowth of axons into the cortical plate, are important for the maturation of the cortex during the fetal stage of prenatal development. In addition, regional differences in the thickness and volume of the subplate zone and their correlation with the regional growth of the cortical plate from 24 PCW, indicate that the subplate zone, the site of the main neurogenetic events crucial for normal growth of axonal pathways, is important for normal growth and maturation of the cerebral cortex.
In conclusion, the results of this study confirm the hypothesis that quantitative indicators estimated from MR images of the human postmortem fetal brains may serve as indicators for the main neurogenetic events that occur in transient fetal zones and thus have a clear potential as biomarkers of normal and abnormal human brain development. |
