Učinak perinatalne hipoksijsko – ishemijske encefalopatije na projekcijske puteve moždanoga debla u nedonoščeta [Impact of hypoxic-ischemic encephalopathy on projection pathways of the premature infant brainstem]

Raguž, Marina (2018) Učinak perinatalne hipoksijsko – ishemijske encefalopatije na projekcijske puteve moždanoga debla u nedonoščeta [Impact of hypoxic-ischemic encephalopathy on projection pathways of the premature infant brainstem]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Introduction: Improved perinatal care has led to increased survival of premature infants. These children often have different motoric, cognitive and psychological disorders. Perinatal hypoxic-ischemic encephalopathy (HIE) is a major cause of white matter injury and long-term neurological deficits in children. The aim of this study is to analyze cerebral volumes and DTI parameters as major site of white matter injury and compare them with recipient areas in pons and cerebellum in order to find possible selective vulnerability for corticospinal tracts, corticopontine pathways, medial lemnisci and superior, medial and inferior cerebellar peduncles. Material and methods: In our research we had three groups of participants. The first group consisted of 5 normal term infants (control), the second group included 16 normotypic premature infants without perinatal HIE lesions (normotypic), and the third group included 22 premature infants with perinatal HIE (HIE). Diagnosis of perinatal HIE was based on both MRI and clinical exams. Parental consent for MRI scanning was obtained and all examinations were controlled and approved by the Institutional Review Board of the University of Zagreb School of Medicine. MRI images were obtained using 3T MRI scanner (Magnetom TrioTim, Siemens, Germany), with high resolution T1 MPRAGE sequence in sagittal plane (voxel size = 1x1x1 mm) and dwi sequences (voxel size 1.6x1.6x3 mm). All groups were scanned at two different time points, first at the term or corrected term age and second at the age of two years. Cerebral and cerebellar volumes were measured using semi-automated software (MNI toolbox, Montreal, Canada), and brainstem (mesencephalon, pons, medulla oblongata) was measured using manual segmentation methods (Analyze 8.1, Mayo Clinic, USA). Axonal pathways (corticospinal tracts, corticopontine pathways, medial lemnisci and superior, medial and inferior cerebellar peduncles) were reconstructed and all parameters (volume, FA- fractional anisotropy and ADC-apparent diffusion coefficient) have been measured using Diffusion Toolkit and TrackVis software. Statistical analysis was done using MedCalc v12. Results: Normotypic group showed decreased volumes at corrected term age, but their volumes compensate during growth and at the age of 2 years correspond to control group. Unlike normotypic, group with HIE lesions shows statistically significant reduction of measured volumes during corrected term age comparing with normal group, and also at the age of 2 years comparing with both normal and normotypic group. Volumetric analysis of brainstem parts (mesencephalon, pons, medulla oblongata) and its layers (base, tegmentum, tectum) follows that pattern as well as volumetric analysis of brainstem in general, cerebellum and total brain volume. Parameters measured during DTI analysis (volume, FA- fractional anisotropy and ADC-apparent diffusion coefficient) for named axonal pathways showed similar pattern in observed groups. Conclusion: Origin, trajectory and termination areas of measured axonal pathways are reduced after perinatal HIE. We have found that all measured pathways are regularly damaged in perinatal HIE, as a part of general white matter pathology. Our finding is in the agreement that pathways which are part of the periventricular fiber system and periventricular crossroads are vulnerable in HIE. Also, due to the topographical relationship, damaged periventricular fibers will contribute to reduction of brainstem, expecially pons, as well as cerebellum.

Abstract in Croatian

Uvod: Bolja perinatalna skrb dovela je do povećanog preživljavanja nedonoščadi. Ta djeca češće imaju različite motoričke, kognitivne i psihološke poremećaje. Perinatalna hipoksijsko-ishemijska encefalopatija (HIE) je osnovni uzrok ozljeda bijele tvari i dugotrajnih neuroloških deficita u djece. Cilj ove disertacije je analizirati moždane volumene i traktografske parametre kao glavno mjesto ozljede bijele tvari i usporediti ih s područjima u ponsu i malom mozgu kako bi se pronašla moguća selektivna vulnerabilnost za kortikospinalni put, kortikopontini put, medijalni lemnisk te za gornje, srednje i donje krakove malog mozga. Materijali i metode: Ovo istraživanje uključuje tri skupine ispitanika. Prva se grupa sastoji od 5 zdrave, terminske djece (kontrola), druga grupa uključuje 16 nedonoščadi bez perinatalne HIE (normotipična skupina), a treća skupina se sastoji od 22 nedonoščadi sa potvrđenom perinatalnom HIE (HIE skupina). Dijagnoza perinatalne HIE se temelji na MR i kliničkim nalazima. Dobiven je pristanak roditelja za MR snimanje, a sva snimanja i pregledi su kontrolirani i odobreni od strane Etičkog povjerenstva Medicinskog fakulteta Sveučilišta u Zagrebu. MR snimke su snimljene uređajem snage magnetskog polja 3T (Magnetom TrioTim, Siemens, Njemačka), a korištena je T1 MPRAGE sekvenca visoke rezolucije u sagitalnoj ravnini (veličina voksela = 1x1x1 mm) i dwi sekvenca (veličina voksala 1,6x1,6x3 mm). Sve grupe ispitanika su snimljene u dvije vremenske točke, najprije u terminskoj ili korigiranoj terminskoj dobi, a onda u dobi od dvije godine. Moždani volumeni su mjereni uz pomoć polu-automatskog volumetrijskog programa (MNI toolbox, Montreal, Canada), a volumen moždanog debla i njegovih dijelova uz pomoć volumetrijskog programa koji zahtijeva manualne metode segmentiranja (Analyze 8.1, Mayo Cllinic, USA). Aksonalni snopovi (kortikospinalni put, kortikopontini put, medijalni lemnisk, gornji, srednji i donji krakovi malog mozga) su rekonstruirani koristeći programe Diffusion Toolkit i TrackVis software. Rekonstruiranim aksonalnim snopovima izmjereni su parametri (volumen, frakcijska anizotropija, FA te difuzijski koeficijent, ADC, eng. apparent diffusion coefficient). Statistička analiza učinjena je programom MedCalc v12. Rezultati: Normotipična skupina ispitanika pokazuje smanjenje mjerenih volumena u korigiranoj terminskoj dobi u odnosu na kontrolnu skupinu, no ta razlika se smanji do druge godine života i ostaje diskretna. HIE skupina ispitanika pokazuje statistički značajnuredukciju mjerenih volumena korigiranoj terminskoj dobi u odnosu na kontrolnu skupinu, a to smanjenje se nastavlja i u dobi od dvije godine kada je značajano u odnosu na kontrolnu i normotipičnu skupinu. Volumetrijska analiza koja je pokazala navedeni obrazac uključuje moždano deblo (mezencefalon, pons, produljena moždina) i njegove segmente (baza, tegmentum, tektum) i mali mozak. Analizirani DTI parametri (volumen, FA, ADC) pokazuju sličan obrazac kod mjerenih aksonalnih snopova promatranih skupina. Zaključak: Ishodište, putanja i ciljno područje analiziranih aksonalnih puteva su reducirani nakon perinatalne HIE. Utvrdili smo da su svi izmjereni aksonalni snopovi redovito oštećeni u perinatalnoj HIE, kao dio opće patologije bijele tvari. Ovakvi rezultati potvrđuju da su putevi koji su dio periventrikularnog sustava vlakana i periventrikularnih raskrižja vulnerabilni u HIE. Također, zbog topografskog odnosa, oštećena periventrikularna vlakna pridonose smanjenju moždanog debla, napose ponsa te smanjenju malog mozga.

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