On March 31st 2009, MD Annette Sidaros succesfully defended  her Ph.D. thesis entitled

MRI in severe traumatic brain injury: Micro- and macrostructural changes

The work was performed at the Danish Research Centre for Magnetic Resonance and at the Department of Neurohabilitation, both at Copenhagen University Hospital Hvidovre. Follow the link above to download thesis.

The comitee:

• Professor John Whyte, Philadelphia, USA
• Professor Jens Christian H. Sørensen, Århus
• Professor Carsten Thomsen, København.
  
  

Supervisors: DMSc Olaf B. Paulson, DMSc Aase W. Engberg, DMSc Egill Rostrup. PhD Terry L. Jernigan, DMSc Palle Petersen.

Abstract in English:

The principal aim of the present PhD project was to study quantitatively the long-term microand macrostructural brain changes in survivors from severe traumatic brain injury (TBI). A total of 31 patients admitted for early rehabilitation following severe TBI were included and underwent magnetic resonance imaging (MRI), including Diffusion Tensor Imaging (DTI), at mean 8 weeks post-injury. Follow-up MRI at mean 12 months post-injury was acquired in 25 of the patients. For comparison, healthy matched controls were scanned twice with a similar time interval. Clinical rating during rehabilitation and at 1-year follow-up was performed by experienced staff. Two papers make up the basis of this thesis. Paper I considers the DTI results. This MRI modality was chosen in order to evaluate diffusional changes in brain tissue, potentially useful for characterising the extent of microscopic white matter injury, as well as for tracking microstructural changes during recovery. Using a region-of-interest approach, four white matter regions were studied with additional regions in grey matter and CSF. At the initial scan, patients had abnormal fractional anisotropy (FA) in all white matter regions, which in the cerebral peduncle correlated with 1-year outcome, suggesting that DTI may have prognostic value. At follow-up, FA had partly normalised in some white matter regions, but deviated even more from normal values in other regions. Although these longitudinal findings warrant cautious interpretation, they might indicate microstructural reorganization. Paper II describes a study on the macrostructural brain changes during recovery. Global and regional brain volume changes between the two scan time points were investigated using voxelwise analyses. Despite remarkable clinical improvement in most patients, they all exhibited continued brain volume loss during the scan interval. Global volume change correlated with clinical injury severity, functional status at both scans, and with 1-year outcome. The areas which underwent the most change were structures particularly susceptible to traumatic axonal injury and consequent Wallerian degeneration, indicating that the long-term atrophy is attributable to consequences of axonal injury. Together, these MRI analyses complemented each other in the quantitative assessment of structural brain changes following severe TBI. Applied in the late subacute/early chronic phase of TBI, DTI may capture biological severity at the microstructural level and provide prognostic information. Serial application of the MRI techniques applied in this study enables the monitoring of the extent and distribution of micro- and macrostructural changes during TBI rehabilitation.

Summary in Danish:

Projektet er udført på Hvidovre Hospital i samarbejde mellem MR-afdelingen og Afdeling for
Neurorehabilitering. Det primære formål var kvantitativt at karakterisere mikro- og makrostrukturelle
ændringer i hjernen efter svær traumatisk hjerneskade (TBI), vha avancerede MR-teknikker, herunder
diffusions-tensor-billeddannelse (DTI).

Patienter indlagt til tidlig intensiv rehabilitering efter svær TBI blev skannet med
konventionelle MR-sekvenser samt DTI, omkring 2 måneder og igen 12 måneder efter traumet.
Kvantitative MR-mål blev sammenholdt med kliniske ratings. To originalpublikationer danner basis for
nærværende afhandling:

Artikel I omhandler DTI-resultaterne. Ved DTI kan den retningsspecifikke diffusion i
hjernevævet kvantificeres, hvilket i hvid substans afspejler fiberbundternes anatomiske anordning.
Denne påvirkes bl.a. ved traumatisk aksonal skade (TAI, også kaldet diffus aksonal skade), en
læsionstype som kun i begrænset omfang kan detekteres ved konventionel billeddiagnostik. Ved første
skanning var DTI-parametre abnorme i de undersøgte hvid substans-regioner, selv når disse var uden
synlige læsioner på konventionel MR. Svarende til pedunculi cerebri var der korrelation mellem DTI-
parametre og klinisk outcome 1 år efter skaden. Ved opfølgende skanning var DTI-parametre delvis
normaliserede i nogle hvid substans-regioner, primært hos patienter med favorabelt outcome.

Artikel II beskriver en undersøgelse af makrostrukturelle ændringer i hjernen efter TBI.
Globale og regionale volumenændringer mellem de to skanningstidspunkter blev kvantificeret ved
voxel-vis analyse. På trods af bemærkelsesværdig klinisk bedring hos størstedelen af patienterne i
denne periode, udviste de alle hjernevolumentab i skanningsintervallet. Global volumenændring
korrelerede med klinisk sværhed og outcome. De regioner som udviste størst volumentab var
strukturer som er særlig udsatte for TAI og resulterende Wallersk degeneration.

Projektets resultater indikerer at DTI kan anvendes til at kvantificere biologisk sværhedsgrad
af TAI, og har potentiale som markør for langtidsprognosen. De longitudinelle DTI-ændringer kan
muligvis repræsentere mikrostukturel reorganisering. Atrofi fortsætter måneder efter svær TBI, trods
klinisk bedring, og synes overvejende at afspejle degenerative følger af TAI.