Pediatric MS MRI Study Methodology

Transcription

1 General Pediatric MS MRI Study Methodology SCAN PREPARATION axial T2-weighted scans and/or axial FLAIR scans were obtained for all subjects when available, both T2 and FLAIR scans were scored. In order to minimize biasing, T2 images were assessed for all patients, then FLAIR images for all patients, and finally T2 and FLAIR images were viewed in combination images were viewed on a dedicated dual high-resolution monitor (1600 x 1200 pixel resolution, Barco Manufacturing Company, Belgium) scans were retrieved from CD and viewed using efilm Lite version (efilm Medical Inc., Toronto) screen layout was arranged to accommodate eight sequential axial images (four images on each of the high-resolution monitors) scans were assessed from the most inferior image to the most superior image when possible, all accessory information was stripped from images prior to scoring. This was not possible for films that had be scanned into the PACs system windowing was used to improve lesion differentiation. No predefined windowing parameters were used LESION COUNTING Size once lesions were identified on an image, the location and size of the lesion was noted and annotated on the images using the efilm annotation tool lesion size was defined as the maximal linear expanse in either the axial (X-Y plane) or longitudinal plane (Z plane) a calibrated measurement tool was used to define lesion size on axial images slice thickness and spacing were used to determine estimated maximal expanse in the longitudinal plane (see Figure 1) Example: for a slice thickness of 5 mm and an interslice spacing of 2.5 mm, a lesion that was seen on two contiguous slices was considered to be a minimum of 7.5 mm (~2.5 mm of inferior slice mm interslice spacing + ~2.5 mm of superior slice) in the 1

2 A B 5 mm 2.5 mm 5 mm 2.5 mm 5 mm A B C 15 mm (2.5 mm mm + 5 mm mm mm) C 7.5 mm (2.5 mm mm mm) Figure 1: Pictorial explanation of lesion thickness in the longitudinal (Z-plane). (Left) Three sequential slices from an axial FLAIR image from a patient with multiple sclerosis labeled A, B, and C moving from superior to inferior. White boxes are regions represented in the diagram on the right. Note that within the boxes there is one lesion in the right frontal juxtacortical white matter that extends from slice C to slice B, an another lesion in the left frontal subcortical white matter that extends through all slices represented. (Right) Diagrammatic 3D representations of inset areas on MR scans on left. Slice thickness is 5 mm and interslice spacing is 2.5 mm. The lesion in the right frontal lobe spanned only two slices. Its minimum longitudinal expanse would be 7.5 mm (as depicted above). The lesion in the left frontal lobe spanned all three slices, and therefore its minimum expanse would have to be at least 15 mm. 2

3 longitudinal plane; a lesion spanning three contiguous slices would be a minimum of 15 mm (2.5 mm of inferior slice mm interslice spacing + 5 mm intervening slice mm interslice spacing mm superior slice), etc. lesions were only counted as relevant if they were greater than two millimeters in maximum diameter lesions greater than two millimeters in diameter were categorized as outlined in detail below (see Category section) lesion size was recorded as 3-10 mm, and then in 10 mm centiles: mm, mm, mm, and greater than 40 mm Continuity on axial images, lesions were considered contiguous if they could not be separated by a band of normal appearing tissue of at least 1 pixel in width variability in intra-lesional intensity did not influence lesion counting (i.e., if there was an area of bright T2 signal within a slighter paler lesion, it was not counted as two lesions) (see Figure 2) in the longitudinal plane, lesions were considered contiguous if they could be followed in sequential images all individual lesions were examined carefully in both the axial and longitudinal plane to ensure that at no point were they in direct contact with what may have appeared to be a separate lesion (i.e., if they touch at any point, they are counted as one and measured in the their maximum dimension) (see Figure 2) Lesion Categorization GENERAL total lesion count refers to the total number of individual lesions on each sequence (T2 or FLAIR) categorical lesion count refers to the total number of lesions belonging to any of the categories defined below (see Categories section) in order to obtain an accurate total lesion count without double counting, lesions that belonged to multiple categories only contributed towards the total lesion count in the category that best described where the majority (>50%) of bulk of the lesion fell Example: if the majority of the lesion was found in the caudate head, but a portion touched the internal capsule, only its deep grey nuclei component was counted towards the total lesion count 3

4 A Discrete Lesions A Confluen t Lesion B B Discrete Lesion Confluen t Lesion Figure 2: Diagrammatic explanation of lesion continuity. (Left) Two sequential axial FLAIR images from a patient with multiple sclerosis labeled A and B. White boxes represent portion of scan depicted to the right. Within the box on scan A, four discrete lesions would be counted. Within the box on scan B, two discrete lesions would be counted; one homogeneous juxtacortical lesion and one large, heterogeneous, subcortical white matter lesion. Intralesional areas of hyperintensity cannot be defined as discrete lesions as they are surrounded by tissue of abnormal signal. (Right) Diagrammatic representations of brain tissue outlined by the white boxes on the MR images to the left. In slice A, there appears to be four discrete lesions when viewed solely in the axial plane. However, when viewed in the longitudinal plane, it is obvious that all of these lesions are actually part of the large, heterogeneous, confluent lesion from slice B. Therefore, since the lesions are contiguous on the axial plane in slice B, and contiguous in the longitudinal axis between slices A and B, they are all counted as one lesion. Note, there is a separate discrete lesion on slice B. 4

5 in order to classify lesion distribution accurately, lesions belonging to multiple categories were noted to be part of each category (e.g., internal and deep grey nuclei) and thus, contributed to the categorical lesion count, but not towards the total lesion count Example: for the lesion described above that involved both the caudate head and the internal capsule, it would be counted as a deep grey lesion for the purposes of calculating total lesion load, but it would also be included as a lesion in both the deep grey and internal capsule categories, and thus contribute to the categorical lesion count for each category lesions in nerves are not included CATEGORIES Periventricular any area that abuts a ventricle (including lateral, third, fourth, cerebral aqueduct) may include gray or white matter this category cannot be combined with deep white matter Juxtacortical White Matter any supratentorial white matter abutting the cortical ribbon of grey matter this category cannot be combined with deep white matter Deep White Matter any supratentorial white matter that is not juxtacortical and not periventricular excludes white matter comprising the corpus callosum Internal Capsule please refer to Figure 3 for details white matter between lentiform nucleus, laterally, and the caudate head and thalamus medially anterior border is a line drawn from the Figure 3: Boundaries of the internal capsule. Anterior boundaries are denoted in red, posterior in blue. Black dotted lines denote lateral boundaries. (Image from University of California website) 5

6 most anterior portion of the caudate head to the most anterior tip of the putamen posterior border is a line drawn from the posterior tip of the putamen to the posterolateral portion of the thalamus does not count towards total lesion count subcategory of deep white matter Corpus Callosum please see Figure 4 for details inferior margin inferior margins of the genu and splenium superior margin contiguous ribbon of cingulate grey lining the interhemispheric A fissure B C anterior and posterior margins line drawn from anterior/posterior tip of the lateral ventricle perpendicular to the long axis of the callosal fibres and then extending to the cortical grey ribbon D E F Figure 4: Multiple axial slices of a T1-weighted image depicting the boundaries of the corpus callosum. Images are in sequential order from inferior to superior (A-F). Red lines depict the anterior boundaries. Blue lines depict the posterior boundaries. Green dotted lines represent the long axis of the callosal fibres. Black dotted lines (image E) depict the lateral borders. 6

7 lateral margin (only utilized when lateral ventricles are no longer visualized) medial margin of the lateral ventricle extrapolated from its location on the most superior axial image showing the lateral ventricles Cortical Grey any supratentorial grey cortical grey matter does not include hippocampus Deep Grey Nuclei include the following structures: caudate, putamen, globus pallidus, thalamus, hypothalamus, mamillary bodies, hippocampus, amygdala, and claustrum Brainstem extends from most inferior aspect of the medulla (dictated by the presence of the pyramids) to the most superior portion of the midbrain (last slice showing red nucleus) encompasses both grey and white matter cerebellar and cerebral peduncles are included Cerebellar entire cerebellum (cerebellar cortices, dentate nuclei, vermis, flocculus, nodulus) excluding cerebellar peduncles no differentiation between white and grey lesions Supratentorial includes subcortical white, juxtacortical, internal capsule, corpus callosum, cortical grey, and deep grey nuclei Infratentorial includes brainstem and cerebellum Size Categories SMALL lesions < 1 cm in the axial dimension and <1.5 cm in the longitudinal dimension includes o axial 3-5 mm/longitudinal mm o axial 3-5 mm/longitudinal mm o axial 6-10 mm/longitudinal mm o axial 6-10 mm/longitudinal mm 7

8 M EDIUM lesions 1-2 cm in the axial dimension, and in the dimension includes o axial 3-5 mm/longitudinal mm o axial 6-10/longitudinal mm o axial mm/longitudinal 3-10 mm o axial mm/longitudinal mm o axial mm/longitudinal mm LARGE lesions > 2 cm in the axial dimension or >2.5 cm in the longitudinal dimension includes o axial 3-5 mm/longitudinal mm o axial 3-5 mm/longitudinal >30 mm o axial 6-10/longitudinal mm o axial 6-10/longitudinal >30 mm o axial mm/longitudinal mm o axial mm/longitudinal >30 mm o axial mm/longitudinal 3-10 mm o axial mm/longitudinal mm o axial mm/longitudinal mm o axial mm/longitudinal mm o axial mm/longitudinal >30 mm o axial mm/longitudinal 3-10 mm o axial mm/longitudinal mm o axial mm/longitudinal mm o axial mm/longitudinal mm o axial mm/longitudinal >30 mm o axial >40 mm/longitudinal 3-10 mm o axial >40 mm/longitudinal mm o axial >40 mm/longitudinal mm o axial >40 mm/longitudinal mm o axial >40 mm/longitudinal >30 mm Contact: dcallen@mcmaster.ca 8