Spatial distributions of white matter hyperintensities on brain MRI: a pooled analysis…, 2023, Coenen et al.

Spatial distributions of white matter hyperintensities on brain MRI: a pooled analysis of individual participant data from 11 memory clinic cohorts
Coenen; Jan Biessels; DeCarli; Fletcher; Maillard; Barkhof; Barnes; Benke; Boomsma; P.L.H. Chen; Dal-Bianco; Dewenter; Duering; Enzinger; Ewers; Exalto; Franzmeier; Groeneveld; Hilal; Hofer; Kuijf

INTRODUCTION
The spatial distribution of white matter hyperintensities (WMH) on MRI is often considered in the diagnostic evaluation of patients with cognitive problems. In some patients, clinicians may classify WMH patterns as “unusual”, but this is largely based on expert opinion, because detailed quantitative information about WMH distribution frequencies in a memory clinic setting is lacking. Here we report voxel wise 3D WMH distribution frequencies in a large multicenter dataset and also aimed to identify individuals with unusual WMH patterns.

METHODS
Individual participant data (N=3525, including 777 participants with subjective cognitive decline, 1389 participants with mild cognitive impairment and 1359 patients with dementia) from eleven memory clinic cohorts, recruited through the Meta VCI Map Consortium, were used. WMH segmentations were provided by participating centers or performed in Utrecht and registered to the Montreal Neurological Institute (MNI)-152 brain template for spatial normalization. To determine WMH distribution frequencies, we calculated WMH probability maps at voxel level. To identify individuals with unusual WMH patterns, region-of-interest (ROI) based WMH probability maps, rulebased scores, and a machine learning method (Local Outlier Factor (LOF)), were implemented.

RESULTS
WMH occurred in 82% of voxels from the white matter template with large variation between subjects. Only a small proportion of the white matter (1.7%), mainly in the periventricular areas, was affected by WMH in at least 20% of participants. A large portion of the total white matter was affected infrequently. Nevertheless, 93.8% of individual participants had lesions in voxels that were affected in less than 2% of the population, mainly located in subcortical areas. Only the machine learning method effectively identified individuals with unusual patterns, in particular subjects with asymmetric WMH distribution or with WMH at relatively rarely affected locations despite common locations not being affected.

DISCUSSION
Aggregating data from several memory clinic cohorts, we provide a detailed 3D map of WMH lesion distribution frequencies, that informs on common as well as rare localizations. The use of data-driven analysis with LOF can be used to identify unusual patterns, which might serve as an alert that rare causes of WMH should be considered.

Link | PDF (NeuroImage: Clinical)

 

3.2.1 Commonly affected locations

Despite the observation that 82% of the white matter could be affected by WMH, only few locations were affected in a substantial subset of participants. For example, only 1.7% of the white matter was affected in at least 20% of participants, 4.6% in at least 10%, and 9.9% in at least 5%. The periventricular areas—including frontal, occipital, and parietal—were most commonly affected. This was consistently observed in all three WMH tertiles. The centrum semiovale and corona radiata were relatively commonly affected by WMH in all three tertiles, but the overall probability increased with total normalized WMH volume.

3.2.2 Moderately frequent affected locations

Subcortical areas, just outside the periventricular areas commonly referred to as “deep”, were affected by WMH with moderate frequency and more often affected in the medium and high WMH tertiles. The frontal, occipital, and parietal areas were equally affected, with increasing probability as total normalized WMH volume increases. The temporal lobe was less frequently affected, compared to these other lobes; and rarely affected in the low and medium WMH tertiles.

3.2.3 Rarely affected locations

A large part of the white matter was rarely affected. For example, 68.3% was affected in less than 0.1% of participants, 30.4% in less than 1.0%, and 20.8% in less than 2.0%. All rarely affected WMH locations were widespread throughout the white matter. Even in the low WMH tertile, WMH could be present dispersed across rarely affected locations. The infratentorial regions were more rarely affected compared to the supratentorial white matter. When the infratentorial white matter was affected, WMH were mostly located in the pons. The basofrontal white matter and the temporal lobes were rarely affected by WMH, especially in the low and medium WMH tertiles. The internal capsule was also rarely affected, but in higher WMH tertiles WMH were sometimes present more cranially and in the anterior limb. Compared to the internal capsule, the external capsule was relatively more often affected in the medium and high WMH tertiles.

In the genu of the corpus callosum, WMH were almost never observed in any of the WMH tertiles. The body of the corpus callosum was hardly affected in the low / medium WMH tertiles and only sometimes in the high WMH tertile. This also held for the splenium, except that the septum pellucidum (at the splenium / CSF boundary) can appear hyperintense on FLAIR or T2 imaging and is sometimes classified as WMH. In Figure 3, the corpus callosum is part of multiple tracts. Given that the corpus callosum itself was rarely affected, the occurrence of WMH in these tracts was thus caused by the lateral extensions of each tract.

The grey matter in the basal ganglia contained some WMH for participants in the high WMH tertile. This is likely owing to the partial volume effect—where a single voxel can contain both gray and white matter—in combination with the used threshold of 30% for the presence of white matter in individual voxels of the MNI probabilistic atlas. In addition, this might also be partially attributed to technicalities, such as errors in the automatic segmentation or misregistration.

Eighteen% of the white mater was not affected by WMH in any of the participants, which mostly include juxtacortical white matter.

 

Really quite impressed by the quality and probable internal consistency of this, from my perspective, totally impenetrable gibberish.

Top work.