Two Classes of T1 Hypointense Lesions in Multiple Sclerosis With Different Clinical Relevance

Abstract

Background: Hypointense lesions on T1-weighted images have important clinical relevance in multiple sclerosis patients. Traditionally, spin-echo (SE) sequences are used to assess these lesions (termed black holes), but Fast Spoiled Gradient-Echo (FSPGR) sequences provide an excellent alternative. Objective: To determine whether the contrast difference between T1 hypointense lesions and the surrounding normal white matter is similar on the two sequences, whether different lesion types could be identified, and whether the clinical relevance of these lesions types are different. Methods: Seventy-nine multiple sclerosis patients' lesions were manually segmented, then registered to T1 sequences. Median intensity values of lesions were identified on all sequences, then K-means clustering was applied to assess whether distinct clusters of lesions can be defined based on intensity values on SE, FSPGR, and FLAIR sequences. The standardized intensity of the lesions in each cluster was compared to the intensity of the normal appearing white matter in order to see if lesions stand out from the white matter on a given sequence. Results: 100% of lesions on FSPGR images and 69% on SE sequence in cluster #1 exceeded a standardized lesion distance of Z = 2.3 (p < 0.05). In cluster #2, 78.7% of lesions on FSPGR and only 17.7% of lesions on SE sequence were above this cutoff value, meaning that these lesions were not easily seen on SE images. Lesion count in the second cluster (lesions less identifiable on SE) significantly correlated with the Expanded Disability Status Scale (EDSS) (R: 0.30, p ≤ 0.006) and with disease duration (R: 0.33, p ≤ 0.002). Conclusion: We showed that black holes can be separated into two distinct clusters based on their intensity values on various sequences, only one of which is related to clinical parameters. This emphasizes the joint role of FSPGR and SE sequences in the monitoring of MS patients and provides insight into the role of black holes in MS.

Keywords: MRI protocol; T1 hypointense lesions; black holes; clinical state; clustering; multiple sclerosis.

Figure 1

Standardized intensities of lesions on FSPGR and SE images. The median intensities of lesions were divided by the median intensity of the CSF, GM, and WM, respectively. Hence, a standardized intensity value of 1 would mean lesion intensity that does not stand out from the surrounding tissue intensity.

Figure 2

Separability of lesion clusters from white matter intensity in FSPGR and SE sequences. Histograms depict the probability density function of standardized lesion distance (see Methods for more details) for the two lesion type clusters on FSPGR and SE sequences. The vertical red line depicts a standardized lesion distance of Z = 2.3. PDF, probability density function.

Figure 3

The two clusters of lesions on FSPGR and SE images. Images on the left (A,C) are examples depict SE whilst images on the right (B,D) depict FSPGR for Cluster 1 (yellow circle) and Cluster 2 (red circle), respectively.

Figure 4

Clinical relevance of the lesion types. The subplots show the significant Spearman correlation plots (EDSS, Expanded Disability Status Scale; DD, disease duration; Cl-2 count, lesion count in the Cluster #2; Cl-2 volume, lesion volume in the Cluster #2; TLV, total lesion volume; NBV, normalized brain volume).