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Diagnostic value of Gd-contrast administration for spinal cord MRI in MS patients and T2 signal ratio as a predictive marker of lesion activity
Kianush Karimian-Jazi1, Ulf Neuberger1, Katharina Schregel1, Gianluca Brugnara1, Daniel Schwarz1, Laura Jäger2, Wolfgang Wick2, Martin Bendszus1, and Michael Oliver Breckwoldt1
1Neuroradiology, University Clinic of Heidelberg, Heidelberg, Germany, 2Neurology, University Clinic of Heidelberg, Heidelberg, Germany

Synopsis

Our study shows that patients with a stable, spinal T2 lesion load do not benefit from the administration of GBCAs. In contrast to our previous cerebral study, there was no indication of spinal lesion re-activation. The T2 signal ratio has a high sensitivity and specificity to “predict” contrast enhancement of a given lesion and could be used as a predictive marker for “lesion activity”. In combination with previously published studies on the limited value of Gd-administration in cerebral MS follow-up investigations, we propose a “single-shot” MS protocol to combine cerebral and spinal MRI investigations in one standardized single MR protocol.

Objectives

MRI is the most important paraclinical parameter for diagnosis and monitoring of patients with multiple sclerosis (MS). Although spinal MS is often associated with coexisting cerebral lesions, 20% of spinal MS lesions are isolated. Also, spinal lesions are a known predictor of disease severity. Similar to cerebral MRI, gadolinium-based contrast agents (GBCAs) are routinely used in follow-up spinal MRI to detect Gd-contrast enhancement (CE) as a marker of acute inflammation. Recently, there have been major safety concerns regarding Gd-accumulation in deep cerebellar nuclei after multiple injections of linear GBCAs. So, assessing the diagnostic value of Gd administration for all indications is warranted. Our recent study on cerebral follow-up MRI examinations of MS patients demonstrated that Gd contrast administration might be dispensable if T2 lesions are stable compared to the previous examination. In cerebral MS we identified a small fraction of lesions (<5%) for which Gd-administration added diagnostic value (re-activated lesions, CE lesions not discernable and T2-w imaging). Previous studies have focused on cerebral MRI, whereas the diagnostic value of Gd-administration for spinal MRI has not been evaluated so far. It is conceivable that the importance of Gd-administration in spinal MRI is higher compared to cerebral MRI given the small anatomical structure of the spinal cord with less signal to noise, artifact-prone scanning and fewer available MR sequences. The present study investigates whether the routine administration of GBCAs is justified in all follow-up spinal examinations in a retrospective design in 65 patients (total of 257 MRIs). This seems relevant because detecting T2 lesions in the spinal cord can be challenging, especially for small and lateral cord lesions due to partial volume effects. We assessed MRI investigations in a cohort of patients to quantify disease activity on T2-w and contrast-enhanced T1-w imaging. Furthermore, we compared spinal and cerebral examinations in each patients during relapses to investigate correlative patterns of disease activity and to evaluate if Gd administration may be justified for spinal MRI if there is proven disease activity on cerebral MRI and vice versa. Furthermore, we investigated whether the degree of lesion “edema” quantified by the T2 signal ratio (T2 signal lesion / T2 signal normal appearing spinal cord) might be a predictor of contrast enhancement.

Methods

We included 65 Multiple sclerosis (MS) patients with at least two spinal MRI follow-up examinations (mean follow-up time: 4.6 ± 2.4 years; mean number of MRIs: 3.9 ± 1.7; total number of MRI follow-up examinations: 192). Spinal MRI was performed at 3 Tesla with a standardized protocol including sagittal and axial T2-w TSE and T1-w TSE post contrast enhanced sequences. Images were analyzed for T2 and T1 contrast-enhancing lesions by two independent neuroradiologists. MS lesions were further assessed for size, localization and T2 signal ratio (T2 SR: signal lesion/T2 signal normal appearing spinal cord). Cerebral MRI investigations of the respective patients were reviewed to determine the odds ratio for concomitant disease activity at each site.

Results

We identified a total of 68 newly developing spinal T2 lesions and 20 contrast-enhancing lesions during follow-up. New T2 lesions were present in 23 % (44/192) of the follow-up scans. Each enhancing lesion had a clear correlate as a new T2 lesion. As a predictive factor for lesion enhancement we found that enhancing lesions had a higher T2 SR compared to non-enhancing lesions (SR: 2.0 ± 0.4 vs 1.4 ± 0.2, ****p<0.001). ROC analysis showed a cut-off value of SR 1.78 to predict lesion enhancement with 82 % sensitivity and 97 % specificity. Disease activity defined as newly occurring T2 lesion on cerebral MRI scans predicted disease activity on spinal MRI and vice versa whereas concomitant enhancement was less frequent.

Conclusion

Our study indicates that Gd-contrast administration is dispensable in follow-up spinal MRI of MS patients if no new T2 lesions are present. As a predictor for enhancing, “active” lesions we show high sensitivity and specificity of the T2 signal ratio. In conjunction with our previous cerebral MS study, we propose a shortened, single MRI investigation for routine follow-up MRI of the clinically stable MS patient combining spinal and cerebral MRI without Gd-contrast administration as a “one stop shop” strategy.

Acknowledgements

The authors thank L. Diebold, Dr. S. Bonekamp and T. Badrow (Neuroradiology Department, University Hospital Heidelberg) for organizational and technical support of this study. K. Karimian-Jazi, M.O. Breckwoldt and M. Bendszus were supported by the Novartis Foundation for Therapeutic Research (Nürnberg, Germany). The funders had no influence in the design, analysis, or interpretation of the study.

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Figures

Fig. 1 Comparison of baseline and follow-up MRI of MS patients: Enhancing and nonenhancing T2 lesions show significant differences in size on baseline-MRI (n=183; n=25) and follow-up MRI (n=135 non-enhancing lesions; n=44 enhancing lesions; A, B; *p < 0.05). Box shows the 25th and 75th quartile. Whiskers indicate the minimum and maximum values.

Fig. 2 T2-w and T1-w contrast enhanced images (A, B). Size of the T2 lesion weakly correlates with the size of the contrast enhancement (C). Pearson correlation analysis, r2 = 0.17, **p < 0.01, n = 44 lesions).

Fig. 3 Representative MRI images of axial T2-w and T1-w CE images showing different lesion morphologies. (A) T2 lesion without corresponding enhancement and a low T2 signal ratio (SR: 1.54). (B) Ring-enhancing lesion with a T2 SR of 1.78. (C) T2 lesion with a high T2 signal ratio (SR: 1.93) and clear contrast-enhancement. (D) Nodularenhancing lesions (n=33) showed significantly higher T2 signal ratios than nonenhancing (n=185, ****p<0.0001) and ring-shaped enhancing lesions (n=5 ****p<0.0001). NASC: normal appearing spinal cord.

Fig. 4 ROC analysis of T2-w signal ratio and likelihood of enhancement. Blue dot indicates the optimal threshold value for the T2 signal ratio of 1.78 (AUC 0.94, sensitivity 0.82, specificity 0.97) to discriminate Gd-enhancing vs non-enhancing lesions. This indicates that the severity of edema correlates with the probability of enhancement.

Table 1 MRI sequence parameters
Abbreviations: FOV = field of view; TE = echo time; TR = repetition time; TSE = turbo spin echo.

Table 2 Clinical characteristics of study patients
Abbreviations: EDSS = Expanded Disability Status Scale; PP = primary progressive MS; RR = relapsing-remitting MS; SP = secondary progressive MS. Values are shown as mean ± SD (range) for age and disease duration (years after first symptoms of MS) and median (range) for follow-up MRI. # number

Table 3 Lesion characteristics
Abbreviations: # number

Table 4

Proc. Intl. Soc. Mag. Reson. Med. 29 (2021)
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