T2-relaxation mapping and fat fraction assessment to objectively quantify clinical activity in thyroid eye disease: an initial feasibility study

Das, Tilak; Roos, Jonathan C. P.; Patterson, Andrew J.; Graves, Martin J.; Murthy, Rachna

doi:10.1038/s41433-018-0304-z

Cited by 47 publications

(49 citation statements)

References 35 publications

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“…The need for improved means by which to assess clinical activity in TED is also highlighted by this case. We used MRI T2-relaxation times with fat fraction mapping [15] in combination with circulating TRAb levels [16] to determine that the disease in our patient was still active despite the patient's clinical activity score [17] being low. With his 'white eye', it would have been relatively easy to assume disease inactivity.…”

Section: Discussionmentioning

confidence: 99%

Sirolimus (rapamycin) for the targeted treatment of the fibrotic sequelae of Graves’ orbitopathy

Roos

Murthy

2019

Eye

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Background Rapamycin (alternatively known as sirolimus) is a macrolide immunosuppressant commonly used for organ transplantation. It acts both on lymphocytes through the mechanistic target of rapamycin (mTOR) pathway to reduce their sensitivity to interleukin-2 (IL-2) and, importantly, also has anti-fibrotic properties by acting on myofibroblasts. The latter have been implicated in the pathogenesis of thyroid eye disease (TED). Aim To describe successful treatment and reversal of extraocular muscle fibrosis in TED with sirolimus. Methods Case report and literature review with clinic-pathological correlation. Results A patient with Graves' orbitopathy (GO) developed significant ocular motility restriction, which was unresponsive to steroids and conventional immunosuppression. Unlike these prior treatments, rapamycin therapy improved the diplopia and fields of binocular single vision over a period of months. There were no adverse effects directly attributable to the treatment. Conclusion With its low renal toxicity and ability to specifically target the underlying fibrotic pathways in GO, rapamycin may prove a useful adjunct to standard immunosuppressive regimes. We encourage further reporting of case series or the instigation of controlled trial. * Rachna Murthy

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Section: Discussionmentioning

confidence: 99%

Sirolimus (rapamycin) for the targeted treatment of the fibrotic sequelae of Graves’ orbitopathy

Roos

Murthy

2019

Eye

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“…In MG there is histological evidence for fat replacement, fibrosis and atrophy of the EOM, 16 while in GO the EOM are known to be swollen and inflamed at an early stage, and fat-replaced and fibrotic at a later stage of the disease. 17 However, the EOM are challenging to assess with quantitative MRI. Since they are small, the high resolution needed for MRI of these muscles results in a poor signal-to-noise ratio (SNR).…”

Section: Introductionmentioning

confidence: 99%

The feasibility of quantitative MRI of extra‐ocular muscles in myasthenia gravis and Graves' orbitopathy

et al. 2020

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Although quantitative MRI can be instrumental in the diagnosis and assessment of disease progression in orbital diseases involving the extra‐ocular muscles (EOM), acquisition can be challenging as EOM are small and prone to eye‐motion artefacts. We explored the feasibility of assessing fat fractions (FF), muscle volumes and water T2 (T2 water ) of EOM in healthy controls (HC), myasthenia gravis (MG) and Graves' orbitopathy (GO) patients. FF, EOM volumes and T2 water values were determined in 12 HC (aged 22‐65 years), 11 MG (aged 28‐71 years) and six GO (aged 28‐64 years) patients at 7 T using Dixon and multi‐echo spin‐echo sequences. The EOM were semi‐automatically 3D‐segmented by two independent observers. MANOVA and t‐tests were used to assess differences in FF, T2 water and volume of EOM between groups ( P < .05). Bland–Altman limits of agreement (LoA) were used to assess the reproducibility of segmentations and Dixon scans. The scans were well tolerated by all subjects. The bias in FF between the repeated Dixon scans was −0.7% (LoA: ±2.1%) for the different observers; the bias in FF was −0.3% (LoA: ±2.8%) and 0.03 cm 3 (LoA: ± 0.36 cm 3 ) for volume. Mean FF of EOM in MG (14.1% ± 1.6%) was higher than in HC (10.4% ± 2.5%). Mean muscle volume was higher in both GO (1.2 ± 0.4 cm 3 ) and MG (0.8 ± 0.2 cm 3 ) compared with HC (0.6 ± 0.2 cm 3 ). The average T2 water for all EOM was 24.6 ± 4.0 ms for HC, 24.0 ± 4.7 ms for MG patients and 27.4 ± 4.2 ms for the GO patient. Quantitative MRI at 7 T is feasible for measuring FF and muscle volumes of EOM in HC, MG and GO patients. The measured T2 water was on average comparable with skeletal muscle, although with higher variation between subjects. The increased FF in the EOM in MG patients suggests that EOM involvement in MG is accompanied by fat replacement. The unexpected EOM volume increase in MG may provide novel insights into underlying pathophysiological processes.

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“…In contrast, inactive phase is characterized by interstitial fibrosis and collagen deposition (2,3). Given that T2RT value could increase in edematous muscle and decrease in fibrotic tissue, it would not be surprising that active TAOs had prolonged T2RT of EOMs than that of inactive ones (26). In addition, T2RT-max and T2RT-hot demonstrated better diagnostic performance than other T2RT-derived indicators, while the variation of AUC between T2RT-max and T2RT-hot was of no significance.…”

Section: Discussionmentioning

confidence: 99%

Utility of T2 mapping in the staging of thyroid-associated ophthalmopathy: efficiency of region of interest selection methods

Chen

et al. 2020

Acta Radiol

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Background Discriminating the stage of thyroid-associated ophthalmopathy (TAO) is crucial for the treatment strategy and prognosis prediction. Utility of conventional magnetic resonance imaging in the disease staging is limited. Purpose To investigate the performance of T2 mapping based on different region of interest (ROI) selection methods in the staging of TAO. Material and Methods Thirty-two patients with TAO were retrospectively enrolled. Two radiologists independently measured the T2 relaxation time (T2RT) of extraocular muscles using two different ROIs (hotspot [ROIHS]: T2RT-hot; single-slice [ROISS]: T2RT-mean, T2RT-max, T2RT-min). Independent-samples t test, Wilcoxon signed rank test, Spearman correlation analysis, receiver operating characteristic (ROC) curves analyses, multiple ROC comparisons, and intra-class correlation coefficient (ICC) were used for statistical analyses. Results No significant difference was found in the measuring time between ROIHS and ROISS methods ( P = 0.066). T2RT-mean demonstrated the highest ICC for measurement, followed by T2RT-max and T2RT-min, and T2RT-hot showed the poorest reproducibility. Active TAOs showed significantly higher values for all the T2RTs than inactive mimics (all P < 0.001). Significant positive correlations were found between T2RTs and CAS (all P < 0.005). T2RT-hot and T2RT-max showed significantly higher areas under the curve than that of T2RT-mean ( P = 0.013 and 0.024, respectively), while the difference between T2RT-hot and T2RT-max was not significant ( P = 0.970). Conclusion The T2RTs derived from both ROI selection methods could be useful for the staging of TAO. The results of measuring time, reproducibility, and diagnostic performance suggest that T2RT-max would be the optimal indicator for staging.

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T2-relaxation mapping and fat fraction assessment to objectively quantify clinical activity in thyroid eye disease: an initial feasibility study

Cited by 47 publications

References 35 publications

Sirolimus (rapamycin) for the targeted treatment of the fibrotic sequelae of Graves’ orbitopathy

Sirolimus (rapamycin) for the targeted treatment of the fibrotic sequelae of Graves’ orbitopathy

The feasibility of quantitative MRI of extra‐ocular muscles in myasthenia gravis and Graves' orbitopathy

Utility of T2 mapping in the staging of thyroid-associated ophthalmopathy: efficiency of region of interest selection methods

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