Lihui Li, Houbin Huang, Zhiye Chen,3＊?

1Department of Radiology, 2Department of Ophthalmology,Hainan Branch of Chinese PLA General Hospital, Sanya, Hainan 572013, China 3Department of Radiology, Chinese PLA General Hospital,Beijing, 100853, China

Key words: T2 fluid-attenuated inversion recovery imaging; magnetic resonance imaging;optic neuritis

Abstract The diagnosis of the recurrent optic neuritis is commonly established clinically, and sometimes it could be challenging because the involved optic nerve does not always show significant enhancement on conventional contrast enhanced-T1 weighted imaging (CE-T1WI). In this paper, we reported a middle-aged female with early diagnosis of recurrent optic neuritis using contrast-enhanced T2 fluid-attenuated inversion recovery imaging (CET2FLAIR). The involved optic nerve presented evident enhancement on CE-T2FLAIR and no enhancement on CE-T1WI. This case suggested that the CE-T2FLAIR may be a useful diagnostic tool specifically for the recurrent optic neuritis in clinical practice.

OPTIC neuritis is a common inflammatory disorder of the optic nerve, and MRI is the optimal modality to visualize the optic nerve. Typical MRI findings of optic neuritis were easily recognized in the posterior intraorbital optic nerve (ION),1where in more than 90% cases it manifests as swollen, high signal on T2WI, and enhancement on contrast-enhanced T1WI (CE-T1WI).2,3For the recurrent optic neuritis, the diagnosis may be challenging. From the clinical viewpoints, the clinical diagnosis of recurrent optic neuritis may be based on the typical clinical characteristics, such as moderate or severe visual loss, accompanied by visual field defects or loss of color vision.4CE-T1WI is regarded as an essential MRI evaluation tool for the imaging diagnosis of recurrent optic neuritis. Conventionally, the enhancement of optic nerve on CE-T1WI suggested the recurrent optic neuritis, and non-enhancement on CE-T1WI indicated the optic neuritis was in silent phase and there was no definite MRI evidence for the recurrence.Although CE-T1WI had shown a good diagnostic validity for the acute optic neuritis, with a high sensitivity of 94%, for recurrence of optic neuritis, the previously affected optic nerves usually present no abnormal enhancement.5Based on the mechanism of enhancement on MRI, the non-enhancement on CE-T1WI may indicate no or mild compromised blood-brain barrier, and concentration of MRI contrast agent in interstitial space may be too low to generate contrast enhancement on T1WI.6,7

The contrast-enhanced T2 fluid-attenuated inversion recovery imaging (CE-T2FLAIR) is sensitive to MRI contrast medium. It can detect low concentration of contrast agent in tissue and present enhancement,even there is no enhancement showed up on CE-T1WI.8This MRI technique had been widely used to detect multiple sclerosis lesions,9and small brain metastases.10CE-T2FLAIR had also been used to evaluate the diabetic retinopathy.8Therefore, CE-T2FLAIR may provide a new opportunity to clearly depict the involved optic nerve in patients with optic neuritis. In the current case of recurrent optic neuritis, the enhancement of ION was demonstrated on CE-T2FLAIR, while no enhancement on CE-T1WI was shown.

CASE DESCRIPTION

A 36-year-old female suffered from a sudden hypopsia of the right eye without definite incentive 3 days ago. She has history of right optic neuritis which was diagnosed 5 years ago. The patient was clinically suspicious for the right recurrent optic neuritis. Fundus photography examination confirmed that right papilla optica presented pale (Fig. 1). Optical coherence tomography (OCT) showed that the thickness of retinal nerve fiber layer (RNFL) in the inferior and temporal quadrant of the right eye decreased compared to that of the left side (Fig. 2). The patient was then subscribed for an orbital MRI examination.

Figure 1. Fundus photography examination of the right eye of a 36-year-old female. The right papilla optica presented pale on fundus photograph.

The MRI examination was performed by a 3.0T MR system with an eight-channel head coil (Magnetom skyra, Siemens, Germany), with the patient in supine position. The MR imaging sequences included axial T2 weighted imaging (T2WI), axial T1 weighted imaging(T1WI), and contrast enhanced T1WI (CE-T1WI). The T1WI parameters of plain and contrast enhanced scan were as follows: repetition time (TR) 600 ms, echo time(TE) 9 ms, Flip angle 150°, field of view (FOV) 18 cm×18 cm, matrix 320×320，slice thickness 3 mm, number of averages 2. The parameters of the plain and CE-T2FLAIR were as follow: TR 8500 ms, TE 86 ms,invertion time (TI) 2500 ms, FOV 16 cm×16 cm,matrix 256×256，slice thickness 3 mm, pixel size 0.625×0.625 mm2, number of averages 2. The contrast agent (Magnevist, 0.1 mmol/kg, Bayer Healthcare Pharmaceuticals Inc., NJ, USA) was manually injected intravenously. CE-T1WI and CE-T2FLAIR were reperformed 2 minutes sequentially after the administration of contrast agent.

Figure 2. Optical coherence tomography (OCT) of the right eye. The thickness of perioptic disc nerve fibers layer in the inferior and temporal quadrant decreased. T:temporal quadrant; N:nasal quadrant; S:superior quadrant; I:inferior quadrant.

On the axial T2WI, the right ION presented slightly swollen (diameter 3.8 mm) compared with the left ION (diameter 2.0 mm), and there was no evident abnormal signal observed. Post-contrast enhanced T1WI showed no abnormal enhancement of the right ION.The plain T2FLAIR demonstrated slight higher signal of the right ION compared with cerebral white matter. On the CE-T2FLAIR, the posterior two third of right ION presented significant contrast enhancement, while the left ION showed no enhancement (Fig. 3).

After admission, the patient received corticosteroid impulse therapy (methylprednisolone, 0.5 g/day,3 days), followed by an oral adapter (starting dose 1 mg/kg/day), neurotrophic therapy (mouse nerve growth factor, 0.00003 g/day, 8 days), and microcirculation improving therapy by using extract of Ginkgo Biloba Leaves Injection (0.0875 g/day, 7 days). The visual acuity of the right eye improved from 0.12 on admission to 0.2 (tested by the standard table of vision logarithms at 5 m) when discharged.

DISCUSSION

In this case, the right ION did not presented enhancement on CE-T1WI, which suggested the right ION was not in active phase of optical neuritis according to the conventional understanding about typical MRI findings in the recurrent optic neuritis. The non-enhancement on CE-T1WI indicated that the blood-optic nerve barrier (BONB) was not destructed and had no MRI contrast leaking into the extracellular space according to the conventional contrast enhancement theory.8

CE-T2FLAIR sequence did provide an opportunity to decode these complicated conditions. T2FLAIR sequence belongs to the inversion recovery (IR) pulse sequences, which has heavy T2WI effect associated with the long repetition time (TR)，long echo time (TE),and a mild T1WI effect related with the long inversion time (TI).8CE-T2FLAIR is sensitive to low concentration of contrast agent in tissue, and could present a contrast enhancement even when there is a negative enhancement on CE-T1WI. As described above, the right ION did present enhancement on CE-T2FLAIR without enhancement on CE-T1WI in this case, which indicated that the inflammation of the right ION was in active phase of optical neuritis, Moreover, the enhancement on CE-T2FLAIR also indicated the destructed BONB and the leakage of contrast agent into the extravascular extracellular space of the ION. Therefore, the quantitative dynamic contrast enhanced imaging11will be helpful to throw a light on the underlying neuromechanism.

According to the characteristics of high sensitivity of T2FLAIR to the low concentration of MRI contrast agent, CE-T2FLAIR had been used in the diagnoses and theraputic evaluation of multiple sclerosis,9,12,13meningeal disorders,14-18small brain metastases,10,19,20pituitary microadenoma,21idiopathic sudden sensorineural hearing loss,22-28inflammatory disorder of cranial nerve,8,29uveitis30and cerebellar hemangioblastoma.31For these disorders, CE-T2FLAIR not only help in early diagnosis of the disease, but also better delineation of the lesions, which may bring about prompt treatment and better prognosis.

Figure 3. MR imaging findings in a 36-year-old woman with recurrent optic neuritis in the right intraorbital optic nerve(ION). A and D, axial and sagital post-contrast T1WI; B and E, axial and sagital pre-contrast T2FLAIR; C and F, axial and sagital post-contrast T2FLAIR. The right ION presented no enhancement on CE-T1WI (A and D, arrowheads), slightly hyperintensity on pre-contrast T2FLAIR (B and E, arrowheads) images compared with the cerebral white matter, and significant enhancement on post-contrast T2FLAIR (C and F, arrowheads) images.

Although the previous study had reported that CE-T2FLAIR could increase the sensitivity, specificity and accuracy of acute optic neuritis,32the recurrent optic neuritis has not been evaluated by the CET2FLAIR by far. In this case, we successfully utilized the CE-T2FLAIR sequence to diagnose recurrent optic neuritis, and thus provided direct imaging evidence for the clinical diagnosis in this patient. Once the diagnosis of recurrent optic neuritis has been established, the glucocorticoid pulse therapy can be performed timely,and to save the visual acuity of the patient can be possible.

The current case study suggested a potential utility of CE-T2FLAIR in diagnosis of recurrent optic neuritis. The benefit of CE-T2FLAIR lies in the following aspects: 1. it can detect the lesion in early stage, especially for inflammatory diseases; 2. as a conventional MRI sequence which can be performed at any MRI scanner, it has a good feasibility in the clinical practice;3. it could provide direct imaging evidence for the recurrence of optic neuritis. Further investigations using quantitative dynamic contrast enhancement are needed to explore the neuromechanism of enhancement on CE-T2FLAIR. Additionally, the relationship between CE-T2FLAIR findings and visual impairment should be studied in the future for the outcome prediction of recurrent optic neuritis.

REFERENCES

1. Khanna S, Sharma A, Huecker J, et al. Magnetic resonance imaging of optic neuritis in patients with neuromyelitis optica versus multiple sclerosis. J Neuroophthalmol 2012; 32(3): 216-20. doi: 10.1097/WNO.0b013e318254c62d.

2. Kupersmith MJ, Alban T, Zeiあer B, et al. Contrast-enhanced MRI in acute optic neuritis: relationship to visual performance. Brain 2002; 125(Pt 4): 812-22.doi: 10.1093/brain/awf087.

3. Rizzo JF, 3rd, Andreoli CM, Rabinov JD. Use of magnetic resonance imaging to diあerentiate optic neuritis and nonarteritic anterior ischemic optic neuropathy.Ophthalmology 2002; 109(9): 1679-84. doi: 10.1016/S0161-6420(02)01148-X.

4. Kurne A, Karabudak R, Yalcin-Cakmakli G, et al. Recurrent optic neuritis: clues from a long-term follow up study of recurrent and bilateral optic neuritis patients. Eye Brain 2010; 2: 15-20.

5. Kupersmith MJ, Alban T, Zeiあer B, et al. Contrast-enhanced MRI in acute optic neuritis: relationship to visual performance. Brain 2002; 125(Pt 4): 812-22.doi: 10.1093/brain/awf087.

6. Kirsch JE. Basic principles of magnetic resonance contrast agents. Top Magn Reson Imaging 1991; 3(2):1-18. doi: 10.1097/00002142-199103000-00003.

7. Lee DH. Mechanisms of contrast enhancement in magnetic resonance imaging. Can Assoc Radiol J 1991; 42(1): 6-12.

8. Lee EK, Lee EJ, Kim S, et al. Importance of Contrast-Enhanced fluid-attenuated inversion recovery magnetic resonance imaging in various intracranial pathologic conditions. Korean J Radiol 2016; 17(1):127-41. doi: 10.3348/kjr.2016.17.1.127.

9. Bagheri MH, Meshksar A, Nabavizadeh SA, et al. Diagnostic value of contrast-enhanced fluid-attenuated inversion-recovery and delayed contrast-enhanced brain MRI in multiple sclerosis. Acad Radiol 2008;15(1): 15-23. doi: 10.1016/j.acra.2007.07.022.

10. Ahn SJ, Chung TS, Chang JH, et al. The added value of double dose gadolinium enhanced 3D T2 fluid-attenuated inversion recovery for evaluating small brain metastases. Yonsei Med J 2014; 55(5): 1231-7. doi:10.3349/ymj.2014.55.5.1231.

11. Paldino MJ, Barboriak DP. Fundamentals of quantitative dynamic contrast-enhanced MR imaging. Magn Reson Imaging Clin N Am 2009; 17(2): 277-89. doi:10.1016/j.mric.2009.01.007.

12. Vuolo L, Absinta M, Sweeney E, et al. MRI-based detection and characterization of leptomeningeal contrast enhancement in multiple sclerosis. Neurology 2014; 82 (suppl 10): P6.134.

13. Reich D, Rao A, Vuolo L, et al. Leptomeningeal contrast enhancement in multiple sclerosis: A possible marker of inflammation in the subarachnoid space.Neurology 2014;82(10 Supplement):S44.001.

14. Splendiani A, Puglielli E, De Amicis R, et al. Contrast-enhanced FLAIR in the early diagnosis of infectious meningitis. Neuroradiology 2005; 47(8): 591-8.doi: 10.1007/s00234-005-1383-7.

15. Utz MJ, Tamber MS, Mason GE, et al. Contrast-enhanced 3-dimensional fluid-attenuated inversion recovery sequences have greater sensitivity for detection of leptomeningeal metastases in pediatric brain tumors compared with conventional spoiled gradient echo sequences. J Pediatr Hematol Oncol 2018;40(4): 316-9. doi: 10.1097/MPH.0000000000000957.

16. Azad R, Tayal M, Azad S, et al. Qualitative and quantitative comparison of contrast-enhanced fluid-attenuated inversion recovery, magnetization transfer spin echo, and fat-saturation T1-weighted sequences in infectious meningitis. Korean J Radiol 2017; 18(6):973-82. doi: 10.3348/kjr.2017.18.6.973.

17. Fukuoka H, Hirai T, Okuda T, et al. Comparison of the added value of contrast-enhanced 3D fluid-attenuated inversion recovery and magnetization-prepared rapid acquisition of gradient echo sequences in relation to conventional postcontrast T1-weighted images for the evaluation of leptomeningeal diseases at 3T. AJNR Am J Neuroradiol 2010; 31(5): 868-73. doi: 10.3174/ajnr.A1937.

18. Kim HJ. Importance of contrast-enhanced fluid-attenuated inversion recovery imaging to detect paradoxical expansion of tuberculoma. Int J Infect Dis 2014;24: 37-9. doi: 10.1016/j.ijid.2014.03.1383.

19. Chen W, Wang L, Zhu W, et al. Multicontrast single-slab 3D MRI to detect cerebral metastasis. AJR Am J Roentgenol 2012; 198(1): 27-32. doi: 10.2214/AJR.11.7030.

20. Ercan N, Gultekin S, Celik H, et al. Diagnostic value of contrast-enhanced fluid-attenuated inversion recovery MR imaging of intracranial metastases. Am J Neuroradiol 2004; 25(5): 761-5.

21. Chatain GP, Patronas N, Smirniotopoulos JG, et al. Potential utility of FLAIR in MRI-negative Cushing's disease. J Neurosurg 2017: 1-9. doi: 10.3171/2017.4. JNS17234.

22. Berrettini S, Seccia V, Fortunato S, et al. Analysis of the 3-dimensional fluid-attenuated inversion-recovery (3D-FLAIR) sequence in idiopathic sudden sensorineural hearing loss. JAMA Otolaryngol Head Neck Surg 2013; 139(5): 456-64. doi: 10.1001/jamaoto.2013.2659.

23. Sone M, Mizuno T, Sugiura M, et al. Three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging investigation of inner ear disturbances in cases of middle ear cholesteatoma with labyrinthine fistula. Otol Neurotol 2007; 28(8): 1029-33. doi:10.1097/MAO.0b013e3181587d95.

24. Gao Z, Chi FL. The clinical value of three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging in patients with idiopathic sudden sensorineural hearing loss: a meta-analysis.Otol Neurotol 2014; 35(10): 1730-5. doi: 10.1097/MAO.0000000000000611.

25. Tanigawa T, Shibata R, Tanaka H, et al. Usefulness of three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging to detect inner-ear abnormalities in patients with sudden sensorineural hearing loss. J Laryngol Otol 2015; 129(1): 11-5. doi:10.1017/S0022215114003028.

26. Ryu IS, Yoon TH, Ahn JH, et al. Three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging in sudden sensorineural hearing loss:correlations with audiologic and vestibular testing.Otol Neurotol 2011; 32(8): 1205-9. doi: 10.1097/MAO.0b013e31822e969f.

27. Lee HY, Jung SY, Park MS, et al. Feasibility of three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging as a prognostic factor in patients with sudden hearing loss. Eur Arch Otorhinolaryngol 2012; 269(8): 1885-91. doi: 10.1007/s00405-011-1834-1.

28. Kato M, Katayama N, Naganawa S, et al. Three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging findings in a patient with relapsing polychondritis. J Laryngol Otol 2014; 128(2):192-4. doi: 10.1017/S0022215113003587.

29. Seo JH, You SK, Lee IH, et al. Quantitative analysis of the facial nerve using contrast-enhanced three dimensional FLAIR-VISTA imaging in pediatric Bell's Palsy.Investig Magn Reson Imaging 2015; 19(3): 162-7.doi: 10.13104/imri.2015.19.3.162.

30. Herrera DA, Franco S, Bustamante S, et al. Contrast-enhanced T2-FLAIR MR imaging in patients with uveitis. Int Ophthalmol 2017; 37(3): 507-12. doi:10.1007/s10792-016-0289-1.

31. Chen Z, Liu M, Ma L. Diagnostic value of contrast-enhanced T2-weighted-fluid-attenuated Inversion recovery MR imaging of cerebellar hemangioblastoma:a case report. Zhong guo yi Xue Ke Xue Yuan Xue Bao, 2017; 39(2): 296-9. Chinese. doi: 10.3881/j.issn.1000-503X.2017.02.022.

32. Boegel KH, Tyan AE, Iyer VR, et al. Utility of coronal contrast-enhanced fat-suppressed FLAIR in the evaluation of optic neuropathy and atrophy.Eur J Radiol Open 2017; 4: 13-8. doi: 10.1016/j.ejro.2017.02.002.