Keiko Toyoda, Takahiro Haruyama, Hiroshi Oba, Tomonori Kanda, Megumi Matsuda, Marie Osawa,

1. Usefulness of Gd-enhanced 3D T2 fluid-attenuated inversion recovery imaging in various infectious meningitis Keiko Toyoda, Takahiro Haruyama, Hiroshi Oba, TomonoriKanda, Megumi Matsuda, Marie Osawa, Shigeru Furui Department of Radiology Teikyo University School of Medicine 53th Annual meeting of the American Society of Neuroradiology Poster #: EP-30 April 2015 Chicago

2. No disclosure

3. Background and purpose • T2-FLAIR imaging with Gd administration is useful for detecting superficial abnormalities, e.g. “sulcal hyperintensity” however, • CSF pulsation artifacts and flow artifacts can be problematic. • lesions may be somewhat difficult to detect in the CSF spaces. • 3D T2-FLAIR imaging on 3 Tesla MR systems • can be acquired in a clinically acceptable scan time. • can obtain 3D volume data with fewer partial volume artifacts. • can eliminate or suppress flow artifacts. • can better suppress signals from the cerebrospinal fluid. • The purpose of this study is • To compared (CE) 3D T2-FLAIR with CE T1WI in the depiction of abnormal leptomeningeal hyperintensities and enhancement in cases with leptomeningitis, and • To determine the usefulness of contrast-enhanced 3D T2-FLAIR.

4. Materials and Methods • The subjects • 35 consecutive cases diagnosed with acute meningitis or meningoencephalitis based on clinical symptoms and spinal fluid findings • 17 y.o. - 81 y.o. 21 male 14 female • Gd-enhanced T1-weighted & Gd-enhanced 3D FLAIR images obtained in the same examination • Between April 2010 and September 2014 • Typesofinfection • Bacterial 13 cases(including: those suspected by polynucleosis in CSF; excluding tuberculosis) • Streptococcus pneumoniae 6 • Others 7 • Tuberculous （adenosine deaminase (ADA) ↑） 8 • Viral （including aseptic; mononucleosis (CSF)) 11 • Others （SLE, autoimmune, unknown） 3

5. MR Protocol for Meningitis • MRI machine: 3T GE Signa HDxt • Enhancement studies{A) & B)} with injection of Gd-DTPA 0.1mmol/kg BW • 3D T2 FLAIR image “Cube” all casesTR 8000; TE 107-108;Inversion time 2200;ETL 150; Slice thickness1.4mm; Matrix 256x192; FOV 24cm; Acquisition time5m55s • T1-weighted imaging: Performedone of the following two techniquesB)-1SPGR (3D GRE) 31 / 35 casesSpoiled Gradient Recalled Echo (SPGR) TR 6.9–7.0; TE 3.15 ; Slice thickness 1.4mm; Matrix 352x256; FOV 22cm; Acquisition time3m51sB)-2 T1 3D Cube (3D TSE) 4 / 35 cases TR 600; TE 10.9; ETL 28; Slice thickness1.4mm; Matrix 352x256; FOV 22cm; Arc 2; Acquisition time 3m45s • Sequence of thetwo enhancement studies: B)　⇒　A):16/35 cases; A)　⇒　B):19/35cases • Other sequences: T2WI: TR6200; TE 84;ETL14;512x320; FOV 22cmEPI DWI: TR 8000;128x192; FOV 24cm or

6. Evaluation • Comparison of: Post-contrast 3D T2-FLAIR(CE 3D T2-FLAIR), and Post-contrast T1WIs(CE T1-WI) on meningeal findings • Abnormal findings in leptomeningens: • CE 3D T2-FLAIR: abnormal hyperintensity (or enhancement) in sulci cistern • CE T1WI: abnormal enhancement in sulci or cistern • Divided cistern and sulci:Each CSF space was visually evaluated on both CE 3D T2-FLAIR and CE T1WI in same slices, side by side, by two experienced neuroradiologists • Determined the better sequence for depicting abnormal findings in each cistern and sulcus • Cistern: 1. medullary cistern; 2. prepontine cistern; 3. interpeduncular cistern; 4. suprasellar cistern; • Sulcus: 5. Sylvian fissure; 6. cerebellar hemisphere; 7. frontal lobe; 8. occipital lobe; 9. parietal lobe; 10. temporal lobe • Other findings: Subdural space; Ventricular wall; White and Gray matter • Axial images mainly used; and coronal or sagittal images.

7. Results • Of 35 cases5 cases No abnormal findings on both CE T2 FLAIR and CE T1WI. • These included one case of bacterial meningitis, and 4 cases of aseptic meningitis. • 30 casessome hyperintensities (or enhancement) in sulci or cistern on CE 3D T2 FLAIR. • In almost all cases, these hyperintensities (or enhancement) were easier to appreciate on 3D CE T2 FLAIR than on 3D T1WI; Lesions were better depicted on CE 3D T2 FLAIR. • In bacterial meningitis, including pneumococcal, scattered nodular hyperitensities wereseen on the brain surface particularly in the deep portion of cistern or sulci (interpeducular cistern, Sylvian fissure, or sulci) • Viral meningitis ( total 11 cases) was mostly of the pial-subarachinoid type, with a thinenhancement effect when there were abnormal findings. On CE 3D T2 FLAIR, cerebral fissure enhancement was seen to be diffuse, being especially prominent in the cerebral sulci of the parietal and occipital lobes. On the contrary, in 4 out of 11 cases no abnormal enhancement effect was present in the sulci or cistern. • In tuberculous meningitis (total 8 cases), diagnosed on the basis of positive ADA, CE 3D T2 FLAIR showed diffuse high signal intensity in the cerebral cistern and sulci in almost all cases.

8. Results Cases of positive abnormal findings (depicting possible abnormalities) in each cistern or sulci, and these are more visible or equal onT2 FLAIR than on T1WI

9. 52 y.o. male with bacterial meningitis (Strept. Pneumoniae) CE T2 FLAIR CE SPGR

10. DWI DWI • CE3D T2 FLAIR shows scattered small or nodular hyperintensities in interpeduncular cistern and Sylvian fissure, with corresponding hyperintensities on DWI. • Localized dural thickening and enhancement effect in frontal subdural space. • These lesions are not depicted on CE SPGR. • Sagittal CE 3D T2FLAIRalso showshyperintensityininterpeduncularcistern.

11. 81y.o. female with bacterial meningitis (Strep. Pneumoniae) CE T2 FLAIR • CE3D T2 FLAIR shows scattered small or nodular hyperintensities in interpeduncular cistern and Sylvian fissure, frontal and temporal sulci, corresponding to hyperintense lesions on DWI. These lesions are not depicted on CE SPGR (Not shown). DWI

12. 46 y.o. male with tuberculous meningitis CE T2 FLAIR CE 3D T2 FLAIR shows diffuse high signal intensity along the cerebral cistern and sulci. Medullary and prepontine cisterns are involved. CE SPGR

13. CE T2 FLAIR 27 y.o. female with tuberculous meningitis CE 3D T2 FLAIR shows diffuse high signal intensity along the cerebral cistern and sulci. Prepotine and interpeduncular cistern are involved. CE T1Cube

14. 79 y.o.female with aseptic meningitis (viral S/O) CE T2 FLAIR CE 3D T2 FLAIR shows pial-subarachinoidal hyperitensity in cerebellar, temporal and occipital sulci, especially on the left side. CE SPGR v

15. CE T2 FLAIR 44 y.o. male with viral meningitis CE 3D T2 FLAIR shows diffuse, thin pial-subarachinoid hyperintensity, especially in occipital to parietal lobes. Hyperitensity is also noted in splenium of corpus callosum. CE SPGR Tanaka Itaru

16. Discussion1/4 Contrast-enhanced FLAIR imaging has been reported as having higher sensitivity for detecting leptomeningeal disease compared with contrast-enhanced T1-WI imaging. However, concerns regarding its utility have been raised. CSF pulsation artifacts on 2D T2-FLAIR images may render the detection of lesions in the CSF spaces difficult. In a large series by Singh et al, they reviewed 74 MR images of suspected leptomeningeal metastases. Results proved that fast FLAIR was less sensitive than standard T1-WI spin-echo sequences for detecting contrast enhancement of neoplastic leptomeningeal disease (2002). Galassi et al also reported that CE T1-WI MR imaging with FS is superior to contrast-enhanced FLAIR imaging in most cases for depicting a variety of meningeal diseases (infections, meningitis or leptomeningeal metastasis). The contrast between the enhancing lesions and non-enhancing tissue was greater on CE T1WI (2005). These studies used 2D techniques on 1.5 T MR systems.

17. Discussion 2/4 Recently, Three-dimensional (3D) T2-FLAIR sequences can be acquired in a clinically acceptable scan time on 3 Tesla MR systems.  3D imaging techniques produce 3D volume data with less partial volume artifacts. With the FLAIR method as a 3D method flow artifacts disappear, and the signals from the cerebrospinal fluid are better suppressed.  Fukuoka and Hirai et al have reported that CE 3D T2 FLAIR provides more additional information than CE GRE (MPRAGE) T1WI.  Leptomeningeal enhancement on postcontrast 3D T2-FLAIR images may indicate true leptomeningeal enhancement. In our study, we focused on non-tumorous, infectious meningitis, and found CE 3D T2 FLAIR was superior to CE 3D T1WIs in depicting leptomeningeal lesions. We evaluated meningeal lesions in cistern and sulci, classified the lesions according to the region and showed there to be some tendency depending on the organism (nextslide). Factor of hyperintensity on CE 3D T2 FLAIR: leakage of contrast material to CSF by increased permeability of vessels or inflammation in leptomeningens

18. Discussion 3/4 • Bacterial meningitis, including pneumococcal; • 35 consecutive cases diagnosed with acute meningitis or meningoencephalitis based on clinical symptoms and spinal fluid findings. • scattered nodular enhancement on the brain surface particularly in the deep regions • high intensity on DWI possibly indicating an accumulation of pus • associated with dural enhancement which can be better detected on CE 3D T2-FLAIR, compared to on CE T1WI. • Viral meningitis; • mostly of the pial-subarachinoid-type enhancement effect, thin enhancement effect and seen to be diffuse. • parenchymal change • no abnormal enhancement effect in half of the cases • Tuberculous meningitis; • diffuse hyperintensity in the cerebral fissure in almost all cases. • Basal cisterns (prepontine and interpeduncular cistern)

19. Discussion4/4 Study limitations • Small number of cases • Few cases with radiologically severe meningitis • No comparable precontrast 3D T2 FLAIR • On CE 3D T2 FLAIR, “hyperintensity” is not exactly the same as “contrast enhancement effect,”  possibly due to pus or dirty CSF. • Further study is needed with a detailed comparison of DWI, and patient follow up.

20. Conclusion In this study Gd-enhanced 3D T2 FLAIR imaging provided more information, compared to Gd enhanced T1-weighted imaging in cases with infectious meningitis. Further, Gd-enhanced 3D T2 FLAIR imaging plays an important role as a postcontrast study in the diagnosis of meningitis.

21. References • TsuchiyaK et al. FLAIR MR imaging for diagnosing intracranial meningeal carcinomatosis. AJR 2001;176:1585-8. 2)Griffiths PDet al: Contrast-enhanced fluid-attenuated inversion recovery imaging for leptomeningeal disease in children. AJNR 2003;24:719-23. 3). Singh SK et al. Intracranial leptomeningeal metastases: comparison of depiction at FLAIR and contrast-enhanced MR imaging. Radiology. 2000 Oct;217(1):50-3. 4) Galassi W et al. Intracranial meningeal disease: comparison of contrast-enhanced MR imaging with fluid-attenuated inversion recovery and fat-suppressed T1-weighted sequences. AJNR 2005 ;26:553-9 5) Fukuoka H, Hirai 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 2010;31:868-73. 6)Oztopriak I et al. Contrast medium-enhanced MRI findings and changes over time in stage 1 tuberculosis meningitis Clincal Radiology 2007;62:1206-15