Spine MRI in Spontaneous Intracranial Hypotension for CSF Leak Detection: Nonsuperiority of Intrathecal Gadolinium to Heavily T2-Weighted Fat-Saturated Sequences

Diagnostic Work-Up

All patients were evaluated according to our standard protocol, as described in previous publications, and are listed below. First, a detailed medical history was obtained, and a physical examination was performed by a neurosurgeon. In most patients, the leading symptom was orthostatic headache; thus, brain MR imaging was performed to rule out any underlying intracranial pathology. The SIH score, based on the 6 most relevant brain imaging findings, which helps predict the likelihood of a CSF leak, was calculated.¹⁴ Further examinations included optic nerve sheath sonography,¹² lumbar infusion testing,¹¹ unenhanced MR imaging of the spine, GdM, CDM with PMCT, and, in selected patients, DCTM.⁶

Spine MR Imaging

Unenhanced spine MR imaging was routinely performed in the morning, and GdM, in the afternoon of the same day. Imaging was performed on a 1.5T scanner (Aera; Siemens) using a 20-element head/neck coil and a 32-element table spine coil. The unenhanced spine MR imaging protocol included 3 sagittal T2-weighted spin-echo blocks (TR/TE = 4370/93 ms, number of averages = 3, section thickness = 3 mm, FOV = 150 × 300 mm, FOV phase = 50%, flip angle = 150°, acquisition time = 2 minutes and 20 seconds, matrix size = 192 × 512) and 4 sagittal, isotropic 3D heavily T2-weighted turbo spin-echo sequences with fat saturation (FS) (3D T2WI FS) (TR/TE = 1400/180 ms, number of averages = 2, section thickness = 1 mm, FOV = 300 × 300 mm, FOV phase = 100%, flip angle 150°, acquisition time = 4 minutes and 33 seconds, matrix size = 640 × 640) including the entire neurocranium.

Before GdM, written consent for the intrathecal off-label use of a Gd-based contrast agent was obtained from patients. Lumbar puncture was performed with a 22-ga needle with the patient in a lateral decubitus position, and a mixture of 0.5 mL of Gadovist (gadobutrol, 1.0 mmol/mL, a nonionic macrocyclic agent; Bayer Shering Pharma) or 0.5 mL of Magnograf (gadopentetate dimeglumine, 0.5 mmol/mL; Berlis) with 9.5 mL of CSF was administered intrathecally.

Three sagittal, isotropic T1-weighted blocks were acquired with the FS technique (T1WI Gd FS) (TR/TE = 9.82/4.77 ms, number of averages = 1, FOV = 288 × 288 mm, FOV phase = 100%, flip angle = 10°, acquisition time = 6 minutes and 9 seconds, matrix size = 288 × 288). Additional high-resolution, axial T1-weighted blocks with FS were acquired if the neuroradiologist was uncertain whether contrast media was truly present in the epidural space on the basis of the sagittal images (TR/TE = 8.62/4.77 ms, number of averages = 1, FOV = 180 × 180 mm, FOV phase = 100%, flip angle = 12°, acquisition time = 3 minutes and 54 seconds, matrix size = 410 × 512). Alternatively, high-resolution T1-weighted spin-echo blocks with FS in a sagittal orientation were acquired.

Conventional Dynamic Myelography and Postmyelography CT

The CDM technique, which has previously been described in detail, is summarized briefly below.¹⁵ For opacification, 20 mL of Iopamiro 300 (iopamidol; Bracco) was injected intrathecally. Patient positioning was adapted depending on the findings of previous imaging: prone when an osteodiscogenic microspur was suspected or lateral decubitus when a spinal nerve root diverticulum was the presumed source of leakage. The patient was tilted into the Trendelenburg position, following the leading edge of the intrathecal contrast. The level at which the contrast exited the intrathecal compartment and started spilling into the epidural space was considered the level of the dural breach (Fig 3). The patient was immediately transferred to the CT imaging suite, and a PMCT was performed (Somatom Definition Edge; Siemens) to identify possible causative pathology at the level of dural dehiscence or a CSF venous fistula. If no epidural contrast was evident in the first PMCT, a late-phase PMCT was performed, usually 4–24 hours after the initial intrathecal injection, to exclude low-flow leaks.

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FIG 3.

A 57-year-old woman with orthostatic headache and tinnitus. A, The sagittal, T2-weighted sequence demonstrates extensive extrathecal CSF and multiple suspicious disc protrusions (black arrowheads). B–D, Conventional dynamic myelography demonstrates a CSF leak at the T10/11 level with progressive contrast media distribution (arrowheads). Even in retrospect, the MR imaging did not demonstrate any suspicious lesion at the corresponding level (A, white arrowhead). The leak was confirmed intraoperatively and surgically closed. The follow-up spine MR imaging did not show any residual epidural CSF collection (not shown).

Data Analysis

Blinded evaluation of brain MR imaging was performed by a neuroradiology fellow (G.P.), who reported the SIH score. The spine MR imaging of all subjects was assessed independently by a board-certified neuroradiologist (A.W.) and 2 neuroradiology fellows (P.S.B., L.G.), blinded to clinical presentation and to all other imaging studies performed. All spine sequences (T2WI, 3D T2WI FS, T1WI Gd) were separated, deidentified, and sorted randomly on an established, nonmodifiable layout and reviewed on a PACS station. The readers were instructed to perform their assessment and report the results on a standardized spreadsheet, and a short educational module before beginning the image interpretation was provided. For unenhanced spine MR imaging sequences, the presence of CSF in the epidural compartment was recorded; for GdM, epidural contrast accumulation unrelated to the puncture site in the lumbar spine was evaluated. In patients with leaks, the craniocaudal extent was noted (the number of vertebrae with epidural CSF). The readers also reported the number of suspicious lesions potentially causing CSF leakage (such as spondylophyte, disc protrusion, or spinal nerve root diverticula) and the lesion they considered the most likely to be the cause of the CSF leak.

In addition, information regarding patients’ demographic characteristics (age, sex) and type of therapy (conservative, epidural blood patch, microsurgical closure) was extracted from the registry.

Standard of Reference

Multimodal imaging including MR imaging, CDM, PMCT, and microsurgical exploration was considered the criterion standard for the proof of a CSF leak. Two neuroradiologists (T.D. and E.I.P. with 8 and 11 years of experience, respectively) who were not involved in the initial analysis reviewed all available images from all patients for the presence of epidural CSF and the level of dural dehiscence. In cases of disagreement, all imaging modalities were reviewed in a joint session to reach a consensus. In patients undergoing microsurgical closure of the CSF leak, intraoperative reports were reviewed to confirm the presence of epidural CSF and verify the localization of the dural breach.

Statistical Analysis

Statistical analysis was performed using STATA (2017, Release 15; StataCorp). Descriptive analysis was performed using frequencies and percentages for categoric variables and mean (± SD) or median (interquartile range) for continuous variables. The results of all 3 readers were aggregated. Continuous measures were averaged among the 3 readers. For dichotomous variables, a qualitative sign was considered positive if 2 or all 3 readers scored it as positive. In cases of categoric variables with >2 categories and about which all 3 readers disagreed, the value given by the first reader was the one taken into consideration. The results are presented for the 3 different MR imaging sequences.

Interrater reliability for categoric data was determined using the Fleiss κ. For continuous data, the intraclass correlation coefficient (ICC) was calculated with the 2-way mixed-effects model estimating absolute agreement. Agreement was defined as almost perfect (κ or ICC > 0.80), substantial (κ or ICC = 0.61–0.80), moderate (κ or ICC = 0.41–0.60), fair (κ or ICC = 0.21–0.40), or poor (κ or ICC ≤ 0.20). If the location was correctly identified, the standard and weighted (with linear weights) κ approach was used.

For each MR imaging sequence, scatterplots were used to graphically depict the agreement among the leak location as reported by the readers and the true location. Sensitivity and specificity were obtained comparing the 3 sequences against the ground truth. To test the diagnostic reliability of different sequences for the diagnosis of a CSF leakage, we determined the agreement between each sequence and the ground truth using κ statistics and bootstrapping methods.