CLINICAL ARTICLE J Neurosurg 134:286–294, 2021 Correlation of spontaneous and traumatic anterior skull base CSF leak flow rates with fluid pattern on early, delayed, and subtraction volumetric extended echo train T2-weighted MRI John W. Rutland, BA,1 Satish Govindaraj, MD,2 Corey M. Gill, BA, BS,1 Michael Shohet, MD,2 Alfred M. C. Iloreta Jr., MD,2 Joshua B. Bederson, MD,1 Raj K. Shrivastava, MD,1 and Bradley N. Delman, MD, MS3 Departments of 1Neurosurgery, 2Otolaryngology–Head and Neck Surgery, and 3Diagnostic, Molecular, and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, New York OBJECTIVE CSF leakage is a potentially fatal condition that may result when a skull base dural defect permits CSF communication between the cranial vault and sinonasal cavities. Flow rate is an important property of CSF leaks that can contribute to surgical decision-making and predispose patients to complications and inferior outcomes. Noninvasive preoperative prediction of the leak rate is challenging with traditional diagnostic tools. The present study compares fluid configurations on early and late volumetric extended echo train T2-weighted MRI by using image tracings and sequence subtraction as a novel method of quantifying CSF flow rate, and it correlates radiological results with intraoperative find- ings and clinical outcomes. METHODS A total of 45 patients met inclusion criteria for this study and underwent 3-T MRI. Imaging sequences in- cluded two identical CUBE T2 (vendor trade name for volumetric extended echo train T2) acquisitions at the beginning and end of the scanning session, approximately 45 minutes apart. Twenty-five patients were confirmed to have definitive spontaneous or traumatic anterior skull base CSF leaks. Semiautomated volumetric segmentation of CSF intensity was performed on both CUBE data sets by using 3D-Slicer software, and volumes were subtracted to obtain accumulated CSF volume. These imaging-derived fluid accumulations were correlated with high- or low-flow states, as well as ulti- mate treatment outcomes including recurrences. RESULTS Of the 45 patients, 25 (55.6%) had definitive evidence of CSF leakage, and 22 (88%) of these underwent surgical repair. Patients with high-flow CSF leaks had higher early (4.058 cm3 vs 0.982 cm3, p = 0.04), late (4.58 cm3 vs 1.096 cm3, p = 0.04), and accumulated (0.53 cm3 vs 0.11 cm3, p = 0.01) fluid volume measurements than patients with low-flow leaks. The 5 (22.7%) patients who exhibited postoperative CSF leak recurrence had significantly greater early (6.30 cm3 vs 1.23 cm3, p = 0.008) and late (6.87 cm3 vs 1.45 cm3, p = 0.008) volumes. Accumulated volume was not sig- nificantly greater in patients with leak recurrence (0.58 cm3 vs 0.22 cm3, p = 0.07). Early, late, and accumulated volumes were significantly correlated with postoperative hospital stay as well as duration of postoperative lumbar drain placement (p < 0.05 for all measures). CONCLUSIONS High-resolution CUBE T2 MRI, coupled with precise volumetric segmentation and subtraction of si- nonasal hyperintensity, not only demonstrated predictive value in differentiating low- and high-flow CSF leaks, but also correlated with postoperative complications such as leak recurrence. These findings may be useful in the clinical workup and neurosurgical management of patients with skull base CSF leaks. https://thejns.org/doi/abs/10.3171/2019.10.JNS192500 KEYWORDS cerebrospinal fluid leakage; flow rate; dural repair; primary spontaneous CSF leak; craniomaxillary trauma; endoscopic surgery; anterior skull base defect ABBREVIATIONS BMI = body mass index; VP = ventriculoperitoneal. SUBMITTED September 11, 2019. ACCEPTED October 22, 2019. INCLUDE WHEN CITING Published online December 27, 2019; DOI: 10.3171/2019.10.JNS192500. 286 J Neurosurg Volume 134 • January 2021 ©AANS 2021, except where prohibited by US copyright law Unauthenticated | Downloaded 09/26/21 12:15 PM UTC Rutland et al. SF leakage is a serious condition resulting from a tients, 90 were excluded from the study for the following defect in the arachnoid and dura mater and breach reasons: prior sinus surgery, nonanterior skull base leak, of the bony skull base contour, which together and iatrogenic etiology. The remaining 45 patients met ordinarilyC prevent CSF from escaping the cranial vault. inclusion criteria for this study and were included in the Potentially fatal complications can arise from CSF leak- analysis. age, including meningitis, which occurs in 10%–25% of patients.20,27,35 CSF leakage has traditionally been classi- Imaging Protocol 24 fied as either traumatic or spontaneous. CSF leakage re- The 3-T MRI was performed using a modified clinical sulting from traumatic cranial fracture has been reported sinus MRI protocol. CUBE T2 (the vendor trade name in as high as 30% of cases, and craniomaxillary trauma for volumetric extended echo train T2) sequences were accounts for approximately 80% of all CSF rhinorrhea 35 obtained as the first scan following the localizer and cases. Another common etiology for anterior skull base cloned to repeat as the last sequence before scan conclu- leak results from thinning and erosion in idiopathic in- sion. These early and late volumetric T2 sequences were tracranial hypertension, a condition that typically occurs thus obtained approximately 45 minutes apart. Additional in middle-aged women with a body mass index (BMI) of clinical sequences obtained as standard of care included 2 6,23,28 above 30 kg/m . Other etiologies include neoplasm, sagittal and axial T1; coronal single-shot T2; and axial hydrocephalus, and congenital abnormalities.4,20,23 What- T2, FLAIR, gradient echo and diffusion sequences, and ever the cause, bony erosion at the skull base and subse- postgadolinium volumetric T1 sequences obtained using quent tear in the arachnoid and dura permits escape of a standard clinical weight-based dosing algorithm. MR CSF between the CNS and compartments of the skull images were examined by an experienced neuroradiolo- base, such as the nasal cavity and paranasal sinuses. gist who was blinded to intraoperative flow rate status, in The goals of surgery for both traumatic and primary order to determine whether there was evidence of CSF spontaneous CSF leaks are to seal the cranial defect and leakage. to separate the cranial vault from the sinonasal tract, while preserving ocular and cranial nerve function. Ad- Image Analysis vancements in endoscopic transnasal sinus surgery have The two volumetric extended echo train sequences permitted high rates of successful CSF leak repair while were transferred to a dedicated workstation for image minimizing the need for transcranial approaches to the 3,7,14 analysis. Using a semiautomated method in 3D Slicer anterior skull base. Despite many advances in the field (http://www.slicer.org), the volume of CSF intensity was of endoscopic surgery, the optimal diagnosis and man- measured using a seed-based region-growing algorithm agement of anterior skull base CSF remains a clinical that included voxels greater than 50% of the maximum challenge. Disease features such as degree of CSF flow CSF signal intensity of the lateral ventricles.12 Volumetric rate can complicate and compromise efficacy of surgi- segmentations were generated for both early and late ac- cal repair, with high-flow leaks increasing the likelihood quisitions, with subtraction of early from late yielding the of numerous adverse outcomes including postoperative 19 volume of interval CSF accumulation (Fig. 1). The semi- leaks. automated volumetric segmentation method used in this Prior studies have shown the importance of distinguish- study is shown in Fig. 2. ing high-flow from low-flow CSF leaks before surgery;21 however, current clinical tools are limited for preopera- Clinical Data tively predicting objective flow rate. An imaging biomark- er for quantifying CSF leak flow rate may prove useful for Disease features and demographic data were obtained surgical planning,29 flap repair choice,15,19,25 indication for from electronic medical records, intraoperative observa- CSF diversion,5,7,14 and predicting the likelihood of post- tions, laboratory testing, and radiological examinations. operative leak recurrence.14,15 The present study examines Definitive evidence of CSF leakage included a positive subtraction of fluid intensity volumes between early and β-transferrin result, obvious CSF pooling in the sinonasal late MRI acquisitions to quantify CSF flow rate noninva- cavities, or intraoperative observation. Determination of sively. We hypothesize that calculated volume differences the CSF leak flow rate was performed intraoperatively af- correlate with the rate of CSF leakage clinically. Results ter exposure of the leak and after identification of its exact from the present study may be useful in the preoperative anatomical location. Criteria described by Esposito et al. workup and neurosurgical management for patients with were used to designate low-flow (small “weeping” leak, primary spontaneous CSF leaks. confirmed by Valsalva maneuver, without obvious or with only small diaphragmatic defect) and high-flow (moderate 11 Methods CSF leak, with obvious diaphragmatic defect) CSF leaks. Participant Selection Statistical Analysis Approval for this study was obtained from the local in- Statistical database software (JMP Pro version 14) stitutional review board. A total of 135 patients with sus- was used for statistical analysis. Variables were assessed pected CSF leaks underwent MRI examination between for normality by using the Shapiro-Wilk test. T-tests and November 2010 and May 2019. Inclusion criteria for the Wilcoxon tests were used for continuous variables, as ap- present study included traumatic or primary spontaneous propriate, and linear regression analyses were performed. anterior skull base CSF leaks. Of the cohort of 135 pa- Data were standardized and nominal logistic regression J Neurosurg Volume 134 • January 2021 287 Unauthenticated | Downloaded 09/26/21 12:15 PM UTC Rutland et al. FIG. 1. Schematic depiction of the pooling mechanism in this study. The image on the left shows the location of details in the im- age on the right.