Journal of Clinical Neuroscience

Journal of Clinical Neuroscience 20 (2013) 107 111 Contents lists available at SciVerse ScienceDirect Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn Clinical Study Preoperative detection of the neurovascular relationship in trigeminal neuralgia using three-dimensional fast imaging employing steady-state acquisition (FIESTA) and magnetic resonance angiography (MRA) QingShi Zeng a,, Qin Zhou a, ZhiLing Liu a, ChuanFu Li a, ShiLei Ni b, Feng Xue a a Department of Radiology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan 250012, China b Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China article info abstract Article history: Received 8 April 2011 Accepted 7 January 2012 Keywords: Comparative study Microvascular decompression Neurovascular compression Trigeminal neuralgia Microvascular decompression is an accepted treatment for trigeminal neuralgia (TN). Preoperative identification of neurovascular compression, therefore, could aid determination of the appropriate treatment for TN. To preoperatively visualize the neurovascular relationship, three-dimensional fast imaging employing steady-state acquisition (3D FIESTA) and magnetic resonance angiography (MRA) were performed on 37 patients with TN in our study. 3D FIESTA in combination with MRA identified surgically verified neurovascular contact in 35 of 36 symptomatic nerves. The offending vessel (artery or vein) was correctly identified in 94.4% of patients, and agreement between preoperative MRI visualization and surgical findings was excellent (k = 0.92; 95% confidence interval, 0.67 1.00). Thus, 3D FIESTA in combination with MRA is useful in the detection of vascular contact with the trigeminal nerve in patients with TN. Ó 2012 Elsevier Ltd. All rights reserved. 1. Introduction Trigeminal neuralgia (TN) is an unbearable syndrome, characterized by paroxysmal, electric, lancinating pain in facial areas supplied by the branches of the trigeminal nerve. Central or peripheral demyelination can be important contributors to the pathophysiology of the disease, and most cases are caused by neurovascular compression (NVC) at the root entry zone (REZ) of the trigeminal nerve. 1 3 Accordingly, microvascular decompression (MVD) of the trigeminal nerve is clearly the pathophysiological strategy for TN therapy, and leads to improvement of symptoms and long-term pain relief in most patients. 4,5 Therefore, preoperative identification of NVC could aid determination of appropriate treatment for TN. However, due to poor resolution, conventional imaging techniques are inadequate for preoperative evaluation of the neurovascular relationship at the REZ. 6 Visualization of complex posterior fossa anatomy has become feasible with the development of three-dimensional (3D) MRI techniques. Three-dimensional fast imaging employing steadystate acquisition (FIESTA) sequence and time-of-flight (TOF) magnetic resonance angiography (MRA) have been used to detect NVC preoperatively in patients with TN. 7 9 A 3D FIESTA sequence produces a very high resolution T2-weighted MRI with an excellent contrast between structures, including cerebrospinal fluid (CSF), Corresponding author. Tel.: +86 13969157080; fax: +1 86 531 86927544. E-mail address: zengqingshi@yahoo.cn (Q. Zeng). trigeminal nerve and adjacent blood vessels; however, it is difficult to distinguish between arteries and veins. 10 3D TOF MRA selectively demonstrates fast-flowing blood and provides visualization of arteries and nerves, but the inherent defect of this technique is that veins are insufficiently visualized. 11 Therefore, a combination of these two MRI techniques may be used to visualize accurately the fine anatomical structures at the REZ of the trigeminal nerve and differentiate vein from artery. Thus, to preoperatively visualize the neurovascular relationship, we performed 3D high-resolution FIESTA sequence and TOF MRA on 37 patients with TN. The aims of this study were to evaluate the ability of 3D FIESTA sequence in combination with 3D TOF MRA to detect NVC and differentiate vein from artery in patients with TN. 2. Methods 2.1. Participants Patients with TN (37, disease group) and volunteers without TN (32, control group) were enrolled in this study. In the disease group, there were 21 male and 16 female patients (age range 26 81 years, mean 55.3 years). They all had unilateral, medically intractable TN (left side involvement, n = 14; right side involvement, n = 23) with median symptom duration of 5.5 years (range 1.5 19 years). Thirty-one patients experienced pain in only one branch of the trigeminal nerve, and the remaining six patients 0967-5868/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jocn.2012.01.046

108 Q. Zeng et al. / Journal of Clinical Neuroscience 20 (2013) 107 111 experienced pain in two or three branches.. In the control group, there were 21 male and 11 female participants (age range 16 83 years, mean 52.9 years). The differences in age (t = 0.52, p = 0.61) and gender (v 2 = 0.57, p = 0.45) between the control group and the disease group were not statistically significant. The participants underwent high-resolution 3D FIESTA and TOF MRA imaging, and the disease group was treated with MVD. Written informed consent was obtained from all patients and volunteers after the examination had been explained fully, and the study was approved by our Institutional Review Board. 2.2. MRI procedures All MRI were performed on a 3.0 Tesla (T) magnetic resonance scanner (Signa; GE Medical Systems, Milwaukee, WI, USA). Each participant underwent MRI using 3D FIESTA and TOF MRA techniques, centered on the pons in the region of the trigeminal nerve. The following pulse sequences were used: (i) 3D FIESTA sequence (6.1/1.5 [repetition time ms/echo time ms], 60 flip angle, 240 240 mm field of view, 512 512 matrix, two acquisitions), and (ii) 3D TOF MRA (22/3.2, 15 flip angle, 240 240 mm field of view, 256 512 matrix, one acquisition). 2.3. Image analysis All 3D FIESTA and 3D TOF MRA were analyzed by an experienced neuroradiologist who was blinded to the clinical details, including side of symptoms and whether symptoms were unilateral or bilateral. The neurovascular relationship was first categorized as absence, contact, or compression (distortion or deviation of the nerve). 12,13 Then, the vessel (artery or vein) was distinguished by a combination of 3D TOF MRA and 3D FIESTA. The vessel was defined as an artery if it was hyperintense on 3D TOF MRA and as a vein if it was visualized on 3D FIESTA but not on 3D TOF MRA. 2.4. Surgical treatment MVD for the treatment of the symptomatic trigeminal nerve was performed using a standard microdissection technique. 4,5 In brief, this technique involves: opening the skull using the suboccipital retromastoid approach, cutting the cerebral dura mater in the shape of? (an inverted T ), exploring the cerebellopontine angle, extensive cutting the arachnoid membrane around the trigeminal nerve, fully revealing the region where the trigeminal nerve enters the pons, identifying and confirming the vessels causing compression, separating and subsequently padding them with teflon-coated cotton. In each patient, the degree of neurovascular contact and the offending vessel (artery or vein) were recorded by the neurosurgeon performing the MVD. 2.5. Statistical analysis Statistical analyses was performed using Statistical Package for the Social Sciences for Windows version 11.5 (SPSS, Chicago, IL, USA). The p values of <0.05 were considered statistically significant. The occurrence of a neurovascular relationship on symptomatic and asymptomatic sides were compared using the Fisher exact test. Based on the surgical findings, the resulting sensitivity, specificity, false positive rate and false negative rate of 3D FIESTA in combination with 3D TOF MRA images were calculated. Agreement between preoperative MRI visualization and surgical findings was assessed using the Kappa (K) statistic. The K values for agreement were categorized as: poor, <0.40; fair, 0.40 0.59; good, 0.60 0.74; and excellent, P0.75. 3. Results The 3D TOF MRA and 3D FIESTA images clearly demonstrated the trigeminal nerve and the surrounding vasculature in all participants (Figs. 1, 2). On 3D TOF MRA, the artery was shown as a high-signal-intensity structure, the nerve as an intermediatesignal-intensity structure, and the CSF as a low-signal-intensity structure. On 3D FIESTA images, the blood vessel and nerve were shown as low-signal-intensity structures, and the CSF as a highsignal intensity structure. 3.1. Detection of NVC by using 3D FIESTA sequence in combination with 3D TOF MRA The neurovascular relationships revealed by MRI in the disease group and control group are summarized in Table 1. A trend toward increased severity of compression on the symptomatic nerve was observed. Compression and contact were shown more frequently on the symptomatic side compared with the asymptomatic side (Fisher exact test, p < 0.0001); however, no statistically significant differences were found between the asymptomatic side of patients with TN and the control group (v 2 = 0.08, p = 0.77). Surgical findings revealed neurovascular contact in 36 of 37 patients (36/37, 97.3%) with TN. In one patient (1/37, 2.7%), there was no vascular contact with the symptomatic nerve visualized at microdissection. On the 3D TOF MRA and 3D FIESTA images, contact of the vessel with the symptomatic nerve was detected in 35 patients (35/37, 94.6%). Of the two patients in whom no vascular contact with the symptomatic nerve was shown radiologically, one demonstrated neurovascular contact at MVD (false negative), and there were no false positive. Consequently, the sensitivity of 3D FIESTA imaging in combination with 3D TOF MRA in visualization of neurovascular contact on the symptomatic nerve was 97.2% (35/36), the specificity was 100% (1/1), the false-positive rate was 0% (0/1), and the false-negative rate was 2.8% (1/36). There were no significant differences in the identification of neurovascular contact between the MRI technique and the MVD procedure (v 2 = 0.35; p = 0.56). 3.2. Identification of the vasculature (artery or vein) using 3D FIESTA sequence in combination with 3D TOF MRA The ability of 3D FIESTA imaging in combination with 3D TOF MRA to identify the blood vessel responsible for NVC as an artery or vein was evaluated. In 28 patients (28/36, 77.8%) in whom an artery was the responsible blood vessel found at surgery, all were detected by MRI except a very small artery embedded in the nerve. In six patients (6/36, 16.7%) in whom the vein was confirmed as the compressing vessel at surgery, all vessels were demonstrated only on 3D FIESTA images but not on TOF MRA. In another two patients (2/36, 5.6%) in whom both a vein and an artery were determined to be the compressing vessels at surgery, the MRI result was consistent with surgical findings in one patient. Agreement between the results of MRI and the findings at surgery was excellent (k = 0.92; 95% confidence interval, 0.67 1.00). In the control group, arterial contact with the trigeminal nerve was shown by MRI in 15 sides and venous contact in three sides. There were no statistically significant differences in the identification of the vasculature between the symptomatic side of patients with TN and the control group (Fisher exact test, p = 0.61). 4. Discussion Trigeminal neuralgia is an unbearable pain syndromes. In most patients, demyelination of nerve fibers in the trigeminal nerve root

Q. Zeng et al. / Journal of Clinical Neuroscience 20 (2013) 107 111 109 Fig. 1. Axial MRI of a patient with right-sided trigeminal neuralgia caused by an artery: (a) three-dimensional (3D) time-of-flight magnetic resonance angiography showing a hyperintense artery, (straight arrow), an intermediate signal-intensity nerve (curved arrows), and hypointense cerebrospinal fluid (CSF, *); and (b) 3D fast imaging employing steady-state acquisition (FIESTA) image, showing the artery (straight arrow) and the nerve (curved arrows) as low-signal-intensity structures and the CSF (*) as a high-signalintensity structure. Fig. 2. Axial MRI in a patient with right-sided trigeminal neuralgia caused by a vein: (a) three-dimensional (3D) time-of flight magnetic resonance angiograph showing the nerve (curved arrows) as an intermediate-signal-intensity structure, and the cerebrospinal fluid (CSF, *) as a low-signal-intensity structure, but the vein is not visualized; and (b) an axial 3D fast imaging employing steady-state acquisition (FIESTA) image showing the vein (straight arrow) and the nerve (curved arrows) as low-signal-intensity structures and the CSF (*) as a high-signal-intensity structure. Table 1 The neurovascular relationships revealed by MRI in participants with and without trigeminal neuralgia Neurovascular relationship Disease group Control group (%) Symptomatic side (%) Asymptomatic side (%) Compression 21 (56.8) 4 (10.8) 0 (0) Contact 14 (37.8) 8 (21.6) 19 (29.7) Absence 2 (5.4) 25 (67.6) 45 (70.3)

110 Q. Zeng et al. / Journal of Clinical Neuroscience 20 (2013) 107 111 results from compression by an overlying artery or vein. 1 3 Therefore, NVC plays a major role in TN, and MVD is a accepted treatment. 4,5 Preoperative identification of the neurovascular relationship can assist in the surgical planning for MVD. In this study, to preoperatively visualize neurovascular relationships, 3D high-resolution FIESTA sequences and TOF MRA were performed on 37 patients with TN. Our results show that: (i) 3D FIESTA imaging in combination with 3D TOF MRA detected surgically-verified neurovascular contact in 97.2% of patients; (ii) the offending vessel (artery or vein) was correctly identified in 94.4% of patients, and agreement between preoperative MRI visualization and surgical findings was excellent. In recent years, there has been rapid development of diagnostic imaging modalities for many neurosurgical conditions. Refined techniques, including progress in MRI and the strength of the magnet has allowed a clear depiction of the trigeminal nerve and the surrounding vasculature. 7 11 3D FIESTA is an MRI sequence that can depict small structures surrounded by CSF with high-contrast and excellent spatial resolution. It is suitable for visualization of the nerves and vessels of the cerebellopontine angle with an unprecedented level of anatomic detail. 14 17 3D TOF MRA is based on the phenomenon of flow-related enhancement of spins entering into an imaging slice. An artery with fast blood flow is shown as a structure of high signal intensity and a nerve is shown as a structure of intermediate signal intensity. 9,11 13,18,19 By combining these two techniques, each can make up for the limitations of the other, and in many ways, draw upon the advantages of each. For instance, contrast between the artery and the nerve was greater in a 3D TOF MRA than in a 3D FIESTA image; however, an intense contrast border between the CSF and solid structures (nerve and vessel) was produced in 3D FIESTA. Additionally, the use of high magnetic-field strength offers new possibilities in MRI. The signal intensity increases almost linearly with magnetic-field strength, whereas the noise remains nearly unchanged. Thus, the signal-to-noise ratio at 3T is approximately twice that at 1.5 T. 20 The most significant benefit of a 3T MRI system is probably the increase in spatial resolution and anatomical detail. 21,22 In this study, 3D TOF MRA and 3D FIESTA sequences at 3T were used to evaluate the neurovascular relationship in patients with TN. Our results show that the combination of the two imaging techniques identified surgicallyverified neurovascular contact in 35 of 36 (97.2%) symptomatic nerves, and there were no false-positive results. In this study, of the 35 patients predicted radiologically to have neurovascular compression on the symptomatic side, 100% were found at surgery to have compression by the identified arterial or venous structure. If a definite conflicting vessel can be detected preoperatively in patients with TN, MVD is clearly the etiological strategy for TN therapy. 12 However, for patients without definite NVC determined preoperatively, surgical management becomes an invasive procedure with uncertain benefit. 10,18 Therefore, in our hospital, MRI is a routine procedure for patients with TN before any treatment regimen is considered. In our study, all patients had unilateral facial pain, yet 32.4% showed vascular contact or compression of the opposite asymptomatic nerve by MRI. Other studies have reported similar or even higher prevalence of NVC on the asymptomatic side. 12,13,18,23 Anderson et al. 18 observed that 71% of patients with clinically unilateral TN showed bilateral compression on a combination of 3D TOF MRA and spoiled gradientrecalled imaging. Similarly, in our earlier studies, neurovascular contact on the asymptomatic nerve was also found in 27% 12 and 48.9% 13 of unilateral TN patients by MRI. In this study, all volunteers in the control group had no facial pain, however, 29.7% had evidence of NVC. There were no statistically significant differences between the control group and the patient asymptomatic side, giving no explanation for symptomatic NVC on the other side for patients with TN. To clarify the pathophysiology, diffusion tensor imaging may be useful because it can produce neural tract images by the measurement of restricted diffusion of water in tissue. In addition the ability of 3D FIESTA imaging in combination with 3D TOF MRA to differentiate vein from artery in patients with TN was evaluated. Demonstration of venous compression is important for treatment of patients with TN, because compression by a vein increases the risk of pain recurrence after surgery. 5,24 Various MRI techniques have been applied to indentify the compressing vessel as an artery or vein. By following the vessel to its origin, Yoshino et al. 11 distinguish between arteries and veins on 3D constructive interference in steady-state (CISS) MRIs. However, this requires subtle judgment and a detailed anatomical knowledge, and can sometimes be misinterpreted. 10 In our study, vessels visualized on 3D TOF MRA were identified as arteries, and those shown on 3D FIESTA images but not on 3D TOF MRA images were determined to be veins. Our results show that the combination of 3D FIESTA imaging and 3D TOF MRA can be used to differentiate arterial and venous vasculature, which has also been shown in previous studies. 12,13,18,23,25 However, methodology in these studies varied. In the previous studies (including our own previous studies), 3D TOF MRA and contrast-enhanced T1-weighted 23 or spoiled gradient-recalled sequences 12,13,18,25 have been used to identify arterial or venous structures. In this study, 3D TOF MRA in combination with 3D FIESTA imaging was applied to differentiate vein from artery. Importantly, no MRI contrast agent was required for the discrimination of artery and vein in this study. The limitation of this study is the relatively small number of patients. Although the neurovascular relationship was determined, it may have been affected by the relatively high prevalence of arterial contact with the trigeminal nerve in our patient population (although this prevalence is representative of other clinical settings 1,2,12,13,26 ). Therefore, further investigations involving larger patient cohorts are required extend these results. 5. Conclusion In conclusion, although TN is a clinical diagnosis that does not depend on the diagnosis of NVC, 3D FIESTA imaging in combination with 3D TOF MRA is useful in the detection of NVC and the differentiation of arterial and venous vasculature in patients with TN. The visualization of NVC using MRI could aid decision-making and planning of MVD of the affected nerve. We expect that, with improvement in MR sequences and hardware, MRI will be increasingly helpful in preoperative identification of patients who will benefit from MVD. Conflicts of Interest/Disclosures The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication. Acknowledgements This work was supported by the National Natural Science Foundation of China (30870684) and Shandong Natural Science Foundation (Y2008C85 Y2008C76) References 1. Jannetta PJ. Arterial compression of the trigeminal nerve at the pons in patients with trigeminal neuralgia. J Neurosurg 1967;26:159 62. 2. Love S, Coakham HB. Trigeminal neuralgia: pathology and pathogenesis. Brain 2001;124:2347 60. 3. Devor M, Govrin-Lippmann R, Rappaport ZH. Mechanism of trigeminal neuralgia: an ultrastructural analysis of trigeminal root specimens obtained during microvascular decompression surgery. J Neurosurg 2002;96:532 43.

Q. Zeng et al. / Journal of Clinical Neuroscience 20 (2013) 107 111 111 4. Burchiel KJ, Clarke H, Haglund M, et al. Long-term efficacy of microvascular decompression in trigeminal neuralgia. J Neurosurg 1988;69:35 8. 5. Barker 2nd FG, Janetta PJ, Bissonette DJ, et al. The long-term outcome of microvascular decompression for trigeminal neuralgia. N Engl J Med 1996;334:1077 83. 6. Caillet H, Delvalle A, Doyon D, et al. Visibility of cranial nerves at MRI. J Neuroradiol 1990;17:289 302. 7. Satoh T, Onoda K, Date I. Preoperative simulation for microvascular decompression in patients with idiopathic trigeminal neuralgia: visualization with three-dimensional magnetic resonance cisternogram and angiogram fusion imaging. Neurosurgery 2007;60:104 13. 8. Benes L, Shiratori K, Gurschi M, et al. Is preoperative high-resolution magnetic resonance imaging accurate in predicting neurovascular compression in patients with trigeminal neuralgia? A single-blind study. Neurosurg Rev 2005;28:131 6. 9. Vörös E, Palkó A, Horváth K, et al. Three-dimensional time-of-flight MRA in trigeminal neuralgia on a 0.5-T system. Eur Radiol 2001;11:642 7. 10. Miller J, Acar F, Hamilton B, et al. Preoperative visualization of neurovascular anatomy in trigeminal neuralgia. J Neurosurg 2008;108:477 82. 11. Yoshino N, Akimoto H, Yamada I, et al. Trigeminal neuralgia: evaluation of neuralgic manifestation and site of neurovascular compression with 3D CISS MR imaging and MRA. Radiology 2003;228:539 45. 12. Ni S, Su W, Li X, et al. Enhanced three-dimensional fast spoiled gradient recalled MRI combined with magnetic resonance angiography for preoperative assessment of patients with trigeminal neuralgia. J Clin Neurosci 2009;16: 1555 9. 13. Chun-Cheng Q, Qing-Shi Z, Ji-Qing Z, et al. A single-blinded pilot study assessing neurovascular contact by using high-resolution MR imaging in patients with trigeminal neuralgia. Eur J Radiol 2009;69:459 63. 14. Chavhan GB, Babyn PS, Jankharia BG, et al. Steady-state MR imaging sequences: physics, classification, and clinical applications. Radiographics 2008;28: 1147 60. 15. Schmitz B, Hagen T, Reith W. Three-dimensional true FISP for high-resolution imaging of the whole brain. Eur Radiol 2003;13:1577 82. 16. Mikami T, Minamida Y, Yamaki T, et al. Cranial nerve assessment in posterior fossa tumors with fast imaging employing steady-state acquisition (FIESTA). Neurosurg Rev 2005;28:261 6. 17. Sheth S, Branstetter 4th BF, Escott EJ. Appearance of normal cranial nerves on steady-state free precession MR images. Radiographics 2009;29:1045 55. 18. Anderson VC, Berryhill PC, Sandquist MA, et al. High-resolution threedimensional magnetic resonance angiography and three-dimensional spoiled gradient-recalled imaging in the evaluation of neurovascular compression in patients with trigeminal neuralgia: a double-blind pilot study. Neurosurgery 2006;58:666 73. 19. Raslan AM, DeJesus R, Berk C, et al. Sensitivity of high-resolution threedimensional magnetic resonance angiography and three-dimensional spoiledgradient recalled imaging in the prediction of neurovascular compression in patients with hemifacial spasm. J Neurosurg 2009;111:733 6. 20. Alvarez-Linera J. 3T MRI: advances in brain imaging. Eur J Radiol 2008;67:415 26. 21. Schmitz BL, Aschoff AJ, Hoffmann MH, et al. Advantages and pitfalls in 3T MR brain imaging: a pictorial review. AJNR Am J Neuroradiol 2005;26:2229 37. 22. Kuhl CK, Träber F, Schild HH. Whole-body high-field-strength (3.0-T) MR Imaging in Clinical Practice. Part I. Technical considerations and clinical applications. Radiology 2008;246:675 96. 23. Patel NK, Aquilina K, Clarke Y, et al. How accurate is magnetic resonance angiography in predicting neurovascular compression in patients with trigeminal neuralgia? A prospective, single-blinded comparative study. Br J Neurosurg 2003;17:60 4. 24. Lee SH, Levy EI, Scarrow AM, et al. Recurrent trigeminal neuralgia attributable to veins after microvascular decompression. Neurosurgery 2000;46:356 61. 25. Zhou Q, Liu Z, Li C, et al. Preoperative evaluation of neurovascular relationship by using contrast-enhanced and unenhanced 3D time-of-flight MRA in patients with trigeminal neuralgia. Acta Radiol 2011;52:894 8. 26. Miller JP, Acar F, Burchiel KJ. Classification of trigeminal neuralgia: clinical, therapeutic, and prognostic implications in a series of 144 patients undergoing microvascular decompression. J Neurosurg 2009;111:1231 4.