54
Original Article
Normal Values for Transbulbar Sonography and Magnetic Resonance Imaging of the Optic Nerve Sheath Diameter (ONSD) in Children and Adolescents
Authors
M. Steinborn1, M. Friedmann1, H. Hahn2, A. Hapfelmeier3, E. Macdonald1, K. Warncke2, A. Saleh1
Affiliations
1
2 3
Department of Diagnostic and Interventional Radiology and Pediatric Radiology, Städtisches Klinikum München Schwabing, Munich Department of Pediatrics, Technische Universität München (TUM), Munich Institute for Medical Statistics and Epidemiology, Technische Universität München (TUM), Munich
Key words
Abstract
Zusammenfassung
"
!
!
Purpose: To establish normal values of the optic nerve sheath diameter (ONSD) in children and adolescents for transbulbar sonography and magnetic resonance imaging. Materials and Methods: In 99 children and adolescents (age: 5.6 – 18.6 years, mean: 12 years) without neurologic or ophthalmologic disease, measurements of the ONSD with transbulbar sonography were performed. For comparison 59 children and adolescents (age: 5.1 – 17.4 years, mean 12.3 years) with a normal MR examination of the brain had measurements of the ONSD on a T2-weighted thin section sequence of the orbit. Besides establishing modality-related normal values, age dependency, accuracy and reproducibility of measurements were assessed. Results: Overall the mean ONSD was 5.75 ± 0.52 mm for transbulbar sonography and 5.69 ± 0.31 mm for MRI. There was no statistical significance between the 95 % percentiles and age for both transbulbar sonography (p = 0.332) and MRI (p = 0.336). As a parameter for the reproducibility of measurements, the repeatability coefficient (RC) was between 0.34 mm and 0.46 mm. The concordance correlation coefficient (CCC) values revealed a high agreement between readers both for transbulbar sonography (0.868) and MRI (0.796). Conclusion: Normal values for ONSD in children and adolescents found in this study are significantly higher than assumed. The values found for transbulbar sonography are confirmed by comparable results for MR measurements. A precise sonographic measurement technique and the consideration of normal values found hereby are essential for correct interpretation of ONSD measurements in children and adolescents.
Ziel: Bestimmung von Normwerten des Optikusnervenscheidendurchmessers (ONSD) bei Kindern und Jugendlichen für transbulbäre Sonografie und Magnetresonanztomografie. Material und Methoden: Bei 99 Kindern und Jugendlichen (Alter: 5,6 – 18,6 Jahre, MW: 12 Jahre) ohne neurologische oder ophthalmologische Grunderkrankung wurde der ONSD mittels transbulbärer Sonografie bestimmt. Als Vergleichsgruppe wurde bei 59 Kindern und Jugendlichen (Alter: 5,1 – 17,4 Jahre, MW: 12,3 Jahre) mit einer unauffälligen MRT-Untersuchung des Schädels der ONSD mittels einer T2-gewichteten Dünnschichtuntersuchung der Orbita ermittelt. Neben der methodenbezogenen Normwertbestimmung wurden Altersabhängigkeit der Messwerte, Messgenauigkeit und Reproduzierbarkeit der Messungen ermittelt. Ergebnisse: Der Mittelwert des ONSD im Gesamtkollektiv betrug für die transbulbäre Sonografie 5,75 ± 0,52 mm und für die MRT 5,69 ± 0,31 mm. Die Überprüfung der Altersabhängigkeit der 95 % Perzentile war weder für die Sonografie (p = 0,332) noch die MR-Tomografie (p = 0,336) statistisch signifikant. Der repeatability coefficient (RC-Koeffizient) als Maß für die Reproduzierbarkeit der Messungen ergab Werte zwischen 0,34 mm und 0,46 mm. Die Werte für den concordance correlation coefficient (CCC) ergaben eine hohe Übereinstimmung der Messungen zwischen den Betrachtern sowohl für die transbulbäre Sonografie (0,868) als auch die MRT (0,796). Schlussfolgerung: Die in dieser Studie ermittelten Normwerte des ONSD bei Kindern und Jugendlichen liegen deutlich höher als bisher angenommen. Die Messwerte für die transbulbäre Sonografie werden durch vergleichbare MRT-Werte bestätigt. Eine exakte sonografische Messtechnik und die Berücksichtigung der hierbei ermittelten Normwerte sind für die Interpretation von ONSD-Messungen bei Kindern und Jugendlichen unabdingbar.
● eye ● MR imaging ● ultrasound " "
received accepted
25.2.2014 11.7.2014
Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1385012 Published online: August 20, 2014 Ultraschall in Med 2015; 36: 54–58 © Georg Thieme Verlag KG Stuttgart · New York · ISSN 0172-4614 Correspondence Dr. Marc Steinborn Department of Pediatric Radiology, Städtisches Klinikum Munich Schwabing Kölner Platz 1 80804 Munich Germany Tel.: ++ 49/89/30 68 22 70 Fax: ++ 49/89/30 68 38 18 [email protected]
Steinborn M et al. Normal Values for … Ultraschall in Med 2015; 36: 54–58
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Normwerte für die transbulbäre Sonografie und Magnetresonanztomografie des Optikusnervenscheidendurchmessers (ONSD) bei Kindern und Jugendlichen
Already in 1870 the German anatomist Gustav Schwalbe demonstrated the communication between the intracranial subarachnoid space and the subarachnoid space surrounding the optic nerve [1]. Later, experimental studies showed that an increase in intracranial pressure leads to a shift of cerebrospinal fluid into the optic nerve sheath and that the optic nerve sheath diameter (ONSD) correlates with the degree of intracranial pressure [2]. Several study groups described the possibility of measuring the ONSD sonographically [3, 4]. Helmke et al. developed a standardized technique for the estimation of intracranial pressure in children by measuring the ONSD with transbulbar sonography. Normal values found in healthy subjects ranged from 1.9 to 3.5 mm in the first 4 years of life and 2.2 to 4 mm in older children up to 18 years [5]. For sonographic ONSD measurements in adults, mean values between 3.2 and 5.4 mm have been reported [6 – 8]. Within the last years several studies on MR imaging of the ONSD revealed normal mean values in healthy adults between 5.3 and 5.7 mm, a range that is already regarded as definitely pathologic by most of the studies using transbulbar sonography [9 – 13]. Whereas the anatomic structures and margins of the optic nerve and nerve sheaths can clearly be defined on MR imaging, a major problem of transbulbar sonography is the unfavorable transmission angle and the limited lateral spatial resolution [14]. Differences in the interpretation of the ultrasound reflexes of the retrobulbar region and high dependence on patient cooperation are further explanations for the discrepancies between MR and sonographic measurements [11].With the development of high-resolution ultrasound probes, the limitations of transbulbar sonography are progressively compensated [15]. In recent studies it could be shown that a good correlation between sonographic and MR measurements of the ONSD can be obtained if the corresponding anatomic structures are depicted and the measuring points are set correctly [16, 17]. The purpose of this study was to reestablish normal values for the ONSD in children and adolescents using high-resolution transbulbar sonography and MR imaging.
250 msec, slice thickness 1 mm, scan time 2:28 min; NT Intera 1.0 T, Philips Medical Systems, Best, Netherlands). Measurements of the ONSD were performed separately for each modality by two independent readers using the measurement tools of a conventional PACS system (Centricity RA 1000, GE Medical Systems). For each eye measurements of the optic nerve sheath were performed 3 mm behind the optic nerve papilla. For transbulbar sonography the measuring calipers were placed on the hypoechoic outer border surrounding the hyperechoic nerve sheath. To distinguish the outer border of the subarachnoid space from the hypoechoic tangential artifact of the dural sheath, the ampullary shape of the bulbar segment with the outer border of the subarachnoid space converging to the papilla had to be dem" Fig. 1). onstrated on the image (● For MR imaging the optic nerve sheath was defined by the distance between two measuring points that were placed on the border between the hyperintense fluid and the hypointense dur" Fig. 2). al sheath (● All measurements were repeated two times with a minimum delay of one week in between. For each modality mean values and standard deviations were calculated. In order to evaluate the age
Methods !
The study was approved by the institutional Ethics Committee. In otherwise healthy children and adolescents who had ultrasound examination for non-neurologic disease, transbulbar sonography was performed after informed consent from parents or legal guardians was obtained. An approved examination program for the orbit was chosen using the lowest mechanical index value (MI 0.1). A 17 – 5 MHz linear array transducer (iU 22, Philips Medical Systems, Best, Netherlands) was placed on the lateral aspect of the closed upper eyelid and angulated medio-caudally. In order to reach a straight course of the optic nerve and its sheaths, the children were asked to locate a sticker straight ahead at the ceiling above them through the closed or opened contralateral eye. At least three images of each side were taken and archived electronically. For comparison a consecutive group of children and adolescents who underwent magnetic resonance imaging of the brain for various reasons (headache/migraine, syncope/seizure, trauma, nonCNS tumor/infection) was selected. All selected patients had a normal MR examination of the brain and no clinical signs of elevated intracranial pressure. In addition to the routine imaging protocol, a T2-weighted axial thin section sequence of the orbit for measurement of the ONSD was acquired (TR 4000 msec, TE
Fig. 1 Transbulbar sonography demonstrating the bulbar segment of the optic nerve sheath with the outer hypoechoic border of the subarachnoid space converging to the papilla (arrows). Measurement of the ONSD is performed 3 mm behind the papilla. The diameter of the optic nerve sheath is measured as the distance between the hypoechoic outer borders surrounding the hyperechoic nerve sheath (white line). N = optic nerve. Abb. 1 Transbulbäre Sonografie mit Darstellung des bulbären Abschnitts der Optikusnervenscheide und Konvergenz der äußeren echoarmen Begrenzung des Subarachnoidalraumes zur Papille (Pfeile). Die Messung des ONSD erfolgt 3 mm hinter der Papille. Der Durchmesser der Optikusnervenscheide wird zwischen den echoarmen äußeren Begrenzungen der echoreichen Nervenhülle gemessen (weiße Linie). N = Nervus opticus.
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Original Article
Original Article
poor image quality. The overall mean value for the ONSD on transbulbar sonography was 5.75 ± 0.52 mm (range 4.6 – 7.7 mm). For comparison MR images of 59 patients (age: range 5.1 – 17.4 years; mean 12.3 years) were available for ONSD measurement. Seven eyes were excluded from analysis due to poor image quality resulting in a total number of 111 eyes that could be measured. The overall mean value for the ONSD on MRI was 5.69 ± 0.31 mm (range: 5.0 – 6.9 mm). Calculating the 95 % quantiles as a function of age showed no statistical significance between ONSD values and age neither for transbulbar sonography (p = 0.332) nor MRI (p = 0.336). For both imaging methods the accuracy of measurements was almost identical. The repeatability coefficient as a parameter for the intraobserver variation ranged between 0.34 mm and 0.46 mm. The concordance correlation coefficient representing the correlation of measurements between the readers was 0.868 " Fig. 3). for transbulbar sonography and 0.796 for MR imaging (●
Discussion !
Fig. 2 Axial T2-weighted MRI of the orbit: The hypointense optic nerve (N) is surrounded by the hyperintense CSF. The dura can be depicted as the outer hypointense border of the optic nerve sheath (arrows). The optic nerve sheath diameter is defined as the distance between the borders of CSF and dura 3 mm behind the papilla (white line). Abb. 2 Axiale T2-gewichtete MRT der Orbita: Der hypointense Nervus optikus (N) wird vom hyperintensen Liquor umgeben. Die Dura stellt sich als äußere hypointense Begrenzung der Optikusnervenscheide dar (Pfeile). Der Optikusnervenscheidendurchmesser entspricht dem Abstand zwischen den äußeren Begrenzungen des Liquors zur Dura 3 mm hinter der Papille (weiße Linie).
dependency of measurements, quantile regression was used to model the 95 % quantile of ONSD measurements as a function of age. The interobserver agreement of measurements was assessed in several ways. Bland Altman plots were calculated and the concordance correlation coefficient (CCC) was determined to quantify the strength of agreement between the readers. To assess intraobserver agreement, the repeatability coefficient (RC), which describes the maximum deviation that is expected for 95 % of two repeated measurements by the same reader, was calculated.
Results !
In 99 children and adolescents (age: range 5.6 – 18.6 years; mean 12 years), transbulbar sonography images of 181 eyes were included for evaluation. In 17 cases one eye had to be excluded due to
Steinborn M et al. Normal Values for … Ultraschall in Med 2015; 36: 54–58
From experimental studies on human cadavers, it is known that elevation of the intracranial pressure leads to a shift of cerebrospinal fluid from the intracranial subarachnoid compartment into the subarachnoid space of the optic nerve causing pressure-dependent dilatation of the optic nerve sheath [2]. Helmke et al. showed that the pressure-dependent changes of the optic nerve sheath diameter are most pronounced in the bulbar segment [14]. They developed a standardized method for transbulbar B-mode sonography in which measurements of the ONSD are performed 3 mm behind the papilla [5]. For children normal values of the ONSD between 1.9 to 4 mm were found and values above 4 mm in children under 4 years and 5 mm in children over 4 years were definitely regarded as abnormal [5, 18, 19]. Similar results were found for adults in whom normal values ranged from 2.4 to 4.7 mm [6]. With the development of advanced ultrasound imaging techniques, subsequent studies found higher normal values for the ONSD in adults with mean values ranging between 4.8 to 5.4 mm [7, 8]. In the last few years several studies focused on measuring the ONSD using MR imaging in various pathologic conditions [20 – 22]. Normal values of the ONSD in adults found with MR imaging were generally higher than those that have been published for transbulbar sonography. Although various imaging techniques were used (different field strength, slice orientation, slice thickness, image resolution), consistent mean values between 5.3 and 5.7 mm were obtained [9 – 12]. There was only one study where MR and sonographic measurements were compared directly [11]. Again measurement values for transbulbar sonography were significantly lower than the results for MRI and factors like examiner experience, incorrect cutting plane and limited spatial resolution of ultrasound were supposed to be reasons for the variation of results [11]. Despite the excellent spatial resolution of high-frequency linear ultrasound probes that are available nowadays, measuring the optic nerve sheath diameter from the transbulbar approach indeed is restricted by technical limitations. A major drawback of transbulbar sonography is the unfavorable intromission angle of 180° and the limited lateral spatial resolution. In addition tangential artifacts cause scattering and refraction of the ultrasound waves and lead to a signal loss and acoustic shadowing [23].
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Fig. 3 Bland Altman plots displaying the agreement between raters for transbulbar sonography (Sono) and magnetic resonance imaging (MRI). The continuous line displays the mean difference between the readers (Rater 0 – Rater 1) [mm]. The interrupted line shows the limits of agreement indicating the maximum difference between readers in 95 % of measurements [mm]. Note: RC = repeatability coefficient (maximum difference of same reader in 95 % of cases) [mm], CCC = concordance correlation coefficient.
Another important aspect is the ultrastructural composition of the subarachnoid space of the optic nerve sheath. Electron-microscopic studies have shown that the subarachnoid space is composed of a complex meshwork of trabeculations which has its highest density in the retrobulbar portion and displays multiple acoustic shadowing surfaces on ultrasound [24]. Thus, the subarachnoid space of the optic nerve, although containing cerebrospinal fluid, is not echo-free but is hyperechoic to varying degrees. On the other hand the inner nerve sheath which covers the hypoechoic optic nerve and represents the continuation of the pia mater is also hyperechoic and might therefore be mixed up with the trabeculated subarachnoid space [16]. As the trabeculation of the subarachnoid space surrounding the optic nerve is not homogeneous, the increase in echogenicity is furthermore variable and the outer border of the trabeculated subarachnoid space might be hard to define. Therefore, the morphology of the retrobulbar portion of the optic nerve sheath with its ampullary configuration and the outer border of the subarachnoid space converging to the papilla is a helpful landmark to define the outer border of the subarachnoid space. If these anatomic characteristics of the optic nerve and its sheath are considered ONSD, measurements with transbulbar sonography reach values that show a good correlation with MR measurements [16, 17]. The present study was conducted to establish normal values of the ONSD in children and adolescents and evaluate the sonographic measurement technique by comparing the results of transbulbar sonography with MR imaging. With mean values around 5.7 mm, our data confirm that normal values of the ONSD in children and adolescents are substantially higher than previously assumed and are in the range of values for healthy adults [11].
Abb. 3 Bland Altman Plots mit Darstellung der Übereinstimmung der Auswerter für die transbulbäre Sonografie (Sono) und die Magnetresonanztomografie (MRT). Die durchgezogene Linie stellt die mittlere Abweichung zwischen den Auswertern (Auswerter 0 – Auswerter 1) dar [mm]. Die gestrichelte Linie zeigt die maximale Differenz der Auswerter in 95 % der Fälle an [mm]. Anmerkung: RC = repeatability coefficient (maximale Differenz eines Auswerters bei Messwiederholung in 95 % der Fälle) [mm], CCC = concordane correlation coefficient.
We did not find age dependency in our study population. This might be due to the fact that only children over 5 years were included and that after the myelination of the optic nerve is completed no further significant growth of the nerve and the nerve sheath appears [25]. There are some limitations of our study that have to be mentioned. The selection of our study group of normal children and adolescents was based on clinical and MR imaging findings only. Especially patients getting MRI of the brain usually have a history of neurologic complaints leading to the imaging study. Although our patients had a normal neurologic status at the time of MR imaging, elevated intracranial pressure cannot be ruled out completely in every patient. Another limitation is the lack of measurement values for children under 5 years of age. As the feasibility and image quality of transbulbar sonography highly depend on patient cooperation, transbulbar sonography in healthy and awake children is limited to older children, usually above 5 years of age. From our own experience we expect that normal ONSD values in younger children will be significantly lower. In summary our study shows that normal values of the ONSD in children and adolescents are substantially higher than described before. This has to be considered when interpreting ONSD values in children and adolescents. Measurement values for transbulbar sonography and MR imaging correlate well if the characteristics of the retrobulbar ultrasound anatomy are considered.
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References 01 Schwalbe G. Untersuchungen über die Lymphbahnen des Auges und ihre Begrenzungen. Arch Mikr Anat 1870; 6: 1 – 61 02 Liu D, Kahn M. Measurement and relationship of subarachnoid pressure of the optic nerve to intracranial pressure in fresh cadavers. Am J Ophthalmol 1993; 116: 548 – 556 03 Skalka HW. Neural and dural optic nerve measurements with A-scan ultrasonography. South Med J 1978; 71: 399 – 400 04 Hansen HC, Helmke K. The subarachnoid space surrounding the optic nerves. An ultrasound study of the optic nerve sheath. Surg Radiol Anat 1996; 18: 323 – 328 05 Helmke K, Hansen HC. Fundamentals of transorbital sonographic evaluation of optic nerve sheath expansion under intracranial hypertension II Patient study. Pediatr Radiol 1996; 26: 706 – 710 06 Ballantyne SA, O`Neill G, Hamilton R et al. Observer variation in the sonographic measurement of optic nerve sheath diameter in normal adults. European Journal of Ultrasound 2002; 15: 145 – 149 07 Geeraerts T, Launey Y, Martin L et al. Ultrasonography of the optic nerve sheath may be useful for detecting raised intracranial pressure after severe brain injury. Intensive Care Med 2007; 33: 1704 – 1711 08 Bäuerle J, Lochner P, Kaps M et al. Intra- and Interobserver Reliability of Sonographic Assessment of the Optic Nerve Sheath Diameter in Healthy Adults. J Neuroimaging 2012; 22: 42 – 45 09 Seitz J, Held P, Strotzer M et al. Magnetic resonance imaging in patients diagnosed with papilledema: a comparison of 6 different high-resolution T1- and T2(*)-weighted 3-dimensional and 2-dimensional sequences. J Neuroimaging 2002; 12: 164 – 171 10 Weigel M, Lagreze WA, Lazzaro A et al. Fast and Quantitative High-Resolution Magnetic Resonance Imaging of the Optic Nerve at 3.0 Tesla. Invest Radiol 2006; 41: 83 – 86 11 Lagreze WA, Lazzaro A, Weigel M et al. Morphometry of the Retrobulbar Human Optic Nerve: Comparison between Conventional Sonography and Ultrafast Magnetic Resonance Sequences. Invest Ophthalmol Vis Sci 2007; 48: 1913 – 1917 12 Rohr A, Riedel C, Reimann G et al. Pseudotumor cerebri: Quantitative InVivo Measurements of Markers of Intracranial Hypertension. Fortschr Röntgenstr 2008; 180: 884 – 890 13 Dubourg J, Javouhey E, Geeraerts T et al. Ultrasonography of the optic nerve sheath diameter for detection of raised intracranial pressure: a
Steinborn M et al. Normal Values for … Ultraschall in Med 2015; 36: 54–58
14
15
16
17
18
19
20 21
22
23 24
25
systematic review and meta-analysis. Intensive Care Med 2011; 37: 1059 – 1068 Helmke K, Hansen HC. Fundamentals of transorbital sonographic evaluation of optic nerve sheath expansion under intracranial hypertension I Experimental study. Pediatr Radiol 1996; 26: 701 – 705 Ertl M, Barinka F, Torka E et al. Ocular Color-Coded Sonography – A Promising Tool for Neurologists and Intensive Care Physicians. Ultraschall in Med 2014, (epub ahead of print) Steinborn M, Fiegler J, Kraus V et al. High Resolution Ultrasound and Magnetic Resonance Imaging of the Optic Nerve and the Optic Nerve Sheath: Anatomic Correlation and Clinical Importance. Ultraschall in Med 2011; 32: 608 – 613 Steinborn M, Fiegler J, Rüdisser K et al. Measurement of the Optic Nerve Sheath Diameter in Children: Comparison between Transbulbar Sonography and Magnetic Resonance Imaging. Ultraschall in Med 2011, (epub ahead of print) Brzezinska R, Schumacher R. Diagnostik eines erhöhten Hirndrucks bei shuntversorgten Kindern unter besonderer Berücksichtigung der transbulbären Sonographie des Nervus opticus. Ultraschall in Med 2002; 23: 325 – 332 Ballantyne J, Hollman AS, Hamilton R et al. Transorbital Optic Nerve Sheath Ultrasonography in Normal Children. Clinical Radiology 1999; 53: 740 – 742 Rohr A, Jensen U, Riedel C et al. MR Imaging of the Optic Nerve Sheath in Patients with Craniospinal Hypotension. AJNR 2010; 31: 1752 – 1757 Watanabe A, Kinouchi H, Horikoshi T. Effect of intracranial pressure on the diameter of the optic nerve sheath. J Neurosurg 2008; 109: 255 – 258 Geeraerts T, Newcombe VFJ, Coles JP et al. Use of T2-weighted magnetic resonance imaging of the optic nerve sheath to detect raised intracranial pressure. Critical Care 2008; 12: R114 Scanlan KA. Sonographic Artifacts and Their Origins. Am J Roentgenol 1991; 156: 1267 – 1272 Killer HE, Laeng HR, Flammer J et al. Architecture of arachnoid trabeculae, pillars, and septa in the subarachnoid space of the human optic nerve: anatomy and clinical considerations. Br J Ophthalmol 2003; 87: 777 – 781 Magoon EH, Robb RM. Development of myelin in human optic nerve and tract. A light- and electron microscopic study. Arch Ophthalmol 1981; 99: 655 – 659
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58
Original Article
Normal Values for Transbulbar Sonography and Magnetic Resonance Imaging of the Optic Nerve Sheath Diameter (ONSD) in Children and Adolescents
Authors
M. Steinborn1, M. Friedmann1, H. Hahn2, A. Hapfelmeier3, E. Macdonald1, K. Warncke2, A. Saleh1
Affiliations
1
2 3
Department of Diagnostic and Interventional Radiology and Pediatric Radiology, Städtisches Klinikum München Schwabing, Munich Department of Pediatrics, Technische Universität München (TUM), Munich Institute for Medical Statistics and Epidemiology, Technische Universität München (TUM), Munich
Key words
Abstract
Zusammenfassung
"
!
!
Purpose: To establish normal values of the optic nerve sheath diameter (ONSD) in children and adolescents for transbulbar sonography and magnetic resonance imaging. Materials and Methods: In 99 children and adolescents (age: 5.6 – 18.6 years, mean: 12 years) without neurologic or ophthalmologic disease, measurements of the ONSD with transbulbar sonography were performed. For comparison 59 children and adolescents (age: 5.1 – 17.4 years, mean 12.3 years) with a normal MR examination of the brain had measurements of the ONSD on a T2-weighted thin section sequence of the orbit. Besides establishing modality-related normal values, age dependency, accuracy and reproducibility of measurements were assessed. Results: Overall the mean ONSD was 5.75 ± 0.52 mm for transbulbar sonography and 5.69 ± 0.31 mm for MRI. There was no statistical significance between the 95 % percentiles and age for both transbulbar sonography (p = 0.332) and MRI (p = 0.336). As a parameter for the reproducibility of measurements, the repeatability coefficient (RC) was between 0.34 mm and 0.46 mm. The concordance correlation coefficient (CCC) values revealed a high agreement between readers both for transbulbar sonography (0.868) and MRI (0.796). Conclusion: Normal values for ONSD in children and adolescents found in this study are significantly higher than assumed. The values found for transbulbar sonography are confirmed by comparable results for MR measurements. A precise sonographic measurement technique and the consideration of normal values found hereby are essential for correct interpretation of ONSD measurements in children and adolescents.
Ziel: Bestimmung von Normwerten des Optikusnervenscheidendurchmessers (ONSD) bei Kindern und Jugendlichen für transbulbäre Sonografie und Magnetresonanztomografie. Material und Methoden: Bei 99 Kindern und Jugendlichen (Alter: 5,6 – 18,6 Jahre, MW: 12 Jahre) ohne neurologische oder ophthalmologische Grunderkrankung wurde der ONSD mittels transbulbärer Sonografie bestimmt. Als Vergleichsgruppe wurde bei 59 Kindern und Jugendlichen (Alter: 5,1 – 17,4 Jahre, MW: 12,3 Jahre) mit einer unauffälligen MRT-Untersuchung des Schädels der ONSD mittels einer T2-gewichteten Dünnschichtuntersuchung der Orbita ermittelt. Neben der methodenbezogenen Normwertbestimmung wurden Altersabhängigkeit der Messwerte, Messgenauigkeit und Reproduzierbarkeit der Messungen ermittelt. Ergebnisse: Der Mittelwert des ONSD im Gesamtkollektiv betrug für die transbulbäre Sonografie 5,75 ± 0,52 mm und für die MRT 5,69 ± 0,31 mm. Die Überprüfung der Altersabhängigkeit der 95 % Perzentile war weder für die Sonografie (p = 0,332) noch die MR-Tomografie (p = 0,336) statistisch signifikant. Der repeatability coefficient (RC-Koeffizient) als Maß für die Reproduzierbarkeit der Messungen ergab Werte zwischen 0,34 mm und 0,46 mm. Die Werte für den concordance correlation coefficient (CCC) ergaben eine hohe Übereinstimmung der Messungen zwischen den Betrachtern sowohl für die transbulbäre Sonografie (0,868) als auch die MRT (0,796). Schlussfolgerung: Die in dieser Studie ermittelten Normwerte des ONSD bei Kindern und Jugendlichen liegen deutlich höher als bisher angenommen. Die Messwerte für die transbulbäre Sonografie werden durch vergleichbare MRT-Werte bestätigt. Eine exakte sonografische Messtechnik und die Berücksichtigung der hierbei ermittelten Normwerte sind für die Interpretation von ONSD-Messungen bei Kindern und Jugendlichen unabdingbar.
● eye ● MR imaging ● ultrasound " "
received accepted
25.2.2014 11.7.2014
Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1385012 Published online: August 20, 2014 Ultraschall in Med 2015; 36: 54–58 © Georg Thieme Verlag KG Stuttgart · New York · ISSN 0172-4614 Correspondence Dr. Marc Steinborn Department of Pediatric Radiology, Städtisches Klinikum Munich Schwabing Kölner Platz 1 80804 Munich Germany Tel.: ++ 49/89/30 68 22 70 Fax: ++ 49/89/30 68 38 18 [email protected]
Steinborn M et al. Normal Values for … Ultraschall in Med 2015; 36: 54–58
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Normwerte für die transbulbäre Sonografie und Magnetresonanztomografie des Optikusnervenscheidendurchmessers (ONSD) bei Kindern und Jugendlichen
Already in 1870 the German anatomist Gustav Schwalbe demonstrated the communication between the intracranial subarachnoid space and the subarachnoid space surrounding the optic nerve [1]. Later, experimental studies showed that an increase in intracranial pressure leads to a shift of cerebrospinal fluid into the optic nerve sheath and that the optic nerve sheath diameter (ONSD) correlates with the degree of intracranial pressure [2]. Several study groups described the possibility of measuring the ONSD sonographically [3, 4]. Helmke et al. developed a standardized technique for the estimation of intracranial pressure in children by measuring the ONSD with transbulbar sonography. Normal values found in healthy subjects ranged from 1.9 to 3.5 mm in the first 4 years of life and 2.2 to 4 mm in older children up to 18 years [5]. For sonographic ONSD measurements in adults, mean values between 3.2 and 5.4 mm have been reported [6 – 8]. Within the last years several studies on MR imaging of the ONSD revealed normal mean values in healthy adults between 5.3 and 5.7 mm, a range that is already regarded as definitely pathologic by most of the studies using transbulbar sonography [9 – 13]. Whereas the anatomic structures and margins of the optic nerve and nerve sheaths can clearly be defined on MR imaging, a major problem of transbulbar sonography is the unfavorable transmission angle and the limited lateral spatial resolution [14]. Differences in the interpretation of the ultrasound reflexes of the retrobulbar region and high dependence on patient cooperation are further explanations for the discrepancies between MR and sonographic measurements [11].With the development of high-resolution ultrasound probes, the limitations of transbulbar sonography are progressively compensated [15]. In recent studies it could be shown that a good correlation between sonographic and MR measurements of the ONSD can be obtained if the corresponding anatomic structures are depicted and the measuring points are set correctly [16, 17]. The purpose of this study was to reestablish normal values for the ONSD in children and adolescents using high-resolution transbulbar sonography and MR imaging.
250 msec, slice thickness 1 mm, scan time 2:28 min; NT Intera 1.0 T, Philips Medical Systems, Best, Netherlands). Measurements of the ONSD were performed separately for each modality by two independent readers using the measurement tools of a conventional PACS system (Centricity RA 1000, GE Medical Systems). For each eye measurements of the optic nerve sheath were performed 3 mm behind the optic nerve papilla. For transbulbar sonography the measuring calipers were placed on the hypoechoic outer border surrounding the hyperechoic nerve sheath. To distinguish the outer border of the subarachnoid space from the hypoechoic tangential artifact of the dural sheath, the ampullary shape of the bulbar segment with the outer border of the subarachnoid space converging to the papilla had to be dem" Fig. 1). onstrated on the image (● For MR imaging the optic nerve sheath was defined by the distance between two measuring points that were placed on the border between the hyperintense fluid and the hypointense dur" Fig. 2). al sheath (● All measurements were repeated two times with a minimum delay of one week in between. For each modality mean values and standard deviations were calculated. In order to evaluate the age
Methods !
The study was approved by the institutional Ethics Committee. In otherwise healthy children and adolescents who had ultrasound examination for non-neurologic disease, transbulbar sonography was performed after informed consent from parents or legal guardians was obtained. An approved examination program for the orbit was chosen using the lowest mechanical index value (MI 0.1). A 17 – 5 MHz linear array transducer (iU 22, Philips Medical Systems, Best, Netherlands) was placed on the lateral aspect of the closed upper eyelid and angulated medio-caudally. In order to reach a straight course of the optic nerve and its sheaths, the children were asked to locate a sticker straight ahead at the ceiling above them through the closed or opened contralateral eye. At least three images of each side were taken and archived electronically. For comparison a consecutive group of children and adolescents who underwent magnetic resonance imaging of the brain for various reasons (headache/migraine, syncope/seizure, trauma, nonCNS tumor/infection) was selected. All selected patients had a normal MR examination of the brain and no clinical signs of elevated intracranial pressure. In addition to the routine imaging protocol, a T2-weighted axial thin section sequence of the orbit for measurement of the ONSD was acquired (TR 4000 msec, TE
Fig. 1 Transbulbar sonography demonstrating the bulbar segment of the optic nerve sheath with the outer hypoechoic border of the subarachnoid space converging to the papilla (arrows). Measurement of the ONSD is performed 3 mm behind the papilla. The diameter of the optic nerve sheath is measured as the distance between the hypoechoic outer borders surrounding the hyperechoic nerve sheath (white line). N = optic nerve. Abb. 1 Transbulbäre Sonografie mit Darstellung des bulbären Abschnitts der Optikusnervenscheide und Konvergenz der äußeren echoarmen Begrenzung des Subarachnoidalraumes zur Papille (Pfeile). Die Messung des ONSD erfolgt 3 mm hinter der Papille. Der Durchmesser der Optikusnervenscheide wird zwischen den echoarmen äußeren Begrenzungen der echoreichen Nervenhülle gemessen (weiße Linie). N = Nervus opticus.
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poor image quality. The overall mean value for the ONSD on transbulbar sonography was 5.75 ± 0.52 mm (range 4.6 – 7.7 mm). For comparison MR images of 59 patients (age: range 5.1 – 17.4 years; mean 12.3 years) were available for ONSD measurement. Seven eyes were excluded from analysis due to poor image quality resulting in a total number of 111 eyes that could be measured. The overall mean value for the ONSD on MRI was 5.69 ± 0.31 mm (range: 5.0 – 6.9 mm). Calculating the 95 % quantiles as a function of age showed no statistical significance between ONSD values and age neither for transbulbar sonography (p = 0.332) nor MRI (p = 0.336). For both imaging methods the accuracy of measurements was almost identical. The repeatability coefficient as a parameter for the intraobserver variation ranged between 0.34 mm and 0.46 mm. The concordance correlation coefficient representing the correlation of measurements between the readers was 0.868 " Fig. 3). for transbulbar sonography and 0.796 for MR imaging (●
Discussion !
Fig. 2 Axial T2-weighted MRI of the orbit: The hypointense optic nerve (N) is surrounded by the hyperintense CSF. The dura can be depicted as the outer hypointense border of the optic nerve sheath (arrows). The optic nerve sheath diameter is defined as the distance between the borders of CSF and dura 3 mm behind the papilla (white line). Abb. 2 Axiale T2-gewichtete MRT der Orbita: Der hypointense Nervus optikus (N) wird vom hyperintensen Liquor umgeben. Die Dura stellt sich als äußere hypointense Begrenzung der Optikusnervenscheide dar (Pfeile). Der Optikusnervenscheidendurchmesser entspricht dem Abstand zwischen den äußeren Begrenzungen des Liquors zur Dura 3 mm hinter der Papille (weiße Linie).
dependency of measurements, quantile regression was used to model the 95 % quantile of ONSD measurements as a function of age. The interobserver agreement of measurements was assessed in several ways. Bland Altman plots were calculated and the concordance correlation coefficient (CCC) was determined to quantify the strength of agreement between the readers. To assess intraobserver agreement, the repeatability coefficient (RC), which describes the maximum deviation that is expected for 95 % of two repeated measurements by the same reader, was calculated.
Results !
In 99 children and adolescents (age: range 5.6 – 18.6 years; mean 12 years), transbulbar sonography images of 181 eyes were included for evaluation. In 17 cases one eye had to be excluded due to
Steinborn M et al. Normal Values for … Ultraschall in Med 2015; 36: 54–58
From experimental studies on human cadavers, it is known that elevation of the intracranial pressure leads to a shift of cerebrospinal fluid from the intracranial subarachnoid compartment into the subarachnoid space of the optic nerve causing pressure-dependent dilatation of the optic nerve sheath [2]. Helmke et al. showed that the pressure-dependent changes of the optic nerve sheath diameter are most pronounced in the bulbar segment [14]. They developed a standardized method for transbulbar B-mode sonography in which measurements of the ONSD are performed 3 mm behind the papilla [5]. For children normal values of the ONSD between 1.9 to 4 mm were found and values above 4 mm in children under 4 years and 5 mm in children over 4 years were definitely regarded as abnormal [5, 18, 19]. Similar results were found for adults in whom normal values ranged from 2.4 to 4.7 mm [6]. With the development of advanced ultrasound imaging techniques, subsequent studies found higher normal values for the ONSD in adults with mean values ranging between 4.8 to 5.4 mm [7, 8]. In the last few years several studies focused on measuring the ONSD using MR imaging in various pathologic conditions [20 – 22]. Normal values of the ONSD in adults found with MR imaging were generally higher than those that have been published for transbulbar sonography. Although various imaging techniques were used (different field strength, slice orientation, slice thickness, image resolution), consistent mean values between 5.3 and 5.7 mm were obtained [9 – 12]. There was only one study where MR and sonographic measurements were compared directly [11]. Again measurement values for transbulbar sonography were significantly lower than the results for MRI and factors like examiner experience, incorrect cutting plane and limited spatial resolution of ultrasound were supposed to be reasons for the variation of results [11]. Despite the excellent spatial resolution of high-frequency linear ultrasound probes that are available nowadays, measuring the optic nerve sheath diameter from the transbulbar approach indeed is restricted by technical limitations. A major drawback of transbulbar sonography is the unfavorable intromission angle of 180° and the limited lateral spatial resolution. In addition tangential artifacts cause scattering and refraction of the ultrasound waves and lead to a signal loss and acoustic shadowing [23].
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Fig. 3 Bland Altman plots displaying the agreement between raters for transbulbar sonography (Sono) and magnetic resonance imaging (MRI). The continuous line displays the mean difference between the readers (Rater 0 – Rater 1) [mm]. The interrupted line shows the limits of agreement indicating the maximum difference between readers in 95 % of measurements [mm]. Note: RC = repeatability coefficient (maximum difference of same reader in 95 % of cases) [mm], CCC = concordance correlation coefficient.
Another important aspect is the ultrastructural composition of the subarachnoid space of the optic nerve sheath. Electron-microscopic studies have shown that the subarachnoid space is composed of a complex meshwork of trabeculations which has its highest density in the retrobulbar portion and displays multiple acoustic shadowing surfaces on ultrasound [24]. Thus, the subarachnoid space of the optic nerve, although containing cerebrospinal fluid, is not echo-free but is hyperechoic to varying degrees. On the other hand the inner nerve sheath which covers the hypoechoic optic nerve and represents the continuation of the pia mater is also hyperechoic and might therefore be mixed up with the trabeculated subarachnoid space [16]. As the trabeculation of the subarachnoid space surrounding the optic nerve is not homogeneous, the increase in echogenicity is furthermore variable and the outer border of the trabeculated subarachnoid space might be hard to define. Therefore, the morphology of the retrobulbar portion of the optic nerve sheath with its ampullary configuration and the outer border of the subarachnoid space converging to the papilla is a helpful landmark to define the outer border of the subarachnoid space. If these anatomic characteristics of the optic nerve and its sheath are considered ONSD, measurements with transbulbar sonography reach values that show a good correlation with MR measurements [16, 17]. The present study was conducted to establish normal values of the ONSD in children and adolescents and evaluate the sonographic measurement technique by comparing the results of transbulbar sonography with MR imaging. With mean values around 5.7 mm, our data confirm that normal values of the ONSD in children and adolescents are substantially higher than previously assumed and are in the range of values for healthy adults [11].
Abb. 3 Bland Altman Plots mit Darstellung der Übereinstimmung der Auswerter für die transbulbäre Sonografie (Sono) und die Magnetresonanztomografie (MRT). Die durchgezogene Linie stellt die mittlere Abweichung zwischen den Auswertern (Auswerter 0 – Auswerter 1) dar [mm]. Die gestrichelte Linie zeigt die maximale Differenz der Auswerter in 95 % der Fälle an [mm]. Anmerkung: RC = repeatability coefficient (maximale Differenz eines Auswerters bei Messwiederholung in 95 % der Fälle) [mm], CCC = concordane correlation coefficient.
We did not find age dependency in our study population. This might be due to the fact that only children over 5 years were included and that after the myelination of the optic nerve is completed no further significant growth of the nerve and the nerve sheath appears [25]. There are some limitations of our study that have to be mentioned. The selection of our study group of normal children and adolescents was based on clinical and MR imaging findings only. Especially patients getting MRI of the brain usually have a history of neurologic complaints leading to the imaging study. Although our patients had a normal neurologic status at the time of MR imaging, elevated intracranial pressure cannot be ruled out completely in every patient. Another limitation is the lack of measurement values for children under 5 years of age. As the feasibility and image quality of transbulbar sonography highly depend on patient cooperation, transbulbar sonography in healthy and awake children is limited to older children, usually above 5 years of age. From our own experience we expect that normal ONSD values in younger children will be significantly lower. In summary our study shows that normal values of the ONSD in children and adolescents are substantially higher than described before. This has to be considered when interpreting ONSD values in children and adolescents. Measurement values for transbulbar sonography and MR imaging correlate well if the characteristics of the retrobulbar ultrasound anatomy are considered.
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References 01 Schwalbe G. Untersuchungen über die Lymphbahnen des Auges und ihre Begrenzungen. Arch Mikr Anat 1870; 6: 1 – 61 02 Liu D, Kahn M. Measurement and relationship of subarachnoid pressure of the optic nerve to intracranial pressure in fresh cadavers. Am J Ophthalmol 1993; 116: 548 – 556 03 Skalka HW. Neural and dural optic nerve measurements with A-scan ultrasonography. South Med J 1978; 71: 399 – 400 04 Hansen HC, Helmke K. The subarachnoid space surrounding the optic nerves. An ultrasound study of the optic nerve sheath. Surg Radiol Anat 1996; 18: 323 – 328 05 Helmke K, Hansen HC. Fundamentals of transorbital sonographic evaluation of optic nerve sheath expansion under intracranial hypertension II Patient study. Pediatr Radiol 1996; 26: 706 – 710 06 Ballantyne SA, O`Neill G, Hamilton R et al. Observer variation in the sonographic measurement of optic nerve sheath diameter in normal adults. European Journal of Ultrasound 2002; 15: 145 – 149 07 Geeraerts T, Launey Y, Martin L et al. Ultrasonography of the optic nerve sheath may be useful for detecting raised intracranial pressure after severe brain injury. Intensive Care Med 2007; 33: 1704 – 1711 08 Bäuerle J, Lochner P, Kaps M et al. Intra- and Interobserver Reliability of Sonographic Assessment of the Optic Nerve Sheath Diameter in Healthy Adults. J Neuroimaging 2012; 22: 42 – 45 09 Seitz J, Held P, Strotzer M et al. Magnetic resonance imaging in patients diagnosed with papilledema: a comparison of 6 different high-resolution T1- and T2(*)-weighted 3-dimensional and 2-dimensional sequences. J Neuroimaging 2002; 12: 164 – 171 10 Weigel M, Lagreze WA, Lazzaro A et al. Fast and Quantitative High-Resolution Magnetic Resonance Imaging of the Optic Nerve at 3.0 Tesla. Invest Radiol 2006; 41: 83 – 86 11 Lagreze WA, Lazzaro A, Weigel M et al. Morphometry of the Retrobulbar Human Optic Nerve: Comparison between Conventional Sonography and Ultrafast Magnetic Resonance Sequences. Invest Ophthalmol Vis Sci 2007; 48: 1913 – 1917 12 Rohr A, Riedel C, Reimann G et al. Pseudotumor cerebri: Quantitative InVivo Measurements of Markers of Intracranial Hypertension. Fortschr Röntgenstr 2008; 180: 884 – 890 13 Dubourg J, Javouhey E, Geeraerts T et al. Ultrasonography of the optic nerve sheath diameter for detection of raised intracranial pressure: a
Steinborn M et al. Normal Values for … Ultraschall in Med 2015; 36: 54–58
14
15
16
17
18
19
20 21
22
23 24
25
systematic review and meta-analysis. Intensive Care Med 2011; 37: 1059 – 1068 Helmke K, Hansen HC. Fundamentals of transorbital sonographic evaluation of optic nerve sheath expansion under intracranial hypertension I Experimental study. Pediatr Radiol 1996; 26: 701 – 705 Ertl M, Barinka F, Torka E et al. Ocular Color-Coded Sonography – A Promising Tool for Neurologists and Intensive Care Physicians. Ultraschall in Med 2014, (epub ahead of print) Steinborn M, Fiegler J, Kraus V et al. High Resolution Ultrasound and Magnetic Resonance Imaging of the Optic Nerve and the Optic Nerve Sheath: Anatomic Correlation and Clinical Importance. Ultraschall in Med 2011; 32: 608 – 613 Steinborn M, Fiegler J, Rüdisser K et al. Measurement of the Optic Nerve Sheath Diameter in Children: Comparison between Transbulbar Sonography and Magnetic Resonance Imaging. Ultraschall in Med 2011, (epub ahead of print) Brzezinska R, Schumacher R. Diagnostik eines erhöhten Hirndrucks bei shuntversorgten Kindern unter besonderer Berücksichtigung der transbulbären Sonographie des Nervus opticus. Ultraschall in Med 2002; 23: 325 – 332 Ballantyne J, Hollman AS, Hamilton R et al. Transorbital Optic Nerve Sheath Ultrasonography in Normal Children. Clinical Radiology 1999; 53: 740 – 742 Rohr A, Jensen U, Riedel C et al. MR Imaging of the Optic Nerve Sheath in Patients with Craniospinal Hypotension. AJNR 2010; 31: 1752 – 1757 Watanabe A, Kinouchi H, Horikoshi T. Effect of intracranial pressure on the diameter of the optic nerve sheath. J Neurosurg 2008; 109: 255 – 258 Geeraerts T, Newcombe VFJ, Coles JP et al. Use of T2-weighted magnetic resonance imaging of the optic nerve sheath to detect raised intracranial pressure. Critical Care 2008; 12: R114 Scanlan KA. Sonographic Artifacts and Their Origins. Am J Roentgenol 1991; 156: 1267 – 1272 Killer HE, Laeng HR, Flammer J et al. Architecture of arachnoid trabeculae, pillars, and septa in the subarachnoid space of the human optic nerve: anatomy and clinical considerations. Br J Ophthalmol 2003; 87: 777 – 781 Magoon EH, Robb RM. Development of myelin in human optic nerve and tract. A light- and electron microscopic study. Arch Ophthalmol 1981; 99: 655 – 659
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