High resolution T2 MRI in the diagnosis of cerebellopontine angle and internal auditory canal lesions

Accepted Manuscript High resolution T2 MRI in the diagnosis of cerebellopontine angle and internal auditory canal lesions

Jonathan T. Maslan, Christopher M. Lack, Michael Zapadka, Tyler G. Gasser, Eric Oliver PII: DOI: Reference:

S0899-7071(17)30088-8 doi: 10.1016/j.clinimag.2017.05.009 JCT 8247

To appear in: Received date: Revised date: Accepted date:

20 July 2016 19 April 2017 9 May 2017

Please cite this article as: Jonathan T. Maslan, Christopher M. Lack, Michael Zapadka, Tyler G. Gasser, Eric Oliver , High resolution T2 MRI in the diagnosis of cerebellopontine angle and internal auditory canal lesions, (2017), doi: 10.1016/j.clinimag.2017.05.009

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT High Resolution T2 MRI in the Diagnosis of Cerebellopontine Angle and Internal Auditory Canal Lesions Jonathan T. Maslan, MD 1,3, Christopher M. Lack, MD, Ph.D.2; Michael Zapadka, D.O.2; Tyler G. Gasser, M.D.2,4; Eric Oliver, M.D., MD, FAAP1 1 Department of Otolaryngology, 2Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA;

US AN M

Corresponding Author: Jonathan Maslan, M.D. Neurotology Fellow Department of Otolaryngology St. Vincent’s Hospital 390 Victoria St Darlinghurst NSW 2010 Australia [email protected] Phone: +61 2 8382 6413

CR

IP

T

Author Email Addresses: Jonathan Maslan ([email protected]), Christopher Lack ([email protected]), Michael Zapadka ([email protected]), Tyler Gasser ([email protected]), Eric Oliver ([email protected]).

Present address: St. Vincent’s Hospital, 390 Victoria St, Darlinghurst NSW 2010, Australia 4 Present address: Scottsdale Medical Imaging, 3501 N. Scottsdale Rd., Ste. 130 Scottsdale, AZ 85251, USA

AC

CE

PT

ED

3

1

ACCEPTED MANUSCRIPT

ABSTRACT

CR

IP

T

HIGH RESOLUTION T2 MAGNETIC RESONANCE IMAGING (MRI) CAN PROVIDE EXQUISITE DETAIL OF INTERNAL AUDITORY CANAL (IAC) AND CEREBELLOPONTINE ANGLE (CPA) LESIONS. IN THIS RETROSPECTIVE CASE SERIES, BLINDED IMAGING SEQUENCES WERE DELIVERED TO THREE RADIOLOGISTS AND COMPARED WITH PREVIOUSLY ARCHIVED CLINICAL READS THAT WERE NON-BLINDED AND INCORPORATED BOTH T1+C AND T2 SEQUENCES TOGETHER. THIS ARTICLE DEMONSTRATES HIGH SENSITIVITY AND SPECIFICITY FOR HIGH RESOLUTION T2 MRI PARTICULARLY WITH LESIONS > 5 MM. THIS SUGGESTS A ROLE FOR HIGH RESOLUTION T2 MRI AS AN INITIAL SCREENING SEQUENCE OR AS A SURVEILLANCE SEQUENCE. INTRODUCTION

US

The evaluation of asymmetric sensorineural hearing loss (aSNHL) for the detection of lesions at

AN

the cerebellopontine angle (CPA), internal auditory canal (IAC), and inner ear involves multiple approaches including clinical examination, audiologic work up and imaging. Lesions of the

M

IAC/CPA include vestibular schwannomas, meningiomas, hemangiomas, lipomas, lymphomas, facial nerve tumors, and aneurysms [1]. However, only approximately 2.4% to 11% of patients

ED

who present to clinicians with complaints of asymmetric hearing loss have pathology in the

PT

IAC/CPA region to account for their symptoms [2-4]. The diagnostic study with the greatest sensitivity and specificity in the evaluation of aSNHL is MRI, and the MRI sequence that is most

CE

widely used for this purpose is T1 with gadolinium (T1+C) [5, 6]. MRI has shown superiority to CT and auditory brainstem response (ABR) in the detection of small IAC/CPA lesions,

AC

particularly for lesions less than 10 mm [5-10].

The utility of MRI is augmented when T1+C is complemented by high-resolution T2 sequences, as the latter can provide exquisite detail of IAC/CPA structures. Several studies have demonstrated that the 3D-SSFP high resolution T2 sequences Fast Imaging Employing Steady State Acquisition (FIESTA) and Constructive Interference in the Steady State (CISS) can obtain results similar to T1+C as screening tools [11-14]. These studies used a variety of methods to

2

ACCEPTED MANUSCRIPT compare high resolution T2 to T1+C, but they did not include a sufficient number of small lesions (<10 mm) and their protocols made it difficult to assess high resolution T2 as stand-alone sequences. An ideal study should completely blind the study radiologists to the diagnosis, should include an adequate number of < 10 mm lesions, and should provide the high resolution T2

T

sequence in isolation for a given patient (without the complementary T1+C available). Such

IP

information could provide a better clinical correlate that high resolution T2 alone can demonstrate

CR

equivalence or non-inferiority to T1+C in the diagnostic work up of aSNHL. The purpose of this study is to determine the equivalence of high resolution T2 sequences as a stand-alone screening

US

study for aSNHL as compared to the standard imaging protocol that includes T1+C. Employing high resolution T2 alone could result in cost savings, greater throughput in MRI scanners, and

M

ED

MATERIALS AND METHODS

AN

obviate the need for intravenous contrast.

After IRB approval was obtained, an internal audit was conducted of patients who underwent an

PT

IAC Screening Protocol MRI at WFUSM, which included a 3D-SSFP high-resolution T2

CE

weighted sequence (3D FIESTA [General Electric, Fairfield, CT] or 3D CISS [Siemens, Munich, Germany]) and a post-contrast T1 weighted sequence (3D SPGR [General Electric] or 3D

AC

FLASH [Siemens]) to assess the cranial base. Patients of all ages who underwent an MRI from January 1, 2005 until September 21, 2012 were included. Because this study utilized a database of patients who had previously undergone IAC Screening Protocols in their clinical evaluations, these patients were scanned using varying MRI protocols, though all at the same institution. Six different scanners were used for MRI studies: four were General Electric (all 1.5T field strength) and two were Siemens (one 1.5T and one 3T field strength). T2 weighted sequences were obtained with a slice thickness of 0.7 to 1 mm and the T1 weighted sequence obtained after

3

ACCEPTED MANUSCRIPT administration of 0.1 mmol/kg of Gd-DTPA (Magnevist) using a slice thickness of 2 to 2.5 mm depending on scanner type.

In order to obtain adequate statistical power, the most recent 120 patient charts from the study

T

period were then selected. These included MRIs from 2010 to 2012. There were no exclusion

IP

criteria in terms of demographic information. Neuroradiologists were asked to study the MRI

CR

sequences and comment on any abnormalities of the IAC, CPA, or adjacent structures that could contribute to otologic symptoms. Vascular loops were excluded. Three neuroradiologists—two

US

fellows and one attending physician—participated in the study. The fellows each had four years of radiology experience and did not have certificates of added qualifications (CAQ). The

AN

attending physician had 10 years of radiology experience and was CAQ-certified in neuroradiology. The patients’ images were presented to the neuroradiologists in random order,

M

and the order presented for the T1+C images was different than the order for the high resolution

ED

T2 sequences. The neuroradiologists did not communicate with each other about their findings, and they could not compare their high resolution T2 images to T1+C images. Each radiologist

PT

was asked to determine whether the study was of adequate quality to rule a lesion in or out. If a

CE

lesion was detected, they were asked to comment on its size. They were also asked if the alternate

AC

sequence would be helpful in their diagnosis.

Radiologist interpretations were then compared with the archived clinical interpretation from each patient’s chart, and on this basis statistical analysis, including true positives and true negatives, was performed. There were several study outcome measurements. For the T1 versus high resolution T2 statistical analysis, Kappa statistics, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated overall (all three raters) and by each rater individually. These were calculated based on the archived clinical interpretation, as most of these lesions were managed conservatively and there was no pathologic diagnosis. The

4

ACCEPTED MANUSCRIPT archived clinical interpretation was established by the combined interpretations of residents, fellows, and attending radiologists with both T1+C and high resolution T2 sequences available, as well as all relevant clinical information. As this study was performed to establish the reliability of high resolution T2 MRI in comparison to the existing radiographic screening standards at our

T

institution, non-inferiority testing was performed. To assess inter-rater reliability, the percent

IP

concordance and Fleiss Kappa were calculated for the T1+C scores and the high resolution T2

CR

scores.

US

RESULTS

One hundred and twenty patient IAC Screening Protocol MRIs were reviewed. Sixty-nine

AN

patients were female and 51 were male. Age at presentation and presenting symptoms could not be reliably assessed because many of the patients were referred from outside providers who made

M

the initial diagnosis. Thirty out of 120 patient images (25%) had positive findings on the

ED

previously archived official clinical reads. Eighty-three percent of patients had presumed schwannomas; on the remainder of the studies, alternative diagnoses were proposed including

PT

paragangliomas, meningiomas, and an arachnoid cyst. One of these patients had

CE

Neurofibromatosis Type 2 and had bilateral vestibular schwannomas. Of the thirty patients with positive findings, only four patients underwent surgery, such that their radiographically detected

AC

lesions could be confirmed with pathology. Three of these patients had schwannomas and the fourth had a paraganglioma. Four of the thirty patients underwent Gamma Knife therapy. Since the remainder of the lesions were either small or exhibited slow growth rates, these patients were managed conservatively and therefore no tissue pathology was available to give a definitive diagnosis. As such, the archived clinical interpretation from the patient’s chart was considered the gold standard for statistical calculation. The archived clinical interpretation involved one attending physician and one fellow, with all patient information available and both T1+C and high resolution T2 sequences available.

5

ACCEPTED MANUSCRIPT For any given patient, there were six reads documented (three neuroradiologists with two sequence types each), for a total of 720 reads. Seventy-eight patient MRIs had uniform agreement by the neuroradiologists that no lesion was present (“true negatives”). There were 14 reads (12 patients) noted by the neuroradiologists as having possible lesions versus artifacts, in which the

T

alternate sequence was requested. Seven were high resolution T2 sequences and seven were

IP

T1+C. In all cases, further review demonstrated that no lesion was present, and this correlated

CR

with the archived clinical interpretation. Of the 14 reads noted, there were three false positive reads, as judged by the level of confidence expressed by the neuroradiologists: two were T1+C

US

sequences and one was a high resolution T2 sequence. There were 18 total false negative reads: 10 were high resolution T2 and eight were T1+C. Where any discrepancies were found between

AN

the archived clinical interpretation and an interpretation by a radiologist in this study, the three radiologists convened together to review both the high resolution T2 and T1+C sequences

M

together to determine the presence or absence of a lesion by consensus. In all cases the consensus

ED

interpretation did not deviate from the original archived clinical interpretation. Non-inferiority testing was calculated at a margin of both 0.1 and 0.05. Using a margin of 0.1

PT

and of 0.05, this study demonstrated that the high resolution T2 sequences were not significantly

CE

inferior to the T1 results (p=0.0003 and p=0.0313, respectively). For high resolution T2, the overall statistics compared with the archived formal read were as follows: sensitivity 88.9%,

AC

specificity 99.6%, PPV 98.8%, NPV 96.4%, and Cohen’s Kappa of 0.92. When comparing the high resolution T2 interpretations of the three neuroradiologists to each other, the Fleiss Kappa was 0.91, suggesting a high inter-rater reliability. For T1+C, the overall statistics compared with the archived formal read were as follows: sensitivity 91.1%, specificity 99.3%, PPV 97.6%, and NPV 97.1%. The Fleiss Kappa was 0.90, which also suggested a high inter-rater reliability. These data are captured in Table 1. There were seven patients in whom at least one radiologist did not diagnose a lesion with at least one MRI sequence (Table 2). If high resolution T2 been used as a stand-alone study,

6

ACCEPTED MANUSCRIPT neuroradiologists 1, 2 and 3 would have missed one, three, and six lesions out of 30, respectively. Four out of seven patient MRIs had findings that were suggestive of a schwannoma, but none had a lesion that was greater than 5 mm. One of these lesions is shown in Figure 1. The fifth patient had a very slight signal (< 2 mm) at the fundus of the left IAC on T1+C that was interpreted as a

T

possible lesion on the archived clinical interpretation. Of the remaining two patients, one had a

IP

jugular foramen lesion that was approximately 1.3 cm and another had an arachnoid versus

CR

epidermoid cyst that was approximately 3.3 x 1.4 cm. When lesions 5 mm or less are excluded, the data are as follows: For high resolution T2, sensitivity 95.0%, specificity 99.6%, PPV 98.3%,

US

NPV 98.9%. For T1+C, sensitivity 91.7%, specificity 99.3%, PPV 96.5%, NPV 98.2%. Overall, the average size of the lesions detected was 10.9 mm (range 1.5 mm to 33 mm). The

AN

average size of lesions in which all neuroradiologists detected the lesions with all reads was 12 mm (range 4 mm to 29 mm). The average size of lesions in which at least one neuroradiologist

M

missed the lesion on at least one read was 8.7 mm (1.5 mm to 33 mm). However, this included

ED

the jugular foramen lesion (13 mm) and the possible arachnoid cyst (33 mm). When these are excluded, the average size of lesions in which at least one neuroradiologist missed the lesion on at

AC

DISCUSSION

CE

PT

least one read was 3 mm (range 1.5 mm to 5 mm).

The purpose of this study was to assess 3D-SSFP high resolution T2 MRI as a possible standalone screening imaging sequence in the evaluation of aSNHL. The sensitivity overall for high resolution T2 was 88.9% and for T1+C was 91.1%; however, for lesions greater than 5 mm the sensitivity of high resolution T2 was 95% versus 91.7% for T1+C. If high resolution T2 is equivalent to T1+C when lesions 5 mm or less are excluded, then the potential for this sequence to be used alone as a screening study could spare numerous patients the administration of contrast. Although Gadolinium-associated contrast reactions are rare, several studies have

7

ACCEPTED MANUSCRIPT demonstrated allergic and non-allergic reactions, ranging from mild to severe. Contrast is also contraindicated in patients with end-stage renal disease (ESRD) [15-18], in whom high resolution T2 alone could be of great utility. There is also emerging data of Gadolinium deposition in the central nervous system (CNS) of patients even without renal dysfunction [19]. The implications

T

of Gadolinium deposition in the CNS is unclear, but it is positively correlated with previous

IP

Gadolinium exposure [19].

CR

Although this study assessed high resolution T2 MRI as a screening sequence, it could alternatively be used as a surveillance sequence once a schwannoma has been diagnosed. This is

US

particularly true in tumors greater than 5 mm. The usage of high resolution T2 as a surveillance sequence would obviate the need for sequential doses of contrast administration for patient’s

AN

whose IAC/CPA lesions are being managed conservatively.

In comparison to previous studies which analyzed high resolution T2 MRI as a screening

M

modality for IAC/CPA lesions, this study establishes high levels of sensitivity and specificity –

ED

especially with lesions greater than 5 mm – with less information available to the neuroradiologists at the time of study. For example, in Rigby (2006) one neuroradiologist

PT

reviewed 50 patient charts retrospectively using high resolution T2 and T1+C concurrently to

CE

qualitatively assess whether each sequence could equivalently detect a cranial base lesion if it was present, and to determine if either high resolution T2 or T1+C provided information that the other

AC

did not [11]. This study design made it difficult to assess high resolution T2 as a stand-alone modality since T1+C was available at the time of image review. Stuckey et al. employed two experienced neuroradiologists to review 125 consecutive patient charts and compare high resolution T2 to T1+C [12]. The high resolution T2 images were evaluated first, without knowledge of the clinical data or of findings on the T1+C sequence, similar to our own study. They found a sensitivity of 100% and a specificity of 98.5% for Observer 1 and a sensitivity of 94% and a specificity of 93.5% for Observer 2. However, of the 18 lesions they detected, only

8

ACCEPTED MANUSCRIPT four were 10 mm or less and only one was five mm or less. This study made it difficult to assess the utility of high resolution T2 for small lesions. The current study demonstrates that both high resolution T2 and T1+C MRI sequences have limitations with regards to the smallest lesions (5 mm or less) when used alone, as well as with

T

two specific lesions: a 13 mm mass in the vicinity of the jugular foramen interpreted as a

IP

schwannoma versus paraganglioma, and a 33 mm arachnoid cyst versus epidermoid lesion at the

CR

transverse-sigmoid sinus junction. With regard to both these lesions, the neuroradiologists stated they were focused on lesions impinging on the auditory neural pathway and therefore these

US

lesions were outside their field of view

In terms of the twelve patients in whom at least one neuroradiologist interpreted a possible

AN

abnormality, 50% of these ambiguous findings occurred with high resolution T2 studies and 50% with T1+C studies. In all cases, when the neuroradiologist saw the complementary MRI

M

sequence, he correctly identified that no lesion was present. These results suggest that for the

ED

smallest signals that are difficult to distinguish from artifact, neither high resolution T2 nor T1+C is better than the other as a stand-alone modality, but together they can offer valuable information

PT

that can help clarify ambiguous findings. Such findings support the utility of having both

CE

sequences simultaneously available when screening studies are conducted. In terms of limitations of the current study, the clinical information provided to the

AC

neuroradiologists was more limited than what one would expect in a true clinical setting: there was no clinical history or side-specific complaints to guide their assessment. Instead, the neuroradiologists were asked to look for lesions in the IAC/CPA regions bilaterally that might account for aSNHL. Without these clinical clues, it is possible that the focus on a particular area or side might not be quite as reliable. This is especially true in cases in which a neuroradiologist felt that there was a notable finding of indeterminate significance. Another limitation of this study was that pathology was not available in most cases, so the gold standard for the true diagnosis was the archived clinical interpretation, which was based on an open format interpretation done

9

ACCEPTED MANUSCRIPT by multiple neuroradiologists with both sequence types and all clinical information available. The disadvantage of using the archived clinical interpretation as the gold standard is that no definitive diagnostic information was available for most of the lesions in this study, yet statistical inferences were made on the basis of presumed diagnoses. Although vestibular schwannomas can be diagnosed with a high degree of confidence with imaging alone, artifactual signals can be

IP

T

problematic, particularly with small lesions. It is possible that the smallest “missed lesions” (see

CR

Table B.2), such as the 1.5 mm lesion, would not have been classified as a schwannoma on subsequent imaging. The sensitivity calculations of high resolution T2 were diminished on the

US

assumption that this was a true positive, as our study design mandated that all calculations be based on the archived clinical interpretation. An alternate study design might have removed such

AN

disputed lesions from statistical calculations and would have dramatically altered the results.

M

CONCLUSIONS

ED

This study compared the sensitivity and specificity of 3D-SSFP high resolution T2 versus T1+C MRIs in the diagnostic evaluation of the CPA and IAC in patients with aSNHL. The results

PT

demonstrated that high resolution T2 was comparable to T1+C in the detection of IAC/CPA

CE

lesions. There was high sensitivity and specificity demonstrated for the high resolution T2 sequence alone, particularly for lesions over 5 mm. When there is an MRI signal that appears

AC

somewhat equivocal with regard to the presence of a lesion, there is greater utility in having the complementary T1+C sequence. Results of this study were similar to previous studies using high resolution T2 MRI sequences to detect lesions at the CPA and IAC regions. High resolution T2 should be considered as a screening sequence, but lesions less than 5 mm will be detected more frequently when both high resolution T2 and T1+C are available together. High resolution T2 should also be strongly considered as a stand-alone surveillance sequence for known lesions to assess growth.

10

ACCEPTED MANUSCRIPT ACKNOWLEDGEMENTS We would like to thank and acknowledge Whitney Hampton, MD, for assistance in data collection, and Nora Fino, MS for assistance with statistical analysis.

T

FUNDING

IP

This research did not receive any specific grant from funding agencies in the public, commercial,

AC

CE

PT

ED

M

AN

US

CR

or not-for-profit sectors.

11

ACCEPTED MANUSCRIPT REFERENCES

AC

CE

PT

ED

M

AN

US

CR

IP

T

[1] F. Bonneville, J.L. Sarrazin, K. Marsot-Dupuch, C. Iffenecker, Y.S. Cordoliani, D. Doyon, J.F. Bonneville, Unusual lesions of the cerebellopontine angle: a segmental approach, Radiographics 21(2) (2001) 419-38. [2] D.A. Carrier, M.A. Arriaga, Cost-effective evaluation of asymmetric sensorineural hearing loss with focused magnetic resonance imaging, Otolaryngol Head Neck Surg 116(6 Pt 1) (1997) 567-74. [3] W. Hollingworth, M.I. Bell, A.K. Dixon, N.M. Antoun, D.A. Moffat, C.J. Todd, Measuring the effects of medical imaging in patients with possible cerebellopontine angle lesions: a four-center study, Acad Radiol 5 Suppl 2 (1998) S306-9. [4] R.L. Daniels, C. Swallow, C. Shelton, H.C. Davidson, C.S. Krejci, H.R. Harnsberger, Causes of unilateral sensorineural hearing loss screened by high-resolution fast spin echo magnetic resonance imaging: review of 1,070 consecutive cases, Am J Otol 21(2) (2000) 173-80. [5] J.P. Stack, R.T. Ramsden, N.M. Antoun, R.H. Lye, I. Isherwood, J.P. Jenkins, Magnetic resonance imaging of acoustic neuromas: the role of gadolinium-DTPA, Br J Radiol 61(729) (1988) 800-5. [6] A.K. Robson, S.E. Leighton, P. Anslow, C.A. Milford, MRI as a single screening procedure for acoustic neuroma: a cost effective protocol, J R Soc Med 86(8) (1993) 4557. [7] W.A. Selters, D.E. Brackmann, Acoustic tumor detection with brain stem electric response audiometry, Arch Otolaryngol 103(4) (1977) 181-7. [8] S.G. Harner, E.R. Laws, Diagnosis of acoustic neurinoma, Neurosurgery 9(4) (1981) 373-9. [9] M.J. Ruckenstein, R.A. Cueva, D.H. Morrison, G. Press, A prospective study of ABR and MRI in the screening for vestibular schwannomas, Am J Otol 17(2) (1996) 317-20. [10] S.S. Chandrasekhar, D.E. Brackmann, K.K. Devgan, Utility of auditory brainstem response audiometry in diagnosis of acoustic neuromas, Am J Otol 16(1) (1995) 63-7. [11] P.J. Rigby, Comparison of FIESTA and gadolinium-enhanced T1-weighted sequences in magnetic resonance of acoustic schwannoma, The Radiographer 53(2) (2006) 11-21. [12] S.L. Stuckey, A.J. Harris, S.M. Mannolini, Detection of acoustic schwannoma: use of constructive interference in the steady state three-dimensional MR, AJNR Am J Neuroradiol 17(7) (1996) 1219-25. [13] R. Hermans, A. Van der Goten, B. De Foer, A.L. Baert, MRI screening for acoustic neuroma without gadolinium: value of 3DFT-CISS sequence, Neuroradiology 39(8) (1997) 593-8. [14] P. Held, C. Fellner, J. Seitz, S. Graf, F. Fellner, J. Strutz, The value of T2(*)weighted MR images for the diagnosis of acoustic neuromas, Eur J Radiol 30(3) (1999) 237-44. [15] M.A. Perazella, How should nephrologists approach gadolinium-based contrast imaging in patients with kidney disease?, Clin J Am Soc Nephrol 3(3) (2008) 649-51.

12

ACCEPTED MANUSCRIPT

AC

CE

PT

ED

M

AN

US

CR

IP

T

[16] C.H. Hunt, R.P. Hartman, G.K. Hesley, Frequency and severity of adverse effects of iodinated and gadolinium contrast materials: retrospective review of 456,930 doses, AJR Am J Roentgenol 193(4) (2009) 1124-7. [17] K.P. Murphy, K.T. Szopinski, R.H. Cohan, B. Mermillod, J.H. Ellis, Occurrence of adverse reactions to gadolinium-based contrast material and management of patients at increased risk: a survey of the American Society of Neuroradiology Fellowship Directors, Acad Radiol 6(11) (1999) 656-64. [18] J.R. Dillman, J.H. Ellis, R.H. Cohan, P.J. Strouse, S.C. Jan, Frequency and severity of acute allergic-like reactions to gadolinium-containing i.v. contrast media in children and adults, AJR Am J Roentgenol 189(6) (2007) 1533-8. [19] T. Kanda, T. Fukusato, M. Matsuda, K. Toyoda, H. Oba, J. Kotoku, T. Haruyama, K. Kitajima, S. Furui. Gadolinium-based contrast agent accumulates in the brain even in subjects without severe renal dysfunction, Radiology 276(1) (2015) 228-232.

13

ACCEPTED MANUSCRIPT Figure A.1.

AC

CE

PT

ED

M

AN

US

CR

IP

T

An intracanalicular lesion < 5 mm is demonstrated in the T1+C (left) and high resolution T2 (right) images above. Lesions of this size were detected at a lower rate than were lesions above 5 mm.

14

ACCEPTED MANUSCRIPT Table B.1. Sensitivity, specificity, PPV, and NPV by Neuroradiologist. Neuroradiologist 2

Neuroradiologist 3

T1+C

T2

T1+C

T2

T1+C

T2

Sensitivity 93.3%

96.7%

96.7%

90.0%

83.3%

80.0%

Specificity 100.0%

100.0%

97.8%

100.0%

100.0%

98.9%

PPV

100.0%

100.0%

93.5%

100.0%

100.0%

96.0%

NPV

97.8%

98.9%

98.9%

96.8%

94.7%

93.7%

CR

IP

T

Neuroradiologist 1

US

Each neuroradiologist reviewed the T1+C images independently and then the High Resolution T2 images. Kappa values were similar for T1+C and T2, but there was some

AN

variability among neuororadiologists in terms of sensitivity, specificity, positive

AC

CE

PT

ED

M

predictive value (PPV), and negative predictive value (NPV).

15

ACCEPTED MANUSCRIPT

Neuroradiologist 2

Neuroradiologist 3

T1+C

T2

T1+C

T2

T1+C

T2

Pos

Pos

Pos

Pos

Pos

Neg

Pos

Pos

Pos

Neg

Neg

Neg

Pos

Pos

Pos

Pos

Neg

Pos

Pos

Pos

AN

4 mm left

Neuroradiologist 1

Pos

Pos

Pos

Neg

Pos

Neg

Pos

Neg

Neg

Neg

Neg

ED

Table B.2. Missed Lesions

Pos

Neg

Neg

Neg

Neg

Pos

Pos

Pos

Neg

Neg

schwannoma 5 mm

1.5 mm

13 mm

lesion

AC

foramen

CE

jugular

Arachnoid

PT

Lesion

M

schwannoma

US

2 mm

CR

schwannoma

IP

2.5 mm

T

IAC lesion

Neg

cyst

16

ACCEPTED MANUSCRIPT There were seven patients in whom at least one neuroradiologist interpretation differed from the official clinical read. A distribution of the neuroradiologist interpretations for

AC

CE

PT

ED

M

AN

US

CR

IP

T

each lesion is demonstrated.

17

ACCEPTED MANUSCRIPT

CR

IP

T

Figure 1

AC

CE

PT

ED

M

AN

US

An intracanalicular lesion < 5 mm is demonstrated in the T1+C (left) and high resolution T2 (right) images above. Lesions of this size were detected at a lower rate than were lesions above 5 mm.

18

ACCEPTED MANUSCRIPT Highlights

T

IP

CR US AN M ED



PT



CE



T1 with contrast MRI is the current gold standard in diagnosing inner ear lesions High resolution T2 sequences offer exquisite detail of inner ear structures and can aid in the diagnosis of inner lesions When used independently, both T1 and T2 lesions may miss lesions 5 mm or less in size The combination of MRI imaging sequences likely provides the greatest diagnostic sensitivity, but high resolution T2 can have a role in lesion surveillance and monitoring if used independently

AC



19