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Reproducibility and Repeatability of Volumetric Measurements for Olfactory Bulb Volumetry

Rationale and Objectives

The aim of this study was to compare different sequences for olfactory bulb volumetry using 3-T magnetic resonance imaging, evaluating reproducibility, repeatability, and systematic biases.

Materials and Methods

Twenty-two volunteers underwent 3-T magnetic resonance imaging of the frontal skull base in this prospective study. Imaging included constructive interference in steady state (CISS), T2-weighted (T2w) three-dimensional (3D) sampling perfection with application-optimized contrasts using different flip-angle evolutions, and T2w two-dimensional (2D) turbo spin-echo sequences. Two observers independently performed two olfactory bulb volumetric studies per bulb and sequence. Intraobserver and interobserver reliability was assessed using intraclass correlation coefficients. For the evaluation of reproducibility, concordance correlation coefficients were determined, and for repeatability and systematic biases, Bland-Altman plots were analyzed.

Results

Intraclass correlation coefficient analysis of the specialized observer yielded almost perfect results for intraobserver reliability (0.94, 0.85, and 0.93 for the CISS, T2w 3D, and T2w 2D sequences, respectively). For the less experienced observer, the results were 0.86 0.78, and 0.74 for the CISS, T2w 3D, and T2w 2D sequences, respectively. Interobserver reliability showed almost perfect agreement for all sequences (0.92, 0.86, and 0.86, respectively). The CISS sequence yielded the highest concordance correlation coefficient (0.84), precision (0.85), and accuracy (0.99). Bland-Altman plot analyses revealed the lowest repeatability coefficients for the T2w 2D sequence. Volumetric measurements of T2w 2D imaging showed systematically lower volumetric results compared to the CISS sequence (−22.7%) and the T2w 3D sequence (−8.3%).

Conclusions

Comparison of three imaging sequences for olfactory bulb volumetry yielded the best values for the CISS sequence in terms of intraobserver and interobserver reliability, reproducibility, accuracy, and precision. Given that even less experienced observers achieve almost perfect results, the CISS sequence is recommended for olfactory bulb volumetry.

Studies indicate a prevalence of about 20% for olfactory dysfunction in the Western world. Within the field of olfactory dysfunction, olfactory bulb (OB) volumetry is a nascent technique that has already been used as a complementary prognostic tool for radiologic diagnosis to predict outcomes in olfactory disorders . Decreases in OB volume have been identified in all five of the most most frequent etiologies of smelling disorders (ie, sinonasal disease , postinfectious , posttraumatic , neurodegenerative diseases , and idiopathic olfactory disorders ), and a volume increase after successful olfactory rehabilitation in sinonasal diseases has been shown. These dynamic changes are most probably due to the fact that the human OB retained the capability for neuroneogenesis and therefore exhibits high structural plasticity, whereby OB volume is correlated with the afferent neural activity transmitted by the olfactory receptor neurons .

In 1997, Yousem et al described magnetic resonance imaging (MRI) as a feasible method for OB volumetry on the basis of T1-weighted (T1w) sequences at 1.5 T. However, further studies using MRI OB volumetry to evaluate olfactory dysfunction were heterogeneous in the application of sequence types , scanning parameters , and technical equipment used . Until now, a systematic radiologic comparison of volumetric results using various standardized sequences to rule out a systematic bias possibly underestimating or overestimating OB volumes has not been performed, and a reference standard for MRI OB volumetry has not been established. The latter and the limited resolution gained at 1.5 T complicate a comparative quantification of volumetric results of this small paleocortical structure. Further development of MRI techniques and the use of MRI at higher field strengths (ie, at 3 T) could help resolve the aforementioned deficiencies, because the increased signal-to-noise ratio can be invested in better spatial resolution .

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Materials and methods

Participant Recruitment and Sampling

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Imaging Procedures

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Data Analysis

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Figure 1, Comparison of sequences applied for olfactory bulb (OB) volumetry at 3 T. (a–c) Constructive interference in steady state (repetition time, 11.68 ms; echo time, 5.84 ms; voxel size, 0.125 mm 3 ), (d–f) T2-weighted three-dimensional sequence (repetition time, 1000 ms; echo time, 132 ms; voxel size, 0.125 mm 3 ), and (g–i) T2-weighted two-dimensional sequence (repetition time, 4800 ms; echo time, 150 ms; voxel size, 0.32 mm 3 ) in the axial (a,d,g) , sagittal (b,e,h) , and coronal (c,f,i) planes. All images are from the same volunteer. Areas of left OB where volumetry was performed (hatched areas) in (a) demonstrate an OB during segmentation: the contours are lined using the segmentation tool with a diameter of 1 mm just before defining the transitional zone between the OB and the olfactory tract ( white short arrowhead ), the left olfactory tract and its transition to the OB ( white short arrowheads ), the accessory vessel at the left anterolateral pole of the OB ( white open arrows ), the proper olfactory artery ( white long arrowheads ), stair-step artifacts ( white lightning symbol and arrows ), bilateral artificial gaps in the horizontal lamella of the cribriform plate ( white star ) due to the overestimation of cerebrospinal fluid, and missing structures ( additional white question marks ). A, anterior; I, inferior; L, left; P, posterior, R, right; S, superior.

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Statistical Analysis

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CR=1.96×∑ni=1(Vi2−Vi1)2n−1,−−−−−−−−−−√ CR

=

1.96

×

i

=

1

n

(

V

2

i

V

1

i

)

2

n

1

,

where CR is the coefficient of repeatability; V 2 is the volumetric result on the second pass, and V 1 is the volumetric result on the first pass.

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Results

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Table 1

CCCs, Interobserver Reliability, and Reproducibility (n = 44)

Sequence CCC ρ c 95% CI Pearson’s ρ (Precision) Bias Correction Factor c b (Accuracy) CISS First evaluation 0.81 0.67–0.89 0.82 0.98 Second evaluation 0.75 0.59–0.85 0.76 0.99 Average 0.84 0.73–0.91 0.85 0.99 T2w 3D First evaluation 0.68 0.49–0.81 0.68 0.99 Second evaluation 0.63 0.44–0.76 0.71 0.88 Average 0.76 0.61–0.86 0.79 0.96 T2w 2D First evaluation 0.63 0.44–0.76 0.71 0.88 Second evaluation 0.67 0.48–0.80 0.70 0.95 Average 0.76 0.61–0.85 0.82 0.92

CCC, concordance correlation coefficient; CI, confidence interval; CISS, constructive interference in steady state; 3D, three-dimensional T2w, T2-weighted; 2D, two-dimensional.

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Figure 2, Systematic bias of compared sequences for olfactory bulb volumetry. Bland-Altman plots of difference of volumetric measurement results (y axis) against average volumetric measurement results (x axis), with mean absolute difference (ie, bias; continuous line) and 95% limits of agreement (dashed lines) for (a) comparison of the T2-weighted (T2w) two-dimensional (2D) and constructive interference in steady state (CISS) sequences, (b) comparison of the T2w 2D and T2w three-dimensional (3D) sequences, and (c) comparison of the T2w 3D and CISS sequences. Dash-dotted lines are related with significant regressions in (a) (slope = −0.428, P < .001) and (b) (slope = −0.309, P = .005). The regression in (c) is not significant (slope = −0.131, P = 0.171). All values are given as absolute values in cubic millimeters.

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Table 2

Repeatability and Test-retest Reliability (n = 44)

Limits of Agreement Sequence Arithmetic Mean Bias Lower Limit Upper Limit Coefficient of Repeatability CISS Observer 1 0.95 −15.63 17.54 16.59 Observer 2 −4.16 −25.18 16.87 21.01 T2w 3D Observer 1 2.64 −17.67 22.94 20.31 Observer 2 −3.09 −29.83 23.64 26.74 T2w 2D Observer 1 0.48 −11.40 12.35 11.88 Observer 2 −1.57 −21.77 18.64 20.20

CISS, constructive interference in steady state; 3D, three-dimensional T2w, T2-weighted; 2D, two-dimensional.

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Discussion

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Conclusions

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