Magnetic Resonance Imaging 33 (2015) 401–406
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Diffusion tensor imaging focusing on lower cervical spinal cord using 2D reduced FOV interleaved multislice single-shot diffusion-weighted echo-planar imaging: comparison with conventional single-shot diffusion-weighted echo-planar imaging Eun Hae Park a, Young Han Lee a, Eun-Kee Jeong b, Yun Ho Roh c, Jin-Suck Suh a,⁎ a
Department of Radiology, Research Institute of Radiological Science, Medical Convergence Research Institute, and Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea b Department of Radiology, Utah Center for Advanced Imaging Research, University of Utah, Salt Lake City, UT, USA c Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Republic of Korea
a r t i c l e
i n f o
Article history: Received 26 April 2014 Revised 16 September 2014 Accepted 10 January 2015 Keywords: Magnetic resonance imaging Diffusion Diffusion tensor Cervical spinal cord
a b s t r a c t Purpose: To evaluate the performance of diffusion tensor imaging (DTI) of the cervical spinal cord by comparing 2-dimensional standard single-shot interleaved multisection inner volume diffusion-weighted echo-planar imaging (2D ss-IMIV-DWEPI) and conventional 2D ss-DWEPI in a clinical population, focusing on the lower cervical spinal cord. Materials and Methods: From July to September 2013, a total of 23 patients who underwent cervical spinal MR imaging with DTI were retrospectively enrolled in this study (M:F = 7:16, mean age 45 years, age range 24–76 years). Exclusion criteria were: previous prosthesis insertion (n = 5), syringomyelia on T2-weighted imaging (n = 4), and spinal cord tumor (n = 0). All MRI examinations were performed using 3.0 T imaging with a phased-array spine coil including two different 2D reduced FOV DTI sequences: 2D ss-IMIV-DWEPI (iDTI) and 2D ss-DWEPI without interleaving (cDTI). For quantitative analysis, two musculoskeletal radiologists who were blinded to the sequence measured fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values throughout the whole cervical spinal cord (C1-T1). For qualitative analysis, the readers rated each image based on spinal cord distortion, dural margin delineation, and depiction of intervertebral disc. Quantitative and qualitative evaluations were analyzed separately for upper and lower segments. The t-test was used for quantitative analysis and two-way analysis of variance (ANOVA) and t-tests were performed for qualitative analysis. Results: FA was significantly higher and ADC was significantly lower on iDTI compared with cDTI (0.679 versus 0.563, respectively, for FA; 631 versus 1026, respectively, for ADC; p b 0.001), and this was consistently observed in the lower segment of the spinal cord. The reviewers rated iDTI as superior in terms of all assessed characteristics. For qualitative analysis, the mean iDTI score was significantly higher than the cDTI score for both the lower and upper segments (p b 0.001). Conclusion: 2D rFOV ss-IMIV-DWEPI demonstrated higher performance than conventional 2D rFOV ss-DWEPI in terms of improving image quality, even in the lower segment of the cervical spinal cord. © 2015 Elsevier Inc. All rights reserved.
1. Introduction Diffusion tensor imaging (DTI) provides not only structural integrity information, but also directional information by measuring
⁎ Corresponding author at: Department of Radiology, Research Institute of Radiological Science, Medical Convergence Research Institute, and Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea, 50–1 Yonsei-ro, Seodaemun-gu, Seoul, 120–752, Republic of Korea. Tel.: +82 2 2228 7400; fax: +82 2 393 3035. E-mail address: [email protected] (J-S. Suh). http://dx.doi.org/10.1016/j.mri.2015.01.007 0730-725X/© 2015 Elsevier Inc. All rights reserved.
water molecule diffusion within tissues. Obtained metrics from DTI are fractional anisotropy (FA), the values of apparent diffusion coefficient (ADC), and eigenvalues, which provide information on the scalar properties of the diffuse translation for extracellular water molecules [1–4]. Previous studies have shown that these metrics reflect the microstructure of the spinal cord and provides visualization of fiber tractography, enabling tracking of the white matter pathways in the brain and spinal cord. Moreover, the application of DTI at the cervical spinal cord allows characterization of microstructural changes including demyelinating disease, infarction, myelopathy, traumatic injury, and spinal cord tumor [5–15].
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However, in practice, the usefulness of DTI at the cervical spinal cord (CSC) has been impeded by 1) the small dimension of the CSC, 2) partial volume artifacts from surrounding cerebral spinal fluid (CSF) and lipid, 3) motion artifacts from breathing, swallowing, and CSF pulsation, and 4) large bony structures that cause abrupt changes in magnetic susceptibility [16–19]. For DTI of the CSC, standard single-shot diffusion-weighted echo-planar imaging (ss-DWEPI) is widely used in clinical cervical MR imaging. However, this protocol has a long readout time and low bandwidth in the phase encode direction, and is therefore prone to distortions and motion artifacts. In previous studies, these limitations were emphasized in the lower CSC [11,20,21]. Degenerative changes of the cervical spine including spondylosis and disc herniation are known to affect the lower segment because of the relative burden of weight and extensive range of motion [22]. However, several previous studies have emphasized the limitations of cervical DTI of the lower segment. This is mainly because of its location close to the lungs and heart, and negative effects associated with the construction of the surface coil [11,20,21]. Over the past decades, there have been several efforts using various EPI-based methods to overcome these limitations, including line scan imaging [23,24], navigated fast spin-echo [3], propeller-based imaging [25–27], parallel EPI [28–30], ZOOM-EPI [31], multichannel coil [32], and more recently, reduced effective field of view (FOV) in the phase encoding direction, an approach that is currently in the limelight. Reducing the FOV in the phase encode (PE) direction enables a drastic shortening of the readout time and also increases the (pseudo)bandwidth in the phaseencoding direction. In addition, geometric distortion in ss-DWEPI is proportional to the FOV in the phase-encoding direction; therefore, susceptibility-related artifacts and pixel misregistration can be reduced in ss-DWEPI [16,18,19]. An equally important method is the interleaved multisection inner volume (IMIV) technique, which provides double inversion/ refocusing radio-frequency pulses at 2D ss-DWEPI. This allows for acquisition of the entire cervical spinal cord with 1 interleaved image in the sagittal plane [7]. A few reports on the application of IMIV techniques at the CSC have been published [7,33–35], but there are no direct comparisons with conventional protocols focusing on the lower CSC. Therefore, the purpose of this study was to evaluate the performance of DTI in the cervical spinal cord by comparing 2D ss-IMIV-DWEPI (iDTI) and conventional 2D ss-DWEPI (cDTI) in a clinical population, focusing on the lower cervical spinal cord.
2. Materials and methods 2.1. Study population This retrospective study was approved by the institutional review board for human research. A total of 34 consecutive patients underwent cervical spinal MRI between July 2013 and September 2013. Any patients with unstable vital signs, history of interbody fixation, syringomyelia, or spinal cord tumor were excluded. As a result, 9 of the 31 patients were excluded; 5 patients had a clinical history of interbody fixation and 4 showed increased signal of the CSC due to compressive myelopathy and syringomyelia. Thus, 23 patients who underwent cervical spinal cord DTI performed by iDTI and conventional cDTI were enrolled in this study. The study population comprised 7 men and 16 women (age range, 24–76 years; mean age, 45.0 years) who underwent cervical spinal MRI for the following reasons: cervical compressive myelopathy, n = 12; neck pain, n = 6; bone metastases, n = 2, anomaly screening, n = 2; health check-up, n = 1.
2.2. Imaging study All MRI examinations were performed using a 3.0 T whole body MR imaging system (Trio, Siemens Healthcare, Erlangen, Germany) with a phased-array spine coil and without cardiac gating. Conventional 2D cervical spinal MR imaging was performed first, followed by DTI. Conventional 2D cervical spinal MR imaging consisted of sagittal and axial T1-weighted fast spin echo (FSE) sequences and sagittal and axial T2-weighted FSE sequences. The parameters for the sequences were as follows. Spin echo sagittal T1WI scans: TR/TE 400/10 msec; FOV 260 mm; acquisition matrix 448 × 336; slice thickness 3 mm with 0.3 mm gap; number of excitations (NEX) 2. Sagittal fast spin-echo fat-suppressed T2WI scans: TR/TE 3500/110 msec; FOV 260 mm; acquisition matrix 512 × 358; slice thickness 3 mm with 0.3 mm gap; NEX 2. Axial T1WI scans: TR/TE 400/10 msec; FOV 180 mm; acquisition matrix 320 × 256; slice thickness 3 mm with 0.3-mm gap; NEX 2. Axial T2WI scans: TR/TE 3800/106 msec; FOV 180 mm; slice thickness 3 mm with 0.3-mm gap; resolution 320 × 256; NEX 2. 2D iDTI was performed with the following parameters: TR/TE 4000/65 msec; FOV 192 × 48 mm; acquisition matrix 128 × 32; 10 sagittal slices; slice thickness 2 mm without gap; voxel size 1.5 × 1.5 × 2.0 mm; EPI factor 32; number of excitations 8; b factors of 0 and 500 s/mm 2; and 10 interleaved sections. Diffusionweighted gradients were applied in 12 noncollinear directions. Total scanning time was 7 minutes. Additional comparison cDTI was performed using the same section thickness and location with TR/TE 1100/65 msec and a total scanning time of 2 minutes (Table 1). 2.3. Image interpretation DTI images were retrospectively reviewed by two musculoskeletal radiologists (one [Y.H.L.] with more than 8 years of experience in musculoskeletal imaging and one [E.H.P.] in musculoskeletal fellowship) who were blind to imaging information. 2.4. Quantitative analysis DTI metrics of eigenvalues were calculated and measured for both iDTI and conventional cDTI as follows: fractional anisotropy (FA), apparent diffusion coefficient (ADC; × 10 −3 mm 2s −1). Regions of interest (ROIs) for FA and the ADC map were measured manually using anatomy and cord morphology from the T2WI scan as a reference. Seven ROIs, ranging from 7 to 13 mm 2 (mean 9.2 mm) in size, were selected from a sagittal section throughout the whole intervertebral disc level of the cervical spine. Each ROI was applied both in white and gray matter, where each level of CSC was depicted in maximum volume, and care was taken to exclude at least 2 voxels from the edge of anterior and posterior margins. 2.5. Qualitative analysis The following three characteristics were rated to evaluate the clinical utility of iDTI and cDTI: spinal cord distortion, dural margin Table 1 Imaging parameters for the DTI sequences.
TR/TE (ms) FOV (frequency × phase encode) (cm) resolution Bandwidth (Hz/pixel) Slice thickness (mm) b value (s/mm2) Acquisition time (min:s)
cDTI
iDTI
1100/65 192 × 48 128 × 32 1562 2 0, 500 1:59
4000/73 192 × 48 128 × 32 1562 2 0, 500 7:00
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delineation (evaluation of anatomy), and depiction of intervertebral disc (evaluation of level identification). Two blinded reviewers assigned scores according to a five-point grading system, as follows. For spinal cord distortion and dural margin delineation, 1 = nondiagnostic, 2 = questionable, 3 = adequate, 4 = good, 5 = excellent for diagnosis. For depiction of intervertebral disc, 1 = not seen, 2 = subtle, 3 = less than 50% visible, 4 = 50–75% visible, 5 = more than 75% visible. The DTI metrics and scoring were evaluated for the entire level through the CSC. Intervertebral disc regions from C1/2 to C4/5 were regarded as the upper segment and those from C5/6 to C7/T1 as the lower segment. The mean values of the upper and lower segments were calculated to compare the performance of cDTI and iDTI.
2.6. Statistical analysis Statistical analysis was performed with SAS version 9.2 (SAS Institute, Cary, NC, USA). DTI metrics were compared between 2 sequences using t-tests. Two-way analysis of variance (ANOVA) and t-tests were performed to compare the scores of spinal cord distortion, delineation of dural margin, and depiction of intervertebral disc. P b 0.05 was considered to indicate a significant difference. The intraclass correlation coefficient (ICC) was used to statistically define interobserver agreement of DTI metrics.
3. Results 3.1. Quantitative analysis The mean values of DTI metrics in whole, upper, and lower CSC using cDTI versus iDTI were as follows: (a) FA value of whole CSC, 0.563 versus 0.679 (p b 0.001); (b) ADC value (× 10 −3 mm 2s −1) of whole spine, 1026.2 versus 631.1 (p b 0.001); (c) FA value of upper CSC, 0.554 versus 0.717 (p = 0.009); (d) ADC value of upper CSC, 1051.2 versus 589.1 (p b 0.001); (e) FA value of lower CSC, 0.574 versus 0.628 (p b 0.001); (f) ADC value of lower CSC, 993 versus 687 (p b 0.001).
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3.2. Qualitative evaluation The iDTI imaging was strongly preferred by reviewers with respect to distortion of spinal cord, delineation of dural margin, and depiction of intervertebral disc. The sequences of iDTI and cDTI were significantly different for all of these characteristics. Even in the lower segment of the CSC, the score of iDTI was significantly higher than that of cDTI for both the FA map and ADC map (Figs. 1, 2). For spinal cord distortion (Fig. 3), the mean score of upper and lower segments for cDTI versus iDTI were as follows: (a) FA map of upper CSC, 3.7 versus 4.7, respectively; (b) ADC map of upper CSC, 3.5 versus 4.4; (c) FA map of lower CSC, 3.0 versus 4.3; (d) ADC map of lower CSC, 3.1 versus 4.2. For dural margin delineation, the mean score of upper and lower segment of cDTI versus iDTI were as follows: (a) FA map of upper CSC, 2.9 versus 4.3; (b) ADC map of upper CSC, 3.2 versus 4.0; (c) FA map of lower CSC, 2.3 versus 4.2; (d) ADC map of lower CSC, 2.6 versus 4.1. Finally, for depiction of intervertebral disc, the mean score of upper and lower segment of cDTI versus iDTI were as follows: (a) FA map of upper CSC, 2.1 versus 2.9, respectively; (b) ADC map of upper CSC, 2.6 versus 3.6; (c) FA map of lower CSC, 1.8 versus 2.9; (d) ADC map of lower CSC, 2.3 versus 3.4 (Tables 2 and 3). The ICC values of repeated measurements of FA at 2-week intervals were 0.572 (95% confidence interval [CI]: 0.459, 0.667) and 0.752 (95% CI: 0.676, 0.812) for cDTI and iDTI, respectively, which indicate substantial agreement for iDTI and moderate agreement for cDTI. The ICC values of repeated measurements of ADC at 2-week intervals were 0.727 (95% CI: 0.646, 0.793) and 0.822 (95% CI: 0.765, 0.867) for cDTI and iDTI, respectively, which indicates almost perfect agreement for iDTI and substantial agreement for cDTI. Agreement between the upper and lower segments is summarized in Table 4. 4. Discussion The present study demonstrates the high performance of 2D ss-IMIV-DWEPI with reduced FOV for cervical spinal DTI. Although an increasing number of studies have demonstrated the feasibility of cervical spinal cord DTI [5–11,23–34], cervical spinal cord DTI was difficult to implement in clinical practice until fairly recently,
Fig. 1. Comparison of cervical spinal cord cDTI (left side of each pair) and iDTI (right side of each pair) of 35-year-old man with FA maps (A) and corresponding ADC maps (B), and color FA maps (C). The iDTI significantly alleviates susceptibility and partial volume effects. While the image quality gets poor at lower segment of the cervical spinal cord (arrowheads) compared with upper segment (double arrowheads) at cDTI, iDTI offers consistently better quality images at lower segment (arrows).
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Fig. 2. Comparison of cervical spinal cord cDTI (left side of each pair) and iDTI (right side of each pair) of 40-year-old woman with FA maps (A) corresponding ADC maps (B), and color FA maps (C). Even though lower segment on cDTI have less distortion compared with upper segments, scores of dural delineation (double arrowheads and double arrows) and depiction of intervertebral disc (arrowheads and arrows) are higher at iDTI (arrows) compared with cDTI (arrowheads).
compared with brain DTI, because of the scan time for DTI acquisition, distortion, and motion-related artifacts. In this study, in addition to reducing the FOV of the PE dimension to 48 mm, we demonstrate the effect of the interleaved multisection inner volume (IMIV) technique to overcome the limitations mentioned above. By directly comparing sequences with and without IMIV, the findings of this work have high value. The FA was significantly higher and the ADC was significantly lower with iDTI compared with cDTI. Additionally, all of the qualitative evaluation characteristics, including distortion, anatomy, and level delineation, showed significantly higher quality in iDTI. Moreover, we observed consistently better quality images at the lower cervical level with iDTI. In our study, we found significant differences in DTI metrics between the two sequences: the FA of iDTI was significantly higher than that of cDTI and the ADC value of iDTI was significantly lower than that of cDTI. Metrics from DTI are a valuable surrogate measurement of microscopic anatomy of the white matter tract of the central nervous system; therefore precise measurement is
essential. Lee et al. [8] reported patients with compressive myelopathy that showed a change in FA and ADC value without a signal change of the T2-weighted image, demonstrating that DTI is more sensitive than conventional T2-weighted imaging and implicating the importance of accurate measurement of DTI metrics. Numbers from previous studies demonstrated such parameters to be significantly different in pathologic conditions including compressive myelopathy, cervical spondylosis, demyelination disease, neuromyelitis, spinal cord arteriovenous malformation, spinal cord injury, and spinal cord tumor [5–10,12–15]. The FA value of the whole CSC was 0.679 for iDTI and 0.563 for cDTI. Our results of iDTI are in general accordance with some of the previous data [11,12,36]. Recently, Vedantam et al. [11] calculated DTI metrics of 25 healthy subjects for both gray and white matter funiculi of the CSC, and the FA throughout the whole spine was 0.63. However discordance was noted with data from several other studies [13,37]. A possible reason for the discordance is that the DTI metrics may show variation in age, location of measured CSC, signal
Fig. 3. Comparison of cervical spinal cord cDTI (left side of each pair) and iDTI (right side of each pair) of 63-year-old woman, with intervertebral herniated disc, with FA maps (A) corresponding ADC maps (B), color FA maps (C), and sagittal T2-weighted (D). The largest distortion located at C5-6 of ADC maps (white arrowhead) of cDTI was eliminated at iDTI. Diagnostically, iDTI (arrows) offers more useful images than cDTI (arrowheads), and drastic improvement is noted at lower segment of cervical spinal cord.
E.H. Park et al. / Magnetic Resonance Imaging 33 (2015) 401–406 Table 2 Qualitative evaluation of FA map of cDTI and iDTI. cDTI Spinal cord distortion Upper segment 3.7 Lower segment 3.0 Dural margin delineation Upper segment 2.9 Lower segment 2.3 Depiction of intervertebral Upper segment 2.1 Lower segment 1.8
Table 4 ICC value of FA value and ADC value on cDTI and iDTI.
iDTI
P value FA
(3.506, 3.906) (2.758, 3.415)
4.7 4.3
(4.593, 4.8195) (4.169, 4.555)
b.001 b.001
(2.793, 3.184) (2.075, 2.620) disc (1.890, 2.370) (1.621, 2.146)
4.3 4.2
(4.155, 4.474) (4.040, 4.481)
b.001 b.001
2.9 2.9
(2.717, 3.224) (2.640, 3.185)
b.001 b.001
ADC map
Note. Unless otherwise indicated, data are mean score of FA map. The scoring was according to a five-point grading system, higher score indicating preferable performance. Data in parenthesis are 95% CIs.
quality, FOV, sample size, techniques for image optimization. However, most FA values from these studies demonstrated higher FA and lower ADC values in control than in pathologic groups. Additionally, two readers showed better agreement in measuring metrics with iDTI than with cDTI. Although the respiratory and cardiac gating have been known to substantially reduces errors related to diffusion measurements for the spinal cord [38,39]; however neither respiratory nor cardiac gating was used in our study. This difference was due to the fact that IMIV allows for efficient DTI measurement by adopting double inversion and refocusing radio-frequency pulses which limit the excited FOV at the phase-encode direction to include only the anatomy of interest [7,34,35]. This technique also enables efficient DTI measurement of anatomic regions where poor accessibility has previously been noted as a result of severe magnetic susceptibility distortion. Other studies have applied IMIV to DTI of fine anatomic structures such as the optic nerve and lymph nodes [7,27,34].Significant improvement in the distortion of the spinal cord was noted using iDTI. IMIV allows the acquisition of the sagittal plane of the entire cervical spinal cord within a single interleaved imaging. Given that geometric distortion in 2D ss-DWEPI is proportional to the FOV in the phase-encoding direction, 2D ss-IMIV-DWEPI reduces the susceptibility distortion by reducing the spatial coverage in the phase-encoding direction [7,34,35]. According to the current study, results for anatomic delineation with iDTI were superior to those with cDTI. The mean score for dural delineation for both the FA map and ADC map was significantly higher with iDTI. These results are particularly important for accurate measurement of DTI metrics. To avoid volume averaging artifact from adjacent CSF, consistent sparing of the outer margin of the CSC is essential when placing the ROI. Therefore, generally in practice, ROI is delineated to exclude approximately 2 voxels away from the margin of the CSC along the anterior and posterior margins. Table 3 Qualitative evaluation of ADC map of cDTI and iDTI. cDTI Spinal cord distortion Upper segment 3.5 (3.380,3.750) Lower segment 3.144 (2.849,3.439) Dural margin delineation Upper segment 3.2 (3.113,3.473) Lower segment 2.6 (2.349,2.896) Depiction of intervertebral disc Upper segment 2.6 (2.368,2.877) Lower segment 2.3 (2.047,2.590)
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iDTI
p value
4.4 4.2
(4.320, 4.636) (3.998, 4.407)
b.001 b.001
4.0 4.1
(3.837, 4.205) (3.871, 4.331)
b.001 b.001
3.6 3.4
(3.349, 3.896) (3.125, 3.686)
b.001 b.001
Note.-Unless otherwise indicated, data are mean score of ADC map. The scoring was according to a five-point grading system, higher score indicating preferable performance. Data in parenthesis are 95% CIs.
segment
cDTI
iDTI
Total Upper Lower Total Upper Lower
0.572 0.542 0.614 0.727 0.683 0.763
0.752 0.752 0.658 0.822 0.767 0.886
The total scanning times required for iDTI and cDTI were 7 minutes and 2 minutes, respectively. The issue of optimazing the protocol of iDTI requires further investigation. By reducing TR from 4000 to 3000 milliseconds, we could shorten acquisition time by 4 minutes 50 seconds without degradation of the quality of images (data not shown in this paper). Additionally, the improved image quality reduced time for quantitative assessment. In addition to better delineation of dural margins, as mentioned above, the score of depiction of intervertebral disc was significantly higher with iDTI, which allowed access to CSC level without registering any other images. The current study is highly valuable as a demonstration of the superior image performance of iDTI of the lower CSC, as the FA value was found to be significantly higher and the ADC value was significantly lower. In qualitative evaluations, iDTI of lower CSC showed superior results for distortion, dural delineation, and depiction of intervertebral disc compared with cDTI. These results are particularly important considering that degenerative changes of the cervical spine including spondylosis deformans and disc herniation are known to predominantly affect the lower segment because of its relative burden of weight and extensive range of motion [22]. Furthermore, several previous studies have emphasized the limitation of cervical DTI for the lower segment [11,20,21], with several studies, even excluding or avoiding evaluation of the lower CSC [19]. This was mainly attributed to proximity of the CSC to lung, trachea, and aortic arch, and negative impact of the surface coil [16–18]. Vedantam et al. [11] reported that the SNR and spatial resolution of the lower cervical segment were lower than those of upper cervical segment and were prone to partial volume effects; consequently, this lower SNR leads to the overestimation of FA [11,20,21]. This study has several limitations. First, the DTI indices were obtained from patients with different kinds of cervical pain. However, this was considered acceptable in the current study because our goal was to focus on direct comparison of iDTI and cDTI in each level, rather than comparing DTI indices between healthy volunteers and patients, or comparing between levels in one sequence. Second, the study included a small number of patients. Third, we only obtained images in the sagittal plane. Axial scanning enables separate measurement of peripheral white matter and central gray matter. In the current study, the ROIs to measure DTI indices were placed in both gray and white matter in the sagittal plane. This was mainly because of time considerations and because sagittal scanning enabled us to obtain multiple diffusion series in a single examination. Fourth, quantitative evaluation comparing the advancement of iDTI over cDTI was limited. We were not able to determine signal-to-noise ratios (SNRs). This is because we could not place the noise measurement ROI box at the background in images with the reduced FOV method. Fifth, when severe distortion was noted, especially at the lower CSC or with cDTI, precise selection of the ROI with placement 2 voxels away from the edge of margins was restricted. Instead, ROIs were selected at a consistent level and location compared to the T2-weighted image to ensure perfect co-localization.
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In conclusion, 2D rFOV ss-IMIV-DWEPI demonstrated a higher performance in terms of improving image quality, even in the lower segment of the cervical spinal cord, and is preferred to conventional 2D rFOV ss-DWEPI. Acknowledgement This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (2012R1A2A1A01011328). References [1] Basser PJ, Mattiello J, LeBihan D. MR diffusion tensor spectroscopy and imaging. Biophys J 1994;66(1):259–67. [2] Beaulieu C. The basis of anisotropic water diffusion in the nervous system - a technical review. NMR Biomed 2002;15(7–8):435–55. [3] Clark CA, Barker GJ, Tofts PS. Magnetic resonance diffusion imaging of the human cervical spinal cord in vivo. Magn Reson Med 1999;41(6):1269–73. [4] Clark CA, Werring DJ. Diffusion tensor imaging in spinal cord: methods and applications - a review. NMR Biomed 2002;15(7–8):578–86. [5] Ciccarelli O, Wheeler-Kingshott CA, McLean MA, Cercignani M, Wimpey K, Miller DH, et al. Spinal cord spectroscopy and diffusion-based tractography to assess acute disability in multiple sclerosis. Brain 2007;130(Pt 8):2220–31. [6] Farrell JA, Smith SA, Gordon-Lipkin EM, Reich DS, Calabresi PA, van Zijl PC. High b-value q-space diffusion-weighted MRI of the human cervical spinal cord in vivo: feasibility and application to multiple sclerosis. Magn Reson Med 2008; 59(5):1079–89. [7] Kim TH, Zollinger L, Shi XF, Kim SE, Rose J, Patel AA, et al. Quantification of diffusivities of the human cervical spinal cord using a 2D single-shot interleaved multisection inner volume diffusion-weighted echo-planar imaging technique. AJNR Am J Neuroradiol 2010;31(4):682–7. [8] Lee JW, Kim JH, Park JB, Park KW, Yeom JS, Lee GY, et al. Diffusion tensor imaging and fiber tractography in cervical compressive myelopathy: preliminary results. Skeletal Radiol 2011;40(12):1543–51. [9] Loher TJ, Bassetti CL, Lovblad KO, Stepper FP, Sturzenegger M, Kiefer C, et al. Diffusion-weighted MRI in acute spinal cord ischaemia. Neuroradiology 2003; 45(8):557–61. [10] Schwartz ED, Hackney DB. Diffusion-weighted MRI and the evaluation of spinal cord axonal integrity following injury and treatment. Exp Neurol 2003;184(2):570–89. [11] Vedantam A, Jirjis MB, Schmit BD, Wang MC, Ulmer JL, Kurpad SN. Characterization and limitations of diffusion tensor imaging metrics in the cervical spinal cord in neurologically intact subjects. J Magn Reson Imaging 2013;38(4):861–7. [12] Wang SQ, Li X, Cui JL, Li HX, Luk KD, Hu Y. Prediction of myelopathic level in cervical spondylotic myelopathy using diffusion tensor imaging. J Magn Reson Imaging 2014; 00:00-00 [Online Version of Record published before inclusion in an issue]. [13] Rivero RL, Oliveira EM, Bichuetti DB, Gabbai AA, Nogueira RG, Abdala N. Diffusion tensor imaging of the cervical spinal cord of patients with Neuromyelitis Optica. Magn Reson Imaging 2014;32(5):457–63. [14] Ellingson BM, Salamon N, Grinstead JW, Holly LT. Diffusion tensor imaging predicts functional impairment in mild-to-moderate cervical spondylotic myelopathy. Spine J 2014;14:2589–97. [15] Chen YY, Lin XF, Zhang F, Zhang X, Hu HJ, Wang DY, et al. Diffusion tensor imaging of symptomatic nerve roots in patients with cervical disc herniation. Acad Radiol 2014;21(3):338–44. [16] Hodel J, Besson P, Outteryck O, Zephir H, Ducreux D, Monnet A, et al. Pulsetriggered DTI sequence with reduced FOV and coronal acquisition at 3 T for the assessment of the cervical spinal cord in patients with myelitis. AJNR Am J Neuroradiol 2013;34(3):676–82.
[17] Mikulis DJ, Wood ML, Zerdoner OA, Poncelet BP. Oscillatory motion of the normal cervical spinal cord. Radiology 1994;192(1):117–21. [18] Saritas EU, Cunningham CH, Lee JH, Han ET, Nishimura DG. DWI of the spinal cord with reduced FOV single-shot EPI. Magn Reson Med 2008;60(2):468–73. [19] Zaharchuk G, Saritas EU, Andre JB, Chin CT, Rosenberg J, Brosnan TJ, et al. Reduced field-of-view diffusion imaging of the human spinal cord: comparison with conventional single-shot echo-planar imaging. AJNR Am J Neuroradiol 2011;32(5):813–20. [20] Jones DK, Basser PJ. "Squashing peanuts and smashing pumpkins": how noise distorts diffusion-weighted MR data. Magn Reson Med 2004;52(5):979–93. [21] Pierpaoli C, Basser PJ. Toward a quantitative assessment of diffusion anisotropy. Magn Reson Med 1996;36(6):893–906. [22] Ahlgren BD, Garfin SR. Cervical Radiculopathy. Orthop Clin North Am 1996; 27(2):253–63. [23] Bammer R, Herneth AM, Maier SE, Butts K, Prokesch RW, Do HM, et al. Line scan diffusion imaging of the spine. AJNR Am J Neuroradiol 2003;24(1):5–12. [24] Kubicki M, Maier SE, Westin CF, Mamata H, Ersner-Hershfield H, Estepar R, et al. Comparison of single-shot echo-planar and line scan protocols for diffusion tensor imaging. Acad Radiol 2004;11(2):224–32. [25] Pipe JG, Farthing VG, Forbes KP. Multishot diffusion-weighted FSE using PROPELLER MRI. Magn Reson Med 2002;47(1):42–52. [26] Fellner C, Menzel C, Fellner FA, Ginthoer C, Zorger N, Schreyer A, et al. BLADE in sagittal T2-weighted MR imaging of the cervical spine. AJNR Am J Neuroradiol 2010;31(4):674–81. [27] Larson PE, Lustig MS, Nishimura DG. Anisotropic field-of-view shapes for improved PROPELLER imaging. Magn Reson Imaging 2009;27(4):470–9. [28] Tsuchiya K, Fujikawa A, Suzuki Y. Diffusion tractography of the cervical spinal cord by using parallel imaging. AJNR Am J Neuroradiol 2005;26(2):398–400. [29] Cercignani M, Horsfield MA, Agosta F, Filippi M. Sensitivity-encoded diffusion tensor MR imaging of the cervical cord. AJNR Am J Neuroradiol 2003;24(6): 1254–6. [30] Holdsworth SJ, Skare S, Newbould RD, Guzmann R, Blevins NH, Bammer R. Readout-segmented EPI for rapid high resolution diffusion imaging at 3 T. Eur J Radiol 2008;65(1):36–46. [31] Wheeler-Kingshott CA, Hickman SJ, Parker GJ, Ciccarelli O, Symms MR, Miller DH, et al. Investigating cervical spinal cord structure using axial diffusion tensor imaging. Neuroimage 2002;16(1):93–102. [32] Cohen-Adad J, Mareyam A, Keil B, Polimeni JR, Wald LL. 32-channel RF coil optimized for brain and cervical spinal cord at 3 T. Magn Reson Med 2011;66(4): 1198–208. [33] Bammer R, Augustin M, Prokesch RW, Stollberger R, Fazekas F. Diffusionweighted imaging of the spinal cord: interleaved echo-planar imaging is superior to fast spin-echo. J Magn Reson Imaging 2002;15(4):364–73. [34] Jeong EK, Kim SE, Guo J, Kholmovski EG, Parker DL. High-resolution DTI with 2D interleaved multislice reduced FOV single-shot diffusion-weighted EPI (2D ssrFOV-DWEPI). Magn Reson Med 2005;54(6):1575–9. [35] Jeong EK, Kim SE, Kholmovski EG, Parker DL. High-resolution DTI of a localized volume using 3D single-shot diffusion-weighted STimulated echo-planar imaging (3D ss-DWSTEPI). Magn Reson Med 2006;56(6):1173–81. [36] Smith SA, Jones CK, Gifford A, Belegu V, Chodkowski B, Farrell JA, et al. Reproducibility of tract-specific magnetization transfer and diffusion tensor imaging in the cervical spinal cord at 3 tesla. NMR Biomed 2010;23(2): 207–17. [37] Banaszek A, Bladowska J, Szewczyk P, Podgorski P, Sasiadek M. Usefulness of diffusion tensor MR imaging in the assessment of intramedullary changes of the cervical spinal cord in different stages of degenerative spine disease. Eur Spine J 2014;23(7):1523–30. [38] Kharbanda HS, Alsop DC, Anderson AW, Filardo G, Hackney DB. Effects of cord motion on diffusion imaging of the spinal cord. Magn Reson Med 2006;56(2): 334–9. [39] Summers P, Staempfli P, Jaermann T, Kwiecinski S, Kollias S. A preliminary study of the effects of trigger timing on diffusion tensor imaging of the human spinal cord. AJNR Am J Neuroradiol 2006;27(9):1952–61.
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Diffusion tensor imaging focusing on lower cervical spinal cord using 2D reduced FOV interleaved multislice single-shot diffusion-weighted echo-planar imaging: comparison with conventional single-shot diffusion-weighted echo-planar imaging Eun Hae Park a, Young Han Lee a, Eun-Kee Jeong b, Yun Ho Roh c, Jin-Suck Suh a,⁎ a
Department of Radiology, Research Institute of Radiological Science, Medical Convergence Research Institute, and Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea b Department of Radiology, Utah Center for Advanced Imaging Research, University of Utah, Salt Lake City, UT, USA c Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Republic of Korea
a r t i c l e
i n f o
Article history: Received 26 April 2014 Revised 16 September 2014 Accepted 10 January 2015 Keywords: Magnetic resonance imaging Diffusion Diffusion tensor Cervical spinal cord
a b s t r a c t Purpose: To evaluate the performance of diffusion tensor imaging (DTI) of the cervical spinal cord by comparing 2-dimensional standard single-shot interleaved multisection inner volume diffusion-weighted echo-planar imaging (2D ss-IMIV-DWEPI) and conventional 2D ss-DWEPI in a clinical population, focusing on the lower cervical spinal cord. Materials and Methods: From July to September 2013, a total of 23 patients who underwent cervical spinal MR imaging with DTI were retrospectively enrolled in this study (M:F = 7:16, mean age 45 years, age range 24–76 years). Exclusion criteria were: previous prosthesis insertion (n = 5), syringomyelia on T2-weighted imaging (n = 4), and spinal cord tumor (n = 0). All MRI examinations were performed using 3.0 T imaging with a phased-array spine coil including two different 2D reduced FOV DTI sequences: 2D ss-IMIV-DWEPI (iDTI) and 2D ss-DWEPI without interleaving (cDTI). For quantitative analysis, two musculoskeletal radiologists who were blinded to the sequence measured fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values throughout the whole cervical spinal cord (C1-T1). For qualitative analysis, the readers rated each image based on spinal cord distortion, dural margin delineation, and depiction of intervertebral disc. Quantitative and qualitative evaluations were analyzed separately for upper and lower segments. The t-test was used for quantitative analysis and two-way analysis of variance (ANOVA) and t-tests were performed for qualitative analysis. Results: FA was significantly higher and ADC was significantly lower on iDTI compared with cDTI (0.679 versus 0.563, respectively, for FA; 631 versus 1026, respectively, for ADC; p b 0.001), and this was consistently observed in the lower segment of the spinal cord. The reviewers rated iDTI as superior in terms of all assessed characteristics. For qualitative analysis, the mean iDTI score was significantly higher than the cDTI score for both the lower and upper segments (p b 0.001). Conclusion: 2D rFOV ss-IMIV-DWEPI demonstrated higher performance than conventional 2D rFOV ss-DWEPI in terms of improving image quality, even in the lower segment of the cervical spinal cord. © 2015 Elsevier Inc. All rights reserved.
1. Introduction Diffusion tensor imaging (DTI) provides not only structural integrity information, but also directional information by measuring
⁎ Corresponding author at: Department of Radiology, Research Institute of Radiological Science, Medical Convergence Research Institute, and Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea, 50–1 Yonsei-ro, Seodaemun-gu, Seoul, 120–752, Republic of Korea. Tel.: +82 2 2228 7400; fax: +82 2 393 3035. E-mail address: [email protected] (J-S. Suh). http://dx.doi.org/10.1016/j.mri.2015.01.007 0730-725X/© 2015 Elsevier Inc. All rights reserved.
water molecule diffusion within tissues. Obtained metrics from DTI are fractional anisotropy (FA), the values of apparent diffusion coefficient (ADC), and eigenvalues, which provide information on the scalar properties of the diffuse translation for extracellular water molecules [1–4]. Previous studies have shown that these metrics reflect the microstructure of the spinal cord and provides visualization of fiber tractography, enabling tracking of the white matter pathways in the brain and spinal cord. Moreover, the application of DTI at the cervical spinal cord allows characterization of microstructural changes including demyelinating disease, infarction, myelopathy, traumatic injury, and spinal cord tumor [5–15].
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However, in practice, the usefulness of DTI at the cervical spinal cord (CSC) has been impeded by 1) the small dimension of the CSC, 2) partial volume artifacts from surrounding cerebral spinal fluid (CSF) and lipid, 3) motion artifacts from breathing, swallowing, and CSF pulsation, and 4) large bony structures that cause abrupt changes in magnetic susceptibility [16–19]. For DTI of the CSC, standard single-shot diffusion-weighted echo-planar imaging (ss-DWEPI) is widely used in clinical cervical MR imaging. However, this protocol has a long readout time and low bandwidth in the phase encode direction, and is therefore prone to distortions and motion artifacts. In previous studies, these limitations were emphasized in the lower CSC [11,20,21]. Degenerative changes of the cervical spine including spondylosis and disc herniation are known to affect the lower segment because of the relative burden of weight and extensive range of motion [22]. However, several previous studies have emphasized the limitations of cervical DTI of the lower segment. This is mainly because of its location close to the lungs and heart, and negative effects associated with the construction of the surface coil [11,20,21]. Over the past decades, there have been several efforts using various EPI-based methods to overcome these limitations, including line scan imaging [23,24], navigated fast spin-echo [3], propeller-based imaging [25–27], parallel EPI [28–30], ZOOM-EPI [31], multichannel coil [32], and more recently, reduced effective field of view (FOV) in the phase encoding direction, an approach that is currently in the limelight. Reducing the FOV in the phase encode (PE) direction enables a drastic shortening of the readout time and also increases the (pseudo)bandwidth in the phaseencoding direction. In addition, geometric distortion in ss-DWEPI is proportional to the FOV in the phase-encoding direction; therefore, susceptibility-related artifacts and pixel misregistration can be reduced in ss-DWEPI [16,18,19]. An equally important method is the interleaved multisection inner volume (IMIV) technique, which provides double inversion/ refocusing radio-frequency pulses at 2D ss-DWEPI. This allows for acquisition of the entire cervical spinal cord with 1 interleaved image in the sagittal plane [7]. A few reports on the application of IMIV techniques at the CSC have been published [7,33–35], but there are no direct comparisons with conventional protocols focusing on the lower CSC. Therefore, the purpose of this study was to evaluate the performance of DTI in the cervical spinal cord by comparing 2D ss-IMIV-DWEPI (iDTI) and conventional 2D ss-DWEPI (cDTI) in a clinical population, focusing on the lower cervical spinal cord.
2. Materials and methods 2.1. Study population This retrospective study was approved by the institutional review board for human research. A total of 34 consecutive patients underwent cervical spinal MRI between July 2013 and September 2013. Any patients with unstable vital signs, history of interbody fixation, syringomyelia, or spinal cord tumor were excluded. As a result, 9 of the 31 patients were excluded; 5 patients had a clinical history of interbody fixation and 4 showed increased signal of the CSC due to compressive myelopathy and syringomyelia. Thus, 23 patients who underwent cervical spinal cord DTI performed by iDTI and conventional cDTI were enrolled in this study. The study population comprised 7 men and 16 women (age range, 24–76 years; mean age, 45.0 years) who underwent cervical spinal MRI for the following reasons: cervical compressive myelopathy, n = 12; neck pain, n = 6; bone metastases, n = 2, anomaly screening, n = 2; health check-up, n = 1.
2.2. Imaging study All MRI examinations were performed using a 3.0 T whole body MR imaging system (Trio, Siemens Healthcare, Erlangen, Germany) with a phased-array spine coil and without cardiac gating. Conventional 2D cervical spinal MR imaging was performed first, followed by DTI. Conventional 2D cervical spinal MR imaging consisted of sagittal and axial T1-weighted fast spin echo (FSE) sequences and sagittal and axial T2-weighted FSE sequences. The parameters for the sequences were as follows. Spin echo sagittal T1WI scans: TR/TE 400/10 msec; FOV 260 mm; acquisition matrix 448 × 336; slice thickness 3 mm with 0.3 mm gap; number of excitations (NEX) 2. Sagittal fast spin-echo fat-suppressed T2WI scans: TR/TE 3500/110 msec; FOV 260 mm; acquisition matrix 512 × 358; slice thickness 3 mm with 0.3 mm gap; NEX 2. Axial T1WI scans: TR/TE 400/10 msec; FOV 180 mm; acquisition matrix 320 × 256; slice thickness 3 mm with 0.3-mm gap; NEX 2. Axial T2WI scans: TR/TE 3800/106 msec; FOV 180 mm; slice thickness 3 mm with 0.3-mm gap; resolution 320 × 256; NEX 2. 2D iDTI was performed with the following parameters: TR/TE 4000/65 msec; FOV 192 × 48 mm; acquisition matrix 128 × 32; 10 sagittal slices; slice thickness 2 mm without gap; voxel size 1.5 × 1.5 × 2.0 mm; EPI factor 32; number of excitations 8; b factors of 0 and 500 s/mm 2; and 10 interleaved sections. Diffusionweighted gradients were applied in 12 noncollinear directions. Total scanning time was 7 minutes. Additional comparison cDTI was performed using the same section thickness and location with TR/TE 1100/65 msec and a total scanning time of 2 minutes (Table 1). 2.3. Image interpretation DTI images were retrospectively reviewed by two musculoskeletal radiologists (one [Y.H.L.] with more than 8 years of experience in musculoskeletal imaging and one [E.H.P.] in musculoskeletal fellowship) who were blind to imaging information. 2.4. Quantitative analysis DTI metrics of eigenvalues were calculated and measured for both iDTI and conventional cDTI as follows: fractional anisotropy (FA), apparent diffusion coefficient (ADC; × 10 −3 mm 2s −1). Regions of interest (ROIs) for FA and the ADC map were measured manually using anatomy and cord morphology from the T2WI scan as a reference. Seven ROIs, ranging from 7 to 13 mm 2 (mean 9.2 mm) in size, were selected from a sagittal section throughout the whole intervertebral disc level of the cervical spine. Each ROI was applied both in white and gray matter, where each level of CSC was depicted in maximum volume, and care was taken to exclude at least 2 voxels from the edge of anterior and posterior margins. 2.5. Qualitative analysis The following three characteristics were rated to evaluate the clinical utility of iDTI and cDTI: spinal cord distortion, dural margin Table 1 Imaging parameters for the DTI sequences.
TR/TE (ms) FOV (frequency × phase encode) (cm) resolution Bandwidth (Hz/pixel) Slice thickness (mm) b value (s/mm2) Acquisition time (min:s)
cDTI
iDTI
1100/65 192 × 48 128 × 32 1562 2 0, 500 1:59
4000/73 192 × 48 128 × 32 1562 2 0, 500 7:00
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delineation (evaluation of anatomy), and depiction of intervertebral disc (evaluation of level identification). Two blinded reviewers assigned scores according to a five-point grading system, as follows. For spinal cord distortion and dural margin delineation, 1 = nondiagnostic, 2 = questionable, 3 = adequate, 4 = good, 5 = excellent for diagnosis. For depiction of intervertebral disc, 1 = not seen, 2 = subtle, 3 = less than 50% visible, 4 = 50–75% visible, 5 = more than 75% visible. The DTI metrics and scoring were evaluated for the entire level through the CSC. Intervertebral disc regions from C1/2 to C4/5 were regarded as the upper segment and those from C5/6 to C7/T1 as the lower segment. The mean values of the upper and lower segments were calculated to compare the performance of cDTI and iDTI.
2.6. Statistical analysis Statistical analysis was performed with SAS version 9.2 (SAS Institute, Cary, NC, USA). DTI metrics were compared between 2 sequences using t-tests. Two-way analysis of variance (ANOVA) and t-tests were performed to compare the scores of spinal cord distortion, delineation of dural margin, and depiction of intervertebral disc. P b 0.05 was considered to indicate a significant difference. The intraclass correlation coefficient (ICC) was used to statistically define interobserver agreement of DTI metrics.
3. Results 3.1. Quantitative analysis The mean values of DTI metrics in whole, upper, and lower CSC using cDTI versus iDTI were as follows: (a) FA value of whole CSC, 0.563 versus 0.679 (p b 0.001); (b) ADC value (× 10 −3 mm 2s −1) of whole spine, 1026.2 versus 631.1 (p b 0.001); (c) FA value of upper CSC, 0.554 versus 0.717 (p = 0.009); (d) ADC value of upper CSC, 1051.2 versus 589.1 (p b 0.001); (e) FA value of lower CSC, 0.574 versus 0.628 (p b 0.001); (f) ADC value of lower CSC, 993 versus 687 (p b 0.001).
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3.2. Qualitative evaluation The iDTI imaging was strongly preferred by reviewers with respect to distortion of spinal cord, delineation of dural margin, and depiction of intervertebral disc. The sequences of iDTI and cDTI were significantly different for all of these characteristics. Even in the lower segment of the CSC, the score of iDTI was significantly higher than that of cDTI for both the FA map and ADC map (Figs. 1, 2). For spinal cord distortion (Fig. 3), the mean score of upper and lower segments for cDTI versus iDTI were as follows: (a) FA map of upper CSC, 3.7 versus 4.7, respectively; (b) ADC map of upper CSC, 3.5 versus 4.4; (c) FA map of lower CSC, 3.0 versus 4.3; (d) ADC map of lower CSC, 3.1 versus 4.2. For dural margin delineation, the mean score of upper and lower segment of cDTI versus iDTI were as follows: (a) FA map of upper CSC, 2.9 versus 4.3; (b) ADC map of upper CSC, 3.2 versus 4.0; (c) FA map of lower CSC, 2.3 versus 4.2; (d) ADC map of lower CSC, 2.6 versus 4.1. Finally, for depiction of intervertebral disc, the mean score of upper and lower segment of cDTI versus iDTI were as follows: (a) FA map of upper CSC, 2.1 versus 2.9, respectively; (b) ADC map of upper CSC, 2.6 versus 3.6; (c) FA map of lower CSC, 1.8 versus 2.9; (d) ADC map of lower CSC, 2.3 versus 3.4 (Tables 2 and 3). The ICC values of repeated measurements of FA at 2-week intervals were 0.572 (95% confidence interval [CI]: 0.459, 0.667) and 0.752 (95% CI: 0.676, 0.812) for cDTI and iDTI, respectively, which indicate substantial agreement for iDTI and moderate agreement for cDTI. The ICC values of repeated measurements of ADC at 2-week intervals were 0.727 (95% CI: 0.646, 0.793) and 0.822 (95% CI: 0.765, 0.867) for cDTI and iDTI, respectively, which indicates almost perfect agreement for iDTI and substantial agreement for cDTI. Agreement between the upper and lower segments is summarized in Table 4. 4. Discussion The present study demonstrates the high performance of 2D ss-IMIV-DWEPI with reduced FOV for cervical spinal DTI. Although an increasing number of studies have demonstrated the feasibility of cervical spinal cord DTI [5–11,23–34], cervical spinal cord DTI was difficult to implement in clinical practice until fairly recently,
Fig. 1. Comparison of cervical spinal cord cDTI (left side of each pair) and iDTI (right side of each pair) of 35-year-old man with FA maps (A) and corresponding ADC maps (B), and color FA maps (C). The iDTI significantly alleviates susceptibility and partial volume effects. While the image quality gets poor at lower segment of the cervical spinal cord (arrowheads) compared with upper segment (double arrowheads) at cDTI, iDTI offers consistently better quality images at lower segment (arrows).
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Fig. 2. Comparison of cervical spinal cord cDTI (left side of each pair) and iDTI (right side of each pair) of 40-year-old woman with FA maps (A) corresponding ADC maps (B), and color FA maps (C). Even though lower segment on cDTI have less distortion compared with upper segments, scores of dural delineation (double arrowheads and double arrows) and depiction of intervertebral disc (arrowheads and arrows) are higher at iDTI (arrows) compared with cDTI (arrowheads).
compared with brain DTI, because of the scan time for DTI acquisition, distortion, and motion-related artifacts. In this study, in addition to reducing the FOV of the PE dimension to 48 mm, we demonstrate the effect of the interleaved multisection inner volume (IMIV) technique to overcome the limitations mentioned above. By directly comparing sequences with and without IMIV, the findings of this work have high value. The FA was significantly higher and the ADC was significantly lower with iDTI compared with cDTI. Additionally, all of the qualitative evaluation characteristics, including distortion, anatomy, and level delineation, showed significantly higher quality in iDTI. Moreover, we observed consistently better quality images at the lower cervical level with iDTI. In our study, we found significant differences in DTI metrics between the two sequences: the FA of iDTI was significantly higher than that of cDTI and the ADC value of iDTI was significantly lower than that of cDTI. Metrics from DTI are a valuable surrogate measurement of microscopic anatomy of the white matter tract of the central nervous system; therefore precise measurement is
essential. Lee et al. [8] reported patients with compressive myelopathy that showed a change in FA and ADC value without a signal change of the T2-weighted image, demonstrating that DTI is more sensitive than conventional T2-weighted imaging and implicating the importance of accurate measurement of DTI metrics. Numbers from previous studies demonstrated such parameters to be significantly different in pathologic conditions including compressive myelopathy, cervical spondylosis, demyelination disease, neuromyelitis, spinal cord arteriovenous malformation, spinal cord injury, and spinal cord tumor [5–10,12–15]. The FA value of the whole CSC was 0.679 for iDTI and 0.563 for cDTI. Our results of iDTI are in general accordance with some of the previous data [11,12,36]. Recently, Vedantam et al. [11] calculated DTI metrics of 25 healthy subjects for both gray and white matter funiculi of the CSC, and the FA throughout the whole spine was 0.63. However discordance was noted with data from several other studies [13,37]. A possible reason for the discordance is that the DTI metrics may show variation in age, location of measured CSC, signal
Fig. 3. Comparison of cervical spinal cord cDTI (left side of each pair) and iDTI (right side of each pair) of 63-year-old woman, with intervertebral herniated disc, with FA maps (A) corresponding ADC maps (B), color FA maps (C), and sagittal T2-weighted (D). The largest distortion located at C5-6 of ADC maps (white arrowhead) of cDTI was eliminated at iDTI. Diagnostically, iDTI (arrows) offers more useful images than cDTI (arrowheads), and drastic improvement is noted at lower segment of cervical spinal cord.
E.H. Park et al. / Magnetic Resonance Imaging 33 (2015) 401–406 Table 2 Qualitative evaluation of FA map of cDTI and iDTI. cDTI Spinal cord distortion Upper segment 3.7 Lower segment 3.0 Dural margin delineation Upper segment 2.9 Lower segment 2.3 Depiction of intervertebral Upper segment 2.1 Lower segment 1.8
Table 4 ICC value of FA value and ADC value on cDTI and iDTI.
iDTI
P value FA
(3.506, 3.906) (2.758, 3.415)
4.7 4.3
(4.593, 4.8195) (4.169, 4.555)
b.001 b.001
(2.793, 3.184) (2.075, 2.620) disc (1.890, 2.370) (1.621, 2.146)
4.3 4.2
(4.155, 4.474) (4.040, 4.481)
b.001 b.001
2.9 2.9
(2.717, 3.224) (2.640, 3.185)
b.001 b.001
ADC map
Note. Unless otherwise indicated, data are mean score of FA map. The scoring was according to a five-point grading system, higher score indicating preferable performance. Data in parenthesis are 95% CIs.
quality, FOV, sample size, techniques for image optimization. However, most FA values from these studies demonstrated higher FA and lower ADC values in control than in pathologic groups. Additionally, two readers showed better agreement in measuring metrics with iDTI than with cDTI. Although the respiratory and cardiac gating have been known to substantially reduces errors related to diffusion measurements for the spinal cord [38,39]; however neither respiratory nor cardiac gating was used in our study. This difference was due to the fact that IMIV allows for efficient DTI measurement by adopting double inversion and refocusing radio-frequency pulses which limit the excited FOV at the phase-encode direction to include only the anatomy of interest [7,34,35]. This technique also enables efficient DTI measurement of anatomic regions where poor accessibility has previously been noted as a result of severe magnetic susceptibility distortion. Other studies have applied IMIV to DTI of fine anatomic structures such as the optic nerve and lymph nodes [7,27,34].Significant improvement in the distortion of the spinal cord was noted using iDTI. IMIV allows the acquisition of the sagittal plane of the entire cervical spinal cord within a single interleaved imaging. Given that geometric distortion in 2D ss-DWEPI is proportional to the FOV in the phase-encoding direction, 2D ss-IMIV-DWEPI reduces the susceptibility distortion by reducing the spatial coverage in the phase-encoding direction [7,34,35]. According to the current study, results for anatomic delineation with iDTI were superior to those with cDTI. The mean score for dural delineation for both the FA map and ADC map was significantly higher with iDTI. These results are particularly important for accurate measurement of DTI metrics. To avoid volume averaging artifact from adjacent CSF, consistent sparing of the outer margin of the CSC is essential when placing the ROI. Therefore, generally in practice, ROI is delineated to exclude approximately 2 voxels away from the margin of the CSC along the anterior and posterior margins. Table 3 Qualitative evaluation of ADC map of cDTI and iDTI. cDTI Spinal cord distortion Upper segment 3.5 (3.380,3.750) Lower segment 3.144 (2.849,3.439) Dural margin delineation Upper segment 3.2 (3.113,3.473) Lower segment 2.6 (2.349,2.896) Depiction of intervertebral disc Upper segment 2.6 (2.368,2.877) Lower segment 2.3 (2.047,2.590)
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iDTI
p value
4.4 4.2
(4.320, 4.636) (3.998, 4.407)
b.001 b.001
4.0 4.1
(3.837, 4.205) (3.871, 4.331)
b.001 b.001
3.6 3.4
(3.349, 3.896) (3.125, 3.686)
b.001 b.001
Note.-Unless otherwise indicated, data are mean score of ADC map. The scoring was according to a five-point grading system, higher score indicating preferable performance. Data in parenthesis are 95% CIs.
segment
cDTI
iDTI
Total Upper Lower Total Upper Lower
0.572 0.542 0.614 0.727 0.683 0.763
0.752 0.752 0.658 0.822 0.767 0.886
The total scanning times required for iDTI and cDTI were 7 minutes and 2 minutes, respectively. The issue of optimazing the protocol of iDTI requires further investigation. By reducing TR from 4000 to 3000 milliseconds, we could shorten acquisition time by 4 minutes 50 seconds without degradation of the quality of images (data not shown in this paper). Additionally, the improved image quality reduced time for quantitative assessment. In addition to better delineation of dural margins, as mentioned above, the score of depiction of intervertebral disc was significantly higher with iDTI, which allowed access to CSC level without registering any other images. The current study is highly valuable as a demonstration of the superior image performance of iDTI of the lower CSC, as the FA value was found to be significantly higher and the ADC value was significantly lower. In qualitative evaluations, iDTI of lower CSC showed superior results for distortion, dural delineation, and depiction of intervertebral disc compared with cDTI. These results are particularly important considering that degenerative changes of the cervical spine including spondylosis deformans and disc herniation are known to predominantly affect the lower segment because of its relative burden of weight and extensive range of motion [22]. Furthermore, several previous studies have emphasized the limitation of cervical DTI for the lower segment [11,20,21], with several studies, even excluding or avoiding evaluation of the lower CSC [19]. This was mainly attributed to proximity of the CSC to lung, trachea, and aortic arch, and negative impact of the surface coil [16–18]. Vedantam et al. [11] reported that the SNR and spatial resolution of the lower cervical segment were lower than those of upper cervical segment and were prone to partial volume effects; consequently, this lower SNR leads to the overestimation of FA [11,20,21]. This study has several limitations. First, the DTI indices were obtained from patients with different kinds of cervical pain. However, this was considered acceptable in the current study because our goal was to focus on direct comparison of iDTI and cDTI in each level, rather than comparing DTI indices between healthy volunteers and patients, or comparing between levels in one sequence. Second, the study included a small number of patients. Third, we only obtained images in the sagittal plane. Axial scanning enables separate measurement of peripheral white matter and central gray matter. In the current study, the ROIs to measure DTI indices were placed in both gray and white matter in the sagittal plane. This was mainly because of time considerations and because sagittal scanning enabled us to obtain multiple diffusion series in a single examination. Fourth, quantitative evaluation comparing the advancement of iDTI over cDTI was limited. We were not able to determine signal-to-noise ratios (SNRs). This is because we could not place the noise measurement ROI box at the background in images with the reduced FOV method. Fifth, when severe distortion was noted, especially at the lower CSC or with cDTI, precise selection of the ROI with placement 2 voxels away from the edge of margins was restricted. Instead, ROIs were selected at a consistent level and location compared to the T2-weighted image to ensure perfect co-localization.
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