Is MR imaging of the cervical spinal cord sufficient for patients with suspected Multiple Sclerosis?

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Isabelle Riederer, Matthias Bussas, Markus Lauerer, Laura Harabacz, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7808342/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Jan, 2026 Read the published version in Clinical Neuroradiology → Version 1 posted You are reading this latest preprint version Abstract Purpose: Lesions in the spinal cord (SC) can be found in up to 83% of patients with multiple sclerosis (MS). As they are mainly located in the cervical segment, many centers exclude the thoracic part from SC imaging. The aim of our study was to quantify the decrease in sensitivity resulting from this approach. Methods: MR images (3T) of 543 consecutive patients with clinically isolated syndrome (CIS) (n: 37) and MS (n: 506) were analyzed retrospectively. Lesions were segmented semi-automatically on axial T2-weighted images of the whole SC using BrainSeg3D. The volume of lesions was related to vertebral levels. Results: Altogether 1782 lesions (CIS: 19; MS: 1763) were found in 409 patients. 70% of the lesion volume was located in the SC above the 3rd thoracic vertebral body, in a segment that is commonly covered by an isolated examination of the cervical SC. However, 26 patients (6%) showed lesions exclusively below the 3rd thoracic vertebral body, thus 94% of all patients with SC lesions could be detected with isolated MR imaging of the cervical SC. Conclusion: Though the majority of lesions can be detected in an isolated examination of the upper part of the SC, some patients showed lesions exclusively below the 3rd thoracic vertebral body. We recommend routine scanning of the whole SC in suspected MS. Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease that affects both the brain and the spinal cord (SC). SC lesions are found in up to 83% of patients with MS[ 1 ]. The recently revised MAGNIMS-CMSC-NAIMS consensus guidelines[ 2 ] emphasize the importance of examining the SC. The involvement of the SC fulfills one of the specific McDonald criteria[ 3 ] for the dissemination in space in addition to intra-/juxtacortical, periventricular, and infratentorial localization on brain magnetic resonance imaging (MRI). Inclusion of the SC in these criteria increases the likelihood of dissemination in space from 66% to 85%[ 1 ]. Furthermore, lesions in the SC may help to exclude differential diagnoses as they are less common in other neurological diseases and do not occur in healthy ageing[ 4 ]. However, MRI of the SC remains technically challenging due to its thin and long structure and artifacts caused by pulsation or respiration. Due to the long structure of the SC, at least 2–3 stacks are necessary to cover the whole SC with MRI. Recommendations for MRI protocols suggest at least two different sagittal sequences, such as T2-weighted and proton density-weighted sequences or short tau inversion recovery (STIR) sequences, supplemented by axial T2-weighted sequences to differentiate between true lesions and artifacts[ 2 ]. However, a detailed MRI protocol is time-consuming and may not be well tolerated by some patients. As most of the lesions (56%) are located in the cervical segment of the SC[ 1 ], many centers, therefore, exclude the thoracic part of the SC in MRI[ 5 – 9 ]. Therefore, the aim of our study was to quantify the decrease in sensitivity resulting from incomplete SC coverage in MRI scans of patients with suspected MS. Methods Patients This study was performed retrospectively as part of the single-centre cohort study on MS at the Technical University of Munich (TUM-MS). The study was approved by the internal review board and conducted in accordance with the Declaration of Helsinki. Patients had given written informed consent for the use of their clinical and paraclinical data for research purposes. Inclusion criteria were a diagnosis of clinically isolated syndrome (CIS) or MS and an age between 18 and 60 years. To achieve a uniform classification of patients, all patients were reclassified according to the 2017 diagnostic criteria[ 3 ] with full access to the neurologist’s medical records. Patients with CIS were defined by a first clinical event suggestive of a relapsing-remitting MS (RRMS) and meeting the criteria for dissemination in space but not for dissemination in time. MS patients included those with a relapsing-remitting course (RRMS) and those with a primary progressive (PPMS) or secondary progressive (SPMS) course. MRI acquisition and analysis Data were analyzed retrospectively, and MRI of the SC were acquired between January 2009 and June 2018 during routine clinical practice. Imaging was performed on 3-Tesla scanners (Achieva dStream, Ingenia, or Ingenia Elition from Philips Healthcare and Magnetom Verio from Siemens Healthineers) using an anterior body coil. All scans included 2D T2-weighted (w) turbo spin echo (TSE) sequences in sagittal and axial orientation with a slice thickness of 2 mm and a gap of 0.2 mm (sagittal) or a slice thickness of 4 mm and a gap of 1 mm (axial). The typical field of view (FOV) of axial scans was 115 mm with an in-plane spatial resolution of 0.4 mm (ranging from 0.3 mm to 0.5 mm) and were acquired in three consecutive stacks. Sagittal scans had a typical FOV of 250 mm with an in-plane spatial resolution of 0.9 mm (ranging from 0.8 mm to 1 mm) and were acquired in two consecutive stacks. All scans were converted to the NIFTI file format and segmented using the BrainSeg3D software, version 2.2.1 ( http://lit.fe.uni-lj.si/tools.php?lang=eng ). First, we segmented the SC area in axial scans using a region-growing algorithm that had to be initialized by manual setting of a seed point within the SC in each slice. Manual corrections of the outlines were performed when necessary. Lesions were segmented entirely manually. This segmentation was performed by two medical students (LH and VP) after an intensive training period supervised by a senior neuroradiologist (JK). While annotating the 4mm axial slices, the students additionally reviewed both the sagittal images and the primary MR report for comparison. Ambiguous cases were resolved by a senior neuroradiologist. We performed a cross-validation (LH and VP) in 25 patients, 15 of whom had SC lesions, indicating very good agreement (mean voxel-wise Dice coefficient of atrophy/lesions: 0.98/0.79). Additionally, the inferior border of the second cervical vertebra (C2) and the medullary cone were marked separately. These segmentations were evaluated using an in-house python-based algorithm. We registered axial and sagittal scans with the SimpleITK software, version 1.20, to combine the segmentations of the consecutive axial stacks. To account for missing slices, we used linear interpolation to insinuate the curvature of the missing region and used a nearest neighbour search to determine the thickness of the interpolated regions. These combined masks, covering the entire SC, were subdivided in a region above the C2 landmark and 19 regions between the C2 landmark and the medullary cone, equally divided based on the total stretched length of the skeletonized spine along the cranio-caudal axis (i.e., the spinal centerline). In analogy to the nerve roots, these 19 regions were named C3-C8, T1-T12, and L1. Assuming equal distances between the root entry zones of the SC, which is roughly the case in the upper SC, a region labelled [C or T]x approximately covers the part of the SC between the root entry zones [C or T]x and [C or T]x + 1, while the maximum of the lumbar enlargement corresponds to T11. Statistical analyses To capture the spatial distribution of the lesion volume along the spine, we computed the mean lesion volume for each segment and each MS type separately. Additionally, we plotted the percentage of detected lesion volume (cranio-caudal direction) against spinal cord levels to visualize the increase in sensitivity with an increasing number of SC levels covered. Furthermore, we computed the ratio of patients with a lesion when only checking the upper segments. Patients with / without lesions are reported as absolute or relative frequencies. Results We identified 575 patients aged between 18 and 60 years with an established diagnosis of CIS or MS and available MRI of the SC. MRI data from 545 patients showed sagittal and axial coverage from at least the inferior border of C2 to the medullary cone; two of these had to be excluded due to poor image quality, leaving 543 MRI data sets for the analysis. The demographics of the resulting cohort are summarized in Table 1 . Table 1 Characteristics of the patients CIS RRMS SPMS PPMS all N 37 442 38 26 543 Females (in %) 20 (54%) 304 (69%) 22 (58%) 12 (46%) 358 (66%) Age (in years) 34.3 ± 9.1 34.9 [20.1–55.4] 36.1 ± 9.6 35.3 [18.0–59.9] 47.4 ± 6.6 49.5 [33.1–59.6] 47.1 ± 8.5 46.8 [30.8–59.6] 37.3 ± 10.0 36.6 [18.0–59.9] Disease duration (in years) 0.5 ± 0.9 0.08 [0.0–3.4] 4.0 ± 6.1 1.1 [0.0–34.8] 14.3 ± 8.7 13.4 [0.3–32.3] 5.2 ± 3.9 3.9 [0.06–13.3] 4.6 ± 6.7 1.3 [0.0–34.8] EDSS 1.1 ± 0.9 1.0 [0.0–3.5] 1.6 ± 1.4 1.5 [0.0–8.5] 5.6 ± 1.6 6.0 [2.0–9.0] 4.1 ± 1.7 3.5 [1.5–8.5] 2.0 ± 1.8 1.5 [0.0–9.0] Patients with SC lesions (in %) 27% 77% 95% 85% 75% Spinal lesion volume (in ml) 0.04 ± 0.09 0.0 [0.0–0.4] 0.4 ± 0.8 0.1 [0.0–11.6] 1.1 ± 1.7 0.6 [0.0–9.6] 0.6 ± 0.7 0.4 [0.0–3.4] 0.4 ± 0.9 0.1 [0.0–11.6] Number of spinal lesions 0.5 ± 1.0 0 [0–4] 3.2 ± 3.6 2 [0–25] 5.8 ± 4.1 6 [0–17] 4.5 ± 3.7 4 [0–12] 3.3 ± 3.6 2 [0–25] Values are given in mean ± standard deviation, median and range. CIS: clinically isolated syndrome; EDSS: Expanded Disability Status Scale; PPMS: primary progressive multiple sclerosis; RRMS: relapsing-remitting multiple sclerosis; SC: spinal cord; SPMS: secondary progressive multiple sclerosis A total of 1782 lesions were detected in 409 patients (Fig. 1, 19 lesions in 10 patients with CIS, and 1763 lesions in 399 patients with MS). The level-wise distribution of the lesion volume is shown in Fig. 2 . The percentage of detected spinal lesion volume above a given spinal cord segment is illustrated in Fig. 3 . Figure 4 shows the percentage of patients with MS lesions detected in relation to the assessment of the different vertebral segments. As the FoV of an isolated examination of the cervical SC mostly included the upper part of the thoracic spine up to the 3rd thoracic vertebral body, following descriptions refer to this level. 70% of the lesion volume was located above the level of the 3rd thoracic vertebral body. 26 patients (6%) (MS, n: 24 (6%); CIS, n: 2 (20%)) had lesions exclusively below the level of the 3rd thoracic vertebral body, i.e., 94% of all patients with spinal lesions were detected when MRI scans of the upper part of the SC were evaluated exclusively. Differences in the percentage of detected patients with MS lesions between groups are best explained by differences in the overall frequency of lesions rather than by differences in lesion distribution, which was very similar in all patient groups (Fig. 2). Discussion The results of our study confirm that most lesions are located in the upper segment of the SC down to the level of the 3rd thoracic vertebral body, an area that represents the FoV of an isolated MRI of the cervical SC as routinely performed in many centers. However, SC lesions occurred at all SC levels down to the medullary cone. Our study is in agreement with a previous study[ 10 ] which showed that the majority of MS lesions were located in the upper part of the SC. However, it was shown that approximately 20% of the lesions occurred in the lower part of the SC in MS patients[ 10 ] and in 41% of patients with myelon oligodendrocyte glycoprotein antibody (MOG-AB) associated diseases[ 11 ]. In addition, a small number (8%) of MS patients had lesions exclusively below the level of the 5th thoracic vertebra[ 10 ]. In contrast to this study, we included a larger cohort of patients and used a different semi-automated segmentation tool. Another unique feature of our study is that we analyzed and segmented the lesion volume on axial images. It might be difficult to detect lesions in lateral localization with sagittal images, which are more prone to partial volume artifacts. Other studies have analyzed lesions primarily on sagittal images, sometimes in combination with selected axial slices[ 1 , 12 – 14 ]. In addition, we analyzed lesions down to the conus medullaris, thus covering the entire SC in a representatively large cohort of patients. We are aware of only a few studies performing whole-spine MRI analysis in MS patients[ 10 , 14 ]. In contrast to a recent article with only 74 patients[ 14 ], we analyzed considerably more patients (n: 543). Furthermore, we performed axial imaging of the entire SC and not only at the level of the lesions found on sagittal images. We also analyzed lesion volume. As recently published, SC lesions are of high prognostic value because patients with SC lesions are more likely to suffer from progression independent of relapse activity[ 15 ]. Total SC MRI in MS patients in early stages could therefore be useful for treatment decisions, such as the prescription of disease-modifying drugs. SC lesion number and SC lesion volume could be added to a prognostic algorithm to support treatment decision making[ 16 ]. Further prospective and multicenter studies are needed for validation, such as the planned study based on the ProVal-MS cohort (ProVal-MS study; German Clinical Trails Register study ID: DRKS00014034). A limitation of our study was the difficulty to count confluent lesions separately or to detect diffuse lesions. However, these types of lesions are more common in patients with a higher disease burden such as PPMS or SPMS, and these patient groups represent only a small part of the patient cohort included in our study. In addition, volumetric calculations using 2D data acquired at 4 mm slice thickness are prone to partial volume artifacts and may be less accurate than 3D data acquired at isotropic spatial resolution, which was not available in this study. Finally, we evaluated only T2w images, but guidelines[ 2 ] recommend at least two different sagittal sequences (T2, PD, or STIR) to improve sensitivity. This limitation can be neglected because we analyzed scans with a slice thickness of 2 mm and a gap of 0.2 mm instead of the more commonly used slice thickness of 3 mm. In conclusion, the FoV of an isolated MRI acquisition of the cervical SC (up to the level of the 3rd thoracic vertebra) is sufficient to detect 94% of all patients with CIS or MS and SC lesions. However, a small percentage (6%) had only lesions below this level. Therefore, we recommend examining the whole SC at least in cases of unclear diagnoses or first diagnoses of CIS and MS in the clinical setting. Abbreviations CIS clinically isolated syndrome EDSS Expanded Disability Status Scale FoV field of view MOG-AB myelon oligodendrocyte glycoprotein antibody MRI magnetic resonance imaging MS multiple sclerosis PPMS primary progressive multiple sclerosis RRMS relapsing-remitting multiple sclerosis SPMS secondary progressive multiple sclerosis SC spinal cord STIR short tau inversion recovery TSE turbo spin echo. Declarations Author Contribution IR: writing the manuscript IR, MB and ML: preparation of the figuresMB, ML, LH, VP, MEH, NS: Acquisition and analysis of the dataCZ, JSK, MM: Conception and interpretation of the dataAll authors reviewed the manuscript.IR and MB contributed equally to the work.JSK and MM contributed equally to the supervision of the work References Bot JC, Barkhof F, Polman CH, Lycklama a Nijeholt GJ, de Groot V, Bergers E, et al. Spinal cord abnormalities in recently diagnosed MS patients: added value of spinal MRI examination. 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Ther Adv Neurol Disord. 2023;16:17562864231161892. doi: 10.1177/17562864231161892 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 21 Jan, 2026 Read the published version in Clinical Neuroradiology → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7808342","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":539846743,"identity":"b3c475fa-4c84-4234-92f4-6f5b9a07df35","order_by":0,"name":"Isabelle 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16:20:49","extension":"xml","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":56105,"visible":true,"origin":"","legend":"","description":"","filename":"50a0a1fccc3b47e081f6c3d44a67181d1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7808342/v1/95001826996a37543b54f3a2.xml"},{"id":95566977,"identity":"6157607f-7d63-46fb-81d4-78735c2e09c9","added_by":"auto","created_at":"2025-11-10 16:20:50","extension":"html","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":64251,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7808342/v1/a25b92cf642ece78ea816569.html"},{"id":95566967,"identity":"f8150588-0d6a-4182-9051-6c2a9ea570bf","added_by":"auto","created_at":"2025-11-10 16:20:49","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":63414,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart showing patients with diagnosis of clinically isolated syndrome (CIS) or multiple sclerosis (MS) and number of patients with lesions. The values given in brackets indicate the numbers of lesions.\u003c/p\u003e","description":"","filename":"OnlineFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7808342/v1/ed8d662bac5589bce2b743ac.png"},{"id":95654681,"identity":"4abcf5b1-a958-4e76-98c1-78103a45ca83","added_by":"auto","created_at":"2025-11-11 16:12:45","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":56273,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of spinal lesion volume (in µl) across spinal cord levels. The shaded areas show the standard error of the mean.\u003c/p\u003e\n\u003cp\u003eCIS: clinically isolated syndrome (\u003cem\u003ered curve\u003c/em\u003e); PPMS: primary progressive multiple sclerosis (\u003cem\u003epurple curve\u003c/em\u003e); RRMS: relapsing-remitting multiple sclerosis (\u003cem\u003egreen curve\u003c/em\u003e); SPMS: secondary progressive multiple sclerosis (\u003cem\u003eblue curve\u003c/em\u003e).\u003c/p\u003e","description":"","filename":"OnlineFigure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7808342/v1/da1391a51b51a1b043df7638.png"},{"id":95566968,"identity":"58ab00d8-07f7-4f60-a19c-aa97ea7505d2","added_by":"auto","created_at":"2025-11-10 16:20:49","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":61374,"visible":true,"origin":"","legend":"\u003cp\u003eDiagram showing the percentage of detected spinal lesion volume above a given spinal cord segment. The shaded areas show the standard error of the mean.\u003c/p\u003e\n\u003cp\u003eCIS: clinically isolated syndrome (\u003cem\u003ered curve\u003c/em\u003e); PPMS: primary progressive multiple sclerosis (\u003cem\u003epurple curve\u003c/em\u003e); RRMS: relapsing-remitting multiple sclerosis (\u003cem\u003egreen curve\u003c/em\u003e); SPMS: secondary progressive multiple sclerosis (\u003cem\u003eblue curve\u003c/em\u003e).\u003c/p\u003e","description":"","filename":"OnlineFigure3.png","url":"https://assets-eu.researchsquare.com/files/rs-7808342/v1/d5e04dcee7ed10c44946fd44.png"},{"id":95566972,"identity":"461a414a-d0bb-470c-b4fb-03b38ccf9b3e","added_by":"auto","created_at":"2025-11-10 16:20:49","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":69041,"visible":true,"origin":"","legend":"\u003cp\u003eDiagram showing the percentage of detected patients with MS lesions in correlation to the assessment of the different segments of the vertebral bodies.\u003c/p\u003e\n\u003cp\u003eCIS: clinically isolated syndrome (\u003cem\u003ered curve\u003c/em\u003e); PPMS: primary progressive multiple sclerosis (\u003cem\u003epurple curve\u003c/em\u003e); RRMS: relapsing-remitting multiple sclerosis (\u003cem\u003egreen curve\u003c/em\u003e); SPMS: secondary progressive multiple sclerosis (\u003cem\u003eblue curve\u003c/em\u003e).\u003c/p\u003e","description":"","filename":"OnlineFigure4.png","url":"https://assets-eu.researchsquare.com/files/rs-7808342/v1/86804af9967b5299a1d37ac9.png"},{"id":101151984,"identity":"7555536d-8faf-4a2d-b511-c5689ccec004","added_by":"auto","created_at":"2026-01-26 16:09:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":865479,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7808342/v1/081d4142-8b57-434a-a8cd-fef395c7e0d6.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Is MR imaging of the cervical spinal cord sufficient for patients with suspected Multiple Sclerosis?","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMultiple sclerosis (MS) is a chronic autoimmune inflammatory disease that affects both the brain and the spinal cord (SC). SC lesions are found in up to 83% of patients with MS[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The recently revised MAGNIMS-CMSC-NAIMS consensus guidelines[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] emphasize the importance of examining the SC. The involvement of the SC fulfills one of the specific McDonald criteria[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] for the dissemination in space in addition to intra-/juxtacortical, periventricular, and infratentorial localization on brain magnetic resonance imaging (MRI). Inclusion of the SC in these criteria increases the likelihood of dissemination in space from 66% to 85%[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Furthermore, lesions in the SC may help to exclude differential diagnoses as they are less common in other neurological diseases and do not occur in healthy ageing[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eHowever, MRI of the SC remains technically challenging due to its thin and long structure and artifacts caused by pulsation or respiration. Due to the long structure of the SC, at least 2\u0026ndash;3 stacks are necessary to cover the whole SC with MRI. Recommendations for MRI protocols suggest at least two different sagittal sequences, such as T2-weighted and proton density-weighted sequences or short tau inversion recovery (STIR) sequences, supplemented by axial T2-weighted sequences to differentiate between true lesions and artifacts[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, a detailed MRI protocol is time-consuming and may not be well tolerated by some patients. As most of the lesions (56%) are located in the cervical segment of the SC[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], many centers, therefore, exclude the thoracic part of the SC in MRI[\u003cspan additionalcitationids=\"CR6 CR7 CR8\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTherefore, the aim of our study was to quantify the decrease in sensitivity resulting from incomplete SC coverage in MRI scans of patients with suspected MS.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003ePatients\u003c/p\u003e\u003cp\u003eThis study was performed retrospectively as part of the single-centre cohort study on MS at the Technical University of Munich (TUM-MS). The study was approved by the internal review board and conducted in accordance with the Declaration of Helsinki. Patients had given written informed consent for the use of their clinical and paraclinical data for research purposes. Inclusion criteria were a diagnosis of clinically isolated syndrome (CIS) or MS and an age between 18 and 60 years. To achieve a uniform classification of patients, all patients were reclassified according to the 2017 diagnostic criteria[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] with full access to the neurologist\u0026rsquo;s medical records. Patients with CIS were defined by a first clinical event suggestive of a relapsing-remitting MS (RRMS) and meeting the criteria for dissemination in space but not for dissemination in time. MS patients included those with a relapsing-remitting course (RRMS) and those with a primary progressive (PPMS) or secondary progressive (SPMS) course.\u003c/p\u003e\u003cp\u003eMRI acquisition and analysis\u003c/p\u003e\u003cp\u003eData were analyzed retrospectively, and MRI of the SC were acquired between January 2009 and June 2018 during routine clinical practice. Imaging was performed on 3-Tesla scanners (Achieva dStream, Ingenia, or Ingenia Elition from Philips Healthcare and Magnetom Verio from Siemens Healthineers) using an anterior body coil. All scans included 2D T2-weighted (w) turbo spin echo (TSE) sequences in sagittal and axial orientation with a slice thickness of 2 mm and a gap of 0.2 mm (sagittal) or a slice thickness of 4 mm and a gap of 1 mm (axial). The typical field of view (FOV) of axial scans was 115 mm with an in-plane spatial resolution of 0.4 mm (ranging from 0.3 mm to 0.5 mm) and were acquired in three consecutive stacks. Sagittal scans had a typical FOV of 250 mm with an in-plane spatial resolution of 0.9 mm (ranging from 0.8 mm to 1 mm) and were acquired in two consecutive stacks.\u003c/p\u003e\u003cp\u003eAll scans were converted to the NIFTI file format and segmented using the BrainSeg3D software, version 2.2.1 (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://lit.fe.uni-lj.si/tools.php?lang=eng\u003c/span\u003e\u003cspan address=\"http://lit.fe.uni-lj.si/tools.php?lang=eng\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). First, we segmented the SC area in axial scans using a region-growing algorithm that had to be initialized by manual setting of a seed point within the SC in each slice. Manual corrections of the outlines were performed when necessary. Lesions were segmented entirely manually. This segmentation was performed by two medical students (LH and VP) after an intensive training period supervised by a senior neuroradiologist (JK). While annotating the 4mm axial slices, the students additionally reviewed both the sagittal images and the primary MR report for comparison. Ambiguous cases were resolved by a senior neuroradiologist. We performed a cross-validation (LH and VP) in 25 patients, 15 of whom had SC lesions, indicating very good agreement (mean voxel-wise Dice coefficient of atrophy/lesions: 0.98/0.79). Additionally, the inferior border of the second cervical vertebra (C2) and the medullary cone were marked separately. These segmentations were evaluated using an in-house python-based algorithm.\u003c/p\u003e\u003cp\u003eWe registered axial and sagittal scans with the SimpleITK software, version 1.20, to combine the segmentations of the consecutive axial stacks. To account for missing slices, we used linear interpolation to insinuate the curvature of the missing region and used a nearest neighbour search to determine the thickness of the interpolated regions. These combined masks, covering the entire SC, were subdivided in a region above the C2 landmark and 19 regions between the C2 landmark and the medullary cone, equally divided based on the total stretched length of the skeletonized spine along the cranio-caudal axis (i.e., the spinal centerline). In analogy to the nerve roots, these 19 regions were named C3-C8, T1-T12, and L1. Assuming equal distances between the root entry zones of the SC, which is roughly the case in the upper SC, a region labelled [C or T]x approximately covers the part of the SC between the root entry zones [C or T]x and [C or T]x\u0026thinsp;+\u0026thinsp;1, while the maximum of the lumbar enlargement corresponds to T11.\u003c/p\u003e\u003cp\u003eStatistical analyses\u003c/p\u003e\u003cp\u003eTo capture the spatial distribution of the lesion volume along the spine, we computed the mean lesion volume for each segment and each MS type separately. Additionally, we plotted the percentage of detected lesion volume (cranio-caudal direction) against spinal cord levels to visualize the increase in sensitivity with an increasing number of SC levels covered. Furthermore, we computed the ratio of patients with a lesion when only checking the upper segments. Patients with / without lesions are reported as absolute or relative frequencies.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eWe identified 575 patients aged between 18 and 60 years with an established diagnosis of CIS or MS and available MRI of the SC. MRI data from 545 patients showed sagittal and axial coverage from at least the inferior border of C2 to the medullary cone; two of these had to be excluded due to poor image quality, leaving 543 MRI data sets for the analysis. The demographics of the resulting cohort are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cb\u003eCharacteristics of the patients\u003c/b\u003e\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCIS\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRRMS\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSPMS\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePPMS\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eall\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e442\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e543\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFemales\u003c/b\u003e\u003c/p\u003e\u003cp\u003e(in %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20 (54%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e304 (69%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e22 (58%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e12 (46%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e358 (66%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e\u003cp\u003e(in years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e34.3\u0026thinsp;\u0026plusmn;\u0026thinsp;9.1\u003c/p\u003e\u003cp\u003e34.9\u003c/p\u003e\u003cp\u003e[20.1\u0026ndash;55.4]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e36.1\u0026thinsp;\u0026plusmn;\u0026thinsp;9.6\u003c/p\u003e\u003cp\u003e35.3\u003c/p\u003e\u003cp\u003e[18.0\u0026ndash;59.9]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e47.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.6\u003c/p\u003e\u003cp\u003e49.5\u003c/p\u003e\u003cp\u003e[33.1\u0026ndash;59.6]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e47.1\u0026thinsp;\u0026plusmn;\u0026thinsp;8.5\u003c/p\u003e\u003cp\u003e46.8\u003c/p\u003e\u003cp\u003e[30.8\u0026ndash;59.6]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e37.3\u0026thinsp;\u0026plusmn;\u0026thinsp;10.0\u003c/p\u003e\u003cp\u003e36.6\u003c/p\u003e\u003cp\u003e[18.0\u0026ndash;59.9]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDisease duration\u003c/b\u003e\u003c/p\u003e\u003cp\u003e(in years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e\u003cp\u003e0.08\u003c/p\u003e\u003cp\u003e[0.0\u0026ndash;3.4]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;6.1\u003c/p\u003e\u003cp\u003e1.1\u003c/p\u003e\u003cp\u003e[0.0\u0026ndash;34.8]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14.3\u0026thinsp;\u0026plusmn;\u0026thinsp;8.7\u003c/p\u003e\u003cp\u003e13.4\u003c/p\u003e\u003cp\u003e[0.3\u0026ndash;32.3]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e\u003cp\u003e3.9\u003c/p\u003e\u003cp\u003e[0.06\u0026ndash;13.3]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4.6\u0026thinsp;\u0026plusmn;\u0026thinsp;6.7\u003c/p\u003e\u003cp\u003e1.3\u003c/p\u003e\u003cp\u003e[0.0\u0026ndash;34.8]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eEDSS\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e\u003cp\u003e1.0 [0.0\u0026ndash;3.5]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e\u003cp\u003e1.5 [0.0\u0026ndash;8.5]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e\u003cp\u003e6.0 [2.0\u0026ndash;9.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e\u003cp\u003e3.5 [1.5\u0026ndash;8.5]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e\u003cp\u003e1.5 [0.0\u0026ndash;9.0]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePatients with SC lesions\u003c/b\u003e\u003c/p\u003e\u003cp\u003e(in %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e27%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e77%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e95%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e85%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e75%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSpinal lesion volume\u003c/b\u003e\u003c/p\u003e\u003cp\u003e(in ml)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003c/p\u003e\u003cp\u003e0.0 [0.0\u0026ndash;0.4]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e\u003cp\u003e0.1 [0.0\u0026ndash;11.6]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e\u003cp\u003e0.6 [0.0\u0026ndash;9.6]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e\u003cp\u003e0.4 [0.0\u0026ndash;3.4]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e\u003cp\u003e0.1 [0.0\u0026ndash;11.6]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNumber of spinal lesions\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e\u003cp\u003e0 [0\u0026ndash;4]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6\u003c/p\u003e\u003cp\u003e2 [0\u0026ndash;25]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/p\u003e\u003cp\u003e6 [0\u0026ndash;17]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/p\u003e\u003cp\u003e4 [0\u0026ndash;12]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6\u003c/p\u003e\u003cp\u003e2 [0\u0026ndash;25]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003cem\u003eValues are given in mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, median and range.\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003cem\u003eCIS: clinically isolated syndrome; EDSS: Expanded Disability Status Scale; PPMS: primary progressive multiple sclerosis; RRMS: relapsing-remitting multiple sclerosis; SC: spinal cord; SPMS: secondary progressive multiple sclerosis\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eA total of 1782 lesions were detected in 409 patients (Fig.\u0026nbsp;1, 19 lesions in 10 patients with CIS, and 1763 lesions in 399 patients with MS). The level-wise distribution of the lesion volume is shown in \u003cb\u003eFig.\u0026nbsp;2\u003c/b\u003e. The percentage of detected spinal lesion volume above a given spinal cord segment is illustrated in \u003cb\u003eFig.\u0026nbsp;3\u003c/b\u003e. Figure\u0026nbsp;4 shows the percentage of patients with MS lesions detected in relation to the assessment of the different vertebral segments.\u003c/p\u003e\u003cp\u003eAs the FoV of an isolated examination of the cervical SC mostly included the upper part of the thoracic spine up to the 3rd thoracic vertebral body, following descriptions refer to this level. 70% of the lesion volume was located above the level of the 3rd thoracic vertebral body. 26 patients (6%) (MS, n: 24 (6%); CIS, n: 2 (20%)) had lesions exclusively below the level of the 3rd thoracic vertebral body, i.e., 94% of all patients with spinal lesions were detected when MRI scans of the upper part of the SC were evaluated exclusively. Differences in the percentage of detected patients with MS lesions between groups are best explained by differences in the overall frequency of lesions rather than by differences in lesion distribution, which was very similar in all patient groups (Fig.\u0026nbsp;2).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe results of our study confirm that most lesions are located in the upper segment of the SC down to the level of the 3rd thoracic vertebral body, an area that represents the FoV of an isolated MRI of the cervical SC as routinely performed in many centers. However, SC lesions occurred at all SC levels down to the medullary cone.\u003c/p\u003e\u003cp\u003eOur study is in agreement with a previous study[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] which showed that the majority of MS lesions were located in the upper part of the SC. However, it was shown that approximately 20% of the lesions occurred in the lower part of the SC in MS patients[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] and in 41% of patients with myelon oligodendrocyte glycoprotein antibody (MOG-AB) associated diseases[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In addition, a small number (8%) of MS patients had lesions exclusively below the level of the 5th thoracic vertebra[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In contrast to this study, we included a larger cohort of patients and used a different semi-automated segmentation tool.\u003c/p\u003e\u003cp\u003eAnother unique feature of our study is that we analyzed and segmented the lesion volume on axial images. It might be difficult to detect lesions in lateral localization with sagittal images, which are more prone to partial volume artifacts. Other studies have analyzed lesions primarily on sagittal images, sometimes in combination with selected axial slices[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In addition, we analyzed lesions down to the conus medullaris, thus covering the entire SC in a representatively large cohort of patients. We are aware of only a few studies performing whole-spine MRI analysis in MS patients[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In contrast to a recent article with only 74 patients[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], we analyzed considerably more patients (n: 543). Furthermore, we performed axial imaging of the entire SC and not only at the level of the lesions found on sagittal images. We also analyzed lesion volume.\u003c/p\u003e\u003cp\u003eAs recently published, SC lesions are of high prognostic value because patients with SC lesions are more likely to suffer from progression independent of relapse activity[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Total SC MRI in MS patients in early stages could therefore be useful for treatment decisions, such as the prescription of disease-modifying drugs. SC lesion number and SC lesion volume could be added to a prognostic algorithm to support treatment decision making[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Further prospective and multicenter studies are needed for validation, such as the planned study based on the ProVal-MS cohort (ProVal-MS study; German Clinical Trails Register study ID: DRKS00014034).\u003c/p\u003e\u003cp\u003eA limitation of our study was the difficulty to count confluent lesions separately or to detect diffuse lesions. However, these types of lesions are more common in patients with a higher disease burden such as PPMS or SPMS, and these patient groups represent only a small part of the patient cohort included in our study. In addition, volumetric calculations using 2D data acquired at 4 mm slice thickness are prone to partial volume artifacts and may be less accurate than 3D data acquired at isotropic spatial resolution, which was not available in this study. Finally, we evaluated only T2w images, but guidelines[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] recommend at least two different sagittal sequences (T2, PD, or STIR) to improve sensitivity. This limitation can be neglected because we analyzed scans with a slice thickness of 2 mm and a gap of 0.2 mm instead of the more commonly used slice thickness of 3 mm.\u003c/p\u003e\u003cp\u003eIn conclusion, the FoV of an isolated MRI acquisition of the cervical SC (up to the level of the 3rd thoracic vertebra) is sufficient to detect 94% of all patients with CIS or MS and SC lesions. However, a small percentage (6%) had only lesions below this level. Therefore, we recommend examining the whole SC at least in cases of unclear diagnoses or first diagnoses of CIS and MS in the clinical setting.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCIS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eclinically isolated syndrome\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eEDSS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eExpanded Disability Status Scale\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eFoV\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003efield of view\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMOG-AB\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003emyelon oligodendrocyte glycoprotein antibody\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMRI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003emagnetic resonance imaging\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003emultiple sclerosis\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePPMS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eprimary progressive multiple sclerosis\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eRRMS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003erelapsing-remitting multiple sclerosis\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSPMS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003esecondary progressive multiple sclerosis\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003espinal cord\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSTIR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eshort tau inversion recovery\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eTSE\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eturbo spin echo.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eIR: writing the manuscript IR, MB and ML: preparation of the figuresMB, ML, LH, VP, MEH, NS: Acquisition and analysis of the dataCZ, JSK, MM: Conception and interpretation of the dataAll authors reviewed the manuscript.IR and MB contributed equally to the work.JSK and MM contributed equally to the supervision of the work\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBot JC, Barkhof F, Polman CH, Lycklama a Nijeholt GJ, de Groot V, Bergers E, et al. 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Retrospective cohort study to devise a treatment decision score predicting adverse 24-month radiological activity in early multiple sclerosis. Ther Adv Neurol Disord. 2023;16:17562864231161892. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/17562864231161892\u003c/span\u003e\u003cspan address=\"10.1177/17562864231161892\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7808342/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7808342/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Purpose: Lesions in the spinal cord (SC) can be found in up to 83% of patients with multiple sclerosis (MS). As they are mainly located in the cervical segment, many centers exclude the thoracic part from SC imaging. The aim of our study was to quantify the decrease in sensitivity resulting from this approach.\nMethods: MR images (3T) of 543 consecutive patients with clinically isolated syndrome (CIS) (n: 37) and MS (n: 506) were analyzed retrospectively. Lesions were segmented semi-automatically on axial T2-weighted images of the whole SC using BrainSeg3D. The volume of lesions was related to vertebral levels.\nResults: Altogether 1782 lesions (CIS: 19; MS: 1763) were found in 409 patients. 70% of the lesion volume was located in the SC above the 3rd thoracic vertebral body, in a segment that is commonly covered by an isolated examination of the cervical SC. However, 26 patients (6%) showed lesions exclusively below the 3rd thoracic vertebral body, thus 94% of all patients with SC lesions could be detected with isolated MR imaging of the cervical SC.\nConclusion: Though the majority of lesions can be detected in an isolated examination of the upper part of the SC, some patients showed lesions exclusively below the 3rd thoracic vertebral body. We recommend routine scanning of the whole SC in suspected MS.","manuscriptTitle":"Is MR imaging of the cervical spinal cord sufficient for patients with suspected Multiple Sclerosis?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-10 16:20:45","doi":"10.21203/rs.3.rs-7808342/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7229095c-7907-4caf-93ab-a59170863cea","owner":[],"postedDate":"November 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-26T16:05:43+00:00","versionOfRecord":{"articleIdentity":"rs-7808342","link":"https://doi.org/10.1007/s00062-025-01613-5","journal":{"identity":"clinical-neuroradiology","isVorOnly":false,"title":"Clinical Neuroradiology"},"publishedOn":"2026-01-21 15:58:01","publishedOnDateReadable":"January 21st, 2026"},"versionCreatedAt":"2025-11-10 16:20:45","video":"","vorDoi":"10.1007/s00062-025-01613-5","vorDoiUrl":"https://doi.org/10.1007/s00062-025-01613-5","workflowStages":[]},"version":"v1","identity":"rs-7808342","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7808342","identity":"rs-7808342","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}